Bad Blood : Two Groups of AIDS Researchers--One American, One French--Are Fighting More Than Just the Disease

For days, anticipation had been swirling among the scientists like the violent squalls that kicked up without warning outside the Hotel Meridien. The researchers had traveled to the island of Martinique, escaping the January cold of Washington and Paris for the beaches of the Caribbean, to compare notes on the scourge of the 1980s, the seemingly inexorable spread of acquired immune deficiency syndrome.

The culprit was a virus, known to American researchers by its scientific acronym HTLV-III and to the French as LAV. It had been discovered two years earlier and could now be isolated and grown in the laboratory. A blood test to detect its antibodies had been in use for nearly a year . But, still, the number of cases of the fatal disease was growing, with no effective cure or vaccine in sight, either under the microscope or in the dry, technical papers and slides presented in the darkened hotel meeting room.

At each session, over the course of several days, Dr. Robert C. Gallo of the National Cancer Institute (NCI), and Dr. Luc Montagnier, a French scientist conspicuous in a business suit among the more casually dressed scientists, would carefully sit on opposite sides of the hall. Gallo had an international reputation as the discoverer of a special class of viruses known as human retroviruses. Usually garrulous and constantly in motion, he seemed at pains to avoid the older, more low-key Montagnier. For his part, Montagnier--the head of the virology department of the Institut Pasteur in Paris, where American actor Rock Hudson sought treatment before he died of AIDS--seemed to associate only with his own close circle of French colleagues.

To an outsider, the standoffishness might have seemed unusual. Gallo, after all, was widely viewed as a brilliant cancer researcher, one whose work on retroviruses had made a dramatic contribution to the quick identification of the cause of the mysterious AIDS epidemic. Montagnier, though lesser known, was at the center of European efforts against the disease, which was beginning to spread on the Continent with the same ferocity with which it had already hit New York, San Francisco, Los Angeles and Miami. Their interests naturally coincided, and they had, in fact, worked together several times before, yet tension had existed between them for many months.

To their colleagues, the source of friction was obvious, almost embarrassingly so. Both men, as members of rival research teams, were claiming to have been the first to find the key to AIDS, to have isolated and identified the virus fewer than four years after the disease was first detected--a feat extraordinary in its speed. A month earlier, the French had begun a legal challenge in the U.S. Court of Claims against the U.S. patent awarded to Gallo’s team. It was far more than a point of national pride, far more than a question of personal and professional reputation. Riding on the competing claims was the right to millions of dollars in royalties from a patented blood test for the HTLV-III antibody, as well as the kind of recognition that often leads to such prestigious international awards as the Nobel Prize. For the Institut Pasteur, which depends to a large extent on funding from private sources, profits from sales of the blood test also would provide sorely needed resources for continued research. For Gallo, who stands to receive little money personally from the U.S. patent, a victory over the French would provide the scientific recognition he and his supporters believe he deserves.

To many scientists, the squabble was an unseemly one that had begun to erode the public belief in the altruism of medical researchers, and some felt that the legal bickering was having a draining effect on further research. “There is nothing wrong with competition,” says Dr. Sam Broder, who directs experimental AIDS drug therapies at NCI and is unabashedly loyal to Gallo. “There are good, creative scientists on both sides of the Atlantic. But the way I’d like to see these people distinguish themselves is by storming into my office with a cure for AIDS, or a vaccine. That’s the issue: Who can help us solve this problem the fastest?

“This virus,” he added, “is quite indifferent to judicial proceedings--that’s how I feel.”

That clearly was not how Gallo and Montagnier felt last January in Martinique. But, inevitably, the time came when they would confront each other. Suddenly, during a coffee break outside the meeting room, they found themselves face to face in a hallway with a crowd gathering. As a hush descended, Gallo eyed his colleague and tried to defuse the tension with a joking reference to the environmental group whose ship had recently been sabotaged by the French. “I’m joining Greenpeace,” he said, smiling gamely. The two men shook hands.

They had started that way, as friends, or at least as friendly competitors. Researchers looking for answers to the same scientific problems often view one another as polite rivals. Still, even when pursuing common goals, it is standard practice to exchange information and theories--even to formally collaborate. Papers published in prestigious medical journals often are co-authored by researchers from several institutions and from different countries. Such had been the case for several years between Gallo’s lab at NCI and a number of international scientists, including those at Pasteur.

“We were collaborating--we were friends,” Montagnier, 53, says of that period in early 1983, when the two camps and other scientists in the United States and abroad were frantically attempting to discover the cause of the then virtually unchecked disease. “There was no problem at the time.”

