Document 0003 DOCN GALLO003 TI GALLO REPORT: INSTITUTIONAL RESPONSE TO THE HIV BLOOD TEST PATENT DISPUTE AND RELATED MATTERS DT 9501 SO U.S. House of Representatives: Subcommittee on Oversight and Investigations Committee on Energy and Commerce TX TABLE OF CONTENTS I. INTRODUCTION A. Background B. Focus and Process of the Investigation II. EARLY ATTEMPTS TO ISOLATE AND GROW HIV A. The LTCB's Misplaced Focus B. Subversion of the Barre-Sinoussi et al. Paper C. Paradoxical Claims D. Consequences of the LTCB's Misplaced Focus III. CLAIMS AND REALITY CONCERNING THE LTCB'S HIV RESEARCH A. Claims about the LTCB's "Early Isolates" 1. Claims in the Scientific Literature 2. Claims in Legal Proceedings 3. Dr. Gallo's Statements to OSI and Subcommittee Staff B. How the LTCB Scientists Benefitted from their Knowledge and Use of LAV 1. Knowledge of the IP Work with LAV 2. Use of LAV at the LTCB (a) Dr. Popovic's Notes (b) What the LTCB Records Show (c) The "Host Range" Experiment 3. What Gallo and Popovic Said About their Use of the IP Virus (a) What Gallo/Popovic Said to Montagnier et al. (b) What Gallo/Popovic Said in 1985-86 (c) What Dr. Gallo Told OSI and Subcommittee Staff C. LAI/LAV by Another Name 1. LAI as "MOV" (a) The Transformation of LAI to "MOV" (b) Gallo/Popovic's Explanations 2. LAI as "HTLV-IIIb" 3. The HUT-78/HT/H9 "Breakthrough" (a) Claims that HT/H9 was "New" (b) Claims of a November 1983 "Breakthrough" (c) H9's Hidden Defect IV. EVENTS LEADING TO THE APRIL 1984 HHS ANNOUNCEMENT A. Further Work with LAI/MOV B. Work Reportedly Done with "HTLV-IIIb" 1. Origins of H9/IIIb 2. Chaos in LTCB "IIIb" Records C. Subsequent Claims by Gallo/Popovic About Their "Breakthrough" Discoveries D. The CDC Data E. Functional Identity of LAV and "HTLV-III" F. The Popovic et al. Science Paper G. Selection of the Isolate for the LTCB HIV Antibody Blood Test 1. The Gallo/Popovic Debate 2. Other Isolates and the LTCB HIVBlood Test -- There Was No Choice 3. There Was No Time for Delay V. COMPARING THE VIRUSES A. The HHS Press Conference B. Comparisons in the Spring/Summer of 1984 1. Serological Comparisons 2. Immunological (Proteins) Comparisons 3. Molecular (Genetic) Comparisons C. Accusation D. Stonewalling the Assistant Secretary E. Aftermath of the Comparisons F. The Sabotaging of Bryant et al. G. Fate of the Comparison Papers H. Dr. Gallo's Explanations VI. GALLO/HHS ON LTCB MATERIALS TRANSFERS A. Practices at the LTCB B. Practices at NCI, NIH, and PHS C. The Unique Role of Dr. Lowell Harmison VII. THE FRENCH/AMERICAN DISPUTE: FIRST PHASE A. Scientific Events Leading to the Dispute 1. Scientific Papers: HIV is Not an "HTLV" 2. Scientific Papers: Too Alike to be Different B. Issuance of the Gallo et al. Blood Test Patent C. The Initial Challenge VIII. HHS' INITIAL RESPONSE A. The HHS Mindset B. Gallo and Popovic Respond C. The "Fischinger Report" D. Beyond the Fischinger Report 1. The Grinstead Response 2. Malcolm Martin's Information 3. CDC's Information 4. "Major Areas of Oversight" 5. Disposition of the Martin and CDC Information 6. Dr. Gallo's Response 7. Dr. Gallo's Explanations E. Key Players at HHS 1. C. McLain Haddow 2. Dr. James Mason 3. Darrel Grinstead 4. Dr. Lowell Harmison F. The Negotiations 1. Bad News From the HHS Attorneys 2. IP's Quest for Information IX. THE FRENCH/AMERICAN DISPUTE: LITIGATION A. Overview of the Proceedings 1. Lawsuit in the Court of Claims 2. Interference Before the USPTO 3. Tort Claim 4. Lawsuit Under the Freedom of Information Act (FOIA) B. THE U.S. GOVERNMENT STRATEGY 1. Major Players 2. Litigation Strategy 3. Government Attorneys in Action C. DEFINING EVENTS 1. The LAI/LAV EM "Mix-Up" 2. The Counter-Offensive to the EM "Mix-Up" (a) Counteroffensive: "CC" (b) Counteroffensive: The "Early Isolates" Nature Letter 3. Potential Disaster at PTO X. THE SETTLEMENT (AND THEREAFTER) A. Terms of the Settlement B. Unravelling of the Settlement STAFF REPORT I. INTRODUCTION A. Background In April 1984, the United States Government announced with great fanfare that government scientists had discovered the virus that was the cause of AIDS, had discovered a method for growing the virus, and had invented a blood test to detect antibodies to the virus. Officials and scientists of the Department of Health and Human Services (HHS) described these claimed accomplishments as "a triumph of science" and "another miracle" added to "the long honor roll of American medicine and science." On April 23, 1984, the same day HHS held a major press conference for the international media, the HHS scientists who claimed these accomplishments (Dr. Robert C. Gallo and his colleagues at the National Cancer Institute's [NCI] Laboratory of Tumor Cell Biology [LTCB]) applied for United States patents on an HIV antibody blood test and a method for propagating the AIDS virus. In the patent applications, Dr. Gallo and his colleagues affirmed, under penalty of criminal prosecution for making false statements, that they were, "... the original, first and joint inventors... of the subject matter which is claimed and for which a patent is sought ..." Gallo et al. also affirmed, under penalty for making false statements, their duty "... to disclose information which is material to the examination of this application ..." Dr. Gallo and his colleagues likewise all signed the declaration at the conclusion of the patent application that contained this affirmation: "... all statements made herein of my own knowledge are true and ... all statements made on information and belief are believed to be true ... with the knowledge that willful false statements and the like ... are punishable by fine or imprisonment, or both, ... and such willful false statements may jeopardize the validity of the application or any patent issued thereon." Announcement of the HHS scientists' claimed discoveries also was made via numerous scientific papers and presentations. But the announcements were no sooner made than suspicions about the claims, followed by overt concerns, began to be voiced. The concerns included the following: the U.S. Government scientists' supposed discovery of the AIDS virus was not a bona fide discovery; the U.S. Government scientists in reality had "discovered" another scientist's virus (that of Dr. Luc Montagnier of France's Institut Pasteur [IP]) and used the IP virus for their putative breakthroughs; the U.S. Government scientists had not appropriately credited the prior work of the IP scientists in discovering the AIDS virus and inventing the HIV antibody blood test; neither had the U.S. scientists acknowledged and appropriately credited the contribution of the IP scientists' virus samples to the LTCB's "discoveries"; the U.S. Government had engaged in "inequitable conduct" before the United States Patent and Trademark Office (USPTO), having failed in its duty of candor and disclosure to that office. In 1985-86, following a breakdown in informal negotiations between HHS and IP, the issues were joined in four formal legal proceedings (a lawsuit for breach of contract, a patent interference proceeding, a tort claim, and a lawsuit under the Freedom of Information Act [FOIA]). The legal battles continued for nearly two years, ending only when a political settlement was negotiated by the President and Prime Minister of the United States and France, respectively. Under the terms of the settlement, the United States Government has received an average of $2,000,000 annually, while Dr. Gallo and his two "coinventors" each have received $100,000 annually, since 1987. During the 1985-87 legal proceedings, United States representatives from the Department of Justice (DOJ) submitted numerous briefs and other pleadings on behalf of the research of Gallo et al. Many of the claims made by the United States representatives mirrored claims made by Dr. Gallo himself, in statements to the media, to colleagues and associates in official correspondence, and to HHS officials and HHS/DOJ attorneys, in memoranda and related documents generated in response to the French/American dispute. The U.S. representatives' and Dr. Gallo's claims have been examined in detail during the Subcommittee's investigation; the Subcommittee has documented numerous instances in which these claims cannot be substantiated and, in fact, are contradicted by the available evidence. The Subcommittee's investigation also has produced evidence that during the 1985-87 legal proceedings, the United States Government significantly disadvantaged the IP by systematically denying its representatives access to key information about the work of Gallo et al., particularly information contained in laboratory records and related documents withheld from the IP. The Subcommittee's investigation has identified a number of key documents and items of information whose very existence was withheld from the IP. IP representatives have told Subcommittee staff that their willingness to agree to the 1987 settlement with the United States was attributable in large part to their lack of awareness of these documents and key items of information, particularly those relating to the LTCB scientists' use of the IP virus, LAI/LAV. The settlement that supposedly ended the French/American dispute once and for all began to unravel almost as soon as it was consummated in March 1987. The unravelling of the settlement was due in significant part to the inherent weaknesses of the U.S. position, plus the work of investigative journalists who documented compelling evidence that profound deceits had been officially perpetuated by representatives of the U.S. Government. Yet it was not until 1991, in the midst of a three-year series of HHS investigations that Dr. Gallo finally acknowledged publicly what for years he had denied was even physically possible: the virus the LTCB scientists used to make their HIV blood test -- the virus claimed by the LTCB as its "prototype" HIV isolate -- was in fact the IP HIV isolate LAI/LAV. Two years earlier, Dr. Gallo acknowledged publicly that the cell line he used to grow the AIDS virus, like the virus itself, was not his own laboratory's discovery, but the discovery of a scientist in another NCI laboratory, Dr. Adi Gazdar. Dr. Gazdar originally pressed NCI officials for inclusion as an inventor on the Gallo et al. patents. Eventually, however, Dr. Gazdar accepted a $10,000 NCI award, and he left off his inventorship claims.) Even with these admissions, and notwithstanding the HHS investigations, many significant questions remained, both about the LTCB's HIV research and about the claims made by the United States Government concerning that research. In fact, from 1987 on, even as several HHS components initiated investigations of Dr. Gallo's claims, other HHS components continued to propound the questionable claims and to suppress evidence that demonstrated their dubious nature. The investigation touches on matters of scientific truth, of institutional integrity, and of national honor. The fact that these issues had their origins a decade ago in no way diminishes their contemporary significance, particularly considering that in some quarters, a cover-up of apparent misconduct has persisted to the present day. The very persistence of the questions concerning the U.S. Government's claims, as well as the actions of U.S. Government officials in defending those claims, demonstrate compellingly that until the Subcommittee investigation, major questions remained unresolved. This report addresses those questions. B. HHS/NIH's Sorry History of Misconduct Investigations The 2 1/2-year investigation by the Subcommittee on Oversight and Investigations focused on the following issues: Possible scientific fraud associated with the putative discovery of the AIDS virus and development of an HIV antibody blood test at the LTCB, NCI, National Institutes of Health, (NIH). At all times during the events examined in the Subcommittee investigation, Dr. Gallo was Chief of the LTCB. Possible patent fraud and inequitable conduct associated with the United States' application for an HIV blood test patent (as well as several associated patents); Apparent inequitable handling of patent applications at the USPTO; A cover-up by senior government officials of the original scientific and patent fraud and inequitable conduct, in the context of several legal proceedings, including the PTO interference and a lawsuit in the United States Court of Claims. As part of the cover-up, these officials and U.S. Government attorneys asserted on behalf of the United States claims that they knew or had reason to know were false, claims that could not be substantiated. The investigation included interviews with several dozen witnesses, along with review and analysis of ten of thousands of pages of documentary evidence. The investigation was significantly delayed by the obstructionism of key officials, past and present, particularly at HHS. In one instance, the Subcommittee held a hearing in Executive session, due to the refusal of a potential witness to appear voluntarily for an interview by Subcommittee staff. In the case of other witnesses who did appear for a voluntary interview, their memories seemed to have been selectively obliterated concerning matters in which they were substantially involved. Agency obstructionism was particularly pronounced vis-a-vis documentary evidence. Because of the passage of time since many key events, because of deliberate as well as genuine forgetfulness concerning these events, documentary evidence was a particularly important element in the investigation. Yet very significant delays, as well as several incidents of actual withholding and destruction of documents responsive to the Subcommittee's requests, took place. II. EARLY ATTEMPTS TO ISOLATE AND GROW HIV A. The LTCB's Misplaced Focus During the first critical months of research on HIV, the work of the LTCB scientists was far behind that of the scientists at the IP. The reason the LTCB scientists lagged behind was a misplaced focus on the "HTLV" (human T-cell leukemia virus) family as the probable source of the cause of AIDS. Not only did this incorrect focus misdirect the work of the LTCB scientists, for a time it misdirected the work of much of the scientific community, due to Dr. Gallo's preeminent position vis-a-vis human retrovirus research. In early 1983, scientists at both the IP (Montagnier et al.) and the LTCB (Gallo et al.), searching for the cause of AIDS, attempted to isolate a retrovirus (a virus that reproduces itself using RNA as well as DNA) from AIDS and pre-AIDS patients. Dr. Gallo frequently asserted it was he who first proposed the idea to look for a retrovirus as the cause of AIDS. But Dr. Gallo's early theorizing about the AIDS virus mistakenly placed that virus in the "HTLV" (for "human T-leukemia virus," later changed to "human T-lymphotropic virus") family (see, e.g., Medical World News, August 14, 1982, p. 9). By Dr. Gallo's own admission (see below), his misunderstanding of the fundamental nature of the AIDS virus associated with the mistaken belief that HIV was an "HTLV" resulted in significant confusion and delay in the work of the LTCB scientists. Even for years after HIV had been discovered and its true defining features identified, Dr. Gallo fought a losing battle to keep the AIDS virus in the "HTLV" family by retaining the name "HTLV-III," rather than HIV (see below ). Dr. Gallo himself acknowledged in his November 1986 sworn declaration before the USPTO, that in the Spring of 1983, "...I thought that the best idea of the causative agent of AIDS was most likely to be a new variant of HTLV-I ... our thinking at the time was that the AIDS virus was likely to be a close relative of HTLV-I" (Declaration of Robert C. Gallo; November 8, 1986, p. 10). The IP scientists isolated and began to grow their virus in January/February 1983. Some of the early IP experiments characterizing this virus used reagents provided by Dr. Gallo, for which contribution Dr. Gallo was acknowledged in the first IP paper, published in May 1983 (Barre-Sinoussi et al., Science, 220, pp. 868-871). In the same issue of the journal, Dr. Gallo and his colleagues published two papers reporting HTLV-I antigens in three AIDS patients and HTLV-I proviral DNA sequences in two of 33 AIDS patients. The IP scientists recognized early on that their virus, first called "LAV" for "lymphadenopathy-associated virus" (lymphadenopathy is a pre-AIDS condition) appeared to be distinctly different from the known human retroviruses, HTLV-I and II. The AIDS virus, unlike the other human retroviruses known in 1983, is strongly "cytopathic," i.e., it kills the cells in which it grows. The IP scientists recognized the cytopathicity of the virus and kept their virus cultures alive by adding fresh cells to the cultures or by "passaging" the virus to fresh cell cultures (see e.g., Barre-Sinoussi et al.,1983; Montagnier et al., 1984; Barre-Sinoussi et al., 1984). By contrast, the LTCB scientists, because they were looking for a variant of HTLV-I (the human T-cell leukemia virus), which immortalizes the cells in which it grows, did not comprehend that the virus they occasionally detected in AIDS patients' samples actually was killing the cells. Consequently, the LTCB scientists, for a prolonged period of time, were unable to keep their AIDS patients' virus cultures alive. Consequently, by their own accounts, the LTCB scientists repeatedly discarded AIDS patient cultures, when the cultures died out or failed to grow. Again and again the LTCB scientists unsuccessfully attempted to grow an AIDS virus using methods suitable for an "HTLV" -- not an HIV-type virus. Meanwhile, throughout all of 1983, the only contribution the LTCB scientists made to the scientific literature and dialogue concerning possible causes of AIDS was to reiterate that "HTLV" was "... a very attractive candidate" (Gallo remarks at 7/18/83 meeting of the NCI AIDS Task Force). B. Subversion of the Barre-Sinoussi et al. paper Dr. Gallo was not content to rely on his own papers to support his thinking about "HTLV" and AIDS; while serving as nominal "peer reviewer," he actually altered the contents of the seminal paper by the IP scientists (Barre-Sinoussi et al.; Science, 1983, 220, pp. 868 - 871), composing a misleading abstract, adding to and otherwise revising the text of the paper to strengthen the apparent relationships between the IP virus and "HTLV," defined by Dr. Gallo as "human T-cell leukemia viruses." Later, during the French/American dispute, Dr. Gallo, HHS officials, and DOJ attorneys compounded the damage to the IP scientists' work by blaming them for the very "errors" of understanding -- particularly the alleged close associations of the IP virus with the leukemia virus -- that Dr. Gallo introduced into their paper (see below ). Dr. Gallo argued to OSI that the changes/additions he made to the IP scientists' paper were fully substantiated by what the IP scientists originally wrote. But the Subcommittee staff's review of various drafts of the paper showed that the most significant passages Dr. Gallo offered to justify the changes/additions he made to the paper were themselves itself written by him! An example is Dr. Gallo's alteration of a sentence in the body of the paper that originally referred to "... this virus [the IP virus] as well as HTLV isolates" to read "... this virus, as well as all previous HTLV isolates ..." Dr. Gallo's actions vis-a-vis the Barre-Sinoussi et al. paper were characterized by the NIH Office of Scientific Integrity (OSI) as, "gratuitous, self-serving, and improper" and by the Office of Research Integrity (ORI) as reflecting, "... Dr. Gallo's propensity to misrepresent and mislead in favor of his own research findings or hypotheses." C. Paradoxical Claims Curiously, despite his admitted failure to grow the AIDS virus, Dr. Gallo frequently claimed it was he who developed the methodology for detecting and propagating the AIDS virus and that he taught these methods to the IP scientists. Like Dr. Gallo's claim concerning the "idea of a retrovirus" as the cause of AIDS, the claims about the method for growing the virus played an important role in the U.S. effort to defend the patent of Gallo et al. In a July 1985 letter to Dr. Claudine Escoffier-Lambiotte, Medical Editor of Le Monde, Dr. Gallo wrote that among his contributions to the IP scientists, he provided, "...the major techniques to grow the T-cells (the same as used for HTLV-I)." In his 1991 book Virus Hunting, Dr. Gallo described an occasion on which allegedly instructed the IP scientists concerning the growth of their new retrovirus: "In January 1983, Chermann called to tell me about their positive reverse transcriptase in this one sample and to ask for my advice about how to keep the culture going. I suggested that he add human T4 blood lymphocytes obtained from the umbilical-cord blood of newborns as target cells, an approach used earlier for HTLV-2. Applying this information he succeeded in saving their virus ... by obtaining and adding new umbilical-cord blood cells every few days" (p. 147). Dr. Gallo repeated to OSI the claims that he taught the IP scientists how to grow the AIDS virus and that Chermann and Montagnier themselves acknowledged this was a Gallo contribution. Here is what Dr. Gallo told OSI: "Both Chermann and Montagnier have acknowledged openly Gallo for suggesting adding cells, either directly, that is Chermann by telephone acknowledges this, or indirectly, that by way of his published work in the case of Montagnier. This was the standard technique of cultivation for retroviruses that our lab had developed. The notion that the French group had enormous clarity of thought while we blundered about with HTLV-I is just a bit of nonsense" (8/3/90 OSI interview; transcript p.236). But Dr. Gallo's claims do not square with the facts. His claims also are contradicted by accounts of the IP scientists, including even Dr. Chermann, an occasional ally of Dr. Gallo. Speaking to OSI, Dr. Chermann was both more discriminating concerning what Dr. Gallo "suggested" to him and more complete in his account of the significance of Dr. Gallo's suggestions. Dr. Chermann said Dr. Gallo told him that, "...we can use also cord blood lymphocytes" to grow the AIDS virus, but according to Dr. Chermann, the basis for Gallo's suggestion of the use of cord blood was not because Dr. Gallo recognized the cell-killing property of the AIDS virus but, "... because in HTLV-I it is better to use cord blood cell" (10/5/90) OSI interview; transcript p. 4). More importantly, according to Dr. Chermann, weeks before Dr. Gallo offered the suggestion of adding cord blood, the IP scientists, having already discerned the cytopathic nature of their virus, were already adding fresh cells to their LAV/BRU cultures. Similarly, in a July 26, 1989 letter to Dr. Gallo, a letter Gallo has frequently invoked as evidence of Chermann's acknowledgement of Gallo's putative contribution, Dr. Chermann made clear how limited was the suggestion reportedly conveyed in the telephone conversation with Dr. Gallo. Dr. Chermann said this: "...we requested to you sera to do immunofluorescence and ... you suggest we also to use cord blood lymphocytes." Dr. Chermann wrote tellingly about these matters in a preface he prepared to the French edition of Dr. Gallo's Virus Hunting. In the preface, Dr. Chermann said that in the telephone call with Dr. Gallo early in the IP scientists' work, "Gallo also told me that the lymphocytes in the blood of the human umbilical cord are very sensitive to human retroviruses ... Gallo and his team had postulated the existence of a cousin to HTLV-I, and the search for this 'cousin,' in addition to attempts to culture it directly, was one of the reasons the American team got behind." Dr. Chermann employed a vivid metaphor to describe the different approaches of the LTCB and IP scientists in their attempts to detect and propagate the AIDS virus, a metaphor that makes clear the limitations and limiting consequences of Gallo's HTLV-I-focused approach. Speaking of Gallo's approach, Dr. Chermann said this: "He [Gallo] used a key for which no one could identify the lock. We, on the other hand, looked for the lock and made the key afterwards." On another occasion, Dr. Chermann used another vivid metaphor to describe the differences in the IP and LTCB approaches to growing the AIDS virus: "We grew the plant until it bloomed and we could see what kind of flower it gave. The Americans kept examining seeds and shoots and trying to see if they would turn into the plant they wanted" (AP story in The Cleveland Plain Dealer, 5/1/84). Drs. Montagnier and Barre-Sinoussi denied outright that they were instructed by Dr. Gallo about how to grow the AIDS virus. Writing to Gallo in December 1989, Montganier said this: "... I did myself the passage of LAV/BRU to human cord blood T lymphocytes as early as March 10, 1983 ... This was the second passage of BRU virus on normal T lymphocytes, the first being on T lymphocytes from an adult blood donor ... I used cord blood lymphocytes for many years for EBV transformation ... I really do not think that it was Chermann who gave the idea after he was told by you" (12/29/89 Montagnier-to-Gallo letter; p. 1). Most recently, Dr. Gallo himself significantly downplayed the significance to the IP scientists' work of his reportedly having "given the protocol" to Dr. Chermann. Speaking to Subcommittee staff in the Summer of 1994, Dr. Gallo said this: "I never said I helped Barre-Sinoussi or Montagnier. I gave the protocol to Chermann. All they had to do was ask Chermann. Chermann doesn't get asked. I don't want to tell you that I believe that was necessary. I don't know that. Montagnier and Barre-Sinoussi would probably disagree with Chermann. I'm just saying I sent it. And Chermann says that. That's the truth. I'm not lying." D. Consequences of the LTCB's Misplaced Focus Not only did Dr. Gallo not teach the IP scientists how to grow the AIDS virus, because of his commitment to the leukemia virus as a potential cause of AIDS, Dr. Gallo and his associates, for a prolonged period of time, failed utterly in their own efforts to grow the virus. The reason Gallo et al. failed was because they did not discern the cell-killing nature of the virus. By Dr. Gallo's own admission, it was the IP scientists who revealed the cytopathicity of the virus to him, and not the other way around. Here is an early account of the circumstances, based in part on an interview with Gallo, as published in June 1984 in the Baltimore Sun: "...Dr. Chermann helped Dr. Gallo solve a problem that had him stymied in his AIDS research ... one day in his NCI laboratory, something Dr. Gallo had heard Dr. Chermann say in France 'hit me like a ton of bricks.' It was, in retrospect, a simple observation. Dr. Chermann had said the cells kept dying because the virus killed them" (6/17/84). The early secret of success in growing the AIDS virus was not the use of cord blood per se. Rather, the secret was in understanding that the virus was killing the cells and the corollary understanding that because of the cytopathicity of the virus, one way to succeed in its propagation would be to replenish virus culture with fresh cells, either by feeding the existing cultures or passaging the virus to fresh culture material. It is on this key point that Dr. Gallo's claims that he taught the IP scientists how to grow the AIDS virus fail on logical as well as substantive grounds, i.e., if Dr. Gallo really knew early on that cell-replenishment was the key to propagating the AIDS virus, and if he disclosed this key methodology to the IP scientists in early 1983, why then, for months thereafter, did Gallo and his associates continue to fail in their efforts to grow the AIDS virus? In particular, why did Gallo et al. not use cell-replenishment themselves? Dr. Gallo recognized the illogic of his claims. When asked by OSI if he fed his cultures with fresh cells, he replied, "Not as fast as I would like to have done. No, we weren't. We were trying to grow with IL-2 [interleukin-2, also known as 'T-cell growth factor," or TCGF]. It is ironic that I am telling Chermann to add more cord blood cells ... We didn't do it with ours. We thought we could grow it with IL-2. I don't know when more primary cells were added back. I don't know who did that the first time" (9/23/90 interview; transcript pages 83-84). In fact, in an earlier OSI interview, Dr. Gallo dated the LTCB's initial use of cell-replenishment to "late summer, early fall of 1983," many months after the IP scientists began using the technique (7/25/90 OSI interview; transcript pp. 51-52). Shortly after this interview, Dr. Gallo gave OSI what is probably his most authentic account concerning the prolonged inability of the LTCB scientists to grow the AIDS virus -- and the reasons for that failure: "... I could kick myself [for] not concentrating earlier and trying alternatives to grow the HTLV-I negative specimens" (7/27/90 OSI interview; transcript p.104). Dr. Gallo attempted to argue that "this is science," but he acknowledged the LTCB scientists' failure to grow the AIDS virus was directly related to their failure to understand its intrinsic nature. Speaking of the many specimens the LTCB scientists failed to grow, Dr. Gallo said this: "... they were always in bad shape. They were in bad shape because they often came far and because the cells were being killed. But we didn't understand yet they were being killed. So, you say, why didn't we just keep -- Yes, now I wish we would have tried other experiments to do anything to keep those samples going. But, if you -- At the time, you are seeing crud and you are losing RT positivity very rapidly, you put it away and you say, 'I will try again. Give me another AIDS specimen.' That is what our whole pathway was" (op cit., p. 104). Indeed, for many months, that was what the "whole pathway was" for the LTCB scientists. Again and again, they attempted the same experiment -- short-term culture of suspected viruses from AIDS/pre-AIDS patients, using the old HTLV-I culture techniques -- failing every time. When they failed, they discarded the cultures, assigning the failure to the circumstance that the "cells were in bad shape," failing to realize why this was so -- i.e., because the cells were being killed by the virus. Actually, long before his admissions to OSI, in a rare moment of candor, Dr. Gallo acknowledged his failure to recognize the cytopathic nature of the AIDS virus, and his consequent failure to grow it. Speaking of the cytopathic effects of the virus, Dr. Gallo said this to Science magazine: "We just didn't believe that is what this kind of virus could do ... It is certainly true that in that period of time in summer and certainly by early fall (1983), Chermann had recognized the cytopathic effect of that virus and I had not ... As I look back now, I could bang my head against a wall that we were so stubborn in trying to grow those cells long term in IL-2 ... We went through loss of months with that problem" (230, 1985; p. 520). Thus, by Dr. Gallo's own admission, he either did not possess the secret of growing the AIDS virus or if he did possess it, he inexplicably failed, for many months, to use it. On multiple grounds, Dr. Gallo's frequent claims that he discovered how to grow HIV and "taught" the method to the IP scientists are without foundation. III. CLAIMS AND REALITY CONCERNING THE LTCB'S HIV RESEARCH A. Claims about the LTCB's "Early Isolates" Although during 1982 and much of 1983, the LTCB scientists' efforts to isolate and grow the AIDS virus failed again and again, during and after the blood test dispute, Dr. Gallo, HHS officials, and DOJ attorneys ascribed extraordinary significance to those early efforts. In particular, Gallo et al. repeatedly asserted that the first HIV isolates were obtained at the LTCB in late 1982-early 1983. The reason for these claims was simple. The Gallo et al. blood test patent application was submitted months after the application of the IP scientists. By the fundamental criterion of priority of invention, the IP scientists should have been awarded the blood test patent. But once the Gallo et al. patent issued (due both to PTO's extraordinary incompetence and Gallo's failures of candor and disclosure), and an "interference" between Montagnier et al. and Gallo et al. had been declared, PTO rules provided a potential "out" for Gallo et al. by which they could attempt to demonstrate that they were first to invent. Under U.S. patent law, a domestic inventor may be able to demonstrate priority by "swearing behind" the submission date of another's patent application, by demonstrating "conception" of an invention prior to the conception date of a competing inventor, together with diligence in practicing the invention to the point of its reduction to practice. An individual who thus conceives and diligently practices an invention may be afforded priority for that invention even if his/her reduction to practice occurs after the reduction to practice of the competing inventor. "Swearing behind" was the central tactic of the U.S. Government, during the blood test patent dispute, in its attempt to defend the patent of Gallo et al. The assertion of "early isolate" claims was an integral element of that strategy. 1. Claims in the Scientific Literature: The LTCB's "early isolates" claims actually began before the formal legal proceedings of the French/American dispute. In early-to-mid 1985, Gallo et al. wrote that, "The first HTLV-III isolates were obtained in this laboratory in November 1982, and HTLV-III was subsequently isolated from approximately 100 patients with AIDS or ARC or from healthy individuals at risk for AIDS" (Gallo et al., in AIDS: Etiology, Diagnosis, Treatment and Prevention," 1985, p. 34). In August 1985, the "early isolates" claim was formally propounded in a particularly significant forum, the Proceedings of the National Academy of Sciences (PNAS). The PNAS article, by Salahuddin et al., made these claims: "Since the fall of 1982, independent isolates of HTLV-III have been obtained in this laboratory ... from 101 AIDS and ARC patients and healthy donors at risk for AIDS" (Salahuddin et al., PNAS, 82, pp. 5530-34). Salahuddin et al. were very precise about how their isolates had been identified, and how they were defined, for purposes of the PNAS paper: "The minimum criteria used to identify new HTLV-III isolates were (i) release of particulate, Mg2+-requiring, viral reverse transcriptase into cell culture supernatant fluids...; (ii) transmission of virus to cultures of normal human peripheral blood mononuclear cells or to permissive T-cell lines with resulting characteristic cytopathic effects and release of virus ...; and (iii) detection of HTLV-III proteins by indirect immunofluorescence assays using virus-specific monoclonal antibody ... or hyperimmune sera ..." (emphasis added; op cit., p. 5531). Elsewhere in the paper, Salahuddin et al. said this: "All 101 virus isolates were classified as members of the type-III subgroup of HTLV based on their immunological reactivity with specific monoclonal antibody or hyperimmune antisera and by their cytopathic effect on normal peripheral blood mononuclear cells in vitro" (emphasis added; op cit., 5533). In other words, according to Salahuddin et al., each and every one of their 101 isolates "since the fall of 1982" had been tested and found reactive with HIV-specific reagents. But there were two fundamental problems with these claims: (1) no laboratory data have ever been produced to substantiate that "101" isolates, still less the "over 200" claimed elsewhere by Dr. Gallo (9/23/85 Gallo-to-Fischinger memorandum) met the criteria specified in the PNAS paper and (2) there is no evidence that any so-called "early isolates," particularly any isolate dating from the Fall of 1982 or early 1983 were ever tested by HIV-specific reagents. In fact, no sample could have been tested with HIV-specific reagents in 1982 -- or at any time prior to February 1984 -- for the simple reason that no such reagents existed before that time. Theoretically, virus isolates obtained in 1982-1983 could have been frozen and tested later, after proper reagents became available. This is what Dr. Gallo claimed to have done. Thus, in January 1987, writing in Scientific American, Dr. Gallo articulated the claim that once he had developed HIV-specific reagents, particularly the hyperimmune rabbit antiserum, he used the reagents to analyze and type archived samples, samples that he dated as early as 1982: "By December (1983) substantial quantities [of virus] were being grown, and soon afterward reagent production was underway. With reagents in hand, we could go back and identify the many stored viral isolates. Initial testing showed that 48 isolates from AIDS patients or members of risk groups were of the same type" (p. 50). The 48-isolate claim and the companion claim that very early LTCB samples had been typed with HIV-specific reagents actually became a part of the settlement agreement, via their inclusion in a "Chronology of AIDS Research." The "Chronology," published by Montagnier and Gallo as a "Commentary" in Nature in April of 1987, was identified as "part of the agreement between the U.S. and French AIDS research groups" (Nature, 326, April 2, 1987; p. 435). Among the "critical published facts" cited in this "official" chronology was the following: "May 1984. Gallo's group (1984) reports ... (2) 48 virus isolations ... The use of anti-p24 hyperimmune sera proves that the 48 isolates belong to the same kind of virus" (op cit., p. 436). And in a 1988 Scientific American article, also coauthored by Gallo and Montagnier, the claim was repeated: "The first reagents for specifically typing this virus were rapidly made. Employing those reagents, it was shown that 48 isolates obtained beginning in early 1983 from AIDS patients and people in risk groups were all the same type of virus, which was called HTLV-III on the American side" (259, October 1988, p. 44). Despite these repeated published claims, when Dr. Gallo was challenged to provide substantiating evidence, he did not, could not, do so. In April 1990, testifying to OSI, Dr. Gallo acknowledged that at the time of publication of the LTCB's May 1984 Science papers, "... we had more than 50 detections and more than 10 true isolates of HIV-I (emphasis added; 4/26/90 OSI interview; transcript p. 58). Elsewhere in the same interview, Dr. Gallo said, "... there was about 10 by the time of our publications" (op cit., p. 62). In September 1990, when he was asked by OSI to document LTCB isolates obtained prior to April 1984 that were tested against HIV-specific reagents, Dr. Gallo listed only nine samples that he said were tested against the rabbit antiserum; no primary data accompanied this response. None of these was a 1982/early 1983 sample. More recently, in May 1994, when Dr. Gallo was asked by NCI Director, Dr. Samuel Broder, to substantiate the claims in the PNAS paper, particularly the claim of 1982 isolates, Dr. Gallo again responded with lists of samples, only one of which dated from 1982. This sample was clearly noted in the data summary provided by Dr. Gallo himself as "ND" (for not done, not determined, or not determinable) against HIV-specific reagents. Other documents in the package submitted to Dr. Broder by Dr. Gallo included several handwritten tallies of samples including six samples started in culture in 1982. None of these samples is indicated to have ever been tested with HIV-specific reagents. Dr. Gallo has suggested the possibility that stored 1982 samples were later sent for testing with HIV-specific reagents; however, he has produced no evidence documenting that this actually occurred. In fact, concerning the late-1982 LTCB samples he later would claim as HIV (see below), Dr. Gallo said this to OSI: "... these cultures did not survive long enough to test with HIV-specific reagents" (9/23/90 OSI interview; transcript p. 81). Finally, on several occasions, Dr. Gallo confirmed to Subcommittee staff that no 1982 sample was ever tested and confirmed to be HIV. 2. Claims in Legal Proceedings: The absence of evidence to substantiate claims for 1982/early 1983 isolates did not stop the United States Government from asserting such claims before the USPTO, during the blood test patent interference proceeding. One document submitted by the U.S. Government particularly laid out the framework for false claims about early AIDS research efforts at the LTCB. This document -- titled "Preliminary Statement of the Party Gallo et al." -- was submitted to USPTO at the outset of the PTO interference. As required by PTO's rules, the Gallo et al. preliminary statement specified the conception and reduction to practice dates Gallo et al. claimed for their invention. PTO rules specify that if a party to an interference fails to submit a preliminary statement, that party is precluded from attempting to "swear behind" the other party's filing date, during the interference. Furthermore, according to PTO rules, as "Junior Party" in the interference, Gallo et al. would not have access to the preliminary statement of Montagnier et al., unless they (Gallo et al.) filed a preliminary statement of their own. Thus, on multiple grounds, a preliminary statement was essential to the U.S. Government's defense of the Gallo et al. patent. But the U.S. Government ran a significant risk in filing a preliminary statement on behalf of Gallo et al., because the contents of a preliminary statement are required to be absolutely truthful; violation of this precept carries significant penalties. The USPTO's "Patent Rules" state that: "A party shall be strictly held to any date alleged in the preliminary statement" (37 CFR, Appendix R, section 1.629)." The rules further state that doubts about the claims in a preliminary statement: "... will be resolved against the party filing the statement by restricting the party to the earlier of its filing date or effective filing date or to the latest date of a period alleged in the preliminary statement as may be appropriate" (op cit.). For Gallo et al., this meant that any doubts concerning accuracy of the dates in their preliminary statement would have resulted in an adverse outcome for the Gallo et al. patent in the interference proceeding, since the Gallo et al. filing date was demonstrably later than that of Montagnier et al. Yet, the facts are clear that Gallo et al. could never have supported the claims in their preliminary statement concerning early AIDS research at the LTCB. The central claims laid out in the U.S. Government's preliminary statement to the USPTO concerning the LTCB's early AIDS research were as follows: "The invention was first conceived prior to May 1, 1982." "The invention was first disclosed to another person prior to May 1, 1982." "The first written description of the invention was made on December 15, 1982." "The invention was actually reduced to practice on October 6, 1983." "Active exercise of reasonable diligence toward reducing the invention to practice began on December 15, 1982." Attached to the Gallo et al. Preliminary Statement was the purported "first written description of the invention" of Gallo et al. -- two pages from the laboratory notebook of an LTCB technician, Elizabeth Read-Connole, dated December 15, 1982. Two samples, "HR" and CM," were circled on these pages, indicating these were the samples the U.S. Government considered proof of Dr. Gallo's priority of invention. Examination of the Read-Connole notebook pages appended to the preliminary statement reveals how weak was the evidence submitted by the U.S. Government in support of Gallo et al. The data were not HIV blood test data, rather, they represented the LTCB's putative initial "isolation" of the AIDS virus. This was at least ironic, because ever since the charge of misappropriation was made, Dr. Gallo and HHS officials alike have argued that the discovery of the AIDS virus was distinct from and not critical to the blood test invention. Even viewed from the limited perspective of virus isolation, the data produced with the preliminary statement to support the Gallo et al. invention were extremely weak. The notebook pages contained only two kinds of data, "RT" or reverse transcriptase data, and anti-p19 (HTLV-I) data, marginal data at that. The RT results recorded for the two circled samples were only "+/-," which in other circumstances, when it suited his purposes (e.g., interpreting results with LAV) Dr. Gallo termed "marginally positive" (Gallo "LAV" submission to OSI; 5/15/90). The data were otherwise exceedingly limited. They were obtained on a single occasion; there was no evidence that the cultures continued to grow, nor was there any evidence that the one-time, December 15 results were replicated. The most anyone could have deduced from the December 15 data was that there were two samples that seemed to be weak producers of reverse transcriptase and thus, apparently contained a retrovirus, a retrovirus that appeared not to be HTLV-I. But there was no testing with HIV-specific reagents performed on the samples. Thus, what the new retrovirus was -- and whether it had anything to do with AIDS -- that information could in no way be deduced from the scanty December 15, 1982 data. Dr. Gallo knew this well. In September 1985, Dr. Gallo wrote a memorandum to Peter Fischinger, responding to a number of questions Fischinger and others had raised about, among other things, the LTCB's putative early HIV isolates. Dr. Gallo's remarks to Fischinger on this occasion made clear the vital significance of HIV-specific reagents. Speaking of his late-1982 "isolates," Dr. Gallo said this: "... there were no reagents to HTLV-III/LAV at that time because the virus could not be mass-produced by anyone then" (September 23, 1985 Gallo-to-Fischinger; p. 1). Dr. Gallo went on to say that until he was able to grow the suspected AIDS virus in large quantities and develop specific reagents, he was not able to link it to AIDS. Gallo said in the memorandum: "What good would it do me or the field to slip in a few sentences that another retrovirus is occasionally detected (at that time it was only occasional) and that it is not HTLV-I or II; but we have no evidence that each time this new virus is detected it is one and the same virus, i.e., this could have been an HTLV-III in patient one, no virus detected in patient two, ... and when detected again in, say, patient seven it could have been an HTLV-IV, i.e., not the same as HTLV-III ... Proper specific viral reagents were, in my mind, required to establish the identity of what was believed to be a new virus" (emphasis in original; p. 1). Dr. Gallo's concluding observation was entirely correct. Until the development of HIV-specific reagents, there was no way to know with certainty if a particular sample was infected with the AIDS virus. Yet, contrary to his own precepts, as described above, Dr. Gallo repeatedly published claims of HIV isolates that -- because the "isolates" were not tested with specific reagents -- could not be substantiated. 3. Dr. Gallo's Statements to OSI and Subcommittee Staff: When questioned by OSI investigators about statements he and government attorneys made concerning his putative discoveries, particularly the claims of early isolates, Dr. Gallo professed naivete about the patent process and, by implication, his obligation to tell the truth, both in the patent applications and in the subsequent legal proceedings in defense of his patents. Dr. Gallo also portrayed himself as entirely dependent on the instructions he received from United States attorneys. Here is what Dr. Gallo said to OSI about his 1982-isolate claims: "... I was asked by the United States Government to draw a lineage to the first time we detected this virus to show lineage of our work. You see what has happened as a scientist I am being put into a legal position, which I am not used to ... "When the government sat down with me they asked me, look, we just want to have lineage from your earliest detection of something that you were reasonably confident was not pure HTLV-1 or 2 ... We went back to our records. I didn't have it in my brain. I didn't make any claim" (5/16/90 OSI interview; transcript pp. 99-100). Dr. Gallo further said: "... we have some samples that were HTLV-I, HTLV-II negative by antisera and that are RT positive. Those were not data that allowed me to publish. They were not data that convinced me of the cause of AIDS. They were not even enough to say with absolute certainty this is a great new virus that I can handle and play with. Therefore, we didn't publish. But when I am asked to go back and draw lineage to our first experiments that have positive indications, that is what I did for the government" (emphasis added; op cit., pp. 100-101). Later in the same interview, Dr. Gallo elaborated on the theme: "...that is obvious that that is lineage, isn't it? You had it detected in December '82, February '83 clearly, it is not HTLV-I, right ... You have got RT positive, yes. That is the lineage. You know, that is what you write. That is the advice from the consulting lawyers. "But that wasn't for me to get scientific credit. Just suddenly I am in a legal thing, I am back to a morality ethics thing issue. They are asking me to draw lineage from the day we first detected a non-HTLV-I and II virus and to show that the mind was a little bit open. "... for a legal case, I was asked to draw the lineage, I presented our notebooks and I sat down with the consulting firm ... and with the Health Department lawyers, who had scientific backgrounds" (op cit., page 109). Asked if he used different criteria in "drawing the lineage" of his work than in writing a scientific paper, Dr. Gallo denied that this was the case, adding: "... you are asking me to defend something that I don't -- I don't claim we had the cause of AIDS discovered in February 1983 or December 1982" (emphasis added; op cit., page 110). What Dr. Gallo did claim was that he isolated the AIDS virus "in February 1983 or December 1982." When he was unable to substantiate the claim with data, Dr. Gallo fell back on his brand of logic, arguing that even though he did not test the early samples, he still knew they were HIV: "You had it detected in December '82, February '83, clearly. It is not HTLV-I, right, no, it is not HTLV-I. You have got RT positive, yes. That is the lineage" (5/16/90 OSI interview; transcript p. 109)/ "Is that HIV in December '82? You bet it is. Is it there in February '83? You bet. You tell me what it is if it is not" (5/25/90 OSI interview; transcript p. 28). But these assertions by Dr. Gallo are contradicted by his own words, in other fora. Dr. Gallo himself told Dr. Fischinger that "proper reagents" were essential to confirm the presence of HIV. Dr. Gallo himself said his standard for accuracy is the peer-reviewed scientific literature. In that literature, Dr. Gallo himself defined an HIV isolate with great precision; he reported numbers and dates for isolates according to that definition. He did not say he merely reasoned back in time and assumed his early non-HTLV-I samples had to be HIV. These kinds of arguments by Dr. Gallo, in an attempt to defend clearly false statements in the scientific literature and in legal pleadings, are at variance with all standards of scientific integrity and responsibility. Dr. Gallo attempted to assign responsibility for his statements in U.S. Government legal pleadings to the lawyers who defended the claims of Gallo et al. In a statement that seemed to sum up his account of his dealings with the patent attorneys, concerning his alleged "early isolates," Dr. Gallo told OSI that, "... I repeatedly emphasized to U.S. Government lawyers and consultants that I never made any claim for priority in any discovery of the AIDS virus based on those samples ... The only relevant dates are dates of peer reviewed publications." But the attorneys involved in the Gallo et al. patent applications and/or the subsequent defense of the patents gave very different accounts. William Bundren, formerly of the contract law firm that prepared the LTCB patent applications, told Subcommittee staff that he and his partner counseled Dr. Gallo and his colleagues on the duty of disclosure and the importance of making truthful statements in the patent application. Bundren also said that the scientific "facts" embodied in the patent applications were supplied by the LTCB scientists and not by the attorneys. As for the claims in the legal papers submitted in defense of Gallo et al., the attorneys pointed to Gallo et al. as the original and sole sources of information used in that defense. One outside attorney asserted that the content of motions he prepared for the U.S. government "were based on what we were told" by Gallo and his colleagues. According to this attorney, "we didn't know enough to lie." Another outside patent attorney said that for the most part, he had to rely on interviews with Dr. Gallo or his associates as a source of information. The attorney said he asked the LTCB scientists, "Do you have data to support these claims?" and, "Sometimes the data were provided; often they were not." But, said this attorney, "I never had any reason to doubt what I was told." When confronted with significant pieces of data that contradict the claims of Gallo et al., this attorney responded, "You're telling me things I know nothing about." Concerning the USPTO preliminary statement, the outside private attorney who prepared the statement said he asked Dr. Gallo to provide him with the earliest documents he had that supported the isolation of HTLV-III, not "documents showing RT+, p19- samples," as reported by Dr. Gallo. In response to the attorney's request, Dr. Gallo reportedly provided the December 15 data pages. Dr. Gallo did not explain to the attorney the contents of the December 15 data pages, particularly how, if at all, they supported his claim to have isolated HIV, much less his claim to have invented the HIV antibody blood test. The attorney said he had no understanding of the data independent of what Gallo told him about them. A U.S. Government attorney provided similar testimony. This attorney said he conducted a number of interviews with Dr. Gallo and his staff. The attorney said he asked Gallo "if he had documents to support his statements and Gallo said 'yes' or he believed so." No one, it appears, asked Dr. Gallo if there were data or other pieces of evidence that would contradict his claims. Another U.S. Government attorney offered this description of the process by which "facts" were obtained and "verified": Here's this guy, almost a Nobel prize winner, you walk in his office and see all these awards all over his walls -- if he tells us he did something, are we going to question it?" Besides the isolate claims in legal pleadings, there is the scientific literature, which Dr. Gallo repeatedly asserted to OSI is the information forum by which he stands. The PNAS paper, of course, is part of the peer-reviewed scientific literature, so the question that must be asked is, is there any substantiation for the claims in that paper, particularly the claims about HIV isolates dating from the Fall of 1982? During one OSI interview, Dr. Gallo was asked about statements attributed to him by the Chicago Tribune, citing a telephone conversation with Gallo in which his "early isolates" data were discussed. According to the Tribune, in the telephone conversation, Dr. Gallo reportedly said: The December '82 data is really marginal ... The data were equivocal. At the time they were not even real data" ( Chicago Tribune, 11/19/89). Of his early 1983 data, Dr. Gallo reportedly said: "We stuffed them in the freezer. When we measured RT we couldn't do anything with it. The cells died. I can't make any claim for that. Some people would" (op cit.). Dr. Gallo did not dispute the Tribune's account. In fact, Dr. Gallo told OSI this: "Probably the bulk of what he has there is right in our conversation" (5/25/90 OSI interview; transcript p. 28). Dr. Gallo added, "It is not much different than what I said here ... I never made a claim in the literature for the December '82 samples. I am saying that we knew we had virus particles that weren't HTLV-I .. I never fully characterized them. We never succeeded in growing them in long term. Have I ever claimed differently? "He is getting me to get into legal issues, rather than the scientific issues, of what is published. We didn't publish these claims in any publication. I am a scientist. I go by what I publish" (emphasis added; op. cit., pp. 26-27). In another OSI interview, when he was quizzed about the PNAS paper, Dr. Gallo professed puzzlement. Asked specifically if he could substantiate the claim of HIV isolates "since the fall of 1982," Dr. Gallo said this: "For all of '82? ... Can I have the reference? I would like to see that in writing if I said that ... I don't believe I would have any reason to say that in PNAS. I mean, it doesn't sound like me" (5/16/90 OSI interview; transcript pp. 103-104). In July 1993, when Dr. Gallo was questioned by Subcommittee staff about the claims in the PNAS paper, he responded by accusing the staff of "not understanding science," adding this: "No one believed we really had that many isolates" and "No one believed we really meant that." In a follow-up conversation with Subcommittee staff, Dr. Gallo claimed he had evidence to substantiate the claim of "101 isolates," in the form of a letter from the former head of Biotech Laboratories, that claimed hundreds of HIV-specific IFAs had been performed by Biotech for the LTCB. But the June 13, 1994 letter, containing the "recollections" of Dr. Robert Ting, provided little useful information, stating only that a number of samples were tested for "HTLV," "which included HTLV-I, HTLV-II and HTLV-III." The letter said nothing about how many of the samples tested positive for HIV, still less about how many met the other criteria specified in the PNAS paper. Also in a follow-up conversation with Subcommittee staff, when he was asked if he really tested any 1982 samples with HIV-specific reagents, Dr. Gallo said it was "absolutely right" no 1982 samples had been tested. Yet in May of 1994, when he was required by Dr. Samuel Broder to substantiate the PNAS claims, Dr. Gallo responded with this: "No one should have any reason to believe we would not have the isolates claimed in view of our past record..." The evidence is compelling that the oft-repeated isolate claims -- concerning both the quantity of isolates and, particularly, the claims of isolates dating from 1982/early 1983, are not true, and were known to be untrue at the time the claims were made. B. How the LTCB Scientists Benefited from their Knowledge and Use of LAV 1. Knowledge of the IP Work with LAV: Following publication of the May 1983 papers, the IP and LTCB scientists continued on their different tracks vis-a-vis the AIDS virus. By mid-summer 1983, the IP scientists had developed an ELISA (enzyme-linked immunosorbent assay) to test human blood samples for antibodies to their newly-discovered virus. The IP scientists also made important discoveries about the characteristics of the virus, including the size of its proteins, its morphology, and, particularly important, its selective tropism for human T-cells. Additional isolates of the virus and results of its further characterization were reported by Dr. Montagnier at the July 1983 meeting of the NCI AIDS Task Force, headed by Dr. Gallo. Particularly important were election micrographs (EMs) of the IP virus, showing its distinctive lentivirus morphology, different from that of the leukemia virus, HTLV-I. Initial results of the IP ELISA and more aspects of the characterization of the virus the IP scientists now called "LAV" (for lymphadenopathy-associated virus) were presented by Dr. Montagnier at a September 1983 meeting at Cold Spring Harbor, New York. Simultaneously, in Great Britain, the IP scientists filed a patent application for their virus antibody blood test. Documentary evidence, witness testimony, and Dr. Gallo's own statements to OSI show that he was present at both the July 1983 and September 1983 meetings. Dr. Gallo heard Dr. Montagnier's presentations at both meetings. Moreover, documentary evidence shows that even before the Cold Spring Harbor meeting in mid-September, 1983, some LTCB scientists, including Dr. Gallo himself, knew about and made use of the IP virus antibody blood test. On September 2, 1983, LTCB scientist Dr. Marjorie Robert-Guroff transmitted to Dr. Montagnier a set of human blood samples, to be assayed "for specific reactivity against your AIDS virus-producing cells by immune fluorescence or against the AIDS virus antigens by your ELISA approach" (emphasis added). Robert-Guroff's letter was copied to Dr. Gallo. About six weeks later, at a meeting in Europe of the Association for Cancer Research, Gallo and Montagnier exchanged written observations and requests concerning the IP's early serology, including serology of the LTCB samples. A note in Dr. Gallo's hand shows that he asked Montagnier to, "Please send enough [virus] particles ... for about 200 assays ... Also, please let me know data with sera recently from us. Also, when available, some of your sera." This note shows there is no question that Dr. Gallo knew about and made use of the IP antibody blood test. It was at the Cold Spring Harbor meeting in September 1983 that Dr. Gallo mounted an aggressive attack on Montagnier, questioning the quality and significance of his data, particularly the data that demonstrated how different the IP virus was from HTLV-I. Dr. Gallo now admits that his aggressive questioning of Montagnier, " ... widened the growing chasm between the two labs ..." (R. Gallo, Virus Hunting, 1991, p. 170 ). Dr. Gallo also was present at a November 1983 meeting in Japan at which Dr. Barre-Sinoussi gave a detailed, wide-ranging review of the IP data, including detection of viral antibodies in significant proportions of pre-AIDS and AIDS patients (74% and 38%, respectively). The detection rate in pre-AIDS patients was particularly impressive because for blood screening purposes, what is most important is the ability to detect virus in individuals who have not already been diagnosed with the disease. The November 1983 data on characterization of the IP virus were also impressive; they showed how far the IP scientists had come in their understanding of the nature of the virus. Dr. Barre-Sinoussi reported on T-cell tropism of the virus, particularly its selective affinity for OKT4+ cells, on the RT (reverse transcriptase) of the virus, and on the identification of viral proteins. Besides attending meetings at which the IP scientists presented their data, Dr. Gallo also received prepublication copies of a number of the IP scientists' papers, including both the Barre-Sinoussi et al. May 1983 paper and a chapter by Montagnier, published in a volume of the Cold Spring Harbor meeting proceedings (Dr. Gallo was editor of this book). None of these circumstances was reported to the USPTO, despite their obvious significance to the patent claims of Gallo et. al. Neither was there any disclosure by Gallo et al. of an important paper by the IP scientists, published weeks before Gallo et al. submitted their patent applications. In this paper (Vilmer et al., The Lancet, 1984, pp. 753 - 757), the authors described the methods of the IP ELISA. Vilmer et al. also reported that antibodies to the core protein of their new retrovirus, "... are widely distributed in the population at risk of AIDS ..." (p. 757). The significance of the IP scientists' work to the claims of Gallo et. al. was confirmed in rulings of the Examiner at the United States Patent and Trademark Office (PTO) who handled both the Gallo and Montagnier HIV blood test patent applications. During 1986, the Examiner repeatedly rejected all pending claims in several Gallo et al. follow-on applications ("continuations-in-part" [CIPs]) to the Gallo et al. blood test patent. In submitting the CIP applications (in July and August of 1984), Gallo et al., under criminal penalty for making false statements, said concerning the material common to the parent blood test: "...we do not know and do not believe that the same was ever known or used in the United States before our invention thereof or patented or described in any printed publication in any country before our invention thereof..." But the USPTO Examiner declared that the work of the IP scientists was "prior art" to Gallo et al. The Examiner substantiated her rejection of the CIP claims of Gallo et al. with the observation that those claims were: "... anticipated by or, in the alternative, ... as obvious over Barre-Sinoussi et al. ... or over the disclosures of Montagnier (Cold Spring Harbor Meeting 9/1983...)" (2/11/86 PTO Office Action, Gallo et al., SN #635,610). "... deemed to be drawn to subject matter which is the same as or substantially the same as that taught by Barre-Sinoussi et al. or Montagnier et al." (2/11/86 PTO Office Action, Gallo et al., SN# 635,610); "... unpatentable over Barre-Sinoussi or Montagnier et al. ..." (4/4/86 PTO Office Action, Gallo et al., SN# 643,715). The Examiner further said that, "... the methods taught by Barre-Sinoussi for the assay of LAV appear inherently to anticipate or render obvious the claimed methods drawn to assay of HTLV-III" (op cit.). The Examiner also cited Vilmer et al. as prior art to the work of the LTCB scientists. The Examiner used this paper to reject numerous claims in Gallo et al. CIPs. 2. Use of LAV at the LTCB: It is clear from the rulings of the USPTO that the work of Gallo et al. benefited from the prior work of the IP scientists. But these benefits were far from the whole story; benefits at least as substantial accrued to the LTCB scientists through their actual use of the virus samples provided to them in 1983 by the IP scientists. One of the major foci of the 1985-87 French/American dispute was the assertion of IP representatives that the LTCB putative "prototype" virus, "HTLV-IIIb," was actually the IP virus, which the LTCB scientists received from the IP long before IIIb reportedly was isolated. For years, Dr. Gallo and his associates, particularly Dr. Popovic, not only denied that they had willfully misappropriated LAV, they also argued strenuously that (1) the viruses were not really identical (see Part E below ) and (2) even if they were identical, there could not have been even an innocent "contamination" of the LTCB cultures with LAV, because, the LTCB scientists claimed, they could not grow the IP virus. Over the years Dr. Gallo modified these claims as the truth gradually was revealed. During the OSI, OIG, and Subcommittee investigations, vital new information concerning the LTCB's use of the IP virus emerged. This information, derived from LTCB laboratory notes, submissions to OSI by the LTCB scientists (principally Gallo, Popovic, and Elizabeth Read-Connole [Popovic's laboratory assistant]), and interviews by OSI and Subcommittee staff produced the following facts. (a) Dr. Popovic's Notes: First, a word about Dr. Popovic's laboratory notes is in order. Dr. Popovic singlehandedly carried out the most important early HIV experiments at the LTCB, yet his laboratory notes are extraordinarily sparse and fragmentary. Numerous experiments claimed to have been performed are not recorded at all; notably absent are records of the inception of several putative cultures, including the "mystery virus," MOV. Moreover, such notes as exist are suspect on several grounds, particularly the dates on which the experiments allegedly were performed. Dr. Gallo told OSI, concerning Dr. Popovic's notes, the following: "As a senior scientist doing cell culture, he did not keep a daily laboratory notebook. He relied on technician notes as far as I can tell, his brain, his observations and cryptic notes periodically" (12/2/90 OSI interview; transcript p. 45). Dr. Gallo described to the OSI the process by which Dr. Popovic's notes were said to have been assembled for OSI: "... we were finding stuff in drawers, pieces of paper ... I mean, we pulled out stuff that Mika didn't even know he had and there it was, you know, old stuff, old archaic papers with scribbles on them ..." (op cit., p. 140). Dr. Popovic himself gave a particularly memorable account of his customary practices concerning laboratory notes: "Part of them existed, part of them I think was put together a little bit later I would say ... Obviously, those protocols are fragmentary and could be used very effectively against me and against the lab ... "... usually I relied on the notes that Betsy had, partly what Ersell had, and also we send the samples out to Sarin, Sarang, that was a part of our protocols ... "So I did not put down on the paper notes for weeks. So this is one thing I have to tell ..." (6/26/90 OSI interview; transcript p. 57 - 59). Concerning the crucial matter of the dates on which experiments were performed, when they were said to have been performed, and when the experiments actually were recorded, Dr. Popovic said this: "... how we recorded certain things we just wrote it on the flask. Others (tissue culture people) I know that they do it. If you don't have time, so you put the particular flask (with the note) away and it is recorded (from the flask) significantly later, into the protocol. So this would be an explanation of my protocols, how it was done. I dated significantly later, some told me that I changed the date, and so. Of course, many experiments were not recorded parallel at all" (op cit., p. 59). Dr. Popovic also made clear how the French/American dispute was the precipitant for the collection (if not the actual creation) of his notes: "And when the litigation started, the patent problem came up, suddenly I was asked for notes. So I was a little bit surprised ... "the system over in the LTCB (tissue culture lab) was that I scribbled on some paper of experiment pointing out some important details and I used to put such notes on the hood (for Betsy, for myself, for Ersell) and then eventually I put it in my protocol or I rewrote it and put it in my protocol, which I didn't consider as a protocol. It became a protocol only when the litigation started and they told me I have to give all notes (any paper regarding my work) otherwise I would go to jail if I would not provide all my notes (obstruction of the [sic.] justice). So I told take whatever I have. I don't want to go to jail" (emphasis supplied; op cit., pp. 57 - 59). (b) What the LTCB Records Show: By the LTCB's own records, the materials sent from the IP to the LTCB included the following: 1. Two shipments (April and July 1983) of DNA from patient "BRU" (the individual who was the source of the original LAV isolate); 2. At least three shipments of BRU serum (July, August, and December 1983). BRU serum was the principal reagent Gallo et al. used, prior to the development of the HIV-specific hyperimmune rabbit antiserum, to test cultures for the presence of the suspected AIDS virus; yet no results from any of the LTCB's experiments with BRU serum were ever reported, neither was any acknowledgement of the serum's use ever made. In fact, during the blood test patent interference proceeding at PTO, attorneys for the Department of Justice submitted a key motion in which they asserted that, "The receipt of sera by Gallo from Montagnier taken from the patient [BRU] ... is ... of no significance ... there is no evidence to indicate that the sera contained any antibodies to the AIDS virus" (Opposition of Gallo et al. to the Motion for Judgement of Montagnier et al., USPTO interference; p. 13). 