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.
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).
Dr. Gallo made similar statements even in his sworn declaration, submitted in response to the IP challenge to the Gallo et al. blood test patent. In the declaration, Dr. Gallo asserted that there was no "meaningful viral activity" in the first virus sample sent from the IP scientists. However, OSI found that this sample did grow and was used for several important experiments at the LTCB. Concerning the second sample, Dr. Gallo made a limited and greatly belated acknowledgement that his laboratory grew the IP virus, but Dr. Gallo said the growth of the IP virus at the LTCB was only "temporary." As confirmed by the OSI investigation, these statements were not true.
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 ..."
The PNAS paper included a detailed specification of the "minimum criteria used to identify new HTLV-III isolates." In addition, the paper asserted that,
"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).
Dr. Gallo made repeated references to his putative other isolates, particularly during the French/American dispute, when he included claims similar to those above in numerous memoranda and similar documents to HHS officials and attorneys. There was just one problem: the claims were not true, as Gallo himself admitted to Subcommittee staff, in 1993, when -- concerning the claim that he had 101 confirmed HIV isolates, including isolates dating from the Fall of 1982 -- Dr. Gallo said this:
"No one believed we really had that many isolates" and "No one believed we really meant that" (July 22, 1993 staff interview).
As for Dr. Gallo's claims that the RF isolate, because it was an alternative to the IP virus for use in the LTCB HIV blood test, was itself proof positive that there was no misappropriation -- these claims cannot be substantiated (see below for a review of the evidence). Even Dr. Gallo's attorney has finally conceded that RF was not ready to be used for an HIV antibody blood test (7/94 "Critique of Dr. Hadley's Response to Nicholas Wade's 'The Vindication of Robert Gallo'").
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 ..."
The real inventors of the HIV blood test were the IP scientists, who had developed and begun to use their blood test the previous Summer (1983). Dr. Gallo knew about the IP blood test. In fact, as early as September 1983, Dr. Gallo and his colleagues actually sent LTCB AIDS patients' samples to Paris to be assayed with the IP blood test.
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."
Shortly after the May 1985 issuance of the Gallo et al. blood test patent, attorneys for the IP came forward to register their strong concerns. The IP scientists had submitted a U.S. patent application for their HIV antibody blood test in December 1983, long before the application of Gallo et al. The IP attorneys argued that because of their filing priority, the IP scientists, not Gallo et al., should have been awarded the HIV antibody blood test patent. In addition, the IP attorneys asserted that Gallo et al. had used the IP virus to make their blood test, a clear violation of the non-commercialization agreement they signed upon receipt of the virus.
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."
Dr. Popovic's response to Dr. Fischinger's request concerning this major area of oversight was a nonresponse, a transparent evasion of Dr. Fischinger's request (see below). Even Dr. Fischinger should have recognized something was being withheld from him, something was amiss. But Dr. Fischinger, so far as is known, did nothing. He permitted his report to stand, a report containing the blanket assertion that,
"There is no evidence that material from any outside laboratory including the French was used in generating the HTLV-IIIb virus ..."
Based on the LTCB evasions and misrepresentations, HHS rejected IP's informal challenge. The matter soon thereafter moved into formal legal proceedings.
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).
A corollary argument was that Gallo et al. were not able to grow the IP virus; thus, there could not have been even an "innocent contamination," still less could the IP virus have been deliberately misappropriated. In case these arguments were not sufficient, the attorneys further argued that because Gallo et al. had numerous other HIV "isolates," they had no motive to misappropriate the IP virus.
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 Subcommittee investigation showed that the HHS/DOJ legal arguments could not be substantiated. The HHS attorneys themselves recognized that they were on very thin ice. In closed door discussions with their counterparts at DOJ, the HHS attorneys described their principal arguments as a "weak thread to rely on" and "a two-edged sword."
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 ..."
Impelled by these developments, in the Fall of 1986, HHS increased its efforts to obtain a settlement of the French/American dispute. A settlement was signed, in March 1987, but the settlement barely managed to paper over the glaring unresolved issues, and it began to unravel almost before the ink on the settlement was dry.
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.
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."
The Myers documents also showed that in early 1989, faced with the evidence, Dr. Gallo was about to "throw in the towel" and admit publicly that the LTCB and IP prototype viruses are genetically identical, with the LTCB virus derived from the IP virus. At the last minute, Dr. Gallo reneged on his commitment to make a public acknowledgment of the viruses' identity, and a year later, when the OSI inquiry was underway, he asserted repeatedly that the viruses could be genetically independent, and even if they were identical, the "contamination" could have occurred at the IP, rather than at the LTCB.
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."
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).
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.
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).
By United States law, a person is entitled to patent an invention unless,
"... 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 later invention that appears to differ somewhat from a prior invention is not patentable if the later invention is obvious from the earlier work:
"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.).
Because prior invention, use, or publication is a bar to a United States patent, applicants for a U.S. patent are required by law to disclose to PTO any information of which they are aware concerning such prior work. U.S. patent applicants thus are charged with duties of candor and full disclosure toward PTO, duties which U.S. courts have called "uncompromising" (Kansas Jack, Inc. v. Kuhn, 219 USPQ 857, 861 (1983).
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).
The PTO Manual says the duty of disclosure applies to information that "... a person ... 'knew or should have known' would be material ...," to "... material information they are aware of, or reasonably should have been aware of ..."
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).
The PTO Manual also specifies the consequences for a pending patent application in the event of fraud or violation of the duty of disclosure:
"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).
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 ..."
Gallo et al. affirmed, under penalty for making false statements, their duty,
"... to disclose information which is material to the examination of this application ... "
Dr. Gallo and his associates also signed this declaration at the conclusion of the patent 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."
More detailed, stringent declarations were made by Gallo et al. during the Summer of 1984, when they submitted several "CIP" (continuation-in-part) patent applications ("follow-up" applications to the parent blood test patent application). In these CIPs, Gallo et al. affirmed again that they believed themselves "... to be the original, first and joint inventors." In addition, again under penalty of criminal prosecution for making false statements, Gallo et al. declared, concerning the matter common to the parent and CIP blood test applications:
"... 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 ..."
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).
1. Knowledge of and Benefit from the IP Scientists' Work With Their Virus: The IP scientists were first to publish on the AIDS virus (Barre-Sinoussi et al., Science, May 1983). The LTCB scientists did not publish on the AIDS virus until nearly one year later; by the time they did so, the IP scientists had made numerous scientific presentations and published a number of scientific papers reporting additional work on the isolation, growth, and characterization of the virus.
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 examiner further said that
"... the methods taught by Barre-Sinoussi for the assay of LAV appear inherently to anticipate or render obvious the claimed methods drawn to assay of HTLV-III" (op. cit., p. 9).
The PTO examiner's realization of the significance of the IP scientists' work came only after the Gallo et al. blood test patent had already issued, too late for the IP work to be cited against that patent. By August 1986, once an "interference" had been declared between the Gallo patent and the IP blood test patent application, PTO was preparing to either suspend all the pending Gallo et al. CIPs or incorporate them into the interference. Either eventuality would have been significantly damaging to both HHS' patent program and HHS' position in the French/American dispute.
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 ... "
2. Knowledge and Use of the IP Blood Test: By mid-Summer 1983, the IP scientists had developed and were using a blood test, known as an "ELISA" (for "enzyme-linked immunosorbent assay") to test for antibodies to their new virus, by this time called "LAV" for "lymphadenopathy-associated virus." Dr. Gallo and his colleagues knew of the existence of this test. In fact, as early as September 2, 1983, LTCB scientist Dr. Marjorie Robert-Guroff sent a large panel of human blood samples to Dr. Montagnier to be assayed by the LAV test,
"... for specific reactivity against your AIDS virus-producing cells by immune fluorescence or against the AIDS virus antigens by your ELISA approach" (emphasis added).
At a scientific meeting in mid-September 1983, Dr. Montagnier presented initial results from the IP ELISA. Immediately after this meeting, the IP scientists submitted a patent application for their antibody blood test in Great Britain. An application for a United States patent, claiming the British priority date, was submitted on December 5, 1983.
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).
The CDC data demonstrated unequivocally that the IP blood test -- developed many months before the LTCB test -- could detect the presence of viral antibodies in AIDS and pre-AIDS patients, with a high degree of accuracy. Even more important, the CDC data, together with the extensive data already accumulated by the IP scientists, showed that the IP virus -- discovered long before the putative LTCB virus -- was the cause of AIDS. In fact, HHS officially pronounced this was so, in an April 1988 letter to the German publisher of a book critical of Dr. Gallo. The letter, written well after the French/American settlement was consummated, and signed by top HHS officials Dr. Robert Windom (the then-Assistant Secretary for Health) and Ronald Robertson (the then-General Counsel), said this:
"... in early 1984, under the auspices of the Centers for Disease Control in Atlanta, Georgia, a series of blind tests was undertaken to ascertain whether the sera from patients with AIDS contained antibodies to HIV. Of significance is the fact that both NCI and Pasteur participated in these tests. Each laboratory was provided with sera and asked to judge whether each specimen contained antibodies to the virus. The results of those tests unequivocally established that HTLV-III/LAV was the presumptive causative agent of AIDS."
