Staff Report
Subcommittee on Oversight and Investigations
Committee on Energy and Commerce
U.S. House of Representatives
...
Executive Summary
I. INTRODUCTION
A. The Subcommittee's Focus on the Institutional Response
Encouraged by prominent scientists, the Subcommittee on Oversight and Investigations in 1987 began a review of the institutional response to cases of alleged or suspected scientific misconduct by scientists involved in Federally supported research. At that time, the problem was readily discernible. When situations of possible scientific misconduct arose, the institution's response generally was to walk the whistleblower out the door, sweep the problems under the rug, and to protect, at all costs, the reputations of the senior scientists. As one scientist explained, "It was as if they had their own fiefdoms whereby they set their own rules."
...
Even as the Subcommittee began to see some progress at research institutions, it was evident that effort had been geared toward research institutions outside the Federal government. At the time, over a billion dollars was being spent at the National Institutes of Health (NIH) on intramural research. Consequently, it was important to determine if the same unwillingness to deal effectively with cases of potential misconduct observed in non-Federal institutions also existed within the Federal government's own research community. As a result, the staff was directed to conduct a case study involving allegations of misconduct in an intramural research program.
B. HHS/NIH's Sorry History of Misconduct Investigations
At this time, the Subcommittee was investigating the Laboratory of Tumor Cell Biology (LTCB) within the National Cancer Institute (NCI) at NIH, due to allegations of kickbacks and diversion of Federal funds by two prominent scientists within that laboratory. Ultimately, both investigations resulted in felony convictions. As a result, in 1989, when allegations of scientific misconduct resurfaced against the chief of that laboratory, allegations which had first been raised in 1985-86, the Subcommittee was in a good position to use the LTCB as its intramural case study.
...
In addition, despite strenuous pressure from attorneys and top officials of the Institut Pasteur (IP), Dr. Varmus refused to even consider a possible reallocation of royalties from the HIV blood test patent until he was confronted with a serious threat of an imminent lawsuit. Even when he finally agreed to a reallocation of the royalties, Dr. Varmus (with HHS' blessing) merely negotiated an increase in the IP share of the royalties, based on a disingenuous explanation of accounting anomalies, rather than the proven fact that the LTCB scientists, contravening a formal transfer agreement, used an IP AIDS virus isolate to make their blood test.
C. Summary of the Subcommittee's Findings
The popular view of the so-called "Gallo case" is that it is about whether Gallo et al. "stole" or misappropriated the IP virus. While this is indeed the central, original issue relative to the LTCB scientists, the case as it bears on the institutional response subsumes other vital issues, including how political and international reputational imperatives at HHS assumed preeminence over scientific integrity, and how defending the claims of the LTCB scientists came to be perceived as tantamount to defending the United States Government itself.
...
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."
...
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.
...
HHS did its best to cover up the wrong-doing. Meanwhile, the failure of the entire scientific establishment to take any meaningful action left the disposition of scientific truth to bureaucrats and lawyers, with neither the expertise nor the will essential to the task. Because of the continuing HHS cover-up, it was not until the Subcommittee investigation that the true facts were known, and the breadth and depth of the cover-up was revealed. This report describes the facts, and how and why HHS went so badly wrong.
II. CHALLENGES TO THE INVESTIGATION
A. Withholding/Altering/Destruction of Documents
The challenges to the Subcommittee's investigation, and to the OSI and OIG investigations as well, were significant, both because of the time that had elapsed since many of the key incidents and because some witnesses were frankly antagonistic to the Subcommittee's objectives. Documentary evidence was vital to the investigation; however, systematic withholding of documents was evident from the outset, on the part of both agencies and individuals. Key documents frequently were withheld for prolonged periods, in many cases, for years. Some critical documents known to exist were never officially produced. Among the more noteworthy such instances were the following:
...