3. Two shipments of LAV virus (as cell-free supernatant) -- in July 1983 and September 1983. The September 1983 shipment of LAV contained two samples with somewhat different identifiers -- "JBB/LAV" and "M2t-/B/LAV." At the time, both samples were believed to contain the same virus, from patient BRU. In reality, as demonstrated in 1991 by Wain-Hobson et al. (Science; 252, pp. 961-965) and confirmed by the Roche analyses, in 1993 (Nature, 363, pp. 466-469), the M2t-/B/LAV LAV/BRU sample had been accidentally contaminated at the Institut Pasteur and overgrown with virus from another patient "LAI." Consequently, in September 1983, Gallo et al. received a sample of BRU (JBB/LAV) and a sample of LAI (M2t-/B/LAV). These samples were both IP HIV isolates. LAI is the source of the LTCB's "HTLV-IIIB." The September virus samples sent from the IP to the LTCB were accompanied by a transfer agreement that stipulated the virus would: "...not be used for any industrial purpose without the prior written consent of the director of the Pasteur Institute." The transfer agreement further bound the recipient, "...not to disseminate the virus in any form (to companies or other scientists) without the prior written authorization of the Director of the Pasteur Institute." Dr. Popovic signed the IP transfer agreement on September 23, 1983, affirming (in addition to the above conditions) that the virus would be used, "... by the recipient himself, exclusively, and only for the following research purposes ...: (a) biological; (b) immunological and (c) nucleic acid studies." The research purposes for which the IP virus could be used -- purposes specified by Dr. Popovic himself -- obviously were quite broad. They even included use of the virus to make an antibody blood test. But what was prohibited by the transfer agreement was industrial use and/or dissemination of the virus to commercial firms. These proscribed acts were precisely what the LTCB scientists did when they distributed the IP virus, wittingly or unwittingly, to the manufacturers HHS licensed to make the LTCB HIV antibody blood test. The transgressions of the transfer agreement were the focus of the suit for breach of contract filed by the IP against the United States government in December 1985 (see below ). The knowledge and experience Dr. Gallo and his colleagues gained from their work with the IP virus, even before it was renamed and claimed as an LTCB isolate, were very substantial. The Richards Committee said on this subject that, "The Gallo lab 'went to school' with the French virus..." (emphasis in original; 2/19/92 Richards to Healy; p. 2). Part of the reason the LTCB scientists benefitted so significantly from their use of the IP virus was the substantial quantity of work on the virus carried out by the IP scientists themselves. Dr. Popovic was clear about the value of the IP scientists' work. Concerning the data Dr. Montagnier presented in September 1983 at Cold Spring Harbor, the same data that Dr. Gallo publicly derided, Dr. Popovic described them as, "very impressive" (6/26/90 OSI interview; transcript p. 46). Dr. Popovic further said that while Dr. Montagnier's data at this time did not prove the cause of AIDS, "... he has excellent data there. He was most advanced. There is no question about that. He picked out the correct virus ..." (op cit., p. 48). Dr. Popovic said, concerning his initial work with the IP virus, in the Fall of 1983, that the initial work, "... was just to repeat the experiment which was described by Montagnier et al. .... They (French) defined it at that point, from the point of a novel retrovirus, relatively well. They (French) had good data in this regard" (op cit., p. 109). The uses the LTCB scientists made of the IP virus included the following: (1) The July 1983 virus sample was used for a number of important experiments at the LTCB. Among these experiments was the electron microscopy (EM) of the July sample that provided the first LTCB identification of the AIDS virus as a "lentivirus." The EM results for the July virus sample were conveyed to Dr. Popovic in an October 3, 1983 letter from the EM specialist, Dr. Matthew Gonda. Gonda's letter, which included the notable observation that the morphology of lentiviruses "is quite distinct from type C or HTLV particles," was copied to Dr. Gallo. Thus, there is good reason to believe that early on, Dr. Gallo know Dr. Popovic was working with the IP virus and knew that virus was clearly distinct from the "HTLV" family. (2) Another important experiment in which a number of samples, including July LAV, were tested by immunofluorescence assay (IFA) against BRU serum and other reagents, showed that LAV was the only sample tested that was positive against both AIDS/pre-AIDS patients' sera while also negative for HTLV-I. During the French/American dispute, DOJ attorneys told PTO that this experiment represented the LTCB scientists' "reduction to practice" of their HIV antibody blood test "invention." The DOJ attorneys did not reveal to PTO that this claimed reduction-to-practice was achieved with the IP virus tested against serum from an IP patient. To have done so would have demolished Dr. Gallo's argument, made under oath in November 1986, that he did not believe the IP and LTCB viruses were even substantially the same. More broadly, Dr. Gallo denigrated the significance of the July sample of the IP virus to the work of the LTCB, even to the point of denying that the sample contained any useable virus. Here is what Dr. Gallo told OSI: "I always took the position that the July sample didn't survive. Because that was our results in our lab at the time. We never went back to reprove the thing ... in my mind, the July specimen was not a useable specimen. There was no significant virus there. That is what I told Montagnier" (7/18/90 OSI interview; transcript p. 65). But Dr. Popovic gave a very different account of his initial experiments with the IP virus. Speaking to OSI about the results and significance of his early work with the virus, Dr. Popovic said this: "That was apparently the first indication in our lab that we can grow this virus, that this virus infects the cells ... The French came out with this one first, as I saw, this virus is here and has this type of characteristics. So we tried to confirm their observations ... we came to conclusion that, of course, this type of virus we have in our samples as well. We are on the same track" (6/26/90 OSI interview; transcript p. 108 - 110). (3) The September 1983 M2t-/B IP virus sample was the first suspected AIDS virus the LTCB scientists grew in permanent cell lines. In fact, the Pasteur virus was the first virus the LTCB scientists even tried to grow in permanent cell lines. The reason the IP virus was used for this attempt was precisely because of the success of the LTCB scientists with the July sample of the IP virus, together with the considerable prior work the IP scientists had done with it. Dr. Popovic told OSI that he chose the IP virus for his first attempts to infect permanent cell lines because: "... it was the best defined isolate from an AIDS-like patient and was available isolate. But most importantly, there was substantial evidence that the virus is not immortalizing T cells" (12/1/90 OSI interview; transcript p.50). The IP virus LAI , under the name "LAV," grew at least two-to-three months at the LTCB, in two permanent cell lines (HUT-78 and Ti7.4); by Dr. Gallo's own account to OSI, the growth of the Pasteur virus was "significant and continuous" (4/8/90 OSI interview; transcript p.25). Confirmation of the successful growth of LAI was obtained in two sets of experiments-- IFA and EM -- whose results were recorded on December 14, 1983. In the IFA experiment, two LAI cell lines -- "HUT-78/LAV" and "Ti7.4 LAV" -- (these were the surviving lines of five originally infected) reacted positively when tested against BRU serum, but did not react with HTLV-I anti-p19. In the EM experiment, the same two LAV cell lines were reported as follows: "Productive lentivirus infection with all forms of virus maturation." (Gonda-to-Popovic letter; December 14, 1983). It bears mention that the two LAI cell lines were the only samples found EM positive, of a total of 33 samples whose results were reported on December 14. (In fact, throughout all of 1983, the only LTCB EMs identifying a new retrovirus in AIDS patients' material were the October and December 1983 LAV EMs.) The LAI/LAV samples were sent for EM on November 15, 1983, a full month before the report was prepared. This makes it all the more remarkable that the samples were reported to be productively infected, "with all forms of virus maturation." The status of these cell lines as observed by EM directly contradicts Dr. Popovic's assertion that in mid-November, because the LAI cell lines were doing poorly, he was forced to reinfect the cell lines with the IP virus. There is no substantiation for this claim. In fact, according to Read-Connole's notes, the entire amount of the M2t-/B sample was consumed in the original inoculation. The only thing that may have happened is that Dr. Popovic added HUT-78 cells to the two LAI cell line cultures (or he passaged both cultures to HUT-78). Betsy Read-Connole told Subcommittee staff she believed the latter event occurred; however, there are no notes to substantiate this occurrence. Even if the LAI cell lines were passaged to HUT-78, the virus remained alive. In other words, the LAI cell lines were continuous. Contrary to the assertions of Drs. Gallo and Popovic, the cell lines did not have to be "restarted." Still other successful experiments were performed with the permanent cell lines infected with LAI/LAV. On November 9, 1983, Dr. Prem Sarin reported the results of RT assays n the five original LAV cell lines, using samples taken on October 27, 1983, one week after the initial infection attempts were made. Dr. Gallo, in his testimony to OSI, described these results as three "marginally positive" and two "negative," but according to Dr. Sarin's notes, one LAV cell line was "?-" three were "+/-," and one was clearly "+." (It is noteworthy that when it came to the LTCB's own cultures, Dr. Gallo cited "+/-" results from Dr. Sarin as "positive." The most important examples of this are the late-1982 LTCB samples, whose "+/-" RT results Dr. Gallo [and later the U.S. Government] would cite as proof that Gallo et al. had "isolated" the AIDS virus before 1983.) The most significant result of the LAV cell line experiments was the demonstration that the new cytopathic retrovirus believed to be associated with AIDS could be grown and produced in substantial quantities in certain specific permanent cell lines. Dr. Popovic and the LTCB scientists, rightly, deserve credit for this accomplishment, an accomplishment that opened the way to numerous other major advances in HIV research. At the same time, it must be recorded that the LTCB success was attained with the IP virus, a virus selected for the initial attempt at infecting cell lines precisely because of the careful early work of the IP scientists, work confirmed in important measure by Dr. Popovic. Here is how Dr. Popovic assessed the significance of the cell line experiments with the IP virus: "In my evaluation the first LAV sample from HUT-78 tested by Sarang [Dr. Sarngadharan] was positive and it was positive enough ... So the conclusion from this experiment was that it can work with HUT-78. We have to continue to use these (permanent) cell lines which are immortal. These cell lines are susceptible to infection with these cytopathic viruses. We can productively infect them ... We picked up these two cell lines, HUT-78 and Ti7.4 as targets (6/26/90 OSI interview; transcript pp. 141 - 142). Subsequently in the same interview, Dr. Popovic reiterated that, "... the first indication came from LAV that LAV can infect the permanent cell line" (op cit., p. 159). Importantly, the data showing the productive infection of the LAI/LAV cell lines were either withheld or obscured, during the HHS response to the IP FOIA request, during the French/American dispute (see below ). Consequently, for a prolonged period of time, the IP scientists and attorneys had no idea how long and how well the IP virus grew at the LTCB. (4) According to Dr. Gallo's testimony to OSI, the LAI/LAV cell line cultures were frozen on January 13, 1984. Dr. Gallo implied that the entire stock of the cell lines was frozen: "In early January of 1984, Dr. Gallo recalls that he asked Dr. Popovic to concentrate on work with isolates from LTCB ... and not give so much time to LAV. Accordingly, on January 13, 1984, Dr. Popovic froze Htu (HUT-78)/LAV and Ti7.4/LAV..." (5/15/90 "LAV" submission to OSI, page 7). Dr. Gallo also gave OSI a notebook page dated January 13, 1984, purporting to show the frozen LAI/LAV cell lines. But this notebook page does not show whether the freezes constituted the entire stock of the cell line cultures, as implied by Dr. Gallo, or were only aliquots of the cultures. This unresolved issue has important bearing on the subsequent uses of LAI/LAV (see immediately below, also PartB2c below ). It also bears mention that the LAI/LAV freeze page was not provided to the IP attorneys under FOIA, during the blood test patent dispute. Furthermore, according to testimony of top NCI officials such as Drs. Vincent DeVita and Peter Fischinger, they were never told that LAV cell lines were frozen at the LTCB, nor were they told the cell lines even existed. Indeed, Fischinger and DeVita said, they were repeatedly told that LAV was not/could not be grown. One of the most significant uses of the LAV cell lines, subsequent to their reported freezing, occurred in February 1984, when what appear to be the LAV cell lines were used for the initial testing of the first HIV-specific reagent -- the hyperimmune rabbit antiserum. Dr. Gallo provided a written submission on the rabbit antiserum to OSI. According to the Gallo submission, the first use of the rabbit serum to characterize a virus culture occurred on February 24, 1984, when the serum was used to test two samples identified as "H/L and "H/TI/L." According to the Gallo submission, these cultures were "coded samples from a now unknown source." The laboratory notebook page on which this experiment is recorded (page 25 of Read-Connole Book III) shows that the two "L" cultures were positive against the rabbit antiserum, as well as positive against both BRU and ET patient sera, but negative against serum from an HTLV-I+ patient and normal rabbit and human sera. These data show that the "L" samples were infected with the AIDS virus. Relatively few samples were tested at this time against the rabbit antiserum; since the "L" samples were the first samples so tested, it is reasonable to assume that Gallo et. al were particularly interested in confirming the identity of the virus in these samples -- or else they were confident of the identity of the virus in the samples and thus, believed the samples would provide a useful test of the rabbit antiserum. There are a number of compelling reasons to believe the "L" samples are the LAI/LAV cell lines. The "L" identification is an obvious clue; Gallo et. al. were unable to provide any other identification for the samples. In addition, a review of the laboratory notes by Subcommittee staff failed to reveal any other sample cultured at the LTCB around this time for which "L" was used as an identifier. The existence of two "L" cultures, in two different cell lines in February 1984, is consistent with the two LAV cell lines established the previous fall. The identifiers for the cell lines match the identities of the LAV cell lines, according to LTCB conventions: "H/L" represents HUT-78/LAV; "H/TI/L represents Ti7.4/LAV, except for the additional "H," which indicates a co-culture of Ti7.4/LAV with HUT-78. In fact , Elizabeth Read-Connole told Subcommittee staff she recalled the Ti7.4/LAV cell line was co-cultivated with HUT-78. Read-Connole also told Subcommittee staff she could not provide any additional information about the "L" samples, which she said were given to her by Dr. Popovic, for testing against the hyperimmune rabbit antiserum. The positive results of the LAI/LAV cell lines against the HIV-specific rabbit antiserum in February 1984 were vitally significant. The results confirmed that LAV was the AIDS virus and thus were proof against any subsequent claims that LAV and HTLV-III were substantially different viruses, or that LAV might not be the cause of AIDS. Yet such claims were made by Dr. Gallo in the Popovic et al. May 1984 Science paper, when he itemized several findings that he said "suggest HTLV-III and LAV may be different." And in his November 1986 sworn declaration, Dr. Gallo said: "At the time the Gallo patent was filed, my colleagues and I did not consider LAV and HTLV-III to be the same or even substantially the same. Quite clearly, the data available to us indicated that the two viruses functioned differently and reacted differently" (Page 13). Similar claims were made by the U.S. Government attorneys during the patent dispute, e.g.: "At no time prior to the filing of the Gallo application, was it appreciated by anyone that LAV and HTLV-III were the same or even similar viruses" (Opposition of Gallo et al. to the Motion of Montagnier et al. for Judgement; page 22). The positive February 1984 results of the tests of the LAI/LAV cell lines against the rabbit antiserum showed that these statements were not true. Thus, it was important to know who knew about the results, and when. In light of Elizabeth Read-Connole's statement that Dr. Popovic cultured the two "L" samples and provided them to her, it was obvious that Popovic was the critical person to be questioned concerning these matters. However, Dr. Popovic declined repeated invitations to appear for a Subcommittee staff interview, and thus could not be questioned concerning these matters. (c) The "Host Range" Experiment: One other experiment said to have been performed with the IP virus needs to be mentioned. The so-called "host range" experiment, said to have been performed in January/February 1984, purportedly included use of LAV to attempt infection of clones of the HUT-78 (HT) cell line. The experiment is important because during the French/American dispute, Dr. Gallo and the U.S. Government attorneys attempted to use it as evidence that LAV and "IIIb" were different viruses because LAV, unlike IIIb, allegedly did not grow in "H9." The evidence said to support this claim was sparse indeed, a single EM report from Dr. Matthew Gonda, dated February 22, 1984. The claims about the significance of the "host range experiment" include Dr. Peter Fischinger's August 1985 report of his "investigation" into the claims of Gallo et al. In this report, based on information obtained from Gallo et al., Dr. Fischinger wrote this: "... Dr. Popovic later attempted to infect the parental uninfected H9 cells with the LAV isolate ... the total amount of reverse transcriptase obtained (~20,000 cpm) was inadequate to initiate an infection of continuous cells" (8/27/85 Fischinger-to-Harmison memorandum; Background Information; p. 8). (Note: notwithstanding Dr. Fischinger's reference to RT results, no such data have ever been produced, and there is no evidence RT assays -- or any assays other than the EMs -- were performed.) In his November 1986 sworn declaration, in which he sought to argue that at the time he submitted his blood test patent application, neither he nor any of his colleagues believed LAV and "HTLV-III" were even substantially the same virus, Dr. Gallo invoked the February 1984 experiment in support of his assertion: "... the data available to us indicated that the two viruses functioned differently and reacted differently. One such difference was shown by the fact that we could grow the HTLV-III using the H9 cell line, and we could not do this with LAV" (11/8/86 declaration; p. 13). Dr. Gallo also said in his declaration that Dr. Popovic, "... tried the H9 cell line with LAV but was not able to produce virus with that cell line," referencing the "host range" experiment (op cit., p. 12). The U.S. Government attorneys told PTO, in their Opposition to the Motion for Judgment of Montagnier et al., that, "He [Popovic] was not able to infect this cell line [H9] with LAV" (Appendix, p. 14). The fact is that the February 1984 experiment was so faulty and so many aspects of it so questionable, that little or no confidence can be placed in any of its claimed findings, particularly for so important a purpose as supporting the assertion that the IP and LTCB viruses were functionally and genetically different. Here are the major defects with the experiment: (a) The entire rationale for the experiment, particularly its performance at the time it allegedly was done, makes no sense. Why would Dr. Popovic, in the middle of the "rush to save the blood supply" with "IIIb," suddenly decide to perform a laborious experiment comparing MOV, LAV, and (allegedly) IIIb (identified in the experiment as "HTLV-A"), an experiment that reportedly involved taking LAV from the previous September from the freezer, thawing it, and using it for attempted cell line infections (of five different cell lines), within two-to-three weeks of Gallo's order to Popovic to freeze LAV and "concentrate on our own isolates"? Up to the time of Dr. Gallo's reported order, Dr. Popovic had been growing LAV quite successfully, in permanent cell lines. Why then would Dr. Popovic, weeks later, suddenly feel the need to attempt the LAV experiments all over again? Dr. Popovic told OSI he did the experiment to, "... discriminate different isolates ...[using] several markers for evaluation" (6/26/90 OSI interview; transcript p. 142). But it is unclear why Dr. Popovic chose the isolates he reportedly did -- MOV, LAV, and "IIIb." MOV reportedly embodied a serious drawback due to its alleged "one-way cross-reaction" with HTLV-II (see Part C1b below). LAV, supposedly, had been ruled off bounds for further experimentation by Dr. Gallo, and in any event, could not legally be used in an LTCB blood test, due to the restrictions in the IP materials transfer agreement. And where was RF, the supposed contender to "IIIb" for the LTCB blood test (see PartG2 below ). In short, the reported design of Dr. Popovic's experiment is entirely out of sync with Gallo/Popovic's accounts of the LTCB's research at this time. This suggests the experiment, if it really was done, was done for a reason other than what Dr. Popovic described, a reason that may be inferred from the use to which the putative results were put. (b) Dr. Popovic's reliance on a single index of viral infection, a notoriously insensitive index -- electron microscopy -- for so important an experiment is another significant enigma. It is informative to recall that whenever it suited his purposes, e.g., arguing the viability of an LTCB isolate, Dr. Gallo argued strongly that a negative EM does not provide definitive evidence of the absence of virus: "... not finding virus by EM is neither qualitatively or quantitatively definitive. It is probably more of an art than a science. Correctly interpreting the complex data is more important than an EM report" (8/3/90 OSI interview; transcript p. 243). In another OSI interview, Dr. Gallo asserted that electron microscopy was less sensitive than other assays, and "... not felt by me ever to be a key criterion except possibly for a first-time publication of a new virus or virus detection ..." (12/2/90 OSI interview; transcript p. 37). In his "rebuttal" to the November 1989 story in the Chicago Tribune, Dr. Gallo wrote that, "... a negative EM report does not mean the cultures are negative" (10/23/90 draft "Rebuttal"; p. 67). The mere fact that the "host range" experiment, if it was performed, relied exclusively on a single, insensitive indicator of virus, further renders the experiment highly suspect. Yet Dr. Gallo repeatedly cited the February 1984 negative EMs as proof positive that the LAV cultures were negative, with no caution or qualification on these assertions. (c) There also is the matter of the laboratory notebook page not provided to OSI, a page associated with the "host range" experiment, bearing an "X" next to six of the 15 samples that were tested. The "Xs" appear next to the two samples that were reported EM+, plus four of the five LAV samples, all of which were reported EM-. This suggests the possibility that there were data from experiments other than the EMs reported in the February 22 Gonda-to-Popovic letter, either alternative EM results, or perhaps more likely, RT or IFA results, results that showed the LAV cell lines were infected and were producing virus. The page bearing the "Xs" is a handwritten copy of another notebook page, a page bearing the same date, but without the "Xs," a page that was given to OSI. Both pages are in the hand of Elizabeth Read-Connole, who was questioned by Subcommittee staff about the hand-copied version of the February 13 notebook page. Read-Connole confirmed the page was written by her, but said she could not recall why she recopied the entire page. Read-Connole also said she could not explain the "X" entries on the page not provided to OSI. She said she was not aware of other data that existed for the cultures, but she made it clear she did not grow them, but merely received samples from Dr. Popovic, for transmittal for electron microscopy. The bottom line is that the data from the February experiment are, at the very least, not conclusive evidence of anything, first because the data consist of nothing more than EMs. Even if the results of the experiment had indicated that LAV and IIIb grew differently in H9, that would not prove the viruses were functionally and genetically independent. Dr. Gallo himself told OSI that the putative differential "target specificity" of two viruses such as LAV and IIIb, "... doesn't mean two viruses are not derived from the same person or sample, because it is conceivable that minor variants might not behave precisely the same way" (4/8/90 OSI interview; transcript p. 28). In 1994, Dr. Gallo told Subcommittee staff he believed he had given too much credence to the February 1984 experiment, and had "overinterpreted" it. Dr. Gallo said he now recognizes he should, at a minimum, have sought to replicate the experiment, at least once. Dr. Popovic went even farther than Dr. Gallo, expressing frank skepticism about his own experiment. Speaking to OSI, Dr. Popovic said of the February 1984 experiment, "It was done in a rush, comparative experiment with IIIb, MOV and LAV. We tried to find out differences between these isolates" (6/26/90 OSI interview; transcript p. 147. Dr. Popovic described the reasons he doubted the experiment: "I was afraid that, okay, god knows what could happened with that sample in February 1984. Those negative data is difficult interpreting ... That comparative study that I did in February was done in rush and not carefully monitored for all the parameters" (op cit., p. 149) 3. What Gallo and Popovic Said About their Use of the IP virus: Concerning the LTCB's use of the IP virus, Dr. Gallo claimed, for years, publicly as well as privately, that the July LAV sample contained no useable virus, and that LAV had not been grown, could not be grown more than "transiently," at the LTCB. Most often, these claims were made in an effort to deny that HTLV-IIIb was derived from LAV, on grounds that since LAV could not be grown, it could not have contaminated LTCB cultures. Dr. Gallo particularly denied the permanent grown of LAV, e.g., in the May 4, 1984 Popovic et al. Science paper, in which Gallo wrote that LAV "... has not yet been transmitted to a permanently growing cell line for true isolation..." This is the statement for which ORI found Dr. Gallo guilty of scientific misconduct, of which the consultants nominated by the National Academy of Sciences to oversee the OSI investigation said this: "The statement that LAV had not been transmitted in a permanent cell line is simply false, and was known to be false at the time the paper was written. This is one of the most glaring faults in the paper and is part of the pattern of misrepresentation in the discussion of the problem of continuous culture. There is no way in which Dr. Gallo can be excused from sharing the blame for this misstatement" (2/19/92 Richards- to-Healy: p. 5). (a) What Gallo/Popovic Said to Montagnier et al.: Drs. Gallo and Popovic acknowledged to OSI that prior to publication of the May 1984 Science papers, they deliberately withheld from the IP scientists information concerning the LTCB's growth of LAI/LAV in permanent cell lines. Dr. Gallo told OSI that Dr. Popovic "...did not give away current research details..." to the IP scientists concerning his (Popovic's) work with the IP virus (Gallo 8/4/90 OSI interview). Dr. Gallo also acknowledged he did not tell the IP scientists he had grown their virus, when he visited the Institut Pasteur in early-April 1984 (Gallo 12/2/90 OSI interview; p. 191). At the same time, Dr. Gallo has frequently asserted that in the comparison papers written jointly with the IP scientists (see PartG below ), he did inform them, albeit after-the-fact, about the LTCB scientists' growth of September 1983 LAV in the "Ti7.4" cell line. This assertion is not true. The collaborative papers never reveal that the LAV cell line for which data were reported was derived from 1983 LAV, and Drs. Montagnier and Barre-Sinoussi told Subcommittee staff they understood the Ti7.4/LAV cell line reported in the papers was infected with the LAV sent to LTCB in the Summer of 1984, both because of Dr. Gallo's repeated denials that he had grown the earlier LAV and because of his urgent demands, in the Summer of 1984, for additional samples to enable him to complete the comparison studies. This understanding is consistent with what Dr. Gallo himself told Dr. Chermann in June of 1984. Speaking of the virus sent to the LTCB in 1983, Dr. Gallo said this: "Obviously we now know that the material you sent to us was inadequate for comparative studies" (6/15/84 Gallo-to-Chermann letter; p. 1). Dr. Popovic acknowledged to OSI that on at least two occasions, he deliberately withheld from the IP scientists information about his growth of LAI/LAV in permanent cell lines: "...when I got the data with the permanent cell lines, including his LAV (Montagnier), in the end of November '83, I again called him up at his home, and I told we got it, learned how to handle the virus... What I didn't tell him was that the virus grows very well in permanent T-cell lines" (6/26/90 OSI interview; p. 111). Popovic added this: "I didn't consider that it was my duty to inform him in detail, that we have a breakthrough with this virus. So at that point we didn't" (op cit., p. 112). Dr. Popovic's choice of words in the above passages is noteworthy, i.e., the statement that in November 1983, the experiments showed that LAI/LAV "grows very well" and "we have a breakthrough with this virus." Clearly, in Dr. Popovic's mind, in the Fall of 1983, LAI/LAV was a virus of great significance at the LTCB, a fact that Dr. Popovic later would attempt -- and because of Dr. Gallo's intercession, would fail -- to acknowledge publicly. As for Dr. Gallo, by at least early Spring of 1984, he knew that Dr. Popovic had grown LAI/LAV in permanent cell lines.. In fact, in an early draft of Dr. Popovic's May 1984 Science paper, Dr. Gallo personally added a statement that LAI/LAV had been grown in a permanent cell line at the LTCB (see Part F below ). But Dr. Gallo deleted this sentence from the paper prior to its submission, and he added to the conclusion of the paper the unqualified assertion that LAV, "... has not yet been transmitted to a permanently growing cell line... " (Popovic et al., p. 500). Furthermore, notwithstanding his knowledge of the growth of LAI/LAV, Dr. Gallo repeatedly and strongly asserted -- to the IP scientists, to HHS officials, and to the world at large -- that the July LAV sample contained no useful virus. As for September LAV, Dr. Gallo variously claimed the LTCB scientists could not grow it at all or they were unable to grow it more than very briefly, and never in permanent cell lines. Thus, in early March 1984, Dr. Gallo wrote to the editor of The Lancet that the IP virus (viruses), "...have never been characterized nor transmitted permanently to recipient target cells. Therefore, no one has been able to work with their particles , and because of the lack of permanent production and characterization, it is hard to say they are really 'isolated' in the sense that virologists use this term" (Emphasis added; 3/5/84 Gallo-to-Ian Munro letter; p. 1). According to Dr. Montagnier's testimony to OSI, Dr. Gallo telephoned him and Dr. Chermann at the end of March 1984, saying that, "... he had a virus growing to a very high titer on a continuous cell line and he believed it was the cause of AIDS. When I asked him whether this virus was similar to LAV, he refused to answer" (6/18/91 Montagnier-to-Hadley letter; p. 1). According to Dr. Montagnier, in April 1984, when he asked Dr. Gallo why he had not already compared LAV to IIIb (since he had received LAV the previous September), Gallo "... said he could not grow the LAV virus well" (op. cit., p. 2). Dr. Gallo's 1984 denials that he grew the IP virus often were associated with his apparent efforts to preempt a charge of contamination/misappropriation of that virus, a charge that -- at the time -- no one but Gallo had raised. In his June 15, 1984 letter to IP scientist Dr. Jean-Claude Chermann, Dr. Gallo said this about the IP virus received at the LTCB in 1983: "What we received from you was minute amounts of extracellular virus on two occasions. The first time there were no detectable virus particles. The second time there were, and we confirmed your transmission of these to fresh T-cells and the ensuing cytopathic effect. We did not 'mass produce' these for characterization of them. We assumed that was your job. We also did not want to cross-contaminate our lines..." (p. 1). (Note that by Dr. Gallo's own definition -- "mass produce" = "continuously produce" [4/26/90 OSI interview, transcript p. 64] -- the claims to Dr. Chermann that the LTCB scientists did not "mass produce" LAV were untrue.) Similarly, on June 28, 1984, Dr. Gallo telephoned the CDC's Dr. Donald Francis. According to Francis' telephone notes, in the course of a long conversation, Dr. Gallo said this about his use of the IP virus: "I don't have their virus growing ... In this field once you receive a virus -- open to criticism. Don't mass produce two viruses in same lab. If I had of waited and mass produced them I would have been told I got cross-contamination." Similarly, in an August 24, 1984 letter Dr. Chermann, Dr. Gallo said this: "The sample of the virus you sent us the first time had, upon arrival, no detectable virus..." (p.1) and this: "... we did not grow LAV. We confirmed your transmission and cytopathic effect. To keep it going in production would have required considerable work which we would have been doing for you, not us. I work for NCI, not you. Second, clearly we would be accused by many of cross-contamination, i.e., we would run the risk of not being able to convince the 'tough' that we had independent isolates" (p. 3). (b) What Gallo/Popovic Said in 1985-86: In public, especially after the onset of the French/American dispute, Dr. Gallo made more strident statements that he had not grown/could not grow LAV. A November 1985 article in Science about the French/American dispute (based in part on interviews with Gallo and Popovic) described the IP claim that "Gallo's group somehow grew the French isolate," reporting Dr. Gallo's reaction as follows: "Gallo indignantly disputes this allegation on several counts, including the fact that the viruses are not identical and that the amount of virus Montagnier sent would not have been sufficient to infect a cell line" (230, p.642). Further, according to the Science article, Gallo and Popovic said the September LAV sample, "...contained 11,000 counts per minute of reverse transcriptase activity, a level that Gallo says is considerably less than is required to infect a cell line ... Gallo and Popovic say they infected fresh lymphocytes with the virus Montagnier sent, but when the reverse transcriptase activity declined they put the material in the freezer" (op cit., p. 643). And in January 1986, according to U.S. News and World Report: "...some experts have speculated that Gallo may have mistakenly contaminated his experiments with the French virus. 'That's the height of outrage,' responds Gallo, who adds that 'it was physically impossible' to grow the particles of virus sent by Montagnier" (1/13/86). In March/April 1986, at the heart of the French/American dispute, there occurred the incident described by the media as "acutely embarrassing," i.e., the revelation that published pictures reported to be "HTLV-III" growing in a permanent cell line, actually were pictures of LAI/LAV (see Part C1 below ; these were the EMs of the HUT-78/LAV cell line, produced in November/December 1983 described above). Following this revelation, Dr. Gallo finally acknowledged he had grown LAV in a permanent cell line, but he said the growth had been very brief. According to the April 12, 1986 New York Times: "...Dr. Gallo said that his lab had been able to infect human cells with the virus sample received from France only 'transiently.'" To the journal Nature, Dr. Gallo was more explicit, saying about his work with the IP virus that he had, "... achieved transient growth ... but for one week only and in small quantity" ( 320 , 1986, p. 96). See Part C1 below , for more information about the incident of the LAV EMs. Dr. Gallo also made strong representations to HHS/DOJ officials/attorneys, throughout the blood test patent dispute, that he did not grow the IP virus and that he gained little or nothing from his use of that virus. These claims were accepted uncritically and were incorporated into official papers and legal pleadings of the U.S. Government. At the very outset of the patent dispute, Dr. Gallo wrote to the official charged with investigating the LTCB scientists' claims -- Dr. Peter Fischinger -- that July LAV "... did not contain detectable virus" (8/19/85 Gallo-to-Fishinger memorandum; p. 2). Concerning September LAV, Dr. Gallo, in the same memorandum, said only that his colleague, Dr. Popovic, "... was able to detect RT in these supernatants ..." (p. 2). In April 1986, Dr. Gallo prepared a document titled "History of Key Events and Side Issue of the HTLV/LAV Discovery." This document, which was widely circulated within the upper echelons of NCI, NIH, and the Public Health Service, as well as DOJ, appears to have been a forerunner of Dr. Gallo's November 1986 sworn declaration. In the April 1986 document, concerning the LTCB's use of September LAV, Dr. Gallo said this: "...there were only two things we could do: a) EM & b) RT. We did both and confirmed it was a retrovirus and immediately told them so. To try to do EM's and to try to grow it, Popovic transmitted it to human cord blood T-cells, to a T-cell line -- HUT-78 and another T-cell line. All transmissions were transient" (p. 3). Dr. Gallo continued the "transient" growth theme concerning LAI/LAV, in his November 1986 sworn declaration before the PTO. In the declaration, Dr. Gallo said that Dr. Popovic succeeded in "temporarily transmitting" the Pasteur virus to two (not the "one" Dr. Gallo previously publicly acknowledged) permanent cell lines. But, said Gallo, "both transmissions were only temporary in nature" (11/8/86 Gallo declaration; p. 12). At no time did Dr. Gallo reveal that the only reason the LAI/LAV cell lines were only "transient" or "temporary" in nature -- if they really were -- was because he ordered the cultures to be frozen. Concerning the July LAV sample, in his 1986 sworn declaration, Dr. Gallo said this: "...we could find no detectable virus in the sample ... subsequently some minute viral activity was noted in the sample but this was so small that nothing could be done with the sample ... the sample I received did not show meaningful viral activity" (op cit., p. 11). (c) What Dr. Gallo Told OSI and Subcommittee Staff: During the OSI inquiry/investigation, Dr. Gallo acknowledged the discrepancy between the facts and his earlier statements that LAV did not grow at the LTCB. Presumably recognizing that OSI's examination of the laboratory notes would make those discrepancies clear, Dr. Gallo said this: "I always took the position that the July sample didn't survive ... So in my mind, the July specimen was not a usable specimen. There was no real significant virus there ... That is what I told Montagnier. But when the report came back six weeks later as EM positive, we knew we had something there and so we saved it" (7/18/90 OSI interview; transcript p. 65). Dr. Gallo here makes clear his awareness of the October 1983 EM+ report for July LAV, an awareness starkly at odds with his subsequent, repeated denials that July LAV contained any virus. In other interviews, Dr. Gallo specifically referred to his earlier denials that he grew the IP virus: "...there has been confusion in the response of what we did to LAV. In my response during the passionate period ...'oh we never grew LAV' and of course we did grow LAV" (5/16/90 OSI interview; transcript p. 87). In a subsequent interview, Dr. Gallo said this: "There is a point where I say I didn't grow LAV. And, of course, LAV was grown ... Quite frankly, it wasn't so germane to me at the time and I was just anguished as to what was coming out of the newspaper. At that moment bombs were going off" (5/25/90 OSI interview; transcript p. 13). More recently, Dr. Gallo told Subcommittee staff, concerning his January 1986 denial to U.S. News and World Report that he grew LAV, "... the statement is somewhat misleading ... If it misled anyone, I am sorry. I am also sorry for my certainty of being right." Yet Dr. Gallo also asserted his January 1986 statements were, "... in no way intentionally inaccurate." The "Richards Committee" was not willing to excuse Dr. Gallo on the basis of his passion/anguish, nor on the basis of "bombs going off." Referring to the May 1984 Popovic et al. Science paper, to which Dr. Gallo added the unqualified assertion that LAV, "...has not been transmitted to a permanently growing cell line for true isolation..." The Richards Committee said this: "The Gallo lab failed to mention the fact that they had propagated the French virus and stated (in the Popovic et al. manuscript) that the French virus had never been transmitted to a permanent cell line. Given the quality of the information derived from propagation of the French virus, we believe that this constitutes intellectual recklessness of a high degree -- in essence, intellectual appropriation of the French viral isolate" (emphasis in original; 2/19/92 Richards-to-Healy; p. 3). Finally, concerning the LTCB's early use of the IP virus, it remains to be noted that the LTCB records relating to the LAI/LAV experiments exhibit a number of forensic anomalies possibly indicative of, among other things, retrospective creation, destruction and/or suppression, and obscuring of relevant records. Particularly noteworthy is the probability that IFA experiments on the LAI/LAV cell lines -- experiments not disclosed to the IP nor to OSI -- were performed in the Fall of 1983. Elizabeth Read-Connole told Subcommittee staff these IFAs were performed; she could not explain why the resulting data were not provided to OSI. C. LAI/LAV By Another Name Laboratory records and Gallo/Popovic's retrospective accounts show that the LTCB's seminal experiments, particularly experiments associated with the development of the LTCB HIV antibody blood test and the genetic sequencing of the LTCB's putative "prototype" HIV isolate, were performed with an isolate called "MOV" (for "MO/Variant") and later, with an isolate called "HTLV-IIIb." MOV and IIIb are LAI/LAV. Experiments performed for OSI by Roche Molecular Systems, using the earliest samples that could be located (samples frozen since 1984), demonstrated conclusively that this is so (Chang et al., Nature, 363, pp. 466 - 469). Drs. Gallo and Popovic asserted to OSI that MOV and IIIb were independent of LAV/LAI. Following revelation of the Roche results, they modified their accounts to claim that MOV and IIIb, originally independent samples, had been accidentally contaminated by LAI/LAV. In a letter to Nature, written shortly after publication of a paper by the IP scientists that demonstrated the LAI/LAV origins of IIIb (Wain-Hobson, et al., Science, 1991) Dr. Gallo said this: "It ... appears that cultures of virus from people with AIDS became contaminated with HIV-LAI at NIH ... (1991, 351, p. 358). But the Wain-Hobson et al. and Chang et al. data did not show that any culture of a person with AIDS became contaminated with LAI at the LTCB. The data did not eliminate the possibility of misappropriation, neither did they substantiate the occurrence of contamination. Indeed, there is no evidence to support the "contamination" scenario with respect to MOV, IIIb, and LAI/LAV; other than Gallo/Popovic's claims, there is no evidence there ever were MOV and IIIb isolates independent of LAI/LAV, to begin with. Moreover, it is important to recall that contamination is precisely what Gallo/Popovic -- for years -- asserted was impossible. The evidence is compelling that "MOV" and "IIIb" were merely different names given to the single readily-usable isolate Popovic/Gallo had in late 1983/early 1984 -- LAI/LAV. Following is an account of the pertinent evidence: 1. LAI as "MOV": Dr. Gallo patented and claimed as his HIV prototype an isolate he identified as "HTLV-IIIb," an isolate he said originated in a pool of virus samples (see below). But IIIb is not the first HIV isolate Gallo et al. produced in large quantities. IIIb is not the isolate Gallo et al. used to develop their HIV antibody blood test or their first HIV-specific reagents. Neither did Gallo et al. perform any of their initial, significant experiments with "IIIb." Rather, these accomplishments all were achieved with another, "mystery" isolate, the existence of which was not acknowledged until the OSI investigation, an isolate identified in LTCB records as "MOV." Yet no scientific paper reported any of these experiments as performed with "MOV." Rather, the experiments were described as performed with "HTLV-III," Gallo/Popovic's generic name for the AIDS virus, or -- in several instances -- experiments recorded as being performed with MOV were reported to have been done with "IIIb." (a) The Transformation of LAI to "MOV": Here is what the LTCB laboratory records and Gallo/Popovic's OSI testimony reveal about LAI/MOV: o The designation "MOV" appeared without explanation in Dr. Popovic's notes for November 22, 1983, alongside two infected permanent cell lines in which LAI/LAV was growing. No HIV isolate other than LAI/LAV ever grew simultaneously in these two cell lines at the LTCB; neither is there any record of any attempt to infect these cell lines with an isolate other than LAI/LAV. o The actual notebook entries that lead to the emergence of the LAI/MOV cell lines are as follows: 10/21/83: Elizabeth Read-Connole inoculated five cell lines with LAV, including HOS, Ti7.4, and HUT-78 (Read-Connole Book 1, p. 222); (Read-Connole performed the inoculations because at the time, Dr. Popovic was travelling in Europe.) 10/24/83: Read-Connole's notes show five LAV cell lines "in culture," including LAV/HOS, LAV/Ti7.4, and LAV/HUT-78. (op cit., p. 223); 11/08/83: Dr. Popovic's notes show these entries: "HOS - dead cells HUT-78 cell increase slow Ti7.4 Giemsa: Giant cells multinucleated More in HUT-78RT - Sarang" (Popovic notebook; p. 29) 11/10/83: "HOS- does not grow - discarded Ti7.4 - O.K. viability 70% HUT-78 - O.K. " 65% (op cit., p. 32) 11/11/83: "HUT-78/V cell number 6 x 105/ml Ti7.4/V cell number 4.3 x 105/ml" op cit., p. 32) 11/15/83: "HUT-78/inf. +++ Ti7.4/inf. +++" (op cit., p.33) 11/22/83: "HUT-78/V; Ti7.4/V = MOV." (op cit., p. 34). A critical entry in the above chronology is the entry for November 8, 1983. It is Read- Connole and Popovic's testimony about the events said to have occurred on this date that conclusively links the so-called "MOV" isolate directly to its origins as "LAV." Here is what Dr. Popovic said about the November 8 entries, which he specifically related to "Our work with the MOV isolate": "Following my arrival back in the U.S. ... sometime between November 1st and 4th, we co-cultured patient cells with HUT-78 and Ti7.4. (I think it is most likely that it was patient HM's cells, but as I said, I am not absolutely sure.) On November 8, 1983, I noticed the presence of giant multinucleated cells in both of these cocultures. Aliquots of culture fluids from these cultures were sent to Dr. Sarnagadharan and he detected reverse transcriptase activity in both, the levels of activity being higher in the HUT-78 culture. We then 'scaled up' the HUT-78 culture for further biochemical and serological analysis" (3/4/91 Popovic submission to OSI; "Final Version of Preliminary Responses" pp. 36 - 37." That Dr. Popovic, in the above passage, was referring specifically to the November 8, 1983 entry in his notebook, detailed above, is evident from, among other things, his statement that, on November 8, "I noticed the presence of giant multinucleated cells" (in the putative "MOV" cultures allegedly begun "sometime between November 1st and 4th"). This statement corresponds to the November 8 notebook notation, "Giant cells multinucleated; more in HUT-78." Further, Dr. Popovic's March 1991 statement that "Aliquots of culture fluids from these cultures were sent to Dr. Sarngadharan and he detected reverse transcriptase activity in both" mirrors the notebook entry "RT - Sarang." It is clear that Dr. Popovic, in his March 1991 statement to OSI, was referring to his November 8 notebook entries as entries for "MOV." But the November 8 notebook entries are entries for the LAI/LAV cell lines; proof of this assertion is seen in the fact that the November 8 entries include not only the two cell lines Popovic referenced in his "MOV" statement -- Ti7.4 and HUT-78, but also HOS, the LAI/LAV-infected HOS cell line that was dying (note that Dr. Popovic's November 8 entry says for "HOS," "dead cells"). Only LAI/LAV was used to infect all three of these cell lines, and Betsy Read-Connole's OSI testimony confirms that the notebook entries Popovic invoked as the origins of MOV actually are entries for LAI/LAV. Here is what Read-Connole said about her initial LAI/LAV experiments: "The initial experiment that I set up in October, I kept until he returned [Dr. Popovic]. I guess only three of the cell lines were struggling along by the time he got back ... I believe soon after that the HOS culture died. I believe, he repeated the isolation from mine because mine were pretty well dead or dying when he returned. So, I had done the initial experiment and I kept them while he was gone and then I gave them all back to him ...So, from the second isolation that he did in the HUT-78, he once again saw the giant cell formation like I had been and that was sort of when we decided maybe we should try using HUT-78 for some other isolates" (6/6/90 OSI interview; transcript p. 46). (See Part B2b above , for Read-Connole's subsequent clarification about Dr. Popovic's further work with the cell lines she started in October 1938.) It remains only to be noted that Read-Connole's mention of Dr. Popovic's observation of "giant cells" in the HUT-78/LAV culture, an observation that reportedly led to the decision to "try using HUT-78 for some other isolates" is directly reminiscent of Dr. Popovic's statement, concerning "MOV," that he observed RT in the November 8 cultures, "the levels of activity being higher in the HUT-78 culture," upon which, "We then 'scaled up' the HUT-78 culture for further biochemical and serological analysis" (3/4/91 Popovic submission to OSI; p. 37). In short, it is clear that the November 8, 1983 entries in Dr. Popovic's laboratory notes reflect the point at which the two identities of the single isolate used for the first attempt to infect permanent cell lines -- the identities "LAV" and "MOV" -- overlap. (b) Gallo/Popovic's Explanations: o Gallo/Popovic told OSI that "MOV" originated with patient HM. But the Roche analysis found no HIV in a sample taken from patient HM, and the LTCB's own records show that HM samples and cultures were repeatedly negative in a variety of tests for the presence of virus; o Gallo/Popovic told OSI that the two virus-infected cell lines were retrospectively-designated "MO/Variant" because they were found to be immunologically cross-reactive with HTLV-II, which the LTCB had designated "MO/Virus." This putative cross-reactivity, according to Gallo/Popovic, caused them to "phase-out" the LAI/MOV cell lines and replace them with H9/IIIb. Dr. Popovic also told OSI that his inability to determine the origins of MOV was one of the reasons he, "phased it out as soon as I could ... avoiding its inclusion in any of the publications (op cit,. page 159). Dr. Gallo made a similar assertion, telling OSI, concerning the origins of MOV, "I don't care which virus. I am not going to ask him [Popovic] what is the patient history of every virus. You know, it wasn't something to focus or to care about and MOV doesn't get -- doesn't really play any further role" (5/16/90 interview, page 64). The claims of Drs. Popovic and Gallo that LAI/MOV played "no further role" after approximately the beginning of 1984 are not correct. In the first place, the putative one-way cross-reaction of MOV with HTLV-II early on was shown to be a generic trait of HIV and thus not a unique problem with "MOV." Dr. Popovic told OSI that Dr. Sarngadharan found that, "... even with IIIb one can get such cross-reactivity and I think even RF or so on" (12/1/90 OSI interview; transcript p. 90). Dr. Sarngadharan said the same thing: "Later on we found the same thing with the IIIb and other viruses too, so the original reason for calling it was suspicion of contamination, but it was not true ..." (1/29/91 OSI interview; transcript p. 55). The LTCB scientists actually published the finding of the one-way HIV/HTLV-II cross reaction (Sarngadharan et al., PNAS, 82, 1985, p. 3481). But they were aware the phenomenon was shared by HIV isolates much earlier. Most importantly, Dr. Sarngadharan himself told OSI that when he received LAI/IIIb from Dr. Popovic, he tested this isolate as he previously had tested LAI/MOV, and, "... concluded that the two virus preparations were antigenically similar" (12/1/90 OSI interview; transcript p. 8). In short, there was nothing unique about the MOV/HTLV-II cross-reactivity, and the LTCB scientists knew it early on. Thus, it should not be surprising that the LTCB records show LAI/MOV was used very extensively, for a number of major experiments for many months after the beginning of 1984. Clear evidence of the following such experiments exists: (a) LAI/MOV was sent in large quantities from the LTCB to its contractor Bionetics, where it was used to make the HIV-specific rabbit antiserum and to make and refine the LTCB HIV antibody blood test. (b) LAI/MOV was sent to LTCB contractor Electro-Nucleonics Inc. and to Biotech Laboratories, for large-scale production, by February 1984. (c) LAI/MOV was repeatedly sent from the LTCB contract laboratories to LTCB scientist Dr. Suresh Arya, throughout at least the first quarter of 1984, for use in the LTCB's seminal HIV molecular biology experiments. One particularly important aspect of the experiments with LAI/MOV was the production of the first cDNA probe for HIV. An additional intriguing aspect of the LTCB's LAI/MOV molecular biology experiments is that, in several instances, they were reported to have been performed with "IIIb." Several clones (identified by the letter "C") were produced by Dr. Arya; according to Arya's notes, as confirmed by him, these clones originated with "MOV." But when three of these clones were partially sequenced, they were published in a 1985 paper which describes the "C" clones as derived from a, "... permanent T cell line... infected with pooled blood samples from a number of different patients with AIDS or ARC," a clear reference to the IIIb "pool" (Nucleic Acids Research, 13, 1985, page 8221). When confronted with the obvious question -- why clones derived from MOV were described as having originated with IIIb -- the first author of the paper, Dr. Lee Ratner, told OSI Dr. Arya told him the clones were from IIIb. Dr. Arya (a coauthor of the paper) was unable to explain the discrepancy, and Dr. Gallo said he did not remember ".. being told who, what, when, or from where samples came" for the clones (May 6, 1991 letter to OSI). Another even more significant instance of LAI/MOV experiments reported as performed with "IIIb" is a paper by Arya et al., published in Science in August, 1984 (225, pp. 927-929). Dr. Gallo is a coauthor of this paper, whose senior author is Dr. Flossie Wong-Staal, at the time, the LTCB's senior molecular biologist. Dr. Wong-Staal, according to Drs. Arya and Wong-Staal, actually wrote the paper. There are several significant points to be made about Arya et al. Submitted on May 1, 1984, one week following submission of the Gallo et al. blood test and cell line patent applications, it was the first published scientific paper ever to specifically cite use of the putative "pool" isolate, "IIIb," described as, "... obtained from pooled supernatants of short-term lymphocyte cultures of AIDS patients" (p. 928). The principal point of the Arya et al. paper was to advance the HIV/HTLV-relatedness theory of Gallo et al. To that end, the authors presented results of a series of experiments that, they said, "... support our proposal that this virus ["HTLV-III"] should be classified within the HTLV family" (op cit., p. 929). The putative homology of the AIDS virus with HTLV-I and -II, reported in Arya et al., was illusory. As early as the end of 1984, Gallo et al. were retreating from their earlier homology claims, and by 1988, Dr. Arya frankly acknowledged that the results reported by Arya et al. were obtained only under "non-stringent conditions." Dr. Arya further wrote, concerning the results in Arya et al., that, "Where we may have slightly erred was the interpretation or rather the over-interpretation of the hybridization results." Arya added this: "This was an honest mistake reflecting our insufficient appreciation of the complexity underlying the hybridization reactions and the theoretical basis of the kinetics of hybrid formation and hybrid stability" (12/22/88 Arya-to-Crewdson letter). During the OSI investigation, Dr. Gallo himself described the HIV/HTLV homology reported by Arya et al. as "limited." Dr. Gallo asked Dr. Arya to prepare his own response to queries from OSI concerning the putative HIV/HTLV homology. In his response, Dr. Arya referred to his experiments as "studies attempting to detect relatedness, however distant, of HIV-1 to HTLV-I and HTLV-II ..." (emphasis added). This response indicates there was a preconceived notion on the part of the LTCB scientists concerning what they expected/hoped to find in the homology experiments, as well as a belated recognition that such "homology" as existed was distant indeed. Even more important than the spurious homology data is the fact, discovered during the Subcommittee investigation, that the experiments reported by Arya et al. as performed with the "pool" virus, "IIIb," actually were performed with LAI/MOV. This is a very significant finding, for it is a concrete instance of what had long been suspected, namely, that "IIIb" was not a genuine, independent isolate, but merely a different name for the isolate the LTCB previously called "MOV," itself merely a new name for what was originally called "LAV." Neither Dr. Gallo nor Dr. Arya denied the validity of the Subcommittee staff's findings with respect to the misreporting of LAI/MOV experiments. Instead Gallo and Arya attempted to explain and minimize the significance of the findings. But in so doing, Gallo and Arya opened up new, even more significant concerns about other possible misrepresentations -- whether witting or not -- in the scientific literature. Specifically, in response to questions posed to him in May 1994, by NCI Director Dr. Samuel Broder, relating to the MOV/IIIb identity, Dr. Gallo said this: "Since it [MOV] came from an early Mika isolate in a cell line ... I think he [Dr. Arya] and others in the molecular biology group assumed that it was equivalent to the pool virus, i.e., IIIb, only later realizing their different history." Dr. Arya himself said he had: "... no recollection of the specifics, but the more I think about it the more I feel that when Dr. Wong-Staal wrote our manuscript for the Science 1984 paper, we used the term HTLV-IIIb as a common or generic term for the various preparations that were thought to have originated in Dr. Popovic's laboratory ..." (5/27/94 Arya-to-Gallo memorandum). These explanations only add to the significant, already-existing questions concerning the quality of LTCB research. Even acknowledging the extreme compartmentalization that existed at LTCB, how could the LTCB scientists, including Dr. Wong-Staal herself, have merely "assumed" the equivalence of one sample with another, never even asking the individual from whose work the samples were derived (Dr. Popovic), about their presumed identity? How could such an assumption have so readily been made, particularly considering that: (1) the paper in question (Arya et al.) was the very first paper in which the "IIIb," "pool-derived" isolate was identified as such; (2) prior to, during, and after the preparation of the paper, "MOV" and "IIIb" were clearly distinguished in Dr. Arya's laboratory notes; and (3) the experiments reported in the paper are clearly identified in the laboratory notes as being performed with "MOV"? The "innocent assumption" explanation for the substitution of "MOV" with "IIIb" is belied by an act of apparent deliberate deception, namely, the deletion -- from a chart provided to OSI -- of information showing that Dr. Arya used "MOV" to make the cDNA reported in (at least) the Arya et al. and Ratner et al. papers as derived from "IIIb" (see Part 2 below for more information concerning these matters). The "assumption" explanation also opens up an entirely new area of concern, namely, how far did this erroneous "assumption" extend? How many LTCB scientists made the same "assumption"? How many papers were published reporting putative "IIIb" experiments which in fact were performed with "MOV"? And since LAI, MOV, and IIIb are now proven to be the same isolate, what if any evidence is there to show that any experiments actually were performed with a genuine LTCB prototype, i.e., Dr. Popovic's putative "pool"? Concerning the issue of scientific papers, Dr. Gallo himself, in his June 3, 1994 response to Dr. Broder, said this: "The papers as I saw them simply called the clones IIIb-derived or pool virus derived. Obviously, I assumed they were from IIIb. Some were. Others were MOV derived." The obvious question is how many "papers" is Dr. Gallo referencing here? How many papers reported MOV experiments as performed with IIIb? It also bears mention that according to Dr. Gallo's statement, at some point, Dr. Arya and his colleagues "later realized the different histories" of "IIIb" and "MOV". The obvious questions are when was this realization achieved, and why -- when it was achieved -- was no effort made to correct the literature concerning the misreporting of the putative "IIIb" experiments? As this report is being written, these questions are before the Director, NCI. It remains to be seen how he will deal with them. (d) MOV was provided by Dr. Arya to Drs. George Shaw and Beatrice Hahn, for molecular studies that extended at least into the Summer of 1984. Among these studies were comparisons performed in April 1984 that, according to Dr. Gallo and his attorney, Joseph Onek, indicated "MOV" was genetically identical to IIIb. Dr. Gallo's attorney actually wrote to Subcommittee staff that these experiments showed MOV had been "contaminated by IIIb," but this is a significant misrepresentation of what the experiments showed, and what the LTCB scientists believed they showed. Testimony of Dr. Gallo to OSI, cited by attorney Onek as evidence to substantiate a IIIb/MOV contamination, actually emphasized apparent differences as well as similarities between MOV and IIIb. Leaving aside for the moment the evidence showing MOV and IIIb never were independent isolates, there is a significant inconsistency between Gallo/Onek's claim that the LTCB scientists knew of a "IIIb/MOV" contamination -- in the Spring/Summer of 1984 -- and the fact that over one year later, they published a paper citing comparisons of MOV and IIIb as if they were genetically independent isolates (Wong-Staal et al., Science, 229, 1985). Finally, even if Gallo et al., in April 1984, did believe MOV and IIIb were cross-contaminants, contrary to Onek's assertion, there was no reason to believe MOV had been contaminated by IIIb, and every reason to believe it was the reverse, since MOV existed well before the putative IIIb was isolated. (e) LAI/MOV was sent from Biotech Laboratories to the Frederick Cancer Research Center, in May 1984, apparently for commercial-level production; (f) LAI/MOV (identified only as "HTLV-III") was used in a number of published serological and protein analysis studies conducted by Dr. M. Sarngadharan and his colleagues (see Part A below ). Several of these studies were included in the Gallo et al. HIV blood test patent application; the description of these studies did not identify the virus isolate as MOV, but merely as "HTLV-III," although the patents declared that the "cell line corresponding to the present invention is H9/HTLV-IIIb." Testimony of Drs. Gallo and Popovic shows that, in the case of Dr. Gallo, he knew or had reason to know that MOV could be the IP virus, and in the case of Dr. Popovic, if his testimony is to be believed, he simply did not care. Speaking of Dr. Popovic's experiments that allegedly led to the "isolation" of MOV, Dr. Gallo said this: "See he [Popovic] has got the two positive samples. One is labelled 'LAV' and one has a number on it. And the one with the number on it he thinks is 'HM,' but we cannot prove it... We didn't know what was going on. Whether cross contamination with LAV, whether the culture would last..." (5/10/90 OSI interview; transcript pp. 63). Later in the same interview, Dr. Gallo returned to this theme. Speaking of Dr. Popovic's cultures that eventually were called MOV, Dr. Gallo said this: "Was LAV the same as this new thing? If so did -- you know, would they cross react with HTLV-2? Was the new thing one thing or a mix? Anyway, I have got these two things growing. And he simply called the virus HUT-78 because it was in HUT-78 virus. He didn't know what name to give it." Dr. Gallo added, "My belief is Mika is not certain as to what the origin is" (op cit., pages 70-71). As for Dr. Popovic, when he was asked if he had attempted in 1983-84 to determine the true identity of MOV, he said he had not, and he evinced considerable disregard concerning the identity of the isolates he used in his early experiments, emphasizing instead his singular focus on obtaining a viable, vigorous isolate that he could grow in large quantities: "At that time it didn't matter too much ... as concerning the AIDS virus, what did matter was its growth in high titer that one could work with it. It didn't matter in terms of its precise origin" (6/26/90 OSI interview; transcript p. 160). Practically speaking, Dr. Popovic was right. With respect to the overriding concerns of (1) growing the suspected AIDS virus in large quantities and (2) using the virus to make an antibody blood test, the "precise origin" of the virus, "didn't matter too much." But for purposes of scientific publication and obtaining a blood test patent, a virus of obscure or suspect origins would not do. 2. LAI as "HTLV-IIIb": For purposes of their patent applications and for many publications, Gallo/Popovic claimed the existence of another HIV isolate, designated "IIIb," an isolate said to be derived from a "pool" of ten patient samples. The "evidence" for the existence of the pool consists of Dr. Popovic's word, plus a few cryptic pages of laboratory notes. But as described in the report of the HHS Office of Inspector General, there is reason to doubt that the IIIb "pool" experiment, as described by Gallo/Popovic, really was done, or if it was done, that it ever produced anything other than LAI/LAV. Among the facts that call into question the putative "pool" experiment are the following: (a) The entire rationale for the experiment -- i.e. that by pooling several virus-positive samples, one would boost the titre of the resulting culture -- is belied by what Dr. Popovic actually did. Specifically, Dr. Popovic (contrary to the claims in his May 1984 Science paper and claims in other fora by Dr. Gallo) did not use only RT+ samples for his "pool," neither did he test the putative pool samples for virus (specifically, for RT) before he pooled them. Dr. Gallo himself said, in a memorandum to the NCI's Peter Fischinger during the French/American dispute, that the samples for the pool came from "several patients who showed high RT activity in primary culture" (8/19/85 Gallo to Fischinger memorandum; p.3). In fact, as revealed by examination of the LTCB laboratory notes, most of the putative pool samples were not tested for RT, or if tested, they were found to be RT-. Consequently, Dr. Popovic had no idea if most of the samples he used contained any HIV, and in fact, fully four of them did not. Yet Dr. Popovic reportedly added the virus-negative samples to the pool at precisely the point at which he feared that "... I would lose the culture ..." (early January 1984). Such an action defies rational explanation. (b) The samples -- contrary to the Popovic et al. Science paper and the Gallo et al. cell line patent application -- did not all come from AIDS/pre-AIDS patients. Two of the patients whose samples reportedly were used for "the pool" were diagnosed with hemophilia and one with "chronic lymphatic leukemia." (c) Many of the samples allegedly used for the pool were noted in the LTCB records to be contaminated with mold, one was terminated the same day it allegedly was used for the pool, and for one sample, there is no indication a viable culture was even in the laboratory at the time it allegedly was used. (d) There is no evidence there ever was a "IIIb" isolate independent of LAI/LAV. There are no laboratory data showing the independent existence of a pool isolate and, notably, there is no sample of "the pool" in the LTCB freezers, although samples of all ten putative constituent samples were found. Every "IIIb" sample sequenced by Roche Laboratories was found to be LAI, except for the earliest putative IIIb sample, one dating from February 1984. This sample was found to contain no HIV at all. While it is possible that -- as asserted by Gallo et al. -- this last sample was a mislabelled, uninfected control, it remains the case that the latter-day claim of Gallo et al. that IIIb was "contaminated" by LAI cannot be substantiated because there is no evidence there ever was a IIIb to be contaminated by anything. The affidavits of Dr. Francoise Barre-Sinoussi concerning Dr. Popovic's reported admission that he deliberately used LAV in the experiment that resulted in the putative "IIIb" may explain the anomalies concerning the nonexistent "pool." According to these affidavits, in 1992, Dr. Popovic told Dr. Barre-Sinoussi he combined LAI/LAV with other virus samples to obtain a high-titre cell line, not knowing that LAI/LAV would grow out of the pool. A Chicago Tribune story about the Barre-Sinoussi affidavits reported that Dr. Popovic now denies admitting to Dr. Barre-Sinoussi his deliberate use of LAI/LAV. Yet Dr. Popovic came very close to making the same admission to OSI. Describing his "pool" experiment, Dr. Popovic said this: "If I have a cell line which is virus positive and I take another virus-positive cell line and mix together and put together LAV, is it bona fide experiment? What is difference if I take from one of these flasks, I have two different and mix together, and then I put in one cell line, or I have cell line which is positive and I take the virus and put it there. What is the difference between these two" (6/26/90 OSI interview; transcript pp. 69 - 70). For more information about the putative pool experiment and the alleged result of that experiment -- "HTLV-IIIb -- see Part B below . 