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Mann (left) has irked Baltimore (right) and others with his criticism of NIH. Credit: AP/TIM SHARP

The former director of the World Health Organization's Global Programme on AIDS, Jonathan Mann, has accused the US National Institutes of Health (NIH) of violating human rights by failing to proceed to large-scale clinical trials of AIDS vaccines.

His remarks were made in an address to the President's Advisory Council on AIDS (PACHA) last month shortly before the council proposed that leadership of AIDS vaccine development be moved out of NIH and into the White House Office of National AIDS Policy.

But leaders of NIH's effort to develop a vaccine argue that the remarks by Mann, who is now dean of the School of Public Health at Allegheny University of the Health Sciences in Philadelphia, are scientifically uninformed and inject politics unnecessarily into what should be a rational scientific debate.

“It's time that Dr Mann sits down with the data and looks at it,” says David Baltimore, president of the California Institute of Technology, and head of a committee that advises NIH on AIDS vaccine research. “He should be involved in a scientific debate, not a political and rhetorical one.”

Such sentiments are shared by Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases: “It's unfortunate that Jonathan has put the difficulties that one encounters in vaccine development, and decisions about vaccine trials into the arena of human rights.”

Addressing PACHA last month, Mann accused Baltimore and Harold Varmus, the NIH director, of incompetence and ethical failure because NIH has not launched large-scale phase III clinical efficacy trials of any HIV vaccine candidate.

After their safety and immunogenicity have been demonstrated, “vaccine candidates are ready to be tested in human trials”, he said. Therefore “the federal government's failure to proceed to vaccine field trials is a human rights violation”.

Mann claimed that Baltimore, a virologist and molecular immunologist who won the Nobel prize in 1975 for his co-discovery of reverse transcriptase, is “not equipped to develop an AIDS vaccine” and that, with Varmus, he is “holding a monopoly lock on the process”.

“This is too big a problem to leave scientists in charge of,” Mann said, arguing that the ten-member committee that Baltimore heads — and which is dominated by basic scientists — should feature equal representation by vaccinologists and public health experts.

Mann, a medical doctor with a master's degree in public health, charged that, because AIDS disproportionately affects the poor and minorities, vaccine development is progressing more slowly than it would if the affluent were primarily afflicted. He also argued that it is “unrealistic and illusory” to wait for scientific consensus on when a vaccine candidate is ready, pointing out that scientists had been in conflict before they launched field trials of vaccines such as polio.

Mann is not alone in his assessment of NIH's vaccine work. “The current federal AIDS vaccine effort is stalled in paralysing scientific debate and bureaucratic delay,” PACHA said in a statement three days after his address. “It is only within the Office of the President that sufficient authority exists to ensure leadership, thorough coordination and collaboration of all requisite constituencies.”

But Mann's speech has piqued NIH leaders, who say he is ignoring the scientific fact that no vaccine candidate is ready for clinical efficacy trials. They point, for example, to a recent study, reported in the Journal of Virology, of 16 individuals who had become infected in phase I and phase II trials, despite vaccination with a gp120 vaccine, which relies for immunogenicity on a single subunit protein of HIV.

This paper concluded that the vaccine conferred no beneficial or adverse effects on the individuals. “There's an enormous amount of evidence here that the kinds of antibodies induced in vaccinees are not antibodies that can neutralize a virus, that can protect people,” says Baltimore.

Baltimore says that Mann's arguments rely on generalities and historical analogies that do not pertain in the AIDS context, and when individual AIDS vaccine candidates are scrutinized.

However, Mann is unapologetic. The consternation he has stirred up at NIH is “appropriate”, he says. “I continue to fail to see the kind of clear, milestone-driven process [at NIH] that includes not only the opinions of basic scientists, but the knowledge and experience of people who have developed vaccines.”

His critics include Gregg Gonsalves, a spokesman for Treatment Action Group, a national AIDS research advocacy organization, who calls Mann's speech “outrageous and irresponsible”. “There is this notion tha t there are these big bad NIH scientists standing in the way of phase III development of an effective HIV vaccine,” says Gonsalves. “The real story is that we don't have an acceptable candidate to put into phase III trials right now.”

Varmus declines to comment on Mann's statements. But Fauci, whose institute carries out most of NIH's AIDS work, called the statements “untrue” and said it was “inappropriate” for Mann “to personally attack Harold Varmus and David Baltimore”.

In 1994, Fauci decided that NIH should not back phase III trials of two gp120 vaccines (see Nature 369, 593; 1994). No other candidate has since been moved into such trials by NIH. But in January, VaxGen, a biotechnology company in South San Francisco, announced that it had gained the approval of the Food and Drug Administration to launch this year a privately funded phase III trial of gp120 vaccine in the United States and Thailand (see Nature 391, 220; 1998).

As chair of the NIH's 15-month-old AIDS Vaccine Research Committee, Baltimore has been meeting scientists, studying candidate vaccines, and developing and awarding ‘innovation’ grants to encourage scientists to work in areas that are not being adequately explored. “There's a very extensive programme designed to understand and produce a vaccine,” he says.

Baltimore says that progress on the vaccine is not being limited by NIH's unwillingness to test new candidates, “but by the limited number of opportunities being presented by the scientific community”. He adds: “It's not necessarily anybody's fault. It's a very difficult problem.”

Gonsalves rejects the advisory council's proposal that control of AIDS vaccine development be mo ved to the White House: “It's a scientific problem. Our best resources, our best talent are at the NIH. And that's where the job should be done.”