But no information about the IP LAV blood test was disclosed to PTO by Gallo et al. when they submitted their patent applications, except as part of the single misleading reference noted above. Neither was there disclosure of an important paper by the IP scientists, published weeks before Gallo et al. submitted their patent applications. In this paper (Vilmer et al., The Lancet, 1984, pp. 753 - 757), the authors described the methods of the IP ELISA. Vilmer et al. also reported that antibodies to the core protein of their new retrovirus (by now there were a number of isolates besides the original LAV),
"... are widely distributed in the population at risk of AIDS ... " (p. 757 ) .
When the PTO examiner, again belatedly, learned of the existence of the Vilmer et al. paper, she cited it as prior art to Gallo et al. and used it to repeatedly reject claims in several Gallo et al. CIPs.
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."
The transfer agreement further bound the recipient,
"... not to disseminate the virus in any form (to companies or other scientists) without the prior written authorization of the Director of the Pasteur Institute."
Dr. Mikulas Popovic, a top LTCB scientist, signed the transfer agreement on September 23, 1983, affirming, in addition to the above, that the IP virus,
"... 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 LTCB scientists performed all their seminal HIV experiments with the IP virus isolate LAI, first identified as LAV, then as "MOV," and finally, as "HTLV-IIIb." Dr. Gallo and his colleagues assert that "MOV" and "IIIb" were genuine LTCB isolates that were accidentally contaminated with LAI. But aside from Gallo/Popovic's assertions, there is little or no evidence to substantiate that MOV and IIIb ever were anything other than LAI (see below).
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).
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.
Subsequently, when suspicions were voiced that the LTCB's putative "prototype" HIV isolate, "IIIb," actually was the IP virus, Dr. Gallo not only denied this was so, he denied it was even possible, because, he said, the IP virus either could not be grown, or was grown no more than "transiently" at the LTCB. But during the OSI investigation, Dr. Gallo acknowledged that these assertions were not true:
"... 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).
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).
Even LAV could be used for the LTCB blood test; the transfer agreement Dr. Popovic signed when he received the IP virus did not proscribe such use. What was proscribed was commercialization (i.e., patenting/licensing) of the virus.
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).
(b) LAI as "IIIb":
- 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 ) .
2. Dr. Popovic's Plea for "RF": At the point the decision was made to proceed with patenting and commercialization of the LTCB blood test, Dr. Popovic raised strong objections to use of the "pool" virus for the LTCB HIV blood test, arguing instead for another HIV isolate called "RF." That Dr. Popovic objected to "IIIb" at this particular juncture is highly revealing. "IIIb" reportedly had been in use for the LTCB blood test for several weeks; it was sent to an LTCB contractor for large-scale production some weeks earlier. "IIIb" had been used to generate most or all of the blood test data reported in the LTCB papers that would be published in Science in May 1984. Dr. Popovic objected to none of this. But suddenly, by his own account, at the point a "IIIb" blood test was about to be patented and commercialized, Dr. Popovic became acutely anxious about the "origins" of the virus supposedly used for the test.
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 denied any awareness that Dr. Popovic's plea for RF over IIIb might have derived from his (Popovic's) concerns that IIIb was (or might be) the IP virus; Dr. Gallo asserted strongly that Dr. Popovic did not explicitly voice such concerns. However, it is difficult to accept that Dr. Gallo did not discern at least the possibility that IIIb might be the IP virus, given the coincidence in time of Dr. Popovic's voicing of his concerns about the "origins" of IIIb and his (Gallo's) reading and rewriting of Dr. Popovic's manuscript reporting growth and use of the IP virus (see below, pp. %%36-37). Because Dr. Popovic refused repeated requests that he appear for a staff interview, it was not possible for the Subcommittee to question him further about these matters.
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).
On another occasion, Dr. Gallo said this:
"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).
But there were two major problems with the possible use of RF for the LTCB blood test. First, contrary to Dr. Gallo's repeated assertions, RF was not ready to be used, and there could be no certainty about when it would be ready and (2) there was no time for delay.
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).
Dr. Popovic told OSI he believed he could have achieved large-scale, high titre production of RF, but he made clear how long this would take:
"... 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).
LTCB records for RF subsequent to Dr. Gallo's decision to use "IIIB" for the blood test show that Dr. Popovic's four-weeks estimate for preparation of RF was overly optimistic. RF was not put into the LTCB's best-growing cell line until late-June 1984, and when it was, the culture failed and had to be restarted the following month. RF was not sent for large-scale production until at least late-November 1984, at which time Dr. Popovic was still trying to boost its titre to the levels "IIIb" reached the previous Winter. RF was not sent to the commercial production facility until "well after" "IIIb," and according to Dr. Larry Arthur, the scientist at the facility who oversaw the growth of these isolates, RF,
"... was a lower producer than the IIIb in our hands" (1/28/91 OSI interview; transcript p. 29).
4. There Was No Time for Delay: Dr. Gallo frequently invoked RF and his putative "other isolates" to argue that he had no motive to deliberately use the IP virus for the LTCB blood test. In so doing, Dr. Gallo greatly overstated the "readiness" of RF and ignored or significantly understated the time that would have been required to ready RF (or any other isolate) for use. Here are examples of Dr. Gallo's statements to OSI in this regard:
"... 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).
Most recently, Dr. Gallo's attorney modified his stance concerning the putative "readiness" of RF, saying RF "could have been made ready for use" in the LTCB blood test" (emphasis added; 7/94 Critique of Dr. Hadley's Response to Nicholas Wade's "The Vindication of Robert Gallo"). But "could have been made ready" was not good enough. Time was of the essence, and Dr. Gallo, by his own account, would not wait for RF, because, he said,
"... it is a few weeks behind. Why make any delay" (12/2/90 OSI interview; transcript p. 102).
Because time was of the essence, in reality there was no choice. Events in motion -- many of them initiated by Dr. Gallo himself -- made it essential to move with all possible speed with the LTCB blood test, using the only virus ready to be used: LAI/"IIIb". Among these events were the following:
- 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.
Whatever the reason for Gallo's advancing the submission date, according to Dr. Popovic, this event in and of itself committed the LTCB scientists to "IIIb" as the LTCB prototype, including its use in the LTCB HIV antibody blood test. Concerning this matter, Dr. Popovic said that advancing the submission date of the papers meant his paper would have,
"... to focus on HTLV-IIIb as a prototype instead of the RF isolate whose origin was more certain" (12/1/90 OSI interview; transcript p. 8)
and
"At that time when we had to go ahead, the best was IIIb and practically it was not difficult to choose whether IIIb or RF would be ... but for sure his [Gallo's] choice was IIIb ... that time what we have the best, we go ahead. That was a decision" (op. cit., pp. 115 - 116).
In light of the numerous disclosures and commitments that had been made, in light of the potential loss of foreign filing rights if the U.S. patent application was delayed, it clearly would have been unthinkable for Dr. Gallo to have suddenly announced a delay of a month or more while he and his associates started over their blood test work, using a virus isolate whose origins were "more certain" than the isolate he originally chose.
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).
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).
Dr. Gallo minimized Dr. Popovic's objections to his (Gallo's) revisions to the paper. Dr. Gallo told OSI,
"... 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).
But Dr. Popovic described a "major disagreement" with Dr. Gallo, in which,
"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).
The manuscript drafts make clear the extent to which Dr. Popovic's work indeed was compromised. In the early drafts of this paper, writing about his experiments with the IP virus (referred to as "LAV"), Dr. Popovic made it clear he considered the IP virus to be functionally the same as the LTCB "HTLV-III" (HIV) isolates. Dr. Popovic wrote that,
"LAV is described here as HTLV-III"
and
"LAV as a reference virus ... had been used in the first series of experiments."
Dr. Gallo struck both of these statements from the manuscript, writing to Dr. Popovic in the margins of the paper, "I just don't believe it. You are absolutely incredible" and "Mika you are crazy." Dr. Gallo then rewrote the methods of Dr. Popovic's early experiments to make it appear they were performed with an LTCB isolate (not specifically identified). Dr. Gallo also wrote a new ending for the paper, which included the assertion that,
"... HTLV-III and LAV may be different ... "
Yet the LTCB laboratory data show -- and Dr. Gallo acknowledged to OSI -- that by the time he wrote that the viruses "may be different," the LTCB scientists knew the viruses were, at least, "of the same virus type" (Gallo 4/17/90 submission to OSI). And in an OSI interview, Dr. Gallo acknowledged this:
"... 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).