3. The HUT-78/HT/H9 "Breakthrough": Dr. Gallo's discovery of how to grow the AIDS virus in quantity occurred when Dr. Popovic used another scientist's cell line (HUT-78; developed by Dr. Adi Gazdar and his colleagues) to grow another scientist's virus isolate (LAI/LAV; isolated by Montagnier et al.). In the process, as was true for the virus, Gallo/Popovic gave the cell line a new name: "HT/H9" -- HT was the parent line, H9 a clone of that line -- giving no credit to the true originators, and thereby, tacitly as well as explicitly claiming the "discoveries" as the LTCB's own. The true origins of the cell line were finally, convincingly, documented in the scientific literature (Mann et al., AIDS Research and Human Retroviruses; 5, 1989, pp. 253 - 255), following an investigation ordered by the Director, NIH. The results of the investigation showed that: "... the original cell line HUT-78, H9 utilized for HIV isolation, and the ATCC versions of these lines are genetically identical and were derived from the same individual" (op cit., 5, Page 254). Dr. Gallo asserted he did not claim the HT/H9 (HUT-78) cell line as an LTCB discovery and that he made reasonable efforts to determine the cell line's origins. But the facts indicate otherwise. Dr. Popovic used a CD4+ T-cell line taken from the LTCB freezers, identified as "HUT-78," in his initial attempts at permanent growth of the AIDS virus, in the Fall of 1983. HUT-78 had previously been provided to the LTCB by the scientist who discovered it and published its derivation, Dr. Adi Gazdar. The cell line originated with a patient diagnosed with Sezary Syndrome, a type of lymphoid leukemia. Shortly after his initial successful experiments growing LAI/LAV in HUT-78, Dr. Popovic cloned the parental cell line on two separate occasions (November 1983 and January 1984), reportedly for two reasons: one, to ensure that the cell line did not harbor any contaminating virus, particularly HTLV-I, and two, to obtain single-cell clones that would maximize the growth of the AIDS virus. These experiments produced over 50 clones, of which Popovic selected the eight "best growers" for use in his "HTLV-III" experiments. "H9," reported to be the best growing of the clones, was obtained in January 1984. Meanwhile, Dr. Popovic renamed the parental cell line, changing the name from "HUT-78" to "HT." The principal reason offered for the change is that Popovic was uncertain that the cell line in which he succeeded growing the AIDS virus was the authentic HUT-78. Subsequently, beginning in the Popovic et al. May 1984 Science paper, and in numerous papers and public speeches, as well as numerous legal briefs, Gallo et al. and the U.S. Government represented "HT" and its H9 clone, as new, "breakthrough" discoveries of the LTCB. Another major theme of the claims by Gallo et al. and the U.S. Government was that the putative "discovery" of the cell line enabled the "isolation" of the LTCB's prototype HIV isolate, which was followed immediately thereafter by the development of HIV-specific reagents and the HIV antibody blood test, all this beginning in the Fall of 1983. These claims, in significant respects, are contradicted by the facts. (a) Claims that HT/H9 Was "New": Statements claiming credit for the "discovery" of HT/H9 appeared first in 1984, in the Popovic et al. Science paper. The published version of the paper contained this description of the cell line in which Popovic grew the AIDS virus: "One neoplastic aneuploid T-cell line, derived from an adult with lymphoid leukemia, was found to be susceptible to infection with the new cytopathic virus isolates. This cell line, termed HT, has produced HTLV-variants in sufficient quantities to permit the development of specific immunological reagents and nucleic acid probes..." (p. 498). The Popovic et al. paper further described the cell line as a "new immortalized T-cell population" and said the cell line was "found" by Popovic and Gallo (emphasis supplied). The evolution of the cell line description through successive drafts of the Popovic et al. paper is informative. Early drafts of the paper correctly reported the cell line, not identified, as originating "from a patient with mature T-cell malignancy (Sezary Syndrome)..." In draft 3, the reference to the patient's diagnosis as "Sezary Syndrome" was dropped; inserted in its place was an obscure reference to a "mature T-cell malignancy." In draft 4 of the paper, Dr. Gallo made an important change that significantly misrepresented the cell line, making it appear to be a de novo discovery, i.e. the addition of the word "new" to the sentence, "We report here the establishment and characterization of a new immortalized T-cell population which is susceptible to and permissive for HTLV cytopathic variants." Finally, in draft 7, the name "HT" was introduced for the cell line. Lest there be any doubt as to whether Dr. Gallo was claiming the cell line as a discovery of the LTCB, his words at the Beecham symposium, delivered shortly after submission of the Popovic et al. paper, bear mention. On this occasion, Dr. Gallo said this: "The breakthrough occurred for us when we learned how to transmit this [the AIDS virus] to a particular cell line developed in our lab. That happens to be H4 [another "HT" clone], a new line" (emphasis added; 4/5/84 Beecham "Symposium on Infective Agents and Their Effects"). The origin of "HT/H9" was obscured even further in December 1984, when Drs. Gallo and Popovic published an important letter in The Lancet, a letter that presented comparative data for several different T- and B-cell lines, with respect to their ability to support growth of the AIDS virus (The Lancet, 1984, pp. 1472-1473). In the December 1984 letter, "HT/H9" were distinguished from HUT-78, as if they were distinct, independent cell lines. HT/H9 were even described as originating from a patient with a different clinical syndrome than that of the HUT-78 patient. At the same time as Gallo/Popovic obscured the HUT-78 origins of H9, Dr. Gallo withheld H9 from a number of scientists who sought to obtain it (see Part A below). HUT-78 was freely available to scientists through the American Type Culture Collection (ATCC), where it was deposited in 1981. But, scientists seeking H9 were not able to avail themselves of this ready access because they did not know H9 was HUT-78. The combination of these circumstances led the Richards committee to make these observations: "... the so-called HTLV-III virus was thus established and introduced to the world with no reference to or discussion of two crucial facts ... the cell line utilized [HUT-78] was one that had been obtained from the Minna laboratory [Dr. Minna was Dr. Gazdar's laboratory chief] ... Although others could have obtained HUT-78 from the ATCC ... the essential identity of HUT-78 with H9 had been effectively obscured" (2/19/92 Richards-to-Healy; p. 3). Dr. Gallo seemed to feel that the true identity of the "H9" cell line was a non-issue. Speaking to Science magazine, Dr. Gallo said this: "The fact is I never really thought it was important. And quite frankly, I still don't and I don't understand the people who do." Dr. Gallo also said, concerning the discovery of the cell line: "I don't consider it so brilliant. In my mind, there is no credit for a cell line. If it happens by accident you have a cell line, so freaking what?" ( Science, 248, 1990; p. 1507). (b) Claims of a November 1983 "Breakthrough": As for the erroneous claims about when the "discovery" of H9 took place, these claims appeared principally in various legal briefs filed during the French/American dispute, including Dr. Gallo's sworn declaration. The claims invariably advanced by several months when the purported "H9 breakthrough" occurred. Thus, in the Opposition by Gallo et al. to the Motion for Judgment of Montagnier et al., submitted by DOJ attorneys to PTO in November of 1986, there appeared this passage: "By the fall of 1983, Popovic had developed such a line [a permanent cell line] using H9 cells" and ".. once the permanent cell line for HTLV-III was developed, HTLV-III was produced in substantial amounts and used to prepare reagents for testing against AIDS sera ..." (Emphasis added; Page 14). The statements in the U.S. Government motion mirrored statements in Dr. Gallo's November 8, 1986 sworn declaration, which was appended to the motion: "... in the fall of 1983, Dr. Popovic discovered that a few cell lines but in particular a cloned cell line, designated H9, was resistant to the retrovirus and could be effectively used to produce the virus in relatively large amounts of a consistent composition. Dr. Popovic accomplished this by November, 1983 ..." (Page 7). Dr. Gallo later would claim that his references to H9 were in error, that he meant to say "H4." Gallo's attorney, Joseph Onek, was quoted in Nature saying that: "... some references to the 'H9' cell line -- one of the most successful lines for growing the AIDS virus -- are actually describing an earlier cell line known as 'H4'" (11/14/91). According to Onek: "... this was a mistake that does not significantly change the conclusion of the declaration or the basis of the agreement." But Gallo/Onek's claims that the H4/H9 discrepancy was merely an isolated error, and not significant at that, are not credible. The claim in Dr. Gallo's declaration that H9 was developed in November 1983 was not an isolated occurrence; Dr. Gallo repeated the claim again and again, including in a formal submission to OSI, in 1990, which Gallo also forwarded to NCI Director, Dr. Samuel Broder. In this submission, titled "History of HIV-1 Detection and Isolation ...," Dr. Gallo represented that both the H4 and H9 clones were developed at the LTCB in November 1983. Dr. Gallo's claim that H9 existed and was infected with the AIDS virus in November 1983 was a material misstatement related to some of the central themes of his declaration, including the claim that Gallo et al. made the breakthrough discovery that led directly to their HIV antibody blood test in the Fall of 1983. But Dr. Gallo's prototype isolate, IIIb, the virus Gallo et al. said "corresponded to" their blood test invention, did not even exist in November 1983, neither was it used to infect the H9 cell line until at least late January 1984. The false claims in the U.S. Government pleadings were anticipated by equally false statements in documents generated by Dr. Gallo and his colleagues at the outset of the patent dispute, in the Summer of 1985. Dr. Peter Fischinger, in his August 1985 report to Lowell Harmison, described "HT" as a "relative" of HUT-78, a relative "developed by Dr. Gallo." Dr. Gallo signed an affirmation that the Fischinger report had been reviewed for accuracy by him and were substantiated by LTCB data (see below ). Dr. Gallo himself wrote to Dr. Fischinger that Dr. Popovic "... developed the H9 clone in early November 1983" (9/23/95 memorandum, page 5), even though Dr. Gallo knew from a September 6, 1985 memorandum from Mikulas Popovic that the final cloning of "HT" and the subsequent infections of the clones did not take place until January 1984. In the September 6 memorandum, Dr. Popovic also said that H9 represented, "... a single cell clone obtained by limiting dilutions from a continuously growing T-cell which we originally thought to be HUT-78" (emphasis supplied). Dr. Popovic described the putative confusion at the LTCB concerning the actual identity of the cell line, and he added this: "Since primary non-cultured HUT-78 cells are not available, we cannot make a definitive conclusion whether the designated HT cells are identical with the original HUT-78 or not." This statement was not true, since Dr. Popovic at any time could have obtained primary HUT-78 from the ATCC. Dr. Popovic never made this effort, because, he said to OSI: "I don't consider so exciting the work aimed at tracking down precisely the origin of HUT-78 cell lines each time" (6/26/90 interview; transcript page 183). Similarly, in a January 1991 response to OSI queries, Dr. Popovic said this: "... I did not consider it my responsibility to work out the confusion surrounding HUT-78..." (p. 9). Dr. Popovic's September 6, 1985 memorandum also stated that "The detailed characterization of the clone, H9, is being prepared for publication and its comparison with HUT-78 cells ... will soon be performed." But, continued the memorandum, "In any case, why would anyone care." A draft of the memorandum bearing handwritten notations by Dr. Gallo shows that this sentence was added by Dr. Gallo himself. (c) H9's Hidden Defect: One other matter relating to the H9 cell line needs to be mentioned; the defect had a significant, deleterious impact on the HIV blood tests licensed under the Gallo et al. blood test patent. Both this patent and the two Gallo et al. cell line patents described H9 as, "... a representative and preferred (cloned) cell line in accordance with the invention." But H9 had an inherent defect that made it particularly problematic for use in a virus antibody blood test, i.e., the presence of HLA Class II antigens, which can cause significant numbers of false positive readings in an antibody blood test. By the Summer of 1985, problems with H9 false positives had become a significant concern for blood banks and the companies that manufactured the LTCB HIV antibody blood test. A significant proportion of the blood that tested HIV+ by the LTCB ELISA appeared to represent false positives. This meant that large quantities of blood were being needlessly discarded. It also meant that blood banks were having to perform a large number of the more costly Western blot confirmatory tests, in an effort to determine the actual HIV status of blood donors who initially tested positive. During 1985, the LTCB scientists published at least two papers referring to the H9 false positives problem. Dr. Popovic told OSI, concerning the second of these papers: "We considered important to stress using the confirmatory (Western blot) assays, because of HLA class II [the defect that caused the H9 false positives]. It was important" (6/26/90 OSI interview; transcript p. 184). But Dr. Popovic, and possibly other LTCB scientists as well, knew about the H9 problem long before the 1985 papers were published, possibly even before the submission of the first of the patent applications that described H9 as "preferred." Here is what Dr. Popovic told OSI concerning this matter: "H9 is a mature T cell. It has characteristics very similar to ATL cells ... It has Class II antigens ... "At the beginning we favored this cell line [H9] because of pressure to have a source of virus as soon as possible for the blood bank assays. Later I was not favoring it and I was not favoring it for a simple reason. When the viral budding occurs it takes also HLA-II with it, so the viral prep has also Class II antigens, cellular antigens. So that means if individuals let's say, got blood transfusion in the past, it can have a false cross-reactivity with the virus in ELISA. This reactivity does not have anything to do with the AIDS virus (HIV). The companies worked hard to establish negative controls ... "At the beginning the H9 was pulled out because of the speed. However, they (Mr. Roberts, patent attorney) told us that we can come later with other T4 cell lines ... The virus which would be produced from such cell lines, for instance, as Molt 3 which doesn't have Class II antigens, gives far less unspecific cross-reactivitiy in ELISA" (6/26/90 OSI interview; transcript pp. 176 - 178). Gallo et al. did submit a "continuation-in-part" (CIP) application to their cell line patent application. In the CIP application, Gallo et al. named several cell lines other than H9 that could be used for growing the AIDS virus. This CIP was submitted in August 1984; one of the cell lines identified was Molt 3, the cell line identified by Dr. Popovic as preferable to H9. "HTLV-III/Molt 3" was deposited at the ATCC. But even in the CIP, even recognizing the defect in the H9 cell line, Gallo et al. still said that, "H9 is a representative and preferred cell line in accordance with the invention." Like the parent application, the CIP application made no mention of the H9 defect and the resulting false positive blood test results. IV. EVENTS LEADING TO THE APRIL 1984 HHS ANNOUNCEMENT During the end of 1983 and through the first quarter of 1984, the LTCB made considerable progress in its work with the AIDS virus, virtually all of it with LAI (as LAV, then as MOV and IIIb). By mid-December 1983, Dr. Popovic was attempting to grow a small number of authentic LTCB isolates in the HUT-78 cell line, based on his successful experience with LAI. Several of these other isolates eventually were established in permanent cell lines. Some were published in the May 1984 Science paper by Popovic et al. But nothing grew in permanent cell lines as well as did LAI. A. Further Work with LAI/MOV During December 1983, work on LAI/MOV moved into high gear. Dr. Popovic's notes show that in December 1983, he sent substantial quantities of MOV to LTCB collaborator Dr. M. Sarngadharan. Sarngadharan performed early protein chemistry experiments with LAI/MOV, the results of which, he told OSI, were "extremely exciting," proving to him that MOV was a new retrovirus (5/10/90 Gallo submission to OSI, Exhibit 5, p. 1). In January 1984, Sarngadharan's associate, Dr. Jorg Schupbach, performed experiments with LAI/MOV that, according to a letter from Dr. Schupbach to OSI, showed him that MOV "had to be the AIDS agent" (10/05/90 letter to OSI, p. 2). In late-December 1983, MOV was used to inject a rabbit, with the objective of producing the first HIV-specific reagent. The experiment succeeded, and by late-February, the resulting hyperimmune rabbit antiserum was available for use to test LTCB samples for the presence of the suspected AIDS virus. (As noted previously, there is compelling evidence that the first cultures so tested were the two LAI/LAV cell lines.) According to Dr. Gallo's own submission to OSI, LAI/MOV was used to raise the rabbit antiserum until June of 1984, when it reportedly was replaced by LAI/IIIb. This circumstance is telling evidence that the allegedly problematic HTLV-II cross-reaction observed with "MOV" -- if it actually occurred -- was not a hinderance to the continued significant use of MOV at the LTCB. Thus, the putative cross-reaction is not a credible explanation for the LTCB scientists' failure to report the existence and use of MOV, and for its alleged "replacement" with IIIb. Besides the rabbit antiserum, LAI/MOV also was used as the source of the antigen for the LTCB HIV antibody blood test. Dr. Sarngadharan reportedly initiated the LTCB ELISA on January 6, 1984, using "MOV" as the source of the antigen. (Note, however, that the antigen source is not identified in the laboratory notes. Dr. Sarngadharan's instructions to his technician describe the source of the antigen merely as "the virus we had been analyzing." According to Dr. Sarngadharan's testimony to OSI, by January 20, 1984, he had fine-tuned the LAI/MOV ELISA to the point that it was "extremely specific and sensitive" for the AIDS virus (5/10/90 "MOV" Submission to OSI; p. 3). (The blood sample used as the standard for AIDS/pre-AIDS in the initial ELISA testing at the LTCB was identified as "LAV." Presumably, this was the BRU serum received from Dr. Montagnier shortly before, in December 1983.) Notwithstanding Dr. Saragadharan's claim about the performance of his blood test as of January 20, 1984, by Dr. Gallo's own testimony, it was not until February 29, 1984, that "the critical serology" (the "Guroff Panel" of sera) was performed. The ELISAs performed on this date were done using LAI/MOV as the antigen. According to Dr. Sarngadharan's testimony to OSI, concerning these assays: "When the test results were analyzed and the code was broken in Dr. Gallo's office he was convinced as I was that we had a reliable test" (5/10/90 "MOV" submission to OSI, Exhibit 5; p. 4). Meanwhile, in January and February 1984, LAI/MOV was sent to two LTCB contract facilities for large-scale production. The contractors in turn provided MOV to the molecular biologists at the LTCB, who used it to, among other things, develop the first cDNA probes for HIV. As previously described, these experiments were reported in at least two papers published by the LTCB scientists to have originated with the "pool" virus IIIb (see Part C1B above). B. Work Reportedly Done with "HTLV-IIIb" 1. Origins of H9/IIIb: As late as January 2, 1984, six-to-seven weeks after the claimed initiation of the "pool" culture on November 15, 1983, the culture, by Popovic's own account, was showing signs of an imminent demise. These circumstances came about despite one reported reinoculation of the culture with fresh material from the same three samples used to start the culture and despite an unknown number of refeedings of the culture with fresh HUT-78 cells. According to Mikulas Popovic, the "pool" culture was, "... not well established ... and I was afraid that I would lose the culture. Therefore, I told myself, oh good god, I won't have it .... So it was a fear behind it, I would say, that I would lose the culture .... So what I tried to save the culture was to reinfect it again" (6/26/90 OSI interview; annotated transcript p. 84). Dr. Popovic reportedly added another seven samples to the pool, most of which, contrary to Dr. Gallo's claims of high RT activity, had never even been tested for RT. Dr. Popovic himself described this as "Obviously ... more or less a blind experiment" (op. cit., p. 103). Yet just two and a half weeks after Popovic's dramatic, last-ditch effort to save the "pool" culture, by Gallo/Popovic's own accounts, the "pool" culture was used to infect the eight "best-growing" clones of the HT (HUT-78) cell line, most notably H9. According to Gallo/Popovic, this cell line became the LTCB prototype HIV cell line, "H9/HTLV-IIIb," and on March 6, 1984, virus from this cell line reportedly was substituted for LAI/MOV as the source of the antigen in the LTCB HIV antibody blood test. Thereafter, according to Gallo/Popovic, this cell line became the centerpiece of the May 1984 Popovic et al. Science paper. But the LTCB laboratory notes and the Popovic et al., paper do not substantiate the reported progression of events concerning "HTLV-IIIb." In fact, the records, insofar as they exist, are remarkably ambiguous and confused, and thus, susceptible to many different constructions. The designation "IIIb" does not appear anywhere in the Popovic et al., May 1984 Science paper, nor for that matter, in any of the Science papers published on the same occasion. Yet other isolates, e.g., "RF," "SN," "BK" are identified by a unique designation. Correspondingly, the experiment that allegedly resulted in the isolation of "IIIb" is described only in very general terms that might describe a "pool," but could equally well describe the culturing of individual isolates. In particular, there is no mention of a "pool," neither is the concept or rationale of pooling described in any manner whatsoever. It is noteworthy that the obscure description of the experiment that does that appear in the published paper was nowhere to be found in the paper when it first was drafted by Mikulas Popovic. In fact, the first approximation to the published version did not appear until draft #7 of Popovic et al. The designation "IIIb" also does not appear in any LTCB laboratory notes before April 12, 1984. The designation "IIIb" does appear in the Gallo et al. blood test and cell line patent applications (submitted April 23, 1984), and it appears in records of Biotech Laboratories, the LTCB contractor that reportedly grew up IIIb in large quantities for transmittal to the Frederick Cancer Research Center, for mass production for an HIV-antibody blood test. But the only Biotech document substantiating the putative IIIb transfer to Frederick is a laboratory technician's calendar, containing an April 9, 1984 "IIIb" entry written over another entry that cannot be deciphered. At the Frederick facility, laboratory notes record the sample that was received merely as "HTLV-III," the generic name Gallo et al. used for the AIDS virus, and not "IIIb," the alleged "pool" virus. Notably, according to testimony of both Biotech and Frederick scientists (Drs. Robert Ting and Larry Arthur, respectively), the alleged "IIIb" virus culture came close to dying shortly after it was shipped to Frederick, leading to a request to Biotech to supply more virus. Shortly after this request, according to Biotech records, Biotech shipped to Frederick a large quantity of LAI/MOV. 2. Chaos in LTCB "IIIb" Records: The confusion in the LTCB records concerning the claimed existence and use of "IIIb" is reflected in Dr. Gallo's own OSI testimony. According to Dr. Gallo, the "pool" virus was given numerous other designations prior to the "IIIb" designation, including these: "HT/pool," "HTLV-A," "HTLV-AIDS," "HT/III," and "HTLV-III" (4/17/90 submission to OSI on "HTLV-IIIb; "Response to Question 3; Page 1.) There is no independent evidence to support the assertion that all these designations actually referred to the "pool" isolate. In fact, there is considerable confusion about the meaning of "HTLV-A," and there are strong indications that Dr. Gallo used the term as a generic one to encompass all AIDS virus isolates, not to designate the "pool" isolate in particular. Dr. Gallo first used the term "HTLV-A" on March 5, 1984, in a letter to the editor of The Lancet. In this letter, Dr. Gallo referred to his "very very exciting patient serological results" with a suspected AIDS virus, and he said, "We are debating whether to call them HTLV-III or HTLV-A (A=AIDS)" (emphasis added). It was not until much later, in fact, as late as April 25, 1984, that Dr. Gallo finally made the decision to forego "HTLV-A" in favor of "HTLV-III" as a generic team to designate the AIDS virus. On April 25, Gallo wrote to Dr. Robert Downing of Wiltshire, England, stating that, "I am now confident that HTLV-A is, in fact, the cause of AIDS." Above "HTLV-A," Dr. Gallo wrote, by hand, "(HTLV-III)," with an asterisk to a footnote below, that read as follows: "We decided to keep the trend of the previous nomenclature so it is HTLV-III." Thus, there is consistent evidence that Gallo used "HTLV-A" as a generic term for the AIDS virus, and there is no evidence to support Gallo's claim that "HTLV-A" referred uniquely to the "pool" isolate. Similarly, Dr. Popovic also used the term "HTLV-A," in the first draft of the Popovic et al. paper, to describe the isolate that was featured in Figure 2A of the paper. In subsequent drafts, "HTLV-A" was struck out and replaced with "HTLV-III." As if this were not confusing enough, there is also the curious matter of "HTLV-IIIA," a designation used for both the putative pool virus and MOV. Dr. Gallo mentioned the "IIIA" designation in his book Virus Hunting, where he said of HTLV-IIIb that, "... the 'b' simply stood for the fact that the sample [the putative "pool" sample] was split into portions, A and B" (page 181). In an OSI interview, Dr. Gallo gave a somewhat different account. Referring to Dr. Popovic's work with the "pool" virus, Dr. Gallo said, "HTLV-IIIA" "... is probably the other part of the pool." Responding to a question about what he meant by "the other part of the pool," Dr. Gallo said this: "He had aliquots. He had two aliquots. One aliquot was 'A' and one was 'B' that he used to infect different clones of HT. It turned out that clones of the 'B' went into H9. H9 was better. So arbitrarily 'B' became the producer" (4/26/90 interview; transcript page 114). Responding to a question about what happened to "HTLV-IIIA," Dr. Gallo said, "Well, 'A' wasn't as good. He just didn't continue with it. The clones that 'A' was used -- 'A' was used ... to infect ... those clones didn't do as well as H9 did, and so H9 was chosen and H9 happened to be this hand instead of this hand, and he called it 'B' as opposed to 'A'" (op cit., page 114). In a subsequent interview, Dr. Gallo said that: "HTLV-A or HTLV-AIDS are early designations for virus from the pool, later named HTLV-IIIa and HTLV-IIIb. B was the one that grew best in H9 eventually and became more standardized" (7/25/90 OSI interview; transcript p. 4). These statements by Dr. Gallo are discrepant with the evidence. Dr. Gallo's claim that "IIIa" did not produce well and was discontinued does not square with the fact that "H4/HTLV-IIIA" was given out to other scientists, e.g., Dr. Robin Weiss, at least as late as the Spring of 1984. Moreover, "HTLV-IIIa" as well as IIIb was specifically cited in a Gallo et al., CIP patent application, submitted in August 1984. This application said that: "... a DNA fusion has led to the conclusion that there are at least two definite fractions to the HTLV-III, namely HTLV-IIIA and -IIIB, particularly susceptible to use by the present assay test kit procedure of the present invention" (Application for United States Patent: "Method and products of immunological test kits useful in assaying retroviruses such as HTLV-III," Serial Number 643,715, page 2). Subsequently, in November 1985, additional claims were incorporated into the "715" patent application, including two claims specifically citing use of "HTLV-IIIA." In short, contrary to Dr. Gallo's claims to OSI, all indications are that "HTLV-IIIA," whatever it was, was not discontinued. Moreover, evidence from several different sources indicates that "HTLV-IIIa," which Dr. Gallo repeatedly said was part of "the pool," and "MOV," the allegedly independent isolate, were one and the same isolate. Provocative testimony and evidence were obtained from Biotech Laboratories, the LTCB contract laboratory that received samples labelled "MOV" and "HTLV-IIIa" and "IIIb" for large-scale production. Dr. Robert Ting, the founder and former President of Biotech, also the scientist who personally initiated the large-scale production of "IIIb" at Biotech, told the OSI that, "... in later freeze cultures (at Biotech) we call H9/MOV is HTLV-IIIa" (2/21/91 OSI interview; transcript page 9). In response to a follow-up question, Dr. Ting reiterated his information: "... in our lab we call HTLV-IIIa so when we tell the technician to grow HTLV-III, which do you want to grow, 'a' or 'b.'" Asked if "HTLV-IIIa" was "MOV," Dr. Ting responded "yes." Dr. Mark Manak, in 1991 the Senior Vice President at Biotech, confirmed Dr. Ting's testimony. Dr. Manak told OSI, in a June 24, 1991 letter, that, "The samples we received from Dr. Gallo's lab were labeled MO(V) and we retained that designation in our records. Our understanding was that this represented a culture of HTLV-IIIA in H4 cells." Dr. Manak further said that, "Our understanding was that HTLV-IIIA and HTLV-IIIB were different cultures and were to be handled separately." The Biotech laboratory records confirm the nomenclature described by Drs. Ting and Manak. A Biotech freezer log entry identified "MOV," frozen 2/29/84, as "= (H4/HTLV-IIIA)." A separate entry in the freezer log was identified as "HTLV-IIIA," said to have been frozen 3/28/84. Dr. Manak told OSI that both the 2/29/84 and 3/28/84 freezes were HTLV-IIIa cultures, with the latter "... possibly in different host cells" (June 24, 1991 letter to OSI). And in 1994, Dr. Ting provided even more definitive evidence concerning the identity of MOV and "HTLV-IIIA." In a June 13, 1994 letter to Dr. Gallo, elicited by Dr. Gallo when NCI Director Dr. Samuel Broder required him to provide evidence about the origins of MOV, Dr. Ting said this: "... I received MOV about a month before I received HTLV-III. Later LTCB designated HTLV-III as HTLV-IIIB. At the time of cryopreserving HTLV-III, I have told the technician to footnote in her log book MOV = HTLV-IIIA to distinguish it from HTLV-III." Finally, there is evidence originating with LTCB scientist Dr. Suresh Arya showing that Dr. Arya believed "HTLV-IIIa" was another name for the isolate previously named "MOV." In September 1986, at the height of the blood test patent dispute, Dr. Arya prepared a list of 1984 entries from his laboratory notes in which he received samples and labelled them as "LAV." Dr. Arya claimed to OSI, as did Dr. Gallo to the United States Government attorneys, that he never worked with the actual LAV isolate from Institut Pasteur, and used the term "LAV" generically to designate the AIDS virus. However, there is at least one notebook page, not provided to OSI, that shows Dr. Arya, on May 6, 1984, was working with "LAV cDNA [Paris]." Dr. Arya confirmed to Subcommittee staff that this notebook page was his, but he claimed he did not remember the experiment. Dr. Arya also said he did not know why the notebook page was not provided to OSI. The Subcommittee staff was not able to obtain any additional information concerning this matter.) Particularly relevant to the present discussion is this entry from the September 1986 Arya list: "Notation on June 28 -- Mika if LAV (MOV) should be HTLV-IIIA; on Aug 8 - Mika, if cells should be HT cells infected with HTLV-IIIA/MOV." The above entry, along with numerous other entries, was deleted from Dr. Arya's list before it was provided to OSI. The fact is that, at best, the designations "MOV," "HTLV-IIIA," and "IIIB" were hopelessly confused in the laboratory notes at the LTCB. In many instances, these terms were used interchangeably. These circumstances cast significant doubt on the claim that MOV and the "pool" isolate were genetically distinct. The Roche Laboratories revelation that both "IIIb" and "MOV" are the IP virus LAI conclusively refutes the claim. C. Subsequent Claims by Gallo/Popovic about Their "Breakthrough" Discoveries During the French/American dispute, Drs. Gallo and Popovic made a number of significant claims about their "breakthrough" discoveries in AIDS research, many of which appeared in the popular and scientific media, as well as (in Gallo's case) in legal briefs filed on behalf of the U.S. Government, which erroneously dated the LTCB discoveries to late 1983, were incorrect and significantly incomplete, and thus, were significantly misleading. The incorrect claims concerning the "discovery" of H9 have already been discussed. Other incorrect claims concerned when Gallo/Popovic "isolated" HTLV-IIIb, the "pool" virus, and when the LTCB HIV antibody blood test was developed. Claims such as these appeared in, for example, the same November 1985 article in Science magazine, previously cited, reportedly based on interviews with Gallo and Popovic, and containing their unqualified assertions that they were not able to grow LAV. According to the article, when Dr. Gallo realized that the new retrovirus he had detected was, "... killing the cells it infected, he began to look for cells that would resist its cytopathic effects. He found what he was looking for in early November." The article went on to say that: "Popovic discovered that clones developed from a line of T cells established from a leukemia patient could be infected with virus from the cells of AIDS patients and go on producing virus indefinitely ... Because virus from some patients appeared to infect the cell line more readily than others, Popovic ... pooled virus isolates from 10 patients and used the mixture to infect the cells. By December,, Gallo's lab was mass-producing virus from a cell line, called H9, infected with virus from the pooled samples" (emphasis added; Science, 230, November 1985, Page 521). The November 1985 Science article continued: "This breakthrough enabled Gallo's group to characterize the virus ... Equally important, mass production of the virus opened the way for development of a sensitive test ... to detect antibodies to the virus in blood samples. The test nailed down, to almost everybody's satisfaction, that the virus was the cause of AIDS." The article then quoted Dr. Gallo directly: "'The data poured in in December and by January we had solved the problem [of the cause of AIDS],' says Gallo" (emphasis added; op cit., Page 521). The evidence presented in this report shows that these claims were not true. Gallo et al. were not "mass-producing" H9/HTLV-IIIb by December; neither the H9 cell line nor the putative IIIb isolate even existed by that time. Nor did the data "pour in" in December -- the LTCB blood test was not even reliably adjusted until late-January, and it was not used for definitive serology on blind samples until late-February. Moreover, what was not revealed by Dr. Gallo was the fact that the only isolate in large-scale production before late-January 1984 was LAI/MOV/, and all the serology prior to March 1984 was based on MOV. That the untrue statements attributed to Gallo/Popovic by Science magazine were not "misquotes" or due to some other journalistic failing is seen in the fact that Dr. Gallo repeated the same claims again and again, always moving events that occurred well into 1984 back to the Fall of 1983, always implying that key experiments were performed with LAI/IIIb, when most actually were performed with the mystery isolate, "MOV," always exaggerating his understanding of the significance of the data at the time they were actually obtained. o Dr. Gallo claimed, at the April 1984 HHS press conference that he had been "mass-producing" the AIDS virus for six months. Further, he said, "I was developing reagents over that period of time to go back and do the analyses." This claim would date the beginning of "mass production" at the LTCB to late October. But the only AIDS virus isolate Gallo, et al., even had in a permanent cell line six months prior to the press conference was LAI/LAV, the isolate Dr. Gallo said for years he could not grow. Moreover, even LAI/LAV was not "mass produced" for six months prior to the news conference, and it was not until December 1983, two months later, that LAI under the name, "MOV" was produced in anything even approaching large quantities. o Dr. Gallo told a February 1985 meeting of the NCI Division of Cancer Treatment (DCT) Board of Scientific Counselors that an HIV blood test "was ready in December 1983" in his laboratory. o As late as November 1986, Dr. Gallo was repeating the same claims, this time to a meeting of scientists at the Royal Postgraduate Medical School in London. According to New Scientist: "Gallo says that by the end of December 1983, he had enough virus to show that AIDS patients had antibodies to it" (February 12, 1987, p. 54). Concerning the meeting in London, New Scientist reported this: "... Gallo said that the results of his test at this time (December 1983) were 'unambiguous evidence that this [virus] and this alone was the cause of AIDS'" (op cit., p. 54). D. The "CDC Data" During the first half of 1984, Gallo et al. continued to refine their HIV antibody ELISA test. The ELISA tests developed by the IP and LTCB became the first-stage (screening) tests employed by blood banks world-wide. Dr. Gallo had known since at least the previous autumn about the IP blood test. In mid-March 1984, Dr. Gallo obtained important information about the performance of the LTCB test and about the IP test as well. The information came from the Centers for Disease Control (CDC) scientist, Dr. James Curran. Dr. Curran had previously sent Dr. Gallo a panel of over 200 sera for blind testing with the LTCB HIV antibody blood test. On March 12, 1984, Dr. Curran met with Dr. Gallo and his colleague Dr. Sarngadharan to "break the code" to determine how accurate the LTCB test was in detecting antibodies to the suspected AIDS virus. Dr. Gallo frequently recounted the meeting with Dr. Curran, asserting that Curran told him the LTCB results were "clear-cut" and that, in Curran's view, Gallo and his colleagues "had determined the cause of AIDS" (4/30/86 Gallo "History of Key Events ..."; 11/8/86 Gallo sworn declaration). But Dr. Gallo's accounts of the meeting with Dr. Curran were highly selective. What Dr. Gallo invariably failed to say is that the LTCB test scored only 48 percent positive in AIDS patients in the CDC tally. (Handwritten tallies by Dr. Curran and another scientist, dated contemporaneously with the meeting, confirm this figure.) Several subsequent tests by Gallo et al. of other large serum panels were no more impressive, e.g., in May 1984 and June 1984, the LTCB test scored only 40 percent and 47 percent positive in sera panels provided by Drs. David Ho and Bijan Safai, respectively (the latter data were published in The Lancet in June 1984 -- see below). Since the HIV blood test was in its developmental stages, these low figures would not be particularly remarkable, were it not for the fact that on numerous occasions, the United States Government and Dr. Gallo himself criticized the IP test for its early AIDS detection rates in the 40 percent range, e.g., "... serum samples from 37.5 percent of patients with AIDS were found to react with it [LAV]" (Popovic et al., Science, 224, 1984, p. 500); "Even in July 1984, the LAV- containing test systems picked up only 41% of AIDS patients" (Fischinger-to-Harmison memorandum; August 27, 1985, p. 9); and "... as late as July 1984, Montagnier reported only about 40 percent positives with his composition" (Submission of Motions by Gallo et al., October 1986, p. 4.) It also bears mention that Dr. Gallo invariably cited the June 1984 Safai et al. paper (The Lancet, 1984, pp. 1438-1440) as an instance of 100 percent accuracy of the LTCB blood test. But this figure was achieved only by combining both the LTCB ELISA and Western Blot (a confirmatory test), using the latter test to assay all samples negative by ELISA, a practice directly opposite the practice in blood screening clinics, where ELISA+, not ELISA- samples are subjected to confirmatory testing. Even more important, what Dr. Gallo invariably failed to reveal about the meeting with Dr. Curran is that Curran told him CDC had sent many of the same sera tested by Gallo et al. to the IP scientists, for testing with their LAV antibody blood test. The IP blood test scored as good or better than the LTCB blood test, and according to Dr. Curran's testimony to GAO investigators, he told Gallo about the concordance of his results with those of the IP, during the March 1984 meeting. Dr. Gallo told Subcommittee staff he did not recall being told by Dr. Curran about the IP blood test results, yet just a few weeks after the Gallo/Curran meeting, while lecturing in Zurich, Dr. Gallo said this about the work of the IP scientists: "... I have heard recently that their serological data has gotten very good, almost as good as I know we have with these" (Symposium on Infective Agents and Their Effects - New Perspectives; Beecham Research Laboratories, April 5, 1984, audiotaped address). Dr. Gallo confirmed to Subcommittee staff that he made the above remarks, but he claimed he could not recollect the basis for them, other than "rumors via the grapevine." The day after the Beecham symposium, an even more significant event relating to Dr. Gallo's knowledge about the IP LAV antibody blood test, took place. On April 6 at the Institut Pasteur in Paris, Dr. Gallo was shown the CDC computer print-out containing a side-by-side tabulation of the LTCB and IP blood test data. Five other scientists who were present in the room (including two scientists from the United States: Drs. Donald Francis and Murray Gardner) substantiate these events, particularly, that: (a) Dr. Gallo saw the data; (b) the data showed convincingly that the IP and LTCB viruses were both associated with AIDS; and (c) the IP blood test was equal to or better than the LTCB test in detecting antibodies to the suspected AIDS virus. Dr. Gallo revealed nothing about the CDC data to the PTO, nor even to the attorneys who prepared the LTCB patent applications, the lawyers who told Subcommittee staff they instructed Gallo and his colleagues concerning their duty of candor and disclosure. Neither did Gallo et al. cite any information about the CDC data or its implications in the May 1984 Science papers, submitted just six days before Gallo saw the data, and by Gallo's own account to OSI, "updated" to the time the galley proofs were reviewed. Instead, in the Science papers, Dr. Gallo cited IP blood test data from the Summer and Fall of 1983, and he contrasted these data with data for his own test from months later, i.e., from the Spring of 1984. Dr. Gallo for years denied his knowledge of the CDC data, and he denied the data's significance; yet in so doing, Dr. Gallo revealed much about his actual knowledge of the data and his understanding of their significance. In OSI interviews, Dr. Gallo made these kinds of statements about what he saw during the April 1984 meeting at the Institut Pasteur: "I saw nothing. I sat where I am and they were working on a corner of a circled table but I didn't know why Don Francis was there. He said, 'oh you know, the results were quite comparable in the blind comparative test. I was saying, 'I am going to get right sucked into this. They are going to -- I said, ' look I am not publishing CDC data sera. We have our own publications planned and gone off already. I was getting worried that they were going -- this is what was happening. I was thinking to myself, what the heck is Don doing here? But I never had a chance to review this data ... I repeat again, I saw that data from six feet away for two milliseconds. I saw no real numbers" (7/27/90 OSI interview; transcript pp. 95-97). "...in that meeting, I never saw the data" (8/3/90 OSI interview; transcript p. 225). "...I knew there was no data from Pasteur or CDC. I mean, I knew it well because I had just been there. I mean, what data was new? There was no new data. It was very little and it wasn't going to be published for another six or seven months" (12/2/90 OSI interview; transcript pp. 79-80). (The above passages illustrate well Dr. Gallo's longstanding, deep-seated antipathy toward the CDC as an institution and particularly toward Dr. Donald Francis, who on a number of occasions spoke out strongly concerning Dr. Gallo's conduct.) Another prime example of Dr. Gallo's denials relating to the CDC data is a December 17, 1991 memorandum Gallo wrote "To the record," titled "Blood Test Patent and Related Information." The memorandum was meant for a top-level audience at the NIH; copies were noted to Drs. Samuel Broder and Bernadine Healy, Directors of the NCI and NIH, respectively, as well as to the NIH Legal Advisor, Robert Lanman, and Thomas Mays, Director of the NCI Office of Technology Development. In the December 1991 memorandum, Dr. Gallo said he had: "... learned of rumors ... [of] still another 'new' argument being made against me, NIH, the patent and the Agreement .... that I 'knew' and reviewed data 'from Pasteur scientists' in early April 1984 (about two weeks before submitting our patent application), which showed that 'their' blood test was about as good as ours." Said Gallo, "This is a big misrepresentation of the facts." Yet, just three months later, in a recorded telephone message left on the answering machine of Dr. Donald Francis, the CDC scientist who showed him the computer print-out on April 6, 1984, Dr. Gallo said this: "I'm well aware of the serology data that you gave for me to look over on one occasion during the visit to Pasteur. I am aware of that happening." When he was interviewed by Subcommittee staff in July 1993, Dr. Gallo said the CDC "had no credibility." He also said that he did not trust the results of the IP blood test because the IP scientists had changed the cut-off score for its test. Dr. Gallo told Subcommittee staff, "You just can't draw the cut-off where you want." In fact, adjustment of cut-off scores is regularly done when a test is in the developmental stages; it is a normal part of the process of maximizing a test's sensitivity and specificity. Gallo et al. adjusted the scoring of their own LTCB blood test on the CDC panel of sera, changing "+/-" scores to "+." This was what resulted in the LTCB test's jumping from 48% to 80% positive in persons diagnosed with AIDS. Notwithstanding Dr. Gallo's denigration of the CDC data, the fact is that HHS itself regarded the data as definitive, and believed the data showed that LAV and the LTCB virus were both the cause of AIDS. The official HHS position on the matter was rendered by Dr. Robert Windom, then-Assistant Secretary for Health and Mr. Ronald Robertson, then HHS General Counsel, in an April 1988 letter to a German publisher: Concerning the CDC data, Windom and Robertson said this: "... in early 1984, under the auspices of the Centers for Disease Control in Atlanta, Georgia, a series of blind tests was undertaken to ascertain whether the sera from patients with AIDS contained antibodies to HIV. Of significance is the fact that both NCI and Pasteur participated in these tests. Each laboratory was provided with sera and asked to judge whether each specimen contained antibodies to the virus. The results of those tests unequivocally established that HTLV-III/LAV was the presumptive causative agent of AIDS" (p. 3). To this day, Dr. Gallo continues to maintain that at the time the CDC data were obtained, the IP scientists "did not have a blood test." E. Functional Identity of LAV and "HTLV-III" Based on the LTCB's own work with LAV and the viruses Gallo et al. collectively called "HTLV-III," as well as the work of the IP scientists with LAV, Gallo et al., as early as February/March 1984, had strong presumptive evidence that LAV was -- at least -- the same kind of virus as the LTCB's own putative AIDS virus isolates. This functional identity was important scientifically as well as clinically, and it was important legally, relative to the patent applications of Gallo et al. The LTCB scientists subjected LAV to the same battery of tests as they used on their own samples. They obtained the same results with LAV as they obtained with what they claimed were genuine LTCB HIV isolates (see Part B2b above). Dr. Gallo told OSI that prior to the publication of the May 1984 Science papers, the LTCB's own data revealed that HTLV-III and LAV "were of the same virus type ..." (4/17/90 written submission to OSI). Dr. Gallo also said that: "... the same virus type was suspected, I would say, by ... the early part of 1984, certainly before the press conference" (4/11/90 OSI interview; transcript p. 62). Dr. Gallo's utterances from March/April 1984 confirm these statements to OSI. In March 1984, in an audiotaped lecture, Dr. Gallo asserted that his "HTLV-III" virus was "very similar" to the Pasteur virus (3/17/84 address at the Association pour la Recherche sur le Cancer; Marseilles, France). Dr. Gallo also made repeated, strong assertions to OSI concerning what he told the Pasteur scientists, during his trip to the IP in the first week of Aril 1984, concerning the likelihood that LAV and "HTLV-III" were the same virus type. Among these many assertions, the following are representative: "I concluded my seminar by saying 'this is the virus that they isolated last year. It is the cause of AIDS ..." (4/8/90 OSI interview; p. 12). "Remember, when I lectured in Paris I said it. I said this is like the cause of AIDS. We've made a blood test for it. I believe it's what they'd published last year" (4/11/90 OSI interview; transcript p. 62). "... I said that, 'this is the cause of AIDS and I believe these guys found it last year and it's the same virus that they found.' There was no bones about it. I mean it wasn't a pulled punch" (op cit., p. 63). "... I said that publicly. I said it in the conference. It said it in front of 500 people from the Pasteur Institute or from all Paris. I closed my final presentation with a slide of a picture of viruses and I said I believe this is the cause of AIDS. I believe they found it last year. I believe we are going to prove it very shortly" (7/27/90 OSI interview; transcript p. 85). Yet, in direct contradiction of these self-described beliefs, shortly before he travelled to Europe, Dr. Gallo edited Dr. Popovic's Science manuscript in such a manner as to delete all references to the functional identity of LAV and HTLV-III (see F below), at the same time adding to the paper the false claim that LAV had not been transmitted to a permanent cell line, plus the assertion that, "... HTLV-III and LAV may be different." Later, during the blood test patent dispute, in an attempt to defend the United States blood test patent, particularly the U.S. scientists' failure to disclose the prior art of the IP scientists, the U.S. Government attempted to argue that there was no need to disclose the IP scientists' work because, at the time of submission of the U.S. patent application, there was no reason to believe the IP and LTCB viruses were even the same kind of virus. Pursuant to this argument, Dr. Gallo asserted, under penalty of criminal prosecution for making false statements, the following: "At the time the Gallo patent was filed [April 1984], my colleagues and I did not consider LAV and HTLV-III to be the same or even substantially the same, virus. Quite clearly the data available to us indicated that the two viruses functioned differently and reacted differently" (11/8/86 Gallo declaration; p. 13). Dr. Gallo has attempted to justify these claims by invoking IP experimental results that Gallo says were described to him by Drs. Montagnier and Chermann. One example cited with great frequency by Dr. Gallo is the IP scientists' reported assertion that they did not see the envelope protein gp41 in their preparations of "LAV," whereas the LTCB scientists identified gp41 as "one of the major proteins of the virus" (Sarngadharan et al., Science, 224, 1984, p. 508). There are a number of significant problems with Dr. Gallo's claim that prior to the April 1984 submission of the Gallo et al. blood test patent application and the May 4 publication of the Popovic et al. paper, he had reason to believe the IP scientists had not seen gp41 in their virus. Chief among these problems is the lack of substantiating evidence. The only pre-May 1984 IP reference that Dr. Gallo cited to support his claim -- the Montagnier et al. paper presented in September 1983 at Cold Spring Harbor -- indicates the IP scientists had identified a protein around the size of gp41 in their virus. According to the IP paper, "A 36K protein, a 42K protein, and an 80K protein were constantly found to be associated with the purified virus and may represent the major envelope proteins" (Montagnier et al., Human T-cell Leukemia/Lymphoma Viruses, 1985; p. 369). Dr. Gallo also has frequently invoked a chart prepared by Drs. Montagnier and Sarngadharan in May 1984 ("Status of the comparison ...") as evidence of the IP scientists' failure to see gp41. In fact, Dr. Gallo has frequently carried the argument further, asserting that the chart shows that Dr. Montagnier himself was arguing for real differences between the IP and LTCB viruses. Thus, in his April 1986 "History of Key Events ..." -- widely distributed among HHS administrators and attorneys -- Dr. Gallo said this: "June 1984: M. Sarngadharan, a close co-worker of Gallo, goes to Paris, brings the cell line producing HTLV-III and with Montagnier makes comparisons of LAV, to our prototype HTLV-III known as the B strain (HTLV-IIIb). They prepare a table signed by Montagnier in which Montagnier argues for significant differences between HTLV-IIIb and LAV" (emphasis in original; p. 5). Dr. Gallo made the same kinds of statements, repeatedly, to OSI. A representative example is the following: "When Sarang visited Montagnier in May 1984, and brought IIIb there and did some work together with Montagnier, Montagnier insisted on differences between LAV and IIIb. I have some of this in writing. For instance, Montagnier said that LAV did not have the major envelope transmembrane component, gp 41" (4/8/90 OSI interview; transcript p. 35). But Dr. Gallo's claims about Dr. Montagnier's position on gp41, as of May 1984, cannot be substantiated. The chart completed by Drs. Sarngadharan and Montagnier actually shows, in the "agree" column relating to the p41-43 proteins, that the scientists agreed, "... there is an actin band in viral preparations." In the "disagree" column, the notations in the chart show that Dr. Sarngadharan said gp41 is "... likely to be viral origin (gp),is recognized by most AIDS patients by Western blotting," while Dr. Montagnier said gp41, "is not seen after labelling." However, importantly, it is clear that Sarngadharan and Montagnier did not consider the matter as resolved, because in the "decide" column of the chart there appeared a number of "things we have decided to do." These entries included Dr. Montagnier's further examining his virus, using "exactly technique of Western blotting of M.S. [Dr. Sarngadharan] who will send it as soon as possible to L.M. [Dr. Montagnier]." Notably, according to the chart, Dr. Sarngadharan also committed to send Dr. Montagnier, "the uninfected H9 cells for this purpose." But as described below, H9 was not sent to the IP scientists until the Fall of 1984, and then only after repeated requests by them to Dr. Gallo (see Part A below ). The above passages show that as of May 20, 1984 (the date on which the Sarngadharan/Montagnier chart was prepared), the presence or absence of gp41 in the IP virus was very much an open question, with a significant amount of experimentation remaining to be done. Shortly thereafter, the presence of identical envelope proteins in both LAV and "HTLVIII" was confirmed, both at the IP and LTCB, indicating the earlier failure of the IP scientists to see gp41 was due to technological deficiencies (see Part B2 below for additional information on this point). As an experienced scientist, Dr. Gallo knew well that the putative gp41 differences between the IP and LTCB viruses, as well as other putative differences Gallo said the IP scientists described to him (e.g., their reported inability to raise rabbit antibodies to their virus), could very well be due to methodological problems, as indeed, they were shown to be. Thus, the invocation of the early IP data as indicative of real, fundamental differences between the IP and LTCB viruses was both factually wrong and scientifically highly suspect. Moreover, Dr. Gallo's invocation of these data, as in his declaration, ignored the substantial quantities of data -- both from the IP and the LTCB -- that indicated the viruses were functionally the same. These were the data that showed Dr. Gallo, by his own account, that the viruses "were of the same virus type." They were the data that led Dr. Gallo, by his own account, to proclaim in Paris in April 1984, concerning the LTCB virus, that, "... these guys found it last year and it's the same virus that they found." Thus, the claim in Dr. Gallo's declaration that "the data available to us" showed that the viruses "functioned differently and reacted differently" is significantly incorrect and incomplete, and is contradicted by his own words. Dr. Gallo has stated that it was the HHS attorneys who advised him that the IP and LTCB viruses were "substantially" different, and that it was on the basis of this advice that he signed his declaration. But Dr. Gallo also told Subcommittee staff he wishes he had said in the Popovic et al. paper that, "LAV and HTLV-III are probably the same," rather than "may be different." Concerning his sworn declaration, Dr. Gallo told Subcommittee staff that the denial in his declaration that he and his colleagues knew LAV and HTLV-III were substantially the same was "not accurate." Dr. Gallo added this: "I wish I hadn't signed it [the declaration]. I'm not proud of that." F. The Popovic et al. Science Paper On May 4, 1984, the LTCB scientists published four papers in the journal Science, announcing their putative isolation of HIV and development of an antibody blood test. One of the LTCB papers, by Popovic et al., described the "continuous production" of HIV in the "HT" cloned cell lines (see below ). Important as the paper was, there were numerous problems with its accuracy and completeness. In addition to the false statements concerning the IP virus, the Popovic et al paper contained numerous incorrect statements and misrepresentations of data. Dr. Popovic was found guilty of scientific misconduct by ORI, based on his responsibility for false statements in the paper. The HHS Appeals Board reversed this finding, based on its own curious definition of scientific integrity, plus its own unique determination that falsification of data is not de facto scientific misconduct. The demonstrable falsehoods in the paper remain unchallenged. The preparation of the Popovic et al. paper was itself remarkable, embodying the elements of an extraordinary conflict within LTCB that would ultimately become public, a conflict between Drs. Gallo and Popovic that was in reality a conflict between the truth and a fiction about the LTCB scientists' use of LAV, and the knowledge that resulted from that use. Dr. Popovic was the LTCB scientist who worked most closely with the IP virus and the LTCB's putative prototype isolates, LAI/MOV and LAI/IIIb. Based on his work, Dr. Popovic was so certain of the functional identity of LAV and HTLV-III that, in the first draft of his Science paper he wrote, concerning his own experiments, that "LAV as a reference virus ... had been used in the first series of experiments," and "LAV is described here as HTLV-III." Dr. Gallo struck out both of these statements, writing in the margins of the paper, "I just don't believe it. You are absolutely incredible" and "Mika you are crazy." Dr. Gallo then added to the conclusion of the paper his rendition of a few highly selective pieces of data (tellingly, Dr. Gallo listed these items on the cover of the manuscript under the heading, "Way to deal with this LAV originally"). Dr. Gallo also wrote, in the conclusion of the paper this passage: "These findings suggest that HTLV-III and LAV may be different. However, it is possible that this is due to insufficient characterization of LAV because the virus has not yet been transmitted to a permanently growing cell line for true isolation and therefore has been difficult to obtain in quantity" (Popovic et al., Science, 224, p. 500). This passage contains several notable assertions, including the following: o The suggestion that "HTLV-III and LAV may be different" -- when the LTCB's own data and chief scientist were saying precisely the opposite and Dr. Gallo himself had publicly proclaimed the viruses were likely to be the same; o The assertion that LAV had been "insufficiently characterized," when in reality, in addition to the LTCB scientists' own work, the IP scientists had presented and published many papers on the characterization of the virus. Dr. Gallo was present for several of the IP scientists' talks and he received several of their papers well in advance of their publication. The IP papers and presentations included the September 1983 Cold Spring Harbor presentation by Dr. Montagnier (described above); the November 1983 Tokyo presentation by Dr. Barre-Sinoussi (described above ); the New York Academy of Sciences presentation concerning the effects of LAV on T-cells; the February 1984 presentation by Dr. Chermann at Park City, Utah, titled "Characterization and Possible Role in AIDS of a New Human T-Lymphotropic Retrovirus"; a highly significant paper by Vilmer et al., containing the first published description of the methodology for the LAV ELISA (The Lancet; April 7, 1984, p. 753); and Montagnier et al. (Annals of Virology, 135E; April 1984, p. 119) on the "further characterization of LAV." o The assertion that LAV had not been transmitted to a permanently-growing cell line, when both the LTCB and the IP scientists, months earlier, had attained this accomplishment, and Dr. Gallo knew this was so. Dr. Montagnier told OSI he informed Dr. Gallo he (Montagnier) was growing LAV in an EBV-transformed B-cell line, well before the publication of the Popovic et al. Science paper. Moreover, it is certain that Dr. Gallo knew that Dr. Popovic had grown the IP virus in a permanent cell line. In the fourth draft of the paper, in his own hand, Dr. Gallo wrote this: "Finally, a T-lymphotrophic retrovirus different from HTLV-I and II and associated with lymphadenopathy syndrome was detected earlier ... We found that this virus, called LAV (provided by L. Montagnier and J.C. Chermann) also grows in H4 and produces similar cytopathic effects on it as HTLV-III." Dr. Gallo deleted the latter statement from the published version of the paper. Dr. Gallo also significantly rewrote the Popovic et al. paper so that it would indicate Dr. Popovic's initial experiments were performed with the LTCB prototype isolate, rather than with LAV. These changes were made over Dr. Popovic's strong objections (see below). (Dr. Gallo's principal defense of the published statements relating to the IP virus in the Popovic et al. paper is that he [Gallo] was referring only to the IP scientists' work, not work at the LTCB. This claim is belied by numerous pieces of evidence, not least of which is the content and structure of the statement itself which manifestly is not qualified in any way, but is a blanket assertion that the IP virus, "has not been transmitted to a permanent growing cell line." Additional evidence that Dr. Gallo intended to make a general and not a limited statement about the growth of LAV is seen in drafts of the Popovic et al. paper. As noted above, drafts of the paper bearing Dr. Gallo's own handwriting show that prior versions of the "LAV" passage included statements about both laboratories' work with the IP virus, not just the work of the IP scientists themselves. Notably, prior versions of the passage contained the phrase, "poor virus production," rather than the phrase "not yet been transmitted to a permanently growing cell line." The latter phrase must have been substituted -- literally -- at the last minute; it does not appear even in the galley proofs of the paper. Finally, even if the published statement had been explicitly limited to the IP scientists work, it still would not be true. Dr. Gallo had known since at least the first week of April 1984 that the IP scientists were growing their virus in a permanent cell line. Dr. Gallo actually mentioned the IP scientists' accomplishment at the HHS press conference, although he misrepresented and minimized its significance by the assertion that, "They believe they're getting it into a cell line just now" [press conference transcript p. 31]). Dr. Popovic secured the drafts of the paper that bore Dr. Gallo's notations with his (Popovic's) sister in Czechoslovakia, because, Dr. Popovic said, he believed that: "... sometime in the future, I might need them as evidence to prove that I gave fair credit ..." to the Pasteur scientists (5/15/91 Popovic-to-Hadley memorandum; p. 7). Dr. Popovic produced the drafts of his paper late in the OSI investigation, when he believed he was likely to be found guilty of scientific misconduct and he hoped the drafts, by revealing the significant involvement of others in the writing of the paper, would be exculpatory to him. Dr. Popovic also repeatedly recounted to OSI the disagreement he had with Dr. Gallo concerning Gallo's deletion from the paper of his (Popovic's) description of his LAV experiments. Of this matter, Dr. Popovic said, "... I would consider (it) a major disagreement" (4/10/91 OSI interview; transcript p. 6). Among Popovic's statements to OSI, reflecting the strength of his (Popovic's) views on the matter, the following are exemplary: "I thought that we should include the LAV data in the paper ... LAV data what we had with the French virus. I think was right because this my paper is suspicious because of those LAV data are not included. Retrospectively it is very obvious it would be better" (12/1/90 interview; transcript p. 103). "Regarding my opinion, I told him if in those time and I am telling it now that it would be better to refer to the French work and present the LAV data what we had, that has been my opinion all along ... and I expressed this" (op cit., p. 156). "I did not agree with Dr. Gallo that the references to the work we did with the French virus should be omitted or even significantly minimized ... I thought it was wrong not to credit Dr. Montagnier's group's contributions more clearly" (4/10/91 OSI interview; transcript pp. 7-8). In Dr. Gallo's account, what Dr. Popovic called a "major disagreement" became "a very brief discussion." Here is what Dr. Gallo said to OSI (prior to Dr. Popovic's revelation of the draft manuscripts): "... there wasn't much emphasis. I think, Mika thought maybe we should make a statement to the effect that LAV was in culture ... don't think that Mika argued forcefully or strongly that we have to have some data on LAV growing in culture. That is not the case. He did mention it in an almost casual way, maybe we should put a statement in that at least for the time being with partial characterization" (12/2/90 OSI interview; transcript pp. 184-186). According to Dr. Popovic, one of the reasons he acceded to the removal from his paper of the account of his LAV experiments was Dr. Gallo's assurance that this information would be included in the collaborative papers that were soon to be produced with the IP. As described below (see below ), three such papers were produced; however, none of the papers was ever published. Moreover, none of the collaborative papers made any mention of the LTCB's growth and extensive use of the IP virus they received in 1983; thus, this vitally important aspect of the LTCB scientists' work -- until the French/American dispute -- was suppressed. G. Selection of the Isolate for the LTCB HIV Blood Test 1. The Gallo/Popovic debate: The question of which isolate the LTCB scientists would use as the antigen for their HIV antibody blood test became critical at the point at which the LTCB patent applications were prepared, during the first three weeks of April 1984. As previously described, none of the four May 1984 LTCB papers mentioned an isolate called "IIIb," including the paper by Sarngadharan et al. that described the LTCB blood test. But for purposes of the patent applications, greater specificity was essential. Clearly, an explicit acknowledgement that LAI/LAV was used for the LTCB blood test would not do, since such use would have violated the noncommercialization agreement signed by Dr. Popovic when he received the IP virus the previous Fall. Acknowledgement of the use of MOV also would not do, since the LTCB scientists -- if their own account is to be believed -- did not know its origins, even if it had come from an AIDS or pre-AIDS patient. So Dr. Gallo and Popovic had to decide which putative LTCB isolate would be used, and according to both these individuals, the choice came down to "IIIb" or another isolate, "RF." It is remarkable that at this time, there should have been any discussion of this issue at all, since according to Dr. Gallo's account, "IIIb" reportedly had been in large-quantity production for several weeks, and had been used, reportedly, as the antigen for the LTCB HIV blood test since March 6, 1984. "IIIb" also, reportedly, had been used to generate most of the blood test data reported in the LTCB papers about to be published in the journal Science. Judging from these circumstances, it would appear that the choice -- IIIb -- had long since been made. Notably, there is no indication Dr. Popovic objected to any of this But suddenly, by his own account, at the point a "IIIb" blood test was about to be patented and commercialized, Dr. Popovic became acutely anxious about the "origins" of the "pool virus," even to the point of advocating the delay in the blood test that would have been occasioned by the choice of an isolate other than the putative "IIIb." The interpretation that Dr. Popovic's precipitous anxiety occurred precisely because he knew or strongly suspected that "IIIb" was LAI is inescapable. Dr. Popovic told OSI that he urged Dr. Gallo not to use IIIb for the LTCB blood test, to use instead the "RF" isolate, whose origins were well-established. Popovic's self-report to OSI of his arguments to Dr. Gallo indicate he (Popovic) was concerned about the uncertain provenance of "IIIb." Dr. Popovic told OSI that although the origin of RF was "more certain," "the best was IIIb," because the latter isolate was farther along in its growth than the former. Still, said Dr. Popovic: "... I personally as well as Betsy [Read-Connole] told let's take out the prototype, the RF. Gallo told 'no, we have to rush because it is blood bank assay. We have to give this one [HTLV-IIIb] because this one is the best one at this time' ... if you ask for clear-cut science data, for sure, it was better to have RF ..." (6/26/90 OSI interview; transcript p. 71). Dr. Popovic told OSI that the work with RF was done in a different laboratory -- a better organized laboratory -- than his own, where he personally performed the major experiments with LAI/LAV, LAI/MOV, and LAI/IIIb: "The major problem is that individual isolates were under more strict control in more organized lab comparing to that where -- I worked myself [with] IIIb, MOV, LAV ... That part of work with individual isolates were done under far better conditions. So not only myself also Betsy was involved in it, we (both of us) pushed for the RF isolate, in which we were more confident, comparing to the IIIb" (op cit., pp. 109-110). In short, according to Dr. Popovic, he was more confident in RF, "... because the origin of it was more clear and handled under better conditions" (op cit., p. 110). (Note: Dr. Popovic's acknowledgement to OSI that he worked with LAV in the same laboratory as the allegedly independent MOV and IIIb is noteworthy. Among other things, it casts significant doubt on a key Popovic-to-Gallo memorandum, written early in the French/American dispute, when Dr. Gallo was still adamantly insisting there was no possibility that LAV had "contaminated" the pool. In the memorandum, Dr. Popovic asserted that his work with the "pool virus," "... was almost entirely confined to the tissue culture room 6B03A where no LAV was ever used" [emphasis in original; Popovic-to-Gallo; September 6, 1985. See below for more information on this memorandum.) Dr. Gallo's OSI testimony, in some respects, mirrored that of Dr. Popovic. Dr. Gallo confirmed the rationale Dr. Popovic gave for favoring RF over IIIb, namely Dr. Popovic's concerns about the murky origins of "IIIb." "... Popovic, in fact, came to me to discuss that he favored RF for the blood test because it came from one individual, as opposed to the pool which could not be traced as well. And my response was -- and it was a big, very long, discussion -- and I said, more or less, 'Why? It's just as good to use IIIB, even if it's from 20 people, because basically we want to move as fast as we can..." (4/26/90 OSI interview; annotated transcript page 72). On another occasion, Dr. Gallo offered a more colorful recollection of the discussion with Dr. Popovic: "I can see Mika standing in front of me with his pipe and saying, you know, 'why don't we go with RF with the blood test' and I saying you know, 'what the hell' -- you know, 'what for.' And he said, 'well, it is -- we have the lineage much better defined. We know exactly what it is all the way.' And I said, 'Look, if this picks up, you know, this is working, it picks up, it is available now in higher amounts.' If we wait two weeks, three weeks, you know, I thought this was worse. So, that was the end of the discussion. I made a decision. You know, I made the decision. Yes, let's go with the pool and I told him" (12/2/90 OSI interview, annotated transcript, page 106). But Drs. Gallo and Popovic's accounts of their discussions also reflect some significant differences. Most notably, Dr. Gallo's accounts consistently overstated the readiness of RF for used in the LTCB blood test, while at the same time, Dr. Gallo suggested that other factors, e.g., patient nationality, were significant factors in his decision to use "IIIb." Instances of Dr. Gallo's overstatements of the readiness of RF include the following: "... we had little reason to use LAV for the blood test, we had RF available, for example, which could have been used instead of IIIB. Having developed the method, having other isolates that could have been ready within weeks, we could have also had other choices" (4/8/90 OSI interview; annotated transcript page 38). "The point is going to be is that RF was almost as good as the pool when we were ready to form the blood test and could have been used. We could have said, 'Use this instead. Maybe you'll have to charge 10 cents or a dollar more -- I don't know -- because you don't get quite the titre'" (4/26/90 interview; annotated transcript p. 21). On another occasion, Dr. Gallo indicated to OSI that RF was only two weeks behind "the pool" relative to its utility for an HIV antibody blood test. Dr. Gallo also invoked nationality as a significant factor in his decision to use "IIIB": "RF was also ready ... You don't have anything to lose. Maybe you lose two weeks. You can give that to anybody to calculate. When we sent out for blood tests, we could have taken RF ... Mika favored RF ... I favored IIIB because it was American instead of Haitian. And because the count was a little bit better and I didn't give a damn if it came from ten or it came from one" (5/10/90 OSI interview; annotated transcript page 88). It is not certain why Dr. Gallo introduced the "nationality" issue as a rationale for his selection of the allegedly all-American "IIIB." One obvious possibility is that the nationality issue was introduced to deemphasize the lack of readiness of RF as a critical consideration. Whatever the reason, the fact is that the nationality argument was bogus -- for one of the alleged "pool" samples, F6367, came from a Jamaican patient; thus, in no way was the "pool" an all-American one. Dr. Gallo nonetheless repeatedly invoked nationality as a reason for his choice of "IIIB" over RF. In his December 2, 1990 OSI interview, Dr. Gallo said this: "With the blood test he (Popovic) favored ... going with RF, and I said, 'Look, the IIIB is ahead of RF by some weeks and it is a U.S. versus Haitian ... The other four or five, six he had in culture were not yet well characterized, were further behind. And he favored going with RF because it came from a single patient and was well characterized, etc., etc. And I said, 'But it is a few weeks behind. Why make any delay? IIIB is from the United States, the other is from Haiti. Why do I want to have a Haitian that is two weeks behind?" (transcript pp. 101-102). Dr. Gallo also asserted to OSI that "RF was available for expansion into large-scale culture almost at the same time as IIIB" (4/26/90 OSI interview; transcript p. 72). But the existing evidence shows that RF -- in 1983-84 and well beyond, was discernibly inferior to "IIIB" in its titre and growth capacity. More importantly, the fact is that whatever its potential capabilities, RF was not expanded at the same time as IIIB, and this circumstance itself was another reason that at the time Gallo and Popovic were debating the issue, RF was not a genuine contender for use in the LTCB blood test. Dr. Popovic emphasized the significance of the demonstrated growth capacity of LAI/IIIB when he described to OSI that factors that weighed in the decision to use IIIB: "... what was in our mind is as follows: If we transfer this system into the large scale production ... would the virus producing cells behave the same way as in the small scale? We didn't know. So this was also one consideration, that if we go, we go with that which is the best, because we still didn't know if a large industrial production can work or not..." (6/26/90 OSI interview; annotated transcript p. 77). These statements by Dr. Popovic demonstrate that large-scale, high-titre production was a critical consideration in the selection of the LTCB HIV prototype. Dr. Popovic expressed confidence that he could have achieved this with RF, but he also said that, "... in order to be in a good position and go ahead with RF, we needed at least four weeks of work to concentrate on that one and that wasn't done" (12/1/90 OSI interview; annotated transcript p. 116). As to whether there was any candidate isolate other than RF that might have been a contender for use in the LTCB blood test, Dr. Popovic made it clear there was not. Dr. Popovic said that aside from RF, "... to do with any other virus isolate it was a question of starting from three to six weeks or something like that ..." (6/26/90 OSI interview; annotated transcript p. 78). 