INVESTIGATION OF THE INSTITUTIONAL RESPONSE TO THE HIV BLOOD TEST PATENT DISPUTE AND RELATED MATTERS

Subcommittee on Oversight and Investigations
Committee on Energy and Commerce
U.S. House of Representatives

Executive Summary

I. INTRODUCTION

A. The Subcommittee's Focus on the Institutional Response

Encouraged by prominent scientists, the Subcommittee on Oversight and Investigations in 1987 began a review of the institutional response to cases of alleged or suspected scientific misconduct by scientists involved in Federally supported research. At that time, the problem was readily discernible. When situations of possible scientific misconduct arose, the institution's response generally was to walk the whistleblower out the door, sweep the problems under the rug, and to protect, at all costs, the reputations of the senior scientists. As one scientist explained, "It was as if they had their own fiefdoms whereby they set their own rules."

In April 1988, the Subcommittee held what it expected to be its first and only hearing on the problems associated with how the institutions were responding to instances of scientific misconduct. What the Subcommittee did not recognize at the time was that rather than pointing out a problem that the community would rally around in an effort to correct, it was, in fact, exposing a not very well-kept secret that the scientific community was not prepared to deal with.

To those who were attempting to expose these problems, the hearing was a breath of fresh air. In the 24 hours after that first public hearing, the Subcommittee received reports of no fewer than 13 new cases of alleged scientific fraud. To those who wanted to maintain the status quo, the Subcommittee became a threat; numerous attempts were made to thwart the Subcommittee's efforts and limit Congressional oversight of Federally funded scientific research.

Given the debate, the Subcommittee felt it was important to go into the issue in further detail, and much as it did with defense contractors, generic drug manufacturers, and the nuclear power industry, the Subcommittee decided to select a case study to determine, in detail, how institutions respond to allegations of scientific misconduct and whether the system, in fact, works.

The case study selected for review was the so-called "Baltimore" case. The primary reasons the Subcommittee focused on this case were that (a) two institutions had already had -- and botched -- an opportunity to properly investigate the matter and (b) the whistleblower had been effectively driven out of science for her efforts in bringing the facts to light. The further the Subcommittee pursued the case, the more the community rallied around the defense. The Subcommittee investigation resulted in a second hearing in April 1989. Emotions were so high at that point that scientists flew in from around the country to be at the hearing to provide moral support for Dr. David Baltimore and his colleagues. In some respects, that hearing was a breakthrough because a number of the scientists who came in on the side of the defense left believing the defense was not credible, and that they had been led into a foolish fight.

Throughout 1989, as the facts unfolded, more and more of those in the community began to realize that there was a serious problem and started considering that it might be necessary to have outside pressures to reform the system. By 1990, discussions started taking place across the country and throughout the scientific community to determine how to better respond to allegations of misconduct or fraud and what institutional systems needed to be put into place to better respond to these problems.

Even as the Subcommittee began to see some progress at research institutions, it was evident that effort had been geared toward research institutions outside the Federal government. At the time, over a billion dollars was being spent at the National Institutes of Health (NIH) on intramural research. Consequently, it was important to determine if the same unwillingness to deal effectively with cases of potential misconduct observed in non-Federal institutions also existed within the Federal government's own research community. As a result, the staff was directed to conduct a case study involving allegations of misconduct in an intramural research program.

B. HHS/NIH's Sorry History of Misconduct Investigations

At this time, the Subcommittee was investigating the Laboratory of Tumor Cell Biology (LTCB) within the National Cancer Institute (NCI) at NIH, due to allegations of kickbacks and diversion of Federal funds by two prominent scientists within that laboratory. Ultimately, both investigations resulted in felony convictions. As a result, in 1989, when allegations of scientific misconduct resurfaced against the chief of that laboratory, allegations which had first been raised in 1985-86, the Subcommittee was in a good position to use the LTCB as its intramural case study.

In contrast to the situation at extramural research institutions, there has been little or no progress at the Department of Health and Human Services (HHS) or NIH in their response to cases of possible scientific misconduct in the intramural laboratories. In fact, the situation at HHS/NIH resembles the situation at extramural institutions more than ten years ago. HHS' response to the HIV blood test dispute and the related misconduct investigations serve as vivid examples of this. Most of the charges raised in 1989 concerned issues previously raised yet never forthrightly addressed during the 1985-87 French/American HIV blood test dispute.

The only real attempt at NIH to vigorously examine the facts of this case occurred when Dr. William Raub was the Acting Director of NIH. Dr. Raub insisted on the appointment of an independent panel, nominated by the National Academy of Sciences (NAS), to review NIH's handling of the case, to ensure an adequate response.

Initially, the NIH assigned its new Office of Scientific Integrity (OSI), assisted by an outside panel of experts, to conduct a formal inquiry and investigation. While this beginning was very positive, it shortly unraveled. In 1991, a new NIH Director was selected: Dr. Bernadine Healy. By the time of her appointment, the OSI investigation had been completed and a draft report had been prepared. OSI found scientific misconduct on the part of Gallo's top AIDS scientist, Dr. Mikulas Popovic. Concerning Dr. Gallo, the entire panel and OSI severely criticized Dr. Gallo and they strongly questioned his fitness to continue to serve as a laboratory chief at NIH. But then, through a series of events described later in this report, Dr. Healy effectively demolished OSI, greatly limited the supposedly independent review of the NAS Committee, and eventually attempted an end-run of its findings. In short, Dr. Healy did everything she could to protect her superstar, senior scientist.

In 1993, the NIH directorship changed again with the selection of Dr. Harold Varmus as Director of the NIH. The atmosphere of overt protectionism of Dr. Gallo was ended. However, although the HHS Office of Inspector General (OIG), the United States Attorney, and the Subcommittee had by this time amassed a substantial body of evidence demonstrating probable misconduct, Dr. Varmus, who was advised throughout by HHS General Counsel Harriet Rabb, refused to forward that evidence to a Surgeon General's Board of Inquiry, the duly authorized disciplinary body for members of the PHS Commissioned Corps. Dr. Gallo is a Captain in the Corps.

In addition, despite strenuous pressure from attorneys and top officials of the Institut Pasteur (IP), Dr. Varmus refused to even consider a possible reallocation of royalties from the HIV blood test patent until he was confronted with a serious threat of an imminent lawsuit. Even when he finally agreed to a reallocation of the royalties, Dr. Varmus (with HHS' blessing) merely negotiated an increase in the IP share of the royalties, based on a disingenuous explanation of accounting anomalies, rather than the proven fact that the LTCB scientists, contravening a formal transfer agreement, used an IP AIDS virus isolate to make their blood test.

C. Summary of the Subcommittee's Findings

The popular view of the so-called "Gallo case" is that it is about whether Gallo et al. "stole" or misappropriated the IP virus. While this is indeed the central, original issue relative to the LTCB scientists, the case as it bears on the institutional response subsumes other vital issues, including how political and international reputational imperatives at HHS assumed preeminence over scientific integrity, and how defending the claims of the LTCB scientists came to be perceived as tantamount to defending the United States Government itself.

Major issues relating to the institutional response include the following: (1) the validity of HHS' claims to the United States Patent and Trademark Office (PTO), in applying for a patent on the LTCB HIV antibody blood test; (2) the integrity of HHS' response to the IP challenge in the mid-1980s, including the tactics and substance of legal briefs filed on behalf of Gallo et al.; and (3) the integrity of HHS' current response to the mounting body of evidence calling into question the actions and statements of both NCI scientists and HHS officials/attorneys.

Also examined in the Subcommittee's investigation of the Gallo case was the response of the scientific community to the revelations in this case, including whether the "self-correcting mechanisms" of science functioned, and if not, why not.

1. Did Gallo et al. Misappropriate the IP Virus? There is no longer any doubt that the IP scientists were first to isolate the AIDS virus. The LTCB scientists eventually did isolate and grow their own AIDS viruses; however, they did not discover the AIDS virus isolate with which they performed all of their seminal experiments. Instead, they performed all of these experiments with the IP virus, first under its own original name ("LAV"), then under two different names -- "MOV" and "HTLV-IIIb."

Drs. Gallo and Popovic claim that the names MOV and IIIb represented distinct, genuine LTCB isolates. These claims cannot be substantiated. According to the HHS OIG, Dr. Popovic merely renamed his LAV cell lines "MOV" (6/10/94 Investigative Memorandum; p. 4). As for the putative "IIIb" isolate, according to the OIG, there is reason to doubt that the experiment that reportedly produced this isolate was performed (op. cit., p. 21), and there is no evidence that a "IIIb" isolate ever existed independent of the IP virus. The Subcommittee investigation produced these same findings -- and more (see below).

With the June 1993 publication of analyses performed for OSI by Roche Molecular Systems (Nature, 363, pp. 466 - 469), it is a proven fact that MOV and IIIb are the IP virus "LAI" (formerly designated "LAV"). The question is how this came to be, i.e., did Drs. Gallo and/or Popovic deliberately and knowingly misappropriate the IP virus or were they unknowing, innocent victims of an accidental contamination of their cultures with the IP virus? Or is the truth some variation of these alternatives?

To answer this question, it is important to understand that misappropriation of the IP virus could have happened by any one of a number of different scenarios: (1) via a deliberate act of relabelling a culture of LAI as "MOV" or "IIIb"; (2) via a deliberate addition of LAI to already-existing LTCB cultures; (3) via subsequent, knowing use of the IP virus under the name "MOV" or "IIIb," claiming it as an authentic LTCB isolate.

Drs. Gallo and Popovic argue that both MOV and IIIb -- which they claim originally were independent, genuine LTCB isolates -- were innocently contaminated by LAI. They argue that the contamination occurred without their knowledge and participation. Drs. Gallo and Popovic further assert that not until 1991 and thereafter was it proven that IIIb and MOV are LAI. As supposed proof that IIIb and MOV were innocently contaminated, Drs. Gallo and Popovic point to the fact that LAI contaminated cultures in other laboratories, including the IP itself.

