IN GALLO CASE, TRUTH TERMED A CASUALTY
Report: Science subverted in AIDS dispute
By John Crewdson
Chicago Tribune 1 Jan. 1995
In March 1987, President Ronald Reagan and French Prime Minister Jacques Chirac appeared in the East Room of the White House to announce that their governments had settled the question of whether scientists at the Pasteur Institute of Paris or the National Institutes of Health had invented the blood test for the virus known as HIV.
The answer, it appeared, was both. The names of the Pasteur scientists were added to the American patent on the AIDS test, and the focal agreement that formed the core of the settlement declared that both countries' scientists had independently "succeeded in isolating a human retrovirus which proved to be the causative agent of AIDS."
Just eight days later, at the Los Alamos National Laboratory in northern New Mexico, a scientist specializing in the genetic analysis of viruses sent senior officials at the National Institutes of Health a confidential memo warning that "a double fraud" had been perpetrated on the scientific community.
The Los Alamos scientist, Gerald Myers, had compared the genetic codes of the French and American AIDS viruses and determined they were not independent discoveries but had undoubtedly come from the same patient.
Moreover, Myers said, the American virus and its progeny could not have been isolated from a pool of blood samples from several AIDS patients, as the NIH publicly had maintained.
"I suggest that we have paid for this deception in more than the usual ways," Myers wrote. "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..."
Myers' memo, which would have undermined the historic settlement before the ink had dried, was promptly buried in the NIH's files where it remained until it was accidentally discovered late last year by investigators for Rep. John Dingell (D-Mich.), who in a few days will relinquish the chairmanship of the House subcommittee that oversees the NIH.
According to a draft report of a three-year investigation by Dingell's staff, the interment of the Myers memo represents a single example, albeit a "particularly egregious" one, of what the report describes as a "continuing coverup" by successive administrations of the role played by American scientists in the discovery of the AIDS virus and the invention of the AIDS test.
While the Department of Health and Human Services, of which the NIH is a part, "did its best to cover up the wrong-doing," the report states, "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."
The Dingell report summarizes the last, and also the most sweeping, of several inquiries into the case of Dr. Robert C. Gallo, the NIH researcher who claimed credit for the discovery of the AIDS virus and the development of the blood test. Subcommittee aides said, however, there was little chance the report would be released as an official subcommittee document after the Republicans, who have their own investigative agenda, assume control of Congress on Wednesday.
A previous NIH investigation of Gallo's AIDS research was narrowly drawn, ultimately focusing on the veracity of a few sentences in one of Gallo's many scientific articles. The Dingell inquiry also scrutinized Gallo's research, but it ranged far beyond Gallo's National Cancer Institute laboratory to examine the roles of past and present officials of NIH and HHS in the events that followed Gallo's highly publicized claim.
The draft report, which one senior Dingell aide said represented "a bipartisan consensus of the staff investigators," is as unstinting in its criticism of the current NIH director, Dr. Harold Varmus, a Clinton appointee, as of Varmus's predecessor, Dr. Bernadine Healy, and other officials of the Reagan and Bush administrations.
Although the report credits Varmus with ending "the atmosphere of overt protectionism of Dr. Gallo" at NIH, it criticizes his recent decision to give the Pasteur Institute a greater share of AIDS test royalties as "based on a disingenuous explanation of accounting anomalies, rather than the proven fact that the [Gallo laboratory's] scientists, contravening a formal transfer agreement, used [the Pasteur's] AIDS virus isolate to make their blood test."
According to the report, the Dingell investigation began as a probe into alleged kickbacks and diversion of federal funds by two of Gallo's assistants, both of whom were convicted of federal felonies. It expanded to include the circumstances surrounding the decade-long Franco-American dispute, and its completion comes at a difficult time for the cancer institute, where Gallo still heads what was once NIH's biggest research laboratory.
The cancer institute's director, Dr. Samuel Broder, announced unexpectedly Dec. 22 that he would be departing after six years in the institute's top job. Several of Broder's senior aides also are leaving or have left, and the Dingell report states that "Dr. Gallo, at the strong urgings of Dr. Broder, is reported to be seeking employment outside of NIH."
What is likely to be the final chapter in the Gallo case comes almost 10 years to the day after the initial revelations that the AIDS virus Gallo called HTLV-3B and claimed as his own discovery was virtually identical, at the genetic level, to the AIDS virus the French called LAV.