2. "Other Isolates" and the LTCB HIV Blood Test -- There was No Choice: As described previously (p. 11), over the years, Dr. Gallo frequently asserted claims of multiple isolates of the AIDS virus, claims that steadily grew in number from 48 to "over 200." As early as April 1984, at the HHS press conference, Dr. Gallo asserted that he had "produced more than 50 isolates" of the suspected AIDS virus; yet in 1990, Dr. Gallo acknowledged to OSI that these putative isolates "are mostly detections ... by our criteria" (7/27/90 OSI interview, transcript p. 17). OSI itself could confirm no more than 10-12 of the LTCB's claimed detections/isolates. Dr. Gallo himself admitted to OSI he had only around ten isolates at the same time he was claiming 50 or more (4/27/90 OSI interview; transcript p. 61). As the HIV blood test dispute began to escalate, Dr. Gallo stepped up his claims about the number of HIV isolates his laboratory had made. Dr. Gallo also frequently emphasized the relationship between the isolate claims and his attempts to refute the IP charge that the LTCB scientists had knowingly used the IP virus for the LTCB blood test. "RF," in particular, was frequently invoked as so worthy a candidate for the LTCB blood test that it alone should lay to rest suspicions about deliberate use of the IP virus. Thus, for example, in his September 23, 1985 response to a series of questions put to him, at the start of the French/American dispute, by NCI Associate Director Dr. Peter Fischinger, Dr. Gallo said this: "... we isolated, mass produced in H9 cells, patented and published on a major variant HTLV-III-RF (Haitian isolate), very different from LAV, at exactly the same time, making all this crap irrelevant. In addition, last month (August 1985) we published in the Proceedings of the U.S. National Academy ofScience on one hundred and one different isolates of HTLV-III/LAV. This paper was submitted for publication six months ago. Now the number of isolates approaches 200" (emphasis in original; p. 5). The PNAS paper referenced in this passage is the paper concerning which Dr. Gallo acknowledged to Subcommittee staff he could not substantiate the claim of HIV isolates dating from 1982, because no 1982 sample was tested by HIV-specific reagents. Concerning the number of isolates claimed in the paper -- 101 -- Dr. Gallo told Subcommittee staff he could document 25 - 50 isolates, but he said he also had circumstantial evidence, including some laboratory data, that up to 200 "isolates" had been tested by LTCB scientists and confirmed to be HIV. Despite repeated requests that he produce the laboratory data, Dr. Gallo failed to do so. What Dr. Gallo did produce was a June 13, 1994 letter from LTCB collaborator Dr. Robert Ting (formerly of Biotech Laboratories), who wrote to Dr. Gallo that during the period "1984 to 1985," "... we have received more than 2000 samples from LTCB during that period and most of the samples were for HTLV tests which included HTLV-I, HTLV-II and HTLV-III. HTLV-III samples included many of LTCB new isolator (sic.). Results of these tests were sent directly to the LTCB staffs right after the test." This letter, obviously, confirms nothing about how many HIV isolates were obtained by the LTCB; the letter shows only that many samples were tested, for several different viruses.. Dr. Gallo's claims about multiple isolates, including "RF," that allegedly could have been used for the LTCB HIV antibody blood test, also were reflected in the Colin Norman November 8, 1985 article in Science. In a box headed "HTLV-III and LAV: Similar, or Identical," Norman wrote, based on interviews with Drs. Gallo and Popovic, that shortly after starting the "pool" culture: "... Popovic also established virus-producing lines infected with isolates from single patients. One of these, infected with virus from a Haitian ["RF"], was included in the patent application for the method of mass-producing HTLV-III. This virus has since been sequenced and it is as different from LAV as ARV is" (p. 643). Norman then noted Dr. Gallo's use of "RF" as a defense against a charge of misappropriation: "Gallo argues that this ought to silence any speculation that he deliberately grew the French virus. If he already had other lines infected with other viruses, why would he sequence the virus from a line he had infected with the French isolate? Gallo also notes that his group had several virus isolates before Montagnier's sample arrived. 'It was no big deal to get supernatant. We got that from many patients for a long, long time before he sent us this virus,' Gallo says. 'Am I going to throw away [my reputation] for a virus that is simple to isolate, and then publish its sequence with multiple collaborators? It just doesn't make sense.'" But, as the OSI report made clear: "... the existence of other isolates would not eliminate the possibility that the French virus was intentionally misappropriated" (p. 15). Clearly, the existence of "other isolates" would have no bearing on the "misappropriation" issue unless any such isolate(s) were demonstrably (1) contemporaneous with LAV and (2) as readily useable as LAV at the juncture the blood test isolate was chosen at the LTCB. In other words, it would never be adequate to assert in the abstract as Dr. Gallo frequently did, that the LTCB scientists had "other AIDS virus isolates," for in the rush to publish and otherwise claim international credit for the discovery of the AIDS virus and the creation of the HIV antibody blood test, in the rush to patent the invention, weeks -- even days -- counted. Dr. Gallo and his associates had some HIV isolates that were genuinely their own. No one disputes that this is so. But the crucial questions with respect to whether there was a motive for misappropriating the IP isolate are these: "Did Gallo et al. have even one other isolate at the critical time it was needed for the LTCB blood test?" and "Was any such isolate as readily useable as LAV?" The answer to these two fundamental questions is clearly "no." Review of the laboratory data for RF -- invariably touted as the LTCB's best contender to LAI/"IIIB" for the LTCB blood test -- demonstrates clearly the inevitable delays that would have been occasioned by the use of RF, due to RF's not having been scaled-up for large-quantity production. The very fact that RF had not been scaled up suggests there may have been concerns about its early growth; laboratory data and testimony of LTCB scientists show there was cause for such concerns. Specifically: -- The initial culture history of RF was decidedly unpromising. RF was put into short-term culture in mid-November 1983; by mid-December, according to Betsy Read-Connole, who worked with RF most intensively, the culture was "dying rapidly" (Gallo 4/26/90 submission to OSI; p. 2). -- The history of RT assays of RF, such as it is, is suspect in several respects. RT assays reportedly were not done for at least the first two-to-three months of culturing of RF. The failure to perform such assays is difficult to comprehend, given the importance that Gallo et al. say they assigned to this isolate. When queried about this matter, Dr. Gallo told OSI that the lack of RT assays on early cultures of RF was due to, "... an enormous backlog of RT samples to be run in Dr. Sarin's laboratory during the period of the RF cultures" (9/23/90 Gallo Written Responses to Follow-up Questions; Response to Question 4d). But according to Dr. Popovic and Ms. Read-Connole, by the time RF was in culture, it was Dr. Sarngadharan, not Dr. Sarin, who was performing RT assays for the LTCB, because Dr. Sarin's assays had earlier proven to be unreliable. -- Such information as does exist about RT assays on RF casts significant doubt on the early viability of the isolate. A January 10, 1984 note, in Read-Connole's hand, states concerning RF that, "Initial cultures negative for p19, RT and EM" (Popovic notebook; page 46). -- The early IFA data on RF also were problematic. Tested against BRU serum on February 2, 1984, RF produced only 5-6% positive readings. On February 20, RF produced only an 11% positive reading against ET serum, while against BRU, RF was listed only as "+," which Read-Connole told OSI was the entry she used for a minimal positive reading. Notably, when describing the LTCB's culturing of the IP virus, both Drs. Gallo and Popovic repeatedly asserted that low IFA readings such as those obtained during the early months for RF, did not indicate successful infection of a permanent cell line. Presumably, Drs. Gallo and Popovic would apply the same determination to RF, meaning the RF cell line could not be considered to be permanently infected until well over two months after the initial inoculation. -- Finally, on February 29 and March 1, RF produced high positive readings against both BRU and ET patient sera, as well as against the hyperimmune rabbit antiserum. But the February 29 assay also indicated a small positive reaction against serum from a patient infected with HTLV-I. In this regard, it is very noteworthy that Dr. Popovic, in the list of "isolates" he gave Zaki Salahuddin to use in preparing the Gallo et al. May 1984 Science paper, listed RF as anti-p19 (HTLV-I) "+/-." -- The LTCB had no EM+ reading on RF before October 1984 (even though RF was published as EM+ in the May 1984 Popovic et al. paper). RF was sent for EMs in December 1983 and January 1984. Both reports were clearly negative for HIV; and Dr. Popovic himself later wrote to Dr. Gallo these telling words: "Because of the lack of EM evidence in the case of HTLV-III RF isolate we decided to pursue the isolate(s) obtained from pooled culture fluids known as HTLV-IIIb" (Popovic-to-Gallo memorandum, 11/28/84; p. 2). Dr. Gallo insisted, contrary to the expert opinion of Dr. Matthew Gonda, that the early EMs on RF were positive; Dr. Gallo even included Dr. Popovic in his (Gallo's assertion): "... Dr. Popovic and Dr. Gallo always considered the RF culture to be EM positive and reported it as positive in our 1984 Science paper ..." (9/23/90 Gallo written responses to OSI follow-up questions; Question 4E). As evidence for his claim, Dr. Gallo produced an EM of a sample labelled "Betsy's cells" (reportedly a code for "RF). Dr. Gallo said this sample was sent to Dr. Gonda on March 13, 1984; according to Gallo, the sample was EM+ for HIV. But no written report was ever produced showing that Dr. Gonda had found Betsy's cells to be EM+, and Elizabeth Read-Connole told OSI that neither she nor Dr. Popovic had ever seen such a report. Read-Connole also told OSI that the "Betsy's cells" EM itself was not located at the LTCB until 1990. Thus, this EM could not have been the basis for the "+" EM entry for RF in Table 2 of the 1984 paper by Popovic et al. Despite his assertions that RF was actually EM+, Dr. Gallo acknowledged to OSI that the EM results for RF were a factor in the decision not to use the isolate for the LTCB blood test. Dr. Gallo told OSI: "It affected us. We did discuss Gonda's negative reports because if it were produced in large amounts it would go to Frederick ... and he's saying that, you know, Gonda didn't -- He's worried that we're going to have to expand it at Frederick, and Gonda is at Frederick and is going to be gossiping, 'Oh, I didn't see anything in it'" (4/27/90 interview, annotated transcript pages 63-66). -- RF was not put into the LTCB's "best grower" clone, H9, until June 28, 1984. This attempted infection did not succeed. RT data up to a week later were negative (Read-Connole Book 5; p. 35), while IFAs against the hyperimmune rabbit antiserum, which were 30-31% positive by day 13, by one week later, had fallen to half those values (Read-Connole Book 3; p. 49). Consequently, a reinfection of H9 with RF took place on July 27, less than a month after the first infection occurred. The fact that an H9/RF reinfection was required less than a month after the initial attempt indicates clearly that if the LTCB had relied on RF for its blood test, it quite likely would have confronted a much more significant delay than the "two weeks" Dr. Gallo frequently cited. "Success" with RF, in other words, was by no means assured. The subsequent history of RF only reinforces the dubious impression of its utility, based on the early data: -- RF was not sent for large-scale production until, according to Gallo et al., "around the end of November 1984" (Gallo submission to OSI on RF; p. 4). This date, if correct, is 9-10 months after LAI/MOV was sent to LTCB contractors for this purpose. But in fact, it is questionable if the transmission for large-scale production occurred even at the end of November, for in his November 28, 1984 "RF" memorandum, Dr. Popovic said that, "At the present time we are intensively pursuing the single-cell cloning and superinfection of H9 cells and other target cells to achieve 80 to 90% positivity for HTLV-III," According to Dr. Popovic, this level of positivity, "should be accomplished within a few weeks." -- As late as April of 1985 , according to the "large-scale production" facility, Electro-Nucleonics, Inc., RF was available to be provided to AIDS investigators only in cases of "urgent need," due to the presence of mycoplasma in the cultures. (Two separate cultures of RF, designated "RF-I" and "RF-II," were identified by the laboratory as being contaminated. The origins of and distinctions between RF-I and -II have not been determined.) According to an April 17, 1985 letter signed by Dr. John Lemp, Director of the Electro-Nucleonics Cell Science Laboratory, the laboratory did not expect to have a mycoplasma-free RF culture for "several months." Thus, even this late, more than one year after the LTCB initiated mass production of virus for its HIV blood test, RF was not ready for even routine use. -- RF-I, at least, was not a satisfactory grower. Minutes of a July 1985 meeting of the NCI Vaccine Development Group record a discussion of the problematic growth of "RF-I," which had been sent to the Frederick facility, presumably for mass production for work on an AIDS vaccine. The minutes show that the meeting participants, who included Dr. Popovic, agreed that RF-I should be replaced with "RF-II," not otherwise identified except as being available from Dr. Popovic. -- Independent testimony from the scientist at Frederick who worked with mass-production of the LTCB's isolates confirms the lower productivity of RF. Dr. Larry Arthur, Director of the AIDS Vaccine Program at Frederick, told OSI that RF, which he received "well after" he first received IIIb, "... was a lower producer than the IIIb in our hands" (1/28/91 OSI interview; annotated transcript pp. 19-29). 3. There Was No Time For Delay: The evidence clearly shows that RF was not a viable candidate for use in the LTCB HIV antibody blood test; the few other theoretically-available isolates (e.g., LS, BK) were even less likely prospects than RF. If Dr. Gallo and his associates had had more time, they might well have been able to scale up other isolates as potential candidates. But there was no more time. At the point at which the isolate choice was made, Dr. Gallo had already told his superiors at the NCI, as well as scientists at CDC and at several meetings in Europe about his putative discoveries. The Assistant Secretary of Health also had been briefed, and provided copies of the four Science manuscripts, which had just been submitted. In this regard, it is very notable that Dr. Gallo himself moved up the submission date for the papers by a full month, indicating clearly the accelerated timetable he had imposed on the laboratory. This event in and of itself committed the LTCB scientists to "IIIb" as the LTCB prototype, including its use in the LTCB HIV antibody blood test. Dr. Popovic told OSI that advancing the submission date of the papers meant his paper would have, "... to focus on HTLV-IIIb as a prototype instead of the RF isolate whose origin was more certain" (12/1/90 OSI interview; transcript p. 8) and "At that time when we had to go ahead, the best was IIIb and practically it was not difficult to choose whether IIIb or RF would be ... but for sure his [Gallo's] choice was IIIb ... that time what we have the best, we go ahead. That was a decision" (op cit., pp. 115 - 116). By April 11, NCI was moving actively to prepare patent applications. There was a particular urgency to this effort. Unless Gallo et al. filed their United States blood test patent application before there was any disclosure of the invention, they would forfeit their foreign filing rights. With news of the Gallo et al. blood test about to appear, much of it due to leaks engineered by Dr. Gallo himself, it was essential that the patent applications be filed immediately. Under these circumstances, it clearly would have been unthinkable for Gallo et al. to suddenly announce a delay of a month or more while they attempted to scale up another isolate and re-run their blood test data with that isolate, whose origins were "more certain" than the isolate they originally had chosen. Heterogeneity of HIV had not been discovered at this time; thus, there was little reason to fear that the use of LAI would be found out. For this reason and because there was no more time, the LTCB scientists had no choice but LAI/"IIIb" for the LTCB blood test. V. COMPARING THE VIRUSES A. The HHS Press Conference On April 23, 1984, HHS held a press conference for the international media. The press conference was scheduled on short notice, when news of the LTCB "discoveries" began to leak to the public. During the press conference, HHS Secretary Margaret Heckler announced that: "... the probable cause of AIDS has been found -- a variant of a known human cancer virus, called HTLV-III ... a new process has been developed to mass produce this virus ... we now have a blood test for AIDS which we hope can be widely available within about six months. We have applied for the patent on this process today" (emphasis added; press conference transcript, p. 4) Secretary Heckler, in her written text, spoke of the IP scientists' work, particularly their prior discovery of "a virus which they have linked to AIDS patients." Secretary Heckler said, "... within the next few weeks we will know with certainty whether that virus is the same one identified through the NCI's work. We believe it will prove to be the same" (Heckler prepared remarks, p. 3). These remarks and others acknowledging the IP contributions -- remarks added at the insistence of the scientists at CDC -- were selectively deleted from Secretary Heckler's spoken remarks. For his part, Dr. Gallo made the aforementioned unsupportable claims that he and his colleagues, "now have produced more than 50 isolates ... in mass production, and in detailed characterization" (op cit., p. 9) and "... we've been mass-producing it for six months" (op cit., p. 31). (Note : Dr. Gallo later would tell OSI that by "mass-producing," he meant "continuously producing" virus [4/26/90 OSI interview; transcript p. 64]. By this definition, Dr. Gallo's repeated claims that he did not "mass produce" LAV were untrue [see above ]). Remarkably, Dr. Gallo also disparaged the IP scientists' virus on grounds that it "did not react with the reagents we had." This statement was significantly misleading, since (1) LAV did react with the LTCB's AIDS/HIV reagents while (2) it not reacting with HTLV-I and II reagents, which is exactly what one would expect with a truly novel retrovirus. Dr. Gallo went on to say that his "HTLV-III" isolates "clearly do belong to the HTLV family." Thus, he said, he was not certain that the IP virus and his own were the same, although he added this: "It's probably because they really didn't have enough material. They didn't have enough material to send to us. That's what's been the delay. They don't have a mass producer. As of a few weeks ago, they didn't have it successful in a cell line ... I'm not sure they have enough quantity to do everything I'd like to do ... The problem before is there could not be a definitive answer from lack of amount of material that was sent to us" (op cit., pp. 31-32). Dr. Gallo's press conference claims that he had not received a sufficient quantity of the IP virus to compare it with "his" virus are belied by the records of his own laboratory, showing the extensive culturing and experimentation carried out with LAV. In addition, Dr. Gallo's professed uncertainty about whether LAV and "HTLV-III" were the same virus were at variance with his own utterances in Europe, just weeks before, with Dr. Popovic's views -- clearly recorded in the drafts of his paper -- and again, by the LTCB's own laboratory notes showing LAV and various "HTLV-III" isolates testing the same on a variety of assays. The tension within the HHS press conference concerning the work of the IP scientists vis-a-vis the claims of Gallo et al. was but one manifestation of a much broader tension, one that broke into public view in the days immediately leading up to the press conference. During this period, first the Associated Press and then, in a front-page story, TheNew York Times heralded the IP's discovery of LAV, plus the development of the LAV antibody blood test. Concerning the blood test, the AP wire story cited the IP test's performance in detecting, "... evidence of the virus in 80 percent to 90 percent of American AIDS patients whose blood samples were sent to Paris by the CDC ..." The AP story also made clear that the suspected AIDS virus: "... is different from the human leukemia virus that Dr. Robert Gallo ... and others have suggested is a possible cause of AIDS ..." The New York Times story, which ran in the Sunday paper the day before the HHS press conference, was even more problematic for HHS, for it featured comments by Dr. James Mason, Director of the CDC, which had collaborated actively with the IP almost from the beginning. The Times story, which led with Mason's saying he, "... believed a virus discovered in France was the cause of the acquired immune deficiency syndrome ..." also included the following observations, all of them problematic for HHS' imminent announcement of the LTCB's "triumphs": "Dr. Mason and other scientists familiar with the research said that they presumed HTLV-III, LAV and a third virus known as IDAV [another IP HIV isolate] were different names given to the same virus. But tests have not yet been made to determine whether the viruses are the same or not. 'Logic would lead you to believe that we are dealing with one agent with perhaps some closely related variants,' Dr. Mason said ... "Isolates of viruses similar to the LAV have been made in several laboratories and dozens of papers from these research groups are being written or have been submitted to medical journals... "One of Dr. Gallo's papers concerning HTLV-I and AIDS appeared in the issue of Science in which the French researchers published their results of the LAV virus last May... "... Dr. Mason said he was speaking out because of the urgency of the AIDS epidemic. 'We have to move forward on the assumption that this virus [LAV] is the cause in order to speed up trials of possible new therapies for the patients who are dying from AIDS,' Dr. Mason said." Dr. Mason's candid observations, entirely truthful, nearly cost him his job. Dr. Edward Brandt, the Assistant Secretary of Health, heard about the New York Times story in a Sunday morning telephone call from C. McLain Haddow, Margaret Heckler's Chief of Staff. According to Brandt's statements to Subcommittee staff, Haddow "turned the air blue" expostulating about Mason's account to the Times. Haddow demanded that Brandt call Mason to account. Later the same day, according to Dr. Brandt, Haddow described Mason's interview with the New York Times as "a deliberate embarrassment"; Haddow also reportedly told Dr. Brandt that Dr. Mason should be fired. The next day, Dr. Mason arrived at HHS, where, according to Dr. Brandt, he and Mason met alone. Dr. Brandt said that some time earlier, Dr. Mason had told him about the IP scientists' discovery of the probable AIDS virus and development of an HIV antibody blood test. Documentary evidence substantiates this account. Dr. Brandt mentioned in particular that on the day of the press conference, Dr. Mason told him about the "triple-sample" testing (i.e., the CDC comparative serology). Brandt said he came away from his meeting with Mason convinced that Mason believed the IP scientists deserved the credit for the discoveries attributed to them in the New York Times story. Dr. Mason told Subcommittee staff he had a vivid recollection of being severely scolded by one of Secretary Heckler's senior "public affairs" officials. Dr. Mason said this official accused him of "demeaning the American contribution" to AIDS research and of having "embarrassed Secretary Heckler." Not surprisingly, it was a very subdued James Mason who appeared at the HHS press conference. By the time of the HHS press conference, Dr. Brandt had determined it was imperative that a careful comparison of "HTLV-III" and LAV be carried out, not to determine if the viruses were genetically identical, for at the time, this issue had not been raised, but to determine if the viruses were the same type and were both the cause of AIDS. (Drs. Gallo and Montagnier agreed between themselves to compare the viruses, during Gallo's visit to the IP, two weeks before the HHS press conference.) Dr. Brandt told Subcommittee staff the imperative for the virus comparisons was partly "political," i.e., the press and the world were demanding to know if the viruses were the same. But also, said Dr. Brandt, the comparison was a matter of public health concern, since development of a blood test, development of possible vaccines, and development of potential treatments all might vary, if in fact there were two distinct viruses etiologically associated with AIDS. Dr. Gallo, in contrast, asserted to Subcommittee staff that comparisons of the viruses "did not affect public health." But Dr. Brandt told Subcommittee staff he considered comparison of the viruses and development of the HIV antibody blood test as his highest priorities, during the days and weeks immediately following the HHS press conference. Accordingly, by Dr. Brandt's account, the very day of the press conference, he relayed an order to Dr. Gallo, via NCI Director, Dr. Vincent DeVita, to move immediately to compare the viruses. B. Comparisons in the Spring/Summer of 1984 Three kinds of comparisons of LAV and HTLV-III (with IIIb as the prototype) were carried out in the Spring and Summer of 1984. No results from these comparisons were ever published. 1. Serological Comparisons: A paper describing the results of the serological comparisons based on the CDC samples (see above ) was written, but never published. Dr. Gallo evidently did not favor publication of this paper. A draft, prepared by CDC scientist Dr. Donald Francis, concluded this: "Overall a high proportion of patients' serum reacted in all laboratories whether HTLV-III or LAV prototype strains were used as antigens." The draft manuscript containing these observations was sent to Dr. Gallo for his comments. When Gallo responded, two months later, he did not deal with the contents of the paper. Instead, Gallo questioned the very existence of the paper, telling Dr. Francis that: "... I hardly think this [the serological comparison]is very important since we have said from the first that the viruses are likely to be the same, and since the data was obtained all of us have publicly reported it. A comparison of sera with both is nice but not of any real concern" (emphasis added; 12/27/84 Gallo-to-Francis letter). Dr. Gallo also told Dr. Francis that until the IP and LTCB scientists published their own comparisons of their virus isolates, "... neither you nor anyone else should be making serological comparative papers." Dr. Gallo devoted the bulk of his letter to Dr. Francis to a declamation on the merits of "HTLV-III" as the designation for the AIDS virus. Dr. Gallo was particularly exercised at Francis' use of the term "LAV/HTLV-III." Gallo told Francis: "I think it is silly ... for you to persist in the LAV (first) HTLV-III nomenclature ... LAV is clearly an inaccurate name and AIDS virus or AIDS related virus is the dumbest name I have yet heard... Clearly, human T lymphotropic virus III is as accurate, as innocuous, and as consistent with the past ... as any name possible." Dr. Gallo went on to assert that, "... last June, Jim Curran and Dr. Murphy assured me this would be the CDC name when our lines(s) and other reagents were distributed." But when Dr. Francis passed a copy of Gallo's letter to Murphy, querying him, "What was the deal," Murphy responded, in writing, "I don't recall any deal whatsoever regarding names." Dr. Gallo further said in his letter to Dr. Francis that, "If LAV procedes (sic) HTLV-III in this paper as a title then I will be last author. If not, I don't care who the last author is." Dr. Gallo added this ultimatum: "One or the other Don, but not both for your friends abroad." And Gallo added to the version of the letter transmitted to Dr. Francis, "If there is a problem for you then let's just forget the whole thing." Apparently, at least as far as Gallo was concerned, "forgetting the whole thing" is precisely what happened. In his letter to Francis, Dr. Gallo promised that he and his LTCB colleagues "will make our input to you soon" concerning the contents of the serology paper. But according to Dr. Francis, there were no further communications from the LTCB scientists concerning the paper. 2. Immunological (Proteins) Comparisons: Besides the serological comparisons, immunological comparisons of the viral proteins and molecular comparisons of the nucleic acids also were carried out. Two manuscripts resulted. Scientists from both the IP and LTCB were coauthors on both papers; the "proteins" paper was authored principally by the IP scientists (Chermann et al.), although the LTCB scientists performed several of the reported experiments. The nucleic acids paper was written by LTCB scientist, Dr. Flossie Wong-Staal. Neither paper was ever published. The comparisons of the viral core proteins of LAI/LAV and LAI/IIIb were accomplished by early-June 1984. These comparisons were initiated in mid-May, when Dr. M. Sarngadharan travelled to Paris, taking with him samples of "H9/HTLV-IIIB," both lysate and live virus. The decision to send a live cell line to the IP scientists seems to have represented a unilateral, last-minute change in plans at the LTCB. It was a decision that would have significant consequences. According to Dr. Montagnier: "At the beginning, the agreement was that we would not exchange live virus, but only detergent-treated lysates. But at the last minute, he changed his mind [Gallo] and on May 15, 1984, his associate Dr. Sarngadharan brought live HTLV-IIIb growing in H9 cells to our lab" (6/12/91 Montagnier-to-Hadley letter, p. 2). Dr. Montagnier's receipt of live virus from the LTCB, in May 1984, would later be used by Dr. Gallo as the basis for an accusation that Dr. Montagnier had contaminated his LAV with the LTCB's IIIb (see below ). Dr. Sarngadharan's OSI testimony did not illuminate why he took live virus as well as lysate; in fact, the testimony made it clear that the agreed-upon immunological comparisons depended on lysate, not live virus. Dr. Montagnier, who had not asked for live virus, may actually have harbored suspicions that he was being "set up," since, according to Dr. Sarngadharan, he (Montagnier) suggested that he might destroy the live virus sample (6/13/90 OSI interview; annotated transcript p. 56). The virus lysate that Dr. Sarngadharan took to Paris was used for proteins comparisons carried out in mid-May. The IP view of these experiments was expressed in a May 21, 1984 telephone call from IP scientist Dr. Jean-Claude Chermann to the CDC's Dr. Donald Francis. According to Francis' notes, the information about the experiments conveyed by Chermann was this: "Competition -- Sarang -- infected cells: competition by Francoise -- p25 [the viral core protein] same ... French side of comparison done." Dr. Gallo himself, writing to Dr. Montagnier, later said this about these experiments: "We have sent Sarngadharan to you to compare the proteins of LAV and HTLV-III using our hyperimmune sera to HTLV-III. As you know, there is substantial cross-reaction as anticipated" (7/3/84 Gallo-to-Montagnier letter; p. 1). Dr. Sarngadharan brought lysate of the IP virus back with him to Bethesda; in early June, he used the lysate to perform both Western blot and homologous competition assays. The latter experiment produced curves of precisely the same slope for LAV and IIIb, showing, according to Dr. Sarngadharan, that the viruses were identical in their antigenic determinants (op cit., p. 108). It is noteworthy that the PTO Examiner of the Gallo and Montagnier blood test patent applications told Subcommittee staff she had no idea that comparisons of the viral core proteins of LAV and IIIb were carried out as early as the Spring of 1984. The Examiner said this information was clearly material to her examination of Gallo et al., and should have been disclosed to PTO. Substantiating this assertion, when a paper by another group of scientists (Casey et al.), reporting similar results, was published in August 1985, the examiner cited it in support of her determinations that LAV and HTLV-III were the same virus and the work of Montagnier et al. was prior art to Gallo et al. The comparisons of the viral core proteins demonstrated the essential functional identity of the IP and LTCB prototype viruses, while the results of the Western blot experiments indicated that the IP scientists' failure to demonstrate the presence of the key envelope protein, gp41, was due to methodological deficiencies, rather than any real difference in the IP and LTCB viruses. Consequently, Dr. Gallo and his associates, around mid-June of 1984, made several on-the-record statements to the effect that the IP and LTCB viruses were "closely related." Thus: "'There is data now that they could belong to the same virus group of the same virus family,' said Gallo head of the team that made the American discovery" (June 14, 1984; Washington Post). And in a paper whose senior author was Dr. Sarngadharan, the LTCB scientists used the results of the proteins studies to induct the IP virus into the HTLV-III family: "Additional observations of a retrovirus likely belonging to the HTLV-III group were independently made by other investigators. A virus designated lymphadenopathy associated virus (LAV) was first reported in cultured lymphocytes from a patient with lymphadenopathy by Barre-Sinoussi et al. (1983). The same group also reported additional isolates called IDAV, from patients with AIDS (Vilmer et al., 1984). Preliminary comparisons between these viruses and HTLV-III demonstrated that they are closely related" (Sarngadharan et al., "Seroepidemiological Evidence for HTLV-III Infection as the Primary Etiologic Factor for Acquired Immunodeficieny Syndrome" (May 1984; Scientific Symposium of the American Red Cross; Published in Dodd, R.Y. and Barker, L.F. (Eds.), Infection, Immunity, and Blood Transfusion, Alan R. Liss, Inc., New York, 1985). In June 1984, approximately one month after the Red Cross symposium, Dr. Sarngadharan was quoted in a story in JAMA, the lead of which was this: "... there is mounting belief that the retrovirus recently identified by National Cancer Institute (NCI) investigators (Bethesda, MD) and the lymphadenopathy virus (LAV) reported last year by a group at the Institut Pasteur, Paris ... are the same. "... from the pattern of antibody reactions, I would be surprised if there is very much difference,' said M. G. Sarngadharan, Ph.D., ... a member of the NCI group" (JAMA, June 8, 1984, 251, No. 22; p. 2901). The contents of the Chermann et al. paper, reporting the results of the immunological comparisons of LAV and IIIb show how definitive were those results. This paper, which Gallo and his associates coauthored, contained the following significant passage in the introduction: "Two human retroviruses have been recently implicated as the causative agents of Acquired Immune Deficiency Syndrome (AIDS). The first virus described was designated Lymphadenopathy Associated Virus (LAV) ... Another human virus, named HTLV-III has been also recently identified as a prime candidate for AIDS ... Several lines of evidences (sic.) argue strongly that both viruses, LAV and HTLV-III, are similar and are indeed the primary cause of AIDS" (Emphasis supplied; "Comparative Immunological Properties of LAV and HTLV-III'; p. 1). Chermann et al. elaborated on the lines of evidence pointing to the functional identity of the IP and LTCB isolates: "They both show a preferential tropism for OKT4+ T lymphocytes ... and have cytopathic effects on this target T cells (sic.) ... A high prevalence of antibodies to each of the viruses have been found in the sera of patients with AIDS or pre-AIDS ... and both viruses have been frequently isolated from all individuals at risk for the disease" (Emphasis added; op cit., p. 1). So far as is known, Dr. Gallo and his colleagues never disputed these statements. Yet during the blood test patent dispute, in contrast to the statement in the Chermann et al. paper that "a high prevalence of antibodies to each of the viruses have been found in sera of patients with AIDS or pre-AIDS," Dr. Gallo wrote to Peter Fischinger in August 1985 that Montagnier et al., "... presented data of only 20% sera reacting with their isolate. With HTLV-III we had 90% or better" (8/29/85 Gallo-to-Fischinger memorandum, p. 1). Similarly, in September 1985, Dr. Gallo wrote to Dr. Fischinger that the IP blood test results were "inconclusive" (9/18/85 Gallo-to-Fischinger memorandum, p. 3). And the "Fischinger report" itself, endorsed as accurate by Dr. Gallo, asserted that the IP's blood test data, in July 1984, were "numerically much less firm" than the LTCB data. The Chermann et al. manuscript also contained the important information that LAV had been grown on the H9 cell line. This information would take on added significance during and after the blood test dispute, when Dr. Gallo would claim Dr. Popovic had not been able to grow LAV in H9, and thus, there was reason to believe LAV was a different virus than IIIb. The information in the Chermann et al. manuscript cast significant doubt on Dr. Gallo's assertion. The "Results" section of the Chermann et al. paper began with this significant observation: "Several reports on the characteristics and properties of either LAV ... or HTLV-III suggest that these viruses are probably the same or closely related viruses" (op cit., p. 4). The "Discussion" section of the paper said this: "... the pattern of antigenic immune recognition presented here demonstrates that LAV and HTLV-III are antigenically identical" (op cit., p. 6). and "... these results indicate that LAV and HTLV-III are either the same virus or variants belonging to a (sic.) same family of retroviruses" (op cit., p. 5). None of these results was ever communicated by Gallo et al. to the PTO, where as late as November 1984, the LTCB blood test patent application was being examined. And notwithstanding the statement in Chermann et al. that, "Several lines of evidences (sic.) argue strongly that both viruses, LAV and HTLV-III, are similar and are indeed the primary cause of AIDS," Dr. Gallo said in his November 1986 sworn declaration: "... I was satisfied that HTLV-III had been proven to be the cause of AIDS, but I saw no evidence of this for LAV up through the allowances of the Gallo patent" (11/8/86 Gallo declaration; p. 14). Dr. Gallo now says that the reference in his declaration to "no evidence" that LAV was the cause of AIDS was exclusively a reference to the published literature, not a general, all-encompassing reference. The declaration, manifestly, contains no qualification limiting Dr. Gallo's claim to the published literature. Moreover, even if the statement was explicitly limited to the published literature, it still would not be correct, since a substantial number of papers published in leading scientific journals by the November 1984 allowance of the Gallo et al. blood test patent, including papers coauthored by some of Dr. Gallo's own colleagues, contained evidence demonstrating that the IP virus was the cause of AIDS. These papers include but are not limited to the following: Brun-Vezinet et al., The Lancet, 1984, pp. 1253 - 1256; Klatzmann et al., Science, 225, 1984, pp. 59 - 62; Feorino et al., Science, 225, 1984, pp. 69 - 72; Kalyanaraman et al., Science, 225, 1984, pp. 321 - 323; Melbye et al., The Lancet, 1984, pp. 40 - 41); Mathez et al., The Lancet, 1984, p. 460; Cheingsong-Popov et al., The Lancet, 1984, pp. 477 - 480. The failure to disclose to PTO the conclusions contained in Chermann et al., plus a number of other papers at around the same time, did not relate merely to the Gallo et al. parent blood test patent application. More detailed declarations than those in the parent application, denying prior art, were made by Gallo et al., in July and August 1984, in submitting two CIPs to the parent application. In submitting these applications, (one for isolation and detection of antibodies to the core protein of "HTLV-III," (the 610 CIP), one for "immunological test kits" for assaying retroviruses such as HTLV-III (the 715 CIP), Gallo et al. said, under penalty for making false statements, that "... we verily believe ourselves to be the original, first and joint inventors" of the claimed invention. Further, Gallo et al. declared, concerning the material common to the parent and the CIP application that: "... we do not know and do not believe that the same was ever known or used in the United States before our invention thereof or patented or described in any printed publication in any country before our invention thereof ..." By the time these affirmations were made by Dr. Gallo and his associates, they knew that LAV and IIIb were at least functionally identical (and that LAV had been discovered long before the putative "IIIb"). They also knew that the IP blood test, invented many months before the LTCB test, was fully the equal of the latter test. Yet despite the PTO requirement for disclosure of material information obtained at any time during the prosecution of a pending patent, Gallo et al. made no disclosure of these clearly material facts to PTO. 3. Molecular (Genetic) Comparisons: The immunological comparisons of LAV and IIIB, significant as they were, did not touch on the issue that soon would become the focal point of the French/American dispute, namely, the genetic identity of the isolates, particularly, whether IIIb was derived from LAV. This issue was reflected in molecular comparisons of the nucleic acids of LAV and IIIb, comparisons conducted at the LTCB in the Spring and Summer of 1984. The circumstances and results of these comparisons were never thoroughly examined prior to the Subcommittee's investigation. OSI was misled and disadvantaged by being given false and significantly incomplete information, and thus failed to recognize telling discrepancies that, when examined by Subcommittee staff, led to important new revelations. Dr. Gallo told OSI that the first molecular comparisons of LAV and IIIb occurred in, "... August to September 1984 after an HIV probe was available" (5/25/90 OSI interview; transcript p. 49). According to Dr. Gallo's testimony, this comparison used DNA from a LAI/LAV sample ("LAV/B") Dr. Popovic had recently received (in July 1984) from Paris. The reason Dr. Gallo asked for this sample is not entirely certain, although it may be inferred from what happened thereafter. There was ample LAV remaining from that received in September 1983, including the freezes of the LAI permanent cell lines. Whatever Dr. Gallo's intent was in making the request, the fact is that the LAV/B supplied in response to the request became the vehicle for a "reverse contamination" accusation aimed at the IP scientists. In addition, Drs. Gallo and Popovic repeated many times the charge that the LAV/B sample they received was contaminated with an animal retrovirus. Concerning the LAV/B sample, Dr. Gallo said this: "This is a B cell line ... which we know has contamination. It was for a monkey retrovirus. This was cultured for a short time and given to Beatrice Hahn for DNA analysis. The cells were found to be contaminated -- Popovic found they were contaminated with squirrel monkey retrovirus ... Therefore, he didn't keep these cells in culture. The contamination was due to the Paris group's use of BJAB, a B cell line now know (sic.) to be contaminated with this lentivirus ... They should never have used that line" (op cit., p. 50). But the evidence shows that the LAV/B cell line received at the LTCB in July 1983 was not a BJAB line, but the EBV-transformed "FR8" line, the same line deposited by Montagnier et al. at the CNCM, in May of 1984. Moreover, there is no evidence that the LTCB scientists treated LAV/B as a suspect, possibly contaminated line. Rather, the evidence shows that the LTCB scientists grew up and extracted DNA from B/LAV, and performed a number of significant experiments with it, experiments that -- as described below -- showed LAV/B and "IIIb" were genetically identical. Dr. Gallo told OSI that the August/September 1984 LAV/IIIb DNA comparisons, in addition to LAV/B, also included a DNA sample designated as "AM." (A prior, undated LAV/IIIb comparison experiment -- in Dr. Beatrice Hahn's notebook -- included only IIIb and LAV/B.) Concerning the AM sample, Dr. Gallo described it as follows: "The AM DNA possibly, it is almost certainly -- refers to Ti7.4/LAV cells because the origin of that cell line, Ti7.4, is Abby Maizel, which Dr. Popovic remembers giving to Dr. Hahn, but neither Popovic or Hahn is certain of the identity of this DNA ... The AM DNA did not show the same restriction enzyme pattern as IIIb. So this is the confusion now. We begin now to document the source of the confusion" (emphasis added; op cit., p. 50). Dr. Gallo described another series of LAV/IIIb molecular comparisons, conducted in the Fall of 1984: "The final analysis of LAV DNA was carried out on November 27, '84 with DNA received directly from Chermann. This DNA hybridized to the HTLV-III probe, that would be IIIb ... November 27, however, '84 is long after there is reagents on both sides of the ocean. The CEM LAV and the HTLV-IIIb DNAs gave identical results with the restriction enzymes used. So that is our first comparison we are the same, but it comes from the November DNA, November 27th DNA. They had had for many, many months by then our IIIb producer cell line" (op cit., p. 51). There are a number of significant points to be made concerning the above remarks by Dr. Gallo: -- the claim that the first molecular comparisons of LAV and IIIb were carried out in August/September 1984 is inconsistent with other statements by Dr. Gallo indicating such comparisons occurred as early as June 1984 (see below for information concerning these other statements); -- the claim that the "AM" sample (of uncertain identity but believed to be Ti7.4/LAV) "did not show the same restriction enzyme pattern as IIIb" is misleading. The statement is contradicted by Dr. Gallo's own testimony elsewhere to OSI that the AM sample, "... could be a subset of the clones in HTLV-III (i.e., HXB2)" (Supplement to IIIb Exhibit 24B; Part 1, p. 3). Confirming these statements by Dr. Gallo, Dr. Beatrice Hahn, the LTCB scientist who performed the August/September comparisons of the "AM," "B/LAV," and IIIb DNAs, told Subcommittee staff the AM DNA had "one form of the various forms that are in IIIb," i.e., the HXB2 clone. It is important to note that by the time of the August/September comparisons, the LTCB scientists had already characterized the HXB2 clone, and thus, would have known the AM DNA was identical to this IIIb clone. -- the assertion that the November 1984 CEM/LAV -- IIIb DNA comparison "is our first comparison we are the same" is not correct. By Dr. Gallo and Dr. Hahn's testimony, LAV/IIIb comparisons from months before, including but not limited to the "AM" sample (which dated from September 1983) and the B/LAV sample received at the LTCB the previous July, showed the IP and LTCB viruses were genetically identical; -- the observation that the November 1984 results showing LAV and IIIb were genetically identical were based on LAV obtained from Paris after the IP scientists "had had for many, many months by then our IIIb producer cell line" is significantly misleading. The implication of this observation is that the IP scientists contaminated their cell lines with IIIb, when the live virus was sent to Paris in mid-May 1984. But at the time Dr. Gallo made this statement to OSI, in May of 1990, he had known for over a year that genetic tests had shown to a high statistical probability that his virus had to be descended from the IP virus, not the reverse (see below for further information on this point). Furthermore, evidence from the LTCB itself shows that by at least as early as December 1984, the LTCB scientists possessed information that cast significant doubt on any possible "reverse contamination" of the IP virus by IIIb. The evidence, a page in Dr. Hahn's notebook "IV," is headed, "First Patient LAV-1"; the page appears to contain a history of the culturing of the IP isolate, during 1983 - 1984 (the unnumbered page appears between numbered pages 44 and 45 in Dr. Hahn's notebook). Particularly relevant to the present discussion, the page shows that the IP virus, "frozen" in "September 1983," was "thawed" and used to infect the CEM cell line in September 1984. This LAV/CEM cell line presumably is the cell line provided by Dr. Chermann to the LTCB scientists (notably, the page in Dr. Hahn's notebook contains the entry, "J.C. Cherman [sic.] 12/10/84]). This "First Patient LAV-1" notebook page is important because the chronology contained on the page shows that the CEM/LAV cell line -- the cell line that, by Gallo's own admission was "identical" to IIIb -- was infected at the IP with LAV from a freeze made the previous September, not LAV that post-dated the transmission of IIIb to the IP scientists, i.e., LAV/B. This information, in conjunction with the LTCB scientists' information that their own cell line, Ti7.4/LAV -- also dating from the previous September -- was identical with IIIb, rendered impossible both the "reverse contamination" scenario and other scenarios posited by Gallo et al. to explain the genetic identity of the LTCB and IP prototype viruses (see below ). As the Subcommittee staff began to review this matter , evidence began to emerge that there were other LAV/IIIb comparisons performed at the LTCB, in the Spring/Summer of 1984, comparisons not disclosed to OSI. The first piece of evidence to this effect was the manuscript by Wong-Staal reporting the results of the molecular comparisons of LAV and IIIb (hereafter, the "Lancet manuscript"). Dr. Gallo did not provide this manuscript to OSI; in fact, he told OSI the paper was "never written" (4 /17/90 "HTLV-IIIb" List of Exhibits; p. 16). A copy of the manuscript reached OSI anonymously; when Dr. Gallo was confronted with it, he confirmed its authenticity. Dr. Gallo then revised his account from the assertion that the manuscript was "never written" to the assertion that he had been unable to locate it. The manuscript was an important source of new information. In particular, the Subcommittee staff's review of the manuscript revealed that it reported a set of comparison experiments different from the August/September experiments described by Dr. Gallo to OSI, i.e., different enzymes were used and several DNA samples other than those in the August/September experiments were analyzed. Of particular note, the Lancet manuscript specifically stated that Ti7.4/LAV was analyzed, although the manuscript did not make clear this was the LAV received the previous September. Most important of all, the results actually reported in the Lancet manuscript -- scanty as they were -- showed that Ti7.4/LAV and IIIb appeared to be genetically identical; yet the manuscript asserted, contrary to the reported results, that, "... LAV and HTLV-III are independent isolations of the same virus" (emphasis supplied; Wong-Staal et al., p. 7). The Lancet manuscript also obliquely alluded to other results, which allegedly, "... showed that each virus isolate, including LAV, could be distinguished provided enough restriction enzyme cleavage sites were examined..." But the referenced results -- that allegedly distinguished the IP and LTCB viruses -- were not included in the paper, and it seems impossible that they actually existed. The reality is that LAI/LAV and LAI/"IIIb" are the same isolate, were derived from the same person. And evidence obtained by the Subcommittee staff shows that Dr. Gallo himself had come to that determination in the Summer of 1984 (see below ). A second piece of evidence indicating the performance of LAV/IIIb comparisons other than those reported to OSI by Dr. Gallo is a letter from Dr. Gallo to IP molecular biologist Dr. Simon Wain-Hobson. In July of 1991, following the publication in Science of the Wain-Hobson et al. paper, reporting the origins of the prototype LAV in patient LAI, Drs. Gallo and Wain-Hobson had an exchange of letters about the IP and LTCB analyses of archived samples of LAV. In one of these letters, Dr. Wain-Hobson chided Dr. Gallo for claiming there were no "M2t/B/LAV derivatives" remaining at the LTCB that could have been analyzed and compared with IIIb (M2t/B/LAV was the September 1983 LAI/LAV sample used by Dr. Popovic to infect the Ti7.4 and HUT-78 cell lines). Dr. Wain-Hobson asserted he had been told by some of Gallo's own LTCB associates that samples of M2t/B/LAV did exist. Dr. Gallo's July 24, 1991 response to Dr. Wain-Hobson adverted to comparisons of September 1983 LAV with IIIb and indicated those comparisons showed the isolates were genetically identical. Here is what Dr. Gallo said: "You say that we had M2t/B derivatives available to us. I imagine this is your greatest misunderstanding. This is not the case. The only Ti7.4/LAV remnant that we have been able to locate is a Southern blot performed by Beatrice Hahn with four to six enzymes using DNA from a culture grown in the Summer of 1984. This pattern looked like that of IIIb and LAV-1, but we had a number of other samples at the time, which looked like IIIb. These all occurred in one incubator, and fortunately did not harm our several other independent isolates like RF, MN, JS and SC, which were cultured and kept elsewhere in the lab. Our conclusion was that we had a serious contamination problem, and as a result, the validity of the blot with Ti7.4 was very much in question. We could not find any freezes of cultures of Ti7.4 despite a very extensive search through our freezers. It was apparently long ago thrown out by Mika (Emphasis in original; 7/24/91 Gallo-to-Wain-Hobson letter)." There are several remarkable aspects to Dr. Gallo's account to Dr. Wain-Hobson of the LTCB's use of Ti7.4/LAV for comparison experiments. The most important points are that: (1) Ti7.4/LAV (M2t/B) was used, i.e., the LAV received at the LTCB in September of 1983; (2) the results showed that LAV "looked like that of IIIb" and "Our conclusion was that we had a serious contamination problem", i.e., LAV and IIIb were genetically identical; and (3) the allusion to the LTCB's having "a number of other samples at the time, which looked like IIIb." The latter allusion dates the LAV/IIIb comparison to May/June 1984, because, according to other testimony by Dr. Gallo and his associates, this was the time at which they discovered the existence of several samples supposedly contaminated by LAI/"IIIb." However, it is important to note that the existence of (apparently) bona fide "IIIb"-contaminated samples did not provide a basis for Dr. Gallo's attempted dismissal of the results of the LAV/IIIb comparison. The other allegedly IIIb-contaminated samples were grown in the H9 cell line, and according to Gallo, H9 was the likely vehicle by which the supposed contamination occurred. But there was no H9 involved in the Ti7.4/LAV culture; thus the occurrence of apparent H9/IIIb contamination of other LTCB cultures did not explain why LAV and IIIb were genetically identical; neither did it show that "IIIb" had contaminated LAV, and not the reverse. Besides the Lancet manuscript and the July 1991 Gallo-to-Wain-Hobson letter, other statements by Dr. Gallo alluded to the possibility of LAV/IIIb comparisons well before the August/September 1984 experiments described by Dr. Gallo as the first molecular comparisons in 1984. In the initial interview of the OSI inquiry, Dr. Gallo said this: Shortly after our papers appeared in May '84, three of these isolates, RF, MN, and JS, as well as the IIIb, of course, were analyzed and shown to be distinct from HTLV-I and HTLV-II, from each other by restriction endonuclease analyses. RF, MN, and JS were also shown to be very different from LAV, but IIIb was similar to LAV" (4/8/90 OSI interview; annotated transcript p. 34). Elsewhere in the same interview, Dr. Gallo returned to the early molecular comparisons, this time providing important additional information: "Originally when the restriction maps gave the same pattern [LAV and IIIb] we were not so surprised. The restriction maps of HTLV-I are usually the same, as are many animal retrovirus isolates. Then we got RF and a couple of other isolates that showed differences ..." (op cit., p. 43). Particularly significant in the above passage is the reported order of the experiments -- first LAV and IIIb were compared and found the same, after which RF and other isolates were found to be clearly different. The experiments with "RF" are known to have been performed on June 5, 1984, which means the LAV/IIIb comparisons were performed late May/early June. In his book Virus Hunting, Dr. Gallo said this: About this time (June-July 1984) Wong-Staal compared the genetic material of LAV with our isolates ... we learned that there was considerable variation in the viral genome when comparing one isolate to another ... "Last, and most unsettling, we discovered that one of our own HTLV-3B isolates was much closer to LAV than was typical of our other isolates ... Practically all were genetically different from one another. Yet LAV and our IIIb isolate(s) were distinctly close to each other" (pp. 197-199). Thus, from a multiplicity of perspectives, there is evidence that LAV/IIIB comparisons were performed, most likely in early-Summer 1984, comparisons that showed the two purportedly independent isolates actually were the same isolate, comparisons not disclosed to OSI. Importantly, those experiments were performed using the LAV received at the LTCB in September 1983, not the LAV received in the Summer of 1984. Because of these circumstances, there was no way the genetic identity of LAV and IIIb could be ascribed to a contamination in Paris. When Dr. Gallo was questioned by Subcommittee staff about these matters, he acknowledged there were earlier LAV/IIIB comparisons than those he reported to OSI. However, Dr. Gallo was unable, during the staff interview, to account for the data from the earlier experiments, although he continued to pursue the matter in follow-up telephone contacts with Subcommittee staff. During these contacts, Dr. Gallo at first asserted that "there are no new data." Gallo asserted that "if it's in the paper [the Lancet manuscript], we have data for it," and he claimed that all the relevant data were in the hands of OSI. Later, Dr. Gallo retreated from those assertions (see below). In one follow-up contact, Dr. Gallo pointed to an experiment dated July 19, 1984, the protocol for which is found in Dr. George Shaw's notebook #3. Dr. Gallo suggested this was one experiment that might be relevant to the Wong-Staal et al. paper. The experiment to which Gallo referred, headed "Characterization of AM infected line," is one of the experiments for which Drs. Shaw and Hahn's data are unaccountably missing; thus, the results of the experiment are unknown. However, the date of the experiment and some aspects of its design indicate it might be the Ti7.4/LAV-IIIb comparison experiment referenced in Dr. Gallo's 1991 letter to Simon Wain-Hobson, in which, according to Gallo, the Ti7.4/LAV restriction pattern was identical to IIIb. However, both the enzymes utilized and the DNAs analyzed are different from those reported in the Lancet manuscript. Thus, it is clear the July 10 Shaw experiment is not the one reported in this manuscript. The data for the manuscript, therefore, have never been produced. Dr. Gallo stated in follow-up telephone contacts with Subcommittee staff that his personal attorney, Joseph Onek, had in his possession data or copies of data that might include the data Drs. Shaw and Hahn said they could not find. Dr. Gallo said the data were given to Onek "for safekeeping" at the time of a "break-in" at the LTCB: "I think we stashed it all with him." Dr. Gallo assured Subcommittee staff he and Mr. Onek were searching for the missing data and when/if the data were found, they would be promptly provided to the Subcommittee. However, no data ever were provided; and when a follow-up written request was made, Dr. Gallo asserted Subcommittee staff had misunderstood him, that no LTCB data were in the hands of Mr. Onek. As for the Lancet manuscript and the July 1991 Gallo-to-Wain-Hobson letter, Dr. Gallo attempted to distance himself from both these documents. Concerning the manuscript, Dr. Gallo initially sought to assert that the Wong-Staal et al. paper was not significantly misleading with respect to the relationship between LAV and IIIb. Dr. Gallo argued that the paper, "... doesn't work in our favor. It says the viruses are the same." and "The paper says the blots are the same." But the paper does not say the blots are the same. Indeed, as noted previously, what the paper actually says is that, "... each virus isolate, including LAV, could be distinguished provided enough restriction enzyme cleavage sites were examined ..." And, as noted previously, the paper makes repeated references to its purported findings that LAV and isolates of HTLV-III, including "IIIb," are "genetic variants" and "independent isolations" of the AIDS virus, i.e., the paper says LAV and IIIb are genetically independent.. Confronted with these statements from the paper, Dr. Gallo acknowledged "there are no data in the paper" to substantiate that LAV and IIIb are independent" (op cit.) and he added this: "The worst interpretation that can be made is that the writer exaggerated the differences between LAV and IIIb. But it was not done by me" (7/27/93 telephone contact with Subcommittee staff). In fact, Dr. Gallo made it very clear he would not accept responsibility for the paper. Initially, Gallo told Subcommittee staff he was "doubtful he ever saw the paper." Gallo also said Dr. Wong-Staal "definitely" wrote the paper and, "I did not do one thing. I got the paper handed to me in the form you saw it" (7/27/93 telephone call to Subcommittee staff). Dr. Gallo also asserted "This was not a paper I had any hand in" (7/28/93 telephone call to Subcommittee staff). These claims cannot be substantiated; the Subcommittee staff obtained an early draft of the paper that bears Dr. Gallo's handwritten notes throughout the entire text. Notably, Drs. Shaw and Hahn, listed as coauthors on the paper, denied ever having seen it before it was presented to them by Subcommittee staff, during interviews in September 1992. In addition, neither Dr. Shaw nor Dr. Hahn had any recollection of performing the experiments reported in the Lancet manuscript or in the July 1991 Gallo-to-Wain-Hobson letter. As for the letter to Dr. Wain-Hobson, Dr. Gallo told Subcommittee staff that another LTCB scientist, Dr. Marvin Reitz, "helped" with the letter, obtaining information from another Gallo associate, Dr. Howard Streicher. Dr. Streicher, according to Dr. Gallo, gathered the information he gave to Dr. Reitz from data previously provided to OSI. But Dr. Gallo eventually acknowledged the data most likely were not provided to OSI. C. Accusation The Subcommittee staff also interviewed witnesses and reviewed a number of documents bearing on what Dr. Gallo said and did in the Summer of 1984 concerning the apparent genetic identity of LAV and "IIIb." The primary focus of the interviews and documents was a telephone call Dr. Gallo made to Dr. Luc Montagnier, variously dated from "early-June" to late-August 1984. In this telephone call, according to Dr. Montagnier and at least one independent witness, plus at least two documents contemporaneous with the events in question, originating with Dr. Gallo, Gallo told Montagnier he had compared LAV/B with IIIb and found they were identical. Dr. Gallo also accused Dr. Montagnier of having contaminated LAV with IIIb. If these accounts of Dr. Gallo's actions in the Summer of 1984 are correct, they would be very significant. If Dr. Gallo actually believed, in the Summer of 1984, that LAV and IIIb were genetically identical, it would raise questions about his subsequent, adamant assertions (as well as those of the U.S. Government) that the isolates were definitely genetically independent. Furthermore, if Dr. Gallo actually accused Dr. Montagnier of having had a contamination in Paris, it raises obvious questions about what possible basis, if any, Dr. Gallo could have had for such a charge, since LAV clearly arrived at the LTCB long before "IIIB" was even "isolated," much less sent to Paris. Dr. Gallo's accounts of the telephone call to Dr. Montagnier were not consistent with those of Dr. Montagnier, the independent witness, and/or the documentary record. Dr. Gallo's accounts emphasized his and Montagnier's alleged nonchalant attitude toward the possibility of a contamination. Dr. Gallo also minimized or omitted altogether his accusation of Dr. Montagnier and his associates. For example, Dr. Gallo said this to OSI: "I called Montagnier to tell him our two are close, but our others -- the IIIb and LAV are close -- but we have others that are not close, and it was like a 'so what,' you know? Groupings of the virus will be one way and others will be other ways. So we didn't make too much about it then, the common restriction enzymes of four or six enzymes" (4/11/90 OSI interview; transcript p. 66). Later in the same interview, Dr. Gallo said this: "To me, down deeply, it didn't matter at all until now ... and I didn't care if it was -- you know, when I called Montagnier, I assumed he made a possible problem" [edited by Dr. Gallo to read, "I then assumed if it was a contamination he made it"]. "I was letting him know. But then he convinced me he was unlikely to be a problem and, more or less, that I thought 'who cares anyway.' And it's okay. He had a virus earlier and he detected things and he has other detections and so what? Why would I want to make a case out of it? You know?" (op cit., p. 80). In another OSI interview, Dr. Gallo said this: "Well, I mean, at the beginning, remember, my first reaction was 'could it be?' An early reaction in time of this data accumulating when I was first thinking about it was 'could it be, could it be cross-contamination,' and quite frankly my early assumption was that if it was, it was in Montagnier's laboratory, and I called him to tell him the result, and I said, 'You know, IIIb and LAV are rather close.' And he said, more or less, 'So what? They should be close. They're the same kind of virus.' And I said, 'Yes, but we have this RF guy,' and now we have another one coming out, MN, and I've forgotten what else ... And his point was different viruses group, and how can you say this on the basis of just two things. But then my thinking, I can tell you exactly what my thinking was. 