But the occurrence of contamination at other laboratories shows only that contamination is possible, not that contamination is what really happened at the LTCB. In this regard, it is very pertinent that Gallo and Popovic claimed, for years, that contamination by the IP virus did not happen, could not have happened at the LTCB, because the IP virus did not grow. Dr. Gallo's own remarks to U.S. News & World Report, one of numerous public statements he made to the same effect, are particularly memorable in this regard. Responding to the suggestion that, "... Gallo may have mistakenly contaminated his experiments with the French virus," Dr. Gallo reportedly said this:

"'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; p. 68).

A substantial body of circumstantial evidence assembled and reviewed during the Subcommittee's investigation shows that at the very inception of their seminal experiments, the LTCB scientists knew or had reason to know that the virus they were working with and claimed as their own was the IP virus. The evidence also shows that within weeks of the announcement of their putative "discoveries," the LTCB scientists had additional, compelling evidence that their virus was the IP virus. In response to this evidence, Dr. Gallo mounted a campaign in which he first attempted to blame the IP scientists for a supposed contamination of their virus with "IIIb." When the attempt to attribute the "contamination" to the IP scientists failed, Dr. Gallo mounted a public campaign, the central assertion of which was that the IP and LTCB viruses clearly were different.

Thus, it is the LTCB scientists' own actions, both at the time they performed their seminal experiments, and even more, within a few weeks of the announcement of those experiments, that make compelling the case that there was something to hide, that the LTCB scientists knew there was something to hide, and that they made every effort to do exactly that.

(a) Evidence relating to the "isolation" of the LTCB virus: The LTCB laboratory notebooks and testimony by Gallo et al. to OSI and the Subcommittee show that the LTCB scientists grew and experimented with LAV for a substantial period. Information about these experiments was withheld from the IP scientists, both at the time the experiments were performed and, subsequently, during the blood test patent dispute, when records of the key experiments were redacted and obscured to remove references to the IP virus. Even top NCI officials were kept in the dark; these officials told Subcommittee staff they were told the LTCB scientists could not grow the IP virus.

Dr. Popovic, who had oversight of all of the LTCB's experiments with the IP virus, and actually performed many of them, attempted to give proper credit to the IP scientists. In the first draft of his seminal paper, one of four published simultaneously by the LTCB scientists in May 1984, Dr. Popovic explicitly acknowledged he had used LAV -- which he called "HTLV-III" -- as a "reference virus." But Dr. Gallo, chastising Dr. Popovic, extensively revised the paper, removing all references to Dr. Popovic's use of the IP virus, and rewriting the paper to make it appear Dr. Popovic's experiments had been performed with an LTCB HIV isolate, which Drs. Gallo and Popovic now claim was "IIIb," although it was not so specified in the paper.

As for the LTCB's putative MOV isolate, the story of its allegedly independent origins is, simply, not credible. The name "MOV" suddenly appeared in Dr. Popovic's notes, overlapping with entries for the IP virus, LAV. Drs. Gallo and Popovic actually claim that Dr. Popovic, returning from a trip, found an unlabelled culture -- growing alongside LAV, in the same cell lines as LAV -- which he suspected was LAV or could have been contaminated by LAV -- but which, because of his supposed uncertainty, he identified as "V," subsequently revised to MOV. Gallo/Popovic also say they believe MOV was isolated from an LTCB sample, but the sample they speculated was "probably" the source of MOV was shown in 1993 to contain no virus. The same 1993 experiments demonstrated that MOV is LAI and only LAI.

Even Gallo and Popovic's own statements show they recognized at the time of its alleged origins -- or shortly thereafter -- that MOV might very well be the IP virus (for details see below). The fact is there is no evidence MOV ever was anything but the IP virus. This almost certainly is the reason no experiments were ever reported as being performed with MOV, although according to LTCB records, MOV was used for some of the LTCB's most important early HIV experiments, including development of the LTCB HIV antibody blood test. Indeed, the very existence of MOV remained a mystery, until the publication of a November 1989 investigative report in the Chicago Tribune.

As for "IIIb," the alleged LTCB "prototype" isolate, Drs. Gallo and Popovic claim that this isolate originated in a pool of samples from ten patients with AIDS/pre-AIDS. However, many important details of the experiment that allegedly resulted in IIIb have been found to be untrue (see below). Moreover, as revealed in 1993, none of the ten samples contains a virus that looks anything like the IP virus (four samples actually contained no virus), yet the IP virus is the only virus that resulted.

According to sworn affidavits provided to OSI and the Subcommittee by IP scientist Dr. Francoise Barre-Sinoussi, Dr. Popovic told her he added the IP virus to the other samples in his pool for the express purpose of boosting the titre of the virus in the culture. Dr. Popovic subsequently said he did not make such an admission to Dr. Barre-Sinoussi. But not only does the addition of the IP virus make sense scientifically (Dr. Popovic told OSI he added additional samples to his pool because "I was afraid that I would lose the culture" [6/26/90 OSI interview; transcript p. 84]), it is fully consistent with and makes comprehensible what happened just a few weeks later, when the LTCB scientists were about to submit their blood test patent application. At this juncture, Dr. Popovic, knowing that his putative pool virus was about to be patented and commercialized, and knowing that such uses of the IP virus were strictly forbidden by the transfer agreement he signed when he obtained the virus, raised strong objections to use of the alleged IIIb for the LTCB blood test, arguing strenuously for another isolate, "RF," because, as he put it, he was "more certain" of its origins.

But RF was not ready to be used, primarily because it had not been "scaled up," i.e., grown in the large quantities necessary for a blood test. Patent exigencies and other circumstances meant that any delay, including a delay to scale up RF, was out of the question (see below). Among these circumstances was the fact that Dr. Gallo had moved up the submission date for the LTCB papers by a full month and had committed to the journal Science that the papers would be submitted on Friday, March 30. Dr. Popovic told OSI he had planned to use this month for further work with RF.

Thus, there was no time to make RF ready for use in the LTCB blood test, and Dr. Gallo has acknowledged that he never seriously contemplated delaying implementation of the LTCB blood test to try to ready RF. Thus, in the meeting with Dr. Popovic, Dr. Gallo insisted that the LTCB would proceed with "IIIb" for its blood test, even in the face of Dr. Popovic's concerns about IIIb's uncertain origins, which may well, in fact, have been based on Dr. Popovic's suspicion/knowledge that "IIIb" contained or actually was the IP virus.

The fact that at the time there was little scientific basis for concern that use of the IP virus would be discovered, gave Dr. Gallo's decision to use "IIIb" -- whether or not Dr. Gallo knew that IIIb really was the IP virus -- an added measure of security.

Dr. Gallo asserts that he did not know IIIb was really the IP virus. Dr. Gallo also has stated that Dr. Popovic, in raising his concerns about the "origins" of "IIIb," never even intimated that the "pool" virus might be the IP virus. There is no confirmed evidence to conclusively refute Dr. Gallo's account; however, the temporal coincidence of Dr. Popovic's expressed concerns about the origins of IIIb and Dr. Gallo's modifications of the Popovic et al. manuscript, including deletion of the information that Dr. Popovic grew the IP virus and substitution of references to an LTCB virus, suggests that Dr. Gallo may well have "put two and two together," and comprehended -- or at least suspected -- that IIIb really was LAV.

The Subcommittee staff believed that to corroborate Dr. Gallo's testimony, it would be important to obtain Dr. Popovic's testimony concerning these matters; unfortunately, Dr. Popovic refused repeated requests that he appear voluntarily for an interview with Subcommittee staff.

(b) Evidence of Knowing Use: The most incriminating evidence of "guilty knowledge" on the part of the LTCB scientists, i.e., knowledge that the virus they claimed as their own really was the IP virus, dates from the Spring/Summer of 1984. In June of 1984, the LTCB scientists began a series of molecular, i.e., genetic, comparisons of several HIV isolates, including LAV and "IIIb." The results showed that all the isolates were clearly different from each other, with one exception -- the IP and LTCB prototype viruses -- which were virtually identical. Importantly, these comparisons were performed with the IP virus received at the LTCB the previous September, well before the putative "MOV" and IIIb even were said to have originated. Consequently, there could be no question but that the IP virus was the original virus, i.e., that "IIIb" came from LAV, and not the reverse.

So far as is known, Dr. Gallo did not disclose the results of these initial LAV/IIIb comparisons to anyone. Instead, he devised a plan to make it appear that the French, in fact, had appropriated the LTCB virus. A month earlier, in May 1984, Dr. Gallo had sent IIIb to the IP scientists for the first time. In late June-early July, and even though he had already compared the IP and LTCB viruses, even though he still possessed the IP virus sent to him the previous September, Dr. Gallo made repeated, urgent requests that Dr. Montagnier send him another sample of the IP virus so the LTCB scientists could perform genetic comparisons with it.

Dr. Montagnier fulfilled Dr. Gallo's request, sending him a fresh sample of LAV in mid-July. When the LTCB scientists subsequently performed comparisons using the fresh sample of the IP virus, they found -- to no one's surprise -- that the viruses were the same. But because these comparisons were performed with the LAV sample that post-dated transport of IIIb to Paris, Dr. Gallo was able to assert that the IP scientists had contaminated LAV with IIIb.

In fact, that is exactly what Dr. Gallo did. In late Summer 1984, Dr. Gallo contacted Dr. Montagnier to tell him he must have had a contamination and that he (Montagnier) had sent the LTCB scientists back their own virus. Dr. Gallo relayed the same information to his superiors at the NCI, and he staged a dramatic scene at the LTCB in front of a number of unsuspecting witnesses, in which he raged at the IP scientists for "wasting his time" by sending him his own virus "when there was so much to do."