As recounted by the Dingell report, the original focus of the Gallo case was what Gallo's laboratory did, and did not do, with a sample of LAV lent to him by Pasteur, and Gallo's assertions to the media, in published articles and under oath about what happened to that sample.
When Gallo announced in April 1984 that he had discovered the virus that causes AIDS, he said his discovery differed from the French virus and implied that the French LAV might not be the cause of AIDS. Eventually it be came clear that the two viruses were more alike than any other known pair of AIDS viruses, and Gallo suggested the French had contaminated their cultures with his virus.
When such a "reverse contamination" proved to be physically impossible, Gallo proposed that the French patient in whom LAV had been discovered had been infected by the American patient, never identified, from whom Gallo's HTLV-3B had come.
Gallo dismissed suggestions that LAV might have contaminated his own virus cultures as "the height of outrage," declaring that it had been "physically impossible" for his assistants to grow the LAV sample. These claims, the Dingell report says, "were not true."
It was not until 1991 -- seven years after Gallo's announcement of his discovery -- that the NIH arranged for a series of experiments proving not only that Gallo had grown the French virus, but that none of the patients he identified as sources for his virus had been infected with a virus even remotely similar to LAV.
Neither Gallo nor his attorney, Joseph Onek, responded to a request for comment on the Dingell investigation, which draws on evidence assembled by the NIH investigation and a subsequent inquiry by the HHS Inspector General, as well as the subcommittee's own interviews with Gallo and nearly 60 past and present officials of NIH and HHS and its own examination of documents gleaned from NIH and HHS files.
Onek told The New York Times in November that Dingell's staff was "famous for leaking documents, generating press stories and acting in ways that one would not expect of a responsible congressional committee. They would decide they didn't like people and then went after them in ways that were inappropriate."
Both the NIH investigators and the Dingell staff were unable to resolve what the Dingell report calls "the central, original issue" in the Gallo case: whether the French virus contaminated Gallo's own cultures by accident or was intentionally "misappropriated" by someone in his lab.
According to the Dingell report Gallo's former chief virologist, Dr. Mikulas Popovic, who performed most of the experiments with the French sample, refused "repeated requests" for an interview by the subcommittee staff.
Even without Popovic's testimony, the report concludes that, intentionally or not, Popovic and Gallo's other assistants "performed all their seminal HIV experiments," including the development of the American AIDS test with what now has been shown to be the French AIDS virus.
The report also disputes Gallo's claim that his staff had isolated a second AIDS virus, code-named RF and unrelated to LAV, that could have been used to make the American AIDS test.
"There were two major problems with the possible use of RF for the [American] blood test," the report says. "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." According to the report, Gallo acknowledged to subcommittee investigators "that he never seriously contemplated delaying implementation of the blood test to try to ready RF."
The portrait drawn in the Dingell staff's report is one of an incremental cover-up in which "defending the claims of the [Gallo laboratory's] scientists came to be perceived as tantamount to defending the United States Government itself," by a succession of federal agencies.
According to the report, the cover-up began with the government's filing of patent applications for the Gallo AIDS test. The applications "contained fundamental assertions that could not be substantiated," the report said, including the affirmation that Gallo and his assistants were the "original" inventors of the test.
Several weeks earlier, the report says, another HHS agency, the Centers for Disease Control, had compared Gallo's AIDS test with one developed at Pasteur "many months before," and found that the two tests "performed equally well, both at high levels of accuracy."
"The real inventors of the HIV blood test," the report says, "were the [Pasteur] scientists. Even more important, the CDC data, together with the extensive data already accumulated by the [Pasteur] scientists, showed that the [Pasteur] virus -- discovered long before the putative LTCB virus -- was the cause of AIDS."
Although the report presents evidence that Gallo knew of the existence of the French test and the results of the CDC comparison, it asserts that he did not pass on his knowledge to the Patent Office despite a legal obligation to "disclose information which is material to the examination of [his patent] application."
As a result, the report says, the Patent Office remained unaware of the French research. Because of a bureaucratic foulup, the patent examiner who awarded the Gallo patent was unaware that Pasteur had applied for a patent on its own AIDS test months ahead of Gallo.
"According to the examiner," the report says, "when she first saw the [Pasteur] application within two weeks of issuing the Gallo [patent], she recognized immediately that [the Patent Office] had 'screwed up' in issuing the Gallo patent" because the two claimed inventions were "directly related."