None of the Myers documents was ever provided to OSI. And when the documents were sought by a journalist under the FOIA, their release was denied, at the behest of a top NCI official -- a nonscientist -- who told the NIH FOIA officer the documents "pertained to the agreement with the Pasteur Institute, the science of which has not yet been resolved."
B. Interview Challenges
Testimony posed at least as great a challenge as documentary evidence, partly because memories of some witnesses had eroded, due to the passage of time. At least as serious was the problem of willful forgetfulness and obstructionism, of which the following instances are exemplary:
...
HHS attorneys manifested particularly severe memory deficits. During his October 8, 1992 interview by Subcommittee staff, HHS attorney Richard Riseberg emitted a remarkable number of "I don't know," "I don't recall," and "I can't help you there" responses concerning a number of critical events at which he personally was present. Riseberg claimed he was merely "asked to go along" to these events. HHS Attorney Darrel Grinstead, in his September 22 and September 30, 1992 interviews, took a similar tack, although on some critical issues, besides repeating, "I don't recall," Grinstead added this:
"I wouldn't tell you even if I did recall. That was between client and attorney."
NCI and NIH Directors Drs. Vincent DeVita and James Wyngaarden each denied any significant responsibility for the defense of Gallo et al. Yet each said the other was importantly involved. Dr. DeVita told Subcommittee staff that Dr. Wyngaarden took on an especially prominent role in matters relating to AIDS and that Wyngaarden "liked to deal with international stuff." Consequently, according to DeVita, Wyngaarden took on responsibility for discussions with IP officials and officials of the French Government, including discussions about possible monetary settlements, creation of an "official" scientific chronology, and other significant matters. Dr. Wyngaarden, by contrast, pointed to numerous instances in which DeVita and NCI by-passed the office of the NIH Director, dealing directly with HHS authorities, Congressional leaders, and even the White House.
Both Drs. Wyngaarden and DeVita, as well as every other key player at HHS, pointed to Lowell Harmison as the man in charge of the U.S. defense of Gallo et al., particularly during the critical early months of the French/American dispute. Attorney Richard Riseberg described Harmison as the "linchpin" of the HHS defense, who "understood the implications of the scientific information." Dr. Wyngaarden described Harmison as "on top of this," and the "chief individual" in the HHS defense. Dr. DeVita described Harmison as "running the show," and attorney Darrel Grinstead described Harmison as his "most regular client."
Despite these characterizations, Dr. Harmison claimed little or no recollection of most major elements of the French/American dispute, particularly his own role. Dr. Harmison claimed he was unable even to describe his job, as in this exchange during a hearing in Executive Session:
Q: Do you remember what your job was?
A: I think I was involved in the policy and the science of it.
Q: You were involved in the policy. And how were you involved in the policy?
A: I think the records that you have collected should express that.
Q: I am asking you. You are here to help us. Please tell us.
A: I have said, there were discussions with people as a normal part of the process of meetings --
Q: Who presided at these discussions?
A: I may have presided. It may have been the AIDS Executive Task Force.
Q: You may have? Do you remember whether you presided? Do you remember if somebody else presided? Do you remember if nobody presided? Do you not remember if anybody presided?
A: I don't remember.
Q: Do you remember there were discussions?
A: I think this is a very circular point. I have explained my policies and how I did things (7/21/93 hearing transcript; pp. 121 - 122).
Dr. Harmison also evinced a curious perspective concerning what was relevant vis-a-vis the French/American dispute. In response to a question about the key issue of the dates on which the IP and LTCB scientists created and began to work with their HIV antibody blood tests, Dr. Harmison said,
"I don't recall with respect to that date. That is to me not relevant. I don't recall, if I knew ... I said I can't recall. To me it is irrelevant because I can't recall it" (op. cit., p. 175).