When Dr. Montagnier vehemently objected and would not acknowledge the "reverse contamination" scenario, (given that the LTCB scientists had LAV long before the IP scientists received "IIIb"), Dr. Gallo switched to the argument that the viruses, although very much alike, were genuinely independent. Dr. Gallo also speculated, without substantiation, that the patients from whom LAI and IIIb were said to have been isolated had had intimate contact in New York City, resulting in the transmission of the virus from one patient to the other, resulting in the remarkable similarity of the IP and LTCB viruses. This explanation was solidly refuted almost as soon as it was offered, but Dr. Gallo continued to promulgate it until at least 1990.

Another element of Dr. Gallo's campaign to counter charges of misappropriation of the IP virus was his claim that because he had numerous other HIV isolates, particularly isolates obtained long before the receipt of the IP virus at the LTCB, he had no motive nor need to use the IP virus. Dr. Gallo particularly singled out "RF" as one isolate that in and of itself eliminated any motive for misappropriation.

One notable example of these claims is an August 1985 paper, published in the Proceedings of the National Academy of Sciences (PNAS). In this paper, Dr. Gallo wrote the following:

"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 ..."

"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 ..." (Salahuddin, Gallo et al.; PNAS, 1985; pp. 5530-5533).

"No one believed we really had that many isolates" and "No one believed we really meant that" (July 22, 1993 staff interview).

2. The Institutional Response: The manner and content of HHS' response to the challenge to Gallo et al. was set as early as April 23, 1984, the day of the HHS press conference. Although a few crumbs were thrown to the IP scientists, the glory was all for Gallo et al. and the United States Government. Numerous unsubstantiable claims were made at the press conference by "our eminent Dr. Gallo," as HHS Secretary Margaret Heckler repeatedly described him. Secretary Heckler also elaborated at some length how the LTCB scientists' "discoveries" proved the administration's commitment to AIDS/HIV research.

Just minutes before the press conference, HHS submitted applications for U.S. patents on an HIV antibody blood test and a method of producing the virus. These patent applications contained the seeds of the French/American dispute; they contained fundamental assertions that could not be substantiated. Chief among these was the assertion that,

"... we are the original, first and joint inventors ... of the subject matter which is claimed and for which a patent is sought ..."

Dr. Gallo and his colleagues did not disclose to PTO their knowledge and use of the IP blood test, nor did they disclose the IP scientists' considerable body of scientific work on their virus and blood test (by April 1984, several IP papers had been published and numerous presentations given, several of them in Dr. Gallo's presence).

The materiality of the IP papers and presentations to the LTCB scientists' work is indisputable. When the PTO examiner finally became aware of the IP papers and presentations, she repeatedly invoked them as "prior art" against the claims of Gallo et al. in several continuation applications to the Gallo et al. blood test patent. Yet in their patent applications, Gallo et al., under penalty for making false statements, affirmed their duty to:

"... disclose information which is material to the examination of this application."

The HHS response to the IP challenge, which at this time was informal, was immediate and reflexive. The response was to defend -- at all costs and irrespective of the evidence -- the claims of Gallo et al. The Subcommittee investigation showed that HHS officials and attorneys conducted a parody of an investigation; they did not seek the truth, but rather sought to create an official record to support the claims of Gallo et al. HHS officials accepted uncritically everything they were told by Dr. Gallo and his colleagues, incorporating the LTCB scientists' information unqualifiedly and without confirmation into official reports of the Department. When these officials encountered hard evidence that contradicted the NCI/HHS claims, the evidence was ignored, discarded, and/or suppressed.

DOJ attorneys, in turn, took the "facts" they were given by NCI/HHS and incorporated them, often nearly verbatim, into U.S. Government pleadings in the Claims Court and before the PTO. At the same time, HHS and DOJ sought by every means at their disposal to thwart IP's discovery of evidence that would reveal the truth about the LTCB claims. According to attorneys' notes and participants' accounts, despite top HHS officials' awareness that many of the claims of Gallo et al. were, at best, highly questionable and without substantiation, HHS determined to "play out" the U.S. defense as long as possible, and "roll over" only when defeat became inevitable.

The HHS agency-level cover-up started early. In August 1985, HHS charged NCI to "investigate" the claims of Gallo et al. The investigation was conducted by a single individual -- Dr. Peter Fischinger -- one of Dr. Gallo's superiors, who even before he started his inquiry, pronounced the LTCB claims solid and entirely valid. Dr. Fischinger's investigation resulted in the so-called "Fischinger Report," which became the central substantive document on which the HHS/DOJ attorneys relied, in their defense of Gallo et al.

The manner in which Dr. Fischinger went about his task makes clear how perverse was the entire effort, and how distorted an account the Fischinger report provided regarding the so-called facts of the case. At the outset, Dr. Fischinger posed a series of questions to Dr. Gallo, questions that focused on demonstrably irrelevant non-issues, most notably, the alleged "other isolates" of Gallo et al. Based solely on the responses of Gallo et al., Dr. Fischinger hurriedly wrote his report, which the Subcommittee investigation found to contain numerous incorrect, misleading claims (see below). Dr. Fischinger took the remarkable step of requiring Dr. Gallo to certify in writing that all the information contained in the report was correct and supported by data.

Only after completing his report did Dr. Fischinger write a super-confidential memorandum to Dr. Gallo, in which he (Fischinger) required Gallo to address "three major areas of oversight," one of which concerned the central issue in the entire dispute, i.e., the question of possible misappropriation of the IP virus. Regarding this issue, Dr. Fischinger asked for a

"... written statement .... that LAV was never used in any connection in ... the isolation of the HTLV-IIIb line."

"There is no evidence that material from any outside laboratory including the French was used in generating the HTLV-IIIb virus ..."

Yet at the very moment HHS was dispatching a September 6, 1985 rejection of the IP demands, HHS officials were confronted with damning new evidence that strongly challenged the claims of Gallo et al. On September 5, HHS officials traveled to the NIH, where they were told by laboratory chief Dr. Malcolm Martin about experiments performed in his laboratory that showed the IP and LTCB viruses were genetically identical, with the LTCB virus descended from the IP virus, and not the reverse. The following day, the same HHS officials travelled to the HHS Centers for Disease Control (CDC) where they learned that the IP scientists discovered HIV and made a blood test fully the equal of the LTCB test, long before Gallo et al. But these dramatic revelations did not in any respect alter HHS' course. In fact, HHS' only action was to ask Dr. Gallo to provide a further response. Meanwhile, HHS officials "deep-sixed" the extensive documentation they had been given to substantiate the Martin and CDC conclusions (see below). Some of this evidence was withheld from the Subcommittee until late 1993.

With their claims rejected, in the Fall of 1985, the IP attorneys filed a request at PTO for an "interference" with the Gallo et al. blood test patent (an interference is a USPTO procedure for determining priority of invention between two or more parties claiming the same patentable invention). In addition, in December of 1985, the IP attorneys filed a suit for breach of contract in the U.S. Court of Claims. The thrust of the interference request was that the IP scientists should have been awarded the U.S. patent on the HIV antibody blood test, because they both isolated the virus and invented the blood test long before Gallo et al. and because their patent application clearly predated that of Gallo et al. The IP further argued that one of the principal reasons the Gallo et al. patent issued was because Gallo et al. had failed in their duty of candor to PTO. In the Claims Court suit, IP's central theme was that the LTCB scientists violated the non-commercialization agreement they had signed by using the Institut Pasteur virus for commercial purposes, thereby inflicting great damage on IP's interests.

The legal pleadings submitted by attorneys defending Gallo et al. were packed with false and misleading claims, hardly surprising, given their exclusive reliance on information provided by the LTCB/NCI. The attorneys argued, in the strongest terms, that the IP and LTCB blood test viruses were distinctly, genetically different, e.g.,

"The scientific evidence is clear that HTLV-III and LAV are not so similar that HTLV-III can be the progeny of LAV" (Defendant's Reply to Plaintiff's Memorandum in Opposition to Defendant's Motion to Dismiss the Complaint; p. 6).

Concerning the inventorship of the HIV antibody blood test, HHS/DOJ attempted to argue that the Gallo et al. test was a different invention from that of the IP scientists. When PTO undercut this argument by ruling that there was one invention and one HIV antibody blood test at issue, the attorneys resorted to the argument that Gallo et al. still were the real inventors, because they "conceived the invention" (i.e., isolated the AIDS virus) and reduced it to practice before Montagnier et al. This argument required the invocation of the claimed "early isolates" of Gallo et al., claims which the Subcommittee investigation found could not be substantiated in a number of vital particulars.

In addition, concerning the failures of candor and the duty of disclosure, the HHS/DOJ attorneys argued this:

"... nothing material or relevant was withheld from the examiner" (Opposition of Gallo et al. to the Motion for Judgment of Montagnier et al., p. A20).

The already-fragile HHS/DOJ arguments were further jeopardized in the Spring and Summer of 1986, first with the public revelation of electron micrographs of the IP virus, published by Gallo et al. as "HTLV-III," showing the virus productively growing in permanent cell lines. (This, of course, was the virus that Dr. Gallo had previously and repeatedly asserted did not grow.) Then, during the Summer of 1986, PTO -- having finally comprehended how badly it had been misled -- began to invoke the IP work as prior art to Gallo et al., threatening to throw numerous pending Gallo et al. applications into the ongoing blood test patent interference. The documented contents of an "off-the-record" conversation between the PTO examiner and an attorney for Gallo et al. summed up the situation well:

"... several in the PTO [are] believing that HHS/NIH are withholding info., i.e., that Montagnier may be the first inventor of most of these cases and that Gallo did indeed steal from him ..."

HHS did its best to cover up the wrong-doing. Meanwhile, the failure of the entire scientific establishment to take any meaningful action left the disposition of scientific truth to bureaucrats and lawyers, with neither the expertise nor the will essential to the task. Because of the continuing HHS cover-up, it was not until the Subcommittee investigation that the true facts were known, and the breadth and depth of the cover-up was revealed. This report describes the facts, and how and why HHS went so badly wrong.