Dr. Gallo also added an unqualified assertion to the conclusion of the Popovic et al. paper that the IP virus,
"... has not yet been transmitted to a permanently growing cell line ..."
But Dr. Gallo knew Dr. Popovic had grown LAV in permanent cell lines, as evidenced by his (Gallo's) admitted order to Popovic to freeze them. In fact, Dr. Gallo himself wrote in an early draft of the Popovic paper that,
"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."
This sentence was deleted from the Popovic et al. manuscript shortly before the claim that LAV had "not yet been transmitted to a permanently growing cell line" was added.
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).
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."
There is no indication that at the time she made these claims, Secretary Heckler believed they were anything but true. But the HHS press conference -- which journalists variously described as "the 'splashiest announcement' in the AIDS saga," "a zoo," and "primarily politically motivated," obviously marked the occasion when HHS claimed the accomplishments of Gallo et al. as accomplishments of the United States itself. This made it essential that HHS defend the claims when the accomplishments were challenged, as happened shortly thereafter. This is precisely what happened.
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).
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).
The "Discussion" section of the paper said the data reported in the paper,
"... demonstrates that LAV and HTLV-III are antigenically identical" (op. cit., p. 6).
No disclosure of any of these results was made by Gallo et al. to PTO, where at the same time the paper was being drafted, the Gallo et al. blood test patent application was being examined. Notably, PTO rules specify that,
"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).
Moreover, Gallo et al. submitted the two blood test CIP applications referenced above well after the principal data in the proteins paper were obtained, again with no mention of those data. And in his 1986 sworn declaration Dr. Gallo affirmed that up through the allowance of the Gallo et al. blood test patent (variously dated to November 1984 - May 1985) he saw no evidence that LAV was the cause of AIDS.
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.)
Dr. Brandt, who ordered the comparison of the viruses, told Subcommittee staff he was never told about the molecular comparisons of the viruses; yet NCI Director Dr. Vincent DeVita forwarded a note to Dr. Brandt reporting the results of the comparison. Dr. DeVita told Subcommittee staff he was sure his note went to Dr. Brandt's office, but according to DeVita,
"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).
A frustrated Dr. Brandt issued one directive after another demanding "a definitive statement on the identity (or otherwise) of LAV and HTLV-III." Dr. Brandt noted that, "In April, he [Dr. Gallo] promised this publicly within 30 days," and Brandt admonished Gallo to give him a report "with scientific content, not only reasons for delay" (8/9/84 Fischinger-to-Brandt memorandum; p. 1).
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).
Another part of the story propounded by Dr. Gallo and his closest associate, Dr. Flossie Wong-Staal, was that the several clones of "IIIb," obviously very similar in genetic make-up, were derived from multiple independent samples allegedly used for the "IIIb" experiment. Using this argument, Dr. Gallo et al. attempted, by extrapolation, to make the case that the striking similarity of the IP and LTCB prototype viruses did not preclude the possibility that these actually were independent isolates.
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).
In 1989, writing to Dr. Anthony Fauci, NIAID Director and Director of the NIH Office of AIDS Research, Dr. Myers said this:
"... I remained deeply disturbed about the claim made for the IIIb viruses ... that they derived from pooled blood of several patients. It was very difficult in 1987 to convince many researchers that the AIDS viruses mutated inordinately rapidly. The IIIb interpretation gave the false impression that the virus was more stable than other signs were indicating" (4/12/89 Myers-to-Fauci; p. 2).
(See above for additional information about Dr. Myers' correspondence relating to the work of Gallo et al.)
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 have been doing for you, not us ... Second, clearly we would be accused by many of cross-contamination, i.e., we would run the risk of not being able to convince the 'tough' that we had independent isolates" (p. 3).
These events set the stage for the HHS cover-up that began in August 1985.
In May 1985, the USPTO awarded a patent on the HIV antibody blood test to Dr. Gallo and his colleagues. The Gallo et al. patent was issued in record time, just thirteen months and one Office Action after it was submitted. At the time the Gallo et al. patent issued, the IP patent application, submitted over four months prior to the submission of the Gallo et al. patent application, had not been touched. PTO assigned the Gallo et al. application to a low-workload unit, while the IP application remained in a heavily backlogged unit. The differential handling of two applications for the same invention has never been satisfactorily explained; the consequences in disadvantaging the IP application are clear.
The IP application was passed among four different examiners; consequently, the application had never been "briefed," i.e., there was no PTO record of the IP claims. When the PTO examiner of the Gallo et al. application conducted an "interference search" just prior to issuing Gallo et al., she found no record of competing claims. According to the examiner, when she first saw the IP application, within two weeks of issuing Gallo et al., she recognized immediately that PTO had "screwed up" in issuing the Gallo et al. patent. The examiner told Subcommittee staff she recognized that the Gallo and Montagnier inventions were "directly related." The examiner also said that had she become aware of the IP application during her examination of Gallo et al., she would have suspended examination of Gallo et al. and "... would have thrown them into an interference."
But by the time the examiner saw the Montagnier et al. application, the Gallo et al. patent had already been issued. Consequently, the burden of seeking an interference fell on the true inventors of the HIV antibody blood test, Montagnier et al.
Once they learned about the issuance of the Gallo et al. blood test patent, IP representatives demanded a meeting with HHS officials, to express their outrage and present their demands for relief. During an early-August 1985 meeting with HHS, chaired by Dr. Lowell Harmison, IP representatives charged that Dr. Gallo and his colleagues, "... either knowingly or mistakenly appropriated Dr. Montagnier's invention." The IP representatives asserted they had cause for action relating to a variety of claims; they demanded formal recognition that Dr. Montagnier and his colleagues were the true inventors of the HIV antibody test kit, a share of all past and future royalties from the sale of the test kit, and reissuance of the Gallo et al. patent, with Montagnier et al. listed as the inventors, or at least joint inventors with Gallo et al.
Drs. Lowell Harmison and Peter Fischinger played key roles in HHS' response to the IP challenge, during the early phases of the dispute. Following the meeting with IP representatives, Harmison commissioned Fischinger to "investigate" the validity of the NCI scientists' claims and produce a definitive report. But the NCI investigation was a sham, for according to testimony from key HHS, NIH, and NCI officials, their minds were already made up: the IP challenge was "an outrage"; "everyone believed Gallo et al. had done the work themselves" and "we couldn't even grow LAV, of course we didn't use it ..."
Dr. Fischinger's "investigation" also was fatally flawed in terms of its procedures. The investigation, completed in just a few weeks, was performed by a single individual who, as a top NCI official, had a significant investment in a favorable outcome. The investigation relied exclusively on Dr. Gallo and his associates for "the facts." The selected "facts" and "evidence" produced by Gallo et al. (via a series of memoranda and data sets examined in detail by Subcommittee staff) were uncritically incorporated -- often nearly verbatim -- into Dr. Fischinger's reports. Contrary facts and evidence were neither sought nor examined. When contrary evidence nonetheless appeared, it was ignored or suppressed. The selective nature of what Dr. Fischinger received from the LTCB scientists is seen in the fact that among the approximately 100 data pages provided to Fischinger by Dr. Popovic, only one page mentioned "LAV," and that page contained no experimental results.
The Fischinger Report included, among many, the following demonstrably false claims:
- "Dr. Gallo and his laboratory were the first to identify the virus and to describe the blood antibody test";
- "Based on the examination of raw data from Gallo's laboratory between June 1983 and September 1983, it can be unequivocally stated that they had ample isolates of typical HTLV-III for use as prototype infectious agents";
- July LAV "did not contain any infectious LAV virus";
- "... recent DNA sequence data show that exceedingly closely matched pairs of viruses have been isolated from different individuals. These pairs are as close as, or closer in relationship than LAV is to HTLV-IIIb";
- "There is no evidence that material from any outside laboratory including the French was used in generating the HTLV-IIIb virus ... It is clear from other sections of this document that LAV was not used in generating the HTLV-IIIb virus strain advertently or inadvertently."
Dr. Fischinger attempted to ensure that responsibility for the accuracy of his report rested not on him, but on Dr. Gallo. Fischinger told Subcommittee staff that,
"My major point of discussion was Bob. No question about that ... I was listening to him as the point person ...
"Bob sort of swears that this is the way it is, and the laboratory data sort of generally support it ... Then, that's going to be his, sort of, ultimate responsibility" (8/6/93 interview).
In the introduction to his report, Dr. Fischinger stated that it was,
"... sent to Dr. Gallo to determine that it was accurate in both its content and interpretation."
And Fischinger required Gallo to sign a "concurrence" statement that said the report,
"... has been reviewed by me relative to the fidelity of specific information presented as well as the accuracy of its interpretation. These data are substantiated by entries in the notebooks, as well as by other records emanating from the Laboratory of Tumor Cell Biology, NCI."