III. THE LTCB HIV BLOOD TEST PATENT
The April 23, 1984 filing of a United States patent application for the HIV antibody blood test of Gallo et al. was a defining event for HHS as well as the LTCB scientists. The commercialization of the IP virus in and of itself would violate the terms of the IP transfer agreement that accompanied the virus sample (see below for further details); the patent application further "upped the ante" dramatically for all concerned. The reputational and potential financial benefits of a blood test patent were very significant. Equally significant were the potential legal consequences of breaching the terms of the transfer agreement, and the potential legal, even criminal consequences for breaching United States patent laws and regulations.
The filing of the LTCB blood test patent application influenced events a decade and more thereafter. Because the consequences of the patent application filing were so far-reaching and profound, this section of the report lays out the relevant statutes and regulations, together with a description of the actions/statements of Gallo et al. subject to those statutes and regulations.
A. Patent Privilege and Responsibility
Rules of the United States Patent and Trademark Office make clear that holding a United States patent is a privilege that entails vital responsibilities, particularly responsibilities for candor and full disclosure. According to the PTO Manual:
...
"No patent will be granted on an application in connection with which fraud on the Office was practiced or attempted or the duty of disclosure was violated through bad faith or gross negligence. The claims in an application shall be rejected if upon examination ... it is established by clear and convincing evidence (l) that any fraud was practiced or attempted on the Office in connection with the application ... or (2) that there was any violation of the duty of disclosure through bad faith or gross negligence in connection with the application ..." (37 CFR §1.56, [d], op. cit., p. 2000-2).
B. What Gallo et al. Said in Their Patent Applications
On April 23, 1984, when Dr. Gallo and his associates submitted applications for United States patents on their HIV blood test and a method for virus production, they affirmed, under penalty of criminal prosecution for making false statements, that they were,
...
"... we do not know and do not believe that the same was ever known or used in the United States before our invention thereof or patented or described in any printed publication in any country before our invention thereof ..."
C. What Gallo et al. Withheld from PTO
The results of the Subcommittee's investigation show that the claims of Gallo et al. to be the "original, first" inventors of the HIV antibody blood test cannot be substantiated. Moreover, there were at least three critical areas in which Gallo et al. failed in their duty of disclosure to PTO: (l) the LTCB scientists' knowledge of and benefit from the IP scientists' work with LAV; (2) the LTCB scientists' knowledge and use of the IP LAV antibody blood test; and (3) the LTCB scientists' receipt and use of the IP virus itself.
...
"... The '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.
...
"... 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,
...
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 Gallo lab 'went to school' with the French virus ..." (emphasis in original); 2/19/92 Richards-to-Healy; p. 2).
IV. THE COVER-UP AT LTCB
A. Growth and Use of the IP Virus
The combined results of the OSI, OIG, and Subcommittee investigations revealed the following uses of the IP virus samples at the LTCB:
...
"... there has been confusion in the response of what we did to LAV. In my response during the passionate period ... 'oh we never grew LAV' and of course we did grow LAV" (5/16/90 OSI interview transcript p. 87).
"There is a point where I say I didn't grow LAV. And, of course, LAV was grown ... Quite frankly, it wasn't so germane to me at the time and I was just anguished as to what was coming out of the newspaper. At that moment bombs were going off" (5/25/90 OSI interview; transcript p. 13).
B. Selection of the Isolate for the LTCB HIV Blood Test
1. Early Work on the LTCB Blood Test:
Dr. Popovic emphasized to OSI that the overriding purpose of his early HIV experiments was to produce the virus in large quantities. This would, among other things, enable development of an HIV antibody blood test at the LTCB. For these purposes, the identity of the virus isolate, as long as it grew well, was of little concern. As Dr. Popovic said:
...
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.
...
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:
...
"... 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:
...
Thus, it is at least possible that a deliberate decision was made to patent and commercialize a blood test using the IP virus, both because there was no alternative to using that virus and because at the time of the decision, there was no discernible risk of discovery. More importantly, the evidence shows that by the Summer of 1984, when Dr. Gallo knew "his" virus almost certainly was the IP virus, he attempted to blame the IP scientists for "contaminating" the cell lines and when this failed, he suppressed the evidence of the viruses' identity and, for years, argued strenuously that they were genetically independent (see below).
