The Body Hunters (23 page)

In 2001, NIH officials had suggested that Jackson might consider offering all of his Chinese subjects antiretrovirals and substitution therapies, treatment that would undoubtedly save many of their lives. Jackson objected. “American-style treatment programs are impractical at this point in China,” he said. “It's unrealistic—even unethical—to think that we could provide Western standards of care to everyone in the world.”
³²

In 2004, he was proved wrong, when the Chinese government announced it would offer free HIV testing to everyone in the country and antiretroviral treatment to all who needed it.
³³
In 2005, officials announced their intention to legalize the use of methadone to treat intravenous drug users and step up needle-exchange programs. Meanwhile, the World Health Organization added both methadone
and buprenorphine to its list of “essential medicines,” drugs so crucial to public health that they should be available to all.
³⁴

Whether or not Jackson would be able to conduct his trial with nevirapine in China—as of 2005, the trial was in limbo—the arguments so staunchly forwarded in its favor had crumbled fast indeed.

VaxGen's trials of its tepid HIV vaccine in the United States and Thailand had, by early 2003, predictably failed. A smaller trial of an Aventis vaccine had a similarly weak showing, interim results revealed in 2002, leading researchers to give up on their plans for a larger trial testing the vaccine in the United States. And yet, in September 2003, NIH researchers chose to plow ahead with a trial that had been planned before the bad results: a massive trial in Thailand of a combination of the two failed vaccines.
³⁵

Critics such as Cornell University's John Moore and AIDS advocacy groups Treatment Action Group and Gay Men's Health Crisis complained loudly. Such data would likely render papers, grants, and scientific satisfaction, but had only a tenuous link to the search for an effective vaccine, they said. Many earlier vaccines had proven effective without scientists ever figuring out how they worked at all. But the researchers exhibited a steely determination to extract some usable data from the trial.
³⁶

By early 2005, ten thousand of a needed sixteen thousand subjects had been rounded up for the vaccine trial. Would the thousands of Thai subjects be informed that between the conception of the trial and its start date, both halves of the experimental vaccine they were being given had been shown ineffective? Local newspapers seemed oblivious, predicting that “the AIDS vaccine work programme will definitely be a success.”
³⁷
Lancet
editor Richard Horton asked one of the safety monitors of the trial about “the propriety of continuing” the experiment. The monitor's response was evasive, as Horton later described in the
New York Review of Books
. “Good question,” the monitor said, smiling anxiously.
³⁸

At the same time, Thai AIDS activists watched prevention campaigns in the country shrivel. “We spent millions of dollars for this no-hope project rather than spending that money on providing antiretroviral drugs for patients,” complained one.
³⁹

As double standards in research ethics for poor people become increasingly acceptable in the research community, new arguments rationalizing the stripping down of subject protections have come into vogue. A popular one dismisses concern about defenseless test subjects as paternalistic. Nobody is forcing Thai sex workers or Chinese drug users to enroll in these experiments, goes the argument. They've decided for themselves. “You can't treat them as incapable of pursuing their own ends,” says Temple. “They are not cavemen; they are just not rich.”
40
In other words, informed and voluntary consent, that cornerstone of research ethics, offers sufficient protection, even for the most powerless. To the sick, poor subjects lining up at their clinic doors in Asia and Africa, clinical researchers might now echo used-car salespeople and the like: caveat emptor.

Neisseria meningitidis
is generally a placid sort of bacterium. Sluggish and round, it tends to quietly reside in the back of peoples' throats, minding its own business.

But every ten years or so, across a stretch of Africa from Ethiopia to Senegal, something different happens. Perhaps people have lost their immunity. Perhaps the bug has evolved into a more sinister form. Whatever the cause, during these episodes, when the dry air comes and
Neisseria
escapes in tiny, coughed-out droplets, the guest turns wild.
Neisseria
speed through the bloodstream of its new hosts—mostly children—finally reaching the meninges, those crucial membranes covering the brain and spinal cord, where it triggers a deadly inflammation.