Curiously, after Peter Fischinger prepared the first draft of his report, containing all of the above conclusions, he wrote a memorandum to Dr. Gallo, a secret memorandum never revealed prior to the Subcommittee investigation, and not provided to the Subcommittee until nearly two years after its initial document request. In this August 23, 1985 memorandum, Fischinger told Gallo that despite Gallo's memoranda and data submissions, there were "three major areas of oversight .. which have to be completed." These areas were as follows:
- "the derivation of the H9 cell line traced to its parental origins ..."
- the "exact sequences and timing of the events which led to the virus-producing line HTLV-IIIb..." and
- "the first time when ELISAs or Western blots [different kinds of blood tests] were attempted on any HTLV-III type isolate ..."
Concerning the request for information about the "events which led ... to HTLV-IIIb," Dr. Fischinger said, "This is considered to be .. very critical." Dr. Fischinger specified a further requirement:
"We would like a written statement from Dr. Popovic, and whoever else partook in the development of the HTLV-IIIb line, that LAV was never used in any connection in that complex infection sequence which led to the isolation of the HTLV-IIIb line."
Dr. Popovic prepared the response to the August 23 memorandum. The response contained numerous unsubstantiable claims. Particularly noteworthy was Dr. Popovic's evasive response to Dr. Fischinger's requirement for a statement concerning non-use of LAV in the "isolation" of IIIb:
"The development of H9/HTLV-IIIb was almost entirely confined to the tissue culture room 6B03A where no LAV was ever used" (emphasis in original; 9/6/85 Popovic-to-Gallo memorandum; p. 2).
The significant qualifications embodied in this affirmation are obvious. Equally clear is that Dr. Popovic did not give Dr. Fischinger the assurance he sought, namely, that LAV was not used to isolate IIIb. Yet there is no evidence that Dr. Fischinger followed up with any further inquiry; and by September 6, when Dr. Popovic wrote his response, the Fischinger Report was already receiving its final approvals at HHS.
At least one top HHS attorney, Darrel Grinstead, had concerns about the Fischinger report, because, in part, the report failed to deal with the central issue of whether NCI developed the HIV blood test prior to the filing date of the IP patent application (September 1983). Grinstead wrote Lowell Harmison about his concerns, saying this:
"... my initialing of this report should not be interpreted as an indication to you ... or other officials in the Department that I am fully comfortable that the Department would prevail if the French were to proceed to press their claims through litigation."
At the same time the Fischinger Report was getting its final sign-offs, Lowell Harmison was obtaining hard evidence from NIH and CDC scientists that (l) the IP and LTCB prototype viruses almost certainly were genetically identical, with the LTCB virus derived from the IP, and (2) the IP scientists were not only the discoverers of the AIDS virus, but also the inventors of the virus antibody blood test.
The revelation of this evidence from within HHS, strongly supportive of the IP claims and damning to the claims of Gallo et al., should, at a minimum, have led to a genuinely objective examination of the claims of Gallo et al. The evidence was highly credible. Concerning the genetic identity of the viruses, the evidence comprised detailed memoranda, plus numerous pages of data from the NIH laboratory of retrovirologist and laboratory chief Dr. Malcolm Martin. The Martin documents -- which vanished from HHS' official files and were withheld from the Subcommittee for nearly two years -- showed the presence in the IP virus of a marker found in only one other isolate, "IIIb," a finding that one top NIH official reportedly said was "very hard to get around."
Dr. Martin also told Harmison about a forthcoming article in Science which was to demonstrate the diversity of numerous HIV isolates, with the notable exception of IIIb and LAV. Martin told Harmison,
"We offer no explanation for the similarity of HTLV-III and LAV, but informed virologists will certainly draw certain obvious conclusions" (9/6/85 Martin-to-Harmison memorandum; p. 3).
In the case of the CDC scientists, who worked with the IP scientists on AIDS research since 1983, the evidence included the comparative blood test data, plus, according to one CDC scientist present at a September 6 meeting with Harmison and HHS attorney Richard Riseberg,
"... a full trip through the record, the chronology, with no holds barred. All the data were described" (Chicago Tribune, December 31, 1991 ) .
Notes of another CDC participant say this scientist,
"... gave the whole BOW [ball of wax] about French, about Gallo trying to steamroll, about possibility LAV = HTLV-III."
But no objective inquiry took place at HHS. What actually happened was that Peter Fischinger provided Dr. Gallo with an opportunity to respond to the Martin and CDC data. A September 23, 1985 memorandum from Gallo to Fischinger, containing numerous unsubstantiable assertions, resulted. Notably, although Dr. Gallo later would tell OSI that the Martin data convinced him that there had been "a contamination" of "IIIb" with LAV, at the LTCB, Gallo's 1985 memorandum to Dr. Fischinger dismissed Martin's data and memoranda as an "unfortunate innuendo."
With this, HHS' "fact-finding" efforts were shut down. And on September 6, 1985, the same day Harmison and Riseberg visited CDC, HHS wrote the IP that HHS found,
"... no basis to support your position that ... [the Gallo et al. blood test patent] is invalid or that the actions you requested be taken by the Department are warranted."
As for the Fischinger report, along with the several memoranda produced by Drs. Gallo and Popovic, it became a template for much of the U.S. Government defense of Gallo et al. In January 1986, shortly after the IP filed its first lawsuit, the Fischinger Report was forwarded by HHS to DOJ, as support for HHS' assertion that the IP claims were "without merit." The DOJ attorney who was lead counsel for the U.S. defense of Gallo et al. told investigators that in pursuing that defense, he relied heavily on the report.
Following his receipt of the clearly problematic scientific evidence, Lowell Harmison sought advice from outside patent attorneys about the ability of the Gallo et al. patent to withstand a formal challenge. Even the most favorable of these opinions, based on "short study of less than one week," plus a "lengthy telephone conversation with Dr. Gallo," concluded that if the IP was able to provide an interference at PTO, "we cannot at this point say what would be left of the Gallo et al. patent."
NIH's own patent attorney produced his own opinion, the most negative of the opinions provided to Harmison. Attorney Leroy Randall told Harmison it was his opinion that the IP would be able to "copy the claims" of Gallo et al., with the exception of a single claim (the claim relating to the HIV "envelope protein") which, Randall said,
"... would remain ours, following any interference."
Thus, by November 1985, both on the legal front and the scientific front, the case for Gallo et al. was in considerable doubt. But instead of addressing the question, "should we defend the Gallo patent?" the concern for HHS officials, at all times, was "how shall we defend the patent?" Thus, according to the testimony of several witnesses, as HHS began to comprehend that the LTCB scientists' claims could not be substantiated, HHS officials still determined to actively defend those claims for as long as possible, by whatever means was possible, while at the same time they negotiated a settlement as favorable as possible to HHS and United States.
Testimony from HHS officials, as well as attorneys' notes and related documents show that HHS officials were not entirely confident in Dr. Gallo's assurances that he did not use the IP virus; consequently, HHS was not confident the United States would win if it came to a showdown. One individual who was privy to many behind-the-scenes meetings and discussions relating to the dispute, said this:
"There was a general impression that we wouldn't win, because Gallo lacked documentation to show there was no use of the French virus, and thus could not refute the main French accusations."
Confirmation of the lack of confidence in Dr. Gallo's claims came from Dr. James Mason, at the time the HHS Acting Assistant Secretary for Health (and Dr. Harmison's boss). In an October 2, 1985 memorandum to Secretary Margaret Heckler, Dr. Mason rated the odds of the U.S. prevailing at only "60/40." Dr. Mason told Subcommittee staff that some time after he left HHS headquarters, he asked HHS Deputy General Counsel Robert Charrow about the reason for the settlement. Charrow, who led HHS' defense of Gallo et al. beginning in 1986, reportedly told Dr. Mason that,
"Gallo's laboratory notebooks were in such disarray, we were not sure we could defend the position."
Despite these doubts, HHS determined to "play out" the defense of Gallo et al. as far as possible, meanwhile disadvantaging the IP to the greatest extent, and if it appeared a settlement could be obtained in which the United States would share in the credit, to take it.
1. Defensive Tactics: As early as late-1985, HHS attorneys were drafting successive versions of a settlement agreement, including at one point, a multi-million dollar cash payment to the IP. Attorneys' notes examined by Subcommittee staff show that HHS attorneys were concerned with avoiding the impression such a payout was an "admission of culpability." Presumably this is the same reason HHS had such difficulty agreeing to a reallocation of the royalties in 1994 (see below).
During 1986, as the Claims Court suit progressed and the PTO interference got under way, the HHS/DOJ attorneys struggled to craft a litigation strategy that fell somewhere between the truth and the law. Notes of a crucial "Lawyers Meeting," on April 8, 1986, referred to what the participants described as the "two-edged sword" that confronted the U.S. Government with respect to the identity of the IP and LTCB viruses. On the one hand, to refute the claim of derivation of the Gallo invention from the IP invention, the U.S. attorneys needed to argue that the IP and LTCB viruses were different. (At one meeting, HHS attorneys called this a "weak thread to rely on.")