The flamboyant, gray-haired Gallo, 49, had several major scientific coups to his credit before 1982, when he decided to tackle AIDS. In 1978, he was the first to isolate and grow HTLV-I, or human T-cell leukemia virus, the first known human retrovirus and the first virus known to cause cancer in humans.

Viruses are special life forms with the ability to invade cells and force them to do their bidding. Human retroviruses are an insidious class of viruses whose genetic material consists of RNA, rather than the DNA found in every other organism. When retroviruses enter a cell, they use an enzyme known as reverse transcriptase to copy their RNA into DNA, which is then integrated into the DNA of its victim. In other words, its genetic material becomes a part of the host’s. And unlike common cold viruses, for example, retroviruses will stay in the body indefinitely, even though they may not always be active. They had long been known to exist in animals but, until Gallo’s work, had not been found in humans.

For Gallo, the discovery of HTLV-I, which causes a type of leukemia, was not without some personal irony: When he was 13, he watched his younger sister battle the disease. “It struck him very seriously,” says Dr. Peter Fischinger, deputy director of NCI. “It had a profound impact on him. He saw there wasn’t much that could be done. He’s been in the field ever since.”

Gallo’s lab, along with a group headed by David Golde at UCLA, subsequently isolated a second human retrovirus, called HTLV-II, from the cells of patients with another form of leukemia, known as hairy cell leukemia. And, in another major development, Gallo and his co-workers identified a hormone called interleukin-2, which plays a critical role in the growth of T-cells. Part of the body’s complex disease-fighting system, T-cells are involved in regulating a cell’s immunity to disease and controlling the production of antibodies to fight off foreign invaders.

The perpetually active Gallo, who always sets his watch 10 minutes fast to keep himself on schedule, commands an intensely loyal following among his staff and colleagues. Although he is no longer as actively involved in the day-to-day lab work as he once was, he still serves as an idea man for the more than three dozen scientists who work for him. “First came God,” says Flossie Wong-Staal, one of his lead researchers, “then came Gallo.” And he travels the country and the world to present his work and share information at scientific gatherings.

“I don’t think anybody had the depth of conviction on this thing that Bob has had,” Fischinger says. “Some scientists plod from A to B to C. That is not creative science. You have to have scientific intuition--a nose. Bob has that--he has the nose.”

In 1982, no one knew exactly what was causing AIDS or how it was being transmitted. Gallo suspected early on that whatever was behind AIDS was attacking T-cells, but not in the same way that HTLV-I does. That virus results in the wild proliferation of T-cells; the AIDS agent was--as researchers were to learn later--causing T-cells to die. (The AIDS virus selects only the critical T-4 helper cells of the immune system, destroying them as it multiplies, leaving its victim vulnerable to one ravaging infection after another.) Gallo began to theorize that the cause of AIDS was a member of the same family of human T-cell lymphotropic retroviruses, perhaps a variant of HTLV-I.

At the same time, Myron (Max) Essex, a professor at the Harvard University School of Public Health, was coming to a similar conclusion based on his studies of a T-cell retrovirus responsible for leukemia in cats. One of his more important observations was that the infection in cats resulted in severe suppression of the animal’s immune system--similar to what was happening to AIDS patients.

Gallo and Essex both began to make their speculation public.

The National Cancer Institute agreed without hesitation to back Gallo’s theory. “We had to make a commitment, and we did,” Sam Broder says. “We could have been wrong. In all fairness, we could have impeded somebody else’s research.”

In those tense days of late 1981 and early 1982, the number of AIDS cases reported in the United States was doubling every six months. A crisis mentality developed among scientists, making even routine chores matters of great urgency. Broder, frustrated with his inability to successfully treat AIDS patients in the National Institutes of Health’s clinical center, in Bethesda, Md., often hand-carried samples of blood and lymph and brain tissue across the NIH campus to Gallo’s lab at NCI and delivered them to Gallo personally, rather than entrust them to a messenger. “It was the fastest way I knew to get them to him,” he says.

Underlying their efforts was a tension of another kind, the unspoken terror that the scientists could possibly be exposing themselves to danger. One of Gallo’s researchers panicked one day when a lesion appeared on his leg. He thought--wrongly, it turned out--that he had developed Kaposi’s sarcoma, a capillary cancer common in AIDS victims but otherwise rare. “The element of risk was an important one,” Broder says. “AIDS was still a new disease then. Although we were using the best precautions, the risk factor had in no way been defined.”