Vomiting, high fever, and mental confusion follow. Around 80 percent of those sickened with
Neisseria
's meningitis die, some within hours. During epidemics, tens of thousands might perish in a matter of months.
¹

One of the largest recorded outbreaks of epidemic meningitis occurred in 1996. The first reports trickled out of Nigeria in January. The next month, the numbers shot up. By March, the eruption was in full force, and emergency response teams from the Nigerian ministry of health along with the World Health Organization, UNICEF, and Médecins Sans Frontières rushed to Nigeria to dispense eight million doses of vaccine for those still well and powerful antibiotics to the ill. Another ten million vaccines were on the way.
²
Among those Nigerian children lucky enough to receive
a rapid IV infusion of antibiotics, the chance of death would plummet to around one in ten.
³

It didn't take long for news of the outbreak to reach Pfizer headquarters in chilly southeastern Connecticut, where it fell upon pricked ears. The company was racking up proof that its experimental broad-spectrum antibiotic Trovan worked on everything from gonorrhea to bronchitis and pneumonia, a potential $1 billion blockbuster in the making.
⁴
It seemed a golden opportunity to prove Trovan's mettle had fallen into the company's lap. In the United States, only about three thousand people contracted meningococcal meningitis every year.
⁵
In Nigeria, Pfizer could test Trovan on hundreds of untreated patients in a few weeks. If the FDA could be convinced that the drug worked for meningitis in these Nigerian kids, they could effectively break open the entire pediatric market. Pfizer's Scott Hopkins, MD, quickly drafted a protocol for a quickie experiment.

The news of the brewing plan alarmed Pfizer's infectious disease specialist, Juan Walterspiel. Walterspiel knew of his employer's eagerness to deliver the new bug fighter in convenient oral form rather than the usual injections proffered by competitors; to see how an oral formulation worked, the trial would administer Trovan in a tablet or a spoonful of syrup to some of the Nigerian children. But sending a drug into the body via the mouth is a circuitous route compared to shooting it straight into a vein, and Walterspiel knew that a rampaging
Neisseria meningitidis
can kill people fast. That's partly why the WHO recommends the use of injected antibiotics to counter meningitis outbreaks.
⁶
Plus, these kids in Nigeria weren't just facing one pathogenic microbe: they were malnourished and reeling from concurrent epidemics of measles and cholera. What if the bug overwhelmed them before the pills and syrup could be absorbed?
⁷
Their blood would be on the company's hands.
⁸

But, according to allegations contained in a later lawsuit, neither Hopkins nor the rest of his six-person team took Walterspiel's
concerns seriously.
⁹
In April 1996, filled with faith in Trovan's prowess, Hopkins and his team boarded a chartered DC-9 headed for the outbreak's epicenter: the dusty northern Nigerian city of Kano. “We had to move quickly,” Betsy Raymond, a Pfizer spokesperson, explained to the
Washington Post
reporter who reported on the trial in 2000.
¹⁰

The facilities in Kano did not impress Hopkins. At the Kano Infectious Disease Hospital, aid doctors conducted mass vaccinations and treated the sick with shots of chloramphenicol, the cheap, off-patent
Neisseria
-killer recommended by the WHO.
¹¹
Chloramphenicol had been developed in the 1940s and had fallen out of favor in the United States in the early 1980s, when it was found to cause fatal aplastic anemia in one out of thirty thousand patients.
¹²
“I wouldn't give my dog [chloramphenicol],” Hopkins said to the
Post
in 2000.

