A year and a half ago, when the National Institutes of Health started investigating the work of his laboratory, Dr. Robert Gallo fell silent. Dogged by accusations that the AIDS virus he identified in 1984 was based on a French laboratory’s tissue sample, the normally ubiquitous scientist seemed to shrink from the spotlight. Last June, for instance, AIDS researchers from all over the world descended on San Francisco for a teeming, weeklong conference. Gallo went to Russia.
The NIH inquiry is still not finished, but Gallo has recently returned, with a bang, to public life. He has just published an outspoken autobiography, “Virus Hunting” (352 pages. Basic Books. $22.95), in which he recounts the discovery of the AIDS virus and the dispute with the French and comments on the newspaper expose that helped spawn the current NIH inquiry. And two weeks ago he and a group of colleagues released new findings in the British journal, Nature, purporting to resolve the question of whether his AIDS virus was really a French import. But if Gallo thought the new findings would lay the old dispute to rest, he could hardly have been more mistaken. The paper has only heightened the furor, and deepened the mystery it concerns.
The controversy dates back to the spring of 1984, when Gallo and his colleagues at the National Cancer Institute in Bethesda, Md., announced they had identified the virus responsible for AIDS and had developed a blood test to screen for it. They called the AIDS virus HTLV-III. A separate team led by Prof. Luc Montagnier of the Pasteur Institute in Paris had isolated specimens of the same virus a year earlier, but they hadn’t yet deciphered its genetic sequence. The French researchers called their virus LAV. Subsequent analysis showed that although different strains of the AIDS virus normally vary in genetic structure, LAV and IIIb (the strain of HTLV-III from which Gallo developed the blood test) were virtually identical. And the French thought they knew why. They had previously sent Gallo samples of the still unidentified virus from a patient they had code-named BRU. They reasoned that since the BRU “isolate” was the source of LAV, it must also have been the source of Gallo’s IIIb. Whether by accident or design, it seemed their virus had ended up in Gallo’s test tube.
After a long, bitter dispute Gallo and Montagnier agreed in 1987 to call themselves codiscoverers of the AIDS virus. In a separate legal settlement, the Pasteur Institute and the U.S. government agreed to apportion the substantial royalties from the blood test. But peace was short-lived. In the fall of 1989, Chicago Tribune reporter John Crewdson published a 50,000-word article resurrecting the question of whether Gallo’s discovery was based on the French isolate. Before long Montagnier was repeating that charge, and NIH officials were announcing they would assemble a panel of independent scientists to help re-examine the matter. Last fall the NIH cleared Gallo of stealing anything from the French. The investigators concluded that since his lab had numerous viral samples at the time it identified IIIb, the discovery and blood test would have been possible with or without the French BRU. Nonetheless, the NIH leadership decided that several issues–including which of those numerous samples was the source of IIIb–warranted further examination. The current inquiry concerns those other issues.
If Gallo’s latest findings are any indication, the review could yield some surprises. For the recent study Gallo and several colleagues, including Montagnier’s former collaborator Jean-Claude Chermann, went back and analyzed three of the five BRU samples Gallo received from the Pasteur Institute in 1983 (the three samples had been frozen and stored at the NIH, but two others had been lost or used up). The researchers found, to their surprise, that the BRU samples were genetically very different from LAV and IIIb. Their conclusion: the French and American discoveries may have come from the same viral sample, but neither one came from BRU, not even LAB.
If Gallo relished placing his old foe on the defensive, he concealed his delight. In a public statement, he said the new findings neither “detract from the fine contributions of the Pasteur Institute scientists” nor invalidate the 1987 agreement. “This report gives no encouragement to anyone who would like to believe that science is more about personalities and secrets than about solving problems,” he said. “It is my sincere hope that we can get on with our work.” Montagnier was not amused. “It’s a question of Gallo’s personality,” he fumed. “He will never recognize defeat. He doesn’t know how to back down. It’s a little like Saddam Hussein.” Not that Montagnier had any thoughts of backing down himself. “I know we’re right,’ he told NEWSWEEK, “and we will prove that his IIIb is LAV.”
Montagnier says the discrepancy between LAV and Gallo’s BRU samples may simply reflect the virus’s rapid mutation in the lab. Montagnier and Chermann, the French researcher who cosigned the Nature article, have both recalled that when they were working with BRU at the Pasteur Institute, its genetic structure changed depending on the medium they used to cultivate it. It is possible, according to this argument, that LAV and IIIb came from one line of BRU and that Gallo’s three surviving BRU samples came from another. If so, the Pasteur Institute should still have BRU samples that match LAV and IIIb. Montagnier plans to check his freezer to see, but Gallo doubts he will find what he’s looking for. In fact, Gallo says forthcoming studies from his lab and others will confirm that BRU is entirely separate from the viral strain common to LAV and IIIb.
That raises the question of where LAV and IIIb did come from, if not from BRU. Gallo doesn’t pretend to know. Montagnier’s discovery was clearly based on a contaminant, he says, but “that doesn’t mean we didn’t have a contaminant, too.” In late 1983, both the French lab and the American lab were having trouble keeping viral samples alive in cell cultures. In frustration, Gallo’s colleague Mikulas Popovic pooled samples from 10 patients to create a viral soup. IIIb emerged from that soup, but no one has succeeded at tracing it back to a single patient. NIH investigators have recovered most of the 10 samples and hired consultants to analyze them. But several samples have been lost or used up, so IIIb’s origins may well remain a mystery.
And so may the uncanny resemblance of IIIb to LAV. In the Nature paper, Gallo and his colleagues make no effort to explain the similarity, but their findings leave open several possibilities. If, as Montagnier asserts, BRU really was the source of LAV, then maybe Popovic’s viral soup was contaminated by one of the two BRU samples not included in Gallo’s recent analysis. It’s also possible that the French and American labs independently received viral samples from the same patient. A third possibility is that, contrary to previous accusations, the French virus originated in Gallo’s lab. By the time Montagnier’s team published a full genetic description of LAV in 1985, each lab had sent viral samples to the other. So it’s conceivable that a sample of IIIb contaminated a culture growing in Paris. There’s a problem with that theory, however. An NIH researcher named Malcolm Martin received a sample of LAV from Montagnier in April of 1984, a month before Montagnier received any IIIb from Gallo. And according to Martin, that early sample bore the same resemblance to IIIb as the later ones.
Martin, for one, believes it is still “critically important” that we find out where this hardy strain of the AIDS virus came from and who found it first. But that’s a minority opinion. Many scientists and activists share the view, expressed in an editorial in Nature, that “the issue has created an unhealthy diversion from the important business of stopping a deadly epidemic.” “A big waste of time,” says Duke University AIDS research Dani Bolegnesi. “An enormous distraction,” says University of Wisconsin Nobel laureate Howard Temin. “Who cares?” shrugs Dr. Gregory Curt of the National Cancer Institute’s treatment division. “Where does it stop?” asks Martin Delaney of Project Inform. No one stands accused of misconduct. No one stands to gain financially from the dispute’s resolution. The French and American teams have acknowledged each other’s crucial contributions. There is no serious doubt that LAV or IIIb causes AIDS. The global death toll is burgeoning. But don’t expect any of that to divert attention or resources from the case of the mystery tissue sample.