'Well, who cares?'" (4/26/90 OSI interview; transcript pp. 48-49). Dr. Gallo continued: "I mean, I wasn't concluding this was a contamination; it was a thought, that it was a possibility and I wanted to discuss this with him ... when I was there in March they hadn't successfully cloned yet. I mean their coworker there said they hadn't cloned anything, and they were certainly successful shortly thereafter, so I wondered if they had a cross-contaminant with IIIb which was growing very, very well. And when we had the discussion, I figured, you know, so what? It was clear that they had a virus before we brought them IIIb and if IIIb became a contaminant in their lab I, quite frankly, wasn't particularly concerned" (op cit., p. 50). In his book Virus Hunting, Dr. Gallo said this about the call to Dr. Montagnier: "In June 1984, I called Montagnier and told him of this last finding [the identity of LAI/LAV and LAI/IIIb] and of how odd I thought it. He seemed rather indifferent, however, remarking that 'they should be very close -- they were all the same virus after all.' I said yes, but also told him that we'd obtained data showing variations between different isolates, data that would be published in late 1984. He commented that maybe there were different groupings. I realized that one possibility was that LAV/BRU and HTLV-IIIb were actually the same isolate, maybe an accidental contamination occurring in his or my lab. I thought his attitude then was appropriate, however, and who would care? After all, there was no doubt that early on he had his own isolate because I knew we had received a bona fide novel retrovirus in 1983 from him, and I knew we had isolates other than the IIIb strain" (Virus Hunting, op cit., p. 199). And to the Subcommittee staff, Dr. Gallo said this: "I wondered about that possibility originally [contamination in Paris], basically because of my concern about their science competence." But, said Dr. Gallo: "It was really not important to me ... I never accused Montagnier of a contamination in his laboratory. I may have speculated about it in the bowels of my lab. But I never accused him ... it was not important to me" (7/22/93 interview with Subcommittee staff). Dr. Montagnier's account was very different; he took particular exception to the statements in Dr. Gallo's book. Responding to questions from OSI, in June 1991, Dr. Montagnier said this about the telephone call from Dr. Gallo: "I believe he called me on [the] telephone in June 84 saying that he had analysed LAV (not the early sample of September 83 'he could not grow,' but the virus produced in B cells (B/LAV) that I sent to him on his request ... and found it having the same restriction map as IIIb. He was surprised since he had analysed other isolates and found different restriction maps and wondered whether I could have contaminated our B/LAV by the IIIb we received on May 15, 1984. I told him (the version in his book is incorrect) that if there were to be contamination, it could only be the other way round, IIIb contaminated by LAV, since we had LAV long before and had sent this virus to other laboratories ... I deny to have said to Dr. Gallo, 'So what? Different AIDS viruses may group together.' This may be rather his reply. On the contrary, I was shocked by Dr. Gallo's accusation and decided soon afterwards to break off our collaboration, including the publication of joined papers for the comparison of LAV and IIIb. Further comments: It is clear now, since Dr. Gallo has admitted the contamination of IIIb by LAV/LAI, that the latter virus was grown in his laboratory, presumably in the continuous lines, for some time in 1983-84. Therefore, Dr. Gallo has not said the truth in 1984, or he was not informed by his collaborators of what was going on in his lab" (Montagnier-to-Hadley; 6/18/91). Several points are particularly noteworthy in these remarks. First, contrary to Dr. Gallo's accounts to OSI, suggesting a nonchalant attitude on the part of both he and Dr. Montagnier, Dr. Montagnier's account indicates there was a sharp disagreement with Dr. Gallo, and he (Montagnier) was particularly angered by "Dr. Gallo's accusation." Second, Dr. Montagnier makes clear that it was his outrage at the accusation that caused him, "... soon afterwards to break off our collaboration , including the publication of joined papers..." This account -- as well as the documentary record -- is at odds with Dr. Gallo's explanation of why the collaborative papers were never published (see below). Most important of all, Dr. Montagnier's account makes clear that he told Gallo there was positive proof that IIIb had to be descended from the IP virus, and not the other way around. That proof was the fact that the IP scientists "... had sent this virus [LAV] to other laboratories..." before IIIb was sent to Paris. In this regard, two scientists in the United States received LAI/LAV before the May 15, 1984 transport of "IIIb" to Paris -- Drs. Malcolm Martin and Murray Gardner. These circumstances would figure importantly in subsequent developments relating to the genetic identity of "IIIb" (see below). Testimony of an independent witness provided additional important information concerning events at the LTCB relative to the LAV/IIIb comparisons in the Spring/Summer of 1984. The witness, Dr. Stanley Weiss, now of the New Jersey College of Medicine and Dentistry, wrote to OSI in 1990, describing events he observed at the LTCB in the Summer of 1984, while he was serving as a Medical Staff Fellow at the NCI. Excerpts from Dr. Weiss' letter to OSI follow: "One afternoon, I came to 37/6A09 [Gallo's office] to meet with Dr. Gallo to discuss data related to a manuscript. Dr. Gallo was delayed. I have a distinct recollection regarding why. Dr. George Shaw was waiting as well; he was scheduled to meet with Dr. Gallo first. While we both were waiting, Dr. Shaw talked to me a bit concerning some data he was about to present to Dr. Gallo, for the first time. This was the result of the molecular analyses (restriction endonuclease maps) he and Dr. Hahn were doing on HTLV-IIIb and LAV-1. They appeared to be the same! At the end of Dr. Shaw's meeting with Dr. Gallo, they both came into the hallway and involved a few of us who were around in a brief discussion. Dr. Gallo clearly did not want to create new troubles, but he felt he needed to let the French know that somehow the French group must have contaminated the LAV-1 stock in France with some of the HTLV-IIIb that Dr. Gallo's group had sent them. The French had sent IIIb back to Dr. Gallo in error! The conversation focused on to whom among the French Dr. Gallo should first communicate this news. No one suggested that the direction of contamination might have been the reverse. It was absolutely clear that the news from Dr. Shaw had been a total surprise to Dr. Gallo. I had had the opportunity to get to know Dr. Gallo well enough that I feel confident that this must have been absolutely new. It was one of those instances where, in the presence of close colleagues, he rattled off his evolving thoughts. This included some harsh words regarding the French -- Dr. Gallo was chagrined at the wasted effort, at all the work that his lab had just done to compare the virus, only to find that they'd been given back IIIb, when there was so much else to do! I did not get to meet with Dr. Gallo privately that day. He retired to his office to solicit advice from other colleagues around the country. I believe he eventually called Dr. Montagnier later that evening to relate that it looked like the French had contaminated their LAV with material from LTCB ... "In summary, it is inconceivable to me that Dr. Gallo knew, or indeed in any way suspected, that the LTCB HTLV-IIIb isolate was derived from LAV-1" (emphases supplied; op cit., pp. 1-2). Dr. Gallo's account of his demeanor during the episode described by Dr. Weiss was not consistent with that of Dr. Weiss. In his book Virus Hunting, Dr. Gallo said this: "Stanley Weiss, an epidemiologist now working in New Jersey, was at NCI at that time and happened to have been near my office when I made this call. My concern, he recalls, was more for the likelihood of a contamination in Montagnier's lab, and he confirms the relaxed attitude I have described. Later I had reason to think that if the two viruses were so closely related that they might have been mixed up (accidental contamination), the mix-up would like have occurred in my laboratory. In any case, because we had many other isolates and had made other key scientific advances, not to mention the enormous scientific-medical problems that still lay ahead of us, my co-workers and I did not think this likelihood terribly important" (emphasis supplied; op cit., p. 199). Clearly, Dr. Weiss' account to OSI did not confirm a "relaxed attitude" on the part of Dr. Gallo. Equally or more important, Dr. Weiss' account shows how the last-minute transmittal of the live, virus-producing IIIb cell line to the IP scientists in May 1984 provided the foundation for the "reverse contamination" accusation (see above for a discussion of the last-minute decision to send the IIIB line to Montagnier). In addition, according to Dr. Weiss' account, there is no indication that any LTCB scientist questioned that LAV and IIIb were genetically identical. This is a significant point, because after the incident described by Dr. Weiss, Dr. Gallo and his associates began to publish papers that claimed LAV and "IIIb" were genetically independent isolates. Dr. Gallo also made repeated public statements to the same effect. Subcommittee staff interviewed both Dr. Weiss and Dr. Gallo about the reported incidents at the LTCB, in an effort to resolve the discrepancies in their accounts. Dr. Gallo seemed to contradict himself, when he denied his previous nonchalant characterizations of his affect: "I don't say anything is casual." Dr. Gallo also asserted to Subcommittee staff that the remarks attributed to him concerning a possible IP contamination, "truly were not an accusation." This claim was at odds not only with Drs. Montagnier and Weiss, but with the contemporaneous documentary record as well (see below ). Finally, although he himself previously referenced Dr. Weiss as a source of information concerning the events in question, Dr. Gallo suggested Dr. Weiss misunderstood what he observed. Dr. Gallo asserted: "Weiss doesn't really know me that well." But Dr. Weiss' testimony to Subcommittee staff was vivid, indicating Weiss had a clear recollection of graphic events: "Bob was emotional. I had never heard Bob curse before.... He was angry and frustrated. Here was everything here to be taken care of and he wanted to get on with the science and here was something else in the way and going to take up his time..." (Subcommittee staff interview, July 9, 1993). As for the documentary record , there are two documents dating from 1984 that bear importantly on these events. These documents show not only that Dr. Gallo, in the Summer of 1984, had proof that LAV and IIIB were genetically identical, but that he shared this information with an apparently credulous Peter Fischinger and Vincent DeVita. The contrast of this 1984 knowledge with the 1985-87 statements of these individuals, particularly the statements of Drs. Gallo and Fischinger, adamantly rejecting the possibility of genetic identity of the two isolates, is striking. The first document is a memorandum "To the record," dated August 24, 1984, referenced "Telephone conversation with R. Gallo - 8/24/84." The unsigned memorandum is written in a manner characteristic of Peter Fischinger; both Gallo and Fischinger acknowledged that Fischinger was the author of the memorandum. The memorandum bears a number of hand-written notations, appearing to be in the hand of Dr. Vincent DeVita. Dr. DeVita confirmed to Subcommittee staff the notations were his. The August 24, 1984 memorandum to the record was never provided by Dr. Gallo to OSI, neither was the memorandum ever provided by the National Cancer Institute or any component of HHS in response to any of the Subcommittee's numerous document requests. Neither the August 24 memorandum nor a related October 25, 1984 memorandum (see below) was ever provided to the IP attorneys, in response to their document requests under the Freedom of Information Act (FOIA). Significant passages of the August 24 memorandum follow: "Gallo's data: Original LAV sent to Bob several months ago has now been cloned and is different from prototype HTLV-III, i.e., it resembles the other HTLV-III that have been cloned, all of which have some variations. The LAV-containing B cell line sent by Montagnier has only a low per cent of cells infected with LAV, i.e., 1 in a 100. When this virus for the B cell line is compared, it is identical to the HTLV-III prototype, nucleotide for nucleotide! Gallo called Luc Montagnier and told him the above data ... It ... implies that what Montagnier is sending out to others as the LAV-infected cell line is HTLV-III and not LAV." The second memorandum relating to the Gallo/Montagnier telephone call was written by Gallo himself. This memorandum, like the August 24 memorandum, was not provided by Dr. Gallo to OSI nor to the Subcommittee. Indeed, when Dr. Gallo was questioned by Subcommittee staff about the memorandum, he said he could not recall why it was written, nor what basis there was for its contents. The memorandum, dated October 25, 1984, was written by Gallo to Drs. DeVita and Fischinger, NCI "Director" and "Associate Director," respectively. The memorandum's subject line reads , "Record of Telephone Conversation with Dr. Luc Montagnier on August 23, 1984." the text of the memorandum, in its entirety, reads as follows: "Montagnier was informed that we routinely find genomic diversity in our isolates of HTLV-III. He stated that he has cloned his virus and finds no variation among isolates. Of the cell line we received from Montagnier, one of one-hundred cells is producing the virus. The cell that is producing the virus has not been fully characterized yet, however, the virus looks like the H9/HTLV-IIIb virus. We went back to the original LAV that they had sent to us and when analyzed it was found to be different from the virus growing in the culture they recently sent. All isolates we have found are microheterogenous (sic.). We presume, therefore, that the cell line we received from them probably contains our virus. They had our producer cell line for months before we received theirs." The most significant fact about both of these memoranda, besides the fact that they substantiate that Dr. Gallo was accusing Dr. Montagnier of contaminating the IP virus with "IIIb," is that both memoranda assert "original LAV" had been compared with IIIb and found to be different. This circumstance was essential, in order for Dr. Gallo to hope to substantiate a charge of reverse-contamination. It is precisely what Dr. Gallo claimed had happened, but there is nothing to substantiate that it was true. Dr. Gallo himself, when he was questioned by Subcommittee staff about the matter, had no answer. In fact, when asked to explain the statements in the memoranda about "original LAV" being analyzed and found different from IIIb, Dr. Gallo acknowledged that, "We have no data analysis of the original LAV until 1991." Dr. Gallo added that any analysis of "early BRU" would have been biological only, which would provide only minimal information concerning the molecular composition of a virus sample. Analyses were done of M2t/B/LAV, of course, and those analyses revealed genetic identity with IIIb. These were the critical analyses. These were the analyses not revealed to OSI, to NCI officials, or to anyone else, until 1991, when Dr. Gallo wrote to Dr. Wain-Hobson. D. Stonewalling the Assistant Secretary Certainly the analyses were not revealed to the official who ordered them in the first place -- the Assistant Secretary of Health, Dr. Edward Brandt. Documentary evidence and testimony of several witnesses, including Dr. Brandt himself, shows that throughout the Spring, Summer, and Fall, Dr. Brandt prodded and questioned NCI administrators and scientists, seeking the results of the virus comparisons. But as Dr. Brandt told Subcommittee staff, "I never got them." What Dr. Brandt did get, in response to his repeated queries, was a series of denunciations of the IP scientists for allegedly delaying the virus comparisons, along with repeated promissory notes for results of the virus comparisons at some future date. But Dr. Brandt continued to push. Thus, according to minutes from the July 30, 1984 meeting of the Public Health Services (PHS) AIDS Executive Committee; cited in a memorandum written by Peter Fischinger: "Dr. Brandt also criticized Dr. Gallo for being so slow to produce a definitive statement on the identity (or otherwise) of LAV and HTLV-III. In April, he had promised this publicly within 30 days. Dr. Brandt says he wants a 2 or 3 page statement detailing the present status of these investigations (with scientific content, not only reasons for delay)" (8/9/84 Fischinger to Brandt memorandum; p. 1). That Dr. Brandt, in late-July 1984, was still seeking a definitive statement from Dr. Gallo concerning the identity of LAV and HTLV-III is noteworthy. The CDC serologial studies, over four months earlier, had provided compelling evidence that both viruses were etiologically associated with AIDS, while comparisons of the core proteins, over two months earlier, had shown that the viruses were "antigenically identical." Dr. Gallo had made statements to the media that the viruses were "close relatives," but, despite Dr. Brandt's order to Dr. DeVita to see that the viruses were compared, apparently NCI/NIH had not provided any authoritative information to the Assistant Secretary for Health concerning the functional identity of the isolates. Still less did NCI/NIH inform Dr. Brandt of the LTCB data indicating that LAV and IIIB were genetically identical. On August 13, not having received a satisfactory response, Dr. Brandt raised the issue again, at another meeting of the PHS AIDS committee. Notes of the meeting, contained in a memorandum to the record written by the Special Assistant to the then-NIH Director, James Wyngaarden, said this: "Dr. Brandt again brought up his concern that the issue of identity versus difference between HTLV-III and LAV is not yet settled publicly. He believes that the continuation of this uncertainty undermines public and congressional confidence that either party knows what it is doing. He is aware of the French foot-dragging, and offered to try to contact his counterpart in the French Ministry of Health to try to break the logjam. Dr. Harmison proposed a meeting next week between NIH and CDC to see if these PHS agencies could settle the issue; they have all the necessary materials. However, no American investigator is happy to proceed to do, with the samples supplied by Institut Pasteur, what the source seems unwilling to do. Possible implications for the commercial concern working with LAV were discussed, but no one present has all the information on legal ramifications" (emphasis added; 8/24/84 "Notes from PHS AIDS Executive Task Force Meeting 8/13/84," pp. 1-2). Dr. Brandt's reported reference to "French foot-dragging" warrants comment; it apparently was based on information contained in Peter Fischinger's August 9, 1984 response to Brandt's July 30 queries. Fischinger's response catalogued a number of alleged failures of cooperation on the part of the IP scientists, none of which had any basis in fact. Appended to Fischinger's memorandum was a July 3, 1984 letter from Dr. Gallo to Dr. Montaganier, a letter copied to no less than four IP scientists and administrators, plus 15 United States scientists and administrators, located throughout the entire East coast of the United States. The letter included this very noteworthy claim: "We acknowledge receiving some extracellular virus from you, but this is, of course, not permanent and small in amount." (Dr. Gallo maintains the above information is what he was told about the growth of the IP virus at the LTCB. If this is true, it would mean that Dr. Popovic, presumably, significantly misrepresented the results of his experiments to Dr. Gallo.) Dr. Fischinger told Subcommittee staff his August 9, 1984 response to Dr. Brandt was based on information provided to him by Dr. Gallo. However, not only is there no evidence that the IP scientists were not cooperating with the virus comparisons, the evidence that exists shows that weeks before Fischinger wrote his memorandum, in mid-July, 1984, Dr. Gallo wrote to thank Dr. Montagnier for sending his LAV/B virus, telling Montagnier this: "Now we each have the proper lines and reagents and I look forward to an era of cooperation and good-will" (7/13/84 Gallo-to-Montagnier letter). Dr. Fischinger was copied on this letter. In addition, on July 16, 1984, Dr. Gallo wrote again to Dr. Montagnier. Apparently referring to his confrontational letter of July 3, Dr. Gallo said this: "Unfortunately in the previous letter I wrote to you recently I neglected to mention that my letter was prompted not by failure of you to cooperate with us but rather by some medical articles in the U.S. which had repeatedly stated that we had not made reagents available to you" (emphasis added). Notably, the July 16 Gallo-to-Montagnier letter was copied only to the four IP scientists/administrators copied on the July 3 letter. The 15 U.S. scientists/administrators copied on the July 3 letter did not receive Dr. Gallo's "clarification." The details of what happened after the August 13 PHS meeting are not entirely clear, but it appears that a strategy for a series of CDC-coordinated comparisons of the viruses was devised. Pursuant to this plan, on August 17, 1984, Dr. Donald Francis wrote to Drs. Montagnier, Chermann, and Gallo, seeking their cooperation. Dr. Francis' letter indicated the recipients already were aware of and had agreed to CDC's involvement: "As you know, the proposal has been made that CDC coordinate the comparisons of prototype strains of LAV and HTLV-III. The data from these comparisons, subject to approval of designated scientists, would be published in a scientific journal with authorship agreed in advance" (8/17/84 Francis-to-Montagnier, Chermann, Gallo letter; p. 1). Dr. Francis' letter stressed that the "need for comparisons is urgent"; the letter also laid out the kinds of comparisons that would be done, and what steps were necessary for the comparisons to get underway. Drs. Montagnier and Chermann responded jointly to Dr. Francis' letter on August 29, 1984, noting their understanding that the proposal for CDC's coordination of the comparison studies "was a specific request from the Secretary of Health in a meeting where NCI and CDC representatives agreed that this comparison should be urgently completed." Montagnier and Chermann also committed immediate shipments of LAV virus and a LAV DNA clone. They also agreed that there should be a paper on the serological study, "dealing with the data obtained by ELISA LAV and HTLV-III on the 300 sera given by CDC to Dr. Gallo and us." Still, Drs. Montagnier and Chermann cited reservations about the comparisons that supposedly were already underway (the reader should keep in mind that the Gallo-to-Montagnier "reverse contamination" call had only recently occurred): "As you are aware, Dr. Gallo had the possibility to do this comparison on its own, since he had our LAV virus at least from September 23, 1983. After the isolation of HTLV-III was announced, we accepted to make a direct comparison with him between HTLV-III and LAV-1." Montagnier and Chermann described their concerns at Gallo's continued refusal to send them the uninfected H9 cell line, which they said was necessary to complete the proteins comparison of LAV and IIIb. (See below for more information on this point.) However, Montagnier and Chermann said that "whatever the conclusion (or lack of conclusion)" of the ongoing comparisons, they agreed that "an official comparison be made under CDC control." And Montagnier and Chermann said that, with respect to the CDC-brokered comparison, "We want to ensure you of our willingness that this comparison will be made by all the concerned laboratories ... It is important for the sake of public health that this comparison be achieved as soon as possible." Montagnier/Chermann's letter to Francis was copied to Dr. James Mason at the CDC, along with, at NIH, Drs. Wyngaarden, DeVita, Fischinger, and Gallo. Dr. Brandt, regrettably, was not copied, and thus continued to operate under the assumption that the IP scientists were not cooperating with the comparisons (see above). Dr. Gallo, for his part, never responded to Dr. Francis' letter; none of his superiors, it appears, ever directed him to cooperate with the supposedly agreed-upon plan. Despite the CDC and IP scientists' willingness to proceed with a CDC-coordinated comparison of LAV and IIIb, the comparison never got off the ground, because NCI and Dr. Gallo would have no part of it. And Dr. Brandt continued to be frustrated in his requests for the facts. In fact, at the very next meeting of the PHS Task Force, on August 27, Brandt addressed the issue again. The official minutes of the meeting say this: "Expressing his concern about the lack of cooperation of L'Institut Pasteur, Dr. Brandt re-stated his belief that a comparison between LAV and HTLV-III should be completed soon ... Reporting this effort to be on track, Dr. Harmison suggested that a meeting between Drs. Gallo and Montagnier may need to occur." By September 10, 1984, the issue of the similarity/dissimilarity of LAV and IIIb had become an even more urgent concern. On this date, Dr. Brandt, still not having received an answer, wrote to NIH Director Wyngaarden, saying this: "I am ... advised that a paper has been prepared that shows that LAV and HTLV-III are essentially the same. It is my understanding that the paper will be presented in Rome in September. Since you and I will be testifying on AIDS on September 17, and since this will be an issue at that hearing, it is imperative that I be advised of the situation." Emphasizing the urgency of the matter, Brandt added to the memorandum, "Please respond this week." There is no record of Wyngaarden's response to Brandt's request. Wyngaarden, like all the other major NIH/NCI players, told Subcommittee staff he had no recollection of these matters. What is known is that on September 17, 1984, when Dr. Brandt (accompanied by, among others, Drs. Mason, Wyngaarden, and Harmison) testified before the Subcommittee on Health and the Environment of the House Committee on Energy and Commerce, Dr. Brandt, after praising the LTCB scientists for their "discovery" of "HTLV-III," said this: "Scientists from the Pasteur Institute in Paris also isolated a retrovirus, termed lymphadenopathy-associated virus (LAV), from a homosexual man with the lymphadenopathy (sic.) syndrome and published their results in April 1983 (sic.). Recently, scientists at the NCI have determined that LAV is an HTLV-III virus. CDC and other groups have described additional virus isolates of the HTLV-III family" (emphasis added; statement of Edward N. Brandt, Jr., M.D.; p. 18). This, then, is how the results of the LAV/IIIb comparison was represented to the Assistant Secretary for Health: not that IIIb and LAV appeared possibly to be the same isolate, the result of (at best) a contamination; not even that IIIb and LAV were the same virus type; but that "LAV is an HTLV-III virus." Thus was the parent inducted into the putative family of the offspring; this was Dr. Gallo at his finest. The failure to provide a full and accurate accounting of the LAV/IIIb comparisons to Dr. Brandt was not Dr. Gallo's alone. According to Dr. Brandt, the original order to make the comparisons was delivered by him to Dr. DeVita, and there are indications Dr. DeVita made some effort to comply. Most notably, the October 25, 1984 Gallo-to-DeVita memorandum bears a handwritten note (confirmed by Dr. DeVita to be his) to Dr. Brandt, that says this: "11/9. Ed. Interesting point. Doubtful that with the variations in the HTLV lines that the line from Montagnier could be coincidentally the same. Vince." Dr. DeVita's notations also indicate that Dr. Gallo's memorandum, together with his note to Dr. Brandt, were to be sent to members of the NCI "Executive Committee." But Dr. Brandt told Subcommittee staff he never received a copy of Gallo's memorandum, nor did he receive a copy of Dr. DeVita's note. No copy of either document was ever produced to the Subcommittee from any member of the NCI Executive Committee. No copy of the typed version of Dr. DeVita's note was provided to the Subcommittee from any source. Dr. DeVita told Subcommittee staff he could not explain why Dr. Brandt would not have received his (DeVita's) note and Dr. Gallo's memorandum. Dr. DeVita said he was "sure" the memorandum had gone to Dr. Brandt's office, but DeVita added this: "By this time, Harmison was there [i.e., was Science Advisor to the Assistant Secretary for Health] ... He could have stopped it ... By this time, Harmison almost assumed ownership of Gallo" (5/3/93 interview with Subcommittee staff). E. Aftermath of the Comparisons Although in the Summer of 1984, Dr. Gallo had told top NCI officials that LAV and IIIb were genetically identical, by late 1984/early 1985, Dr. Gallo was taking a very different line. Following Dr. Montagnier's rejection of Dr. Gallo's assertion that he (Montagnier) had contaminated LAV with IIIb, Dr. Gallo began to assert that the two isolates, although very much alike, actually were independent. Thus, as previously described, the Wong-Staal et al. manuscript reported -- without substantiation -- that, LAV and HTLV-III [IIIb] are independent isolations of the same virus." Similarly, a February 1985 letter by Ratner et al. (including Gallo and Wong-Staal) to the journal Nature claimed that, "LAV is closely related to HTLV-III" and "HTLV-III, LAV, and ARV are variants of the same virus (emphasis supplied; 313, 1985, pp. 636-637). Ratner et al. also introduced the geographical/temporal proximity explanation for the identity of the IP and LTCB prototype viruses, i.e., the viruses were said to be so much alike, "... because the individuals from whom these isolates were derived acquired the virus at a similar time and place." This argument was repeatedly proffered by Gallo et al., without substantiation, and despite the fact that such data as did exist indicated there was no evidence for isolates from the same geographical area to be more alike in their genetic makeup. Other papers by Gallo et al., published in the Fall of 1984, did little more than note the existence of LAV and give brief mention to the results of the immunological comparisons that had been performed, including the LAV/IIIb comparisons. The already-completed molecular comparisons were not revealed; in fact, molecular comparisons were described as work remaining to be done in the future. Thus, Hahn et al. wrote in Nature, in November 1984: "The availability of the cloned HTLV-III genome should also now allow direct comparison of this virus with a similar group of retroviruses described by other investigators ... which has also been linked to the pathogenesis of AIDS and which appears to be immunologically and morphologically indistinguishable from HTLV-III (M. Sarngadharan et al., unpublished)" (312, 1984, pp. 166-169). The following month, Shaw et al., wrote this in Science: "The availability of molecular clones of HTLV-III will now permit the direct comparison of this virus to other retroviruses detected in patients with AIDS or ARC. These viruses, named variously as LAV, IDAV1, IDAV2, and ARV (27, 33), are morphologically indistinguishable from HTLV-III and, for those isolates tested, immunologically indistinguishable as well ... On the basis of these results and of our detecting viral sequences in LAV-infected cells using HTLV-III probes ... we believe that HTLV-III, LAV, IDAV1, IDAV2, and the most recently described AIDS-associated viral isolate, ARV, are all essentially the same virus. However, given the diversity in the genomic restriction pattern of HTLV-III reported herein, we would expect similar differences to be present in these other viral isolates" (226, 1984, pp. 1165-1171). In reality, Gallo et al. had known for quite some time that two of the isolates they mentioned -- LAV and "HTLV-III" (IIIb) -- did not show differences, but rather, appeared to be molecularly identical. These findings, they failed to report. F. The Sabotaging of Bryant et al. Dr. Gallo's reversal of his original conclusion that LAV and IIIb were genetically identical and his adoption of the "close but not the same" argument may account for his strongly negative reaction to a manuscript he received during the Fall of 1984. Coauthored by Dr. Murray Gardner, a specialist in simian AIDS at the University of California, and a young postdoctoral fellow, Dr. Martin Bryant, the paper reported a comprehensive series of studies, including molecular studies, comparing LAV, IIIb, and ARV ("AIDS-related virus," isolated by Dr. Jay Levy, University of California). The Bryant et al. virus comparisons were precisely the kind of studies Dr. Gallo attempted to prevent in his materials transfer agreement (see below ). Dr. Gardner, who obtained IIIb from an LTCB contractor, was not required to sign the "no comparisons" agreement, and he apparently had no idea what a transgression the Bryant et al. comparison studies would represent. Nor could Gardner have anticipated what a threat the results of the comparison studies would pose. Notably, neither the Bryant et al. manuscript nor any of the correspondence related to it were provided to OSI or to the Subcommittee by the LTCB or any other component of HHS. The Bryant et al. draft reported, concerning the molecular comparisons, that "ARV can be readily distinguished from the LAV and HTLV-III," but "LAV and HTLV-III are identical" (emphasis added). The paper also reported that LAV was found to contain "two nearly identical viruses," i.e., "strain polymorphism." The same Hind III polymorph was found independently in LAV, by Dr. Malcolm Martin, and it was found in IIIb by Gallo et al. (Hahn et al., Nature, 1984; Shaw et al., Science, 1984). The presence of two identical virus variants in both LAV and IIIb, i.e., the Hind III polymorph, was compelling evidence that these two allegedly independent isolates were, in fact, one and the same. Dr. Gallo acknowledged to OSI that Dr. Martin's data convinced him (Gallo) that IIIb was identical to LAV and that IIIb was derived from LAV and not the reverse: "... I assumed that we made a cross-contamination ... and I kept thinking, well, what the hell is the difference, and then also we know that a person, as you know, who is not friendly to me [Martin], had said that he received the Pasteur virus about two weeks before we gave Montagnier IIIb ... Therefore, if he made the same analysis, I always assumed that it had to be -- that there was a contamination but who really cared?" (7/10/90 OSI interview; transcript p. 8). "In time, because of one individual's data and because of realizing that we had crowded conditions, I, in my mind, accepted the notion, if it was contamination, if it could be proven to be contamination, it probably happened in our laboratory, one because of the crowded conditions and the move that Popovic made, and secondly because Dr. Martin at NIH had stated that he got LAV just before we brought IIIb to France" (4/26/90 OSI interview; transcript p. 50). Dr. Gallo's admission to OSI concerning the significance of Dr. Martin's data occurred very belatedly, nearly five years after Dr. Gallo saw the data. In 1985 , when Dr. Gallo first learned about Dr. Martin's data, he adamantly rejected their legitimacy and significance [see below]. The reason for Dr. Gallo's attitude is obvious. Drs. Gardner and Martin obtained their LAV samples from Dr. Montagnier in April 1984, several weeks before Dr. Gallo sent IIIb to Paris, a circumstance of which Gallo was aware, at least by September, 1985, if not sooner. Dr. Gardner actually received his LAV during his April 1984 visit to the Institut Pasteur, at which Dr. Gallo also was present, when the CDC data were reviewed. The identity of the Martin and Gardner LAV samples with IIIb, besides demonstrating that the putative LTCB prototype virus was not an LTCB isolate, could only mean that IIIb was derived from LAV and not the reverse. When Dr. Gallo saw the draft of the Bryant et al. paper that Dr. Gardner sent to him for comment, Gallo's reaction was strongly negative. According to Dr. Bryant, at first there was no reaction from the LTCB. Weeks went by following the transmittal of the manuscript, and when Dr. Gallo finally contacted Gardner, he (Gallo) alternately harangued and pleaded with him to delay or abort altogether publication of the Bryant et al. paper. Dr. Gallo reportedly did not question any of the results on scientific grounds. Rather, Dr. Gallo reportedly stated that he and Dr. Montagnier were "sorting out" the virus comparisons, that the LTCB scientists were more expert at such studies, and that he and his colleagues desired to inform the scientific community about the virus comparisons in their own terms, according to their own timetable. Dr. Gallo also reportedly appealed to Dr. Gardener's patriotism, implying it was unAmerican to publish the Bryant data. Dr. Peter Fischinger also reportedly became involved, telling Gardner, "You would be well-advised not to get in the middle of this." Dr. Gardner was so upset by these communications that he called a colleague at the University of California, Dr. Jay Levy, to tell him about the pressure being exerted on him by NCI. Levy in turn called Dr. Malcolm Martin, who memorialized the conversation in a November 28, 1984 memorandum to the record stating this: "At 4:30 today I received a telephone call from Dr. Jay Levy. He was quite upset because of pressure being put on Dr. Murray Gardner by the NCI staff not to publish data presented at the Montana workshop [the molecular data in Bryant et al.]. He likened the situation to a 'Watergate coverup' and stated that all data pointed to apparent theft of the French AIDS virus." Dr. Gardner, who held several NIH grants and contracts, and who feared he might lose them, acceded to Dr. Gallo's demands. The Bryant et al. paper eventually was published, but not until almost a full year had passed. The paper was not published in the more prestigious journal for which it was originally intended, but in an obscure journal, Hematological Oncology. The published version of the paper had been substantially revised vis-a-vis the original version. Notably, the statement that LAV and IIIb were "identical" was changed to "nearly identical." Other changes on the same theme were made throughout the paper. Dr. Bryant, who described himself as "devastated" by the entire affair, told Subcommittee it was one of the reasons he left Dr. Gardner's laboratory. G. Fate of the Comparison Papers None of the three virus comparison papers was ever published. The serology paper died due to Dr. Gallo's evident lack of enthusiasm and his failure to provide any input to the paper other than objecting to the virus designation and the order of authorship (see above). Concerning the proteins and nucleic acid papers, Dr. Gallo for years asserted that Dr. Montagnier stopped publication of both papers. Here are examples of Dr. Gallo's statements on this issue over the years: "We worked together ... We made the comparison. We planned the publication. The papers are written. The drafts are ready. Montagnier decides we don't need to publish. I get blamed for not making comparisons" (8/3/90 OSI interview; transcript p. 105). Pressed about these statements, asked if, "You wanted to publish those papers," Dr. Gallo responded with this: "Of course I wanted. No, I wanted him with it. If he didn't want it I would ... I was all for the publication of the papers at all times. Montagnier convinced me. I said it is not unreasonable since the sequence is going to be out, why would we really need it?" (op cit., p. 105). In a subsequent interview, referring to both of the collaborative papers, Dr. Gallo said this: "It was planned to make new publications with the Pasteur group in the Summer of 1984 ... This was worked on in June of 1984 in which some of our isolates would be compared to their LAV/BRU. You will recall from multiple times mentioned in these inquiries that I told you, we wrote two papers, one in which Chermann was coauthor, one in which Flossie was coauthor, Wong-Staal. But on Montagnier's suggestion to me, we did not publish those papers" (9/23/90 OSI interview; transcript pp. 14-15). Dr. Gallo made similar comments to journalist Mark Caldwell. As quoted by Caldwell, based on audiotaped interviews, Dr. Gallo said this: "'... we were set to publish an analysis of IIIb and LAV to show how close they were: Flossie Wong-Staal had a paper written on the molecular biology, Chermann had one on the protein comparisons. He wanted to publish, we wanted to publish, but Montagnier changed his mind and decided we shouldn't: he said he thought it was superfluous, no longer needed. Once the sequencing had been done for both LAV and IIIb, anybody could see the similarity. I agreed'" (Mark Caldwell, "Robert Gallo and the Virus," unpublished manuscript, p. 96). Most recently, responding to a set of questions posed to him by NCI Director Samuel Broder, Dr. Gallo said this: "I actively pushed for a joint comparison of HTLV-IIIB and LAV. In April of 1984, before publication of the Science papers, I visited the Institute Pasteur, described some of our data and arranged for a collaboration to compare the two viruses. Approximately two weeks after publication of the Science papers, one of my associates (Sarngadharan), visited the Pasteur and began the initial comparison of the viruses. That summer and fall, further analysis took place, resulting in two joint manuscripts. (Ultimately, Dr. Montagnier chose not to publish the two manuscripts because the separate sequencing work was moving ahead so rapidly.)" (6/3/94 Gallo-to-Adamson). The facts do not substantiate Dr. Gallo's account of the fate of the collaborative papers. In reality, Dr. Montagnier did not object to publication of either paper. Rather, as seen in the contemporaneous documentary record, what Dr. Montagnier said was that he did not wish to coauthor the Wong-Staal et al. paper, for reasons explicated by him and reasons that may be inferred from events that had gone on before. On January 2, 1985, Dr. Montagnier wrote to Dr. Gallo, "... to let you know our opinion (Francoise, Jean-Claude, Simon and I) about the projects of joined papers." Dr. Montagnier's letter described the IP scientists' views about the status of each of the two papers: "1) Paper on proteins: This paper is close to the final form. We gave a copy to Sarngadharan at the NCI meeting, with the original figures. He basically agreed on this version and proposed some minor corrections. If you also agree, please send back to Jean-Claude the copy with original figures and the proposed corrections, so that he can send it to the Editor of Lancet. 2) Molecular biology paper: We do not wish to co-sign this paper because a) it is essentially the work of Flossie, and we have not really participated; b) sequence data on LAV, HTLV-III will be published very soon, so that the paper may be obsolete when it will appear." Clearly, Dr. Montagnier was prepared to complete and submit the proteins paper. As for the nucleic acids manuscript, Dr. Montagnier did not say it should not be published. Rather, he said he and his IP colleagues did not wish to be associated with it, hardly a surprise, considering Dr. Gallo's "Paris contamination" accusation of the previous summer, followed by the contradictory inexplicable assertion in the Wong-Staal et al. paper that LAV and IIIb were "independent" isolates. It was Dr. Gallo, not Dr. Montagnier, who stopped the preparation and submission of both the comparison papers. Dr. Gallo responded to Dr. Montagnier's letter on January 25, 1985, saying this about the nucleic acids paper: "Flossie has spent a lot of time to prepare that paper, and it is unfair to her at the final stage to say you do not want to publish. Although she did most of the work, had your group provided the data, she would have gladly incorporated them. Therefore, I feel that we should either publish both papers or neither. I hope you can understand my position." One more letter remained to be exchanged concerning the LAV/IIIb comparisons. Dr. Montagnier wrote to Dr. Gallo on March 4, 1985, noting without elaboration that the recently-published sequences of the IP and LTCB prototypes showed them to be "remarkably similar." Dr. Montagnier then voiced the concern underlying much of the tension between the IP and LTCB scientists, ever since the HHS announcement: "Wasting time on both sides should have been avoided from the beginning, if in one of your Science papers of May 1984, you had published the comparison with the LAV1 sample you had received from us six months earlier." H. Dr. Gallo's Explanations When Dr. Gallo was questioned by Subcommittee concerning the Summer 1984 comparisons of the IP and LTCB viruses, he initially responded with such comments as, "I don't know why this is interesting" and "It wasn't important to me." Subsequently, Dr. Gallo acknowledged that in the Summer of 1984, he had believed the viruses were identical, but he offered a variety of explanations he said he entertained concerning these circumstances, explanations that according to Dr. Gallo, reflected "absolute proof there is confusion" at the LTCB concerning the genetic identity of the viruses . Dr. Gallo's explanations are itemized below, to permit the reader to make an independent evaluation of their credibility; however it first is important to note that if, as he now admits, Dr. Gallo actually believed or suspected -- during the Summer/Fall of 1984 -- that the LTCB and IP viruses were genetically identical, no matter how this came about, it would be very significant. The greatest significance lies in the fact that no disclosure of the possible identity of the LTCB and IP viruses was ever made to the USPTO nor to the U.S. Court of Claims, nor -- for a prolonged period -- to the scientific community or the general public. Instead, even before the blood test patent dispute was formally initiated, Dr. Gallo asserted in the scientific literature that the IP and LTCB viruses were different isolates of the AIDS virus. Subsequently, with the initiation of the blood test patent dispute, Dr. Gallo asserted vehemently that the viruses were not, could not be the same isolate. Based on these assertions, the attorneys representing the U.S. Government made unqualified, strident representations in numerous briefs and pleadings, of which the following are representative: "The scientific evidence is clear that HTLV-III and LAV are not so similar that HTLV-III can be said to be the progeny of LAV" (Defendant's Rely to Plaintiff's Memorandum in Opposition to Defendant's Motion to Dismiss the Complaint; p. 6; U.S. Claims Court); "Continuing research revealed that LAV and HTLV-III were two different isolates of the AIDS virus" (Brief for Appellee the United States; p. 4; U.S. Claims Court). In light of the strong arguments put forward in 1985 -87 by Dr. Gallo as well as the U.S. Government attorneys to the effect that the IP and LTCB viruses were unquestionably distinct isolates, it is striking that Dr. Gallo told Subcommittee staff that by the end of 1986, "... we were hanging onto straws" in continuing to argue that the viruses were different. Asked if he shared this insight with the attorneys who, at the end of 1986, were striving mightily to defend the U.S. against charges of patent fraud and misappropriation of the IP virus, Dr. Gallo said that by March 1987 (the month in which the French/American settlement was consummated), "all of us knew the viruses were the same -- from the same person." Among the explanations proffered by Dr. Gallo concerning how the IP and LTCB viruses might have come to be identical, Dr. Gallo said that based on Dr. Popovic's report to him -- "even earlier than the Summer of 1984" -- that the September 1983 IP virus sample behaved differently from the July 1983 sample, he (Gallo) and Popovic believed it was possible that the IP virus had been contaminated by Dr. Popovic with one of his own viruses, at the LTCB! But this extraordinary assertion is suspect on many grounds. In the first place, the mere fact of apparent biological differences in the July and September IP virus samples might have been due to a number of circumstances other than possible contamination by another virus; Dr. Gallo offered no explanation for why he and Dr. Popovic -- reportedly -- seized so readily on the contamination explanation. Casting further doubt on the credibility of Dr. Gallo's account of his and Dr. Popovic's speculations, there is no known likely candidate among Dr. Popovic's contemporaneous samples for the supposed LTCB contaminant virus; Dr. Gallo did not himself identify a candidate. Finally, the claim of a possible LTCB-to-IP virus contamination is completely undercut by Dr. Gallo's knowledge -- in the Summer/Fall of 1984 -- of Dr. Murray Gardner's data showing genetic identity of LAV and IIIb, data based on LAV obtained directly from IP (see above), and later, of comparable data from Dr. Malcolm Martin. In short, the explanation of a possible contamination of LAV by an LTCB sample is entirely bogus. Dr. Gallo offered two other possible scenarios to explain the identity of the IP and LTCB viruses, both of them variations on a theme of deliberate sabotage. According to the first scenario, as related to Subcommittee staff by Dr. Gallo, Elizabeth Read-Connole (one of Dr. Popovic's research assistants) reported to him (Gallo) -- in February 1984 -- that some of the cultures in her hood had been "tampered with." According to Dr. Gallo, Read-Connole told him that on one occasion, she found the quantities of some of her cultures had changed: "the volumes changed overnight," according to Dr. Gallo. But Read-Connole gave a very different description of this incident to OSI. According to Read-Connole's testimony to OSI, on the occasion in question, she returned from a weekend to find a strange coffee cup next to her incubator, and some of her cultures "turned around." Read-Connole made no mention of changes in the volume of any of her cultures, neither did she mention the possibility of "tampering." Read-Connole told OSI she gave the same account to Dr. Gallo. When the discrepancies in their accounts was described to him by Subcommittee staff, Dr. Gallo said he would have to check into the matter. Dr. Gallo never raised the matter again. The second sabotage scenario described by Dr. Gallo was alleged to have occurred later than the "tampering" incident, i.e., in June 1984. Dr. Gallo insisted to Subcommittee staff that he would not identify the alleged perpetrator, a person who Gallo said "stood to economically gain," who according to Dr. Gallo, approached Frederick scientist Dr. Raymond Gilden, telling him it could be to their mutual benefit to "set up Gallo," i.e., to "show the identity of LAV and IIIb." According to Dr. Gallo, the individual in question -- a former NCI scientist -- had been "in and out" of the LTCB on several occasions; it was one of these occasions, presumably, that the deed was done, i.e., the supposed pilfering of "IIIb" and its transfer to the IP scientists in France. Dr. Gallo hardly needed to have been so reticent about naming names in connection with the alleged "set up Gallo" incident. As early as August of 1985, Dr. Gallo wrote a memorandum to Dr. Fischinger, telling him about the alleged approach to Gilden, including the name of the suspect scientist. Later, in his widely disseminated April 1986 "Key Events ..." document, Dr. Gallo repeated the allegation, twice, naming the individual both times. And Dr. Gallo repeated variations of the story, on several occasions, to OSI. But there is no independent substantiation for Dr. Gallo's account. Even if it were substantiated that some sort of an approach had been made to Dr. Gilden, there is no evidence that it had anything to do with the fact that IIIb is actually the IP virus, LAI. If, in fact, Dr. Gallo and his colleagues were "confused" about the origins/identities of the LTCB and IP prototype viruses, in the Summer/Fall of 1984, they managed to hide their confusion well, insisting in numerous published papers in late-84/early 85 and thereafter that the viruses, while functionally the same, were genetically independent (see above ). Dr. Gallo's own accounts to Subcommittee staff varied from one occasion to the next, ranging from the sabotage scenarios to the supposed "contamination" of the IP virus by an LTCB sample, to the assertion that Dr. Montagnier had contaminated the IP virus with IIIb, at the IP laboratories in Paris. In the final analysis, according to Dr. Gallo' s statements to Subcommittee staff, eventually he "learned certain things" that made it "too likely the contamination is in our lab" (the contamination of the LTCB virus by the virus from the IP). Dr. Gallo acknowledged to Subcommittee staff that he had "held out for more proof ... perhaps I held out longer than I should have." But, added Gallo, "... there is something subjective about being human" (7/22/93 interview with Subcommittee staff). Dr. Gallo's "bottom line" assessment of his actions vis-a-vis the genetic identity of the viruses was this: "There is nothing I can be criticized for" (7/28/93 telephone call to Subcommittee staff). VI. GALLO/HHS ON LTCB MATERIALS TRANSFERS A. Practices at the LTCB Immediately upon publication of the May 1984 Science papers, the LTCB received numerous requests for its IIIb-infected cell line, its "H9" uninfected cell line, and related reagents. According to commonly-accepted standards for scientific collaboration and exchange, these materials should have been readily and unconditionally provided to qualified scientists, since they had already been published. From a public health standpoint, one could even argue that the materials should have been unconditionally shared well before their May 1984 publication, considering the devastation of the AIDS epidemic and the potential benefits the materials had for AIDS/HIV research. Dr. Gallo and his associates provided their cell lines and reagents to many who requested them. Dr. Gallo frequently recites the numbers of scientists who received these materials; the LTCB also has prepared several lists of scientists who allegedly received LTCB materials. On numerous occasions, these lists have been adduced as evidence of the generosity of Gallo et al. But the lists of scientists who allegedly received LTCB materials (some scientists who were listed by the LTCB as recipients did not receive the requested materials) cannot obscure the reality that, at the same time as he provided materials to some scientists, Dr. Gallo withheld reagents and cell lines from others. Dr. Gallo also gave special treatment to some scientists, actually offering materials under favorable conditions to selected collaborators, while at the same time, he delayed responding to the requests of others less favored. Most problematic of all, for some scientists, Dr. Gallo imposed conditions on transfers of materials that were blatantly at odds with accepted principles of conduct in research, at odds with Dr. Gallo's professed commitment to public health, and that apparently were driven at least in part by the intention to keep others from demonstrating the uniquely close genetic relationship of "HTLV-IIIb" and LAI. Dr. Gallo was aware of and professed adherence to principles of free access to research materials. Dr. Gallo articulated those principles in 1981, during a deposition in the U.S. District Court of Maryland, in the lawsuit, Hoffman-LaRoche, Inc. v. David W. Golde, et al. The Roche/Golde et al. lawsuit focused on sharing of cell lines; Dr. Gallo, whose use and transmission of a disputed cell line was an important issue in the lawsuit, was questioned at some length about his understanding of accepted scientific practices relating to the sharing of research materials, and about his own conduct. Dr. Gallo's answers in the deposition provide informative context for his later statements and actions. Asked if he freely gave out cell lines from his laboratory, Dr. Gallo said this: "Yes. The policy is to make them available to everybody on publication who asks who's a qualified investigator, whether they work in any place, any affiliation, race, color, or creed, and so. The lines are available on publication" (7/15/81 deposition of Robert C. Gallo; transcript p. 90). Later in the deposition, Dr. Gallo responded to questions about the rationale for the free exchange of research materials: Q: "Is your sending out of cell lines or other things which you feel free in your laboratory to send out something that you do to further medical research or scientific research? A: I mean, that's what we grew up -- when you're growing up, you get taught certain rules of behavior, and that was one of the rules of behavior in science that we sort of followed ... Q: Is it also fair to say that one of the reasons why NCI has historically encouraged the sending out of cell lines and other things is to further medically useful research? A: Of course. They have useful cooperation with outside people and useful interrelationships rather than any hostilities of holding this or holding that. I think that's obvious" (op cit., pp. 93-94). The reality of Dr. Gallo's actions vis-a-vis his AIDS research materials was far different: Dr. Gallo required every scientist who received his cell lines and reagents to sign a restrictive transfer agreement, which besides routine safety and noncommercialization provisions, included a requirement that, "performed will be on a collaborative basis with Dr. Gallo and his laboratory unless stated otherwise." Dr. Gallo has claimed that the collaboration requirement included in the LTCB transfer agreement was a mere "formality," and that he never actually mandated that research performed by recipients of LTCB materials be collaborative with LTCB scientists. But the facts show otherwise. For Dr. Gallo's close colleagues, the collaboration provision of the transfer agreement was modified to make it less restrictive, as happened for Dr. Robin Weiss, on whose transfer agreement Dr. Gallo added handwritten notes modifying the requirement that "work performed will be on a collaborative basis," to this: "Collaboration at will for Dr. Weiss O.K. R. Gallo." For other scientists -- those deemed by Gallo et al. to be potential or actual competitors, the collaboration provision, as well as other provisions of the LTCB transfer agreement, were modified to make them even more restrictive (see below ). Contrary to Dr. Gallo's claims to OSI, to NIH Director Bernadine Healy, and others, the transfer agreement was not imposed on Gallo by NCI/HHS officials, contrary to his wishes. In March 1992, in an attempt to defend himself against possible disciplinary action for his withholding and restricting use of LTCB materials, Dr. Gallo wrote this to Dr. Healy: "The restrictions on distribution of HTLV-IIIb were made at the request of NIH and HHS administrators, Drs. Fischinger and Harmison ... the more restrictive non-disclosure form was actually Dr. DeVita's form, not mine." But according to NCI Associate Director Dr. Peter Fischinger (10/23/85 Fischinger-to-Blout letter) the transfer agreement mandating collaboration was "spontaneously drafted" by the Gallo laboratory. As for the "more restrictive, non-disclosure form," it was not Dr. DeVita's form. Dr. Gallo personally was party to the decision by which an extraordinary "confidentiality/secrecy" provision was added to the agreement. In fact, when Dr. Gallo was asked directly by OSI, "Someone made you use that form?" his response was this: "No, it was just what they prepared. They didn't make me. They said you got to use this ... Well, I didn't pay too much attention to it ... "It either came from Peter Fischinger or Harmison. I don't know who else it could be from. I really don't know. But, anyway that is what we were advised to do" (9/23/90 OSI interview; transcript pp. 64-65). Dr. Gallo failed to even respond to a written request for the HIV-specific rabbit antiserum, from Dr. Jay Levy (notes in Gallo's hand show he pondered with his staff how to respond to the request; yet well before publication of the May 1984 Science papers, Dr. Gallo had provided the antiserum to his close colleague, Dr. Daniel Zagury); Other unique reagents also were withheld from qualified scientists, while favored scientists were given ready access. On April 25, 1984, Dr. James K. McDougall, of the Fred Hutchinson Cancer Research Center in Seattle wrote to Dr. Gallo requesting "an HTLV probe" to assay what McDougall described as "a large number of DNA samples" from lymphadenopathy and AIDS patients. Gallo responded on May 10, telling McDougall, that, with respect to an HTLV-III probe, "... we are still in the middle of characterizing some clones. It will be awhile before we can distribute them." Gallo added, in a handwritten "P.S." at the bottom of the letter, "Jim, write to me again in about 6 weeks. Bob." Apparently taking Dr. Gallo at his word, Dr. McDougall wrote again on July 3, 1984, saying, "If the HTLV-III clones are now available for distribution, we would be delighted to receive them." A one-word note, in Dr. Gallo's hand, appears at the top of McDougall's letter -- "No." In contrast, another scientist, a close Gallo colleague who requested the probes on May 31, 1984, received a reply from Gallo that said this: "We will definitely make the molecular clones available to you as soon as they are published. Please remind me then" (Gallo-to-Alfred Prince [undated]). At the same time as he freely provided the uninfected H9 cell line to such close colleagues as Drs. Robin Weiss, Daniel Zagury, Dani Bolognesi, Wade Parks, Myron Essex, and Barton Haynes, Dr. Gallo significantly delayed providing the line to other scientists. The most noteworthy instance of this conduct was Dr. Gallo's delay in providing H9 to the IP scientists, who made repeated requests for the cell line so they could complete the LAV/IIIb collaborative comparison studies agreed to by Gallo. Dr. Gallo agreed in mid-May 1984 to provide H9 to the IP scientists, but Montagnier and his colleagues did not receive the line until September/October 1984. Dr. Gallo claimed to Dr. Chermann that "... the U.S. Government position is to hold this line" until it was fully characterized. And despite his previous commitment to provide the H9 line to the IP scientists, Dr. Gallo insisted the line was not necessary to complete the virus comparisons: "... good God, how does the uninfected cell line affect comparison between LAV and HTLV-III[b] ... Don't use this argument to get the uninfected HT cells. We will send them to Pasteur Institute soon, but when I think it is scientifically and administratively appropriate" (August 24, 1984 Gallo-to-Chermann letter). (As previously discussed, see above , Dr. Gallo claimed the IP virus did not grow in H9 at the LTCB. Dr. Gallo's desire to prevent other scientists from disproving this claim almost certainly accounts for Gallo's reluctance to provide H9 to the IP scientists. When the IP scientists did, finally, receive H9, they were readily able to grow their virus in the line.) Dr. Gallo refused outright to provide the uninfected H9 cell line to, among others, Drs. Michael Gottleib, Carel Mulder, Frederick Jensen and Malcolm Martin, of the NIH's National Institute for Allergy and Infectious Diseases (NIAID). Concerning the uninfected cell line, Dr. Gallo told Dr. Martin and others he would not provide the uninfected line to them because it was "still being characterized" for a planned "detailed publication." No such publication ever appeared. Dr. Gallo also demanded to know what Dr. Martin planned to do with the H9 line, if he did obtain it, and -- clearly trying to head off the possibility of LAV/IIIb comparisons -- Gallo told Martin this: "... I do not think it would be appropriate for you to put the French isolate in them [H9 cells]. That is for them [the IP scientists] to do in collaboration with me and my co-workers and is ongoing" (6/22/84 Gallo-to-Martin letter). Dr. Gallo's claims about an ongoing collaboration with the IP scientists was, clearly, a sham. Even as Dr. Gallo wrote to Dr. Martin that the IP scientists would be growing their virus in H9, in collaboration with the LTCB, Gallo was refusing to send H9 to Dr. Montagnier and his colleagues, and -- as described above -- mocking their requests for the line. In 1990, when he was challenged by OSI/ ORI about his withholding and restricting use of the uninfected cell line, as well as other LTCB materials, Dr. Gallo (and his associates) commenced a chorus of claims about the numbers of scientists who had received the cell line. Dr. Gallo's associates went so far as to launch a world-wide fax survey (at U.S. Government expense) of LTCB materials' recipients, in an attempt to substantiate Dr. Gallo's claimed generosity. The results of the survey -- for all the cost and time involved -- were largely irrelevant, since they frequently referred to reagents other than the H9 cell line, and covered periods of time considerably later than the period in which the withholding/restrictions took place. In 1993, confronted with irrefutable evidence that he withheld H9 from some scientists, Dr. Gallo acknowledged the withholding, for what he claimed was a limited period of time in the Summer of 1984, claiming the line was withheld due to his concerns that it was contaminated with "IIIb" or some other AIDS virus isolate. Dr. Gallo told Subcommittee staff he withheld the line from Dr. Malcolm Martin and other scientists he felt he "could not trust," who would "stab me in the back," who "would embarrass me or call me dishonest if there was something wrong with the cells" (July 22, 1993 staff interview). But these claims by Dr. Gallo were highly suspect. First, according to the May 1984 Popovic et al. Science paper, the parental "HT" -- actually HUT-78 -- cell line, was, "... tested for HTLV before being infected in vitro and was negative by all criteria including lack of proviral sequences" (Popovic et al., 224, p. 498). Further, according to both Gallo and Popovic, H9 and the other clones were derived from HUT-78 -- in part -- precisely in order to ensure that no adventitious agent was present. More significantly, Dr. Gallo's claims that he withheld the H9 line in the Summer of 1984 because he feared it was HIV-contaminated are contradicted by documentary evidence and his own claims in other fora, i.e., the claim to NIH Director Dr. Bernadine Healy that, "From about the time of publication of the papers [the four LTCB Science papers] in May 1984 to August of 1984, I had made uninfected H9 available to approximately 45 investigators" (3/20/92 Gallo-to-Healy letter; p. 2). Dr. Gallo's claim that he provided the H9 line to 45 scientists by August 1984 is almost certainly an exaggeration. But documentary evidence shows that he did indeed provide it to several scientists during this period, with no warning that a possible contaminating virus might be present, a circumstance which, if true, could have devastated the recipient scientists' experiments. Yet at the same time, as noted previously, other scientists' requests were denied or simply ignored. Dr. Gallo cannot have it both ways. Either he arbitrarily and capriciously withheld H9, a vital laboratory commodity from selected scientists, or he knowingly provided a possibly contaminated cell line to several scientists with no warning to them of the potential pitfalls they faced in using the line. The selective withholding of the H9 cell line and the restrictions placed on its use compounded the harm from the failure of Gallo/Popovic to disclose the true origins of the cell line, i.e., HUT-78, at a time when ready availability of the first published cell line permissive for HIV might have significantly advanced AIDS/HIV research. Writing in the journal Science, noted virologist Albert Sabin said this about the utility and origins of H9: "According to a special National Institutes of Health (NIH) committee chaired by Alan Rabson of NCI, the H9 cell line was identical with HUT-78. This is not a trivial or irrelevant matter, as it was called by Gallo and Popovic, because the use of such uncontaminated, continuous lines of human T4 lymphocytes was crucial to the regular isolation of the new retrovirus from patients with AIDS and to the development of the antibody test by which it was possible to establish the etiological association of the virus discovered by Montagnier and his colleagues and of subsequently isolated viruses related to AIDS" (1990, p. 466). Concerning the restrictions imposed by Dr. Gallo on the transmittal of H9 to other scientists, the Richards Committee said this: "We consider failure to distribute uninfected H9 cells freely after publication of the article by Popovic et al. to be essentially immoral in view of the growing seriousness of the AIDS epidemic" (p. 3). For a few select scientists, Dr. Gallo crafted a one-of-a-kind transfer agreement, tailor-made to restrict as tightly as possible the use of his cell lines and reagents by the recipient. Some of these agreements prohibited certain kinds of research. Others , like the agreement created for Harvard University's Dr. James Mullins, itemized the only kinds of research that could be done. Specifically, Mullins' transfer agreement specified that he could obtain the uninfected H9 cell line only by agreeing in advance to the following: "Use of H9 will be limited to my immediate laboratory for the specific purpose of transfection of CTV and HTLV-I DNA. No other experiments will be carried out with this cell line without prior discussions with Dr. Gallo." Even more restrictive was the collaboration provision developed for the transfer agreement for Harvard University's Dr. William Haseltine. (LTCB records show this restrictive provision was crafted by Dr. Gallo's close associate, Dr. Flossie Wong-Staal. It also appears that Dr. Wong-Staal, with Dr. Gallo's knowledge and approval, crafted the restrictive provision imposed on Dr. Mullins -- cited The collaboration restrictions imposed on Dr. Haseltine were daunting. They not only specified the LTCB scientists with whom collaboration was mandated, they also -- as was true for Dr. Mullins -- limited the kinds of research Dr. Haseltine was able to perform with the LTCB's materials: "Work performed will be on a collaborative basis with Dr. Gallo, Dr. Popovic, Dr. Wong-Staal, and their colleagues (to be specified by them) for the specific purpose of studying expression of HTLV-LTR linked genes in these cells. No other experiments should be initiated with these cells without prior discussion with the above named people." For Malcolm Martin and the CDC scientists and only for these individuals, whom Dr. Gallo knew possessed LAV, there were special restrictions added to the transfer form required of most scientists who sought the infected cell line (Dr. Martin did not request the infected line, but Dr. Gallo "offered" it to Martin at the same time as he [Gallo] refused to provide him the uninfected line). One of the special restrictions common to both Martin and the CDC scientists, said this: "Work with HTLV-III will not be published without prior approval by Dr. Gallo." The second special restriction had this element in common to both Martin and the CDC scientists: "Reagents will not be used in comparisons with other viruses." For the CDC scientists, there was an additional condition: "They [Gallo's materials] will only be used for seroepidemiologic studies and blood bank assays." Dr. Frederick Murphy, in a June 11, 1984 memorandum he wrote to CDC Acting Director, Dr. Walter Dowdle, gave a vivid description of the meeting with Dr. Gallo at which Gallo reportedly threatened he would not provide the CDC scientists the HIV research materials they were seeking: "... it was a tense moment, fraught with the possibility of non-delivery. Our tack, stated orally in several different ways as we discussed the matter with Dr. Gallo, was that public health purposes were paramount. Dr. Gallo agreed. In our conversation, it became clear that comparison of his HTLV-III prototype with the French prototype LAV occupied a separate niche -- the comparison was seen as having both academic and public health purposes. Because of the latter, I offered, using several tacks, to have certain comparative tests between his HTLV-III and the French LAV done at CDC; Dr. Gallo declined each time, stating that such would be done in his lab. It was quite clear from our discussion that this was the only subject which engendered such difficulty -- when we switched to other themes ... there was no problem." Dr. Murphy also said he understood the prohibition on "comparisons with other viruses" to mean comparisons with LAV. B. Practices at NCI, NIH and PHS It is clear that the impetus for selective withholding and imposition of restrictive conditions of LTCB research materials came initially from Dr. Gallo. But it is equally clear that for a prolonged period, Dr. Gallo's superiors at the NCI, particularly Drs. Fischinger and DeVita, gave Gallo license to give and withhold his materials at will. It also is clear that at the PHS level, Dr. Lowell Harmison institutionalized the selective withholding of research materials, as a matter of political and commercial policy. The documentary record from early Summer 1984 shows that NCI and NIH officials were aware of problems concerning Dr. Gallo's failure to unconditionally share his research materials. Minutes of the June 18, 1984 meeting of the NIH AIDS Executive Committee show that NIH Director Dr. James Wyngaarden ordered Dr. Gallo to "immediately" furnish the uninfected H9 cell line to Malcolm Martin and CDC. Dr. Gallo provided the line to CDC; he did not obey the order to provide the cell line to Dr. Martin. Dr. Wyngaarden also ordered Drs. Gallo and Fischinger to prepare a response concerning Gallo's provision of LTCB materials to other scientists. Dr. Fischinger's memorandum transmitting Dr. Wyngaarden's order to Dr. Gallo was typical of the boosterism Fischinger typically displayed toward Gallo: "If you did not honor an isolated request, you may state your reasons. As we discussed, it seems reasonably clear that your past concerns can be easily validated" (6/19/84 Fischinger-to-Gallo memorandum; p. 1). Fischinger also told Gallo that: "Dr. J. Wyngaarden was highly supportive of your stated position and defended your perspective over the objections of Dr. K. Sell [of NIAID] at this meeting" (op cit., p. 1). But Dr. Wyngaarden told Subcommittee staff his support for Dr. Gallo extended only to his (Gallo's) position regarding his desire to obtain samples from CDC. Dr. Wyngaarden said he would never have supported Dr. Gallo's actions in imposing conditions like those imposed on James Mullins and the scientists at the CDC, or conditions like those Gallo attempted to impose on Malcolm Martin. No document prepared by Gallo in response to Dr. Wyngaarden's directive was ever provided to the Subcommittee. Dr. Wyngaarden told Subcommittee staff that he questioned Gallo about the matter, but according to Wyngaarden, Gallo "insisted he was sharing his samples as fast as he could." Moreover, said Wyngaarden, Gallo showed him a "two-inch thick" list of names of scientists to whom he supposedly sent his cell lines and reagents. According to Dr. Wyngaarden, Dr. Gallo told him there was only one person to whom he had refused to send materials, i.e., Malcolm Martin. Restrictive conditions on materials, apparently, were not discussed. On July 2, 1984, at a follow-up meeting to the June 18 meeting of the NIH AIDS Executive Committee, Dr. Peter Fischinger presented to the Committee the "Policy on Requests for the Distribution of NIH Cell Lines Used in AIDS Research and Development." According to minutes of the July 2 meeting, "Dr. Fischinger, who prepared the Policy, said that it was discussed at a meeting of Drs. Wyngaarden, DeVita, Chabner, Gallo and Harmison on July 2 ..." The "Policy" actually institutionalized and/or provided cover for some of Dr. Gallo's more arbitrary actions relative to withholding and/or restricting use of LTCB materials. The two most problematic provisions of the July 1984 Policy were these: (1) Concerning the "IIIb"-infected cell line, "... all further transfer (sic.) to non-profit organizations should also include a signed confidential disclosure agreement" (p. 2). (2) Concerning the uninfected cell line: "Release of the uninfected cell line to non-profit concerns shall presently be at the discretion of Dr. Robert Gallo, LTCB, NCI, with a discussion of the resulting collaborative plan. The standard caveats of non-release to third parties for commercial purposes, and the prudent containment practices on infection shall be heeded as per the required confidential disclosure agreement" (emphasis added; p. 2 ). The "confidential disclosure" provisions of the NCI/NIH transfer agreement were as follows: "It [the recipient institution] will maintain in confidence all information relating to these materials and not disclose this information to others without specific written permission, in advance, from the Director, National Cancer Institute, or his designee... It is understood that you will obtain secrecy agreements from all employees to whom the proprietary materials or information will be made available as may be necessary to insure their compliance with the terms of the agreement." Prospective imposition of these conditions, especially in academic research settings, was bad enough. But in August 1984, when NCI attempted to impose the conditions retrospectively, the result was a series of strong protests from officials of those organizations, protests both at the infringement on academic freedom and the attempted suppression of