But this argument had the potential to damage the case of Gallo et al. at PTO because, according to the April 8 meeting notes,
"... saying there are two viruses ... would substantially narrow the scope of the patent to make it almost useless. Narrowing claims may make the patent unenforceable ..."
In late-April 1986, when PTO declared an interference between Gallo and Montagnier, it named Montagnier et al. as the "Senior Party," formal recognition that the IP application was submitted first. More importantly, for purposes of the interference proceeding, PTO defined the invention as the blood test itself. This key determination seriously undercut the U.S. Government's main argument in defense of Gallo et al., namely, that the Gallo et al. blood test was a different invention from the IP blood test because the Gallo test used virus from a permanent cell line. These PTO rulings were widely regarded as favorable to the IP cause.
The U.S. Government attorneys then decided to attempt the argument that Gallo et al. invented before Montagnier et al. The lawyers indicated that for this argument to succeed, one essential element was proof that Gallo et al. isolated the AIDS virus before the IP scientists did so, i.e., in 1982. No such proof existed, but that did not stop the attorneys from trying to manufacture it. Thus, in May 1986, when Gallo et al. published a letter to the journal Nature concerning their putative "early isolates," HHS and DOJ attorneys had significant input into its contents.
The Nature letter was written as a hasty rebuttal to the highly negative publicity associated with what the media called the "acutely embarrassing" revelation in March/April 1986 that a virus EM published by Gallo et al. in 1984, identified as an EM of "HTLV-III," actually was an EM of the IP virus. HHS and particularly, DOJ attorneys played a significant role in preparation of the Nature letter. DOJ attorney Thomas Byrnes edited Dr. Gallo's letter, adding a significant assertion that could not be substantiated, i.e., the claim that,
"The experimental results shown were obtained shortly after receipt of the samples, usually a matter of weeks" (Gallo et al., Nature, 321, 1986, p. 119).
In addition, in a cover letter to Dr. Gallo, Byrnes made clear why "early isolates" and early dates of experimental results were so important to the U.S. Government case:
"The dates set forth in this letter will be perceived as our earliest dates; for this reason the dates must be as early as possible. Another sample before September 1983 showing by EM the presence of an HTLV-III particle would be highly desirable."
No pre-September HIV EM was ever produced, for the simple reason that none existed. (Similarly, in late-Summer 1986, when PTO sought laboratory notes from Dr. Popovic pre-dating the IP priority dates, no data were produced.) The single example in the Nature letter of an alleged February 1983 HIV EM was significantly misleading. The EM was not even made until May 1983; the putative HIV particles were not identified until December 1985; and HIV was not isolated from the sample until 1986.
2. Offensive Tactics: Meanwhile, as the U.S. Government attorneys scrambled vainly trying to find evidence that the LTCB scientists' "invention" predated that of the IP, while they argued vehemently in court papers that the LTCB and IP viruses were not and could not be the same, the attorneys also planned and, in several instances, actually carried out a number of offensive actions against the IP and its supposed allies.
The most significant of the actions of U.S. officials and attorneys concerned their thwarting of the IP's discovery/Freedom of Information Act (FOIA) document requests. U.S. attorneys argued strenuously in the Claims Court that the IP should not be able to obtain documents under discovery, because this would be duplicative of document production under the FOIA. Yet at the same time, the U.S. Government seriously delayed and obstructed document production under FOIA, until IP attorneys filed suit to compel production.
The Subcommittee staff's review of the IP court papers, plus detailed review of the documents IP received under FOIA showed the following:
- HHS produced fewer than half the documents it originally estimated were responsive to the IP FOIA request, and only after significant delays; numerous material, responsive documents were withheld. Often, the very existence of these documents was not disclosed to the IP attorneys, although such disclosure is required by the FOIA. Among the most significant withheld documents were the memoranda and data showing the genetic identity of the IP and LTCB viruses, provided by Malcolm Martin to Lowell Harmison, the records relating to the development of the LTCB HIV blood test, and the drafts of the Popovic et al. paper, showing the significant use of LAV at the LTCB.
- Documents were produced in a scattered, haphazard fashion, with documents from several different LTCB scientists co-mingled, in no particular order, and without regard to dates.
- Many documents were copied in such a manner that they were entirely illegible. When the IP attorneys sought access to the originals of these documents, they were denied.
- Key entries in laboratory notes and related documents that would have undercut the U.S. position were whited out or otherwise obscured, with the result that highly significant data showing the success of the LTCB in growing LAV in permanent cell lines were eliminated (for details see above).
The information deficit resulting from the U.S. Government's abuse of the IP's FOIA request significantly disadvantaged the IP in its efforts to confirm its suspicions and learn the truth about the LTCB scientists' research. IP attorneys told Subcommittee staff that had they -- in 1986-87 -- possessed information wrongfully withheld from them that has only recently come to light, they would never have entered into the 1987 settlement with the U.S. Government.
In addition to obstructing the flow of information to the IP, the U.S. Government also contemplated a variety of other strategies to disadvantage the IP and its blood test. Among the actions that were considered, and recorded in U.S. attorneys' notes, were the following:
- Hindering the U.S. manufacturer of the IP blood test (Genetic Systems, Inc., [GS]) by extraordinary, stringent enforcement of import restrictions on the IP virus;
- Suing GS for infringement of the Gallo et al. patent;
- Adding Dr. Gallo as an inventor to a generic blood test patent application, an application submitted prior to the IP patent application, and thus that would have patent priority. When the named inventors of this test indicated they would expect reciprocity by being added to the Gallo et al. patent, this idea was quickly dropped.
- Surreptitiously monitoring and recording conversations of U.S. Government employees believed to be communicating with the IP attorneys. DOJ told HHS this was a "hot potato," and urged "extreme care." It is not known if the surveillance was actually carried out.
- Lobbying against the GS blood test at FDA, even though HHS officials knew the GS test was superior to those manufactured under the Gallo patent. Notes of HHS attorneys show they actually considered whether U.S. manufacturers might somehow adopt the technology of the GS kit.
1. Origins of the Misinformation: Dr. Gallo has frequently asserted that he is not responsible for the contents of the U.S. Government pleadings, even his own sworn declaration, on grounds that the attorneys created the documents, and that he was guided by their instructions to him. But the attorneys gave very different accounts to Subcommittee staff, saying they relied entirely on Dr. Gallo and to a lesser extent, his subordinates, for their information. An outside contract attorney put it this way:
"Believe me, I didn't know enough to lie."
The attorneys said they asked Dr. Gallo if he had data to support his claims, and invariably, they were assured that he did. No one, it appears, demanded proof. As one U.S. Government attorney said,
"Here's this guy, almost a Nobel prize winner, you walk in his office and see all these awards all over his walls -- if he tells us he did something, are we going to question it?"
The significance of Dr. Gallo's personal involvement in the preparation of motions in the PTO interference is documented in motions for extensions of time filed by the U.S. Government, during the Summer of 1986. In these motions, the U.S. Government attorneys described Dr. Gallo's extensive travel schedule, and they asked for additional time to consult with Dr. Gallo because,
"The complex nature of the subject matter of this interference and the voluminous experimental work which led to the development of the patented invention also require the personal participation of Dr. Robert C. Gallo ... Only Dr. Gallo is thoroughly familiar with the records relating to these developments and with the details of any communications with Institut Pasteur ... "
Referring to "new information which may have an important bearing" on the contents of the U.S. Government's filings, the attorneys said this information needed further investigation and,
"... the personal assistance of Dr. Gallo is of the utmost importance in pursuing these investigations" (June 30, 1986 motion for extension of time; pp. 3 - 5).
2. The Misinformation: The U.S. Government pleadings, particularly those in the Claims Court and at PTO, contain numerous misleading claims. They also reflect numerous material omissions. The misinformation and material omissions are traceable directly to documents and statements prepared by Dr. Gallo and his LTCB colleagues, including numerous statements in the scientific literature, and documents and statements originating with Dr. Gallo's NCI and HHS superiors, including but not limited to Drs. Peter Fischinger and Lowell Harmison.
Variations of the principal items of misinformation appeared in numerous legal pleadings. The following are examples of the most egregious such items, with a brief reference to the information that demonstrates their falsity.
- "In late l982 - early 1983, [Gallo] obtained a number of viral isolates including HTLV-III" (Opposition of Gallo et al. to the Motion of Montagnier et al. for Judgment; p. A8); (The LTCB scientists never tested any 1982 sample to confirm that it contained HIV; Dr. Gallo personally acknowledged this to Subcommittee staff. Thus, there was no evidence to substantiate that the claim of 1982 HIV isolates was true.)
- " ... in February 1983, a further detection of the virus which would later be called HTLV-III was made which this time included electron microscopy as well as RT ..." (Gallo declaration; p. 1; appended to the U.S. Government motion above); (No EM of HIV was made at the LTCB in February 1983; the earliest EM, from May 1983, was not known to contain HIV-like particles until December 1985; see above).
