The Body Hunters: Testing New Drugs on the World's Poorest Patients by Sonia Shah (The New Press, 242 pages, $24.95)
The Great Starvation Experiment: The Heroic Men Who Starved so that Millions Could Live by Todd Tucker (The Free Press, 288 pages, $26.00)
What brings a moral transgression up to the level of a full-blown ethics scandal? In clinical medicine, a handful of scandals have been memorialized in textbooks as case studies of unethical research. The Tuskegee Syphilis Study is the most notorious, but there are many others, such as the study at the Willowbrook State School in New York, where mentally retarded children were intentionally infected with the hepatitis A virus in the early 1960s, or the study at the Jewish Chronic Disease Hospital in Brooklyn, where 22 elderly patients were injected with live cancer cells. The most recent candidate for notoriety took place in 1999 at the University of Pennsylvania, where the 18-year-old Jesse Gelsinger died in a gene-therapy study.
Yet other cases, arguably just as sensational, have barely registered in the public mind. For sheer corporate hubris, it is hard to match the story of Pfizer's Trovan trial in Nigeria, first reported in The Washington Post seven years ago and now one of the cases recounted in Sonia Shah's lucid new book, The Body Hunters. In 1996, Trovan was an investigational antibiotic that had showed promise against a broad range of infections and could be administered in oral form rather than by injection. When news broke of a deadly meningitis epidemic in Nigeria, Pfizer flew a team of researchers to the industrial city of Kano to conduct a quick trial of Trovan on afflicted children. Pfizer set up shop next to the relief group Doctors Without Borders, which was desperately attempting to treat the meningitis victims, and quickly tested Trovan on 200 children, half of whom received Trovan and half ceftriaxone, a proven treatment for meningitis. Eleven children died, and many others suffered others suffered meningitis-related symptoms such as deafness, blindness, and seizures.
What is truly shocking about the trial, however, is not the death rate, which was comparable to that found with standard treatments for meningitis, but the revelations that emerged later in press accounts and also in a lawsuit brought against Pfizer by the families of the dead children. According to these allegations, not only did the Pfizer researchers fail to rescue desperately ill children whose condition was clearly deteriorating; they also gave the children in the control arm of the trial an inadequate dose of ceftriaxone. If this is true, the success of Trovan in the trial was won at the expense of the lives of the undertreated children.
Somehow a Nigerian government report investigating the Kano study mysteriously disappeared until it suddenly surfaced last year and was leaked to the press. According to the report, Pfizer never informed the parents, much less the children, that the treatment was part of an experiment. A letter of approval from a Nigerian ethics committee, which Pfizer used to justify its actions, had apparently been concocted and backdated by the company's primary researcher in Kano. In the meantime, the Nigerian families have still not been able to get a hearing in a U.S. court.
As Shah points out, the backdrop to this depressing story is the economics of drug development over the past two decades. The job of proving that a drug is safe and effective for human beings has become, as Shah puts it, "a spectacularly complex, expensive and time-consuming endeavor." One big kink in the drug pipeline is human subjects themselves, who are not always eager to test experimental drugs. To launch a single drug, according to CenterWatch, a company has to persuade 4,000 subjects to undergo 161 procedures each in more than 65 separate trials. Drug firms have a much easier time finding willing subjects in the developing world, where medical facilities are crumbling and health-care budgets are miniscule, partly because the alternatives to a trial are so grim. By 2004, according to the Food and Drug Administration, drug companies were launching more than 1,600 new trials a year overseas.
The Body Hunters is an engaging and valuable book. As an investigative journalist for The Nation Institute, Shah is an experienced muckraker, and if any business has muck that deserves to be raked, it is the clinical trials industry. In fact, the sheer scale of clinical research in the developing world has become so vast that it is probably too large a topic for a single writer. Shah does an admirable job, yet she may not have quite enough sense of the history and principles of research ethics to tell a comprehensive story about what's gone wrong. For instance, she tells the Kano story as a failure of informed consent, though this aspect of Pfizer's conduct is not nearly as outrageous as the deaths of intentionally underdosed children.
Clinical research has always depended on the availability of people whose circumstances were bad enough that medical experiments looked like a good option. Today it is often the poor who are recruited, but during World War II it was conscientious objectors. The Civilian Public Service (CPS) was set up as an alternative to the military for conscientious objectors, many of whom belonged to pacifist denominations such as the Quakers, the Mennonites, and the Brethren. Many CPS jobs involved menial labor, but another option for objectors was to volunteer for medical research, which was conducted at camps all over the United States. Some volunteers gargled pneumonia-infected sputum. Others wore lice-infested underwear in order to contract typhus. Another group of participants allowed mosquito-filled boxes to be strapped to their bellies so that they would get malaria. And as Todd Tucker documents in his thoroughly absorbing book, The Great Starvation Experiment, one extraordinary group at the University of Minnesota was intentionally starved.
The Minnesota study was conducted toward the end of the World War II in order to understand how best to treat malnourished citizens in the newly liberated countries of Eastern Europe. The experiment's chief scientist, Ancel Keys, placed 36 young men on semi-starvation rations for six months. The subjects emerged looking like concentration-camp victims, but the drama in Tucker's book comes from the psychological effects of starvation: the slow narrowing of desire, the obsession with food, the disturbing dreams of cannibalism. One subject wound up "accidentally" chopping off his fingers with an ax so that he would be dropped from the trial.
Why are the CPS medical studies not considered scandalous today? It is not as if the CPS subjects were fairly treated. The government did not pay them for their work. As Tucker points out, even German POWs received 80 cents a day. If CPS volunteers were killed or disabled during their service, they got no compensation. Overall, 30 people died in CPS camps, and 1,500 were discharged without compensation for disabilities.
Yet there is also a crucial difference between the starvation experiment and much of today's medical research on healthy volunteers. The CPS subjects understood the starvation study and were proud to take part. In fact, the rigors of the study were precisely what gave the experiment such an appeal. The stigma of being a conscientious objector was the accusation of cowardice, and according to some CPS subjects, the starvation study was a way to demonstrate bravery without picking up a gun. Today, however, the drug industry conducts most healthy volunteer studies on participants who have no interest in the aims of the studies and no confidence in the pharmaceutical companies. Yet these subjects enroll in studies simply because they desperately need money -- or, in the case of sick subjects, because they desperately need medical care. The surprising thing is that such recruitment tactics are now seen as standard operating practice, rather than as case studies in exploitation.
Carl Elliott is a professor at the University of Minnesota's Center for Bioethics and the author or editor of six books, including Better Than Well: American Medicine Meets the American Dream (Norton).