II. CHALLENGES TO THE INVESTIGATION

A. Withholding/Altering/Destruction of Documents

The challenges to the Subcommittee's investigation, and to the OSI and OIG investigations as well, were significant, both because of the time that had elapsed since many of the key incidents and because some witnesses were frankly antagonistic to the Subcommittee's objectives. Documentary evidence was vital to the investigation; however, systematic withholding of documents was evident from the outset, on the part of both agencies and individuals. Key documents frequently were withheld for prolonged periods, in many cases, for years. Some critical documents known to exist were never officially produced. Among the more noteworthy such instances were the following:

• At least one incident of document destruction occurred during the pendency of the Subcommittee investigation, at the NIH Office of Scientific Integrity (OSI). This incident led to an investigation by the NIH Division of Management Survey and Review (DMSR).

• Documents in the possession of key participants in the HHS defense of Gallo et al. were claimed to be destroyed or lost. Former NCI Associate Director Dr. Peter Fischinger, for example, claimed that hurricane Agnes flooded his home, with the consequent loss of all relevant documents in his possession.

• Dr. Lowell Harmison, formerly the Science Advisor to the HHS Assistant Secretary of Health, upon his retirement from HHS in late 1987 removed several boxes of documents from his office over a weekend with the assistance of the then-Deputy Assistant Secretary for Health. When HHS learned of Dr. Harmison's surreptitious document removal, it belatedly changed the locks on the door of his office and conducted a perfunctory "investigation" (an HHS attorney telephoned Harmison to ask him for an explanation). Harmison claimed that he disposed of most of the documents he removed from his office in the trash, and he asserted all his "official" correspondence should be available through the HHS Executive Secretariat. No such correspondence was ever produced for the Subcommittee. In fact, in stark contrast to Harmison's top-level, central role in the HHS defense of Gallo et al., only two documents bearing his signature were provided to the Subcommittee.

• A substantial number of highly significant documents were either withheld or heavily redacted before they were provided to OSI by Dr. Gallo and his colleagues. As a consequence, OSI was seriously misled concerning such significant matters as what experiments were performed with the IP virus, how the putative LTCB prototype HIV was "isolated," and what Dr. Gallo knew about these experiments.

• o Several critical sets of data never were produced to the Subcommittee, including primary data from LTCB experiments comparing the IP and LTCB prototype isolates. Dr. Gallo initially told Subcommittee staff that his attorney possessed copies of some of these data, but when he was asked to produce the copies, Dr. Gallo claimed he had been misunderstood, and that his attorney possessed only documents associated with a lawsuit Dr. Gallo had filed against a French newspaper. The missing data were never produced.

• A particularly egregious instance of document withholding at NIH came to light in late 1993, when Subcommittee staff learned from an outside source about the existence of a large cache of documents at the NIH FOIA office. These documents, never produced to OSI, the HHS Office of Inspector General, or the Subcommittee, included a set of documents (the "Myers documents") showing that in 1987, within days of the signing of the French/American settlement, leading American scientists had concluded that Dr. Gallo's claims for the origins of his "IIIb" virus amounted to a "double fraud."

None of the Myers documents was ever provided to OSI. And when the documents were sought by a journalist under the FOIA, their release was denied, at the behest of a top NCI official -- a nonscientist -- who told the NIH FOIA officer the documents "pertained to the agreement with the Pasteur Institute, the science of which has not yet been resolved."

B. Interview Challenges

Testimony posed at least as great a challenge as documentary evidence, partly because memories of some witnesses had eroded, due to the passage of time. At least as serious was the problem of willful forgetfulness and obstructionism, of which the following instances are exemplary:

• HHS attorneys manifested particularly severe memory deficits. During his October 8, 1992 interview by Subcommittee staff, HHS attorney Richard Riseberg emitted a remarkable number of "I don't know," "I don't recall," and "I can't help you there" responses concerning a number of critical events at which he personally was present. Riseberg claimed he was merely "asked to go along" to these events. HHS Attorney Darrel Grinstead, in his September 22 and September 30, 1992 interviews, took a similar tack, although on some critical issues, besides repeating, "I don't recall," Grinstead added this:

  "I wouldn't tell you even if I did recall. That was between client and attorney."

• NCI and NIH Directors Drs. Vincent DeVita and James Wyngaarden each denied any significant responsibility for the defense of Gallo et al. Yet each said the other was importantly involved. Dr. DeVita told Subcommittee staff that Dr. Wyngaarden took on an especially prominent role in matters relating to AIDS and that Wyngaarden "liked to deal with international stuff." Consequently, according to DeVita, Wyngaarden took on responsibility for discussions with IP officials and officials of the French Government, including discussions about possible monetary settlements, creation of an "official" scientific chronology, and other significant matters. Dr. Wyngaarden, by contrast, pointed to numerous instances in which DeVita and NCI by-passed the office of the NIH Director, dealing directly with HHS authorities, Congressional leaders, and even the White House.

• Both Drs. Wyngaarden and DeVita, as well as every other key player at HHS, pointed to Lowell Harmison as the man in charge of the U.S. defense of Gallo et al., particularly during the critical early months of the French/American dispute. Attorney Richard Riseberg described Harmison as the "linchpin" of the HHS defense, who "understood the implications of the scientific information." Dr. Wyngaarden described Harmison as "on top of this," and the "chief individual" in the HHS defense. Dr. DeVita described Harmison as "running the show," and attorney Darrel Grinstead described Harmison as his "most regular client."

• Despite these characterizations, Dr. Harmison claimed little or no recollection of most major elements of the French/American dispute, particularly his own role. Dr. Harmison claimed he was unable even to describe his job, as in this exchange during a hearing in Executive Session:

  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 (7/21/93 hearing transcript; pp. 121 - 122).

  Dr. Harmison also evinced a curious perspective concerning what was relevant vis-a-vis the French/American dispute. In response to a question about the key issue of the dates on which the IP and LTCB scientists created and began to work with their HIV antibody blood tests, Dr. Harmison said,

  "I don't recall with respect to that date. That is to me not relevant. I don't recall, if I knew ... I said I can't recall. To me it is irrelevant because I can't recall it" (op. cit., p. 175).

III. THE LTCB HIV BLOOD TEST PATENT

The April 23, 1984 filing of a United States patent application for the HIV antibody blood test of Gallo et al. was a defining event for HHS as well as the LTCB scientists. The commercialization of the IP virus in and of itself would violate the terms of the IP transfer agreement that accompanied the virus sample (see below for further details); the patent application further "upped the ante" dramatically for all concerned. The reputational and potential financial benefits of a blood test patent were very significant. Equally significant were the potential legal consequences of breaching the terms of the transfer agreement, and the potential legal, even criminal consequences for breaching United States patent laws and regulations.

The filing of the LTCB blood test patent application influenced events a decade and more thereafter. Because the consequences of the patent application filing were so far-reaching and profound, this section of the report lays out the relevant statutes and regulations, together with a description of the actions/statements of Gallo et al. subject to those statutes and regulations.

A. Patent Privilege and Responsibility

Rules of the United States Patent and Trademark Office make clear that holding a United States patent is a privilege that entails vital responsibilities, particularly responsibilities for candor and full disclosure. According to the PTO Manual:

"A patent by its very nature is affected with a public interest. As recognized by the Constitution, it is a special privilege ... At the same time, a patent is an exception to the general rule against monopolies and to the right to access to a free and open market. The far-reaching social and economic consequences of a patent, therefore, give the public a paramount interest in seeing that patent monopolies spring from backgrounds free from fraud or other inequitable conduct and that such monopolies are kept within their legitimate scope" (Emphasis added; Precision Instrument Mfg. v. Automotive Maintenance Machine Co., 324 U.S. 806, 65 USPQ 133, 138 [1945]; cited in op. cit., 2010.01 "The Elements of 'Technical' or 'Affirmative' Fraud"; p. 2000-13).

"... the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for patent ..." (35 U.S.C. 102[a]);

"A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains" (35 U.S.C. 103; op. cit.).

The PTO Manual of Patent Examining Procedures says this about the duties of candor and disclosure:

"A duty of candor and good faith toward the Patent and Trademark Office rests on the inventor, on each attorney or agent who prepares or prosecutes the application and on every other individual who is substantively involved in the preparation or prosecution of the application ... All such individuals have a duty to disclose to the Office information they are aware of which is material where there is a substantial likelihood that a reasonable examiner would consider it important in deciding whether to allow the application to issue as a patent" (emphasis added; 37 CFR §1.56 [a], cited in Manual of Patent Examining Procedures, 2001, "Duty of Disclosure, Candor, and Good Faith," p. 2000-2).

Importantly, according to PTO rules,

"The duty to disclose material information extends to information such individuals are aware of prior to or at the time of filing the application or become aware of during the prosecution thereof" (emphasis added; op. cit., pp. 2000-4 - 2000-6).

"No patent will be granted on an application in connection with which fraud on the Office was practiced or attempted or the duty of disclosure was violated through bad faith or gross negligence. The claims in an application shall be rejected if upon examination ... it is established by clear and convincing evidence (l) that any fraud was practiced or attempted on the Office in connection with the application ... or (2) that there was any violation of the duty of disclosure through bad faith or gross negligence in connection with the application ..." (37 CFR §1.56, [d], op. cit., p. 2000-2).

B. What Gallo et al. Said in Their Patent Applications

On April 23, 1984, when Dr. Gallo and his associates submitted applications for United States patents on their HIV blood test and a method for virus production, they 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 ..."

"... to disclose information which is material to the examination of this application ... "

"... 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."

"... 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 ..."