Gallo tested the samples Broder had given him for the presence of the HTLV-I or -II virus. The tests were negative, but he persisted in thinking that the cause of AIDS was not only a virus but a variant of HTLV-I. He tried to re-create the conditions in which such a virus might grow, using the same techniques he had employed in isolating HTLV-I. And while he was able to detect some reverse transcriptase activity, indicating that he was dealing with a retrovirus, the virus would inexplicably stop growing after several days. What Gallo did not know then was that the AIDS virus was doing what it was programmed to do: kill the T-cells, just as it did in the human body. But nobody had yet made the connection.

“Those were the problems that everybody faced at that time--they couldn’t get it to grow,” Broder says. “You’d get a little action going--and then it would die.”

Gallo’s team and the French scientists were coming up against the same obstacle--researchers can’t do very much to crack a virus until it can be grown in large amounts. Everyone immersed in the investigation at the time was more than willing to share and exchange whatever sparse information was available.

Montagnier often attended meetings at NIH and other sessions around the country. “Montagnier came to Bob early in 1983 and said, ‘We want to be involved,’ ” says Dr. Howard Streicher, a senior staff fellow in Gallo’s lab. “I think Bob was very glad someone else was interested too. He supported it. He encouraged it.”

In Paris in the fall of 1982, the scientific director of the Institut Pasteur came to Montagnier, the head of the virology department, with a problem. The director’s laboratory was about to begin producing a new hepatitis B vaccine from plasma, including plasma from America. He was worried that whatever was causing AIDS might be present in the plasma and contaminate the vaccine. “We already had AIDS in France at the time,” Montagnier says. “He asked me if I would like to work with them.”

And so Montagnier joined France’s AIDS task force.

In January, 1983, he received samples of a lymph node biopsy from a French homosexual in his 20s. The man was not suffering from AIDS but did exhibit signs of lymphadenopathy, or swollen lymph nodes, often a precursor of the disease. The man had been very sexually active and, in 1979, had visited New York City, which was to become one of the cities hardest hit by the disease. Montagnier says the man is healthy today.

The idea, Montagnier says, was to isolate what he suspected was a virus from someone with pre-AIDS--which would come to be called AIDS-related complex, or ARC--rather than from a victim of the disease itself, because there would be more infected cells present: A person suffering from full-blown AIDS often has less virus in his system because many of the T-cells have already died.

“We were quite certain we were looking for a virus because there already had been cases with blood that had been filtered. A bacterium cannot pass through a filter, but a virus can,” Montagnier says.

Montagnier, Jean-Claude Chermann, head of the Pasteur lab, and Francoise Barre Sinoussi, another researcher in the virology unit, cultured the cells with fresh lymphocytes and T-cell growth factor and tried to grow the virus. Like Gallo, they saw some early growth--but then the cells began to die. The virus was killing the T-cells just like it did in the human body.

“It’s the way the virus behaves, but at the time we didn’t know that,” Montagnier says. “We thought something went wrong.”

Yet the Pasteur group caught on more quickly than the American group. Perhaps this was what was supposed to happen, the researchers thought. But they still weren’t sure what they had.

Like Gallo, Montagnier wanted to be certain his virus wasn’t HTLV-I or -II. He asked Gallo if he would send him some special reagents (substances used in chemical reactions to detect, measure or produce other substances) for HTLV-I and -II, so he could test his virus samples. Gallo complied immediately. “He helped us at the time,” Montagnier says.

According to a series of articles in the professional journal Science, which also was to publish all of the subsequent papers written by both research teams, the Pasteur group did additional work to further characterize its virus and obtained electron micrographs of virus particles budding from the surface of infected cells. Montagnier wrote a summary of his results and sent the paper to Gallo, asking if he thought it should be submitted for publication. Gallo made several suggestions, including one to add a phrase saying that the new virus appeared to be a member of the HTLV family. Montagnier agreed to the change, an action, the journal later noted, that “would come back to haunt him in a subsequent dispute over the naming of the virus.”

Montagnier’s paper and papers written by Gallo and Essex describing additional lab work linking the still-unidentified AIDS virus with the other HTLVs were published in the same edition, in May, 1983.

Science, in one article on Montagnier’s paper, commented that “one problem was that, because the paper reported only a single virus isolation, there was no way to tell whether the virus was a cause of the disease or an opportunistic infection (as a result of AIDS). Another problem was that the electron micrographs were not of high quality, and some scientists suggested that they did not even depict a retrovirus.”

