On the afternoon of the day before his 50th birthday, the American scientist Robert C. Gallo sat down at a small desk in a hotel room in Germany. In the chair next to his was Luc Montagnier, one of the French researchers from whom Gallo had been trying for nearly three years to steal the credit for discovering the cause of AIDS.
Neither Montagnier nor Gallo, the unchallenged AIDS superstar at the National Institutes of Health, was there by choice. The two scientists had been forced together by pressure from their governments, and their peers, to write a combined history of their research that would end their increasingly acrimonious dispute.
The Pasteur Institute, where Montagnier works, had formally challenged the patent on the blood test for AIDS developed in Gallo`s lab, and the American government was eager to settle the case. Any settlement would turn on the question of who had been first to find the virus that causes the disease and use it to make a test.
The `definitive scientific history` that emerged from that hotel room in Frankfurt made possible an agreement between the French and American governments, the first ever to resolve an international conflict over a scientific discovery. Officially, the dispute has been settled forever. In reality, the scientific world has been left with more questions than answers about who really discovered the cause of AIDS, and when and where and how.
In an effort to distinguish scientific truth from gossip, rumor and professional jealousy, The Chicago Tribune undertook a reconstruction of the discovery of the AIDS virus that has included the examination of more than 5,000 pages of government documents and interviews with 150 scientists in this country and abroad.
The story that emerges is less heroic than generally portrayed, but no less dramatic: misstated data and secret experiments, phantom viruses and disappearing genes, unreproducible results and muddled lab notes, mislabeled cultures and misleading photographs.
What also emerges is that the history-inelegant, vastly incomplete and technically inaccurate – even begins with a lie. Between the Gallo and Montagnier laboratories, it says, there had always been `a spirit of scientific cooperation and a free exchange of ideas.`
As with many histories, the biggest lie is in what it doesn`t say. Utterly missing from the account of this great scientific achievement is the story of an influential and intimidating scientist who chased the wrong virus for more than a year, only to reverse course and emerge with a virtual genetic twin of the virus that had really been discovered by his rivals in Paris and delivered to him months before.
What happened in Robert Gallo`s lab during the winter of 1983-84 is a mystery that may never be entirely solved. But the evidence is compelling that it was either an accident or a theft.
1. `WE FORGOT TO WRITE THE SUMMARY` The beginning of the 1980s looked like the beginning of the end for infectious diseases in America. Smallpox had been eradicated, polio was nearly nonexistent and the childhood illnesses were on the ropes. Then, in the spring of 1981, doctors noticed that a few young men in large American cities were dying horrible deaths. Something was ravaging their immune systems, but what? As the death toll mounted, so did the theories. Because all the early patients were homosexuals, some scientists thought the disease that would later be called AIDS must be a byproduct of the gay lifestyle. But when the same symptoms began turning up in hemophiliacs and in heterosexuals who had received blood transfusions during surgery, the possibilities narrowed. Any number of infectious micro-organisms might be transmitted in semen or blood, but the only thing small enough to evade the filters used to screen the clotting factor given hemophiliacs was a virus.
In May of 1983, less than two years after the first AIDS cases had been recognized by physicians at UCLA, an anxious nation was relieved to learn that scientists at Harvard and the National Institutes of Health had found the likely cause. As many researchers had been predicting, it seemed that AIDS was indeed caused by a virus. What came as a surprise was that the virus had apparently been around for years.
Its scientific name was human T-cell leukemia virus, HTLV for short, and it belonged to a relatively small group of viruses known as retroviruses. So far HTLV had been linked only to a rare leukemia found mostly in the fishing villages of southern Japan. Now the experts were suggesting it might also be responsible for what would soon become the biggest public health emergency since half a million Americans perished in the great influenza epidemic of 1918.
One of those making the announcement was Robert Charles Gallo, a veteran researcher and laboratory chief at the National Cancer Institute, the biggest and richest of the research institutes that make up the multibillion-dollar federal biomedical complex known as the National Institutes of Health in Bethesda, Md. Not coincidentally, it was in Gallo`s laboratory at NIH that the leukemia virus had first been isolated a few years before, a discovery that had propelled Gallo to the top rank of American medicine. Just six months before the announcement, when Gallo was awarded the Lasker prize, the top honor in American biomedicine and a frequent precursor of the Nobel prize, the citation had lauded his ”revolutionary discovery of the first retrovirus known to be associated with a human malignancy.”
