Waiting for the End of the World

Half a century ago, when poliomyelitis reached its epidemic peak in the United States, a team of researchers funded by a nonprofit organization and led by a charismatic physician embarked on a campaign to stop the disease with a prophylactic vaccine. The funding agency was the March of Dimes, the doctor was Jonas Salk, and within a decade the effort had reduced the number of cases from 57,879 to 1,312.

It was not a perfect formula. The vaccine immunized only 60 percent of those who received it, and a number of people -- children, even -- were accidentally infected along the way; some died. Well-publicized failures in the preceding decades cast doubt on Salk’s efforts. But Salk and his fellow immunologists managed to halt the epidemic with a measure of public support, faith and professional efficiency that would seem shocking today. It was a situation, Jon Cohen notes in Shots in the Dark: The Wayward Search for an AIDS Vaccine, that stands in stark contrast to the present quest to immunize humans against the most lethal virus of our day, HIV.

”There‘s no one running the show,“ Cohen explains over the phone from his home near San Diego, on a brief respite from his national book tour. ”And the culture of American science hates any type of directed organization.“ Given that the United States has spent far more than all other countries combined on AIDS-vaccine research -- $230 million in the past year -- American science culture has become an international issue. ”We influence the world,“ says Cohen.

As with just about everything HIV-related, attempts to fix the problem only seem to compound its complexity. ”There’s a basic research engine in place in the U.S. that makes us good at creativity and innovation,“ says Cohen, ”and if industry comes along, picks up the ball and finds a way to apply that research, it works pretty well. But the [pharmaceuticals] industry now cannot handle an AIDS vaccine. It cannot handle the liability issues. It will not agree on ethical issues.“ Nor is there much motivation for it to try; drugs will always be more lucrative. ”Let‘s face it,“ says Cohen. ”If you take 10 to 20 pills a day for the rest of your life, that creates a market over time. With a vaccine, after three or four shots, you’d be done.“

In 1998, notes Cohen, sales for the acid-reflux drug Prilosec reached $4 billion, while the entire market for vaccines was $3.8 million. ”One blockbuster drug makes more money than the whole vaccine market. Do we have to wonder why the industry doesn‘t race in to create an AIDS vaccine?“

Without a doubt, part of the blame for our slow progress lies not just with the financiers of medicine, but with the virus itself. ”HIV is really crafty,“ Cohen says. ”If HIV were a simpler virus, there would be a vaccine today. That said, after you accept that this is a really tricky bug, it gets interesting to analyze over time why things haven’t moved more quickly. Yes, science is the biggest hurdle, but so many forces beyond the science are at work, too. There are scientific leads that go nowhere. Why didn‘t people at least conclude in a convincing way why each one of them wouldn’t work?“

That question remains unresolved at the end of Cohen‘s book, which took him 10 years to research and write -- an unexpected 10 years, because at the time he started, he was confident, as was the scientific community, that a vaccine for AIDS could be available in five. He had meant to do an aftermath evaluation of the history of the vaccine’s development; instead, his book became an account of science gone awry. ”There‘s no closure,“ Cohen admits. ”The big question of any book proposal is ’What‘s your ending?’ So I very consciously sold the book as a narrative around a polemic, using the example of Randy Shilts‘ And the Band Played On. And what’s the ending of Shilts‘ book? There isn’t one.“

Cohen isn‘t completely comfortable with Shots in the Dark’s distinction as And the Band Played On‘s natural sequel; he describes that book’s characterization of notorious AIDS pioneer Robert Gallo -- Shilts‘ central villain -- as ”deeply flawed.“ (”I don’t think Randy ever sat next to him in a room and watched him work,“ says Cohen. ”He‘s a force of nature.“) But the two books inevitably have much in common: Like the struggle Shilts chronicled, to isolate and contain the virus, the fight to immunize humans against HIV has suffered mightily from politics -- from journalists who invent controversy, from the country’s litigious climate, from the shallow understanding of well-meaning activists. But one overwhelming impediment to vaccine research remains the absence of leadership, says Cohen. The reason dead ends pile up in Shots in the Dark like so many rejected grant proposals is that AIDS-vaccine research is a field that has no center, no agreed-upon principles and no clear direction. ”There‘s no there there,“ says Cohen. ”And so, by writing the book, that’s what I was trying to do -- be the there there.“