information in the fact of an devastating epidemic. By March 1985, NCI Director Vincent DeVita had found it necessary to prepare a form letter to respond to the protests. DeVita's letter included this: "If you interpret that the 'Confidentiality Research Agreement' may preclude publication in scientific literature without NCI's prior approval, you are overly restrictive. The government's position has always been that general dissemination of new research information by publication is very much appropriate and that such information would only serve to ameliorate the current status of treatment and prevention of AIDS. Accordingly, please feel free to publish your research results. Should you want to consider alternative dissemination methods which could in some way adversely affect our current licensees, please contact us for further discussion." It is unclear what "alternative dissemination methods" might have adversely affected HHS' five blood test licensees. But the mere inclusion of this provision in DeVita's letter is revealing with respect to NCI/HHS' motives in restricting access to the LTCB's research materials, i.e., to protect "our current licensees." Moreover, it is clear that in other significant respects, HHS was more-than-zealous in its protection of its licensees, even at the cost of public health (see below). Concerning the policy on the uninfected cell line, the codification of the provisions that placed release of the line "at Dr. Gallo's discretion" clearly refutes Dr. Gallo's assertion that the materials transfer restrictions were forced on him by higher officials. The codification also is noteworthy, considering that Dr. Wyngaarden, at least, was on notice that there were problems with Dr. Gallo's inequitable release of the line. In light of Dr. Gallo's demonstrated inequitable conduct, the provision vesting authority for releasing the line at "Dr. Gallo's discretion" provision was clearly at odds with Dr. Wyngaarden's dictum, recorded in the minutes of the June 18 NIH AIDS Executive Committee meeting, that, "... we need a tight and consistent policy, and ... we have to have objective criteria as soon as possible." Consistency and objectivity vs. "at Dr. Gallo's discretion" -- these conditions were mutually exclusive. Yet, so far as is known, Dr. Wyngaarden made no objection to the NCI policy, when it was forwarded to him from Fischinger, through DeVita. Whatever NCI/NIH officials said and did in 1984 concerning Dr. Gallo's actions vis-a-vis his reagents, in 1992-93, these officials professed dismay and indignation when they were confronted with the documented evidence concerning those actions. In 1993, when Dr. Wyngaarden was shown Dr. Gallo's transfer agreement mandating prepublication review and no-comparison restrictions for the CDC scientists, Dr. Wyngaarden's reaction was immediate and unequivocal: "Clearly inappropriate." Dr. Fischinger told Subcommittee staff he believed that Dr. Gallo, as a Federal employee, had a "special responsibility" to make his materials freely available. Dr. Fischinger said, concerning the restrictions Dr. Gallo placed on Malcolm Martin and CDC's receipt of his cell lines, "I wouldn't do it, but Bob must answer for himself." Dr. Fischinger was adamant on one fundamental point: "DeVita, Wyngaarden and I all believed the reagents should go out!" As for DeVita, he expressed himself more vividly, saying that All restrictions are anti-science." Shown the restrictions Gallo placed on Malcolm Martin and the CDC scientists, Dr. DeVita's response was, "I think it's terrible." C. The Unique Role of Dr. Lowell Harmison Dr. Lowell Harmison alone, to this day, defends Dr. Gallo's imposition of restrictive conditions on his research materials, particularly relating to the CDC. Dr. Harmison's statements in this regard seemed to reflect Dr. DeVita's observation that by the Summer of 1984, Dr. Harmison had "assumed ownership of" Gallo. When questioned by the Subcommittee in Executive Session, Dr. Harmison initially denied knowledge of the conditions imposed on the CDC scientists' use of LTCB materials. Yet when he was confronted with the actual transfer agreements the CDC scientists were forced to sign, Dr. Harmison defended them: "At this period of time, no one knew the degree of infectiousness of this particular virus. There were very small quantities of this virus available. There were a limited number of people with detailed knowledge and experience in working in this area. The most competent laboratory in this area was clearly that of Dr. Gallo's laboratory on retroviruses. The CDC did not have this capacity of the level of Dr. Gallo. CDC was not charged to do retroviral laboratory research... So to me, as I look down over the seven conditions here, they are all very responsible and very logical when you did not know the nature of the infectious disease ... each one of these have a level of specific responsibility that would be required of any prudent scientific laboratory director. So I find no difficulty whatsoever in those conditions" (7/21/93 hearing of the Subcommittee on Oversight and Investigations; transcript pp. 54-55). But there was no factual basis for Dr. Harmison's assertions supporting Dr. Gallo's restrictions on the CDC scientists. The claim that "there were very small quantities of this virus available" is directly contradicted by the fact that as early as March/April of 1984, LAI/MOV and LAI/IIIb were being grown in liter quantities at the LTCB contractor, Biotech Laboratories. Likewise, Dr. Harmison's claim that the CDC did not have the required competency to work with the AIDS virus is simply absurd, considering that by the Spring of 1984, when they sought Dr. Gallo's cell lines, the CDC scientists had been working with the IP virus and their own isolates, for nearly one year. Dr. Harmison even defended Dr. Gallo's proscription of CDC's publishing without his (Gallo's) prior approval, although Dr. Harmison was not able to explain why this condition, like the "no comparisons" condition, should have been uniquely imposed on the CDC and Malcolm Martin's laboratory. Dr. Harmison acknowledged that the "prior approval" condition was "an absolute constraint" on publication, yet he maintained, "I think that was appropriate at this time..." Dr. Harmison also promulgated and, to this day, adamantly defends, HHS' withholding of LTCB materials from foreign governments and from any commercial firms other than the five HHS blood test licensees, three of whom, (both at the time of their selection and thereafter) were contractors of the LTCB. The 1984 NCI/NIH policy actually incorporated protection of the HHS licensees as an overarching principle, placing patents and potential financial rewards above public health. The policy included these elements (concerning the uninfected cell line): "Because patent protection does exist on this cell line, and because a number of ongoing useful experiments are taking place within NCI which could lead to further patents by the Government, release of this cell line to non-license for-profit organizations shall not take place at this time. An additional reason is that a number of parallel uses of this cell line, which could readily lead to analogous AIDS blood tests, is obvious. It is considered prudent that the effectiveness and rapidity of the realization of the AIDS blood test by the existing licensees should not be compromised by additional competing technological thrusts" (p. 3). In other words, by NCI/NIH policy, competition in developing the best HIV blood test was to be artificially constrained by restricting the availability of a uniquely permissive cell line for growing the virus. HHS officials and Dr. Gallo himself asserted that their strategy for commercializing the LTCB blood test, including limiting the number of licensees, was first and foremost a means for ensuring that only quality tests would be developed. Thus, in late Summer 1984, in denying a request from the Commonwealth of Australia for a license to scale up production of "IIIb" to make a government-issue HIV antibody blood test, Dr. Edward Brandt (the letter was actually written by Lowell Harmison) said this: "With regard to your request for permission to scale up production of the HTLV-III antigen for non-research purposes ... in June of this year we entered into licensing agreements with five organizations ... These five licensees were selected after scientific and technical reviews ... This licensing process has now been completed and we do not contemplate any further licensing, at least for the time being ... "We think that the shortest pathway to obtaining accurate, sensitive, and highly selective blood test data is through the process that we have established for the assay. It should provide a reliable and effective screening tool in assuring a safe supply of blood and blood products. These assays will be made available through our licensees for use as specified in the product license to be issued by the Food and Drug Administration. Thus, the benefits of these efforts would offer to you a quality assay in minimal time" (Brandt-to-McCarthy; undated). Dr. Gallo said this about the U.S. Government policy of restricting access to LTCB HIV-related materials: "Now, there are things that we had to be certain about. Remember I could get in trouble for sending this out to anybody. The Government was concerned about fraudulent blood tests, unfair blood tests by somebody else, by some companies, quote. The Government was also concerned that I would give somebody AIDS by mailing this stuff out. So, we were under reasonable restrictions about who we could give it to. They had to show that they had the right facilities to grow the virus, enough technical competence and that they weren't about to make a test with it. Okay. This was not something I had full control over" (8/3/90 OSI interview; transcript pp. 124-125). Dr. Harmison, during the July 21, 1993 Subcommittee hearing, also asserted the "quality control" argument as a rationale for restricting commercial firms' access to the LTCB materials: "The issue as it emerged in late August of 1984 hinged on the following point. When you grant a license to a company or to any organization, you have granted them a license to do something. In return they have committed to do something. During the period of late August, the virus was going from research labs out, and different organizations were coming up to try to produce different blood tests without getting the proper clearances for those blood tests. When five companies had gone through a rigorous process to qualify the most expert and capable organizations to deliver that blood test acceptable to the Red Cross, acceptable to the FDA, and clean up the blood supply, so what was occurring, we had a lot of me-too organizations coming around all over the country wanting to get virus. Suddenly they were testing a blood test. And that was infringement of the license granted. So when research quantities were moved out for research purposes, the only objective was to have that you have got to use it for commercial purposes, you have to come back and say, we would like a license now to commercialize, only to have a level playing field. That is the only basis upon which any conditions would have been applied to a virus, to my knowledge (transcript; pp. 49-50). But the fact is that despite numerous requests, including requests from such reputable manufacturers as SmithKline Beckman, HHS adamantly refused to issue licenses beyond the initial five. Moreover, the whole "quality control" argument for limiting the licenses was bogus; quality control and reliability are the responsibility of the Food and Drug Administration (FDA), and only the FDA. No matter how many licensees developed an HIV antibody blood test, only the tests approved by the FDA could be marketed in the United States. There was nothing to substantiate that allowing more companies to develop antibody blood tests would result in lower quality tests. Indeed, logic suggests that greater competition would have spurred improvements in some of the worst performing of the first-generation U.S. tests developed by HHS' allegedly rigorously screened/carefully selected licensees, particularly the tests developed by Abbott Laboratories and Electro-Nucleonics. These tests embodied significant specificity deficits, and in the case of Abbott, significant sensitivity deficits as well. Elsewhere in his Subcommittee hearing testimony, Dr. Harmison made it clear that the limited number of HHS licensees was a calculated strategy to reduce competition and thereby heighten the likelihood of profitable returns for the five licensees: "... to get industry's effective participation, you must do something that offers them a grant or a contract. They must have within their hands the capacity to move forward. And that is basically removing the degree of uncertainty that you can remove" (op cit., p. 21). Dr. Harmison also specifically invoked protection of the HHS licensees as the reason that foreign governments were denied licenses to make their own blood test: "... you have to keep in mind that the participation of industry to invest -- and I am giving you my estimate -- something in excess of $10 to 12 million of their money, which wasn't available within the department to get this blood test available. The government went through a very elaborate process to license, I believe, five contractors ... and they had a license to practice this invention not just in the U.S. but worldwide" (op cit., p. 37). Even in the face of clear documentary evidence to the contrary, Dr. Harmison denied that foreign governments' requests to use LTCB materials were refused. Following a question about whether Great Britain and Australia were denied licensing or permission to use the LTCB virus, (Canadian public health officials also were denied), there was this exchange: A: "No, no. They were not denied. The U.S. license did not permit -- you can't give someone limited exclusive license or say to them, 'if you invest your money and take this blood test from a laboratory toy to a useful blood test that I can go down here to a clinic on the corner of X street and produce the virus, those companies invested their money and did those tests to get this approved to be marketed, with the hope of making some return on those investments. We, the government, gave them that license. You can't then turn around and say, I am going to give this government the license or that government the license ... you are not being responsible to your agreements. So that is a big misunderstanding. Q: You are not being responsible to these licensees? A: "We absolutely were responsible to the governments and to the licensees. We were honoring the commitment the government made to have the virus and the license produced and marketed in this country, and that was part of international commerce. That is how it is done. Q: That is how you did it. A: No, that is how the department did it. That is the standard (op cit., p. 38). It is important to note that Dr. Harmison's authority at HHS concerning these matters was absolute. Thus, Dr. Harmison's expression of his personal views was, in fact, a statement of HHS policy. But there is no substantiation for HHS/Harmison's assertion that in order to entice manufacturers to make HIV blood tests, it was necessary to limit the number of licensees. In June 1984, when HHS announced the availability of licenses, it was inundated with dozens of applications, at a time when there was no mention that the number of licenses would be limited. Moreover, when the limitation policy was announced, manufacturers demanded that HHS issue additional licenses. Any company that could manufacture a reliable test, at a competitive price, stood to make money. All the HHS/Harmison policy achieved was to enable a select few companies, most notably Abbott Laboratories, to make a great deal of money on the HIV antibody blood test, because competition had been artificially restrained. VII. THE FRENCH/AMERICAN DISPUTE: FIRST PHASE A. Scientific Events Leading to the Dispute 1. Scientific Papers: HIV is Not an "HTLV": August 1985 marked the beginning of the French/American dispute. Several events earlier in 1985 heightened tensions even before the confrontation in August. First was the publication in January/February 1985 of several scientific papers, including publication of the complete nucleotide sequences of LAI/LAV, LAI/IIIb, and a third early HIV isolate, ARV. One major revelation in these papers, a revelation in direct opposition to the prior theorizing of Gallo et al., was that the AIDS virus had little or no relationship to HTLV-I and/or the HTLV family of retroviruses. A paper on the morphology of "HTLV-III" actually included Gallo and his associate, Dr. Flossie Wong-Staal, among the coauthors. Published in January 1985, the paper made clear that the AIDS virus was far more likely to be a member of the lentivirus (visna) family of retroviruses than a member of the oncovirus or "HTLV" families. First author of the paper was Dr. Matthew Gonda, the expert electron microscopist at the Frederick Cancer Research Facility who performed the majority of the most significant EM work for the LTCB in late-1983/1984. From the outset of his work for the LTCB on putative AIDS virus samples, beginning with LAV, Dr. Gonda identified the virus as a "lentivirus," clearly distinguishable from the HTLV family. Notably, Gallo et al. did not report Dr. Gonda's classification in their seminal papers. The January 1985 Gonda et al. paper contained these very significant observations: "HTLV-III ... is morphologically distinct from HTLV-I and II and type C viruses ... Morphologically, HTLV-III resembles visna and equine infectious anemia viruses, both members of the lentivirus family, more closely than HTLV-I or -II or type C viruses ... "On the basis of their morphology, the viruses now classified as Lentivirinae are indistinguishable from HTLV-III. There are also other features that the lentiviruses have in common with HTLV-III, such as their cytopathic ... effects in vitro and their ability to produce persistent debilitating diseases in vivo. In contrast, HTLV-I and -II cause T-cell malignancies, immortalizing the infected cell" (Gonda et al., Science, 227, 1985, pp. 174 - 176). The Gonda et al. paper made clear that the lentivirus classification of the AIDS virus was no mere academic issue, but an issue with important implications for understanding the very nature of HIV. Speaking of previously-identified members of the lentivirus family, Gonda et al. made these important, prophetic observations: "... by a process called 'antigenic drift,' these viruses mutate rapidly in the env gene, thus allowing variants to escape the immune system and induce a new cycle of disease ... Isolates of HTLV-III also show heterogeneity in the env gene region ... This further similarity between HTLV-III and lentiviruses indicates that development of a vaccine to prevent AIDS may prove to be a considerable challenge (op cit., pp. 176 - 177). Gonda et al. summarized the principal findings of their paper as follows: "... a greater extent of nucleotide sequence homology exists between HTLV-III and visna virus than between HTLV-III and any of the other viruses ... The data provide strong evidence for a close taxonomic and thus evolutionary relation between HTLV-III and the Lentivirinae subfamily (op cit., p. 173). Publication of the Gonda et al. paper occurred only over the strong opposition of Dr. Gallo. Dr. Gonda told OSI about the impassioned telephone call he received from Dr. Gallo and how he (Gonda) dealt with it: "You know, I am at home. The guy is calling me from Japan or Germany or wherever it is, and he was very upset because I submitted a paper to him proving it was a lentivirus ... "... he yelled and screamed and I sat there and listened to the first 15 minutes of his argument and I said, now you have to listen to mine ... "I said ... something looks like a duck, I don't care if its feathers are black and white. It looks like a duck. It is still a duck. I am not going to call it something different" (8/13/90 OSI interview; transcript pp. 86 - 89). Dr. Gonda spoke about his understanding of the origins of Dr. Gallo's angst: "I think what they are saying, and I know that I have heard that the patent hinged on something being HTLV-related or something like that ... if it wasn't an HTLV then he had nothing" (op cit., pp. 99 - 102). Dr. Gonda was so concerned about Dr. Gallo's telephone call that he reported it to the General Manager of the Frederick facility; according to Dr. Gonda, eventually even NCI Director Dr. Vincent DeVita was drawn into the controversy. Dr. Gonda and his boss, Dr. Raymond Gilden, seized on the clever expedient of a proposed schema for classification of the viruses that, due to an ingeniously-drawn border, placated Dr. Gallo without doing significant damage to the truth. Concerning the paper, Drs. Gonda and Gilden, for the most part, stood by their ground, although they did agree to remove from the paper several passages that Dr. Gallo deemed offensive. The paper was published, but the difficulties Dr. Gonda encountered illustrate vividly the fervor with which -- even at this late date -- Dr. Gallo continued to pursue HIV/HTLV linkages. As for the sequence papers, the papers other than those by Gallo et al. also made clear how different the AIDS virus was from the known human retroviruses, the "HTLVs." Thus, the paper by Wain-Hobson et al., from the Institut Pasteur, reporting the sequence of LAI/LAV, concluded this: "These data place LAV apart from the previously characterized family of human T-cell leukemia/lymphoma viruses" (Wain-Hobson et al., Cell, 40, p. 9). A parallel paper by Dr. Jay Levy and his associates, reporting the sequence of the HIV isolate "ARV-2," reported that: "... ARV-2 was as closely related to murine and avian retroviruses as it was to human T-cell leukemia viruses (HTLV-I and HTLV-II)" (Sanchez-Pescador et al., Science, 227, p. 485). Most telling of all, a paper reporting the sequence of LAI/IIIb by an independent research team, comprising scientists from the CDC as well as from the private biotechnology firm, Genentech, reported this: "Our results establish that LAV/HTLV-III has no nucleotide homology with previously characterized animal and human retroviruses ... (Muesing et al., Nature, 313, p. 450) and this: "... the HTLV-III genome seems to be entirely unrelated by nucleotide homology to previously characterized retroviral sequences, ... including HTLV-I and HLTV-II ..." (op cit., p. 456). Muesing et al. noted that their data were "inconsistent" with the LTCB reports by Arya et al. (August 1984) and Hahn et al. (November 1984) of an HTLV-III/HTLV-I homology. Muesing et al. added that: "These results and the observation that the virus is morphologically distinct from the type C viruses ... lead us to propose that LAV/HTLV-III is a member of a novel class of retroviruses, perhaps including the equine infectious anaemia virus, which has a similar morphology and a serologically-related major core protein" (op cit., p. 457). Dr. Gallo later said it was the sequence data that finally convinced him how different the AIDS virus was from HTLV-I and II. A July 1985 letter from Dr. Gallo to LeMonde's Claudine Escoffier-Lambiotte said this: "... since the nucleic acid sequence data has become known, it is clearly much more different than we or the Pasteur group knew or even suspected before ... we all recognize now that they (LAV/HTLV-III) are only distantly related to HTLV-I or HTLV-II ..." (7/1/85 Gallo-to-Escoffier-Lambiotte letter; p. 3). But in the January 1985 LTCB paper reporting the "HTLV-III" sequence, there was no such admission. Indeed, there were repeated references to similarities and linkages among HTLV-I, -II, and -III (Ratner et al., Nature, 313, 1985, pp. 277-284). One immediate result of the demonstrated absence of HIV/"HTLV" homology was an important news article that appeared in the scientific media, an article dealing with what it correctly termed Dr. Gallo's "misclassification" of the AIDS virus. The article, published in the February 7, 1985 issue of New Scientist, was written by reporter Omar Sattaur. Sattaur's article asserted that the publication of the sequences of LAV and HTLV-III proved that Gallo "has misclassified the virus that causes AIDS." Furthermore, said Sattaur, not only had this misclassification deprived the IP scientists of rightful recognition for their discovery of the AIDS virus, much more serious consequences were involved: "While large sums of research time and money are spent on trying to understand how the AIDS virus fits into the HTLV group, thousands continue to die from AIDS" (O. Sattaur, "How Gallo Got Credit for AIDS Discovery," New Scientist, 2/7/85; p. 3). Sattaur's story noted the IP team's long-standing belief that the AIDS virus might belong to the lentivirus group. The article quoted the chairman of the AIDS Working Group of the British Medical Research Council saying this: "'HTLV-I and LAV have similarities in that they are both retroviruses that attack T-cells. But their genes are very distinct and they therefore cannot be closely related. Experience of taxonomy shows that it is wrong to rush to name a virus when you've got only partial information'" (op cit., p. 4). The New Scientist article also dealt with the scientific, political, and financial implications of the obvious functional identity of the IP and LTCB prototype viruses. In this regard, Sattaur quoted IP scientist, Dr. Simon Wain-Hobson: "'The viruses LAV and HTLV-III are so close that it proves that Montagnier was right and that he was the first to discover it'" (op cit., p. 3). Sattaur described the patent and financial implications of the functional identity of the viruses: "Deciding who has priority on the discovery of the virus is important for reasons other than to glorify the discoverers. The total U.S. market for diagnostic kits alone, to screen blood for the presence of the AIDS virus, is estimated at $80 million. Who receives the money from patent rights obviously depends on who first patented the procedure for isolating the AIDS virus" (op cit., p. 3). Whether or not one accepts the proposition that "who first patented the procedure for isolating the AIDS virus" would determine "who receives the money from patent rights," the fact is that by the time of the Sattaur story, the IP patent application was no secret. As early as July 1984, the journal Nature reported that the IP (and its commercial ally, Genetic Systems, Inc. [GS]), "... claims patent priority for the venture over the test developed by Dr. Robert Gallo ... The basis for the GS claim is that the Institut Pasteur in Paris filed for world-wide patent rights ... in September 1983 ..." (310, 1984, p. 174). Dr. Gallo was quoted as saying that the LTCB test "can identify AIDS patients with 100 per cent efficiency," presumably based on the idiosyncratic study of Safai et al. Referring to the IP scientists and their GS affiliates, Dr. Gallo said, "... 'they're only in it for the money'" (op cit.). The scientific media were not the only ones who noted the patent/financial implications of the LAV/IIIb identity. The February 28, 1985 issue of The Financial Times carried a story by Paris reporter David Marsh, headlined, "French Evaluate AIDS Test as Patent Row Continues." Marsh's story described "a unique trans-Atlantic battle over patent rights which has not yet been resolved" (The Financial Times, 2/28/85; p. 8). The story also noted the different names Montagnier and Gallo had given their prototype AIDS virus isolates, adding this: "Publication almost simultaneously in January this year by the French and Americans of the genetic structure of the two viruses ... showed them to be virtually identical" (op cit., p. 8). The Financial Times story noted that the LAV/IIIb sequences also showed that the AIDS virus "... shows some significant differences from the earlier-discovered HTLV-I and -II viruses discovered by Dr. Gallo"; the story further noted that the AIDS virus, unlike HTLV-I and -II, "kills T-cells which control the body's immune response, whereas HTLV-I and -II make them multiply in an uncontrolled manner" (op cit., p. 8). And the story added this: "These two pieces of evidence, throwing doubt on whether the AIDS virus really forms part of the HTLV group, seem to clinch the Pasteur team's claim to paternity of the virus discovery. Much more than scientific prestige is at stake. Patent rights on the soon-to-be-marketed diagnostic tests -- as well as on an eventual vaccine for the disease -- will be worth a fortune both to the research institute and to the individual scientists who can prove they were first in the AIDS field" (emphasis added; op cit., p.8). Omar Sattaur's February 1985 article evoked an outcry among Dr. Gallo's colleagues, who wrote a long letter to New Scientist, the theme of which was that: "Dr. Gallo and his colleagues never reported close relatedness of HTLV-III to HTLV-I or to HTLV-II." Presumably, the author of this letter, Dr. Dani Bolognesi, a close Gallo associate, never saw the Gallo et al. blood test patent, which contains the affirmation that: "The biological properties of HTLV-III and immunological analysis of its proteins show that this virus is a member of the HTLV family and closely related to HTLV-II" (emphasis added). Sattaur's story was but one of many in early 1985 that questioned the "HTLV-relatedness" claims of Gallo et al. concerning the AIDS virus. The name "HTLV-III" itself soon was called into question; and in March 1985, the International Committee on Taxonomy of Viruses commissioned a special subcommittee, under the leadership of now-NIH Director, Dr. Harold Varmus, to make an authoritative determination about the correct name for the AIDS virus. Dr. Gallo, who was determined to keep the AIDS virus in "his" "HTLV" family, immediately initiated an exchange of correspondence with Dr. Varmus about the nomenclature issue; Dr. Gallo's theme, propounded at extraordinary length and with great ardor, was that, "'HTLV-III' is a fair, accurate, and safe term to use" (4/8/85 Gallo-to-Varmus letter). Dr. Gallo's pleas were unavailing. In 1986, the subcommittee announced that "human immunodeficiency virus" ("HIV") would henceforth be the official name of the virus. Dr. Gallo refused to accept the new name, and because of the ongoing French/American dispute, not to mention their own awe of Gallo, HHS attorneys once again became involved in an issue that should have been resolved by scientific consensus. On May 6, 1986, PHS attorney Richard Riseberg sent to attorney Darrel Grinstead an "Eyes Only" memorandum headed "HIV Designation." Riseberg told Grinstead about the international committee's decision to adopt the name "HIV." Riseberg said that, "In view of the prestige of the subcommittee the new designation is likely to be adopted rapidly by the research community, although ... Bob Gallo and Max Essex opposed the change." Riseberg said he expected that questions would soon arise within PHS concerning, "... what effort, if any, PHS should make to resist the change and to what extent PHS should persist in using the traditional terminology in its own publications." Riseberg told Grinstead he (Riseberg) believed the shift in terminology would not have any important, predictable effect on the ongoing litigation. Accordingly, "... to the extent the new reference becomes widely accepted, there would be no legal objection to PHS switching as well." However, Riseberg added this: "In light of Dr. Gallo's opposition, I doubt that PHS would take the lead in adopting HIV." 2. Scientific Papers: Too Alike to be Different: The other major revelation associated with the early-1985 publication of the sequences of the first HIV isolates was the confirmation of what had been observed earlier, based on comparisons of viral nucleic acids, namely that: (1) HIV isolates overall are markedly heterogeneous in their genetic make-up, yet (2) in contrast to other HIV isolates, LAI/LAV and LAI/"IIIb" were virtually identical. Dr. Gallo and his associates attempted to deal with the obvious implications of the sequence identities of LAI/LAV and LAI/IIIb by, among other things, submitting the Ratner et al. letter to Nature. But the Ratner letter's indication, without substantiation, that the very close relationship of LAV and IIIb fell within the normal range for HIV isolates, plus the equally unsubstantiated argument that these isolates were so much alike because "the individuals from whom these isolates were derived acquired the virus at a similar time and place" -- these efforts did not head off the growing awareness on the part of alert scientists that "LAV" and "IIIb" were too much alike to be different. One such scientist was NIAID laboratory chief, Dr. Malcolm Martin. As early as November 1984, Dr. Martin had concluded not only that the IP and LTCB prototype viruses were almost certainly identical, but that the LTCB virus was descended from the IP virus, and not the other way around. Dr. Martin's November 1984 conclusions were based in part on his discovery of the existence in LAI/LAV of a Hind III polymorph identical to that found by Gallo et al. in LAI/IIIb. In a November 23, 1984 memorandum to the record, Dr. Martin wrote this: "... I learned from presentations by both the Pasteur and Gallo groups that a restriction polymorphism of the LAV/HTLV-III [IIIb] proviral DNA exists; at least two species of viral DNA are present in infected cells. This clears up an enigma we had encountered during the week of November 11, 1984 when we were analyzing the viral DNA present in infected A3.01 cells (LAV). The interpretation of our experiments is that two discrete species of proviral DNAs containing an extra Hind III and an extra SacI (SsI) site ... are present in infected cells in a 2:1 ratio. Both proviral DNAs are present in LAV and HTLV-III virus stocks. I obtained my pool of the LAV virus on April 13, 1984 ... Since Dr. Gallo's laboratory provided a sample of the HTLV-III virus to Montagnier in mid-May, 1984, our results would indicate that the LAV variant was present in the French virus stock at least one month earlier ..." With the early-1985 publication of the nucleotide sequences of the IP and LTCB viruses, Dr. Martin believe it was important to focus the attention of the scientific community on their evident molecular identity. Accordingly, in March 1985, Dr. Martin and an NIAID colleague, Dr. A. B. Rabson, published a "Minireview" in the journal Cell, titled "Molecular Organization of the AIDS Retrovirus." The Rabson/Martin review included a number of important observations about the common and distinguishing features of the three principal AIDS virus isolates to date: LAV, IIIb, and ARV, which Rabson and Martin termed, collectively, "the AIDS RV." The most volatile observations in the Rabson and Martin review concerned the molecular relationships of different AIDS RV isolates to each other. Rabson and Martin noted that the Shaw et al. (1984) and Luciw et al. (1984) reports: "... indicate that AIDS RVs isolated from different individuals exhibit striking structural heterogeneity as monitored by restriction enzyme polymorphisms" (op cit., p. 479). Further, said Rabson and Martin: "... superficial inspection of published cleavage maps and Southern blots suggests that HTLV-III and LAV are closely related to one another, whereas ARV and many other isolates are substantially different" (op cit., p. 479). Rabson and Martin reviewed the recently-published LAV, IIIb, and ARV-2 sequences; their analysis of the sequences showed that while LAV and ARV differed from each other by 9.3 percent, LAV and IIIb differed from each other by only 1.8 percent. Rabson and Martin said this: "A comparison of HTLV-III [IIIb] and LAV proviruses generated virtually identical results, indicating that HTLV-III was no more different from LAV than molecular clones of HTLV-III were from one another. In contrast, striking differences were apparent when LAV was compared to ARV" (op cit., pp. 479-480). The Cell review concluded with these comments about the LAV/IIIb relationship: "The analysis of nucleotide sequence heterogeneity presented in Table 1 indicates that HTLV-III and LAV are virtually identical. This result is surprising in view of their independent isolation and published reports, cited above, which show that extensive restriction enzyme polymorphisms exist among different AIDS RV isolates" (op cit., p. 480). B. Issuance of the Gallo et al. Blood Test Patent On May 28, 1985, the United States Patent and Trademark Office (USPTO) awarded patent number 4,520,113 to Drs. Gallo, Popovic and Sarngadharan, the named inventors of the LTCB HIV blood test. PTO's action in issuing a patent on the Gallo blood test came despite the fact that another patent application for substantially the same invention -- the IP application -- had been submitted to PTO months before the submission of the Gallo application. PTO officials told Subcommittee staff they issued a patent to Gallo et al. because they were unaware of the existence of the IP application. PTO records show that from the time the IP application was submitted -- December 5, 1983 -- to the time of issuance of Gallo et al., the IP application was assigned to no less than three different patent examiners. None of these examiners performed the vital process of "briefing" the IP application, i.e., abstracting its claims and entering them into PTO's then-antiquated central records system. Because the IP application had not been briefed, its existence was not identified when the Gallo et al. examiner performed the last-minute "interference search," in which the claims of an about-to-be issued patent are checked against the claims of other pending applications. The fact that Dr. Gallo and his fellow "inventors" had not disclosed to PTO their knowledge and use of LAV was another significant reason why PTO issued a patent to Gallo et al., with no consideration of the IP prior art. PTO's slow pace in examining the IP application was less remarkable than the near-record rapid pace of prosecution for Gallo et al. It is in this area that concerns about apparent inequitable handling by PTO of the IP and LTCB blood test patent applications are most obvious. At the outset, the Gallo et al. application was assigned to a low-workload PTO unit, on grounds that the claimed invention involved use of radioactive labelling and thus, was deemed to be high priority. The decision to assign Gallo et al. to the low-workload, high priority unit was made by PTO. Yet the IP application, whose invention also included use of radiolabelling, was assigned by PTO to a high-volume, high backlog unit, guaranteeing a protracted examination process. The examination processes for the LTCB and IP applications -- performed by the same examiner -- also were dramatically different. PTO issued but a single office action on the Gallo et al. application, passing it to issuance in a near-record seven months (April-November 1984; the further delay in publication of the patent, to May 1985, appears to have been due to the HHS contract attorney's failure to promptly pay the issuance fee). The examiner's review of Gallo et al. was manifestly inadequate; e.g., she identified but dismissed Barre-Sinoussi et al.; she failed altogether to identify such significant publications by the IP scientists as Vilmer et al. In contrast, once the PTO examiner finally began her examination of the IP application (in June of 1985), she issued innumerable office actions, raising one "red-herring" issue after another, including issues the IP attorneys successfully rebutted as "totally erroneous in law and in fact" (IP Response to PTO Office Action, December 16, 1985, pp. 8-9). On one occasion, the examiner even attempted to assert that Dr. Montagnier's own presentation (at the July 1983 meeting of the NCI AIDS Task Force) might be a bar to an IP patent. Other curious actions of the PTO examiner relating to the blood test patent application of Gallo et al. occurred in the Spring of 1985, just before the Gallo patent issued. On May 31, 1985, the PTO examiner sent to Gallo et al. a notice that prosecution of the "610" CIP (one of the follow-up applications to the parent LTCB blood test patent) would be suspended for six months because, "... a reference relevant to the examination of this application may soon become available." PTO's citation of a "reference relevant to the examination of this application" appears to have been a citation to a paper by Casey et al., that was about to be published in The Lancet, in August 1985. The Casey et al. paper was important because, among other things, it reported that the amino acid sequence of the LAI/LAV core protein was identical to that of LAI/IIIb. Because of these findings, the Casey et al. paper, following its publication, was cited by the PTO examiner as evidence that LAV and HTLV-III were functionally the same virus, and therefore, that the work of Montagnier et al. was prior art to Gallo et al. Using Casey et al., the PTO examiner repeatedly rejected the claims of Gallo et al. in two CIPs to the parent blood test patent. (See the PTO chronology appended to this report for further information about the PTO examiner's use of Casey et al.) Several aspects of the May 1985 PTO suspension notice on the 610 CIP are worthy of note. Since the examiner believed the forthcoming reference was relevant to the examination of the 610 CIP, it would be reasonable to believe the reference could be relevant to the parent blood test patent as well (the same individual examined both the Gallo et al. parent application and the Gallo et al. CIPs). Yet there is no indication that the Casey et al. reference was considered vis-a-vis the about-to-be issued Gallo et al. blood test patent. Notations on the copy of the suspension letter indicate the letter was prepared on April 22, 1985, over a month prior to issuance of the Gallo et al. blood test patent, yet the patent was permitted to issue with no apparent consideration to the implications of Casey et al. The May 28 issuance of the Gallo et al. blood test patent reportedly came as a great shock to the IP scientists and patent attorneys, along with the attorneys for Genetic Systems, Inc., U.S. licensee for the IP HIV antibody blood test. The attorneys, apparently, had been operating under the assumption that, since the IP application was submitted well before the application of Gallo et al., the IP scientists were certain to be awarded the patent on the HIV blood test. There are indications that shortly after the issuance of the Gallo et al. patent, IP/GS patent attorneys contacted PTO to inquire about the IP application. What is certain is that on June 10, 1985, the examiner who had just passed Gallo et al. to issuance was presented with the IP blood test patent application by one of her supervisors, and told to expedite its handling. According to the examiner, when she reviewed the IP blood test patent application, she recognized that the IP application and the just-issued Gallo et al. patent were "directly related." The examiner said PTO recognized it had erred by missing the IP application during prosecution of Gallo et al.: "We screwed up." Importantly, the examiner said that had she become aware of the existence of the IP application during prosecution of Gallo et al., she would have suspended that prosecution, examined the Pasteur application thoroughly, and, "... probably would have thrown them into an interference." But this did not happen, and the losers in the process were the real discovers of the AIDS virus and true inventors of the virus antibody blood test, Montagnier et al. Because of the failure of Gallo et al. in their duty of disclosure to PTO, because of PTO's own negligence in leaving the IP application untouched for years, and because of the incompetent examination of Gallo et al., the PTO examiner, at the time she passed to issuance Gallo et al., was not aware of the IP application nor even of the IP scientists' prior art. Because Gallo et al. received the patent on the HIV blood test, the IP scientists, although they discovered the AIDS virus long before Gallo et al., although they created and used the HIV blood test long before Gallo et al., were significantly disadvantaged, and were forced to shoulder the burden of petitioning for an interference. Even when the IP requested an interference, it was nearly nine months before the interference was granted, and over two years before the IP scientists finally were awarded a U.S. patent, in late 1987, nearly four years after they filed their U.S. patent application. C. The Initial Challenge On August 6, 1985, IP attorneys, plus attorneys for Genetic Systems, met with officials of HHS to formally register their objections to the Gallo et al. blood test patent. Dr. Raymond Dedonder, the then-IP Director, led the IP/GS delegation. Participants for the United States included Lowell Harmison as chair, Harmison's "Senior Assistant," Dr. Ann Rose, HHS attorney Darrel Grinstead, Thomas Byrnes (DOJ), NIH patent attorneys Leroy Randall and Thomas Ferris, NCI's Dr. Peter Fischinger and Dr. Berge Hampar, and Robert Auber of the Patent Licensing Program, National Technical Information Services (NTIS). Several sets of handwritten as well as more formal notes of the August 6 meeting exist. According to a memorandum prepared for HHS Secretary Margaret Heckler's Chief of Staff by the HHS Executive Secretariat's Tim Miller (present at the meeting), the "basic claim" of Dedonder et al. was that Gallo et al. "... either knowingly or mistakenly appropriated Dr. Montagnier's invention..." Further, according to Miller, the IP/GS delegation, "... made three oral demands which they say are necessary to avoid litigation over who should be credited with the HTLV-III patent and who should derive the commercial benefits: (1) Recognition that Dr. Montagnier of the P ****TEXT MISSING**** VIII. HHS INITIAL RESPONSE A. The HHS Mindset The overriding tenor of the HHS response to the IP assertions and demands seems to have been one of instinctive defense of the U.S. claims, rather than concern as to whether those claims were valid. There was no effort on the part of HHS to mount an objective inquiry into the facts; instead, every effort at HHS was devoted to how best to defend the HHS patent and the HHS scientists. Whether or not they warranted defense, whether or not they could legitimately be defended -- these, apparently, were not among HHS' concerns. The prevailing attitude, indeed mind-set, was well-exemplified by Peter Fischinger, who played a crucial role during the early months of the French/American dispute. Fischinger described his reactions to the IP challenge to Subcommittee staff in these terms: "I was somewhat incensed, because the feeling was that 'you've gotten the virus from us... and you might have stolen it or at best, you might have mixed it up'" (8/6/93 Subcommittee staff interview; tape 4, side 2). Explaining his "incensed" reaction, Dr. Fischinger said: "Well, it was kind of extraordinary -- based on what I knew, I thought it was kind of a very significant contention ... "I thought there was a pretty good track record of discovery of the virus in Gallo's laboratory. And the fact that the two viruses might have been very close, but there was enough of a distinction that Gallo and Montagnier isolated the same sub-type of virus ... my feeling was, 'so what?'" (op cit.). Dr. Fischinger's further statements to Subcommittee staff showed the extent to which Dr. Gallo's assertions about his alleged "early isolates" of the AIDS virus, together with his assertions about his inability to grow LAV influenced his (Fischinger's) reactions to the IP challenge: "My whole attitude was he [Gallo], obviously -- and everybody else with him -- 'of course we didn't use LAV,' I mean, 'we couldn't even grow it. How could we?' ... "It could not have happened, and the fact that the two viruses were the same, there were other matched pairs ... The facts that I had, I was incensed, it was outrageous, an outrageous sort of a claim. I had a full sense that this was an independent isolation, verification, putting together the first definite association between the test and the disease ... I really felt that the U.S. team had a very significant claim and priority" (op cit.). Then-NIH Director Dr. James Wyngaarden confirmed this perspective to Subcommittee staff. Describing the HHS approach to the IP challenge, Dr. Wyngaarden said this: "... almost everyone at NIH really believed Bob was ... maybe not generous to the French but that he had the data himself, had done it himself. The feeling was very strong that the French were trying to muscle in, trying to take credit ... that Bob had earned ... "At the time, everyone in the system thought the French were trying to take credit for Bob's work, that they were putting more credit on Montagnier than was warranted. Everyone up and down the line felt that -- of course, we were relying on Bob's account of what he had done" (9/27/93 interview with Subcommittee staff). Queried as to how the entire HHS fact-finding process could have relied so heavily - nearly exclusively -- on Dr. Gallo's assertions about his research, Dr. Wyngaarden said this: "He can be very persuasive ... Bob is exceptional in his capacity to integrate information from lots of sources and integrate it into a persuasive, coherent statement of what it means ... His mind in my view is in a class by itself for that sort of thing" (op cit.). Reflecting his awareness of the potential pitfalls of so "persuasive" a presentation, Dr. Wyngaarden added this: "I gather he made some scientific claims in the 70s and 80s that hurt his reputation .... Usually the scientific process takes care of that -- if someone is out on a limb, someone else saws it off. It's not uncommon to overinterpret. You can be overwhelmed by it" (op cit.). NCI/HHS' mind-set was in evidence immediately after the meeting with the French delegation. HHS officials, still under the chairmanship of Dr. Lowell Harmison, met to plan their strategy for dealing with the IP challenge. According to Tim Miller's memorandum to Secretary Heckler, in the HHS officials' meeting, Peter Fischinger discounted the IP claim that Gallo et benefitted from their access to confidential information from the Pasteur scientists. According to Miller, Fischinger said: "... the key to the invention is not its isolation [the AIDS virus]; rather the key was the development of the 'cell line' necessary to produce the virus in large quantities..." Miller also recorded that: "Dr. Peter Fischinger believes we can develop evidence to show that Dr. Gallo had isolated the retrovirus on his own as early as February 1983, although he had not specifically identified the retrovirus at that time." B. Gallo and Popovic Respond The practical outcome of the HHS meeting was that the National Cancer Institute (NCI) was charged with conducting "an internal mission" to determine if any evidence existed to substantiate the IP claims. Peter Fischinger, quite clearly, had already made up his mind about the principal points of contention; yet Fischinger was placed in charge of the "internal mission," which nominally included the NIH patent attorneys, but in reality was a solo mission for Dr. Fischinger. Pursuant to his mission, the day after the meeting of IP and HHS representatives, Dr. Fischinger wrote a memorandum to Dr. Gallo, describing the major points made by the IP representatives. Fischinger said the thesis of Robert Nowinski, the chief scientist for GS, was that: "... the basis for the filing of the U.S. patents for the blood tests was incorrect. The reason was that (the) key component of the test, i.e., the virus, was not of U.S. origin .... His thesis ... was that LAV and the HTLV-IIIb were actually one and the same, and that your laboratory somehow re-isolated the LAV and proceeded to deal with it as HTLV-III from then on" (8/7/85 Fischinger-to-Gallo memorandum). Dr. Fischinger described the objectives of his HHS-mandated mission, and he told Dr. Gallo what was needed from the LTCB: "NCI was to examine the events leading to the discovery of HTLV-III. In that context, the documents cited by Mr. Weisser (sic.) will be necessay (sic.) if available. These include all correspondence between your laboratory regarding the timing [of] the acquisition of LAV from France and the reciprocal transmission of HTLV-III and cells to the IP. Second, the documentation of the review process of the Barre-Sinoussi Science paper with input from the editors and other reviewers will be needed" (op cit., pp. 2-3). The final element of Fischinger's document request to Gallo is noteworthy. It shows how, at the very outset of his inquiry, Dr. Fischinger had determined to rely on the "other isolates" defense against the IP charge that Dr. Gallo used LAV for the LTCB blood test: "Third, please assemble adequate documentation from your laboratory data that you have isolated an HTLV-III agent(s) prior to the receipt of LAV. Standard virus differentiating criteria would be useful, such as electron micrographs, inability to immortalize T4 cells and negativity of reactions with antibodies to p19 or p24 internal proteins which identify HTLV-I or -II" (op cit., p. 3). Dr. Fischinger's memorandum to Dr. Gallo concluded with this: "Your response will be useful in determining the future course of actions of HHS. Obviously, because these allegations have a significant negative bearing on your personal reputation and scientific integrity, please feel free to discuss alternative actions which would rectify the thrust of the above-cited allegations" (op cit., p. 3). Dr. Fischinger's memorandum to Dr. Gallo was the starting point for a series of memoranda from Gallo and his staff to Fischinger, along with selected pages of data. The significance of the LTCB scientists' submissions and the resulting so-called "Fischinger report" cannot be overstated. In numerous instances, the memoranda were forwarded from NCI to HHS officials and to HHS and DOJ attorneys. In a number of instances, the contents of the memoranda were incorporated, often nearly verbatim, into official HHS and DOJ documents, including the Fischinger report. This report, initially provided to Lowell Harmison, was forwarded to HHS attorneys and later, to the Department of Justice, where it was represented as the definitive NIH/HHS statement of facts concerning the substantiation for the claims of Gallo et al. The August/September 1985 Gallo/Popovic memoranda, supplemented by interviews with Gallo, Popovic and other LTCB scientists, also were incorporated into briefs and pleadings filed by DOJ attorneys on behalf of the U.S. Government. (Notably, most of the Gallo/Popovic memoranda, along with Fischinger's August 7 memorandum and the "Fischinger report" itself, were withheld from the IP under FOIA. One memorandum -- an August 23, 1985 memorandum from Fischinger to Gallo -- also was withheld, but unlike the other memoranda, was not included on the legally-mandated "Vaughn index" of putative FOIA-exempt documents, almost certainly due to its extraordinary sensitivity (see below). In short, the documents generated by the LTCB scientists formed the framework for the entire U.S. Government defense. But many important facts were not revealed by the LTCB scientists; numerous significant items of data were not provided by them to HHS and DOJ officials. Moreover, many of the assertions contained in the LTCB scientists' submissions could not be substantiated. Thus, the entire U.S. Government defense was constructed on a false and defective infrastructure. But incomplete and incorrect information emanating from the LTCB was not only problem with the HHS inquiry. From the beginning, the inquiry was directed away from the issues that were the real focus of concern, the issues on which Gallo et al. were most vulnerable, toward a number of irrelevant, "red-herring" issues behind which HHS apparently hoped to find cover (e.g., the LTCB's alleged "other isolates"). It is clear from accounts of the August 6, 1985 meeting that two sets of issues, above all, were the real foci of concern: (1) what did Gallo and his colleagues do with LAV at the LTCB, in particular, could Gallo et al. document that IIIb/H9 was derived independently of LAV and (2) what HIV isolate did Gallo et al. use to make the LTCB HIV antibody blood test, and when was the blood test created? Curiously, neither of these sets of issues was posed by Dr. Fischinger to Dr. Gallo, in Fischinger's August 7 memorandum. Fischinger was asked by Subcommittee staff what questions he was trying to answer in his inquiry and why, for example, he sought from Dr. Gallo evidence of "HTLV-III" isolation "prior to the receipt of LAV." Dr. Fischinger's response revealed how, even at the outset of his inquiry, he believed he knew the facts: "I guess I was so convinced of the fact that the charge was so outrageous, and I thought, 'if you can show that you obviously had it (HTLV-III) -- if you got it and had it growing, it was fine, and you can develop a test with it, you really wouldn't have to do it [misappropriate the IP virus]" (8/6/93 interview with Subcommittee staff; tape 3, side 2). Dr. Fischinger agreed with Subcommittee staff that he felt he already knew the truth, i.e., that the IP claims were false. Thus, Dr. Fischinger said, he believed his task with respect to the LTCB scientists was this: "Show me that these charges were kind of outrageous. That was my feeling at the time." What is remarkable about Peter Fischinger's indirect approach to his investigation is that documentary evidence shows Dr. Fischinger knew well that the indirect approach would not be adequate, recognized well what were the central issues in the dispute and what kinds of data Gallo et al. would have to provide to substantiate their claims. This is evident from an August 23, 1985 memorandum from Fischinger to Gallo. The sensitivity of its contents are seen in the fact that the memorandum was not produced by NIH to the Subcommittee until September 1993, more than 18 months after the Subcommittee's initial document request, well after the staff's interview with Dr. Fischinger, and only after numerous communications to HHS concerning document withholding, particularly at NIH. The August 23 memorandum specifically targeted the major issues embodied in the IP challenge, identifying them as, "three major areas of oversight" in Gallo's data/document production "which have to be completed." The "major areas of oversight" included issues about which Subcommittee staff questioned Dr. Fischinger, e.g., the origins of "IIIb" and the development of the LTCB blood test. Dr. Fischinger downplayed the significance of these issues, yet his memorandum makes clear he recognized well they were central to the validity of the claims of Gallo et al. Dr. Fischinger's obvious awareness of the critical nature of the "major areas of oversight" makes it all the more remarkable that at the time Dr. Fischinger wrote the August 23 memorandum to Dr. Gallo, the first draft of the "Fischinger report," including its conclusions, had already been completed. These circumstances demonstrate graphically that HHS was determined to proceed with its defense of Gallo et al., no matter what the truth might be. (See below for information on Gallo's response to the August 23 memorandum.) The LTCB information production process began on August 14, 1985, when Dr. Gallo and his associates, particularly Mikulas Popovic, commenced the transmittal to Dr. Fischinger of a series of memoranda, some of them accompanied by selected laboratory notes, apparently intended to address the issues raised by Fischinger in his August 7 memorandum, and later, his August 23 memorandum. The inaccuracies and omissions in the LTCB documents were incorporated, often nearly verbatim, into key documents in the U.S. Government defense of Gallo et al. Examples of these false and misleading claims appear in the Executive Summary of this report. The most important such items from the Gallo/Popovic August 1985 memoranda are as follows: Responding to Dr. Fischinger's requirement for "documentation from your laboratory data that you have isolated an HTLV-III agent(s) prior to the receipt of LAV," Dr. Gallo provided no data that met the stated requirements. Several samples were identified, including the suspect December 15, 1982 samples. But no evidence was supplied to show that any of these samples had ever been tested and found positive for HIV. In fact, no such evidence existed. (Gallo-to-Fischinger; August 14, 1985). Concerning the LAV samples received at the LTCB in 1983, Dr. Gallo said July LAV "... did not contain detectable virus" (Gallo-to-Fischinger; August 19, 1985). An appended memorandum by Dr. Popovic made no mention whatsoever of July LAV. Concerning September LAV, Dr. Gallo said only that, "Dr. Popovic reports he was able to detect RT..." (Gallo-to-Fischinger; August 19, 1985). Dr. Popovic, in his appended memorandum, described the September LAV sample as "a small amount of extracellular virus particles." Dr. Popovic did not mention any of the positive IFA results with LAV prior to December 1983. Popovic did mention the infection of Ti7.4 with LAV, but he dated it to December 1983, rather than October. There was no mention of the LAV infection of HUT-78. Dr. Popovic said the LTCB scientists had determined that LAV and "HTLV-III" "had cross reactive major proteins," but Dr. Popovic did not say when this determination was made. Most significantly, Dr. Popovic did not reveal that LAI/LAV was tested and found positive against the rabbit antiserum; neither did he or Dr. Gallo make any mention of the LTCB's molecular analyses of LAI/LAV, including the comparisons that showed LAI and IIIb were identical. Concerning the putative "pool" virus, Dr. Gallo made the following statement, contrary to all available evidence: "Material placed into the permanent cell line H9 and published in May 1984 to develop reagents and molecular clones was pooled from several patients who showed high RT activity in primary culture" (Gallo-to-Fischinger; August 19, 1985). Dr. Gallo asserted, without substantiation, that the uniquely close relationship between IIIb and LAV, "... probably represents the similarity within the known range of variation of viruses isolated from different patients at different times" (Gallo-to-Fischinger; August 19, 1985). Besides their memoranda, Drs. Gallo and Popovic also submitted approximately 100 pages of data to Dr. Fischinger. The data pages were essentially useless. Numerous pages were illegible; on many pages, identifying information for individual samples had been removed, making it impossible to trace what was done with particular samples. Other pages contained no data, only lists of samples sent for, e.g., RT or EM analysis. Most significant, the data pages included only one page that even mentioned "LAV." This page, dated "9/22/83," showed LAV was used to infect four cord blood cell lines. However, no pages containing results for these cultures were provided to Dr. Fischinger, neither were any data included from the LAI/LAV infections of the five permanent T-cell lines. As for the LTCB HIV antibody blood test, the data package contained none of Dr. Sarngadharan's ELISA data. Thus, Dr. Fischinger had no way to determine when the first LTCB blood tests were performed; neither was he able to recognize that the LTCB HIV ELISAs for two months were performed with antigen from a virus called "MOV," not with the patented isolate, "IIIb". Betsy Read-Connole gave important information to Subcommittee staff concerning how the data package was created for Dr. Fischinger. Read-Connole initially said she was "told to copy everything," but then she added, "I helped select it." Most important, according to Read-Connole, "We were told not to put the LAV stuff [in the August data package] ... they wanted the other stuff." Read-Connole said she did not know the origin of these specifications, neither did she know to whom the data were sent, once they were assembled. Dr. Fischinger, apparently, did little more than glance at the data he was given by Gallo et al. When Subcommittee staff showed him the data pages provided in August 1985, Dr. Fischinger said this: "This is much more than I remember seeing. I don't think I've seen all of that" (8/6/93 interview; tape 3, side 2). Asked if he had reviewed the data pages one-by-one, and if he knew why he was given those particular pages, and not others, Dr. Fischinger's response was this: "There were others?" Dr. Fischinger was informed that among the pages he was given, there was only one page that even mentioned "LAV." Asked if this had struck him as odd, Dr. Fischinger said: "I don't think it would have struck me as odd, because again, my sense was, 'show me that you developed the test on your own, independently'" (op cit.). Yet when Dr. Fischinger was asked if he received and reviewed actual data related to the LTCB HIV blood test, his response was this: "I don't remember the specific development of the ELISA test in the laboratory." Attempting to explain his evident inattention to the LTCB data, Dr. Fischinger said, "A lot of it was very hard to understand, very difficult." Dr. Fischinger was asked if he asked Popovic or Gallo or anyone from the LTCB to interpret the data for him. Fischinger's response was revealing: "I tried to rely on some of the summaries of the data, as opposed to going through it page by page ... I think I remember sort of receiving sort of an occasional sort of summary of what happened, but I did not go with Popovic through this page by page." Because Dr. Gallo claimed to Subcommittee staff that in August/September 1985 he had no idea of the seriousness of the French/American dispute, Dr. Fischinger was asked if he attempted to instruct Dr. Gallo about the matter. Fischinger's response showed that he attempted to keep the focus of responsibility on Dr. Gallo: "Yes I did. In terms of the point, you have to get all the data ... in terms of what he had in hand. And then refine it for us, because of the difficulties of the notebooks. And I did tell him that he would have to stand or fall in terms of those data and that ... he would basically have to swear to the fact that that's what it is ... that if it ever came to a more significant sort of examination, that he would have to then go into a wealth of detail that wasn't feasible in that timeframe" (op cit.). Dr. Fischinger made clear that Dr. Gallo was his principal contact and source of information and the person ultimately responsible for the LTCB scientists' work. Asked if he consulted with Dr. Sarngadharan, who performed the ELISAs, made the HIV-specific rabbit antiserum, and performed the seminal protein analyses for the LTCB, Dr. Fischinger said this: My major point of discussion was Bob. No question about that. In terms of him trying to organize or find some of the data, some of the things that were going on. I was listening to him as the point person ... I had a sense, at least from my perspective, there is laboratory data, Bob sort of swears that this is the way it is, and the laboratory data sort of generally support it, as opposed to no data. Then, that's going to be his, sort of, ultimate responsibility. That was my feeling. So, I would rely, myself, from a scientific point of view, in terms of what they did in the lab, he has the best knowledge, he should have the control of it" (op. cit.). Dr. Fischinger added this: "My feeling was that Gallo has to go, and demonstrate this, and he has to defend what he has done, he has kind of sworn to the fact that he did what he did, and the fact that this is something that could stand in terms of his own laboratory's merit. And he sort of claims it even in terms of specifics, and has an argument that I could sort of believe in that is strong enough, as opposed to my going -- kind of a detailed, detective-type investigation, which I didn't do. I mean, that was clear. That wasn't done until sometime later. I said, 'Look, this is what you did. This is the summation of [what] you had and said in your laboratory data to prove it. And let's take it from there" (op cit.). C. The "Fischinger Report" Peter Fischinger's response to Lowell Harmison's directive to him to "examine the events leading to the discovery of HTLV-III" was a written report in the form of a memorandum, identified herein as "the Fischinger report." The report was prepared in a great hurry; an initial draft was prepared by August 21, two weeks to the day after Fischinger started his "inquiry." The final version of the Fischinger report was dated August 27. The report was routed through NCI Director DeVita, NIH Director Wyngaarden, and HHS attorney Darrel Grinstead. Grinstead's sign-off apparently occurred on or about September 9, a notable date because of several significant events that occurred prior to that time (see below ). The final version of the report comprised these elements: (1) an 8-page memorandum from Fischinger to Harmison, (2) an addendum titled "Further considerations Based on the Documents Sent to HHS by the Institut Pasteur Director, Dr. Dedonder," (3) an August 21 memorandum from Gallo to Fischinger attesting to the accuracy of the information in document (4), and (4) a document titled "Background Information: U.S. Patent Applications." The Fischinger report was a compendium of irrelevant, misleading, and outright false claims; the report also reflected many significant omissions (see below ). The inclusion of numerous misleading elements in the Fischinger report is noteworthy, given that both Fischinger and Gallo signed statements attesting to the accuracy of the report and asserting that the statements in the report could be substantiated by laboratory data and records. Specifically, in a cover page for the "Background Information" document, Dr. Fischinger signed a statement that said this: "NCI requested specific documentation of data from Dr. Gallo's laboratory, and received about 100 pages of copies of laboratory notebooks, as well as abstracted summaries of these data. Although some of these data are cryptic and very difficult to follow, enough clarity emerged to make the enclosed comments." Dr. Fischinger added that "the resulting document," compiled by his office "... was next sent to Dr. Gallo to determine that it was accurate in both its content and interpretation." Dr. Fischinger cited an "enclosed concurrence statement" signed by Dr. Gallo; the statement, in the form of an August 21 memorandum from Gallo to Fischinger, said this: "The enclosed attachment 'Background Information, U.S. Patent Applications,' has been reviewed by me relative to the fidelity of specific information presented as well as the accuracy of its interpretation. These data are substantiated by entries in the notebooks, as well as by other records emanating from the Laboratory of Tumor Cell Biology, NCI." Dr. Gallo added this: "I stated previously, and I furthermore still believe myself to be the first inventor of subject matter covered by Patent Application #602,946, and the issued patent number 4,520,113, which are critical to the realization of the blood antibody test which measures exposure to the HTLV-III/LAV virus." Following is a listing of the most significant problematic statements in the Fischinger report. In most instances, the extensive evidence demonstrating the inaccuracy of these statements has been discussed. Pertinent page references are noted as appropriate. (1) "The examination of data from Gallo's laboratory showed that in mid-December 1982, the first HTLV-III-type isolates had been identified from AIDS patients" (8/27/85 Fischinger-to-Harmison memorandum; p. 2. "The Gallo laboratory already had very analogous data from AIDS patients as early as December 1982 ... the Institut Pasteur observations corroborated analogous pre-existing data in the NCI laboratory" (op cit., p. 7). The LTCB December 1982 data did not substantiate "HTLV-III-type isolates"; see above . Dr. Gallo himself repeatedly asserted he made no claims of priority based on the 1982 data. Dr. Gallo's data also were not analogous, much less "very analogous" to those of the IP scientists. The IP scientists' data were considerably more extensive and informative than the LTCB data. Moreover, the IP scientists' understanding of their data was well advanced compared to that of Gallo et al. (see above). (2) "Based on the examination of raw and compiled data ... between June 1983 and September 1983, it can unequivocally be stated that the Gallo laboratory had more than ample isolates of typical HTLV-III which could have been used as prototype (sic.) infectious agents" (op cit., p. 3). "... 17 different retrovirus isolates were obtained from AIDS patients during that time ... Aliquots of some of these virus samples are still available. Therefore, the above isolates had the same criteria as the infectious LAV subsequently received at the end of September 1983" (op cit., pp. 3-4). The statement that the LTCB scientists had "ample isolates of typical HTLV-III" by September 1983 is untrue. The LTCB's putative "isolates" between June and September 1983 were, virtually all, not isolates but, at the most, occasional detections. More importantly, none of them was known at the time to be "typical HTLV-III." The great majority of them were never tested and found to be HIV. None was useful as a prototype, because none was grown in sufficient quantity to be useful (see above ). Also significantly misleading is the unqualified assertion that Salahuddin/Markham's "isolates" "had the same criteria as the infectious LAV subsequently received at the end of September 1983." This statement is not correct. The data on both July and September LAV were considerably more substantial than the data on any of the Salahuddin/Markham "isolates." Both July and September LAV were tested and found positive by IFA against pre-AIDS patients serum and both were found positive for lentivirus by electron microscopy. None of the Salahuddin/Markham isolates "had the same criteria" (see above). (3) "... how complete or convincing was the French data in May 1983? What was described was reverse transcriptase (RT) activity in a single lymphadenopathy patient, without p19 and p24 HTLV-I cellular reactivity, and electron micrographs of budding particles from degenerating cells ... At that time , the French also considered their virus isolate to be a member of the HTLV family" (op cit., p. 2). Dr. Fischinger's statement that the IP scientists, in their May 1983 paper, showed there was no "HTLV-I cellular reactivity," is noteworthy because it is true. The statement thus stands in marked contrast to repeated statements by Dr. Gallo, the most notable of which is the statement in Gallo's November 1986 declaration that, "... the Pasteur group reported a major cross reaction with HTLV-I" (Emphasis supplied; 11/8/86 Declaration of Robert C. Gallo). Notwithstanding his accurate statement about the absence of HTLV-I reactivity, Dr. Fischinger asserted incorrectly that "the French also considered their virus isolate to be a member of the HTLV family." Dr. Fischinger either did not know about or deliberately withheld information concerning Dr. Gallo's role in rewriting the IP paper, including adding the assertion that LAV was a member of the "HTLV family" (see above). (4) "The receipt of the following materials from L. Montagnier is acknowledged by Gallo's laboratory: 1. 