- Upon examination of the July LAV sample, "... no virus was found in this sample and it appears that virus initially present may have been killed in transit" (Opposition of Gallo et al. ..., p. A12); (by Gallo/ Popovic's own subsequent admissions, the July LAV sample was used for a number of significant experiments that confirmed the presence of virus associated with pre-AIDS and AIDS; see above).
- "The receipt of sera (sic) by Gallo from Montagnier taken from the patient [BRU] ... is ... of no significance ... there is no evidence to indicate that the sera (sic) contained any antibodies to the AIDS virus" (op. cit., p. A13); (BRU serum was used for months at the LTCB to test virus cultures for the presence of the suspected AIDS virus. The BRU serum was the only serum the LTCB scientists possessed that reacted specifically with AIDS samples).
- Concerning the IP virus received at the LTCB in September 1983, "Dr. Popovic did succeed in temporarily transmitting LAV to a cell line called HUT-78 and one other T-cell line. However, both transmissions were only temporary in nature" (Gallo declaration; p. 11); (By Dr. Gallo's own admission to OSI, growth of LAV at the LTCB was "significant and continuous"; see p. %%25).
- "At no time prior to the filing of the Gallo application was it appreciated by anyone that LAV and HTLV-III were the same or even similar viruses" (Opposition of Gallo et al.... p. A22); "... there was no recognition by Gallo, Montagnier or anyone else of such similarity ... In fact, there was every reason to believe that the two compositions are substantially different (op. cit., p. 4); (Numerous pieces of evidence show that these statements are false. The evidence includes Dr. Gallo' s contemporaneous statements, as well as his admissions to OSI, plus Dr. Popovic's account of his own experiments, in the draft of Popovic et al. see above).
- "... I was satisfied that HTLV-III had been proven to be the cause of AIDS, but I saw no evidence of this for LAV up through the allowance of the Gallo patents (Gallo declaration; p. 14); (Dr. Gallo's own papers [particularly the collaborative manuscripts dating from the Summer of 1984] plus numerous other items [e.g., Feorino et al., Science, July 6, 1984; Morbidity and Mortality Weekly Report, July 13, 1984; T. Beardsley, Nature, July 19, 1984; Cheingsong-Popov et al., The Lancet, September 1, 1984] show that at the specified time, LAV was widely recognized as the cause of AIDS).
- "Neither of these inventions [the Gallo et al blood test and cell line] depended on or is derived from LAV. Isolates of the virus that is responsible for AIDS were available from many sources, and, in fact, it was from these independently established isolates that HTLV-III was found" (6/11/86 Defendant's Motion for Summary Judgment; pp. 8 - 9); (The Gallo et al. blood test "invention" benefitted significantly from the IP and LTCB's scientists' work with LAV, not to mention the LTCB scientists' actual use of LAI/LAV to make their own test; see above).
- "The scientific evidence is clear that HTLV-III and LAV are not so similar that HTLV-III can be said to be the progeny of LAV" (Defendant's Reply to Plaintiff's Memorandum in Opposition to Defendant' s Motion to Dismiss the Complaint; p. 6); (There was no scientific basis for this claim; by his own admission, as early as the Summer of 1984, Dr. Gallo believed his virus and the IP virus were derived from the same source; by 1985, HHS was aware that Dr. Martin' s data showed "IIIb" was derived from LAI/LAV. Dr. Gallo has recently acknowledged to Subcommittee staff that by 1986, he knew the viruses were genetically identical.
- "Continuing research revealed that LAV and HTLV-III were two different isolates of the AIDS virus" (Brief for Appellee the United States, p. 4); (see above).
- The difference in nucleotide sequences of LAV and IIIb "... conclusively establishes that HTLV-III is not LAV by another name" (Defendant's Reply to Plaintiff's Opposition to Defendant's Motion to Stay Discovery); p. 4; (see above).
- "... Pasteur's statement that ''[I]t appears that Dr. Gallo and certain of his colleagues essentially took LAV, renamed it HTLV-III and the (sic) claimed and exploited it as their own' ... is an outrageous attempt to impugn the reputations of one of the world's foremost virologists and his coworkers" (Brief for Appellee the United States; pp. 4 - 5); (see above).
- "... nothing material or relevant was withheld from the examiner" (Opposition of Gallo et al. ...; p. A20); (In fact, virtually everything Gallo et al. knew about the IP virus and the IP scientists' work was withheld from the PTO examiner. The materiality of the withheld information concerning the IP scientists' work was compellingly affirmed by PTO when it repeatedly cited that work as prior art to Gallo et al; see above).
In mid-1991, early in her tenure as NIH Director, Dr. Bernadine Healy told Chairman Dingell, concerning Dr. Gallo, that she felt she had to "save Bob." At the time Dr. Healy made this curious pronouncement, Dr. Gallo was facing charges of scientific misconduct and serious violations of protections for human research subjects, not to mention the imminent prospect of a criminal conviction of his deputy laboratory chief for embezzlement and related charges. (Another long-time Gallo associate previously pled guilty to conflict of interest and receiving an illegal gratuity.) Dr. Healy attempted, by every means possible, to fulfill her pledge and at the same time, to save the blood test patent for NIH.
- Dr. Healy demanded that an OSI draft report sharply critical of Dr. Gallo be rewritten. When her order for a rewrite was refused, Dr. Healy replaced the chief investigator with one more malleable. The resulting OSI final report was greatly "watered-down"; the majority of the negative comments about Dr. Gallo were incorporated into a confidential memorandum, never publicly released, that included these observations:
"... Dr. Gallo's conduct had in numerous respects fallen well short of the conduct expected of a responsible senior scientist and laboratory chief (p. l); The investigative team saw this as a significant failure on Dr. Gallo's part to comprehend the need for accuracy and complete truthfulness in research (p. 6); ... he [Dr. Gallo] thereby fostered conditions which provided the opportunity for the creation of falsified/fabricated data and falsified scientific reports" (p. 7) (2/18/92 Hallum-to-Diggs memorandum).
- Simultaneous with Dr. Healy's rewrite order, NIH and HHS attorneys reviewed and dismissed as "not a problem" an OSI memorandum that documented the numerous misleading statements in the Gallo et al. patents and Dr. Gallo's 1986 sworn declaration. When the media obtained the OSI memorandum, in August 1991, NIH officials disparaged it as unofficial and unauthorized, and thereafter, studiously ignored its contents.
- In early 1992, when the NAS-commissioned "Richards Committee" produced a report sharply critical of Dr. Gallo, Dr. Healy bypassed the committee and commissioned her own committee of top NIH scientists whom she called her "wise men." Dr. Healy told her "wise men" that everything about the committee and their participation would be completely confidential. In return, she -- without any advance warning -- required the committee members to sign a secrecy agreement. As a consequence, the very existence of the committee remained hidden for nearly two years.
Despite Dr. Healy's efforts to handpick and control her "wise men," they decided Dr. Gallo should be fired as an NIH laboratory chief. One committee member expressed this determination as follows:
"... Gallo failed in his responsibilities as the head of the Laboratory. His behavior was seriously discordant with the 'Guidelines for the Conduct of Research in the Intramural Research Program at the NIH' ... The consequences of Gallo's failings have been substantial. At a minimum, an enormous amount of time and effort has been spent on these investigations, the efforts of both the French and American groups have been diverted into unproductive activities and considerable damage has been inflicted on the scientific enterprise, in general ... I recommend that you remove Dr. Gallo from his position as Chief of the Laboratory ..."
Faced with a finding she clearly did not want, Dr. Healy convened a second meeting of her committee. At this meeting, the "wise men," who had been assured that everything about the committee was entirely secret, suddenly found themselves confronted with Dr. Gallo and his attorney. The committee members were required to sit through a lengthy and entirely one-sided presentation by Dr. Gallo and his attorney in which all wrongdoing was denied, and in which it was suggested that Dr. Gallo was being hounded for accidental errors and inadvertent sloppiness in laboratory notekeeping -- "that could happen to any of you." At the conclusion of the meeting, Dr. Healy demanded a ruling from the committee as to whether Dr. Gallo had committed scientific misconduct. The committee members, who had examined none of the evidence, said they could not make such a judgment.
Dr. Healy's immediate response was to grant interviews with the Washington Post and Science, during which she disclosed the existence of her committee, and claimed Dr. Gallo "rather effectively refuted" the charges against him. At the same time, Dr. Healy quoted selectively from memoranda written by the committee members, attempting to trivialize the negative aspects of Dr. Gallo's conduct. Dr. Healy never acted on her committee's recommendation that Dr. Gallo be fired.