Unlike the stereotypical science pundit sneering at the uninitiated, Cohen is a garrulous storyteller who delivers lofty concepts, from cell-mediated immunity to the structure of a virus, in metaphor-rich vernacular. ”I‘m bilingual,“ he says. ”I speak both science and English fluently.“ In that same spirit, and in these days of otherworldly advances in biotechnology, he contends that a straightforward, trial-and-error approach to solving the HIV-immunization problem might have netted more profound results than the narrowly focused efforts of biotechnologists, who spend more time studying the structure of the virus under a microscope than they do observing the results of practical experiments. ”We already have a good animal model in monkeys and SIV [simian immunodeficiency virus],“ says Cohen, ”and granted, SIV is not HIV, but it’s a close cousin. It‘s conceivable that something could be learned from it. But instead, they get hung up on the mechanism. And I’m as fascinated as the next person by biotechnology, but we have to ask ourselves, ‘How much do we need to know to solve the problem?’“

Which brings Cohen back to his own hero of sorts: Jonas Salk reluctantly became involved with the AIDS vaccine in 1986 when, as he told Cohen, ”I was seeing a drowning person, or somebody who was about to be hit by a great passenger train.“ To be sure, Salk in his heyday had the luxury of plowing into human trials without the approval of ethics committees or government agencies -- but researchers today could benefit from his empirical approach.

”That‘s why I like him,“ Cohen says. ”He’s a kind of mirror to the field. He holds up the past for everyone to see. Science today is driven by technology, and technology leads to grants from the National Institutes of Health. But Edward Jenner made the smallpox vaccine by taking pus out of a cowpox sore on a dairymaid‘s hand without even knowing that viruses existed.“ And while HIV is not smallpox, ”We do have people who resemble dairymaids,“ Cohen says, people who after repeated exposures and years of high-risk behavior, have managed to avoid contracting HIV.

”From the bodies of those clearly protected people could come information that could be used for vaccine development. But it isn’t being used. Why not? Is it because the information isn‘t valuable? It might not be. But then again, what if it is?“

HIV, as Cohen points out in his prologue, infects 16,000 people per day. The virus effectively ”crumbles sub-Saharan Africa,“ he writes, ”shaking it like an earthquake that will not stop.“ The Bill and Melinda Gates Foundation has pledged $25 million to the International AIDS Vaccine Initiative (IAVI), and the U.S. dedicates more than $200 million annually to AIDS-vaccine research. But the world is a long way from the kind of unfettered, not-for-profit ”March of Dollars“ (the 21st-century version of polio’s March of Dimes) Cohen argues is necessary to make progress toward immunization.

”I‘d like this book to provoke people to debate these ideas and question whether everything is done that could be done,“ Cohen says. ”But I’d also like to see it have impact in the future, when the next bug shows up. Polio wasn‘t an epidemic disease until the late 1800s. And new bugs will always take the world by surprise. It’s going to happen next month, next year, in the next century. The question will be, how do we respond? Are we effectively organized? Have we been seduced by technology allowing the corporate agenda to take us places we don‘t want to be? Are we addressing ethical problems head-on or doing everything ad hoc?

“There may very well be a proven vaccine next year, even though there is only one in efficacy trials [funded by VaxGen, a spinoff of Genentech]. But could this have happened five years earlier? That’s the real measure in my mind. At the end of the day, when there is a working AIDS vaccine, the question will be ‘Did we have to wait this long to get here?’ I‘m convinced that the answer will be no.”

Jon Cohen reads from Shots in the Dark at Midnight Special, Tuesday, February 27, at 7:30 p.m.


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