The Pasteur researchers, as they began to isolate their virus from additional AIDS patients, became convinced that it was different from HTLV-I. They insist today that it is not even a member of the same family. They call it LAV--for lymphadenopathy-associated virus. “We think this virus is closer to what we call lentivirus,” Montagnier says, explaining that lenti , or “slow,” refers to the long incubation period of the disease, from several months to five or more years. “We believe this is the first human lentivirus. We are both dealing with the same virus--but he is calling it HTLV-III. It’s just a matter of semantics.”

Recently, a committee of scientists appointed to settle the dispute over naming the virus came up with yet another proposal: “human immune deficiency syndrome.” Unfortunately, the committee, which includes Gallo and Montagnier, has no authority to force scientists to adopt the name, and Gallo, who opposes the new name, has predicted that “the names of the virus that are already in the literature will be maintained.”

At one point in the summer of 1983, Montagnier sent samples of the virus from his lab to Gallo’s, an act that would figure in the future lawsuit. “We gave the LAV to Gallo, but he said he could not grow it,” Chermann says. “We sent another batch. He told us he took the virus and put it in the fridge. If it were me, I’d take the virus and try to grow it and see what it was. Why not? It’s not a crime.”

The NCI’s Fischinger says that “Bob tried to work with it and it didn’t grow. So he didn’t do much with it. If Bob hadn’t had anything of his own, it might have been useful. But Bob had a number of isolates of his own at the time. The French, however, are implying theft.”

Meanwhile, the Pasteur scientists began developing a test that would detect antibodies to their virus in human blood, although their test could not be mass-produced because LAV could not be grown in great quantities. According to Science, Montagnier reported that they had detected antibodies to LAV in 22 of 35 lymphadenopathy patients, 7 of 40 healthy homosexuals and 1 out of 54 controls. They filed for a patent on their test in Europe in September, 1983, and in the United States the following December.

Gallo, like his French counterparts, was also still having problems getting the virus to grow. But Gallo’s team, finally recognizing that the virus was knocking off T-cells, began searching for a cell line--a group of human cells that can be maintained outside the body--that was resistant to the effects of the virus. Mikulas Popovic, a cell biologist in Gallo’s lab, discovered that a mixture of cells taken from leukemia patients seemed to successfully resist destruction. The line, called H-9, finally enabled the scientists in Gallo’s lab to mass-produce the virus.

“The cells still die, but they grow at a faster rate,” says Dr. Prem Sarin, deputy chief of Gallo’s lab. “You can keep enough cells alive to grow the virus. When we found out that these cells grew--and (the entire cell line) didn’t die--that’s when we got excited.”

With that major breakthrough, Gallo’s lab could finally analyze the virus, to precisely understand its genetic makeup. Also, the team was able to develop its own antibody test--one that, unlike the Pasteur group’s test, could be mass-produced because larger amounts of the virus were now available.

Gallo called his virus HTLV-III. The U.S. government filed for its patent of the antibody test in April, 1984, four months after the French, and the application was granted several months later. It was the first of Gallo’s discoveries to be patented, a decision made by the U.S. government to protect the drug companies that would be manufacturing the test.

“The commercial concerns will tell you they won’t invest if you don’t protect them,” says NCI deputy director Fischinger. “The question was: How do you best stimulate the largest number of companies to do this and guarantee them the best protection possible?”

The French scientists at Pasteur were angered by the decision and argued their case for months with the U.S. government, without success. Finally, they filed a suit with the U.S. Court of Claims, saying, in effect, that the LAV samples Montagnier had sent to Gallo were eventually used in developing the blood test. The suit is pending.

Meanwhile, in a separate action, the U.S. patent office ruled in late April that it will hold a hearing--which could take as long as two years--on whether or not to revoke the patent from the U.S. government and give it instead to the Institut Pasteur.

At the heart of the controversy are varying interpretations by both sides of the detective work that finally solved the mystery: the identification and isolation of HTLV-III, or LAV, and the conclusive proof that it was indeed the cause of AIDS.

There are two things that no one disputes: Everyone agrees that the Pasteur researchers were the first to publish a scientific paper, in May, 1983, that identified and described a case report of a virus that turned out to be the right one. Everyone also agrees that Gallo--along with Harvard’s Max Essex--was the first to propose that the villain was a human retrovirus--a theory that sent scientists scurrying down the right path.

The agreement ends there.

Critics of the Pasteur group point out that its paper described only the isolation of a virus--it did not distinguish whether the virus was the underlying agent of the disease or simply the cause of one of the many opportunistic infections that were afflicting AIDS victims.

Supporters of Gallo and his co-workers argue that Gallo, when he published his work a year later, could demonstrate that he could grow large amounts of the virus and had a blood test that could find antibodies to it in nearly 90% of AIDS patients. Gallo also insists privately that he had found the virus as early as 1982 but had felt that it would be irresponsible to publish then. “We didn’t publish on principle,” he says, “because we didn’t understand the virus well enough then to stick our necks out.”

