by Sonia Shah
Jackson designed a study in which he would administer three different regimens and count how many babies became infected. Around five hundred infected pregnant women would receive a few tablets of AZT during their labor and delivery; another five hundred a single dose of nevirapine. The third group of five hundred women would receive a placebo. Since “the current standard of care [in Uganda] involves no antiretroviral therapy . . . ethically . . . this study will not deny women access to a proven therapy to which they would otherwise have access,” he wrote in his proposal to the NIH. None would be encouraged to feed their infants formula rather than infected breast milk, either. “They really can’t not breastfeed,” Jackson said. “The stigma is a huge problem. If you don’t breastfeed either you are HIV positive or you don’t care about your baby. Two, they don’t even have the money to buy the charcoal to heat up the formula let alone buy the formula.”36
Jackson received a generous grant from the National Institute of Allergy and Infectious Diseases. He’d direct the trial from his new office at Johns Hopkins University in Baltimore, where he’d taken a post as professor of pathology in 1996. Staying on the cutting edge was crucial for Jackson, and it just wasn’t possible in Uganda. “You don’t have access to journals, and you don’t have the meetings and the company, the technology, that you have here,” he says, from the vantage point of his spacious, book-lined office, complete with secretaries and hot coffee on request. “Just everything takes longer. Just to send an e-mail takes like ten times longer!” he says, still amazed. “It is slow, it freezes all the time! I mean, you go to work and half the time you get a flat tire! Everything is just . . .” He stops, at a loss for words. Instead, Jackson would pop some malaria-preventing mefloquines and visit the study site for a week or two at a time.37
Jackson’s trial would be among the largest of the mother-to-child HIV prevention studies going. The CDC planned to conduct placebo-controlled trials, too, testing how a few weeks of AZT given during pregnancy worked in comparison to placebos in hundreds of HIV-positive pregnant women in Côte d’Ivoire and Thailand.38 The race was on.
No drug companies supported the trials, save by shipping a few free doses to use. By then, the 076 regimen already had slashed the number of American babies born with HIV by over 40 percent.39
But just as Jackson prepared to launch his trial, the first inklings of its slippery rationales caught the attention of Peter Lurie, an HIV researcher turned activist whose full-throttle condemnation would later spell the trial’s undoing. Lurie, a wiry, bearded man with twinkly blue eyes, grew up in Cape Town, South Africa, nearly abandoning medical school before he realized, during a stint at a health advocacy nongovernmental organization (NGO), that medical research could be used to promote public health. After gaining his MD and a master’s degree in public health, Lurie took a plum job at the Center for AIDS Prevention Studies in San Francisco. From there he’d conduct HIV prevention research and use it to make political interventions, for example by producing a seven-hundred-page report that undermined conservative politicians’ claims that needle-exchange programs encourages drug use. In 1995, Lurie published a paper describing how World Bank structural adjustment programs undermined developing country economies and could thereby help spread HIV. “It was a very radical argument at the time,” he says. “It made a huge ruckus when it came out.”
In February 1997, the up-and-coming AIDS researcher flew back to Africa to give a presentation about AIDS and the World Bank to a gathering of African journalists in Abidjan, Côte d’Ivoire. It was a meeting that would change the course of his career.
The meeting was held in French. After giving his talk Lurie settled in to listen to the other speakers. Some scientists from the CDC shuffled to the podium. Lurie was sympathetic to CDC scientists, as the agency had funded his work on needle-exchange programs. The CDC scientists offered a routine description of their ongoing studies on HIV-infected pregnant women. The 076 regimen was too costly, they mentioned, so they were administering “half doses” to the women.
According to Lurie, the audience erupted. Local journalists started yelling. “Who do you think we are?” they shouted. “How dare you give us half doses!”
Lurie stepped to the microphone to pose a question. He didn’t think the half doses were such a bad idea—they would certainly be less toxic and more affordable than the full dose, and might work just as well—but wondered what treatment the CDC was comparing this regimen to. The answer: placebos.
“I remember standing there, with my mouth open, and waiting there for maybe fifteen seconds, thinking about it.” Meanwhile, he recalls, the journalists at the conference “went insane.”
Lurie’s mind was reeling. How could the CDC scientists be in equipoise about whether the short AZT regimen—the half dose—was any better than placebo? The long course was remarkably better than placebo, slashing the rate of transmission of the virus from nearly 25 percent to less than 8 percent. Given what researchers understood about how AZT blocked the transmission of the virus, it was logical to assume that a little bit of AZT would be better than nothing at all. If so, how could researchers justify looking these HIV-positive pregnant women in the eye, and allowing them to deliver their babies without any protection?
