CHONBURI, Thailand -- Inside a ramshackle Buddhist temple here on the country's southeastern coast, curious villagers gathered last fall as part of the United States' biggest gamble yet on stopping the AIDS pandemic.
The informational meeting was almost like a game show as attractive young hosts revved up the crowd, working up to the big question, boomed out over loudspeakers: Would the audience be willing to volunteer to test an experimental HIV vaccine?
The villagers hesitated. No one moved for a full 60 seconds. Then, tentatively, they approached the three stands set up at the front, marked "Join,""Not Join" and "Unsure."
For the past three years, such gatherings have been held all over Thailand, exhorting young adults to take part in the largest, most expensive, most resource-intensive AIDS vaccine trial ever. Funded by the National Institutes of Health, it ultimately will involve 16,000 people and last 3 1/2 years.
But as the trial moves forward, at a cost of more than $120 million, some researchers are raising questions about its validity. They disparage its science, question its ethics and doubt its efficacy.
One of the chief dissenters is Robert C. Gallo, who helped discover the human immunodeficiency virus. He scoffs at the notion that the trial will be successful. "I thought we'd learn more if we had extract of maple leaf in the vaccine," he said derisively.
NIH scientists defend the study, arguing that even if the vaccine doesn't work, the trial may reveal new things about HIV. "With 5 million new infections each year, the luxury of time is absent," four researchers wrote in the journal Science.
When scientists identified HIV as the cause of AIDS 21 years ago, they predicted that a vaccine to prevent the infection would be ready long before a treatment for the symptoms could be developed. The opposite turned out to be true. Many people today, especially in wealthy countries, are keeping the virus in check with drugs, but a vaccine, desperately needed in poor countries, has eluded modern medicine.
Despite years of effort, investment in the billions of dollars, and dozens of small tests in people around the world, there's still no scientific proof that a vaccine is even possible. HIV is a diabolical virus that disables the very immune responses a vaccine needs to trigger in order to work.
And yet the need is so urgent that scientists have gone forward with preliminary human tests of many vaccines on the basis of data they acknowledge is weak. The one in Thailand is the largest.
The fact that no one has ever been cured of AIDS increases the urgency of finding a vaccine. "In contrast to virtually every other microbe we've come across, there isn't a documented case of anyone who . . . ultimately cleared HIV from the body completely. That's why more and more research is being directed at trying to stop infection from happening in the first place," said Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, part of the NIH.
The U.S. government last year spent 22 percent of its $3 billion AIDS research budget on vaccines and other preventive drugs, compared with less than 8 percent a decade ago. (Most of the rest is devoted to developing treatments or a cure for those already infected.) Meanwhile, the Bill & Melinda Gates Foundation this year designated up to $360 million for AIDS vaccine research, and Congress is encouraging more research with bills that would provide liability protection and tax benefits for drug companies.
But the science is daunting and subjects hard to come by. Scientists have been forced to travel to remote corners of the world to find communities where the infection rate is high enough to show results in a reasonable amount of time.
Thailand, where AIDS is a leading cause of death, has been among the most accommodating places. The NIH effort there involves two vaccines that individually have been disappointing in previous trials. One of them, developed by a once-revered scientist in the AIDS world, flopped spectacularly after an expensive test funded by private investors. The other showed little promise in early trials. Researchers cling to the hope that using them simultaneously will attack different aspects of the disease and prove effective.
A vaccine is basically a trick: Take a germ or part of a germ, kill it or alter it so that it doesn't cause disease, then inject it into the body. The body thinks it is being attacked and produces an immune response that will protect it when it is exposed to the real thing.
But because HIV comes in 11 subtypes that constantly mutate, it must be treated differently. Enter Donald Francis, a longtime government researcher who is credited with helping to eradicate smallpox and develop vaccines for Ebola and hepatitis B. Francis had great credibility in the AIDS community. He was immortalized as an early hero in Randy Shilts's book "And the Band Played On" because he recognized the danger of AIDS long before it became an epidemic and argued forcefully for government action.