C. Popovic et al.: The Rewriting of Science
The cover-up of the LTCB's work with the IP virus advanced to a more active phase in mid-March 1984, when Dr. Gallo systematically rewrote the manuscript for what would become a renowned LTCB paper (Popovic et al.; Science, 225, 1984, pp. 497-500), deleting Dr. Popovic's explicit references to his use of the IP virus and making it appear Dr. Popovic's seminal experiments had been performed with an authentic LTCB isolate. The extent of Dr. Gallo's revisions to Dr. Popovic's paper became clear during the OSI investigation, when Dr. Popovic suddenly produced two drafts of the paper bearing Dr. Gallo's edits. Dr. Popovic had secured these drafts with his sister in Czechoslovakia because, he said,
...
"The Gallo lab ... failed to mention the fact that they had propagated the French virus and stated (in the Popovic et al. manuscript) that the French virus had never been transmitted to a permanent cell line. Given the quality of the information derived from propagation of the French virus, we believe that this constitutes intellectual appropriation of the French viral isolate" (emphasis in original; Richards-to-Healy; p. 3).
D. The HHS Press Conference
On April 23, 1984, the same day as Gallo et al. submitted their blood test and cell line patent applications, HHS announced the NCI scientists' putative discoveries at a press conference for the international media. Emphasizing the alleged uniqueness of the American accomplishments, HHS Secretary Margaret Heckler termed them "a triumph of science," "another miracle" added to "the long honor roll of American medicine and science." Secretary Heckler repeatedly referred to "our eminent Dr. Gallo." She added that "We have applied for the patent [on the blood test] today." And Secretary Heckler took the occasion to defend the Administration's record on AIDS research:
...
"we've been mass-producing it [the AIDS virus] for six months" (the only virus the LTCB scientists grew at all, let alone that was "mass produced" "for six months" prior to the HHS press conference was LAI. Dr. Gallo attempted to justify his statement by saying that by "mass producing," he meant "continuously producing" virus [4/26/90 OSI interview; transcript p. 64]. Even by this idiosyncratic definition, the only virus that would qualify is LAI. By commonly accepted definitions of "mass producing," Gallo et al. had no viruses that had been mass produced for six months as of the date of the HHS press conference).
"we have over 50 isolates" (by Dr. Gallo's own admission to OSI, he had no more than 10 genuine HIV isolates at the time).
"Montagnier couldn't grow enough virus to send us for comparisons" (as described above, there was more than enough of the IP virus for the LTCB scientists to perform any experiment they wished).
E. Comparisons of the IP and LTCB Viruses
During the Summer and Fall of 1984, the IP and LTCB scientists attempted to compare their respective HIV prototype isolates. The HHS Assistant Secretary of Health, Dr. Edward Brandt, personally ordered that the comparisons be made, not because there was suspicion at the time that the viruses were genetically identical -- i.e., were derived from the same person -- but because, for public health reasons, it was essential to confirm that the IP and LTCB viruses were functionally the same and both were the cause of AIDS. Put another way, it was essential to confirm that there was only one virus that was causing the disease.
...
These events set the stage for the HHS cover-up that began in August 1985.
V. COVER-UP AT HHS
A. Improvident Issuance of the Gallo et al. Patent
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.
...
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.
B. The Critical Roles of Drs. Fischinger and Harmison
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.
...
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.
C. HHS' Grand Strategy
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."
...
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.
D. HHS/DOJ Tactics
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).
...
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.
...
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.
E. False and Misleading Claims
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:
...
"... 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.
...
"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).
VI. THE CONTEMPORARY COVER-UP
A. The Healy Era: NIH on the Offensive
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.
...
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).
B. The Varmus Era: Will NIH/HHS Face the Facts?
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
...
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.
...
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.
...
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.
VII. CONCLUSIONS
A. Significance of the Investigation
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.
...
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.
B. The Subversion of Science and Public Service
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:
...