Another Aids Teaser

By Christine Gorman

Research on aids is like a relentless pendulum that swings between great expectations and great disappointment. Every time there's a hint of a breakthrough in the so far futile quest for a cure, the press blares it to the world, raising the hopes of AIDS sufferers. Almost every time, however, the initial excitement gives way to doubts, criticism, caveats and, eventually, renewed despair. And when rival scientists, competing to boost their reputations, as well as help humanity, disagree about the validity of a "breakthrough," no one knows whom or what to believe.

The AIDS pendulum took another big swing last week, thanks to a claim by biologist Ara Hovanessian of France's Pasteur Institute that his research team had made a major advance in understanding how the AIDS virus infects a healthy cell. The news created an instant stir, since the prestigious Paris-based institute is where HIV was first identified. Even before Hovanessian had a chance to present his findings to a Pasteur-sponsored conference and before other scientists were able to evaluate the research, the press got wind of the story and ran with it. Countless TV and newspaper accounts, including feature articles in Le Monde and the New York Times, heralded the possibility of new AIDS treatments.

When Hovanessian finally stepped up to the conference podium in the Paris suburb of Marnes-la-Coquette, he faced an animated throng of 200 fellow scientists and a large contingent of reporters. But by the time the Lebanese- born biologist had finished flashing 20 graphs and charts on the screen beside him, a buzz of doubt had filled the room, and the long-standing rivalry between American and French AIDS researchers had once again surfaced.

Since 1984, investigators have known that HIV assaults the cells of the immune system by latching on to a protein "receptor," named CD4, found on the cells' surface. When an invader attacks the body, the CD4 molecule normally helps mobilize the immune system's defenses. In this case, though, HIV fools the CD4 receptor into allowing viral particles into the cell. Hovanessian reported last week that his team had found a second receptor, called CD26, that helps the virus enter the cell after it has attached itself to CD4. If Hovanessian is correct, scientists might be able to devise drug treatments that block access to the CD26 receptor -- and thus prevent infection.

But many other prominent researchers attending the conference, including Robert Gallo of the National Cancer Institute in Bethesda, Maryland, did not seem at all convinced that a cure was any closer. Gallo, among others, has failed in efforts to design an effective treatment based on the original discovery of the CD4 receptor. After Hovanessian's talk, Gallo tried to avoid reporters but was finally cornered. "Why is the press so excited about this?" he demanded. "I'm flabbergasted. I thought it was an interesting presentation, but I can't say more than that." Gallo's lack of enthusiasm was + hardly surprising: he's still smarting from a losing battle with another Pasteur researcher, Luc Montagnier. For six years, both scientists claimed to have been the first to identify the AIDS virus, until Gallo finally admitted in 1991 that the virus he "discovered" had been previously isolated by Montagnier.

Sitting atop a desk in a corridor of the conference hall, Hovanessian was incensed at the skepticism he faced. "It's very shabby of these American colleagues who questioned the results," he said. "While I was talking, Gallo was sitting in the front row laughing all the time." Alternating between French and English, Hovanessian rejected the idea that his announcement was premature. "You don't think I would just come up with something like this, throw it out there and say, voila, take it?" he asked. "We have had these results in hand since April and have repeated the whole series of experiments a dozen times. We applied for a patent several months ago. We have proved it is reproducible."

Not all the skeptics were Americans, however. "I don't see the beginning of a proof," fumed Jacques Liebowitch of the Raymond Poincare Hospital near Paris. "The press has already whipped this up into a major breakthrough, and now we find that there is nothing to it." Even Hovanessian's own colleagues at Pasteur seemed somewhat reserved. "It's a very interesting paper," said Francoise Barre-Sinoussi, who helped Montagnier isolate the AIDS virus. "The danger is that whenever there is something interesting in this field, it gets blown out of proportion. There are other experiments to do, and I'm sure Hovanessian already has follow-up work under way. The problem is that these are preliminary data."

Hovanessian and his team have submitted their research to the journal Science, where experts will review it before publication. Pasteur's head of vaccine research, Marc Girard, nicely described the promising but precarious place in which his colleague's research stands: "If these results are reproduced in the next weeks or months by one or two other labs in the U.S. and elsewhere, then it's fantastic, because that would mean Hovanessian has really discovered something new. But we have to get to that stage before we can get excited."

With reporting by Thomas A. Sancton/Paris