- In the early Spring of 1992, while the Gallo case was still under review at the Public Health Service's Office of Scientific Integrity Review, Director Healy wrote to Dr. James Mason, HHS Assistant Secretary of Health, that HHS should take steps to:
"... clear Dr. Gallo's reputation with regard to accusations of misconduct -- and also to accusations that he knowingly and willfully misappropriated a French virus, for which there is no apparent evidence" (3/27/92 Healy-to-Mason memorandum; p. 6).
- Shortly thereafter, Dr. Healy launched two further initiatives to redeem Dr. Gallo and the blood test patent. The first of these, a press conference for Dr. Gallo, to be held under the auspices of the NCI Cancer Board, was abruptly halted when HHS General Counsel Michael Astrue determined the meeting was "unauthorized and inappropriate" and
"... a guaranteed circus that will undermine years of effort to ensure public confidence in the fairness of this Department's review of the Gallo matter."
- Dr. Healy's other initiative was no more successful, although it was far more costly. This initiative, a decidedly nonindependent review of the validity of the Gallo et al. blood test patent (the "Allegretti & Witcoff report"), cost American taxpayers nearly $150,000 (funded by the National Cancer Institute). The review relied almost entirely on information prepared by the NCI (particularly a "Statement of Material Facts," prepared by NCI patent attorney Thomas Mayes) and interviews with Dr. Gallo. The NCI "Statement of Material Facts" reflects numerous significant omissions, e.g., there was no mention of the LAI permanent cell lines nor of the "mystery virus," "MOV." At the same time, the NCI "Statement" contained the same demonstrably incorrect statements as previously propounded by NCI/HHS, e.g.,
"Gallo et al. obtained about 21 isolates of HTLV-III prior to September 1983, and approximately 7 more isolates during the month of September 1983" (NCI "Statement of Material Facts"; p. 7).
The Subcommittee staff's review of NCI's "Statement of Material Facts" showed it was nothing more than a modern-day version of the Fischinger Report. With the NCI "Statement" as a "fact base," it was not surprising that the Allegretti & Witcoff report pronounced the Gallo et al. blood test patent valid and entirely sound. Neither was it surprising that the report was no sooner received at NIH than it was immediately leaked to a friendly reporter at the Washington Post.
- Dr. Healy led the United States' trustees of the French/American AIDS Foundation (FAAF) in adamantly rejecting the IP's request for a reallocation of the blood test patent royalties, in September 1992. HHS' rejection of the IP request, which was based on Dr. Gallo's belated 1991 admission that he used the IP virus to make the LTCB blood test, occurred despite the recommendation of HHS General Counsel Astrue. Shortly before the trustees' meeting, Astrue wrote to HHS Secretary Dr. Louis Sullivan that,
"... it would be in the public interest to relinquish future royalties" to the IP" (Astrue-to-Sullivan; approximate date 9/10/92; p. 4).
- Astrue told Sullivan that the continuing French/American dispute
"... is and will continue to be if we let it, a considerable distraction both for key AIDS researchers and senior officials ... the controversy is a strain on our relations with the French ... the controversy ... has discouraged international scientific cooperation ... For two millions dollars a year for ten years, I think HHS is buying more negatives than positives" (op. cit., p. 4).
Two fundamental issues relating to the French/American dispute -- and the misrepresentations that gave rise to that dispute -- confronted the current NIH Director, Dr. Harold Varmus, during the first year of his tenure. These issues, arising out of the numerous significant revelations of the OSI, OIG, and Subcommittee investigations, were (l) the question of Dr. Gallo's fitness to serve as chief of a multi-million dollar NIH laboratory and (2) the IP request for a reallocation of the royalties on the HIV blood test patents.
Dr. Varmus appeared to possess significant advantages for dealing with these issues. Dr. Varmus was not part of HHS' cover-up in the mid-1980s; neither did he participate in Dr. Healy's "save Bob" campaign in the early 1990s. At the same time, as a Nobel laureate who aroused Dr. Gallo's ire when he (Varmus) headed a commission that changed the name of the AIDS virus to "HIV," over Dr. Gallo's strenuous objections, Dr. Varmus had first-hand experience with the manner in which pride and zealotry about one's scientific theories can distort scientific truth and mislead much of the scientific community. In short, there was reason to believe Dr. Varmus might be able and willing to deal forthrightly with the implications of the compelling, recently-revealed body of evidence. Dr. Varmus did not fulfill these expectations.
1. Dr. Varmus' Failure to Deal With Questions of Fitness: In February 1994, when Chairman Dingell wrote to Dr. Varmus to inform him about the revelation of the Myers Documents (see above, p. %%15), telling him the documents "raise additional concerns about Dr. Gallo's candor and forthrightness," Dr. Varmus first attempted to deflect responsibility for dealing with the concerns, on grounds that they "had already been pursued" by the U.S. Attorney and the HHS OIG, and were unlikely to be productively dealt with by ORI. In a March 14 letter to Chairman Dingell, Dr. Varmus pledged to "keep in touch" with Subcommittee staff during his deliberations over the distribution of blood test patent royalties and "... any internal NIH actions appropriate on the record." Dr. Varmus also assured Chairman Dingell
"... of my intent to act expeditiously and fairly to all concerned."
To date, there has been no substantive response to the Chairman's February 1994 letter.
Meanwhile, Dr. Varmus was briefed by ORI and shown a large body of evidence indicating systematic, deliberate attempts by Dr. Gallo and some of his associates to mislead OSI investigators, including both withholding of vital evidence and alteration of evidence to remove potentially incriminating information. Dr. Varmus refused to consider the possibility of convening a Surgeon General's Board of Inquiry to deal with this matter; to date, no action has been taken by NIH/HHS.
2. Redistribution of Blood Test Royalties: Dr. Varmus' actions concerning the redistribution of royalties were equally problematic. The decision on a possible reallocation was nominally that of HHS; however, officials at the Department made clear they would defer to Dr. Varmus as the principal decision-maker.
The royalties issue was first raised to Dr. Varmus by IP Director Schwartz in early 1994. Schwartz both met with and wrote to Varmus, emphasizing that since the 1987 French/American settlement, "many facts and documents have surfaced," and asserting that in light of the new information, "some action is imperative" to reallocate the royalties in a ratio more favorable to the IP.
- The royalties question had already been raised anew by the United States Attorney for the District of Maryland. In January 1994, despite a presentation by the HHS OIG (see below), the U.S. Attorney declined to prosecute Drs. Gallo and Popovic for a variety of potential criminal offenses relating to their HIV patents and the defense of those patents. Notwithstanding the declination decision, which was based on a number of technical issues, including the statute of limitations, the U.S. Attorney made clear some action concerning the royalties, possibly including recapture of royalties previously paid to Drs. Gallo and Popovic, might well be in order:
"Our decision not to seek prosecution of Drs. Gallo or Popovic does not mean that we believe they should continue to receive their annual royalty payments. On this issue, we express no opinion other than to observe that Dr. Gallo, as of approximately May of 1991, has acknowledged that it was the French Institute Pasteur sample sent to his lab which formed the basis for the AIDS test. Whether he and Dr. Popovic should continue to receive their royalties under such circumstances, or whether the government should make any effort to recoup any payments made to them since then, are matters which are more appropriately addressed by the Department of Health and Human Services" (1/10/94 Battaglia-to-Maddox letter; p. 3).
In closing her letter, the U.S. Attorney made pointed observations about the broader implications of Gallo/Popovic's actions:
"... we recognize that this case transcends the normal type of criminal case in that the conduct of these two noted scientists reflects upon the integrity of the scientific process, the National Cancer Institute, and indeed the conduct of our government as a whole."
- Because of these broader issues, the HHS OIG, in a departure from its usual practices, decided to prepare a final report of its 2 1/2 year investigation, for presentation to Dr. Varmus and various PHS/ HHS officials, for consideration of any administrative actions they might deem appropriate. Dr. Varmus knew about the imminent issuance of the OIG report; yet on June 8, 1994, after remaining silent on the royalties question in the face of several additional letters from IP Director Schwartz, Varmus wrote to Schwartz that,
"... no alteration of our shared royalty arrangement is warranted."
Two days later, the HHS OIG report was signed, a report that made clear Dr. Gallo seriously failed in his duty of disclosure to PTO and made numerous statements -- in memoranda to HHS fact-finders, in published scientific papers, and in sworn legal statements -- that cannot be substantiated. HHS officials acknowledged to Subcommittee staff that Varmus' June 8 letter was written without his having seen the OIG report; the ostensible reason the June 8 letter was written without benefit of the OIG report was that Dr. Varmus did not wish to further delay responding to Dr. Schwartz. Yet previously, HHS officials and Dr. Varmus told Subcommittee staff they were awaiting the OIG report to ensure the royalties decision would be informed by the OIG's findings.
- o After receiving an outraged response from Dr. Schwartz and (presumably) reviewing the OIG report, on June 23, Dr. Varmus wrote another letter to Dr. Schwartz. Varmus indicated HHS might be willing to entertain an IP proposal for an HHS acknowledgement that "the French virus was used by National Institutes of Health scientists in developing the American test kit." Yet Varmus strongly disputed the assertion in Dr. Schwartz's June 13 letter that,
"... a coverup of the true facts was deliberately undertaken so that we would settle ..."