The Pfizer scientist set to work taking over a ward of the crumbling cinder-block facility for his Trovan test. A nurse at a triage desk would direct the stream of ailing patients stumbling into the hospital either to the aid workers or to the Pfizer test clinic, where Hopkins would offer what he considered to be superior treatment options. Around one hundred lucky children would get Pfizer's Trovan and another one hundred Roche's Rocephin, a brand-name meningitis drug approved in 1993.
¹³

Like many drug companies taking their trials overseas, Pfizer hadn't fussed with filing an application with the FDA before jetting over to Kano. Pfizer's researchers knew that in terms of patient protections, all the company needed to do was follow the mostly philosophical edicts of the Declaration of Helsinki and the FDA would likely happily accept the forthcoming data. This wasn't a high-profile experiment funded with public money, but a proprietary experiment that few outside the FDA and Pfizer would probably ever review in detail. The only concrete requirements entailed acquiring approval from a local ethics committee and, of course, written evidence of the subjects' informed consent.

* * *

Underneath the layers of oversight fashioned to protect human subjects from harm in medical experiments lies a hard inner core, forged when the horrors of coerced human experimentation were finally laid bare after World War II. It is the subject's own informed and voluntary consent—the oldest and most universally accepted ethical standard in research. “Ultimately,” wrote NBAC researchers in a typical formulation of the standard's centrality, “research can go forward only if participants understand what the research entails.”
¹⁴

Few researchers, however, ever bother to verify whether their subjects do, in fact, understand. It wouldn't be difficult. Medical researchers routinely double-check, duplicate, and re-analyze nearly every other aspect of clinical trials by means of a profusion of journal articles, conferences, workshops, and lectures. “Relentless scrutiny of details” could be said to be the research industry's motto. But in the area of informed consent, an atypical atmosphere of “don't ask, don't tell” prevails.

One survey found that while over half of researchers admitted that it would be a good idea to verify their subjects' understanding of experiments, a scant 16 percent had ever done so in their own trials.
¹⁵
Partly that's because when researchers have attempted to confirm the integrity of informed consent, the bedrock has revealed itself to be made of very soft shale indeed.

In standard practice, to “consent” a subject, the investigator holds a single meeting with a prospective participant, explains the trial and the consent form, answers a few questions, and passes over the form for a signature. It is a brief, legalistic exchange that satisfies sponsors, oversight committees, and regulatory authorities, protecting all concerned from liability. But the evidence suggests it does little to enlighten test subjects about the risks of experimentation. This comprehension gap is even wider in the case of Western-sponsored trials conducted in developing countries.

Indrek Kelder, an accountant from Estonia, wasn't even sure what drug he'd been given in the 1998 industry trial he participated in.
“Maybe it was written between all this mumbo jumbo,” he offered to the
Washington Post
. His fellow trial subject, Estonia's Irme Petrimae, was similarly confused. “They told me something about skin disease,” he allowed. “All these forms, and we didn't get any copies. I didn't like it . . . but it was too late to change our minds.”
¹⁶
Despite having signed informed consent forms, no fewer than thirty of thirty-three Thai volunteers enrolled in one trial of an experimental HIV vaccine later said they shared the mistaken belief that “the vaccine they received was effective,” according to a 1997 study published in the
Journal of the Medical Association of Thailand.
¹⁷
In Haiti in 2002, when researchers turned around and quizzed subjects on the basic outlines of the HIV transmission experiment they had just agreed to, 80 percent flunked.
¹⁸
In a 1998 study in Brazil all subjects in a trial of an experimental contraceptive enrolled under the erroneous impression that the experimental intervention “would be good for them.”
¹⁹

Disturbing signs that test subjects' participation in trials is not particularly voluntary have also emerged. In a 1998 analysis by South African epidemiologists, more than eight out of ten South African women inducted into an HIV prevention trial, all of whom had already been through an informed consent process, professed to feeling coerced into remaining in the trial.
²⁰
“Two little bottles of blood was taken from us without asking our permission,” complained an HIV-positive South African woman who enrolled in a trial after being approached by a recruiter on her street.
²¹
A similar proportion of Bangladeshi women in a 1998 trial on iron supplements revealed that they had no idea they were free to abandon the experiment.
²²