No, the CDC scientists responded, they really didn’t know whether the short course of the 076 regimen would work. In fact, they suspected that the 076 regimen was “scientifically inapplicable” in Africa. Their rationalizations seemed strangely familiar to Lurie.40
Just that month Alfre Woodard and Laurence Fishburne had starred in an HBO movie about the Tuskegee Syphilis Study. The film highlighted how the study hinged on a racist presumption of the time: the sense among scientists that there were biological differences between black people and white people.41 Was this the argument being made about the 076 regimen in Africa? That drugs proven effective for Westerners would somehow not work in black Africans? Only such a presumption, Lurie realized, could explain the researchers’ state of confusion over whether the short course of AZT would be any different from placebo. Lurie got up again to try to pose the question, but he never got that far. As soon as the word “Tuskegee” escaped his mouth, the organizer, a French AIDS advocate, announced, “I disagree with that!,” ordered Lurie’s microphone to be cut off, and instructed the translators to stop translating.42
Later, when he got back to the United States, a bit of sleuthing revealed to Lurie that the CDC, the United Nations’s Joint Programme on HIV/AIDS, UNAIDS, and others were conducting no fewer than fifteen different trials testing experimental interventions to block mother-to-child HIV infections in developing countries. All fifteen trials pitted their experimental therapies against placebos, reasoning, as Jay Brooks Jackson had, that placebos were no worse for HIV-infected women in poor countries than what they would normally encounter, that is, no treatment at all. This meant that Western scientists were allowing hundreds of HIV-infected pregnant women in their care to deliver their babies unprotected.
Lurie knew that his colleagues had a fondness for placebo-controlled trials. And such trials certainly had their place, Lurie agreed. But if researchers knew that effective treatments were available, they had a clear ethical obligation to provide them, whether that muddied their data or not. Not only would these trials condemn scores of infants to HIV infection, but the trials would set a dangerous precedent. “With the increasing globalization of trade . . . it is likely that studies in developing countries will increase,” he’d later write. In the years ahead drug industry researchers could use the same argument—it’s no worse than what they would have received anyway—to dole out second-rate care to test subjects in poor countries, or, indeed, to poor patients in rich countries as well.43
Of course the interventions under study were important and urgent. Lurie understood that as well as any HIV prevention researcher did. The question was how to balance the rights of research subjects with the goals of the research. If AIDS researchers were seen as undermining hum
an rights, or exploiting people’s poverty, their grand collective aim—saving the world from the virus—would be gravely undermined. And in any case, innovative study designs using sophisticated statistical techniques made it possible to both provide the best care to research subjects and gather relevant data for impoverished societies. A Harvard researcher, Marc Lallemant, was doing just that, testing short courses of AZT against long courses of AZT among HIV-positive pregnant Thai women, an “active-controlled” trial in which all test subjects would be treated with something that might prevent their babies from falling ill. Such a trial might take a bit longer and require more test subjects to render a result, but the risks to the participants was greatly lessened. Surely the others could do the same, Lurie thought.
With the help of the health watchdog group Public Citizen, Lurie held a press conference to publicize his critique. With any luck, bringing the problem to public attention would persuade researchers to redesign their studies, averting hundreds of unnecessary HIV infections in African and Asian babies. Although he often spoke in expletives, Lurie was a man of reason. And the outspoken physician had already taken on powerful foes—the White House, the World Bank—and survived to tell the tale. His critiques of the grand poobahs of AIDS research would be no different, he assumed.
He couldn’t have been more mistaken.
In September 1997, the New England Journal of Medicine published a paper by Lurie and Public Citizen’s Sidney Wolfe, MD, articulating their objections to the trials. In a bold editorial accompanying the paper, editor Marcia Angell applauded Lurie’s critique and condemned researchers’ justifications that substandard care to research subjects wasn’t unethical when it was no worse than what they might have received if left to their own devices. The Declaration of Helsinki couldn’t be clearer, she argued: research subjects were owed the best standard of care, not whatever might be locally available. “That reasoning is badly flawed,” she wrote. “It seems as if we have not come very far from Tuskegee after all.” It was that word again. When the New York Times saw it they promptly pasted the controversy on the front page of the paper. Now one of the cardinal rules of the research community—never involve the lay press—had been breached.44
The reaction was swift and hostile.
Within weeks members of the Journal’s editorial board—David Ho and Catherine Wilfert—had resigned in outrage. Johns Hopkins University’s Alfred Sommer, dean of the school of public health, publicly announced he was “quite honestly appalled at these people.” Angell and the South Africa–born Lurie, he said to the Baltimore Sun, were “Americans who have absolutely zero experience, have never been involved in changing scientific paradigms or changing policies. They are getting involved in an issue about which they know nothing.”45 Lurie’s boss in San Francisco called to say that Lurie’s conduct was unethical and unprofessional, and that he would be making that point to the surgeon general, the head of the NIH, and the head of UNAIDS—the top funders in Lurie’s field. Johns Hopkins University’s Neal Halsey called the vice president for research at the University of Michigan, where Lurie was temporarily stationed, to press him to open an investigation into Lurie’s “unprofessional conduct.” Even Lurie’s brother, Mark, then a doctoral candidate at Johns Hopkins, suffered from the fallout. One of his thesis advisers, AIDS researcher Andrea Ruff, who spearheaded one of the controversial trials, withdrew from his committee.