C. What Gallo et al. Withheld from PTO

The results of the Subcommittee's investigation show that the claims of Gallo et al. to be the "original, first" inventors of the HIV antibody blood test cannot be substantiated. Moreover, there were at least three critical areas in which Gallo et al. failed in their duty of disclosure to PTO: (l) the LTCB scientists' knowledge of and benefit from the IP scientists' work with LAV; (2) the LTCB scientists' knowledge and use of the IP LAV antibody blood test; and (3) the LTCB scientists' receipt and use of the IP virus itself.

The attorneys who prepared the April 1984 patent applications for Gallo et al. told Subcommittee staff that they instructed Gallo et al. about their duty of disclosure. Yet according to these attorneys, even they were not told by Gallo et al. about the IP prior art, nor were they told about the LTCB scientists' own work with the IP virus. Both the attorneys and the PTO examiner told Subcommittee staff that numerous aspects of the IP and LTCB work were material to the claims of Gallo et al. and should have been disclosed.

At best, Gallo et al. were grossly negligent in claiming that they were the "original, first ... inventors" of the HIV antibody blood test and in failing to disclose what they knew about their own work and that of others with the IP virus. In this regard, it is noteworthy that the PTO Manual makes clear that gross negligence may connote "fraudulent intent":

"... The 'inference that there was fraudulent intent' is warranted when ... there is proof that the party making the misrepresentation had knowledge of its falsity ... Under circumstances where 'public policy' demands a complete and accurate disclosure it may suffice to show nothing more than that the misrepresentations were made in an atmosphere of gross negligence as to their truth ... " ("The Elements of 'Technical' or 'Affirmative' Fraud," p. 2000-14).

Dr. Gallo and his colleagues were aware of and in several cases, had extraordinary access to the presentations and publications of the IP scientists' work. This included the paper by Barre-Sinoussi et al. Dr. Gallo received an advance copy of this paper; he also played an unusual dual role of editor and peer reviewer. It also included a book chapter by Montagnier et al. (presented at a meeting in September 1983), for which Dr. Gallo played the role of editor.

Gallo et al. did not disclose any of the IP publications to PTO, save for a single, misleading reference in one LTCB paper cited in one of the Gallo et al. patent applications, a reference that implied the LTCB and IP viruses were different. Neither did Gallo et al. disclose any of the IP scientists' papers, presented at meetings which Gallo and his colleagues attended. Consequently, the PTO examiner had to discover them on her own. The IP publications unquestionably were material to the Gallo et al. applications. In fact, when she belatedly became aware of the IP publications, the PTO examiner declared that both Barre-Sinoussi et al. and Montagnier et al. were "prior art" to the blood test CIPs of Gallo et al. For this reason, she repeatedly rejected every claim contained in these CIPs.

The PTO examiner cited both sections 102[a] and 103 of 35 U.S.C. as the basis for her rulings. Concerning claims in the Gallo et al. blood test CIP applications, the examiner said the claims:

"... are rejected ... as anticipated by or, in the alternative, ... as obvious over Barre-Sinoussi et al. ... or over the disclosures of Montagnier 9/1983 ..." (2/11/86 PTO Office Action, Gallo et al., SN# 635,610; p. 4).

"... are 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." (op. cit., p. 5).

"... are rejected under 35 U.S.C. 103 as being unpatentable over Barre-Sinoussi or Montagnier et al. ..." (4/4/86 PTO Office Action, Gallo et al., SN# 643,715; p. 9).

"... 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., p. 9).

These developments occurred unbeknownst to the IP and its attorneys. PTO's intentions were recounted in a memorandum describing an extraordinary "off-the-record" conversation between the PTO examiner and an attorney for Gallo et al. In this conversation, the examiner reportedly said that HHS' responses to PTO's recent office actions, plus the fact of Dr. Gallo's editing of the book containing the Montagnier et al. chapter,

"... have several in the PTO believing that HHS/NIH are withholding info., i.e., that Montagnier may be the first inventor of most of these cases and that Gallo did indeed steal from him ... "

"... for specific reactivity against your AIDS virus-producing cells by immune fluorescence or against the AIDS virus antigens by your ELISA approach" (emphasis added).

By his own admission, Dr. Gallo was present at the September meeting and heard Dr. Montagnier present his data. Dr. Gallo also was present two months later in Tokyo, Japan, when another IP scientist, Dr. Francoise Barre-Sinoussi, presented a comprehensive report on the IP scientists' work, including updated results for the LAV blood test.

By mid-March 1984, the LTCB scientists had developed their own antibody blood test. At this time, Dr. Gallo was informed of the results of a blind comparison of the LTCB and IP tests, a comparison performed by scientists at the HHS Centers for Disease Control (CDC). Documentary evidence and witness interviews show that the CDC comparison revealed the IP and LTCB blood tests performed equally well, both at high levels of accuracy, in detecting viral antibodies in both AIDS and pre-AIDS patients.

Several witnesses told Subcommittee staff that Dr. Gallo personally was told about and, during the first week of April 1984, actually saw the data from the CDC comparison. Even before he saw the computer print-out of the data, Dr. Gallo acknowledged that he knew of their contents and significance. Speaking at a scientific symposium in Zurich, Switzerland on April 5, 1984, Dr. Gallo said this about the work of the IP scientists:

"... I have heard recently that their serological [blood test] 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, audiotaped address).

"... 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."

"... are widely distributed in the population at risk of AIDS ... " (p. 757 ) .

3. Receipt and Use of the IP Virus: Beginning in July 1983, the LTCB scientists received repeated shipments of the IP virus, along with serum from patient "BRU," the patient from whom the first IP virus isolate was obtained. (At the time, the virus samples were all designated "LAV" and were believed to have originated with patient BRU; however, one sample, received at the LTCB in September 1983, had been accidentally contaminated in Paris with another IP virus, from patient LAI. These circumstances were revealed in 1991 in a paper by the IP scientists and confirmed in 1993 in a study by Roche Molecular Systems, Inc., commissioned by the NIH Office of Scientific Integrity. The critical fact is that both BRU and LAI are IP virus isolates.)

The IP virus received at the LTCB in September 1983 was 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."

"... 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."

"... will be used by the recipient himself, exclusively, and only for the following research purposes ...: (a) biological; (b) immunological and (c) nucleic acid studies."

The knowledge and experience the LTCB scientists gained from their use of LAI as "LAV" was very substantial (see below for details). The "Richards Committee," the oversight committee for the OSI investigation appointed by the National Academy of Sciences (NAS), 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).

IV. THE COVER-UP AT LTCB

A. Growth and Use of the IP Virus

The combined results of the OSI, OIG, and Subcommittee investigations revealed the following uses of the IP virus samples at the LTCB:

• The BRU virus sample received at the LTCB in July 1983 was used to obtain the first LTCB electron micrograph (EM) correctly identifying the suspected AIDS virus as a "lentivirus." Subsequently, a culture of BRU virus, as well as BRU serum received from the IP scientists were used for an experiment the U.S. Government attorneys later would represent to PTO as the "reduction to practice" of the LTCB blood test invention.

• The LAI virus sample was the first isolate the LTCB scientists grew in permanent cell lines. In fact, it was the first virus the LTCB scientists even attempted to grow. Dr. Popovic told OSI he chose the IP virus for this crucial experiment because it "... was the best defined isolate from an AIDS-like patient ..."

• The IP virus, under its own name, grew at least two-to-three months at the LTCB, in two permanent cell lines; by Dr. Gallo's own admission to OSI, the growth of the IP virus was "significant and continuous."

  Yet in their patent applications -- and from the very first of their scientific papers on the AIDS virus, the LTCB scientists failed to disclose their work on the IP virus, particularly the fact that they had grown the virus for several months in permanent cell lines. Drs. Gallo and Popovic even hid their growth of the IP virus in permanent lines from the IP scientists. Dr. Popovic told OSI that when he telephoned Dr. Montagnier to tell him that he (Popovic) had "learned how to handle the virus,"

  "What I didn't tell him was that the virus grows very well in permanent T-cell lines ... I didn't consider that it was my duty to inform him in detail, that we have a breakthrough with this virus" [the IP virus, "LAI"] (emphasis added) 6/26/90 OSI interview; pp. 111 - 112).

• Samples of the two LAI cell lines were successfully assayed by EM and immunofluorescence assay (IFA) in mid-December, 1983. In fact, as late as the end of 1983, the only AIDS virus cultures for which Gallo et al. had EMs correctly identifying the presence of a lentivirus were the LAI cell lines. One of the LAI EMs was published by Gallo et al., identified as an LTCB isolate of the AIDS virus (see below).

  The Subcommittee's investigation showed that records of both the EM and IFA experiments on the LAI cell lines were redacted/obscured before they were produced to the IP attorneys during the French/American dispute. It seems impossible that this was anything other than a deliberate act of deception, an act that significantly disadvantaged the IP, because it was impossible to discern that the IP virus grew productively and was used for successful experiments months after the virus arrived at the LTCB. The redacted/obscured records permitted Gallo et al. to continue to promulgate the myth that the IP virus did not grow more than transiently at the LTCB.

• The LAI cell lines, with the virus name identified only by "L," were the first two cultures tested by the LTCB scientists using their first reagent specific for the AIDS virus, a reagent itself made with the IP virus. Both LAI cultures were positive in the IFA, confirming they were infected with the AIDS virus. These are vitally important data; they directly contradict Dr. Gallo's subsequent sworn statements that (l) prior to the submission of the LTCB patent applications, he and his colleagues had no evidence the LTCB and IP viruses were the same kind of virus and (2) prior to the allowance of the LTCB blood test patent, he saw no evidence the IP virus was the cause of AIDS (see below).

• The IP virus LAI, first renamed "MOV" and later renamed "IIIb," was used by the LTCB scientists for numerous significant experiments, including these: (l) the first large-scale production and mass production of the AIDS virus; (2) creation of the first HIV-specific reagents; (3) development and refinement of the LTCB antibody blood test, followed by its commercialization world-wide; (4) creation of the first cDNA probes and molecular clones of the AIDS 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).

"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).