Streicher, of Gallo’s lab, says: “Bob didn’t want to go public until he was sure. We had a fear of misleading everyone. Bob has such leadership in the field of human retroviruses that a mistake might have killed the field.”

Gallo’s case wasn’t helped, however, by his recent admission that when he published his lab’s findings on the AIDS virus, it was accidentally illustrated with a photograph of the LAV virus Montagnier had sent him.

Complicating the dispute are differing perceptions of what constitutes discovery. Did the French researchers truly discover the virus because they were the first to publish a case history on the right one? Or would they--or anyone else--have ever even looked at retroviruses if Gallo had not first proposed the theory?

“I suggested this was a retrovirus,” Gallo says. “They got the idea from us. That’s the way science works. To me, discovery is a complicated word. The idea counts for something. The idea and the technology came from here--the technology was ours. Who reported the discovery of a virus? They did. But if the idea comes first--that was us. Look at what we did first. Then look at what they did.”

Gallo doesn’t hide his anger at the behavior of the Pasteur team. “I said to the world: I know the cause of AIDS. They didn’t know. Science is proving. They are just trying to rewrite history for self-serving reasons.”

Montagnier counters: “He says, ‘You were first, but we did the work to characterize it and prove it caused AIDS.’ I don’t agree with this. Good science is not only done in the United States. It’s important to have several groups working independently. If I’d been working in the United States, I never would have found this virus because the intellectual pressure from Gallo is so high that no one can work independent of him.”

As the feud began to escalate late last year and people began to talk about it, Gallo found himself constantly being asked about his problems with “the French.”

“It’s not ‘France’ or ‘the French,’ ” he would respond, bristling. “France is a nation. We collaborate with French scientists. It’s just a few of the French”--meaning Montagnier and Raymond Dedonder, the director of the Institut Pasteur, who initiated the legal action.

Indeed, Gallo can count many non-Pasteur French AIDS researchers among his ardent supporters. He even maintains a long-running friendship with Chermann, the tall, suave, 46-year-old head of the Pasteur lab.

“Jean-Claude and I are old friends,” Gallo says of a relationship of nearly 20 years. “We’re drinking buddies,” he says, laughing, and then grows serious. “I’m not going to destroy that kind of friendship over something like this.”

Indeed, it is equally painful for Chermann, who is in the uncomfortable position of having to challenge his old friend’s claim to a major scientific triumph. “There have been a lot of exchanges between my lab and the American lab,” says Chermann, who has trained in Gallo’s lab. “The suit is between the Institut Pasteur and the U.S. Department of Health and Human Services--not between the scientists. It’s not between Gallo and me--our enemy is the disease. I don’t ever question the honesty of Gallo.”

Despite his regard for Gallo, Chermann is loyal to his own institution. “The recognition is already made,” he says. “All the scientists in the world know we found the virus first.”

The issue of who owns the rights to HTLV-III or LAV is not likely to be resolved quickly. Millions of dollars worth of royalties from sales of the test are at stake. The Institut Pasteur, which is funded by both government and private funds, says it needs the money.

“It would be used not to make profits, but to fund more research,” Montagnier says. “Nobel juries don’t like this kind of fighting. So this will not help--it’s not a question of that. It’s money for the Institut Pasteur, and principle. There is nothing immoral in this. You have to follow some kind of scientific ethics. If we don’t do anything on this case, we’ll never do anything on future cases.”

As for Gallo, he stands to gain little financially from having his name on the patent: Most of the profits will go into the U.S. Treasury. And he complains that he is wasting precious time dealing with legal depositions.

“If I wanted to make money, I wouldn’t work at NIH,” Gallo says. “If I get any money from this at all, I will give it to charity. This patent is the worst thing that ever happened to me. What am I getting out of it? I’m getting nothing out of it but a lot of pain.”

The scientists who surround Gallo and Montagnier view the battle with a mixture of discomfort, anger and sadness. Most of all, they fear its effects on the vital work itself. “This kind of scientific work is not done as a contest,” says Streicher. “Clearly, people have egos--everyone is driven by egos, but it’s not a zero-sum game.”

Meanwhile, hundreds of new cases of the fatal disease are being reported every week. Scientists continue their desperate search for both a cure and a vaccine, and Sam Broder, articulating the ultimate frustration of virtually everyone involved in the war on AIDS, laments that--as the legal battle rages--” we’re the guys who have to watch these patients die.”