In October 1997, the Johns Hopkins department of epidemiology held a “discussion” in which Halsey, Sommer, and others aired their defense to the swirling accusations. The Western standard of care would “never be applicable” in Africa, they insisted. Active-controlled trials would render “uninterpretable results,” they said. Lallemant’s active-controlled study wasn’t just bigger and slower than placebo-controlled trials, they said; it was a “disaster.”46 Meanwhile, thousands were dying every day, not for want of the unaffordable antiretroviral therapies that were saving lives in the West but for lack of the kinds of easier, cheaper interventions that researchers from Hopkins and elsewhere were looking for. Sommer himself had spent years trying to convince developing countries of the benefits of vitamin A supplements on child mortality but had found that no volume of data would persuade government officials save placebo-controlled trial after placebo-controlled trial. Sommer kept at it, continuing to deprive children in his placebo groups the simple vitamin well after he had proven to himself that the vitamin could save their lives. Such was the business of saving lives in the third world, he insisted.
Sommer and company were angry. What really rankled was comparing their well-intentioned trials to the Tuskegee study. “It is really inappropriate and pejorative to compare this to the Tuskegee study,” said bioethicist Norman Fost in a National Public Radio program on the controversy. It was “gratuitous and almost insulting,” added South African AIDS researcher Jerry Coovadia.47 It didn’t help that the implied accusation hailed from Lurie. “Here was this white South African,” University of Virginia bioethicist Jonathan D. Moreno remembers, “saying we are racist.”48
But more important, they were threatened. A whole body of research was in jeopardy. If known effective treatments were always provided to test subjects, researchers would only be able to garner useable data when their experimental drugs and methods were as good or better than the stuff already known to work. It was a dangerous idea, as Halsey and others detailed in a flurry of articles in the medical press. How would researchers ever be able to discover affordable interventions like oral rehydration, or micronutrient supplementation, or low-cost surgical techniques if they had to compare them to the standard of care in the cash-flush, technology-rich West? These techniques were, indeed, less effective than the Western standard of care—but more relevant for saving the lives of people with little access to health facilities and inadequate budgets.49 “There is a global obligation to diminish the worldwide disparities in health care,” leading HIV researchers and bioethicists allowed in a joint 1999 Lancet paper. But “to expect this profound global injustice to be rectified soon is unrealistic.”50
In March 1999, CDC scientists announced results from their placebo-controlled trials. The short course of AZT halved the transmission of HIV, compared to placebo. In Bangkok and Abidjan thousands of HIV-infected pregnant women had jostled for entry into the trials, where the white-coated docs might—or might not—dole out drugs to save their babies from infection. Over three hundred of those who made it into the trials did not receive AZT, but rather sugar pills. Nearly seventy of their babies came into the world infected with HIV.51
The top AIDS researchers and bioethicists who defended the studies wrote a bold “consensus statement” that accompanied the CDC results. The statement began by arguing that these kinds of trials were important and necessary, despite breaching the ethical principle of assuring research subjects the best care. They said the ethical principles themselves had been misinterpreted. According to the statement, placebo treatment of people who couldn’t afford to buy effective medicines was the de facto best standard of care. Researchers, no matter how richly endowed with NIH grants, owed such patients no more than that. “You don’t want to deny treatment to anyone who would otherwise get the treatment,” said Sommer. But “you’re going into Africa where nobody gets anything because the drug is too expensive.”52
The statements’ authors argued that it was “ethically permissible” to administer placebos to HIV-infected pregnant women in countries where antiretrovirals were unavailable. Researchers should provide only the “highest standard of care practically attainable in the host country,” they opined. “There is no obligation to provide study participants with the highest standard of care attainable elsewhere in the world.”53 UNAIDS agreed, in a guidance document released the following year.54
As for Lurie, he had found himself out of a job within two months of the publication of his New England Journal paper. His employers at the Center for AIDS Prevention Studies held a major international conference on H
IV prevention and failed to even invite Lurie to speak. Enraged and hurt, Lurie quit. “I was furious! I felt incredibly betrayed!” he says passionately, years later. According to Lurie, his former boss had spoken to the surgeon general and the head of the NIH about Lurie’s activities. He hasn’t worked in AIDS prevention research since.55
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VaxGen’s trials of its gp120 vaccine in five thousand gay men in the United States and twenty-five hundred intravenous drug users in Thailand commenced in 1999. Several AIDS researchers took exception to VaxGen’s bypassing the NIH decision by moving forward with the Thais. “Majority scientific opinion,” said AIDS researcher John P. Moore, had condemned the gp120 vaccines as failures, but still VaxGen and others “cling to their investments.” Furthermore, they had seduced desperate health ministers and scientists from developing countries with false hope, then paraded their newfound supporters at international conferences to back them up. “I despise . . . Don Francis and all the evil corporate politics you stand for,” railed Moore. “Trying to make money out of the dying is pretty pathetic, really.” VaxGen was “abusing the Thai people for selfish reasons,” he said. Aaron Diamond AIDS Research Center’s David Ho agreed. During a visit to Bangkok Ho warned, “For me as part of the Asian minority in the U.S., I feel it’s important for the Thai people to be aware of the possibility of exploitation. . . . If a product is rejected elsewhere, why should you take it? . . . It’s wrong for some U.S., European, and other researchers to look at this only as an opportunity to develop a product.”56