BRIAN DEER: THE VAXGEN EXPERIMENT Page 4

Every six months, a ten-strong committee of doctors and scientists crowds into VaxGen's boardroom. This is the "data safety and monitoring board", recruited to keep an eye on the experiment. On one side of the table sits a Harvard infectious disease specialist. On the other is a Yale ethicist. There are three Thai physicians and a Seattle statistician. Dr Walter Dowdle, a former CDC deputy director, presides. The Americans are casual, in open-necked shirts, but Dowdle runs proceedings with care. Piled around the table are printouts on the volunteers, with blood tests and other results. Using codes which nobody else gets to look at, they can see who's getting AidsVax and who the placebo and whether any difference the number of HIV infections has emerged between the groups.

By the convention for vaccines, any difference would be vast for the product to be declared effective. Measles vaccine, for instance, is 95% effective, tetanus 90%, and hepatitis B 85%. But the committee's brief is to watch for just 30% effectiveness. Such is the threat from Aids, it's argued, that this figure is enough for success.

I asked a professor of medical statistics to number-crunch this percentage. To reach the 30% mark, he said, there would only need to be 28 more infections among junkies on the placebo than among those receiving AidsVax. If VaxGen recruits 2,500 - and on its assumption that in a year about 7% (87 people) on placebo will become infected due to needle-sharing - then if the number who become infected after getting AidsVax is 59 (4.7%) or fewer, the committee can rule that the product works.

VaxGen critics think that even this meagre difference couldn't appear, and that Dowdle, 68, will one day emerge to drape a consoling arm on Francis's shoulder. But an alternative scenario is predicted by some with long research experience. Nobody can recall an HIV product being ditched after reaching a full-scale efficacy trial. And, such is the desire for "something to be done" about Aids that science could be pushed to one side.

The most powerful pressure for something to be done comes from the White House, anxious to appease the Aids lobby. In May 1997, President Clinton threw his weight behind urgent action. "If the 21st century is to be the century of biology," he declared. "Let us make an Aids vaccine its first great triumph."

How such pressures can translate date back to 1989 and the first anti-Aids drug, AZT. A board like Dowdle's monitoring a trial among HIV-positive volunteers with no obvious illness, saw data suggesting that full-blown Aids could be prevented. At the time, AZT was licensed only for terminal disease, but this finding caused the trial to be halted and the product to be approved for this use. But the decision was based on a transitory data "blip", which had caused the board to act prematurely. A longer study, published four years later, found no preventative effect.

Stopping trials in this way before their scheduled completion is now standard in Aids product development. "If efficacy is observed at the time of a scheduled interim efficacy analysis," Nowinski explains, "the monitoring board will recommend termination of the trial."

But could bodies such as the Food and Drug Administration and the European Medicines Evaluation Agency license a vaccine that doesn't work on the basis of an AZT-style blip? Evidence suggests that agencies under political pressure take just such paradoxical steps. The National Institutes of Health, for instance, vetoed the VaxGen experiment as a waste of money and volunteers. But after being accused of "a human rights violation" by Dr Jonathan Mann, 51, former WHO Aids chief (and who died with his wife, Clements-Mann, also 51, in the Swissair crash), the institutes not only reversed themselves, but granted Francis $4.6m.

Sometimes the clamour may be marshalled by persons who may not be as detached as they seem. The Journal of Aids Research and Human Retroviruses, for instance, has an editorial board that's a Who's Who of Aids. But Francis paid the publisher $10,000 for the "special issue", which Berman edited as a "guest". As for some of the contributors, Francis helped to set up Berkley's international vaccine initiative and advised Bill Gates's charity foundation to give it $25m. He has done a deal to supply proteins to the rival manufacturer which employed Clements-Mann. And he has offered the CDC's Heyward the post of VaxGen vice-president, starting next January.

Pressure also comes from powerful bodies which have long-held institutional agendas. The CDC, which mostly collates disease data, first became a significant health service body due to polio vaccine, launched in April 1955. The WHO's singular success was smallpox eradication, accomplished in October 1977. Mass immunisation is what they know best. It's simply what they do. "Don Francis reminds them of when they were young," Dr John Moore, of New York's Aaron Diamond Aids Research Center, told me.

What worries critics such as Moore is that political and institutional pressures may lead to millions of people being injected with AidsVax before the benefits and risks are clear. The WHO estimates that annual demand for the first vaccine will be 650m doses and UNICEF leaders are thinking about adding it to programmes for 100m children.

Francis anticipates that the CDC, which has already granted him $8m, is to finance a US immunisation campaign and, in Europe, national health services will pick up the tab. "In addition, the International Aids Vaccine Initiative has started a campaign to fund the development and purchase of an HIV vaccine for the developing world," VaxGen documents say. "In meetings with us, the World Bank has indicated that it's exploring the potential for low-interest loans to support the purchase."

One of the snags which may be overlooked in this rush is the effect on recipients' behaviour. Common sense says that somebody who thinks that they may be protected is more likely to take chances with risky activities than a person who knows that they aren't. One study of this effect in 1997 found that unsafe sexual behaviours doubled among gay men in preliminary vaccine tests. If this was repeated globally, the impact of an even vaguely effective AidsVax may be that the Aids epidemic gets worse.

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This report is copyright, Brian Deer. Responses, information and other feedback concerning this resource on VaxGen and AidsVax and the "world's first Aids vaccine" are appreciated - via the briandeer.com homepage.