In the summer and fall of 1982, just as the AIDS epidemic was beginning to grip the public`s attention, the most important thing on Gallo`s mind was finding out how many people around the world had been infected with his new leukemia virus and the even newer substrain, called HTLV-2, that one of his assistants had just isolated from a Seattle seafood salesman.
Arthur Levine, then chief of the cancer institute`s pediatrics branch, remembers a conversation with Gallo about AIDS in June of 1982. From colleagues on the West Coast Levine had become aware of the AIDS epidemic early on, and he also knew a thing or two about retroviruses.
”It was a phone call from me to Bob Gallo,” recalled Levine, now scientific director of the National Institute of Child Health and Human Development. ”I said, `Bob, have you heard of this bizarre syndrome that`s happening in San Francisco and New York?` He hadn`t heard of it. I described it to him, and he agreed that it was very intriguing. And then I said the most intriguing thing is that I think the cause of this syndrome is going to be a retrovirus related to HTLV. He said that`s very interesting and got off the phone.”
The ”bizarre syndrome” was being watched most closely by the federal Centers for Disease Control in Atlanta, where a small group of researchers was hunting frantically for its cause. In the fall of 1982, it occurred to a young CDC virologist named Cy Cabradilla, who had done his postdoctoral fellowship at the cancer institute a few years before, that one of Gallo`s two human retroviruses might have something to do with AIDS.
”We were looking at every virus we could get our hands on to see if there was any relatedness,” Cabradilla said. ”The only one we hadn`t really looked at was the human retrovirus. I made an appointment to go up and talk to Bob about evaluating some blood samples for us against HTLV. I spent an afternoon up there. He didn`t seem that interested. I don`t think he wanted to get involved with a gay disease. I think what turned him around was Max.”
”Max” was Myron T. Essex, one of Gallo`s longtime collaborators and a senior researcher at the Harvard School of Public Health. Using an established laboratory technique called an immune fluorescence assay, Essex had been testing blood samples from young homosexual men with this newly reported wasting disease.
In the Essex test, the patient samples were exposed to cultures of white blood cells that were known to be infected with the leukemia virus. If the blood contained antibodies to the virus-antibodies are proteins manufactured by the immune system to neutralize invading viruses and other microbes-they would presumably stick to the virus in the cells. When the cells were examined under an ultraviolet light, those to which antibodies had become attached would glow with an iridescent sheen.
Essex was finding that impressive percentages of the samples were positive, an indication that the AIDS patients were infected with the leukemia virus. According to Essex, however, his test was not picking up antibodies to the leukemia virus itself but to a mysterious new protein that seemed to appear on the outer surface of the virus-infected cells as a product of the process of infection.
Essex`s data were hardly conclusive, but they were tantalizing nonetheless. As one member of Gallo`s staff recalled later, when Gallo first heard about what was going on in Essex`s lab at Harvard, ”it was like Christmas.” For Gallo, the idea that his obscure leukemia virus might be the cause of AIDS made a certain amount of scientific sense.
For one thing, the leukemia virus infected a particular kind of white blood cell known as a helper T-cell, and it was a shortage of helper T-cells that was apparently causing AIDS patients to fall ill with various exotic diseases by robbing their immune systems of the ability to respond to infection. For another, the leukemia virus was a retrovirus, and there was evidence that an animal retrovirus, feline leukemia virus, could cause the same kind of immune deficiency in house cats.
Because so many AIDS patients were homosexual men, many scientists assumed that whatever was causing the disease was transmitted sexually – and so, they thought, was HTLV.
But even if Essex was right, finding antibodies to a protein on the surface of leukemic T-cells was like finding the footprint outside the window after the burglar had fled. Gallo wanted to catch the burglar in the act by finding AIDS patients who were infected with the leukemia virus itself.
From doctors and hospitals around the world, blood and tissue cells from patients with AIDS or pre-AIDS, the collection of lesser symptoms that often precede the disease, had begun arriving in cartons of dry ice at Gallo`s laboratory on the top floor of Building 37 on the NIH campus. After the samples were logged in they were tested for reverse transcriptase, the enzyme that retroviruses manufacture in order to reproduce themselves. Those that tested positive were examined for evidence that Gallo`s leukemia virus was present in their cells.