B. Selection of the Isolate for the LTCB HIV Blood Test

1. Early Work on the LTCB Blood Test: Dr. Popovic emphasized to OSI that the overriding purpose of his early HIV experiments was to produce the virus in large quantities. This would, among other things, enable development of an HIV antibody blood test at the LTCB. For these purposes, the identity of the virus isolate, as long as it grew well, was of little concern. As Dr. Popovic said:

"... as concerning the AIDS virus, what did matter was its growth in a high titre that one could work with it. It didn't matter in terms of its precise origin" (6/26/90 OSI interview; transcript p. 160).

The IP virus was used for the LTCB blood test. Even HHS -- ten years after the fact -- finally acknowledged this is so. But the truth about the LTCB scientists' use of the IP virus should never have been so long in coming; evidence of this use existed all along.

The Subcommittee staff's review of LTCB laboratory notebooks and related documents, plus testimony from Drs. Gallo and Popovic and their LTCB colleagues provided substantial circumstantial evidence that the LTCB scientists, particularly Drs. Gallo and Popovic, at the time of their alleged "discoveries" in 1984, knew or had reason to know that "HTLV-IIIb, " the HIV isolate claimed as the LTCB prototype, was the IP virus (LAI). There also is substantial evidence that Gallo and Popovic knew or had reason to know that the "mystery isolate "MOV" -- the isolate used to make the first HIV-specific reagents and the isolate actually used to make the LTCB HIV blood test -- this isolate also was LAI. This evidence is described in sections l(a) and l(b) below. Further, the evidence shows that in the critical closing days of 1983 into early 1984, Gallo/Popovic had one useable virus isolate -- LAI -- which was successively renamed according to the then-existing exigencies, and ultimately was patented and claimed as the LTCB's own.

(a) LAI as "MOV":

• January 6, 1984 was the first recorded use of an LTCB HIV antibody blood test. The virus was not identified in the laboratory notes, but was said by Gallo et al. to be "MOV." Drs. Gallo and Popovic have long asserted that "MOV" was a genuine LTCB isolate independent of the IP virus. But there is no evidence to substantiate this claim and much evidence to support that MOV always was and was known to be the IP virus.

• The Roche analysis showed that MOV is the IP virus "LAI."

• By Dr. Popovic's own account, the name "MOV" was added to his laboratory notes well after the date the experiments were done. According to the report of the HHS OIG, the cell lines Dr. Popovic retrospectively identified as "MOV" in reality were the "LAI" cell lines (6/10/94 Investigative Memorandum; p. 4).

• Drs. Gallo and Popovic claim that "MOV" most likely originated with patient "HM." But even Dr. Gallo acknowledged there was no evidence to substantiate this claim (see below), and such records as exist cast considerable doubt on it. The LTCB's own records show that samples from patent HM repeatedly tested negative for virus, in 1983-84, and an HM sample analyzed by Roche in 1990-91 found the sample contained no HIV.

• Dr. Popovic's OSI testimony directly traced the origins of "MOV" to the LAI cell lines (3/4/91 Popovic submission to OSI, pp. 36 - 37). And Dr. Gallo's testimony shows he knew or had reason to know that MOV originated with the IP virus. Speaking about Dr. Popovic's experiments in the Fall of 1983 that allegedly resulted in the isolation of MOV, Dr. Gallo said this:

  "Two of those cultures are RT positive. One is labeled LAV, the others have numbers on them. The numbers, he [Popovic] believes, MOV came from the one that was labeled [HM] ... But I don't find anything in the notes that prove that that is what it is ... at this time he is really trying to get anything to grow ... his overwhelming goal was to get something to grow in culture in large scale and in permanent production, and that he wasn't giving the full attention to all the kinds of records . . .

  "We didn't know what was going on. Whether cross contamination with LAV, whether the culture would last. This was the beginning of the culture ...

  "Was LAV the same as this new thing? ... Was the new thing one thing or a mix? ... My belief is Mika is not certain as to what the origin is" (emphasis added; 5/10/90 OSI interview; excerpted from transcript pp. 58 - 71).

• On March 6, 1984, according to Gallo at al., the LTCB prototype virus, "HTLV-IIIb," allegedly derived from a pool of samples taken from ten patients, replaced "MOV" in the LTCB blood test. The laboratory notes do not reflect this change.

• Drs. Gallo and Popovic claim that IIIb, like MOV, was a genuine LTCB isolate, independent of LAI. But the Subcommittee's investigation found that aside from Gallo/Popovic's assertions, there is no evidence to support this claim and there is ample reason to question it.

• As confirmed by the Roche analysis, "IIIb" -- like "MOV" -- is the IP virus LAI.

• According to the report of the HHS OIG,

  "... there is no evidence there ever was a IIIb isolate independent of LAV [LAI] (6/10/94 Investigative Memorandum; p. 22)

  and

  "There is reason to doubt that the 'pool' experiment ... really was done, or if done, that it ever produced anything other than LAV/LAI" (op. cit.; p. 21).

  The Subcommittee's investigation resulted in numerous findings that cast doubt on the pool experiment. Contrary to the claims of Gallo and Popovic, including claims in their patent applications, several of the putative pool samples contained no HIV, while others did not even come from AIDS or pre-AIDS patients . Furthermore, as seen in the LTCB's ' s own laboratory notes, contrary to the claims of the Popovic et al. paper, claims reiterated in official memoranda by Dr. Gallo, the putative constituent "pool" samples did not show "high RT activity in primary culture" (8/19/85 Gallo-to-Fischinger memorandum; p. 3). Only one of the ten putative pool samples was tested and found to be RT+ before the supposed pool experiment; several of the samples were not tested at all, while others were tested and found to be RT-. The notion that Dr. Popovic used such samples in an effort to obtain a high-titre virus-producing cell line defies credulity.

  It also is noteworthy that there is no mention of a pool in the Popovic et al. Science paper that allegedly reported the isolation of "IIIb." In fact, no "IIIb" virus appeared in any of the four May 1984 Science papers published by the LTCB. And in the first paper in which "IIIb" did appear, the experiments said to have been performed with IIIb were discovered by Subcommittee staff to have been performed with "MOV," i.e., the name of the virus was simply changed. (At least one other paper has been found with the same name change; the total number has not yet been established.)

• The evidence above points to the very real possibility that the name "IIIb" and the putative "pool" experiment were created after the fact, specifically to obscure the origins of the virus used for the LTCB HIV antibody blood test. "MOV," reportedly used for the development and first several months of the test's use, could not be reported in scientific papers, since the LTCB scientists knew or had reason to know it was the IP virus. Certainly the cover story that the LTCB scientists were uncertain of the origins of MOV provided no real cover, for by this account, Gallo et al. could not even be certain that their "MOV" AIDS virus came from a patient with AIDS! Thus, none of the seminal experiments said to have been performed with "MOV" were ever so reported in the scientific literature.

  To publish and patent a blood test, the LTCB scientists needed to provide a plausible origin for their prototype virus; the first official document in which the name "IIIb" appeared was the LTCB blood test patent application. By introducing a supposed "new" virus, "IIIb, " one said to be derived from a pool of ten samples, and by claiming they did not know which of the ten putative viruses "took," the LTCB scientists attempted, for years, to divert attention from the possibility -- now confirmed as true -- that the virus that "took," in fact the only virus that existed, was LAI.

• Several important pieces of evidence point to the probability that if the "pool" experiment actually was done (versus LAI/MOV merely being renamed "IIIb"), LAI was deliberately used as part of that experiment. According to three sworn affidavits of Dr. Francoise Barre-Sinoussi, the IP scientist widely regarded as the true discoverer of the AIDS virus, in 1992, Dr. Popovic acknowledged that he mixed LAV (LAI) with other LTCB samples, as part of his "pool" experiment. According to Dr. Barre-Sinoussi, Dr. Popovic told her he did this to obtain a high-titre cell line, not knowing the IP virus alone would grow out of the pool. Use of the IP virus in this manner would not have been proscribed by the IP/LTCB transfer agreement. What was specifically proscribed, however, was commercialization of the virus, which is precisely what Gallo/Popovic did when they patented and licensed the LTCB blood test made with LAI/LAV.

• Dr. Popovic denies making such an admission to Dr. Barre-Sinoussi; however, Dr. Popovic himself came very close to making the same statements to OSI. Describing the rationale for his "pool" experiment, Dr. Popovic said this:

  "We told ourselves it should be the AIDS virus, whatever AIDS virus was if that we can get it is fine. It wasn't the question of precise isolation ...

  "I was fully aware of it (of the problem of precise origin of the viral isolate). But what is wrong about using this approach when precisely the agent is not determined and I wanted to repeat the experiments and to show that really I can repeat it to achieve infection and long-term production of the virus. So one of the approaches was to pool culture fluids from samples of several AIDS patients ...

  "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, it is 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?" (emphasis added; 6/26/90 OSI interview; excerpted from transcript pp. 68 - 70 ) .

The interpretation that Dr. Popovic's anxiety developed precisely because he knew or strongly suspected "IIIb" was LAI -- and because he knew commercialization of LAI would violate the terms of the transfer agreement, with far-reaching, potentially disastrous consequences -- is entirely plausible, and is consistent with all the available evidence. Dr. Popovic's statements to OSI -- statements in which he said the origins of "RF" were "more certain" than IIIb, statements in which he said, "... if you ask for clear-cut science data, for sure, it was better to have RF ..." (6/26/90 OSI interview; transcript p. 71) -- point directly to this interpretation.

Dr. Popovic also voiced concerns about his own work with the three supposedly independent isolates LAI, "MOV," and "IIIb":

"The major problem is that individual isolates [e.g., "RF"] 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 [Elizabeth Read-Connole, Popovic's assistant] was involved in it, we (both of us) pushed for the RF isolate, in which we were more confident, comparing to the IIIb" (12/1/90 OSI interview; transcript p. 109).