20 micrograms of 'LAV proviral DNA' was received April 1983. No viral DNA was present, only cellular DNA. 2. Supernatant fluids of one patient's T cells, not with AIDS but with lymphadenopathy, were received in July 1983, which did not contain any infectious LAV virus. 3. In late September, a second sample supernate from T cells of the above patient was received and did contain the first infectious LAV. It was successfully transmitted only to normal T cells and a human cell line Ti7.4. Thus there was no logic for the motivation to use the Institut Pasteur derived LAV in any infection sequence for any purposes other than a comparative analysis" (op cit., p. 4). The numerous false and misleading aspects of the above passage are readily obvious from the prior discussion of the LTCB's use of the IP virus. Most notable are the assertions that July LAV "did not contain any infectious LAV virus" and that September LAV "was successfully transmitted only to normal T cells and a human cell line Ti7.4." The claim that "no viral DNA was present" in the LAV DNA sent to the LTCB in April 1983 was seriously misleading and could not be substantiated. The only claim that could be substantiated was the claim that no HTLV-I or -II DNA was present, as one would expect, because these were the only human retroviruses for which Gallo et al. could test the LAV DNA. (5) "Dr. Popovic later attempted to infect the parental uninfected H9 cells with the LAV isolate from the Institut Pasteur. The total amount of reverse transcriptase activity obtained (appr. 20,000 cpm) was inadequate to initiate an infection of continuous cells" (op cit., p. 8). The authenticity of the experiment cited by Fischinger is suspect on many counts (see above). The claim concerning RT activity is particularly questionable, for no RT data associated with the putative attempt to infect H9 with LAV are known to exist. (6) "... an innovative technique of pooling of several highly RT-positive samples was used to infect the H9 subclone. Although under normal circumstances, pooling of isolates would be considered unusual, up to that time no one had been able to stably infect a continuous T cell line with HTLV-III despite repeated single isolate attempts" (op cit., p. 4). Only one of the samples allegedly used for the "pool" experiment was known to be RT+ at the time it was used. Several of the samples were never tested and others, when tested, were RT-. As for Dr. Fischinger's attempt to justify the "unusual" pooling methodology, on grounds that all previous single isolate attempts had failed, this statement fails to take into account the successful growth of LAI/LAV and LAI/MOV. (7) "The subsequent virus-releasing cell subline, designated HTLV-IIIb, has multiple DNA proviruses in it, based on hybridization and DNA sequence data. Two of these have been cloned and they are related but not identical. Neither of these proviruses is identical to LAV, and although they are close, they differ significantly by about 1-2% from LAV ... recent DNA sequence data show that exceedingly closely matched pairs of viruses have been isolated from different individuals. These pairs are as close as, or closer in relationship than LAV is to HTLV-IIIb" (op cit., p. 5). Dr. Fischinger's statements about the "IIIb" cell line embodied several interrelated, highly speculative, unsubstantiated assertions: the implication that the "IIIb" clones represented different "proviruses" derived from different samples placed in "the pool"; the implication that the sequence similarity of the IIIb clones showed that independent isolates from different individuals can be much alike; by extrapolation, the assertion that sequence similarity of the IIIb "proviruses" to LAV -- misleadingly described by Fischinger as differing "significantly" -- permitted the possibility that "LAV" and "IIIb" were independent isolates. As for the "closely matched pairs .. as close as or closer in relationship than LAV is to IIIb," Dr. Fischinger did not specify the pairs to which he was referring, and there is no evidence that they actually existed. Dr. Gallo did publish on one isolate pair -- "MN" and "SL" -- (Wong-Staal, et al., Science, 229, pp. 759-762. But Dr. Gallo later told OSI that, "... the close similarity of isolates MN and SL is now believed to be due to a mix-up of samples" (4/27/90 OSI interview; transcript p. 76). (8) "On detailed analysis of their more than 130 isolates, the conclusion is that there are not a few strains of HTLV-III/LAV but a continuum. Any one isolate has closely related 'relatives' (1 to 2% difference) and distantly related 'relatives' (more than 5% genomic diversity)" (op cit., pp. 5-6). The discussion of item 7 above demonstrates the dubious nature of the assertion that "any one isolate" has "closely related" virus relatives, where "closely related" is defined as "1 to 2% difference." Notwithstanding Gallo/Fischinger's claims, there was no reliable evidence that genuinely independent HIV isolates might be only 1 - 2% different in their genetic make-up. (9) "... the French could not develop an effective diagnostic test until more than one year after this publication [Barre-Sinoussi et al., May 1983], and after Gallo's discovery as defined in the U.S. patent application #602,946" (op cit., p. 3). "... no effective action was taken by the French group to develop a meaningful diagnostic test" ("Background Information: U.S. Patent Applications"; p. 1). "Who first linked the correct virus unequivocally to human AIDS? Dr. Gallo's group had precedence in this area as well by more than two months ... the subsequent joint manuscript from the Centers for Disease Control (CDC)and the Pasteur group was numerically much less firm" (op cit., p. 2). "Even in July 1984, the LAV-containing test systems picked up only 41% of AIDS patients" (op cit., p. 9). The fact is that the IP scientists developed an effective, accurate HIV blood test long before Gallo et al. did so. The evidence is compelling that Dr. Gallo knew about this blood test when he filed the patent application for his own test (see above here and also here ). Dr. Fischinger's assertions relating to the CDC/IP paper (the July 1984 "LAV-containing test systems) were significantly misleading. The paper in question reported results for two kinds of LAV antibody blood tests. One test, a blood test technologically different from that of Gallo et al., scored 41 and 72 percent positive in AIDS and pre-AIDS patients, respectfully. However, the other test, comparable to the test of Gallo et al., was fully as good as the LTCB test -- 70-95 percent positive in AIDS patients; 95 percent positive in LAS or pre-AIDS patients. During the entire patent dispute, up to the present day, Drs. Fischinger and Gallo never cited the latter set of results. Rather, they and the U.S. Government attorneys as well invariably cited the former set of results, never mentioning the differences in the nature of the tests that produced those results. Nor did Gallo, Fischinger, or any of the U.S. representatives ever mention the CDC data, of which Dr. Gallo had personal knowledge, that showed the IP and LTCB blood tests performing equally well in detecting antibodies to the AIDS virus. (10) "To get the LAV ELISA operational, the Institut Pasteur and their U.S. licensees also had to adapt LAV to a continuous human leukemic T cell line. It is of interest that they eventually used the HUT-78 cell line which is a relative of the HT cell line developed by Dr. Gallo" (op cit., p. 10). These statements were entirely incorrect. The IP scientists did not use HUT-78 to grow the virus for their HIV blood test. The cell line of which they made principal use for their blood test was CEM. Moreover, contrary to Dr. Fischinger's assertion that HUT-78 and HT are "relatives," the fact is that HT is HUT-78. There is evidence that by the time Fischinger wrote his report, both Popovic and Gallo knew or had reason to know that HT was HUT-78. Based on Dr. Fischinger's August 23, 1985 memorandum to Dr. Gallo, it appears that Fischinger himself remained uncertain and was seeking information about the origins of HT/H9. Yet despite his uncertainty, Dr. Fischinger wrote unqualified assertions about the origins of "HT" into his report to Harmison, assertions that neither Fischinger nor Gallo could substantiate. In addition, it bears mention that this passage is but another instance in which Gallo, contrary to his latter-day denials, endorsed the claim that he "developed" the HT cell line. (11) "There is no evidence that material from any outside laboratory including the French, was used in generating the HTLV-IIIb virus" (op cit., p. 3). "It is clear from other sections of this document that LAV was not used in generating the HTLV-IIIb virus strain advertently or inadvertently" (op cit., p. 8). "It is acknowledged that Dr. Gallo reviewed the French, May 1983, manuscript, and supported its publication, and that Dr. Popovic received the LAV isolate and signed the appropriate forms. However, because none of the above information or material was used in the generation of the U.S. inventions, the above acknowledgements are not germane to primacy of inventorship" (op cit., p. 4). The only reason there was "no evidence" of the use of outside material in the isolation of IIIb was that Dr. Fischinger did not look for the evidence, and such evidence as he had, he failed to examine. In this regard, it is important to remember that approximately one year before Dr. Fischinger wrote his report, he (Fischinger) was told by Gallo -- not once but on two occasions -- that IIIb and LAV were genetically identical. Dr. Fischinger's assertion, one year later, that there was "no evidence" that LAV was the source of IIIb is directly contradicted by the documentary record, including documents generated by Drs. Gallo and Fischinger themselves (see above). It also must be noted that in his August 23, 1985 memorandum to Dr. Gallo, Dr. Fischinger made it clear that a "critical," "major area of oversight" in the information Dr. Gallo had previously provided was Gallo's failure to describe "the exact sequences and timing of the events which led to the virus-producing line HTLV-IIIb." In light of these fundamental unresolved issues, Dr. Fischinger's unqualified, definitive assertions to Harmison and other HHS officials that LAV was not used for the LTCB blood test are impossible to fathom. D. Beyond the Fischinger Report 1. The Grinstead Response: When the Fischinger report reached HHS, a telling exchange took place between Darrel Grinstead, Assistant General Counsel in the Business and Administrative Law Division of the HHS OGC, and Dr. Lowell Harmison. Grinstead reviewed and, on September 9, 1985, signed off on the Fischinger report. But Grinstead, apparently, was not comfortable with an unqualified sign-off; consequently, on September 9, Grinstead wrote an extraordinary memorandum to Harmison. Grinstead's memorandum is exceedingly important. It shows that Grinstead, the HHS attorney who would soon occupy a key role in HHS' defense of Gallo et al., had significant reservations about the claims of Gallo et al., reservations that were on point and well-founded. Notwithstanding those reservations, Grinstead and other HHS officials gave tacit or explicit endorsement to the Fischinger report, which thereby came to represent the official HHS position concerning the claims of Gallo et al. In his September 9 memorandum to Lowell Harmison, Darrel Grinstead said he had reviewed and initialed the Fischinger report. Yet at the same time, Grinstead's (at best) tepid observations about the report made clear he was not enthusiastic about its contents. Here is what Grinstead said: "... I think Dr. Fischinger's report is a useful analysis of the scientific and legal issues that appear to have been raised by the French ... Of course, our ultimate conclusions regarding the legal issues in this matter will require further examination of additional facts that may be presented by the French and by other components of this Department." Grinstead made clear that, given the outstanding facts, although he was signing off on the Fischinger Report, he did not regard this as the end of the matter: "... my initialing of this report should not be interpreted as an indication to you, Dr. Mason, or other officials in the Department that I am fully comfortable that the Department would prevail if the French were to proceed to press their claims through litigation." Grinstead itemized the points on which he believed sufficient information was lacking: "Our inability to reach such a conclusion does not stem from any inadequacies in Dr. Fischinger's report but rather from our lack of information regarding the details that the French may have to support their claims and from our lack of expertise to fully understand the complex scientific issues that have been raised." Grinstead concluded his memorandum with a telling observation, the observation of a major deficiency in the U.S. Government's attempt to substantiate its claims: "One of the factual issues that has not been fully explicated is the development by NCI of the patented invention, i.e., the test kit, prior to the date of the French patent filing in the European Patent Office in September of 1983." There are several important aspects to the statements by Darrel Grinstead. The first is Grinstead's explicit specification of the "invention" as "the test kit," i.e., not the virus, not the cell line, but the blood test itself. The second important element is Grinstead's specification that Dr. Gallo, in order to establish priority vis-a-vis the invention, would have to be able to show development of the blood test "prior to ... September of 1983." Yet Lowell Harmison told the Subcommittee he did not even recall seeing Grinstead's memorandum. When Harmison read Darrel Grinstead's memorandum, in 1993, Harmison said the issues raised by Grinstead were further examined by HHS, but Harmison was unable to identify when, how, or by whom this examination was conducted, nor with what results. Shortly after the IP filed suit against the U.S. Government in the U.S. Claims Court, notwithstanding his concerns and even though no additional supportive information had accumulated concerning the claims of Gallo et al., (indeed, substantial damaging information had accumulated; see below ), Darrel Grinstead transmitted the Fischinger report to DOJ, representing it as the authoritative HHS account of Dr. Gallo's research. Thomas Byrnes, the DOJ attorney who was lead counsel for the U.S. defense of Gallo et al., told investigators that in pursuing that defense, he relied heavily on the report. 2. Malcolm Martin's Information: During the first week of September 1985, several significant events occurred that should have broken wide open the HHS defense of Gallo et al. These events, occurring within the space of just a few days, included the emergence of hard evidence, originating within HHS itself, that demonstrated (1) the strong probability that LAV and HTLV-IIIb were genetically identical, IIIb having been derived from LAV and (2) that Pasteur was not only the discoverer of the AIDS virus, but also, unquestionably, the inventor of the HIV antibody blood test. The revelation of this evidence should have given rise to a searching examination of the evidence supposedly supporting the claims of Gallo et al. But from the beginning, HHS officials had committed themselves to one thing only -- defending the blood test patent of Gallo et al., and by extension, defending the claimed international political and scientific preeminence of the United States and Dr. Gallo. Facts like those revealed in early September posed a serious threat to the patent and the associated financial and reputational benefits; consequently, the HHS officials who were confronted with these facts ignored and, in some instances, actively suppressed them. This section of the report describes how this occurred. During the first week of September 1985, the Fischinger report was receiving final sign-offs, even though, astonishingly, Gallo/Popovic's answers to the "three major areas of oversight" identified in Peter Fischinger's August 23 memorandum had not yet been received. Although the Fischinger report was an accomplished reality and HHS was on the brink of informing the IP that HHS had found its claims were groundless, Lowell Harmison decided to canvass scientists in other HHS agencies for information they might have bearing on the validity of the claims of Gallo et al. The reason for Dr. Harmison's decision remains unclear. The absence of all but a few Harmison documents (most of Dr. Harmison's documents vanished when he retired from HHS), together with Dr. Harmison's near-complete amnesia for key events, make it nearly impossible to determine why the belated canvassing was undertaken. But accounts from other participants make clear both what happened during the contacts with Harmison and what happened -- more accurately, what did not happen -- as a result. Two information-gathering trips were taken by Dr. Harmison and PHS attorney Richard Riseberg. The first trip, on September 5, 1985, was to the NIH campus. The second trip, the following day, was to CDC headquarters, in Atlanta. At NIH, Harmison and Riseberg met with a group of NIH scientists, including NIAID laboratory chief Dr. Malcolm Martin. According to Dr. Martin's account to OSI, he did not know why he was invited to the meeting; he was merely "told to show up." Presumably, Martin's invitation had much to do with his authorship of the March 1985 Cell review, plus his coauthorship of an about-to-be-published article for Science demonstrating the unique genetic identity of LAV and "IIIb" among numerous other HIV isolates and debunking the "geographical proximity" arguments of Gallo et al. (Benn et al., Science, 230, 1985, 949-951). Dr. Martin told OSI about the discussions at the NIH meeting: "Initially it was very open-ended: 'What is a viral variant?' I remember that question being asked. After discussing what a viral variant is, the question was -- 'is HIV a variant of HTLV-I?' ... it went on for about three hours. When it was all done Harmison asked the group, 'do any of you have any information that you think is relevant to the origin of HTLV-IIIb or LAV?' I said, probably foolishly, 'yes.' I focused then on genetic variation of the virus at that time. I told him that we were in possession of some information that raised some concerns in our minds about that ..." (8/8/90 OSI interview; annotated transcript pp. 22-24). The information to which Dr. Martin referred was the data from Dr. Martin's analyses of LAI/LAV, the analyses that showed the presence of the Hind-III polymorph in the virus Dr. Martin received from Dr. Montagnier in April 1984. According to Dr. Martin, Dr. Harmison asked him to write a memorandum describing his results and their meaning. Dr. Harmison promised Dr. Martin the memorandum would be treated "administrative confidential." What actually happened was that Dr. Martin wrote two memoranda to Dr. Harmison. Dr. Harmison picked up both memoranda in person; neither memorandum was routed through official channels. The memoranda were not produced by NIH to the Subcommittee until nearly two years after the Subcommittee's initial document request; the memoranda were never produced from any official files at HHS. Apparently, the memoranda were never placed in these files, or once placed there, they subsequently were removed. In short, as far as HHS' official records are concerned, it was as if the Martin-to-Harmison memoranda had never existed. The first of the two memoranda, dated September 6, 1985, included a substantial number of scientific papers and abstracts (including several by Gallo et al.) and related attachments. The memorandum, titled "Discovery of the AIDS Virus," was a wide-ranging one, encompassing (1) Dr. Gallo's early view that AIDS was associated with HTLV-I; (2) what Dr. Martin called "obfuscations" concerning the alleged relationship of the AIDS virus to HTLV-I; (3) a brief description of Martin's LAI/LAV experiments that revealed the existence of the Hind III polymorph and the coincidence of these results with the "IIIb" results of Gallo et al. Dr. Martin concluded his September 6 memorandum with a reference to the Benn et al. paper, about to be published in Science. Martin summarized the paper's findings as follows: "... with the exception of HTLV-III and LAV, seven North American and three Zairian AIDS virus isolates are all different from one another" (September 6, 1985 Martin-to-Harmison memorandum; p. 3). Dr. Martin's closing lines describing the conclusions of Benn et al. were these: "We offer no explanation for the similarity of HTLV-III and LAV, but informed virologists will certainly draw certain obvious conclusions" (op cit., p. 3). According to Dr. Martin's account to Subcommittee staff, Dr. Harmison asked him for clarification/elaboration of the information in the first memorandum concerning the apparent genetic identity of LAI/LAV and LAI/IIIb. This led to the second Martin-to-Harmison memorandum, dated September 11. This memorandum, accompanied by several pages of data from Martin's laboratory, added other important details relating to the genetic comparisons of the IP and LTCB viruses, including the fact that, in addition to the Hahn et al. Nature paper showing virus variants identical to those in LAI/LAV also present in LAI/IIIb), the Gallo laboratory had published a second pertinent paper (Shaw et al., Science, 226, 1984). According to Dr. Martin, the Shaw et al. paper described, "... a molecular clone (HXB2, Figure 1) derived from HTLV-III [IIIb] stocks which contained the aberrant Hind III site in question. This clearly indicates that the Hind III variant is present in HTLV-III [IIIb] preparations" (op cit., p. 2). Dr. Harmison did not keep his word to Dr. Martin that his (Martin's) memoranda would remain "administrative/confidential." The contents of the memoranda were shared with a number of NCI/NIH officials and scientists, including Dr. Gallo. Among the individuals who reviewed Dr. Martin's data, Dr. Fischinger and Dr. J. E. Rall, the then-NIH Deputy Director for Intramural Research, found Dr. Martin's data impressive. Dr. Rall reportedly said "Mal's arguments are very hard to get around." Dr. Gallo himself told OSI that Dr. Martin's data convinced him both that there had been a "contamination" of the IP and LTCB viruses and that the "contamination" had occurred at LTCB, i.e., the LTCB virus originated with the IP virus, and not the reverse. Yet within a few weeks, HHS dismissed Dr. Martin's work and suppressed every trace of Martin's correspondence with Lowell Harmison. And within little more than a year, DOJ attorneys would strenuously argue in court assertions such as these: "... HTLV-III is not LAV by another name" (Defendant's Reply to Plaintiff's Opposition to Defendant's Motion to Stay Discovery, U.S. Court of Claims; 5/19/86; p. 4); "Continuing research revealed that LAV and HTLV-III were two different isolates of the AIDS virus" (Brief for Appellee, U.S. Court of Claims; 11/13/86; p. 4); The DOJ attorneys also asserted that the IP suit for breach of contract was, "... founded on the untenable scientific theory that LAV and HTLV-III are exactly identical" (Brief for Appellee; p. 40). 3. CDC's Information: At the CDC meeting in Atlanta, on September 6, 1985, Lowell Harmison and Richard Riseberg met with several administrators and AIDS researchers, including Drs. Walter Dowdle, James Curran, and Frederick Murphy. Dr. Donald Francis, who by this time had left Atlanta to work in California, participated in the meeting by telephone. Despite the importance of the Harmison/CDC meeting, only the scantiest records of the meeting exist. Notes of a CDC staffer, headed "Meeting with Lowell Harmison re: French suit for antibody test royalties," include references to Jean-Claude Chermann's February 1984 trip to CDC, during which, by common account, Dr. Chermann's data convinced the CDC scientists that LAV was the cause of AIDS. Shortly after this meeting, the CDC scientists contacted Assistant Secretary of Health, Dr. Edward Brandt, to tell him they were "convinced French LAV was the virus." The meeting notes also reference the CDC comparative serology study, as well as the Gallo/Francis meeting at the IP on April 6, 1984. Dr. Donald Francis, participating in the meeting by telephone, made his own notes, in his telephone log. Francis' notes for the September 6 meeting included the following entries: "Lowell Harmison -- conf. call Dowdle, Murphy, Curran, Riseberg. DF -- gave the whole BOW [ball of wax] about French, about Gallo trying to steamroll, about possibility LAV = HTLV-III... Harmison: 'caution -- call administratively confidential.'" The first public revelation of the Harmison/CDC meeting appeared in the Chicago Tribune, in a December 31, 1991 story headlined, "In bid to claim AIDS test, U.S. concealed evidence." The Tribune report included accounts of several CDC participants showing how substantial a presentation the CDC scientists made. Quoting CDC scientist Dr. Frederick Murphy and others, the Tribune story said this: "'A lot was said about the CDC data. There was a full trip through the record, the chronology, with no holds barred. All the data were described. 'They wanted to know who shared what with whom when,' recalled Dr. James Curran, who currently heads the CDC's AIDS research program. 'I remember going through my own notebooks. We told the lawyers anything about this that we had. I certainly didn't hold anything back in my files.' Dr. Donald Francis, the CDC official who had worked most closely with Pasteur and who had by then been transferred to California, remembered being asked to 'copy all my files' for Harmison.'" Dr. Francis sent Dr. Curran, who transmitted them to HHS, a vivid letter expressing his views about Gallo's scientific conduct, along with a package containing some of his (Francis') notes, his correspondence with the IP scientists, and copies of a number of CDC/IP collaborative papers. Dr. Francis spoke candidly in his September 5, 1985 letter, which was especially significant because of Francis' long-term dealings with both the LTCB and IP scientists. Francis began with this: "I am not familiar with the legal issues being addressed by the French litigation, but there are really important ethical scientific issues that the Public Health Service should consider before putting up a strong defense" (9/5/85 Francis to Curran letter; p. 1). Francis elaborated on his concerns: "I am sure that I am not alone in believing that Bob Gallo exceeded ethical bounds in his dealings with the French. If this litigation gets into open court, all of the less-than-admirable aspects will become public and, I think, hurt science and the Public Health Service. The French clearly found the cause of AIDS first and Dr. Gallo clearly tried to upstage them one year later" (op cit., p. 1). Francis itemized what, in his view, were "the major questions that could come out in public": "1. Is HTLV-III actually derived from a culture of LAV? LAV was certainly sent to Gallo's lab. The nucleic acid sequences of the two isolates (LAV and HTLV-III [IIIb]) are identical ... No other isolates are identical. Could this occur by chance? Probably not. 2. Did Dr. Gallo practice good scientific ethics regarding this subject? Science must build on the work of others. Gallo was certainly aware of the French work. He reviewed their first paper, co-edited a book with the earliest serologic description and was consulted by phone and in person on multiple occasions. Yet, he was very reluctant to acknowledge their work in his papers and in his presentations. In fact, he actually depricated (sic.) their work. The major question is: did he, in fact, suspect that the two viruses were the same? Before his press conference and his papers he knew the highly unusual morphology of the two isolates was the same. He knew that CDC supplied sera from patients reacted to ELISA antigens in a similar manner..." Francis continued: "Even with the knowledge that they were the same virus, he actively prevented the comparison which is required by ethical scientific practices. He was very reluctant to send his virus to Paris. He was reluctant to send it to CDC and only did so after making us promise not to use our comparative assay (RIA) which was the only one available at the time." Dr. Francis concluded his letter with this: "With these serious violations of normal practices, we should caution the PHS regarding the defense of the NCI stance." As for the materials Dr. Francis appended to his letter, it was a remarkable collection, comprising published papers, CDC/IP correspondence, and Francis' own telephone notes and draft letters. The contents of these documents, which substantiated and elaborated the themes of Dr. Francis' September 5 letter, should have produced an immediate understanding at HHS that there were significant concerns about the claims of Gallo et al. But the entire Francis package, together with the other CDC documents, like Malcolm Martin's data, was simply ignored by HHS. 4. "Major Areas of Oversight": Before describing the fate of the Martin/CDC evidence, it is necessary to examine a memorandum, dated September 6, 1985, purportedly written by Mikulas Popovic, to Dr. Gallo. The Popovic-to-Gallo memorandum, a vitally important one, was ambiguously titled "Origin of H9 Cells." In fact, the memorandum covered far more than the "origin of H9 cells." In addition to a discussion of Popovic/Gallo's rationale for renaming HUT-78 "HT," the memorandum contained an account of the purported "isolation" of "HTLV-IIIb," as well as information on key dates pertaining to Dr. Sarngadharan's earliest work with HIV serology. The greatest significance of the September 6 memorandum, unrecognized until the Subcommittee's investigation, is that the memorandum contained the responses of Gallo et al. to Peter Fischinger's August 23 memorandum, the memorandum in which Fischinger required Gallo to provide information concerning "three major areas of oversight which have to be completed." These "major areas of oversight," as detailed by Dr. Fischinger, were as follows: -- "The derivation of the H9 cell line traced to its parental origins, i.e., the patient." -- "The exact sequence and timing of the events which led to the virus-producing line HTLV-IIIb that is now in current use. This is considered to be is (sic.) very critical ... We need an oral description as well as copied pages from relevant notebooks. We would like a written statement from Dr. Popovic, and whoever else partook in the development of the HTLV-IIIb line, that LAV was never used in any connection in that complex infection sequence which led to the isolation of the HTLV-IIIb line (emphasis added)." -- "It is important to define the first time when ELISA's or Western blots were attempted with any HTLV-III-type isolate and human patient sera." The September 6 Popovic-to-Gallo memorandum responding to Fischinger's queries, contained a number of false and misleading statements. According to Dr. Popovic, Dr. Gallo personally edited Popovic's draft of the September 6 memorandum. A copy of the memorandum exists with edits in Dr. Gallo's hand. Among the more significant inaccuracies in Dr. Popovic's September 6 memorandum are the assertions that: -- "Since primary non-cultured HUT-78 cells are not available, we cannot make a definitive conclusion whether the designated HT cells are identical with the original HUT-78 or not." Dr. Popovic's premise was not correct. Primary HUT-78 cells were available. Dr. Popovic made no effort to contact Dr. Adi Gazdar, whose cell line HUT-78 was, neither did Popovic seek HUT-78 from the ATCC. Had Dr. Popovic sought HUT-78 from either source, he would have readily been able to "make a definitive conclusion" about the identity of H9 and HUT-78. Indeed, that is what happened in 1988-89, when by order of the NIH Director, the testing was finally done. -- "Months after our publication Montagnier with CDC published production in a cell line for the first time. They used BJAB, a B-cell line heavily contaminated with squirrel monkey retrovirus." As noted above , Gallo/Popovic's claims that the IP cell line was contaminated with a squirrel monkey retrovirus were entirely without foundation. Dr. Gallo finally admitted this to Subcommittee staff, in the Summer of 1993. -- Most important of all, the September 6, 1985 Popovic/Gallo response concerning the "isolation" of IIIb both contained several significant misrepresentations and was a significant evasion of what Dr. Fischinger had asked. The memorandum cited the use of at least one sample that, according to LTCB records, was not available at the LTCB at the time of its alleged use for the "pool" experiment. In addition, what is most noteworthy is what Dr. Popovic said about his use of the IP virus, relative to his "isolation" of IIIb: "The development of H9/HTLV-IIIb was almost entirely confined to the tissue culture room 6B03A where no LAV was ever used" (emphasis in original; op cit., p. 2). Dr. Popovic's statement completely evaded Dr. Fischinger's request for a formal statement that he (Popovic) did not use the IP virus for the isolation of "IIIb." Dr. Popovic did not provide the assurance Dr. Fischinger sought. Moreover, what Dr. Popovic did say was significantly problematic, on several counts: Dr. Fischinger asked for a blanket statement that LAV "was never used in any connection ... in the infection sequence" that resulted in IIIb, but what Dr. Popovic said was merely that the isolation of H9/IIIb took place in a room where no LAV -- allegedly -- was used. By Dr. Popovic's own account, the H9/IIIb cell line was not developed until at least mid-January 1984. Thus, Popovic's response failed to account for the first two months of the reported existence of IIIb, which took place in a room (6B22) where LAV was frequently used. Dr. Popovic's statement that "no LAV was ever used" in Room 6B03A (of Building 37) is subject to question. By Popovic's own account, he thawed LAV and used it (late January/early February, 1984) for his "host range" experiment. So far as is known, at this time, Popovic's only laboratory space was 6B03; so if the "host range" experiment really was carried out, it almost certainly was done in 6B03. Dr. Popovic qualified his response to Dr. Fischinger's question by the phrase "was almost entirely confined to" rather than "entirely confined to," thus indicating Popovic was leaving himself some leeway in his response. The words "almost entirely" should have alerted Dr. Fischinger to the possibility that Dr. Popovic was unable or unwilling to give an unconditional assurance that he did not use LAV in "isolating" IIIb. Dr. Popovic failed to give Dr. Fischinger a straightforward affirmation that he (Popovic) did not use LAV to isolate IIIb. The curious statement Dr. Popovic did make, concerning the room in which H9/IIIb allegedly was isolated, was so clear an evasion that Dr. Fischinger should have recognized it at once and sought the reason for Popovic's evasiveness. There is no indication Fischinger did anything of the sort. -- "The first antibody against HTLV-III was obtained by Dr. M. Sarngadharan on December 13, 1983, and the first ELISA was performed by him on January 6, 1984" (op cit., p. 2). It is important to note that Dr. Fischinger's August 23 query about the LTCB HIV blood test was itself deficient. Dr. Fischinger failed to ask the identity of the HIV isolate used for the LTCB blood test; Dr. Fischinger also failed to ask for and inspect any laboratory notes relating to the blood test. Drs. Popovic and Gallo did not supply any information on the identity of the isolate, which as previously described, was LAI/"MOV," neither did they reveal that the serum they used as the AIDS standard for their initial ELISAs was from patient BRU. Moreover, the information Popovic/Gallo did supply was incorrect and misleading in several significant respects, particularly in regard to the claim that "the first antibody against HTLV-III was obtained ... December 13." There is no known basis for this claim. Development of the rabbit hyperimmune antiserum, a polyclonal antibody, was not even initiated until December 29; the antiserum was not available for use until February 24, 1984. As for the ELISAs, the January 6 date appears to be correct, but what Popovic/Gallo failed to tell Fischinger was that the LTCB ELISA did not work satisfactorily until the end of January 1984. Given Dr. Fischinger's very limited knowledge of the facts (not to mention his evident determination not to know them), it is unlikely he would have recognized the misrepresentations in the September 6 Popovic/Gallo memorandum. Dr. Fischinger could and should have recognized well the memorandum's evasions of his questions. But there is no indication Fischinger did recognize the evasions or, if he did, that he did anything about them. 5. Disposition of the Martin and CDC Information: As for the CDC and Malcolm Martin materials, the former items made their way to HHS and ultimately to DOJ, but very belatedly. The Francis-to-Curran letter, together with the appended documents, was sent by Richard Riseberg to Darrel Grinstead, but not until January 24, 1986, four and one half months after the letter was written. Once the Francis materials reached Grinstead, they apparently went nowhere. Grinstead told Subcommittee staff he did not know if the Francis materials were transmitted to DOJ; the Subcommittee staff's review of the DOJ files of attorney Byrnes revealed none of the Francis documents. But the documents obviously resided at HHS from 1985 to 1992, when they were officially provided to the Subcommittee. In November 1992, when he was interviewed by Subcommittee staff and shown the Francis materials, James Curran's response revealed his frustration at HHS' evident disdain for CDC's information: "We at CDC never tried to encourage the United States to support the Gallo patent. They had Don's stuff -- they had it all this time" (11/19/92 interview). What was found at DOJ was extremely significant, i.e., a copy of the CDC computer print-out of the comparative serology data -- the data showing the equivalent performance of the IP and LTCB blood tests. Subsequent to the Subcommittee's discovery of the computer print-out in the DOJ files, DOJ officials refused to make attorney Thomas Byrnes available for a Subcommittee staff interview. Consequently, it was not possible to determine when and how Mr. Byrnes obtained the CDC data, whether he understood their significance, why he failed to act on the obvious implications of those data, and most important, why he continued to submit legal pleadings whose contents was refuted by materials in his own files. Concerning Malcolm Martin's memoranda and data, one important question that remained unanswered for years was what, if anything, Harmison did with those items before they vanished from the official record. Finally, in late 1992, when Dr. Gallo gave up documents from his laboratory, documents withheld from the Subcommittee since early in the year, the answer was revealed, for almost as soon as he received the memoranda from Malcolm Martin, contravening his assurances to Martin that he would keep the materials confidential, Lowell Harmison sent copies of the memoranda, together with (at least) the data attached to the September 11, 1985 memorandum to Peter Fischinger. Fischinger in turn, sent them directly to Dr. Gallo. Evidence of these events came from a package of documents provided to the Subcommittee from the LTCB in November 1992, well after Dr. Gallo had affirmed in writing that he had provided all documents responsive to the Subcommittee's document requests. Among these documents was a copy of Martin's September 11, 1985 memorandum to Lowell Harmison, accompanied by Martin's laboratory data. Martin's name had been deleted from the top of the memorandum, but as described below%%, Dr. Gallo obviously knew the memorandum's source. Penned across the top of the September 11 Martin memorandum, in Peter Fischinger's hand, was this note written to Dr. Gallo: "This information was transmitted to us from Dr. Harmison OASH to help you formulate a precise answer. PJF." Someone, most likely Gallo, marked the contents of the memorandum as he read it. Two passages of the memorandum were underscored by hand, the two key passages that told Gallo what Dr. Martin had found: "... we concluded that at least two viral variants were present in the LAV virus stock we had received from Dr. Montagnier in late April 1984" (emphasis added by reader). "Two viral variants" and "late April 1984." These were the critical items that told Dr. Gallo, who hardly needed to be told, that (1) his virus was genetically identical to the IP virus and (2) his virus was derived from the IP virus and not the reverse (because Malcolm Martin's LAV was obtained from Paris well before Gallo sent IIIb to Montagnier). Rather than convening an independent panel of experts or otherwise attempting to deal responsibly with Malcolm Martin's data and the information obtained from CDC, HHS turned once again to Dr. Gallo. Peter Fischinger wrote yet another memorandum. In this September 10, 1985 memorandum, Dr. Fischinger told Dr. Gallo that based on discussions "... emanating from our compilation of your data," a letter had already been sent to the Institut Pasteur, "... stating that the position and the resulting claims of the Institut Pasteur were not supportable" (9/10/85 Fischinger-to-Gallo memorandum; p. 1). Dr. Fischinger's memorandum did not mention Lowell Harmison's trips to NIH and CDC, rather the memorandum described a scenario (that apparently did not occur) in which, according to Fischinger, his report was sent to HHS agencies other than NCI engaged in HIV research, so that: "... any other intra-departmental concern, which would be incongruent with the position outlined by NCI, would be voiced and answered" (op cit., p. 1). Fischinger told Gallo that, as a result of this "critique" process: "There was some consensus on a number of issues. However, several additional concerns (were) raised which related to both the flow of HTLV-III-oriented research in your laboratory and referred to the possibility that there might have been a common origin of the presently analysable LAV and HTLV-IIIb virus stocks" (op cit., p. 1). Dr. Fischinger asked Dr. Gallo to respond to several questions, "... raised by the NIH/HHS legal counsel in order to arrive at a final departmental position." The questions in Peter Fischinger's September 10 memorandum are noteworthy, both because of their avoidance of the central issues raised by the CDC scientists and Malcolm Martin, and because of the "coaching" they reflected. The first four questions, aimed at encouraging Dr. Gallo to elaborate on the putative "continuity" of his work, while at the same time denigrating the IP work, were as follows: "1. Since you demonstrated in November-December 1982, the presence of a virus which clearly did not seem to be HTLV-I or II, why was this fact never mentioned in your many ensuing publications over the next year? Ostensibly, all of the papers mention the HTLV-I association with AIDS, but none address the fact that you were aware of the existence of other agents which were of the HTLV-III type. 2. Would it be possible to establish a flow of continuity of your thinking and experiments in your laboratory on the non-HTLV-I isolates from your first idea to May 1984? Had you abandoned the experiments searching for a non-HTLV-I agent between December 1982 and June 1983? 3. What was the progression of your thinking and experiments leading to the successful HTLV-III ELISA tests? When did you and/or your contractors first apply the ELISA technology to human AIDS/ARC sera in conjunction with an HTLV-III type isolate? Did the Biotech contract use your input and technology to develop their August 25 [1983] patent application, which appears to claim to have had a generic ELISA test for all HTLVs, including those in AIDS? Did Biotech work with any of the early HTLV-III transmissible isolates in 1983? 4. According to some researchers, the first clear linkage of LAV to AIDS was accomplished by Dr. Chermann at the Park City, Utah meeting in February 1984, rather than your May 4 Science papers. Would you comment on the extent and the surety of information presented at that meeting by the French team?" (op cit., pp. 1-2). The fifth question Fischinger posed -- the question pertaining to Malcolm Martin's LAV experiments -- was prefaced by a lengthy introduction, a nearly verbatim excerpt from Martin's September 6 memorandum to Lowell Harmison. Fischinger recognized well the seriousness of Martin's data and their implication. Fischinger said this to Gallo: "Because of the scientific nature and the nonscientific implications and seriousness of the next concern, the allegation below is presented in almost verbatim form. The scientist's name is not mentioned" (op cit., p. 2). Following the excerpt from Malcolm Martin's memorandum that described the molecular identity of the IP and LTCB viruses, Dr. Fischinger concluded his memorandum to Dr. Gallo with this series of questions: "Could you discuss the possible origins of such a common 'contaminant' virus? Based on known sequence differences of LAV and HTLV-IIIb, can one jump to conclusions (emphasis added) of identity (emphasis in original) of this second species in the LAV and HTLV-IIIb stocks, based only on (emphasis added) restriction endonuclease patterns? Have you seen more than one virus in any of your > 100 isolates if you did not purposely infect with virus from more than one individual?" (op cit., p. 3). Fischinger's concluding instruction to Gallo also was highly revealing, implying as it does a clear admonition that Gallo was not to "rock the boat" with his response: "The Department requests a prompt reply to these questions so the previously outlined position is satisfactory to the Office of the General Counsel" (emphasis added; op cit., p. 3). 6. Dr. Gallo's Response: Dr. Gallo's September 23, 1985 reply memorandum to Peter Fischinger was a key document in the French/American dispute. The memorandum was sent to the Department of Justice, where the attorneys representing the United States Government in defense of Gallo et al. incorporated a number of the memorandum's assertions into U.S. Government pleadings. Both Fischinger's September 10 request memorandum and Gallo's response memorandum made their way to the Office of the Director, NIH, and to a number of HHS officials and attorneys. The memorandum is notable both for its candor on one key issue, i.e., "early isolates" (see above ) -- candor dramatically at odds with Dr. Gallo's statements on the same issue on other occasions -- and for its extravagance, exaggeration, and clearly wrong information on other key issues. The latter such statements included the following: (1) "Remember, at this stage [March 1983 to the Fall of 1983] the Pasteur group had one claim of one virus and they reported that it was significantly cross-reactive with HTLV-I ..." (emphasis in original; op cit., p. 2). "In the May 1983 papers (sic.) Montagnier and co-workers stated their virus was an HTLV. They showed a cross-reaction-with HTLV-I. Clearly the virus was human T-l ymphotropic virus, as they said" (emphasis in original; op cit., p. 5). As described above , these incorrect perceptions of the AIDS virus as related to the leukemia virus were Dr. Gallo's own, not those of the IP scientists. (2) "It was not until our November 1983 breakthrough on mass production of HTLV-III were any specific reagents made enabling us to link the virus to the cause of AIDS" (op cit., p. 1). This statement failed to reveal that the LTCB's November 1983 "breakthrough" was achieved with "MOV," and not with "IIIb," with H4 and not H9. More importantly, the statement clearly implied that HIV-specific reagents were created in November 1983 or very soon thereafter, when in reality, the first such reagent was not prepared until late-February 1984. (3) "We did our first test in December 1983 with bona fide mass-produced HTLV-III ... We did not test sera by ELISA with non -mass-produced viruses because quite obviously the results would be crappy. The Pasteur group elected to do so; ie., they used the few virus particles transiently released on the dying primary blood T-cells and that is why they got such inclusive results" (op cit., p. 2). There are a number of misleading aspects to the above passage, which addresses one of the central issues in the blood test patent dispute. The LTCB ELISA was not even attempted until January 1984, and it was not until the end of January that the test reportedly performed satisfactorily. Moreover, as noted above, the initial LTCB ELISAs were all performed with LAI/MOV, which Dr. Gallo described as "mass-produced HTLV-III." As for the assertion that the IP's blood test results were "inconclusive," the IP results, in fact, were fully as good as those of Gallo et al. (see above). (4) Attempting to rebut the Martin/CDC assertion that the IP results, as of the February 1984 meeting at Park City, Utah, constituted "the first clear linkage of LAV to AIDS," and thus, predated the LTCB data published in May 1984, Dr. Gallo said this: "Even if the above three points did not matter, the conclusion would still be erroneous since 1) I had already lectured at the Pasteur Institute in Paris in January 1984 and told a very extensive audience I was sure we had the cause of AIDS by numerous virus isolates plus wide seroepidemiology with 90 to 100% linkage to ARC and/or AIDS depending on which of many already completed studies we quoted. In a private meeting with Dr. Chermann and Montagnier I gave many of these details. 2) Also in January 1984 I called Jim Curran and requested a large panel of CDC sera ... to be sent to me 'blind' (all our testing was and still is done with coded sera). I told him then I was sure we had the cause of AIDS and that it might be the virus identified in the lymph node patient by the Montagnier group. Obviously, to tell Jim Curran this meant that we already had the data and simply wanted to convince him. Sera were sent some weeks later. At the beginning of March 1984 Jim Curran, my collaborator Dr. Sarngadharan, and myself met for lunch at LaMiche in Bethesda. The code was broken and verified our conviction. It was also at this time that I let NCI officials know: a) the etiology was conclusively solved and b) we had developed a real blood test for this virus. No one in the world ever made these claims before this time" (emphasis in original; op cit., pp. 3-4). At least three major events are misrepresented in the above passage, both with respect to the timing of their occurrence, and with respect to what took place. In every instance, the events were purported to have occurred earlier than they actually did, in one instance, by a matter of several months. Specifically: (a) Dr. Gallo visited Paris and lectured at the Institut Pasteur in April, not January 1984 (see above); Dr. Gallo met with Dr. Francis as well as other scientists, and during this meeting, Dr. Gallo saw the CDC comparative serology data indicating LAV, like "HTLV-III," was the cause of AIDS. (b) Dr. Gallo telephoned Dr. Curran in mid-February 1984, after he (Gallo) heard Chermann at the Park City meeting, not in January. Dr. Gallo could not have told Curran during the telephone call he was "sure" he had the cause of AIDS. At the time the call was made, Gallo et al. still had no HIV-specific reagents and still had not performed what Gallo himself would describe as the "critical" serology (see above; 5/10/90 MOV Submission to OSI; p. 2). (c) Dr. Gallo and Dr. Curran did not meet at the Bethesda restaurant "at the beginning of March." The meeting took place on March 12 (see above). Moreover, during this meeting, Dr. Gallo learned that the IP LAV blood test performed as well as the LTCB's test in detecting viral antibodies in AIDS and pre-AIDS patients. (5) Dr. Gallo attempted to deal with the obvious implications of Malcolm Martin's data, what Gallo termed "the unfortunate innuendo," using several different arguments: (a) "Our laboratory had multiple isolates from the beginning and we were the first to discover heterogeneity among isolates from analyses of the genomes of some of these (published first, in fact, in 1984 from data originated in December 1983)" (op cit., p. 4). Concerning the LTCB's putative "multiple isolates," Dr. Gallo said this: "... we isolated, mass produced in H9 cells, patented and published on a major variant HTLV-III-RF (Haitian isolate), very different from LAV, at exactly the same time, making all this crap irrelevant. In addition, last month (August 1985) we published in the Proceedings of the U.S. National Academy ofScience on one hundred and one different isolates of HTLV-III/LAV. This paper was submitted for publication six months ago. Now the number of isolates approaches 200" (emphasis in original; op cit., p. 5). The facts are otherwise. Gallo et al. did not isolate RF "at exactly the same time" as LAV; RF was not cultured at all until November, 1983. It was not co-cultured with HUT-78 cells until mid-December, and this event occurred because the RF primary culture was "dying rapidly." The LTCB scientists did not attempt to infect H9 with RF until June, and as noted previously (see above ), they had to repeat the infection in July; they did not patent RF at any time. The false claims relating to the PNAS paper have already been elaborated in detail above (see above). Besides the previously-discussed irrelevance of the LTCB's alleged "other isolates" to the issue of whether or not LAV and IIIb were identical, the above passage is noteworthy for the false claim that Gallo et al. possessed molecular data "originated in December 1983." There is no basis for this claim, as Gallo admitted to Subcommittee staff in July 1993. (b) Dr. Gallo identified three instances in which HIV isolate pairs had been found that allegedly were as close as or closer to each other than were LAI/LAV and LAI/IIIb. Two of these instances were recounted only anecdotally by Gallo; no substantiation for the claims is known to exist. As for the third instance, the instance of MN and SL, this instance later was ascribed by Dr. Gallo to a "mix-up of samples" (4/27/90 OSI interview; transcript p. 76). (c) Dr. Gallo's response to Fischinger's query, "Have you seen more than one virus in any of >100 isolates if you did not purposely infect with virus from more than one individual?" is not comprehensible. However, it is notable that: (1) Dr. Gallo admitted the presence of the same multiple virus variants in both LAI/LAV and LAI/"IIIb"; and (2) Dr. Gallo acknowledged that the variants in both LAV and IIIb could represent "polymorphic variants generated in vivo." Yet Dr. Gallo still invoked the geographic proximity argument, in an effort to make the case that LAI/LAV and LAI/IIIb, although they shared two identical viral variants, could still be of independent origins: "If LAV and HTLV-IIIb are similar because they are derived at the same period of time from New York at a time only shortly after the virus entered the U.S., then all the polymorphic variants would also be expected to be highly related." Dr. Gallo's implied argument that geographical and temporal proximity could have accounted for the identity of LAV and IIIb is both factually and logically flawed. In the first place, there was no evidence showing that "IIIb" was "derived from New York." Some of the samples allegedly used for the IIIb "pool" came from New York, but several did not, and as Gallo himself stated, "... it is hard to know which or how many viruses [if any] actually took." There was even less substantiation for the assertion that LAV and IIIb were "derived ... at a time only shortly after the virus entered the U.S." The first AIDS cases in the United States were reported in 1981, while LAV/BRU and the putative "IIIb" samples were obtained in 1983. Considering the well known, extraordinarily rapid mutation of the AIDS virus, it was rank speculation to assert that by 1983, isolates as alike as the IP and LTCB viruses could be anything other than commonly derived. In addition, the implied assertion that LAV and IIIb could be independent and still contain "polymorphic variants ... highly related," could not hold water. What Malcolm Martin's data showed was that not only the dominant virus in LAV and IIIb was identical, but the secondary virus was identical as well. Moreover, the viral variants were present in the two putative independent isolates in substantially the same proportions. What Dr. Gallo was trying to argue was that two independent events produced two identical products, in the same relative quantities, an argument that was scientifically and logically incredible. Elsewhere in the memorandum to Fischinger, Dr. Gallo invoked the argument that the variant viruses in IIIb could be associated with the pooling of several patient samples, in the process making vague allusions to a possible appropriation of "his" virus by the IP: "As an alternative interpretation of point 4: There are several proviruses in the H9/HTLV-IIIb cell line. We stated in our paper we used samples from several patients. Montagnier used only one patient. When analyzing virus from a single patient at any one fixed time we found only one form. How did Montagnier get more than one form?") (op cit., p. 5). (d) Still attempting to refute Malcolm Martin's data and conclusions. Dr. Gallo said this about September LAV: "We received an extraordinarily small amount (11,000 CPM reverse transcriptase) of Montagnier's virus September 24, 1983. Mika developed the clone H9 in early November 1983. Can anyone possibly imagine mass production of this amount of virus in five weeks?" (op cit., p. 5). This statement contains the notable inaccuracy that H9 was created in "early November 1983," an error of two and one-half months. Equally significant is the implied assertion that it would have been impossible for Popovic, in November 1983, to productively infect a permanent cell line with September LAV. In fact, that is precisely what Dr. Popovic did. Dr. Gallo knew this. He wrote, in the Popovic paper, that LAV grew in H4. Dr. Popovic knew it well. He told OSI that LAV grew "very well" in permanent cell lines. Dr. Fischinger could have known it, had he only asked for the LTCB's LAV data. But Fischinger did not ask, and Gallo/Popovic did not tell. Thus the falsehoods about the impossibility of productively growing September LAV lived on. (e) Finally, concluding the September 23 memorandum, Dr. Gallo said this: "... once we characterized HTLV-III (by December 1983) we never claimed anywhere that it was closely related to HTLV-I" (op cit., p. 6). The dubious quality of the claims about the relationship of "HTLV-III" to -I and -II has already been discussed. Even more problematic is the claim in the above passage that the LTCB scientists had "characterized HTLV-III" by December 1983. Dr. Gallo acknowledged to Subcommittee staff that this claim could not be substantiated. Even LAV, by far the best characterized isolate at the LTCB by December 1983, could not credibly be described as "characterized ... by December 1983," in the usual meaning of the term. 7. Dr. Gallo's Explanations: Considering the significance of the Popovic/Gallo August/September 1985 memoranda to the subsequent U.S. defense of Gallo et al., and the clear evidence that those memoranda contained numerous misstatements and reflected numerous material omissions, it is instructive to see how Dr. Gallo views his own role in these matters. During his July 1993 interview with Subcommittee staff, Dr. Gallo was asked about the documents he transmitted to Peter Fischinger, during Fischinger's brief "investigation," and about the "Fischinger report" itself. Faced with the statement he signed affirming the accuracy of the statements contained in the report and affirming that they were supported by data, Dr. Gallo acknowledged, "Yes, I signed it." But Dr. Gallo added, "I didn't read it [the report] as carefully as you might think." Attempting to explain his claimed indifference to his attestation of the accuracy of the report, Dr. Gallo said this: "I didn't even know what was going on. They didn't tell me about the meeting with the lawyers that day" (7/22/93 Subcommittee staff interview). In fact, Dr. Gallo was told about the "meeting with the lawyers," in Peter Fischinger's August 7 memorandum to him. Shown this memorandum, in July 1993, Dr. Gallo responded, "Oh well, you're right. But it doesn't change my mood too much. My first involvement with the story was not medical or scientific" (op cit.). Dr. Gallo described the basis for the information he transmitted and the statements he made to HHS as "a memo from Mika" that summarized his (Popovic's) experiments. But, said Gallo: "You just give up science-- you can't look at every last thing. He told me in a memo. Mika said he got temporary growth [of LAI/LAV] in HUT-78" (op cit.). Otherwise, Dr. Gallo said, "I don't know what I relied on." Yet Dr. Gallo also said, concerning his sources of information, that he "would have" relied on Popovic, Read-Connole ("on specific things") and Sarngadharan. Dr. Gallo said: "I probably called a meeting. Boy, I don't know. Maybe I called him [Dr. Popovic] back up on the phone. I don't know" (op cit.). Dr. Gallo added this: "Lowell (Harmison) must have talked to me about this. At the very beginning I was just meeting him. If problems occurred, I'd see him -- more and more. He'd come visit me many times. He's been in the lab and he's talked to people in my lab many times without my being there" (op cit.). (This statement by Dr. Gallo directly contradicts Dr. Harmison's sworn testimony concerning his contacts with Gallo; see below.) Concerning who selected and assembled the data he provided to Dr. Fischinger, Dr. Gallo said this: "Mika would refuse outright. He doesn't like administrative ... This would be Ann [Slisky] or Prem [Sarin]" (op cit.). Dr. Gallo described his attitude in responding to Fischinger's questions in August and September of 1985; he attempted to account for the several incorrect statements in his September 23, 1985 memorandum to Peter Fischinger. Concerning the claim that "... we did our first test in December 1983 ...," Dr. Gallo acknowledged this could not refer to the LTCB ELISA. "I wasn't thinking about a patent. I don't know. If the ELISA was in January, this must be immunofluorescence. But it would be small in amount, and non-definitive" (op cit.). Responding to questions about the claims in the memorandum that "... we isolated, mass produced in H9 cells, patented and published ..." on RF "... at exactly, the very same time ..." Dr. Gallo admitted that "'mass produced' is not the right phrase," but he argued it was proper to say he had "patented" RF, merely because it was one of the examples shown in a table of one of the patent applications. In sum, concerning the statements in the memorandum about "RF," Dr. Gallo said, "No one should care about this ... It could have been true; we could have mass produced it at Frederick" (op cit.). As previously described, there is cause to question what could have been done with RF. Even allowing for the possibility that RF possibly could have been "mass produced," this does not change the reality that it was not, contrary to what Dr. Gallo claimed in his memorandum to Dr. Fischinger. Even Dr. Gallo boggled at the statement in the memorandum that he had "characterized HTLV-III" by December 1983. The best Dr. Gallo could do in defending the statement was to say, "It would have been mostly serological." But serological studies do not constitute virus characterization; the statement written in the memorandum was not true. Finally, offering an account of his emotional state as he wrote the September 23 memorandum, an attempted explanation for the extraordinary statements the memorandum contains, Dr. Gallo said this to Subcommittee staff: "I'm sky-high writing this thing. It's the first time my integrity is being doubted. I was infuriated ... My emotions were to get this out of my life ... I responded with fulminating anger" (op cit.). E. Key Players at HHS HHS' September 6, 1985 rejection of the IP demands did not close the door entirely on discussions with IP representatives. Further correspondence between Mac Haddow and Professor Dedonder, during September and October 1985, led eventually to discussions in Washington between HHS (with attorney Darrel Grinstead playing a leading role) and one of the U.S. firms representing the IP's interests, Weil, Gotshal & Manges. But even as the attempted negotiations moved ahead and, eventually, collapsed, both sides were preparing for the possibility of litigation. To understand HHS' actions in 1985 and thereafter, it is useful to examine what key players told the Subcommittee staff they believed they were doing, and why, relative to the French/American dispute. Several themes emerged from the statements of these individuals, including prominently, denial of responsibility, even on the part of officials who, according to the documentary record, clearly played key roles in the HHS/U.S. response to the IP challenge. Concerning the substance of the U.S. response, it is clear that the overriding concern at HHS was never "should we defend the Gallo patent?'; rather, at all times the concern was how to defend the patent. No one, it appears, asked the question, "What is the truth about the claims of Gallo et al.?" No one, it appears, ever asked, "What is the right thing to do?" Indeed, from the testimony of some witnesses, it became clear that even when HHS began to suspect Gallo's claims could not be substantiated, HHS still was determined to actively defend those claims for as long as possible, by whatever means possible, while at the same time negotiating a settlement that would be as favorable as possible to HHS and the United States. C. McLain Haddow: The individual who first described the HHS stance with particular clarity was C. McLain Haddow. Haddow played an active role in the dispute in 1985. As Margaret Heckler's Chief of Staff, Haddow communicated frequently with IP officials, denying strongly the validity of the IP claims. Yet in 1990 and thereafter, Haddow asserted he had been suspicious of the claims of Gallo et al. all along. Haddow spoke out first to the Chicago Tribune, where he was quoted on March 18, 1990 as follows: "'There was a point where it became very clear to me that the NIH people were not being truthful,' Haddow recalled. 'These people would sit down for one meeting and then in a subsequent meeting the stories were different ... They weren't even smart enough to get their stories straight before they talked to me,' he said. 'How in the world could they get through a court proceeding?'" (p. 16). Because Mac Haddow is a convicted felon, his testimony might be subject to some question. However, much of Haddow's information was independently confirmed by documentary evidence, as well as testimony of other witnesses, including one of Haddow's top assistants, a career civil servant of unchallenged integrity. Haddow recounted to Subcommittee staff meetings and telephone calls with Gallo. Haddow recalled one meeting in which Gallo adamantly recited his claims, and becoming heated, pounded the table and asserted Haddow was trying to deprive him of a Nobel prize. According to Haddow, when Gallo left, Haddow's assistant remarked of Gallo, "He's lying through his teeth." Haddow's assistant substantially confirmed Haddow's account, telling investigators that Gallo provided "personal assurances of the integrity of his work," including the fact that, he said, the LTCB scientists always kept LAV separate from the LTCB's own cultures. But, according to Haddow's assistant, "it was difficult to believe him." Haddow's assistant recalled making a remark, "He's lying," or "Something's rotten in the state of Denmark," or similar. According to Haddow, the HHS attorneys believed they could sustain a defense for some time, based on Gallo's strong statements and the fact that he had the support of the entire NIH leadership. But the HHS attorneys were not confident that HHS would win if it came to a showdown. Haddow's assistant said there was: "... a general impression that we wouldn't win, because Gallo lacked documentation to show there was no use of the French virus, and thus could not refute the main French accusations" (10/92 interview with the HHS OIG). According to Haddow: "... so our attorneys recommended, the Department attorneys, perhaps in some conflict with the NIH attorneys, recommended that we fold, that we roll over but play it out until we saw how strong the French were on it but our strategy was play it out as strong as we could but if we got to the point where we knew we were going to court that we should roll over and accept a reconciliation and settlement of this problem. The French attorneys, the attorneys representing the French government, didn't know how weak our case was and they never discovered it. We were able to craft an agreement that probably disadvantaged the French, but it was because we hid our weakness fairly effectively" (BBC interview; broadcast in "Taking the Credit," May 11, 1992). In an interview with The New York Times, Haddow echoed both his statements to the BBC, as well as the account of his former executive assistant. According to the Times: "The officials at Health and Human Services 'believed that Gallo was incorrect when he said he did not use the French virus,' Mr. Haddow said. 