The early results were encouraging. Within weeks, Gallo`s assistants had detected the leukemia virus in the white blood cells of two East Coast homosexuals, a young Haitian woman named Marcellin who had died of AIDS in Paris, and a 31-year-old Frenchman named Claude Chardon who had been given a blood transfusion in Haiti after losing his left arm in a motorcycle accident. Including the two East Coast homosexuals and Marcellin, nearly all of those outside Japan in whom the leukemia virus had been found were black. Daniel Catovsky, a researcher London`s Hammersmith Hospital, had recently discovered it in several Caribbean immigrants there, and some scientists were beginning to wonder whether blacks were somehow genetically predisposed to infection with HTLV-1. Most of the infected blacks didn`t have AIDS. On the other hand, nearly all of those who were sick with AIDS were both white and homosexual. Chardon seemed to represent some kind of bridge. He wasn`t black, and according to his widow he wasn`t gay. If Chardon had the leukemia virus and he also had AIDS, then perhaps the two really were connected.
The cells from Marcellin and Chardon had been brought to Gallo in February of 1983 by a French immunologist named Jacques Leibowitch, one of a small group of doctors in Paris who were also searching for the cause of AIDS. Since the summer before, the Harvard-trained Leibowitch had been telling his colleagues in France that the cause was probably a retrovirus, and when he heard about Chardon`s case from doctors at the Saint-Lazare Hospital he was quick to recognize its significance. ”I was there at the seminar where they presented the case,” Leibowitch recalled, ”and I was strongly motivated to get the cells of this guy. It could serve the purpose of demonstrating that the cause of AIDS was not homosexually related.”
In early March of 1983, Gallo sent a paper reporting the detection of his leukemia virus in the two East Coast homosexuals to Science magazine, a weekly published by the American Association for the Advancement of Science and second only to the British journal Nature as a prestigious forum for biomedical research. In a cover letter to the magazine`s editors, Gallo made clear he was not claiming the leukemia virus caused AIDS. Rather, he hoped his findings might ”direct research in AIDS toward a class of agents not addressed in the literature to this point.”
Within a few weeks Gallo had sent Science a second paper, this one reporting that the leukemia virus had now actually been isolated from one of the two East Coast homosexuals and had also been detected in the cells of Marcellin and Claude Chardon. In the meantime Essex had submitted a paper of his own to Science, reporting that up to 40 percent of the AIDS patients whose blood he had tested had antibodies to the mysterious protein on the surface of leukemic helper T-cells. Harvard University, which like most universities owns its faculty members` inventions, promptly applied for a patent on the Essex test.
A few weeks before publication of the papers, Gallo presented his superiors at the National Cancer Institute with a bold proposal. The NCI, he wrote, should move quickly to take the lead in what seemed likely to become a fierce scientific and medical battle against AIDS. A special AIDS working group was needed, Gallo said, and he suggested that he be named its chief of research, an additional responsibility that would require more laboratory space and personnel, but only ”until the problem is solved or (for) three years, whichever comes first.”
When the papers from Gallo and Essex appeared in the same issue of Science in May of 1983, they made a considerable splash. The Washington Post called the possible involvement of Gallo`s leukemia virus ”the strongest clue yet to the cause of AIDS.” The Boston Globe nominated the virus as ”the leading suspect for causing the illness.” Even Science`s archrival, Nature, took note of ”an important group of papers” that ”confirms that HTLV is indeed somehow linked with AIDS.”
More than 1,200 Americans were already sick with AIDS. Physicians in San Francisco, New York and other big cities were seeing new patients each week, and they were becoming increasingly anxious to know more about the mysterious and deadly disease with which they were confronted. Now they were being told that AIDS might be caused by a leukemia virus. To some, the idea that a cancer virus might underlie an immune deficiency didn`t make immediate sense, but most of those who read the articles in Science put their confusion down to lapses in their own understanding of retroviruses and AIDS. The relatively small number of scientists who knew something about retroviruses did have some questions, however.
The curious thing about Essex`s data, they thought, was that his numbers were neither high nor low-not high enough to show a conclusive link between the leukemia virus and AIDS and not low enough to be a coincidence. But Gallo and Essex agreed that Essex`s test needed to be refined, and they had answers for the other objections as well. When it was pointed out that there was no AIDS in southwestern Japan, where the leukemia virus was most common, Gallo suggested that maybe AIDS hadn`t been noticed there yet, or that Japanese people perhaps responded differently to the disease.
The news accounts about the possible link between HTLV and AIDS-and there were many in the spring and summer of 1983-barely mentioned a fourth paper in the same issue of Science. The lapse was perhaps understandable since the magazine itself, in an accompanying news article, had dispensed with the paper in a single sentence. When the nonscientific press referred to the paper at all, it was mostly as an afterthought, to note that researchers at the Pasteur Institute in Paris had provided confirmation of the findings by Gallo and Essex.