Dr. Gallo's statements to OSI otherwise bore out Dr. Popovic's statements about his plea for RF; in some respects, Dr. Gallo's statements were more graphic regarding Dr. Popovic's concerns about the origins of "IIIb." Describing the "big, very long discussion" he and Dr. Popovic had about the matter, Dr. Gallo said this:

"... 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 ..." (4/26/90 OSI interview; transcript p. 72).

"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'" (12/1/90 OSI interview; transcript p. 106).

3. RF Was Not Ready: "RF," the putative contender to "IIIb" for use in the LTCB blood test, was not ready to be used at the point the "go-ahead" decision for the blood test was made. (Other potential contenders occasionally mentioned by Gallo et al. were even farther behind.) RF at all times lagged behind "IIIb" in its growth and titre, and there were troublesome anomalies and gaps in the data for RF. Specifically, prior to the Gallo/Popovic discussion about which isolate to use for the LTCB blood test:

• Early RT assays for RF were negative;

• IFAs of RF against AIDS serum, for weeks, were markedly low; moreover, on at least one occasion there was a positive reaction of RF to HTLV-I, suggesting the possibility of double infection or contamination of RF with the leukemia virus. Either possibility would have rendered RF unusable for an HIV blood test.

• Contrary to the claims of Dr. Gallo, there was no positive EM of RF; a positive reading was not obtained until November 1984.

• Most importantly, in contrast to "IIIb," RF had never been put into large-scale production. Consequently, there was no way to know whether/how well RF would serve for commercial production of an HIV blood test. The significance of this circumstance cannot be overstated. Here is what Dr. Popovic said about it:

  "... 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; transcript p. 77).

"... 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" (emphasis added; 12/1/90 OSI interview; transcript p. 116).

"... was a lower producer than the IIIb in our hands" (1/28/91 OSI interview; transcript p. 29).

"... 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" (4/8/90 OSI interview; transcript p. 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" (4/26/90 OSI interview; transcript p. 21).

"... we isolated, mass produced in H9 cells, patented and published on a major variant HTLV-III-RF ... very different from LAV, at exactly the same time, making all this crap irrelevant" (emphasis in original; 9/23/85 Gallo-to-Fischinger; p. 5).

"... it is a few weeks behind. Why make any delay" (12/2/90 OSI interview; transcript p. 102).

• By at least February 1984, by Dr. Gallo's own account, he had told top NCI officials he believed he had isolated the AIDS virus and was working on a virus antibody blood test. Documentary evidence and testimony shows that during the following weeks, these officials pressed Gallo and his associates with increasing urgency concerning when he would be ready to announce his "discoveries."

• By mid-March 1984, Dr. Gallo had told the CDC scientists, in general terms, about his "discoveries," including his plans to publish several papers in in the near future. By this time, work on several of the papers, including the blood test paper, had commenced.

• In mid-March 1984, Dr. Gallo lectured in Marseilles, France, announcing the isolation of "HTLV-III" from patients with AIDS.

• On March 30, 1984, Gallo et al. submitted four papers, including the blood test paper (reportedly based largely on the so-called "IIIb") to Science, for publication on May 4. Dr. Gallo had communicated with Science some weeks earlier and made special arrangements for submission and publication of the papers. Also on March 30, Drs. Gallo and DeVita travelled to HHS headquarters to brief the Assistant Secretary of Health Dr. Edward Brandt about the LTCB "discoveries."

• On April 5 - 6, 1984, Dr. Gallo lectured to large audiences, first at Zurich and then at the IP, describing his laboratory's work with "HTLV-III" and recommending to his audience,

  "following the literature over the next few months carefully and the story will be told in some detail."

• On April 9, 1984, Dr. Gallo gave a tape-recorded interview to BBC reporter Martin Redfern, giving Redfern prepublication copies of the four Science papers. Within a week, news stories about the LTCB's "discoveries" began to appear in the Washington Post, the Wall Street Journal, and then in the international media.

• On April 9, 1984, "IIIb" reportedly was sent for mass production preparatory to its release to the manufacturers/licensees of the Gallo et al. invention.

• On April 11, 1984, Dr. Peter Fischinger telephoned the NIH patent attorneys to tell them that Gallo et al. had,

  "... made a very important invention with world-wide significance. The Surgeon General intends to make an announcement in the very near future ... NCI wants a patent application on file before there is a statutory bar" (4/11/84 notes by NIH patent attorney Thomas Ferris).

  The "statutory bar" to which Dr. Fischinger referred was a vital consideration. 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 throughout the world. With news of the Gallo et al. blood test about to appear, much of it engineered by Dr. Gallo himself, it was essential that the Gallo et al. application be filed without any further delay. This is the reason Thomas Ferris reportedly told Peter Fischinger he (Ferris) would need the disclosures for the LTCB patent applications "ASAP."

• Perhaps most important of all, around mid-March 1984, before the discussion with Dr. Popovic, Dr. Gallo moved forward by a full month the submission date for the four Science papers. The reason Dr. Gallo moved up the submission date is not certain; one plausible reason is that Dr. Gallo was concerned about establishing priority over the IP scientists, in light of the information Dr. Gallo was given in mid-March concerning the accurate performance of the IP blood test in the CDC comparative study.

"... 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)

"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).

Dr. Gallo has said he would never have knowingly used the IP virus, if for no other reason than his desire to avoid the problems that would result in the event of discovery of that use. But at the time the decision was made to use "IIIb," in late-March/early-April 1984, even if Dr. Gallo knew with certainty that IIIb was LAI/LAV, he would have had little reason to fear discovery. The reason is because at that time, no one knew that individual HIV isolates would be discriminable from each other. Isolates of HTLV-I and -II, the only human retroviruses known prior to HIV, show very little inter-isolate differences. HIV is very different. Individual isolates are clearly discriminable from each other. But this "heterogeneity" of HIV, i.e., the fact that different HIV isolates exhibit substantial molecular/genetic differences -- and the contrasting, stand-out, virtual identity of IIIb and LAV -- would not be discovered until late-Spring/early-Summer 1984.

Thus, it is at least possible that a deliberate decision was made to patent and commercialize a blood test using the IP virus, both because there was no alternative to using that virus and because at the time of the decision, there was no discernible risk of discovery. More importantly, the evidence shows that by the Summer of 1984, when Dr. Gallo knew "his" virus almost certainly was the IP virus, he attempted to blame the IP scientists for "contaminating" the cell lines and when this failed, he suppressed the evidence of the viruses' identity and, for years, argued strenuously that they were genetically independent (see below).

C. Popovic et al.: The Rewriting of Science

The cover-up of the LTCB's work with the IP virus advanced to a more active phase in mid-March 1984, when Dr. Gallo systematically rewrote the manuscript for what would become a renowned LTCB paper (Popovic et al.; Science, 225, 1984, pp. 497-500), deleting Dr. Popovic's explicit references to his use of the IP virus and making it appear Dr. Popovic's seminal experiments had been performed with an authentic LTCB isolate. The extent of Dr. Gallo's revisions to Dr. Popovic's paper became clear during the OSI investigation, when Dr. Popovic suddenly produced two drafts of the paper bearing Dr. Gallo's edits. Dr. Popovic had secured these drafts with his sister in Czechoslovakia because, he said,

"... I believed that sometime in the future, I might need them as evidence to prove that I gave fair credit to Dr. Montagnier's group ... 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 ... " (4/10/91 OSI interview; transcript pp. 7 - 8).

"... there wasn't much emphasis ... don't think that Mika argued forcefully or strongly that we have to have some data on LAV growing in the culture. That is not the case. He did mention it in an almost casual way ..." (12/2/90 OSI interview; transcript pp. 184 - 186).

"I thought it was wrong not to credit Dr. Montagnier's group's contributions more clearly. I was also upset because I had lost control of the paper and feared that my major contribution to the discovery was significantly compromised" (5/15/90 Popovic memorandum to OSI; pp. 7 - 8).

"LAV is described here as HTLV-III"

"LAV as a reference virus ... had been used in the first series of experiments."

"... HTLV-III and LAV may be different ... "

"... by ... the early part of 1984, certainly before the press conference ... we knew that this was likely to be of the same virus type. I mean it stood to make sense" (4/11/90 OSI interview; transcript pp. 62 - 64).

"... has not yet been transmitted to a permanently growing cell line ..."

"We found that this virus, called LAV ... also grows in H4 [a clone of the HUT-78 cell line] and produces similar cytopathic effects on it as HTLV-III."

Concerning Dr. Gallo's statements about the IP virus, in Popovic et al., 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 appropriation of the French viral isolate" (emphasis in original; Richards-to-Healy; p. 3).

D. The HHS Press Conference

On April 23, 1984, the same day as Gallo et al. submitted their blood test and cell line patent applications, HHS announced the NCI scientists' putative discoveries at a press conference for the international media. Emphasizing the alleged uniqueness of the American accomplishments, HHS Secretary Margaret Heckler termed them "a triumph of science," "another miracle" added to "the long honor roll of American medicine and science." Secretary Heckler repeatedly referred to "our eminent Dr. Gallo." She added that "We have applied for the patent [on the blood test] today." And Secretary Heckler took the occasion to defend the Administration's record on AIDS research:

"Those who have disparaged this scientific search -- those who have said we weren't doing enough -- have not understood how sound, solid significant medical research proceeds ... the President has requested an additional $54 million to pursue this effort. The work ... inspired by the progress made to date will keep the research and investigation throttle on the floor."

For his part, Dr. Gallo took the occasion of the press conference to propound a number of misleading/unsubstantiable claims concerning the LTCB and IP scientist's work as, for example, these claims:

• "we've been mass-producing it [the AIDS virus] for six months" (the only virus the LTCB scientists grew at all, let alone that was "mass produced" "for six months" prior to the HHS press conference was LAI. Dr. Gallo attempted to justify his statement by saying that by "mass producing," he meant "continuously producing" virus [4/26/90 OSI interview; transcript p. 64]. Even by this idiosyncratic definition, the only virus that would qualify is LAI. By commonly accepted definitions of "mass producing," Gallo et al. had no viruses that had been mass produced for six months as of the date of the HHS press conference).