It was after the French protested that something was amiss within the Patent Office and suggested that Gallo had used their virus to make a commercial AIDS test, the report says, that "public health concerns were subjugated to 'scientific' intrigues."
What ensued at NIH and HHS, according to the report, was "a parody of an investigation" in which Gallo's superiors "did not seek the truth, but rather sought to create an official record to support the claims of Gallo." The report asserts that HHS even considered tapping the telephones of NIH employees "believed to be communicating with" the Pasteur lawyers, but that "it is not known if the surveillance was actually carried out."
The person charged with assembling an internal report on Gallo's AIDS research was Dr. Peter Fischinger, a senior NCI official who, the Dingell report asserts, "had a significant investment in a favorable outcome." The report maintains that "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."
Fischinger's report set the tone for the American defense against the French challenge, and the Dingell report maintains that it included several "demonstrably false claims," among them the assertions that no material "from any outside laboratory" was used to isolate HTLV-3B, and that Gallo was "the first to identify the virus and to describe the blood antibody test."
The Dingell report faults Fischinger for having "relied exclusively on Dr. Gallo and his associates for 'the facts,'" and not seeking "contrary facts and evidence" about Gallo's receipt and use of LAV from the French. Fischinger told the Dingell staff that the "responsibility for the accuracy of his report rested not on him, but on Dr. Gallo."
With the filing by the French of several lawsuits and a formal complaint with the Patent Office the defense of Gallo's research moved to HHS. But the Dingell report states that, like their counterparts at NCI and NIH, "HHS officials accepted uncritically everything they were told by Dr. Gallo and his colleagues," incorporating that information "unqualifiedly and without confirmation into official reports of the Department."
Early in the case, the Dingell report says, senior HHS officials were presented with evidence from another NIH researcher, Dr. Malcolm Martin, that "strongly challenged" Gallo's claim to have discovered HTLV-3B, and with the CDC data showing that the Pasteur's AIDS test was "fully the equal of the [Gallo] test."
But the report asserts that "these dramatic revelations did not in any respect alter HHS's course." When Pasteur lawyers attempted to obtain the Gallo laboratory's notebooks to help prepare their case, the report says, key documents "were whited out or otherwise obscured" to remove evidence of the Gallo laboratory's work with LAV "that would have undercut the U.S. position."
Some government lawyers worried privately that the U.S. would not prevail in a formal patent showdown, the report says, stating that "the HHS attorneys themselves recognized that they were on very thin ice." Some of them described the American position in their internal communications as a "weak thread" and a "two-edged sword."
The report quotes one unnamed individual "privy to many behind-the-scenes meetings and discussions relating to the dispute" as recalling that "There was a general impression that we wouldn't win, because Gallo lacked documentation to show there was no use of the French virus."
Instead of debating whether the Gallo patent should be defended, the report says, "The concern for HHS officials, at all times, was 'How shall we defend the patent?'
"As HHS began to comprehend that the [Gallo laboratory's] claims could not be substantiated," the report says, "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 the United States."
As the Justice Department parried with the Pasteur's attorneys in court and before the Board of Patent Appeals, the report says, its legal pleadings "were packed with false and misleading claims," including assertions that the Gallo and Pasteur viruses were independent discoveries, and that Gallo had isolated the AIDS virus before the French.
"The subcommittee investigation," the Dingell report says, "showed that the ... legal arguments could not be substantiated," and it maintains that "the misinformation and material omissions are traceable directly to documents and statements prepared by Dr. Gallo" and his assistants.
When Dingell's staff tried to determine who had been responsible for the misleading statements, the report says, Gallo asserted that "the attorneys created the documents, and that he was guided by their instructions." But the report says 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."
One unnamed lawyer is quoted in the report as saying, "I didn't know enough to lie" about Gallo's research. Another said, "Here's this guy, almost a Nobel Prize winner, you walk into his office and see all these awards all over his walls if he tells us he did something, are we going to question it?"
Confronted with the government's official assurances that Gallo's HTLV-3B was not LAV by another name, the French agreed in 1987 to an out-of-court settlement that paved the way for the unprecedented announcement by Reagan and Chirac.
But the Dingell report dismisses that settlement as having "barely managed to paper over the glaring unresolved issues," and the matter was reopened two years later following a 1989 Tribune article that examined the discovery of HIV in considerable detail.