The origins of the AIDS work in Paris traced back to the end of 1981, when a group of physicians began meeting informally to discuss what one member, a young immunologist named David Klatzmann, called ”a disease which at that time interested nobody.” Jacques Leibowitch was also a part of the Paris group, and it was he who focused the group`s attention on the possibility that a retrovirus was responsible for AIDS.
”None of us was a retrovirologist and we had no idea what this virus was,” Klatzmann recalled. ”We discussed how to isolate such a virus, and we reasoned that maybe the lymph node was the best point to look at.” Another member, Francoise Brun-Vezinet, had taken a course in virology at the Pasteur Institute and remembered the name of one of her lecturers. In mid-December of 1982 Brun-Vezinet put in a call to Luc Montagnier, the chief of the Pasteur`s department of viral oncology. Yes, Montagnier said, he had heard about AIDS and had thought about the possibility that a retrovirus was involved. If the clinicians would bring him a lymph node from someone with AIDS, he would look for such a virus.
The French physicians had already decided the best place to look was the cells of someone who did not yet have full-fledged AIDS. If a virus was present, and if the virus was infecting the helper T-cells, then a person in whom the disease was not so advanced might have more infected cells in which to find the virus. As it happened, another of the Paris clinicians, a tropical disease specialist at the Claude Bernard Hospital named Willy Rozenbaum, had been seeing just such a patient, a young homosexual named Frederic Brugiere.
A fashion designer, Brugiere had been suffering for several months from the persistently swollen lymph glands that often precede AIDS. Other than that, however, he was healthy. On the afternoon of Jan. 4, 1983, Francoise Brun-Vezinet delivered a slice of Brugiere`s lymph node to Jean-Claude Chermann, who worked under Montagnier as a lab chief at the Pasteur. Chermann gave the sample to Montagnier, who minced the tissue and put the T-cells he extracted into a flask filled with nutrients to keep them alive. To encourage the growth of any virus that might be present in the cells, Montagnier added an antibody designed to counter the effects of interferon, a protein produced by the immune system that protects T-cells against viral infections.
Because the flask was stored in an incubator that kept it at body temperature, if a virus was present it should begin reproducing in the laboratory just as it would in Brugiere`s body. If it happened to be a retrovirus, the first evidence of its existence would be the activation of an enzyme called reverse transcriptase as it assembled DNA copies of the virus`s native RNA.
In one sense, the AIDS epidemic could not have come at a better time. If AIDS had appeared even a decade earlier, researchers would not have known where to begin searching for its cause. Helper T-cells had not yet been recognized as a separate class of white blood cells, retroviruses in humans were unknown and there were no reliable tests for reverse transcriptase. Now, however, there was such a test. Every three days Montagnier drained fluid from the culture and gave it to Francoise Barre, another Pasteur scientist who worked for Chermann and who was skilled at using radioactive isotopes to measure the amount of DNA being synthesized by a retrovirus.
Seven times, at three-day intervals, Barre tested the culture fluids for reverse transcriptase, and seven times the results were negative. But on Jan. 26, 1983, when the radioactivity in the fluids reached 5,600 counts per minute-about three times the background radiation at the Pasteur-Barre began paying attention. Three days later, when the radiation level reached 22,000, it seemed only one conclusion was possible: a retrovirus was growing in Frederic Brugiere`s cells. Then the numbers on the radiation meter began to fall.
”The first reaction was to think that we had tissue culture problems,”
Barre recalled, and such a conclusion was understandable. When Gallo`s leukemia virus, then the only known human retrovirus, was growing in a culture, the reverse transcriptase level didn`t rise and fall; it simply continued to rise as the virus transformed increasing numbers of white blood cells into cancer cells. But the cells in the French AIDS virus culture weren`t multiplying as they would have in the body of a cancer patient; they were dying.
If AIDS was characterized by a decline in the number of helper T-cells, and if a virus was infecting those same cells, then perhaps there was nothing wrong with the culture medium after all. Perhaps it was the virus that was killing the cells. That would explain not only the decline in reverse transcriptase activity and the dying cells, it would also explain the clinical progression of AIDS.
The Pasteur group`s solution to the question of how to keep the virus growing was both simple and elegant. ”We decided,” Barre says, ”to add fresh cells.” When a second attempt was made to grow the virus, Brugiere`s cells were mixed with fresh T-cells from blood recently donated by a Spanish tourist at the Pasteur`s hospital. There was nothing special about the Spaniard. ”I was in a hurry,” Montagnier recalled. ”The first donor who came along was the right one.”