• "we have over 50 isolates" (by Dr. Gallo's own admission to OSI, he had no more than 10 genuine HIV isolates at the time).

• "Montagnier couldn't grow enough virus to send us for comparisons" (as described above, there was more than enough of the IP virus for the LTCB scientists to perform any experiment they wished).

E. Comparisons of the IP and LTCB Viruses

During the Summer and Fall of 1984, the IP and LTCB scientists attempted to compare their respective HIV prototype isolates. The HHS Assistant Secretary of Health, Dr. Edward Brandt, personally ordered that the comparisons be made, not because there was suspicion at the time that the viruses were genetically identical -- i.e., were derived from the same person -- but because, for public health reasons, it was essential to confirm that the IP and LTCB viruses were functionally the same and both were the cause of AIDS. Put another way, it was essential to confirm that there was only one virus that was causing the disease.

Yet almost immediately, these public health concerns became entangled with the volatile issue of whether the IP and LTCB viruses were genetically identical, and thus, whether "contamination" or misappropriation of the IP virus had occurred. Even the relatively benign "contamination" scenario would have been extraordinarily embarrassing, given the accolades and media attention surrounding the alleged LTCB discoveries. Consequently, when the genetic identity of the IP and LTCB isolates began to emerge as a focus of concern at NCI, public health concerns were subjugated to "scientific" intrigues, and the public and scientific community were misled about the nature of HIV.

Three papers were drafted reporting the results of the "IIIb"/"LAV" comparisons -- serological (containing the results of the CDC-coordinated blood test comparisons); immunological (comparisons of viral proteins); and molecular (i.e., genetic; comparisons of viral nucleic acids). None of the papers was ever published, but manuscripts of all exist. The manuscripts and associated data from the LTCB show that no later than the Summer of 1984, Gallo et al. knew that IIIb and LAV were -- at least -- functionally identical and were the cause of AIDS.

A manuscript on the comparison of viral proteins, coauthored by, among others, Drs. Gallo and Montagnier, reviewed and edited by the LTCB scientists in the Summer/Fall of 1984, said in the introduction:

"Two human retroviruses have been recently implicated as the causative agents of Acquired Immune Deficiency (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 added; Chermann et al., unpublished manuscript; p. 1).

"... demonstrates that LAV and HTLV-III are antigenically identical" (op. cit., p. 6).

"The duty to disclose material information extends to information such individuals [inventors and others associated with a patent application] are aware of prior to or at the time of filing the application or become aware of during the prosecution thereof" (PTO Manual; pp. 20004 - 20006).

The results of the molecular comparisons of the IP and LTCB isolates were even more significant. The molecular comparisons, carried out entirely at the LTCB during the Summer and early Fall of 1984, showed that the two supposedly independent isolates were genetically identical and thus, almost certainly came from the same person. But it was not until the Subcommittee's investigation that the significance of the events associated with this discovery was understood.

Here is what happened at the LTCB in the Spring/Summer of 1984 concerning molecular comparisons of LAV and IIIb:

• May 15, 1984: Dr. Sarngadharan carried a live sample of "IIIb" to Paris, the first LTCB-to-IP HIV transfer.

• Late May/early June 1984 (dates are approximate): The LTCB scientists compared "IIIb" with LAI/LAV (received the previous September ["Ti7.4/LAV"]) and found they were genetically identical. No data for this experiment have ever been produced, neither was the experiment disclosed to OSI; however, Dr. Gallo admitted to Subcommittee staff that the experiment was done. In 1991, Dr. Gallo also acknowledged the LAV/IIIb comparison to IP scientist Dr. Simon Wain-Hobson, but Gallo asserted to Wain-Hobson that in 1984, the demonstrated identity of LAV and IIIb had been attributed to wide-spread contamination by IIIb. This explanation cannot be substantiated, and in fact, is contradicted by a number of significant facts.

  Notably, several weeks earlier (April 24 - 29, 1984), another series of molecular comparisons showed that IIIb was genetically identical to MOV. Dr. Gallo's attorney wrote to the Subcommittee staff that the April 29 experiment demonstrated "the likelihood that MOV had been contaminated by IIIb" (8/5/93 Onek-to-Jaruzelski letter). This is a curious interpretation, i.e., the interpretation that MOV was contaminated by IIIb, since by Popovic and Gallo's own accounts, "MOV" was isolated well before IIIb and was (at least) suspected to be the IP virus. In reality, the MOV/IIIb comparison provided additional evidence that IIIb might be LAV.

• June 27, 1984: Dr. Gallo sought a new sample of LAV, "B/LAV."

• August/September 1984: The LTCB scientists compared B/LAV with IIIb and found they were identical. In the presence of several witnesses, Dr. Gallo accused Dr. Montagnier of having contaminated B/LAV with IIIb. Shortly thereafter, Gallo telephoned Montagnier, telling him about the genetic identity of B/LAV and IIIb, but not about the identity of Ti7.4/LAV and IIIb. Dr. Gallo told Dr. Montagnier he must have contaminated his cell lines with IIIb, but Montagnier told OSI he told Dr. Gallo any "contamination" could only have happened at the LTCB, since Gallo (as well as several other United States scientists) had had LAV long before "IIIb" went to Paris.

• Late August 1984: Dr. Gallo telephoned NCI Associate Director Dr. Peter Fischinger and told him about the recent telephone call to Dr. Montagnier. Dr. Gallo did not tell Dr. Fischinger about the Ti7.4/LAV results; in fact, Gallo told Fischinger the LTCB scientists had analyzed "original LAV" and found it different from IIIb. (In 1993, Dr. Gallo acknowledged to Subcommittee staff that at the time of the telephone calls to Montagnier and Fischinger, he had not performed any molecular analyses of "original LAV." Thus, Dr. Gallo's statements to Drs. Montagnier and Fischinger were not true.)

"By this time, Harmison was there [Dr. Lowell T. Harmison, a key player in the HHS defense of Gallo et al.]. He could have stopped it. By this time, Harmison almost assumed ownership of Gallo" (5/3/92 interview with Subcommittee staff).

What Dr. Brandt received, in mid-September 1984, was a statement from NCI that its scientists had "determined that LAV is an HTLV-III virus," i.e., the IP and LTCB prototype viruses were the same virus type.

Having failed in his efforts to convince Dr. Montagnier to accept responsibility for contaminating LAV with IIIb, in the Fall of 1984, Dr. Gallo abruptly changed tactics, and began asserting that LAV and IIIb were independent isolates. The most notable example of this claim was the unpublished molecular analysis paper, a paper Dr. Gallo initially told OSI was "never written." The molecular comparisons paper reported -- without substantiation -- that "LAV and HTLV-III are independent isolations of the same virus" (Emphasis added; Wong-Staal et al., unpublished manuscript).

Similarly, a letter to the journal Nature by the LTCB scientists claimed that "HTLV-III, LAV, and ARV [a third isolate named "AIDS-Related Virus,"] are variants of the same virus" (Ratner et al., Nature, 313, 1985, p. 636). The Nature letter also introduced the geographical/temporal proximity explanation for the identity of the IP and LTCB prototype viruses, i.e., the viruses were claimed to be so much alike,

"... because the individuals from whom these isolates were derived acquired the virus at a similar time and place" (op. cit., p. 637).

The negative consequences of this argument were profound. 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. Noted HIV geneticist Dr. Gerald Myers later decried the delay in scientists' understanding of HIV heterogeneity, a delay caused in part by Dr. Gallo's claims about the origins of "his virus," which Dr. Myers termed a "double fraud."

Dr. Myers wrote about these concerns to colleagues at the NIH National Institute Of Allergy and Infectious Diseases (NIAID). In 1987, Dr. Myers said this:

"... 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, p. 4).

"... 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; p. 2).

At the same time that he was publishing misleading accounts of the LTCB's own comparisons of the IP and LTCB viruses, Dr. Gallo went to considerable lengths to prevent scientists whom he knew had obtained the IP virus from using "his" virus and "his" cell line (see this section of the Subcommittee report) to make their own comparisons. When one group of scientists compared the LTCB and IP viruses and pronounced them genetically "identical," Dr. Gallo intervened to stop publication of an associated manuscript. The paper was delayed for almost one year, when a greatly watered-down version was published, in an obscure journal rather than the prestigious journal for which the paper was originally intended.

Dr. Gallo has attempted to divert attention from his withholding of his virus and cell line, and his imposition of restrictive conditions on their use, by citing the number of instances in which he did provide his laboratory materials to other scientists. The virus and cell line undoubtedly were provided to some scientists, but this in no way alters the reality that in other instances, the virus and cell line were withheld and/or their use, particularly for comparison experiments, greatly circumscribed. These events happened; they are well documented; they cannot be denied. Former NIH Director Dr. James Wyngaarden told Subcommittee staff these actions by Dr. Gallo were "clearly inappropriate"; the Richard Committee said the withholding of the uninfected cell line in particular was "essentially immoral in view of the growing seriousness of the AIDS epidemic."

Meanwhile, throughout the Summer of 1984, whenever any opportunity presented itself, Dr. Gallo made strenuous representations to the CDC and IP scientists that because (l) there was no virus in the sample he received from the IP in July 1983 and (2) the September IP virus was not grown beyond mere confirmation of its cell-killing effects, there was no possibility that the IP virus could have contaminated his cell lines. There were many such claims by Dr. Gallo (6/15/84 Gallo-to-Chermann letter; 6/28/84 Gallo-to-Francis telephone conversation; 8/24/84 Gallo-to-Chermann letter).

The last-named letter was particularly vivid. Here is what Dr. Gallo said to Dr. Chermann:

"... 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 ha