'There was some question about the significance of the use, but they were aware that it had been used in some fashion. Their recommendation was to play it out as best we can, and if we can get a settlement where we share the credit, let's do it'" (The New York Times, 6/25/92). (2) Dr. James Mason: Dr. James Mason dealt with the French/American dispute from a unique perspective. At the time of the April 1984 HHS press conference, Mason was serving as Director of the Centers for Disease Control. As CDC Director, Dr. Mason presided over an agency that attempted behind the scenes -- largely unsuccessfully -- to prod HHS into giving rightful credit to the prior discoveries of the IP scientists. Dr. Mason actually put his job on the line by speaking out with the truth. But during the blood test dispute, as Acting Assistant Secretary of Health (ASH), Dr. Mason was more subdued, possibly because, as he told the Subcommittee staff, in 1985, he "was led to believe we had a very strong case" (9/10/93 Subcommittee staff interview). In this regard, Mason said he relied on individuals such as Lowell Harmison and Darrel Grinstead for his information about the dispute. Mason acknowledged to Subcommittee staff that rather than accepting the assurances of his subordinates, he should have investigated on his own whether the claims of Gallo et al. were defensible. "It would have been a good idea to do that," he said. But Dr. Mason did not. According to Dr. Mason, despite what he was told about the "very strong case" of Gallo et al., he was concerned with the issue of fairness to the IP vis-a-vis the patent royalties. Mason in fact was in the forefront of those who urged Secretary Heckler to continue to negotiate with the IP representatives, to determine if an equitable agreement could be reached. Dr. Mason told Subcommittee staff that because of the repeated assurances he was given about the U.S. Government's "very strong case," he was greatly surprised when he learned the Government had entered into a settlement agreement with the IP. (Mason returned to his permanent position as CDC Director by the end of 1985, long before the agreement was signed in March 1987.) Mason said that sometime after the settlement was signed, he encountered Robert Charrow, a key player in HHS' response to the dispute, beginning in 1986. Dr. Mason said he asked Charrow why, if the U.S. case was so strong, the United States Government had agreed to a settlement in the dispute. According to Dr. Mason, Charrow responded with this: "'Gallo's laboratory notebooks were in such disarray, we were not sure we could defend the position'" (op cit.). (3) Darrel Grinstead: Prior to Robert Charrow's arrival on the scene, Darrel Grinstead was the top HHS attorney dealing with the French/American dispute. Grinstead's perspective on the dispute, as described to Subcommittee staff and substantiated by the documentary record, diverged sharply from that of Lowell Harmison on several fundamental issues. Most notably, Grinstead said the two central legal issues in the dispute, in his view, were 1) the isolation of the virus and 2) the reduction to practice of the HIV antibody blood test. Grinstead 's belief that the isolation of the virus was a central issue is noteworthy, particularly in light of Lowell Harmison's adamant insistence, which HHS maintains to this day, that the discovery of the virus was immaterial to the French/American dispute. Mr. Grinstead also displayed a pervasive absence of any sense of responsibility for HHS' actions. But meeting notes and correspondence contemporaneous with the dispute make clear that Grinstead was importantly involved in virtually every meeting and event, particularly during the first half of the dispute. Grinstead at least was candid in his description of what HHS was attempting to accomplish in the dispute: "I think there was a motivation to come up with support for the patent." Grinstead said he believed the monetary aspects of the dispute were "trivial" to HHS. Far more important, he said, was "scientific pride," which Grinstead called "positive pride". Asked who gave him the minimum terms for a resolution of the dispute, Grinstead said he did not remember what he was told about terms, and, "I wouldn't tell you even if I did -- it was between client and attorney." Asked who his client was, Grinstead responded that Lowell Harmison was "my most regular client." Grinstead added that Harmison "... had been the driving force from the beginning." Mr. Grinstead acknowledged he was the principal patent attorney at HHS at the time of the French/American dispute; his responsibility, Grinstead said, was to, "... determine if our position in court is defensible" (9/22/92 Subcommittee staff interview). Yet Grinstead actively rejected any investigative role for himself or his office; Grinstead said he "expected the information to come to me." Grinstead also claimed it did not occur to him that the Gallo patent actually was in jeopardy. He asserted it was "not unusual to have to rely on the client for information," but he stressed that the "outside counsel," Cushman, Darby, & Cushman, hired by HHS in the summer of 1986 to handle HHS defense in the PTO interference, "... would have to see the data. I agree it was important to verify data. Cushman, Darby was supposed to do that" (op cit.). But the Cushman, Darby attorneys told Subcommittee staff they looked at very little data; what they did examine they generally did not understand. The data submitted to PTO in support of the Gallo et al. "Preliminary Statement" is a notable example. Yet, according to Grinstead, "To the extent I had concerns about Gallo's reliability, I was very reassured by the DOJ and Cushman, Darby work" (op cit.). Grinstead said that, when questioned, Gallo and his people "had perfectly good explanations" for their statements and actions. Grinstead said if at any point, he had felt Dr. Gallo was lying, he (Grinstead) would have gone to the HHS General Counsel and told him, "We have a problem." But, said Grinstead, "that never happened." Yet according to Darrel Grinstead, Dr. Gallo told him the first sample of LAV was "not useable," and the second sample, "did not help us." Grinstead said he remembered going to Dr. Gallo's laboratory on several occasions, partly for "education about the science," in which, said Grinstead, "I relied heavily on Gallo." Grinstead said that, among other things, he looked at scientific papers and other documents Gallo showed to him. Grinstead said he never attempted to trace any of these documents to putative primary data. Not surprisingly, according to Grinstead, "Nothing came to my attention that indicated there was cause for concern" (op cit.). In fact, there were a number of items of information that did not come to Darrel Grinstead's attention, that certainly should have done. According to Grinstead, he was not told about the Harmison/Riseberg trips to NIH and CDC, neither was he told about the Malcolm Martin memoranda. And, incredibly, according to Grinstead, "To this day, I do not remember knowing Pasteur had a blood test" (op cit.). (4) Dr. Lowell Harmison: By common account (except his own), the leader of the HHS effort during the early phases of the French/American dispute was Dr. Lowell Harmison. NIH and HHS officials and attorneys unanimously described Harmison as "the lynchpin" of the HHS defense, "the chief individual," "the man running the show." During the Subcommittee's July 22, 1993 hearing, Dr. Harmison was questioned at some length concerning his role in the French/American dispute. Several themes were evident in Harmison's testimony. These themes included (1) the assertion that the provenance of the virus was irrelevant to the dispute and (2) the assertion that PTO was the proper/sole authority for dealing with the dispute. What was most striking about Dr. Harmison's testimony, curious for one so centrally involved, were his pervasive denial of responsibility and his inability or unwillingness to describe what he did and why, relative to the dispute. Dr. Harmison denied it was his job to investigate the claims of Gallo et al.: "I was interested in determining the policy issues that were part of that particular issue to understand that at a policy level. I was not in there to check notebooks and laboratory notes. That is the kind of thing that was independently pulled out and provided to the Patent Office, to provide an objective, clear, independent assessment ... "And if they couldn't substantiate the claims and the data, that was their issue, and if the infringement showed infringement, the patent would have been declared invalid. That is not a role, in my opinion, for health people such as myself... (7/22/93 Subcommittee hearing; transcript p. 34). Dr. Harmison acknowledged he asked Dr. Fischinger to examine the claims of Gallo et al., yet he (Harmison) said he did not remember discussing the Fischinger report with Fischinger or with James Mason, the person to whom Harmison reported, who delegated the day-to-day handling of the dispute to him. Harmison said he read the Fischinger report, but when asked what it said, his answer was only this: "I said the report is very clear, and I am not repeating verbatim what the report said. The report clearly articulated the nature of the NCI work that was the foundation for the patent" (op cit., pp. 134-136). Asked if he personally inquired into the basis for the conclusions contained in the Fischinger report, Harmison said this: "I think looking behind, that came from people in the various members of the institutes who came to the meetings on a regular basis and expressed opinions and positions and attitudes on these efforts. That explains -- that is the integrity of the scientific and the personnel involved in the process. You are asking me to comment on their integrity?" (op cit., p. 137). Dr. Harmison repeatedly asserted that the PHS AIDS Executive Task Force was the body that reviewed and ruled on the adequacy/significance of key documents related to the French/American dispute, e.g., the Fischinger report and Malcolm Martin's memoranda. Concerning the Fischinger report, when asked if he provided the report to independent experts who could evaluate it, Lowell Harmison responded, "That was not something that was a part of my responsibility ... I think the Task Force and the other members that would have gotten the report in its normal distribution was a part of looking at that result." Dr. Harmison also said that Dr. Fischinger "presented the essence" of his report to the Task Force." But there is no evidence that any members of the Task Force ever saw the Fischinger report, much less that the Task Force discussed the document and/or the merits of Dr. Gallo's claims. The Task Force minutes contain only one cryptic reference that appears to pertain to the French/American dispute, during the Fall of 1985: "Dr. Harmison, reporting on Science, briefed the members on issues relevant to the patent filed by the Department in connection with the test for HTLV-III antibody" (9/9/85 minutes of the PHS AIDS Task Force; p. 5). Dr. Harmison also denied speaking to Dr. Gallo about the matters at issue in the French/American dispute, a denial starkly at odds with Gallo's own testimony (see above). Dr. Harmison invoked the bureaucracy's "chain of command" as the reason he allegedly did not speak to Dr. Gallo: "I personally, in this matter, did not, as I recall, speak to Dr. Gallo, because this was a matter of not inserting myself between his immediate levels of supervision, and I worked with Dr. Fischinger ..." (op cit., pp. 43-44). It bears mention that Dr. Harmison's concerns about "inserting himself" into "immediate levels of supervision" clearly did not inhibit his direct dealings with such individuals as Peter Fischinger and Malcolm Martin. Indeed, Dr. Harmison went to extraordinary lengths to keep Dr. Martin's superiors out of the Martin/Harmison exchanges. Yet, Dr. Harmison told the Subcommittee this: "... this was something which I guarded very carefully, the importance of having the levels of supervision that were involved that we are working with the laboratory to collect information to have the dialogue. And it was not my area. I wasn't responsible for going in and talking to a given NIH researcher. This was the responsibility of the system... "I think I am pretty astute, not jerking around and jumping over levels of management" (op cit., p. 152). Dr. Harmison's denials of direct contacts with Dr. Gallo are belied by at least one vitally important, direct exchange of documents between the two (see below , for further discussion of this matter). When he was questioned about these documents, Dr. Harmison said he did not remember them. Dr. Harmison's claimed lack of recall for critical events in HHS' response to the blood test dispute was particularly pronounced as regards Malcolm Martin's input. Asked if he recalled the NIH meeting and Malcolm Martin's statements about the identity of the IP and LTCB viruses, Dr. Harmison said, "I do not" (p. 104). Asked if he recalled receiving Malcolm Martin's memoranda, Harmison said, "No, I don't" (p. 104). Asked if he requested Martin to assemble articles and other materials relating to his views of the work of Gallo et al., Dr. Harmison responded, "I don't remember" (p. 105). Asked if the information in Martin's memoranda bore any significance to the IP charges against Dr. Gallo and his colleagues, Dr. Harmison responded, "In my view, very little, if any" (op cit., p. 112). Dr. Harmison even claimed lack of recall concerning his own job, as in this exchange: Q: Do you remember what your job was? A: I think I was involved in the policy and the science of it. Q: You were involved in the policy. And how were you involved in the policy? A: I think the records that you have collected should express that. Q: I am asking you. You are here to help us. Please tell us. A: I have said, there were discussions with people as a normal part of the process of meetings -- Q: Who presided at these discussions? A: I may have presided. It may have been the AIDS Executive Task Force. Q: You may have? Do you remember whether you presided? Do you remember if somebody else presided? Do you remember if nobody presided? Do you not remember if anybody presided? A: I don't remember. Q: Do you remember there were discussions? A: I think this is a very circular point. I have explained my policies and how I did things (pp. 121-123). Concerning one key point, Dr. Harmison repeatedly asserted to the Subcommittee that the IP scientists, "... didn't have a blood test until much, much later" (op cit., p. 129). Yet, Dr. Harmison could not identify any basis for his clearly incorrect assertion. When Dr. Harmison was asked if he was aware of when the IP scientists and Gallo et al. actually created and began working with their respective HIV antibody blood tests, his response was this: "I am not going -- I don't recall with respect to that date. That is to me not relevant. I don't recall, if I knew" (op cit., p. 175). Pressed about his statement that the respective dates were not relevant, Harmison responded, "I said I can't recall. To me it is irrelevant because I can't recall it" (op cit., p. 175). F. The Negotiations The IP/HHS negotiations got underway in mid-November. Within three weeks of the initiation of the talks, HHS and IP representatives were discussing the elements of a possible agreement, as embodied in a document titled "Possible Points of Agreement to Resolve Pasteur/HHS Dispute." These elements included: issuance of a joint statement recognizing contributions of both the IP and LTCB scientists licensing of Genetic Systems to market its blood test in the United States an agreement by the IP to drop all current and future legal proceedings. 1. Bad News From the HHS Attorneys: The United States' willingness in early December 1985 to discuss terms of a possible settlement, in the face of (allegedly) a strong case may have been due to, in part, the results of an exercise set in motion on November 19, 1985, by Lowell Harmison. On this date, Harmison commissioned a review by outside legal counsel of the strength of the Gallo et al. patent, particularly the prospects for the patent in the event PTO declared an interference with the Montagnier et al. application. Three opinions were obtained, two from outside patent counsel, one from NIH patent attorney Leroy Randall. The opinions were not encouraging to HHS. The most favorable of the opinions, that of outside counsel Sheridan Neimark, was also the most superficial, uninformed opinion of the three. Neimark, who had no prior involvement with the work of Gallo et al., made clear how rushed and limited his review had been: "Because of the shortness of time and the necessity for me to present my answers to a series of questions by the close of the business day on November 26, 1985, it was not possible to study this matter as thoroughly as I would have liked to do." Elsewhere in his opinion, Neimark referred to "our short study of less than one week." Even more significant, it was evident from Neimark's opinion that he relied heavily on Dr. Gallo for information to substantiate his (Neimark's) opinion; in the opinion, Neimark referred to a "lengthy telephone conversation with Dr. Gallo." Concerning whether the IP would be able to "copy the claims" of Gallo et al. and thus be able to provoke an interference, Neimark said this: "These questions are very difficult to answer at present ... I am inclined to believe that Institut Pasteur cannot make the claims of the Gallo patent ... However, this does not end the matter, because it would be possible for the Patent Office to structure an interference based on claims which differ from the Gallo et al. patent claims ... The examiner could decide what the invention is, and draft one or more claims of his own which he feels would cover the invention and which could be made by both parties." (In fact, this is exactly what happened. In April 1986, when it declared an interference between Gallo et al. and Montagnier et al., PTO defined the invention that was in dispute and then identified the claims of each party that corresponded to that invention [see below]). Neimark said he considered it "very unlikely" the IP would prevail if an interference were declared, but should this happen, said Neimark, "... we cannot at this point say what would be left of the Gallo et al. patent." Neimark cited the telephone conversation with Dr. Gallo in discussing the prospects for Gallo et al. "swearing behind" the IP. Notably, Neimark identified as the "earliest date" behind which Gallo et al. would have to swear, not the September 1983 filing date of the IP blood test patent application, but the May 20, 1983 publication date of the Barre-Sinoussi et al. Science paper. Neimark said Gallo et al. could swear behind Montagner et al.: "... either by proving that the invention was made before that date by reducing the invention to practice (which may be difficult to do), or by showing conception of the invention coupled with due diligence from a time earlier than May 20, 1983 through April 23, 1984." Neimark cited his conversation with Gallo: "... he advised us that his work on this invention started in the summer of 1982 and that such work included a conception of the invention, and that there has been continuous and daily diligence six or seven days per week, every week, since that time." Neimark said Gallo et al. would have to prove due diligence, "only to a date prior to September 15, 1983, the earliest date to which the Institut Pasteur team would probably be entitled." But importantly, Neimark said there were two circumstances under which IP might be able to obtain an earlier date: "... Institut Pasteur might be able to obtain a[n] earlier date if they could prove the introduction of their invention into the United States at an earlier date; second, they would be able to attempt to prove an earlier date on the issue of derivation, i.e., that the Gallo et al. team derived their invention from the Institut Pasteur team." Here, contrary to Lowell Harmison's claims, was a strong assertion that the identity of the virus used by Gallo et al. and the fate of the Gallo et al. blood test patent were inextricably intertwined. But Neimark asserted the burden of proof on Pasteur in proving derivation would be "very great." Without substantiation, Neimark said this: "... the evidence seems strong that Dr. Gallo's team did not put the sample or samples received from France to any use relative to the invention." Lowell Harmison, of course, knew better; he knew well that at least one respected NIH scientist, Malcolm Martin, could offer proof that derivation did occur -- that the LTCB scientists did "put the samples received from France to use relative to the invention." Thus, even the most favorable of the legal opinions provided to HHS in November 1985 must have been deeply disquieting to Lowell Harmison and others who had been made privy to the data from Malcolm Martin's laboratory, not to mention the data from Gallo's own lab! The other two legal opinions supplied to Lowell Harmison were rendered by attorneys with more knowledge of the work of Gallo et al. John Roberts, who rendered one of the opinions, was the senior partner in the law firm that prepared both the LTCB blood test and cell line patent applications, plus numerous subsequent LTCB applications. Roberts' opined that, "... the broadest definition in the claims of the [IP] British application could overlap the U.S. claims." However, according to Roberts, the IP claims, "may contain an inherent flaw which makes them unpatentable (and therefore not capable of being used in interference proceedings) ..." i.e., the IP patent application did not indicate, "... the need for or inclusion of an immortalized cell line." Roberts was wrong in his judgment of a possible "inherent flaw" in the IP blood test patent application. Within a few weeks of the preparation of Roberts' opinion, PTO would rule in the Montagnier et al. application that a permanent cell line was not necessary for the HIV antibody blood test. Another of Roberts' determinations, one that was largely correct, was that the IP, "... British application supports copying U.S. claims 1, 5, 6, 7, 8, and 9 ... U.S. claims 2-4 and 10 have no basis in the British disclosure ... and therefore should not be subject to interference proceedings." In fact, when PTO finally declared an interference between Gallo et al. and Montagnier et al., all but one of the Gallo et al. claims was included. But Roberts' determination that six of the ten Gallo et al. claims were subject to an interference would itself have been a daunting prospect for HHS, since the IP application predated the Gallo application by several months and the feasibility of Gallo et al. "swearing behind" Montagnier et al. was in considerable doubt. The third legal opinion provided to Lowell Harmison came from the head of the NIH Patent Office, attorney Leroy Randall. Randall's opinion debunked a favorite HHS argument against the IP blood test, i.e., that it was (allegedly) not commercially viable and thus, was not patentable. Roberts made clear that arguments about the commercial utility of the IP blood test were unlikely to be successful in derailing the IP application. Said Randall, "... the holdings have generally been that research purposes are sufficient for patent ..." Concerning whether or not the IP would be able to copy the claims of Gallo et al., Randall offered a potentially devastating scenario: "It would appear difficult for Pasteur to copy our claims to the envelope (p41) protein, and the test based thereon. However, Pasteur does appear to be able to copy our claims directed to 'HTLV-III or fractions thereof' ... It would therefore appear that our claims directed to the envelope protein (p41) would remain ours, following any interference" (emphasis added). The latter half of this passage is interesting, focusing as it does on what would "remain ours," following an interference at PTO. The obverse, of course, was what would not "remain ours," i.e., what HHS might lose following an interference. In this regard, what Leroy Randall apparently concluded, in late-November 1985, was that although Gallo et al. might retain their claim to a blood test based on the envelope protein (claim 3 of the 10 Gallo et al. claims), they would not retain their other blood test claims. That Randall rendered this opinion in the Fall of 1985 is extraordinary, given that the U.S. Government later would argue that Pasteur's blood test was inherently defective and Gallo et al. were entitled to the entire patent, because the LTCB blood test relied on the envelope protein. Randall's opinion concerning the IP scientists' priority vis-a-vis the majority of the blood test claims was clearly prophetic. Not only was the IP named "Senior Party" in the PTO interference, which encompassed all but one of the Gallo et al. claims, by the Summer of 1986, the Gallo et al. claims in a number of blood test "CIP" patent applications were repeatedly rejected by PTO, on grounds that they were anticipated by the prior art of Montagnier et al. (see below). 2. IP's Quest for Information: At the same time that HHS was weighing the legal prospects for Gallo et al., the IP attorneys were making efforts to obtain information about the LTCB scientists' use of LAV. IP attorneys at the law firm of Townley & Updyke prepared a massive FOIA request to be filed at HHS and the Department of Commerce, but IP's Weil, Gotshal attorneys sought to obtain the documents relating to use of LAV via a more informal route. In meetings with Mac Haddow, the Weil, Gotshal attorneys agreed to provide HHS a copy of the IP's United States patent application. In return, according to a November 26, 1985 Riseberg-to-Fischinger memorandum: "... Mr. Haddow agreed to supply Pasteur's lawyers, by November 29, with copies of existing materials documenting what happened to the two shipments of LAV provided to NCI by Pasteur in 1983." The contents of the documents provided to the IP attorneys purportedly "documenting what happened to the two shipments of LAV" are revealing; they show vividly how vitally important information was deliberately withheld from the IP. Riseberg's memorandum to Fischinger indicated Fischinger had told him "certain key individuals" would be "away from Bethesda through at least November 29," for this reason, Fischinger agreed to, "... provide Grinstead with a partial package by November 27, with the remainder to be collected as soon as possible." In reality, it appears only one delivery to the IP attorneys was made. This delivery comprised two memoranda -- one written by Dr. Gallo to Lowell Harmison, one written by Dr. Popovic to Dr. Gallo -- together with eight pages of laboratory notes purportedly representing the LTCB's experiments with LAV, none of them provided to Peter Fischinger for his "investigation." Both the Gallo and Popovic memoranda were dated November 26, 1985, the same date as the Riseberg-to-Fischinger memorandum. Both memoranda mention the short notice given for submission of the LAV records. Dr. Gallo's memorandum to Lowell Harmison made clear Gallo understood well the nature of the request: "Attached is the information which has been requested on experiments performed with the supernatant samples of 'LAV' sent to this laboratory. This information was prepared quickly since we had less than 48 hours notice that it was needed." The remainder of the Gallo-to-Harmison memorandum comprised a lengthy complaint about what Gallo apparently perceived as the inequities of the blood test dispute, in which, according to Gallo, he was "constantly subject to responding to their accusations..." Dr. Popovic's memorandum to Dr. Gallo was more substantive, containing a number of important elements, several of which were demonstrably incorrect or incomplete. Also significantly incomplete was the scanty collection of data pages appended to Dr. Popovic's memorandum. The data pages appended to Dr. Popovic's memorandum consisted almost entirely of protocol pages (i.e., pages describing methods, rather than results of the LAV experiments) or pages reporting exclusively negative experimental results. The one data page that reported positive results for an LTCB LAV experiment -- the vitally important October 6 IFA experiment that produced positive results against BRU serum for a cord blood culture of July LAV -- had been photocopied in such a way that the results were entirely illegible. In fact, it is impossible even to discern from the page that it includes results from an experiment using LAV. Even more significant is what was not appended to Dr. Popovic's memorandum. Among the LAV data pages not appended to the memorandum, and thus not provided to Lowell Harmison, Mac Haddow, or the IP attorneys were the following: the September 20, 1983 data pages from the notebook of Dr. Prem Sarin, reporting positive RT results for one of the two cord blood cultures infected with July LAV; the October 3, 1983 letter from Matthew Gonda to Mikulas Popovic reporting the LTCB's first identification of the suspected AIDS virus as a "lentivirus"; the October 21, 1983 notebook pages of Elizabeth Read-Connole showing the infections of five T-cell lines with LAV; the several pages dated between October 21, 1983 and January 13, 1984 showing the repeated positive results with the two successful LAI/LAV permanent cell lines, HUT-78/LAV and Ti 7.4/LAV. Particularly noteworthy among the omitted pages are the December 14, 1984 letter from Matthew Gonda to Dr. Popovic, reporting "productive lentivirus infection" of the two LAI/LAV cell lines and the December 14, 1983 IFA data from Read-Connole showing positive results for the same two cell lines, when tested against BRU serum. Also noteworthy among the data pages not appended to Dr. Popovic's memorandum were the November 9, 1983 RT results from Dr. Prem Sarin, showing that three of the five LAI/LAV T-cell lines were RT positive. Dr. Sarin's RT data were never provided to the IP attorneys. -- the January 13, 1984 freezer log indicating that freezes of both the LAI/LAV cell lines existed on this date (this log was never provided to the IP attorneys); As for Dr. Popovic's November 26 memorandum, it is a curious blend of clearly incorrect and partially correct statements. The very subject of the memorandum is provocative -- "Review of Memo of August 19, 1985, to Dr. Howard Streicher" -- suggesting someone had questioned the accuracy of Popovic's earlier memorandum. Although it purportedly was a "review" of the earlier memorandum, the November 26 memorandum perpetuated and expanded on several of the falsehoods in the earlier memorandum, asserting, for example, that Popovic's July LAV experiments had been entirely unsuccessful. Thus, in the November memorandum, Dr. Popovic said, concerning July LAV, that: "Using this sample, we did not succeed in transmitting the virus into cells. We conducted these experiments twice with consistently (sic.) negative results." Concerning September LAV, in the November 26 memorandum Dr. Popovic provided vital new information, never-before-revealed (so far as is known), to HHS officials. Yet, Dr. Popovic stopped well short of the whole truth. Concerning September LAV, Dr. Popovic said this: "In this case, we did succeed to transmit the virus in cord blood T-cells assayed on October 6th and 18th, 1983 ..." (note: Popovic and Gallo later would tell OSI the October 6 experiments were performed with July LAV; in the 1991 Guo et al. letter to Nature, Gallo and his associates said that the September LAV samples were not used for LTCB experiments before "late October" 1983). Yet, Dr. Popovic did make some significant, albeit imperfect revelations: "We successfully transmitted LAV into permanent cell lines in December 1983. The positive immunofluoresence was scored on December 14, 1983, in Ti7.4 ... This cell line was used for comparative studies with H9/HTLV-IIIb (protocols will be provided at a later date from Drs. George Shaw and Beatrice Hahn). Attempts to transmit LAV ... to H9 cells and other clones of HT cell line on February 13, 1984, gave negative results ..." There are several significant points to be made about these statements by Dr. Popovic: The mere admission of the successful transmission of LAV to permanent cell lines is significant, but Dr. Popovic's dating of this event to December 1983 is fully two months later than it actually occurred. Dr. Popovic specifically indicated that LAV was transmitted to more than one permanent cell line ("We successfully transmitted LAV into permanent cell lines in December 1983"), yet Popovic described the experiments with only one line, Ti7.4. An obvious question was what other cell lines were used to grow LAV, and with what results. But there is no indication Lowell Harmison or anyone else at HHS pursued these important questions. Dr. Popovic's revelation that Ti7.4/LAV was compared with HTLV-IIIb is a very significant one. The fact that, according to Popovic's memorandum, the comparison experiments were performed by Drs. Shaw and Hahn confirms that the comparisons were molecular/genetic. Almost certainly, the experiments described by Popovic in his memorandum are the experiments that (as described above) were performed in the late Spring/early Summer of 1984, showing that the IP and LTCB viruses were identical. But Dr. Popovic provided no information about the outcome of the LAV/IIIb comparisons, referring merely to "protocols" yet to be provided by Shaw and Hahn. No "protocols" showing the use of September LAV for molecular comparisons were provided to the IP. Consequently, the IP was left in the dark about what kinds of genetic comparison experiments were performed with September LAV, at what time, and with what results. Dr. Popovic invoked the putative February 13, 1984 "host range" experiment to substantiate his claim that LAI/LAV could not be grown in H9 and other clonal cell lines derived from "HT." As previously discussed (see above), this experiment is highly suspect, on many grounds. Deficient as it was, the November 26 package of data was transmitted to the Weil, Gotshal attorneys on December 6. The transmittal letter, from Darrel Grinstead to attorney Nancy Buc, described the enclosures as: "... documents responding to your request for laboratory notes and other information relating to use of the LAV samples provided to the Department by Dr. Luc Montagnier to scientists at the National Cancer Institute in 1983." Grinstead's letter specifically noted that: "Because some of the scientists who may have worked with the samples are not immediately available, I cannot assure that these are all of the extant documents that respond to your request. However, as soon as the remaining scientists who worked with these samples are available and can search their records we will provide you the remaining documents, if any." But no additional documents were provided, and with the initiation of the IP's civil suit for breach of contract, the matter moved to a new arena. IX. THE FRENCH/AMERICAN DISPUTE: LITIGATION A. Overview of the Proceedings By mid-December, the IP attorneys apparently had decided they had no choice but to proceed with formal litigation to obtain redress for the wrongs they believed had been done. Eventually, the IP would initiate four separate legal actions: a lawsuit in the United States Court of Claims alleging breach of contract; a patent interference proceeding at the USPTO; a tort claim alleging damages in the amount of $200 million; and a lawsuit under the Freedom of Information Act (FOIA). All four proceedings were ended pursuant to the terms of the March 1987 settlement agreement, but while they were still active, the proceedings involved three law firms for the IP, with the United States represented by the Department of Justice, HHS' top attorneys, and two outside law firms hired by HHS to augment its expertise. The first legal action, the breach of contract suit filed in the U.S. Claims Court on December 12, 1985, attracted considerable media attention. Lowell Harmison professed surprise that the IP had gone to court; Harmison was quoted as saying he was "a bit amazed" to learn of the lawsuit (12/14/85 AP story, "French Sue Over AIDS Research." In a masterpiece of irony/sarcasm, Harmison also said this: "I think there has been a very sound and constructive dialogue between the parties over time, and everyone involved has been extremely concerned about the sensitive matters being raised" (op cit.). Dr. Gallo, characteristically, was more outspoken. According to a December 14, 1985 AP story, Dr. Gallo reportedly said this: "'... the French exaggerated their contributions ... We helped them a lot more than they helped us.' In an interview with The New York Times, Dr. Robert Gallo of the National Cancer Institute said the French didn't receive a patent for their work 'because they didn't have a working blood test.'" In a December 16, 1985 story in the Wall Street Journal, Dr. Gallo was said to have "hotly denied the French charges" that he used the IP virus. Further, according to the Journal, Gallo, "... called their bid for royalties and damages [the IP scientists'] 'irrational' and 'obscene.'" The Wall Street Journal further reported that the central theme underlying the IP lawsuit was the allegation that, "... Dr. Gallo misappropriated the French virus and presented it in his work, which later was patented." Attempting to rebut this charge, Dr. Gallo drew on all the arguments he had been practicing during the previous year. Thus, according to the Journal: "Dr. Gallo refutes this, saying that the LAV and HTLV-III strains, although related, aren't identical, differing by 2% of their genetic building blocks. Besides the single LAV sample was too small to be of practical use, he argues; moreover, he had isolated 48 virus samples of his own on which to base his publications and patent." The Executive Summary of this report contains a representative compendium of the more outrageous false and misleading claims proffered as part of the defense of Gallo et al. Concerning the process of the legal actions, following is an overview of each: 1. Lawsuit in the Court of Claims: The complaint filed by the IP in the U.S. Claims Court was centered on the charge that Gallo et al. used the IP virus to make the LTCB HIV blood test, and thereby contravened the terms of the noncommercialization transfer agreement (the "contract") signed by Mikulas Popovic on September 23, 1983. HHS officials, to this day, argue that the actual identity of the virus Gallo et al. used to make their blood test is inconsequential. But the reality is that the identity of the virus was at the very center of the Claims Court suit. This is the reason U.S. Government attorneys argued so strenuously in the court that the viruses were indisputably distinct. But HHS officials knew there was good reason to believe the LTCB's putative prototype virus was the IP virus; these officials must have understood that their defense of the Claims Court suit was a very precarious one indeed. According to the IP complaint, the LTCB scientists' use of LAV to make their HIV blood test and the subsequent patenting, manufacture, and sale of that test: "... constitute breach of the express contract wherein defendant agreed to use the LAV strain received exclusively for biological, immunological and nucleic acid study research purposes, and agreed not to use said specimen for any industrial purpose and not to disseminate the virus without the prior written consent of Pasteur" (Institut Pasteur v. United States of America, Case No. 730-85; p. 9). To redress the "great damage" claimed to have been done, the IP Claims Court complaint sought the following: "... the Court should order, adjudge and decree that plaintiff was the first to isolate the viral agent of AIDS named and known as LAV or HTLV-III ... and to recognize the significance thereof in the development of methods of detection of AIDS and pre-AIDS conditions, and accordingly that plaintiff is entitled to all rights and benefits which legitimately flow therefrom"; "... that defendant be directed and ordered to pay all future royalties pursuant to any said license agreements over to plaintiff"; "That plaintiff be awarded its damages, an amount which plaintiff cannot presently ascertain but which exceeds one million dollars ..."; "That this court order, adjudge and decree that defendant correct all applicable records concerning the discovery, research and development relating to the viral agent of AIDS named and known as LAV or HTLV-III ... and regarding the recognition of the significance of said viral agent in the development of methods of detection of AIDS and pre-AIDS conditions" (op cit., pp. 11-12). The U.S. Government's response to the IP Claims Court suit combined obfuscation with denial, braggadocio, and outrage. The U.S. Government attorneys denied that Mikulas Popovic had authority to sign a contract on behalf of the United States. They insisted that, "Neither of these inventions [the Gallo et al. blood test and cell lines] depended on or is derived from LAV" (6/11/86 Defendant's Motion for Summary Judgment; p. 8). The U.S. attorneys further asserted that, "The full story of defendant's scientific accomplishments has been told in the scientific literature ..." (op cit., p. 10). And the attorneys attacked the IP's misappropriation charge as, "... an outrageous attempt to impugn the reputations of one of the world's foremost virologists and his coworkers" (11/13/86 Brief for Appellee; p. 5). During the first half of 1986, HHS and IP submitted to the court a series of motions, countermotions, and other legal pleadings associated with the Claims Court suit. The arguments during this period concerned substantive issues as well as a number of procedural issues, most notably, the issue of "discovery," which became intertwined with the IP attorneys' FOIA requests, to the detriment of the IP case (see below). In May 1986, the Judge in the Claims Court case raised the question of the Court's jurisdiction, i.e., whether a valid IP/LTCB contract actually existed and, if so, if it fell within the scope of the Contract Disputes Act (CDA). The CDA stipulates that a prerequisite for Claims Court jurisdiction is the presentation of a certified claim to the relevant U.S. Government agency and a decision (or failure to decide) by that agency. In July 1986, the judge ruled that the LAV contract did fall under the CDA. Because the IP had not previously submitted a claim to HHS, the judge declared the Claims Court did not have jurisdiction over the matter, and he dismissed the IP complaint. But the IP appealed, and in March 1987, just days before the signing of the settlement agreement, the Court of Appeals ruled in IP's favor. The Appeals Court ruled that on multiple grounds, the Claims Court erred in its finding that the CDA was applicable to the IP/LTCB LAV transfer agreement. Accordingly, the Appeals Court reinstated the lawsuit and remanded it to the Claims Court for consideration of whether a breach of contract actually did occur. The signing of the settlement agreement, however, ended the Claims Court suit. (2) Interference Before the USPTO: The first discussions between the IP attorneys and PTO concerning the Gallo et al. patent recorded to have taken place occurred in August 1985. The first formal request that PTO declare an interference between the IP application and the Gallo et al. patent was made in early October 1985. Yet it was not until April 29, 1986, that PTO finally granted the IP request (see Appendix A for details about the delay). When the interference finally was declared, it embodied several elements that augured well for the IP case. First, Montagnier et al. were named "Senior Party," while Gallo et al. were named "Junior Party;" this was a formal recognition of the IP's priority in filing its patent application. Second , and more significant, were (1) the contents of the interference count (PTO's definition of the invention) and (2) PTO's determination that all pending claims of Montagnier et al. and importantly, all pending claims of Gallo et al. save one corresponded to the invention that was the subject of the interference. The definition of the invention, as formulated in the interference count, was as follows: "A method for the detection of antibodies in samples of the body fluids of patients with Acquired Immune Deficiency syndrome or pre-AIDS which comprises contacting antigenic material selected from the group consisting of HTLV-III, LAV, IDAV1, IDAV2 and antigenic fractions thereof with said samples and measuring the formation of antigen-antibody complexes by an immunoassay selected from the group consisting of strip radioimmunassay based on Western Blot technique, enzyme-linked immmunosorbent assay, indirect immunofluorescence assay and radioimmune precipitation assay." The interference count, which contained no mention of a permanent cell line and no limitation to the envelope protein GP41, made clear that in PTO's eyes, the disputed invention was the HIV antibody blood test, pure and simple. The count, together with PTO's determination that the Gallo et al. "cell line" claim did not correspond to the count, was a clear repudiation of the claim of HHS/Gallo et al., a claim still made today, that the LTCB blood test was fundamentally different from -- and superior to -- the blood test of Institut Pasteur, because the test of Gallo et al. was based on virus grown in a permanent cell line. Clearly, according to PTO, the invention was the blood test itself; the source of the virus, whether from successive passages of short-term cultures or from permanent cell lines, was irrelevant. PTO's determinations concerning the interference were widely seen as favorable to the position of IP. In London, the Times said the PTO determinations, "... appeared to give the Pasteur a prior right, and an out-of-court settlement looked likely." In the United States, Colin Norman wrote in Science in May 1986, that PTO's determination that IP was the senior party in the interference was a "key determination that favors the French application." Norman also said that the decision about the content of the interference count, "would also seem to favor the French application by narrowing the case to a determination of which group has precedence in patenting the detection technology alone." PTO rules prescribe the process of an interference, the main elements of which are motions for judgment and oppositions to those motions by the two sides. Each such motion is required not only to be submitted to PTO, but also to be delivered to the opposing party. The filing of motions is supposed to be governed by strict deadlines; in the Montagnier/Gallo interference, the initial deadline for filing of preliminary statements and motions was set for July 29, 1986. But Gallo et al. did not meet the deadline; in fact, the U.S. Government, on behalf of Gallo et al., filed numerous requests for extensions of the PTO deadlines. The first such request sought to delay the initial deadline from July 29 to September 29, 1986. The IP opposed this request for extension, which PTO nonetheless granted. The contents of the June 30, 1986 HHS motion for extension of time are very revealing. They show the heavy reliance the U.S. Government placed on Dr. Gallo in preparing its motions. Thus, in its June 30, 1986 motion, the U.S. Government argued at some length that the extension was necessary to ensure Dr. Gallo's personal involvement in preparing the Government's case. The June 30 motion stated that: "Dr. Gallo has been out of the country on official travel from May 21, 1986, until at least June 27, 1986 ... Moreover, Dr. Gallo's current schedule for the months of July, August, and September includes substantial time away from his laboratory." (pp. 3-4). Further, according to the U.S. Government motion: "The complex nature of the subject matter of this interference and the voluminous experimental work which led to the development of the patented invention also require the personal participation of Dr. Robert C. Gallo ... Only Dr. Gallo is thoroughly familiar with the records relating to these developments and with the details of any communications with Institut Pasteur" (Emphasis added; op cit., p. 3). The U.S. Government motion also mentioned in very general terms "new information" that, again, was said to require the personal involvement of Dr. Gallo: "Recently, a preliminary investigation has revealed new information which may have an important bearing on the contents of the preliminary statement to be filed by Gallo et al. and which may necessitate the filing of one or more preliminary motions ... Further and more extensive investigations are needed to assess fully the significance of this information. Again, the personal assistance of Dr. Gallo is of the utmost importance in pursuing these investigations" (emphasis added; op cit., pp. 4-5). Eventually, on October 14, 1986, the parties to the interference submitted their respective motions for Judgement. Gallo et al. submitted four such motions, plus several "Contingent Motions." Montagnier et al. submitted a single, broad motion for Judgment. Each side then submitted an "Opposition" to the other party's Motion(s) for Judgment. The Montagnier et al. Motion for Judgment and the U.S. Government's "Opposition by Gallo et al. to Motion of Montagnier et al. for Judgment...," submitted on November 18, 1986, were vitally important documents in the French/American dispute. Dr. Gallo's sworn declaration was appended to and extensively incorporated into the text of the U.S. Government Opposition. To comprehend the significance of these documents, and the statements they embodied, as well as the strength of the IP case, it is necessary to comprehend why the opposition and declaration were written, i.e., to what they were responding, namely, the principal arguments in the Motion for Judgment of Montagnier et al. The IP arguments were straightforward, i.e., that the claims of Gallo et al. were "unpatentable to Gallo et al. on the following grounds: "... anticipation by or obviousness from prior public knowledge of the LAV virus and its use in the detection of antibodies to that virus in blood samples" "...obviousness from the above-described prior public knowledge relating to LAV in view of the LAV virus itself which was prior art to Gallo et al...." "...a culpable breach of the duty of disclosure defined by 37 C.F.R. section 1.56 in failing to disclose adequately to the U.S. Patent and Trademark Office (PTO) the above-described prior art" (Motion of Montagnier et al. for Judgment; p. 1). The Montagnier et al. Motion give particular emphasis to the failure of disclosure on the part of Gallo et al. The IP Motion noted that: "... the prosecution history of the Gallo patent is devoid of any substantive consideration of the effect of the well publicized French work on LAV on the patentability of Dr. Gallo's claims" (op cit., p. 6). Further, according to Montagnier et al.: "It appears from the records of the involved applications that the PTO's lack of awareness of the substantial identity of the LAV and HTLV-III viruses and of the significance of earlier public disclosures relative to LAV resulted in the improvident issuance of the Gallo patent in the first place. That lack of awareness appears to have been the direct result of a failure on behalf of representatives of DHHS to apprise the PTO during pendency of the Gallo application of the existence and significance of prior art describing the LAV virus and its use to detect antibodies to the virus in blood" (op cit., p. 6). Montagnier et al., cited particularly the following items not disclosed to PTO by Gallo et al.: Montagnier's presentation at the July 1983 NCI Task Force meeting; Montagnier's presentation at the September 1983 CSH meeting; the July and September 1983 LAV shipments from the IP to the LTCB. (Unbeknownst to Montagnier et al., shortly before the submission of the interference motions, the PTO examiner was citing some of these very elements as prior art against the CIP applications of Gallo et al. [see below ]). For their part, Gallo et al. attempted to argue in their Motions for Judgment that the LTCB and IP blood tests were different inventions because Montagnier et al. did not specify the requirement that the blood test antigen be obtained from virus grown in a permanent cell line and because the Montagnier et al. blood test focused on the p24 (core) protein rather than GP41 (the envelope protein). Gallo et al. went further, charging that the IP blood test was "fatally defective" and "not useful." Gallo et al. even alleged, contrary to the LTCB's own data from the Spring of 1984 (see above), that, "... Montagnier's p25 protein might not even be a viral protein" (Motion by Gallo et al. for Judgment ...; p. 2). It was in their "Opposition" to the Motion for Judgment of Montagnier et al. that Gallo et al. strayed farthest from the facts. The U.S. Government attorneys faced a severe challenge in the Opposition; they had somehow to account for the reality of a substantial body of IP prior art, and for the clear failure of Gallo et al. to disclose that art to the PTO. Attempting to deal with these issues, Gallo et al. sought to assert that (1) Gallo's work predated that of Montagnier et al. and (2) Gallo did not believe the IP virus was the same as his virus, neither did he know the IP virus was the cause of AIDS. Therefore, by implication, the U.S. Government argued that Gallo et al. were not obligated to disclose the IP scientists' work nor the LTCB's own work with the IP virus to PTO. The arguments that Gallo et al. proffered to support these tenets were as follows: The "disclosures" of Montagnier et al., including the transmittal of LAV virus to the LTCB, "... are not prior art against Gallo. Priority evidence which Gallo will submit in these proceedings will antedate the Montagnier disclosures ... Gallo can and will show dates of invention at least as far back as December, 1982" (emphasis added; Opposition by Gallo et al. to "Motion for Judgment of Montagnier et al. p. 2; Appendix; p. 1). "... Gallo correctly felt that nothing in Montagnier's publications in 1983 or the LAV samples was prior art to Gallo who clearly was in possession of more information regarding his invention than Montagnier disclosed. The LAV samples added nothing to what Gallo had already learned from his own isolates containing novel retroviruses, which subsequently were named HTLV-III. Likewise the publication by Montagnier in May, 1983 and his presentation at Cold Spring Harbor in September, 1983, did not in any sense teach Gallo anything more than he already knew. Clearly, in the circumstances, there was no need for Gallo to disclose the Montagnier 'disclosure' to the Examiner" (emphasis added; op cit., Appendix; p. 20). "At no time prior to the filing of the Gallo application, was it appreciated by anyone that LAV and HTLV-III were the same or even similar viruses" (emphasis added; op cit., Appendix; pp. 21-22). Dr. Gallo's declaration was appended to and liberally incorporated into the U.S. Government opposition. The most blatant of the numerous false and misleading statements in the declaration, include these claims -- discussed elsewhere in this report: Prior to the filing of the Gallo blood test patent application, neither Gallo nor any of his colleagues believed LAV and "HTLV-III" were even substantially the same virus (see above); Prior to the issuance of the Gallo et al. patent, Dr. Gallo saw no evidence that the IP virus was the cause of AIDS (see above); July LAV contained no useful virus (see above); September LAV grew only "transiently" in T-cell lines (see above); Dr. Popovic "discovered" H9 in November 1983 (see above); The LTCB scientists possessed EMs of HIV as early as February 1983 (see below). Concerning his declaration, apparently by way of explanation, Dr. Gallo told OSI, "... there was a lot of semantics in this." When Gallo was confronted with one false statement after another, his attorney, Joseph Onek, offered this for him: "I should point out that, of course, this is a statement like any affidavit, but I am sure was prepared largely by lawyers, not by Bob ..." (8/3/90 OSI interview; transcript p. 153). As noted previously, the lawyers' position, plain and simple, was that they, "didn't know enough to lie" (see above). The PTO interference proceeded through motions, oppositions to motions, and replies to oppositions before it -- like the other legal proceedings -- was terminated by the 1987 settlement. (3) Tort Claim: The tort claim by the IP against the U.S. Government is the least-known of the IP actions during the French/American dispute. Submitted on April 24, 1986 by the law firm of Townley & Updike, the claim was based on allegations of: "... tortious and malicious conversion of Pasteur's property, i.e. samples of the virus LAV and other scientific and biological materials, as well as willful misappropriation of Pasteur's valuable trade secret information" (Swire-to-Bowen; 4/24/86). The IP complaint, which sought $200 million in damages, said to consist of lost profits to the IP, further alleged that: "... various agents of the Department converted and misappropriated same [LAV, etc.] in order to gain for the United States and/or themselves scientific recognition, valuable patent rights and other pecuniary rewards rightfully belonging to Pasteur" (op cit.). HHS responded to the IP tort claim with a few sentences. In a letter dated October 23, 1986, HHS attorney Timothy White wrote to IP attorney James Swire the following: "The claim of Institut Pasteur is denied. The evidence of record does not substantiate that the alleged injury was due to the negligence, wrongful act or omission of a federal employee. Moreover, the claim is excluded from coverage under the Federal Tort Claims Act, see, e.g., 28 U.S.C. section 2680(h)." No additional information was provided to the IP concerning the basis for deni X. THE SETTLEMENT (AND THEREAFTER) In the Fall of 1986, the momentum for a negotiated settlement of the French/American dispute accelerated. At the same time, charges and countercharges continued at PTO and in the U.S. Claims Court. One individual who played a unique role in the discussions leading to the settlement was Dr. Robert Windom, the then-recently-appointed Assistant Secretary of Health. Dr. Windom told Subcommittee staff that President Ronald Reagan personally ordered U.S. officials to seek a settlement of the dispute. To this end, IP and HHS representatives exchanged visits in the Fall of 1986. Shortly after these visits, the settlement discussions became more deliberate, with more senior attorneys on both sides taking more leading roles. Dr. Windom's perspective on the French/American dispute, as described to Subcommittee staff, is revealing; it shows how senior officials operated with only a modicum of the "facts," selected misrepresentations fed to them by others who clearly knew better. In this regard, Dr. Windom told Subcommittee staff his principal sources of information were Drs. Harmison and Fischinger, with lesser roles for Drs. Wyngaarden and DeVita. Dr. Windom singled out Dr. Harmison as "very helpful," one who "knew the science very well." Dr. Windom also said he personally knew very little about the charges being litigated before PTO and the Claims Court: "I really did not know what was being alleged ... I probably was not given the fundamentals" (Subcommittee staff interview; 10/30/92). Confirming he was "not given the fundamentals," Dr. Windom told Subcommittee staff he was never told the IP had developed an HIV antibody blood test before Dr. Gallo did so. Subsequently, while conditionally acknowledging the prior existence of an IP blood test, Dr. Windom said, "... but we marketed it first." Because of these considerations, Dr. Windom said, he thought the French were getting better than they deserved" in the 1987 settlement. When challenged as to why -- in light of the alleged superiority of the U.S. case -- the United States had any interest in negotiating a settlement, Dr. Windom responded with this: "There were some uncertainties -- some points could be interpreted -- it was gray, not black and white." A. Terms of the Settlement When it was finally consummated, in March 1987, the French/American settlement embodied agreements concerning the blood test patents, the pending litigation, patent royalties, and scientific events. Drs. Montagnier and Gallo agreed to call themselves "co-discoverers" of the AIDS virus. They collaborated in a jointly-authored "Chronology of AIDS Research" that supposedly reflected the most significant contributions of the IP and LTCB scientists. The chronology was introduced with this disingenuous claim: "... from the beginning there has been a spirit of scientific cooperation and a free exchange of ideas, biological materials and personnel between Dr. Gallo's and Dr. Montagnier's laboratories. This spirit has never ceased despite the legal problems and will be the basis of a renewed mutual cooperation in the future" (Nature, 326, 1987, p. 435). Dr. Gallo was adamant concerning the necessity for an agreed-upon scientific chronology as part of the settlement agreement, apparently believing he could claim by fiat what he could not substantiate by data. Numerous memoranda and related documents show that Dr. Gallo insisted there could be no settlement without a scientific history, one that supposedly would be the definitive account for all time. Dr. Gallo repeatedly cited the 1987 chronology (and a similar, narrative chronology coauthored by Montagnier and Gallo in Scientific American in 1988) to OSI as the authoritative accounts of his work. These chronologies, which contained a substantial number of suspect claims concerning the work of the LTCB scientists, obviously, did not end the scientific controversy. As for the blood test patents, working in conjunction with PTO, the two sides agreed that both the LTCB and IP patents would remain in place (the IP patent issued in late 1987). The names of each side's scientists were added to the other side's patent, under the fiction that an inadvertent error was made in listing the inventors, when the patent applications were filed. The two sides also agreed to donate the bulk of the royalties from their blood tests to a foundation established as part of the agreement. Only one-quarter of the combined donated royalties were committed for AIDS research; HHS and IP received the remaining three-quarters, with no strings attached, in equal shares. This arrangement was altered, in July 1994, to provide a larger royalties share to the Institut Pasteur, ostensibly because HHS belatedly realized that since the 1987 settlement, the IP had not received an equitable share. Dr. Gallo's use of the IP virus for the LTCB blood test was given only passing mention by HHS. B. Unraveling of the Settlement: Even as the terms of the French/American settlement were hammered out, the underpinnings of the settlement were being eroded. Investigative journalists continued to pursue the questionable claims of Gallo et al. One article, Steve Connor's February 1987 article in New Scientist -- "AIDS: Science Stands on Trial" -- actually threatened to derail the settlement negotiations. Shortly thereafter, also in 1987, the first edition of Randy Shilts' memorable And the Band Played On was published. Other books and articles followed, both in the United States and abroad, culminating in the November 1989 expose in the Chicago Tribune by journalist John Crewdson. Meanwhile, research was underway that itself had significant potential to demolish the settlement's underpinnings. The results of this research were described in a remarkable exchange of correspondence between Dr. Gerald Myers, a leading HIV geneticist, and several NIH scientists and senior scientific administrators, including Dr. Gallo and Drs. Anthony Fauci, Director of the NIH National Institute of Allergy and Infectious Diseases (NIAID) and Director of the NIH Office of AIDS Research, and Dr. Samuel Broder, Director, NCI.. Dr. Myers was and is Director of the Los Alamos HIV Sequence Data Base and Principal Investigator of a contract funded by NIAID. The existence of the "Myers documents" was made known to the Subcommittee by a source outside of NIH, in late 1993. Despite numerous document requests to NIH, the Myers documents were not previously provided to the Subcommittee. Not only were the documents withheld from the Subcommittee, their existence was not disclosed to OSI, to ORI, nor to the HHS/OIG. The documents, directly relevant to the investigations of all these entities, bore on the still-unresolved central issue of the entire case, i.e., the possible misappropriation of the Institut Pasteur (IP) virus, LAV. The significance of the information contained in the Myers documents, as well as details of events instigated by the documents, are described in the following. Just one week after the settlement agreement was signed, Dr. Myers wrote to a number of HIV scientists, principally at NIAID, including officials close to NIAID Director Anthony Fauci. Dr. Myers described results of some of his recent analyses of the IP and LTCB prototype viruses as follows: "Literally a 'double fraud' took place when the H9 cell-derived isolates [clones] -- HXB2, BH10, BH8, BH5, HXB3, PV22 ... were declared to be i) independent from LAV (BRU) and ii) derived from blood pooled from several patients. The probability of either account being true is very small by this analysis, and I predict that it will become smaller with each U.S. isolate sequenced in the future ... ... it is the astonishing and unforeseen variation of the virus which exposes the fraud ... I suggest that we have paid for this deception in more than the usual ways. Scientific fraudulence always costs humanity ... but here we have been additionally misdirected with regard to the extent of variation of the virus, which we can ill afford during the dog days of an epidemic let alone during halcyon times." (4/8/87 Myers-to-LaMontagne et al. letter; p. 4). Dr. Myers' April 1987 letter was closely held in the succeeding years. The potential of its information for demolishing the premises of the settlement agreement was evident. Dr. Myers later made clear the difficulties he encountered in trying to avoid the patent dispute. Writing in April 1989 to Dr. Fauci, Dr. Myers said he had encountered two problems "unavoidably entangled with the dispute about the discovery of HIV." Dr. Myers said his analyses, "... immediately drew attention to the close similarity of the IIIb and LAV sequences," and that his "tree" analyses, "... were generated at precisely the time ... the U.S. and French were settling the legal disputes that had arisen." Dr. Myers told Dr. Fauci that he (Myers) and his Data Base colleagues, "... agreed that the database would steer absolutely clear of the issue but that we would not suppress scientific data" (4/12/89 Myers-to-Fauci memorandum; p. 1). But Dr. Myers' scientific/ethical concerns remained. In his April 1989 memorandum to Dr. Fauci, Dr. Myers said this: "... I remained deeply disturbed about the claim made for the IIIb viruses -- that they derived from pooled blood of several patients. It was very difficult in 1987 to convince many researchers that the AIDS viruses mutated inordinately rapidly. The IIIb interpretation gave the false impression that the virus was more stable than other signs were indicating" (4/12/89 Myers to Fauci memorandum; p. 2). Dr. Myers told Subcommittee staff he had hoped and believed the issues raised by his data would be resolved "within the tradition" of the scientific process. Despite his best efforts, this did not occur. By the Fall of 1988 , Dr. Myers' data had not only confirmed that LAV and IIIb were genetically identical, but that IIIb was derived from LAV, and not the reverse. Dr. Myers believed it was his ethical and scientific obligation to share this information with Dr. Gallo. Accordingly, in September 1988, Dr. Myers wrote to Dr. Gallo, summarizing for him the results of the most recent HIV Sequence Data Base analyses and telling him the following: "From our earliest tree analyses, it was patently evident that the LAV and IIIb viruses had to have had a recent common ancestor .... By including all of the available gene sequences in a single analysis for the IIIBs, it is actually possible to define the branching order of the variants to a high degree of statistical precision. There is no doubt but that it shows the LAV source of the IIIB viruses: the NL43 clone of the BRU isolate is the oldest sequence; the published BRU follows it; the IIIBs follow thereafter...." (emphasis added; 9/20/88 Myers-to-Gallo memorandum; p. 1). By the spring of 1989, Dr. Myers and his Data Base colleagues had accumulated important new data showing LAV and IIIb were situated squarely in the middle of the "sibling" cluster of sequences, all pairs of which, with the alleged exception of LAV and IIIb, were known to be derived from the same person. According to Dr. Myers, Dr. Gallo at this time, at the urging of his closest colleagues, including Drs. Mikulas Popovic and Flossie Wong-Staal (herself an editor of the HIV Sequence Data Base), was prepared to "throw in the towel" and admit that IIIb originated with LAV. Dr. Gallo prepared an ambiguously worded, but still compelling statement that was to be published in the April 1989 issue of the Data Base. The statement read, in pertinent part: "Can we conclude ... that HTLV-IIIb and LAV BRU did indeed originate from the same individual? If that is indeed the case, it would only have resulted from a mix-up in my laboratory when the LAV from Luc Montagnier was temporarily growing along side the other isolates we had obtained. We certainly cannot rule this out, particularly since we and, I am told, many other investigators have often experienced the phenomenon of laboratory contamination of HIVs .... "I do ... think that it is necessary as a result of the data compiled in this book to acknowledge the distinct possibility that HTLV-IIIb and LAV BRU are the same isolate" (4/17/89 Gallo draft statement). Dr. Gallo's statement was never published in the HIV Sequence Data Base. According to Dr. Myers, on the eve of its publication, the statement was precipitously withdrawn by Dr. Gallo who told Dr. Myers he had "discussed the matter with the lawyers" and they advised him not to publish the statement (the "lawyers" were not identified to Dr. Myers, and there is no confirmation that any such advice actually was given). According to Dr. Myers, Dr. Samuel Broder also objected to the publication of the Gallo statement in the Data Base, on grounds that the Data Base "is not peer reviewed." In fact, the findings published in the Data Base are peer reviewed by an exceptional group of editors, including at the time Drs. Howard Temin, Walter Fitch, and James Mullins. Dr. Myers said Dr. Broder telephoned him and in addition to voicing his concerns about peer review, raised questions about the strength of Dr. Myers' data. Dr. Broder reportedly asked Dr. Myers to "write down some of my thoughts." Dr. Myers responded in an April 24, 1989 memorandum. Dr. Myers sent Dr. Broder a copy of the April 1989 Myers-to-Fauci memorandum, cited above. Myers told Broder that although he and his colleagues had earlier remained silent, "... new questions are rapidly emerging in relation to viral sequences that just happen to be in the territory of the 1987 dispute. Bob Gallo's problem is whether to go ahead and speak out now, when he can take some initiative or to wait until he could be placed into a more passive and reactive position" (4/24/89 Myers-to-Broder; p. 1). Myers further said, "Is there any evidence on Gallo's side? Not really" (op cit., p. 1). The Myers/Broder discussions took place after Dr. Gallo backed out of the commitment to publish the previously described acknowledgement. According to Dr. Myers, a fall-back plan was then developed, according to which Dr. Gallo was to make the admission that IIIb originated with LAV "on a natural occasion," i.e., in the text of a scientific paper on a broader subject. Dr. Gallo failed to keep this commitment, and the promised paper containing Dr. Gallo's admission was not published. Dr. Myers said he was never given any explanation for the failure to publish the paper. Dr. Myers' findings and conclusions must be considered in context of Dr. Gallo's previous actions as well as his (Gallo's) failure to disclose Dr. Myers' findings to OSI. As previously described, as early as the summer of 1984, Dr. Gallo knew, based on data from his own laboratory, that LAI/LAV and LAI/IIIb were genetically identical. After failing in the effort to convince Dr. Montagnier to admit responsibility for contaminating LAV with "IIIb," Dr. Gallo changed tactics and began to claim, in numerous scientific fora, that LAV and IIIb actually were genetically distinct. Dr. Gallo further maintained, adamantly, that LAV could not have "contaminated" his cell lines because "it was physically impossible to grow LAV." Another part of the story propounded by Dr. Gallo and his closest associate, Dr. Flossie Wong-Staal, was that the several clones of IIIb, obviously very similar in genetic make-up, were derived from multiple independent samples allegedly used for the "pool" experiment. By extrapolation, using this argument, Dr. Gallo attempted, among other things, to make the case that the striking similarity of LAV and IIIb did not obviate the possibility that they actually were independent isolates. The rapid mutation and resulting heterogeneity of the AIDS virus are now widely recognized as posing significant obstacles to the development of effective strategies for prevention and treatment of AIDS. Dr. Myers' concerns about the delay in scientists' recognition of HIV heterogeneity -- a delay caused in part by what Dr. Myers termed the "double fraud" associated with Dr. Gallo's account of the origins of "his" virus -- are a poignant reminder of the damage that resulted from the "fraud." It also must be noted that Dr. Gallo's testimony to OSI concerning these matters was substantially less than forthcoming. Despite having agreed, just one year earlier, on the need for a public acknowledgement that IIIb and LAV were genetically identical, and an acknowledgement that IIIb was derived from LAV and not the reverse, Dr. Gallo in 1990 made numerous misleading statements to OSI of which the following are only a few examples: "With time and more sequences available the relative similarities of this pair (LAV and IIIb) remains unusual but not unique" (4/8/90 "Opening Scientific Statement" to OSI; p. 5). "... I would conclude that there can't be a conclusion today ... I don't think we can make any conclusive statement .... Also, please keep in mind that though I said if this possibility or probability exists ... I didn't tell you where it [contamination] happened with certainty also. I believe that question is open, no matter what information you may have, and I believe that question [where the contamination took place] could be solved in the immediate future" (4/11/90 Gallo OSI interview; transcript p. 72). Elaborating on the "Paris contamination" theory, thoroughly discredited by Dr. Myers' data, Dr. Gallo's attorney asserted this to OSI: "... IIIb was sent to Paris in May of 1984. It could be that what they then tested ... was a contaminant. It's at least possible." Dr. Gallo then added: "The other direction" (4/11/90 interview; transcript p. 75). Dr. Gallo also, once again, made explicit the linkage between his "other isolates" claims and the LAV/IIIb identity: "I have felt it's an irrelevant question, for the most part ... scientifically, ethically, medically and historically, because there are so many other isolates and if anybody had half as many in tissue culture within the next year I would be surprised, so I've never felt it to be an important question. It's only in this context of the questioning that I'm getting here that it becomes important or for politics that have been played in newspapers ..." (4/11/90 interview; transcript p. 71). Yet, less than a week before he made these statements to OSI, Dr. Gallo wrote a letter to Dr. Myers, in which Dr. Gallo said: "I have wanted to tell you for some time -- that you were certainly right, and I should have listened to you ... as early as 1984 I told her [a reporter for the journal Science] IIIB could be a contaminant of LAV. Because of everything else we did and because of other isolates and because of the help I gave Montagnier early on, I just could not believe anyone would really care" (4/5/90 Gallo-to-Myers letter). Dr. Gallo described his allegedly nonchalant attitude toward the genetic identity of the IP and LTCB viruses in more vivid terms to OSI: "I'm interested in a vaccine and in curing the disease. I'm interested in basic science and how the virus works. Do you think I'm going to get back there in the mud of whether IIIb and LAV came from this lab or the other lab when I have all kinds of other isolates and things are moving like a bullet? And I want to be worried about that, and did it happen in my lab, or their lab ... I mean, who bloody cared?" (4/11/90 OSI interview; transcript p. 82. Dr. Gallo's characteristic utterances speak volumes, and are an apt note on which to end this staff report. DISTRIBUTED BY GENA/aegis, your online global gateway to a world of people, information, and resources. 714.248.2836 * 8N1/Full Duplex * v.34.