Varmus' response was this:
"... I cannot fail to comment on the statement in your June 13 letter declaring that there has been deliberate U.S. Government behavior to your Institute's detriment. Neither the United States Attorney nor the Inspector General has established the deliberateness that you assume. None of the forums in which your cases were pending ever made a finding of deliberate misconduct by the Government."
Dr. Varmus, presumably, will find the Subcommittee's report illuminating.
In this regard, it bears mention that long before Dr. Varmus' deliberations on the royalties were concluded, Subcommittee staff briefed the HHS General Counsel about the Subcommittee investigation's findings indicating the strong likelihood of misconduct on the part of HHS scientists, officials, and attorneys. The General Counsel, who advised Dr. Versus throughout his deliberations, told Subcommittee staff she kept Dr. Varmus fully informed about the information provided to her by the staff. Thus, it is difficult to comprehend how Dr. Varmus could have made his strong denials of official misconduct.
- After down-to-the-wire negotiations, threatened with the imminent filing of a new IP lawsuit, Dr. Varmus finally acceded to the IP proposal for a reallocation of blood test royalties more favorable to the IP. But in the process, Dr. Varmus and HHS showed that they still have not come to grips with the truth about the U.S. Government's misconduct during the French/American dispute.
- Dr. Varmus' official statement about the royalties' reallocation, at the July 11, 1994 meeting of the French/American AIDS Foundation trustees, propounded the fiction that,
"The reallocation of royalties is being made because the U.S. has been collecting significantly more in royalties than France."
The only concession to the truth HHS and Dr. Varmus could bring themselves to make was an official acknowledgement, under heavy IP pressure, that -- as was known for years --
"... scientists at NIH used a virus provided to them by Institut Pasteur to invent the American test kit."
- At a press conference following the trustees' meeting and in interviews with selected media, Dr. Varmus repeatedly denied that Dr. Gallo's conduct had any bearing on the reallocation decision. Dr. Varmus told the press conference that the question of deliberate use of the virus "was not part of today's decision," adding he did not expect any further action concerning Dr. Gallo at ORI. Dr. Varmus told Science magazine that,
"'We're not contemplating wrongdoing here'" (265, 1994, p. 313).
Concerning the OIG report, Dr. Varmus told the press conference the report had "very little" impact on his change of mind. Responding to a specific question, Varmus said that it was a change in his way of thinking about the royalties, between June 8 and June 23, that produced his more forthcoming letter on the later date. Yet after the press conference, Varmus told Science the OIG report,
"... had some catalytic role in my own thinking."
Whether the Subcommittee report, the OIG report, or anything else will further "catalyze" Dr. Varmus' thinking remains to be seen.
3. Will Dr. Varmus Support NCI? Dr. Varmus has frequently asserted that personnel/administrative decisions concerning Dr. Gallo and the LTCB are the responsibility of NCI. As this report is being written, Dr. Gallo, at the strong urgings of Dr. Broder, is reported to be seeking employment outside of NIH. Dr. Broder has told Subcommittee staff that if Dr. Gallo remains at NCI, he (Broder) intends to significantly restructure Gallo's responsibilities to address some of the concerns that exist about his leadership and management of the LTCB.
There is reason to question whether Dr. Varmus will support Dr. Broder's efforts. Dr. Varmus recently met with Dr. Gallo, against Dr. Broder's urging, while Broder was absent from the NIH campus. Following that meeting, Dr. Gallo contacted several journalists, telling them the media restrictions imposed on him in 1991 had been lifted. Shortly thereafter, Dr. Gallo began appearing on television and in other media interviews. Dr. Broder was not consulted about the lifting of the restrictions; Dr. Broder has said that as far as he is concerned, the restrictions remain in place.
Dr. Varmus also has raised procedural questions about Dr. Broder's plan for an interim relocation of the LTCB to provide better supervision for Dr. Gallo and his colleagues. Consequently, it remains unclear whether Dr. Varmus will support or obstruct Dr. Broder's long-range plans for dealing with the fitness questions raised by the several investigations of Gallo et al.
During the pendency of the Subcommittee's inquiries into this matter, questions occasionally were raised about the need for an exhaustive investigation of events that began well over a decade ago; some suggested the severity and urgency of the AIDS epidemic demand that the energies of scientists and government officials be focused entirely on eradicating the disease.
There are compelling reasons why an investigation into these matters was needed. The very severity and urgency of the AIDS epidemic make it all the more necessary that research into the disease and the virus that causes it be scrupulously performed and honestly reported. Correspondingly, the scourge of AIDS makes it all the more necessary that public policy relating to the disease be guided by and responsive to the public trust, not protective of individual egos and careers or singularly responsive to politics and international prestige. Because of the misrepresentations relating to the discovery of HIV and the invention of the antibody blood test, and the continuing cover-up of the misrepresentations, these imperatives were not honored. It was essential to understand the reasons why, not just to understand the instant case, but to understand its implications for any of the myriad of "high stakes" science policy issues that Government scientists and officials confront with increasing frequency.
Because of the misrepresentations and subsequent cover-up, until the OSI, OIG, and Subcommittee investigations, the truth about these matters was never fully revealed. The very endurance of the issues shows that they are important, yet they were not resolved. Without the investigations, without an authoritative accounting of the facts, the falsehoods would have remained as the definitive record. The people and the scientific community deserved to know the truth.
One of the most remarkable and regrettable aspects of the institutional response to the defense of Gallo et al. is how readily public service and science apparently were subverted into defending the indefensible. To comprehend the significance of the subversion of public service in the cover-up, it is useful to review the Guidelines of the Ethics Committee of the Washington D.C. Bar Association concerning the roles of government attorneys. According to the guidelines:
"A government lawyer in a civil action or administrative proceeding has the responsibility to seek justice and to develop a full and fair record, and he should not use his position or the economic power of the government to harass parties or to bring about unjust settlements or results" (EC 7-14; p. 51).
These guidelines, although they focus on government attorneys, apply at least as well to the NCI/HHS science administrators who played such a crucial, "make-or-break" role at the outset of the French/American dispute. The deliberately negligent "fact-finding" conducted by these individuals, combined with their deliberate suppression of incriminating evidence, set the stage for everything that happened thereafter. But the attorneys bear significant responsibility as well, for they clearly did not seek diligently to "develop a full and fair record" of the facts about the claims of Gallo et al.
Neither did HHS/DOJ officials and attorneys, once the dispute was under way, deal responsibly with the accumulating evidence that there were serious problems in the U.S. Government's claims. Instead, they pushed on with their "litigation strategy," all the while adding deception to deception, consuming untold resources and squandering scientific and international good will. The fraud became self-perpetuating. Defending the indefensible became a reflex, until ultimately, the cover-up was so burdened with falsehoods that its collapse was inevitable. HHS officials and attorneys should have recognized early on that the falsehoods could not be indefinitely sustained. But HHS sought only to "defend the position." HHS did not seek the truth. HHS did not honor the public trust.
The violence to principles of responsible, ethical science was just as profound. At a crucial point early in the LTCB's HIV research, international politics and the technocrats committed to those politics virtually took over that research, claiming the laboratory's putative accomplishments as accomplishments of the United States administration and by extension, the United States itself. Once done, the LTCB's interests became the Government's interests; defending the LTCB scientists' reputations and claimed accomplishments became necessary for defending the honor of the United States. The defense thus became a consuming effort for significant portions of the U.S. Government.
The result was a costly, prolonged defense of the indefensible in which the LTCB's "science" became an integral element of the U.S. Government's public relations/advocacy efforts. The consequences for HIV research were severely damaging, leading, in part, to a corpus of scientific papers polluted with systematic exaggerations and outright falsehoods of unprecedented proportions.
To comprehend how far from the ideal the defense of Gallo et al. led the scientific community, it is useful to note the words of two esteemed scientists, Drs. John Cairn and Paul Doty:
"... science is the pursuit of a truth that is external to our wishes. This truth is quite unlike the verdict of a court of law because it does not depend on advocacy" (John Cairn; Nature, 352, 1991, p. 101).
"This challenge to readdress the fundamental tenets of acceptable behavior in science comes at a time when the traditions of the scientific enterprise are under new threats arising from new stresses and temptations ... As a result, the scientific community may already be experiencing a gradual departure from the traditional scientific standards ... In this way we risk sliding down toward the standards of some other professions where the validity of action is decided by whether one can get away with it. For science to drift toward such a course would be fatal -- not only to itself and the inspiration which carries it forward, but to the public trust which is its provider" (Paul Doty; Nature, 352, 1991; p. 184).
There could be no better description of the disastrous consequences of the U.S. Government's defense of Gallo et al.
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