Issue 11.01 | January 2003
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Testing the First AIDS Vaccine
Medical establishment, government, and Genentech be damned - Don Francis has never stopped believing. Now he's about to finish testing the first human AIDS vaccine.
By Richard Martin
Sometime in the next several weeks, in an anonymous office building south of San Francisco, medical science will reach a milestone in the long and terrible history of the AIDS epidemic. Researchers at a small biotech firm called VaxGen are testing blood samples from thousands of volunteers inoculated with AIDSVax, the first AIDS vaccine to make it to phase 3 trials. It's the final, full-scale test before FDA approval, and the company is expected to announce preliminary results early in the year. If it works, AIDSVax could mark a turning point in the worst plague in modern history.
Controversy is endemic to AIDS research, but Francis' single-minded crusade has made him a professional lightning rod. As an epidemiologist at the Centers for Disease Control in the early '80s, he denounced the Reagan administration's tepid reaction to the growing epidemic and called for a concerted national response. He has been labeled a hero and a horse's ass, with plenty of less printable terms thrown in. His nickname, St. Francis, refers to both his role in saving millions of lives and his bottomless reserves of self-righteous indignation. While no one doubts his commitment, many question his judgment. "If Don Francis tells you this is going to work," says one researcher close to the trials, "he's either deluded or he's lying."
Francis, of course, demurs. "I'm confident we'll show some level of efficacy," he says. "The question is whether it will work broadly enough and long enough to make a viable vaccine."
Even if AIDSVax doesn't work, though, the trial itself amounts to a breakthrough. Before Francis blazed the trail, researchers held little hope that an AIDS vaccine would make it into clinical trials, much less complete phase 3. Now there are several in the FDA pipeline. Though almost comic in its modesty, Francis' achievement is nonetheless substantial: He proved that an AIDS vaccine could clear all the bureaucratic, political, and financial hurdles. Sooner or later, someone will make an effective AIDS vaccine. When that happens, it will be Don Francis' victory as well.
Like the fight against polio in the '40s and '50s, and smallpox in the '60s and '70s, the effort to develop an AIDS vaccine is one of the most urgent undertakings of our time. Despite the drug cocktails that have transformed AIDS from a death sentence into a chronic illness, the statistics remain staggering. Forty million people worldwide are infected with HIV. AIDS killed 3 million people in 2001 (the most recent year for which statistics are available), more than 15,000 of them in North America. In some African countries, it afflicts more than 30 percent of the population. As Francis puts it, "On 9/11, we tragically lost 2,800 people in the World Trade Center. That day, 8,000 people died of AIDS. And the day before that, and the day after, and every day since."
Early in the epidemic, optimism prevailed regarding the prospects for stopping the virus. Margaret Heckler, Secretary of Health and Human Services under Ronald Reagan, famously predicted a vaccine within two years - in 1984. Researchers immediately went to work on a vaccine, using the virus' protein sheath to stimulate the immune system and trigger antibody production. But over the following decade, the best virologists in the world tried and failed.
The virus attacks helper T cells - the very agents that coordinate immune response - making HIV invisible to the body's defenses. Moreover, it mutates prodigiously, varying its protein sheath faster than drug designers can keep up. By the late 1990s, most researchers had abandoned the notion that a classic vaccine could stop HIV. Instead, they started exploring exotic methods that might awaken the body's other line of defense, killer T cells, which destroy infected cells.
Not Francis. He championed a preparation initially developed by California biotech leader Genentech. That vaccine used a genetically engineered protein subunit of HIV's sheath, gp120, to jolt the immune system into producing antibodies. Although this approach had fallen out of favor, Francis found reason to believe in it. In a controversial 1989 experiment, Phillip Berman - then at Genentech, now VaxGen's chief scientist - had shown that gp120 could protect chimpanzees from infection. Critics challenged Berman's experimental design, but his results have fueled Don Francis' struggle to bring AIDSVax to market, and they provide a pinpoint of light for developing countries deep in the tunnel of the AIDS nightmare.
"If you can't risk failure, you should never do a vaccine trial," Francis says with a rasp born of years spent shouting into the wind. "People say we shouldn't have gone forward. It's the same thing Albert Sabin said about Salk: 'That vaccine will never work, you need to wait for mine. It's just around the corner.' It took Sabin another 10 years. You can fiddle around in the lab forever, but at some point you've got to put it into people and see if it works."
Lab work can be solitary, but its impact is often decided in the public forums where science and policy collide. The fate of gp120 was nearly sealed in a Bethesda, Maryland, hotel ballroom on June 17, 1994, at a meeting of the AIDS Research Advisory Committee of the National Institute for Allergy and Infectious Diseases. It has since become part of AIDS lore, a critical turning point in HIV vaccine research that essentially destroyed the field for much of the mid-'90s.
The committee met to decide whether to fund final testing of Genentech's vaccine. Francis himself presented the case for moving forward. Only two months earlier, he explained, a scientific subcommittee known as the Vaccine Working Group had recommended moving gp120 into phase 3 trials. But the committee faced pressure from other quarters. Phase 2 had been racked by press leaks that the test vaccine infected a few volunteers. (As disturbing as these reports must have been, the claim was ludicrous; gp120, a protein, lacks the viral DNA that causes infection. Moreover, since no vaccine is 100 percent effective, some at-risk subjects are bound to become infected in the course of a vaccine trail.) At the same time, groups like ACT UP charged that money for gp120 trials would divert funds from research into drugs for treating the disease, then regarded as 100 percent fatal. The allergy institute's director, Anthony Fauci, confirmed that funding would come out of the existing National Institutes of Health AIDS research budget, which at the time was only $543 million a year. Overwhelmed by opposition, the committee scuttled the trials. Anyone attending the meeting would have concluded that gp120 was dead - anyone except Don Francis.
Contributing editor Richard Martin (firstname.lastname@example.org) wrote about photographing extrasolar planets in Wired 10.11.
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