The Tribune article reported, among other things, that despite Gallo's denials his assistants had indeed grown the French virus and used it in many of their principal experiments. The article also presented evidence that HTLV-3B and LAV were the same virus, concluding that the only explanation was "either an accident or a theft."
The article prompted the NIH investigation, which ultimately confirmed the Tribune's principal assertions about Gallo's research and provided the first conclusive laboratory evidence that Gallo's HTLV-3B was actually the French LAV.
That inquiry, conducted by what was then the NIH's Office of Scientific Integrity, found Popovic guilty of having published false statements about some aspects of his work with HTLV-3. The finding was later overturned by an HHS appeals board that held that the statements in question could be read in ways that did not necessarily make them false.
An HHS agency, the Office of Scientific Integrity Review, later concluded that Gallo had also committed scientific misconduct by maintaining, in an article published several months after the French virus had grown successfully in his own laboratory, that it had never been continuously grown.
The agency said Gallo's misstatement "virtually ensured" his own laboratory's preeminence in AIDS research and "impeded potential AIDS research progress" with the French virus.
Gallo lodged an appeal, claiming the questioned statement was true because he had intended it to refer to his belief that the French had been unable to grow their own virus.
In late 1993, after nearly a year of legal wrangling, HHS withdrew the finding, saying it would have been "extraordinarily difficult" to argue its case in the face of the appeals board ruling in Popovic's case that published statements did not necessarily mean what they appeared to mean.
Although Gallo claimed vindication, the Dingell report says Gallo and his colleagues withheld "a substantial number of highly significant documents" from the NIH agency investigators and heavily edited others before surrendering them.
"As a consequence," the report says, "OSI was seriously misled concerning such significant matters as what experiments were performed with the [Pasteur] virus ... and what Dr. Gallo knew about these experiments."
It was in the midst of that investigation that Dr. Bernadine Healy, a Cleveland cardiologist, assumed the directorship of NIH, and the Dingell report says Healy ordered a rewrite of the OSI's report, which was "sharply critical of Dr. Gallo." When the chief OSI investigator, Suzanne Hadley, refused to change her report, Healy ordered Hadley replaced.
The OSI report was softened considerably before it reached Healy, and according to the Dingell report, "the majority of the negative comments about Dr. Gallo were incorporated into a confidential memorandum, never publicly released." It included the observation that Gallo's conduct had "fallen well short of the conduct expected of a responsible senior scientist and laboratory chief."
Dingell subsequently asked NIH to let Hadley assist his staff in investigating the Gallo case. Hadley, who remains an NIH employee, was temporarily assigned to the Dingell subcommittee and played a central role in its investigation.
The Dingell report says Healy personally told Dingell that "she felt she had to 'save Bob.'" It faults her for having "bypassed" the conclusions of a committee of distinguished non-government scientists established by her predecessor to oversee the Gallo investigation.
The driving force behind that committee's report, which accused Gallo of "intellectual recklessness of a high degree," was Dr. Alfred Gilman, who shared last year's Nobel Prize in medicine.
The French, spurred by the NIH's determination that their virus had indeed been used in Gallo's experiments leading to the development of the American AIDS test and was still being used in the manufacture of that test began pressing HHS for an increased share of the patent royalties allocated under the Reagan-Chirac agreement.
Despite a recommendation by the then-HHS general counsel that they agree to the proposal, Healy and other HHS officials rejected the French request out of hand.
The French renewed their appeal following Healy's departure.
Last summer, following the completion of an HHS Inspector General's inquiry that found no support for the American claim that Gallo was first to invent the AIDS test, NIH Director Varmus agreed to award the French the lion's share of future royalties generated by the joint AIDS test patent, a sum that could amount to $6 million over the next eight years.
"After down-to-the-wire negotiations, threatened with the imminent filing of a new [Pasteur] lawsuit," the Dingell report says, "Dr. Varmus finally acceded to the [Pasteur] proposal for a reallocation of blood test royalties more favorable to [Pasteur]."
But the report concludes that "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." *
Following are excerpts from the Dingell staff's report:
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. Neither (HHS nor Justice Department) officials and attorneys, once the dispute was under way, (dealt) 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 honor the public trust.
The violence to principles of responsible, ethical science was just as profound. At a crucial point early in the (Gallo laboratory'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 (Gallo laboratory's) interests became the government's interests; defending the (Gallo laboratory) 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 (Gallo laboratory'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. *