Pappworth's Human Guinea Pigs, the American edition of which was published by Beacon Press, stands alongside Henry Beecher's famous article in The New England Journal of Medicine as a major catalyst of the revolution in research ethics which took place in the early 1970s. Pappworth, a British physician, catalogued over 200 cases of the most flagrant kinds of research abuse, many of which still seem astonishing today: injecting patients with cancer cells, with live polio virus, with malaria parasites, often without even telling the subjects. Many studies were conducted on children or mentally incompetent adults. One particularly noteworthy study took place at Presbyterian and Frances Delafield Hospitals in New York, where researchers bored holes in the skulls of 18 patients awaiting other procedures and inserted "trephine buttons" into their brains. Then they subjected the patients to a variety of procedures to see what would happen to their cerebral circulation. They compressed the main veins on the necks of the subjects, had them inhale carbon dioxide, injected them with nicotinic acid and alcohol, subjected them to "cutaneous pain," and made them apprehensive by threatening to thrust their legs into iced water. The researchers also noted that there was no need to remove the "trephine buttons" from the brains of the subjects once the study was over. They were left in place indefinitely.

These studies were not done in secret. Most of them had been published in reputable medical journals. Unlike Henry Beecher, who in his New England Journal article simply described cases of unethical research without naming the researchers, Pappworth provided full citations. This did not make him popular with his medical colleagues. Many had urged him not to publish the book, and when he did, he was roundly attacked. When Pappworth died in 1994, his obituary in the BMJ said, somewhat admiringly, that he was widely regarded among his colleagues as a "pestilential nuisance."

Human Guinea Pigs is not exactly a gripping read. For the most part, Pappworth simply catalogues the varieties of research abuse, like a particularly obsessive taxonomist ("Experiments on Pregnant Women," "The Inducement of Illness in Subjects," "Experiments on Infants and Children"), describing the studies in clinical detail while adding the occasional editorial comment or criticism. After only a few chapters the book feels highly repetitious. Yet in his preface, Pappworth claims this effect was intentional -- that he wanted to make the book feel repetitious, in order to mimic the effect produced by reading medical journals, which unnecessarily report virtually identical studies again and again. Pappworth attributes this to "the maniacal impulse which dominates the world today to publish research papers, promotion and success often depending on it."

Today the research landscape looks very different. The primary drivers of clinical research are not university researchers looking for promotion, but pharmaceutical companies looking for profit. Most drug studies are conducted not in academic settings, as they were as recently as fifteen years ago, but in private clinics and independent testing sites. These studies are overseen by private, for-profit ethics boards (for-profit IRBs), which are themselves funded largely by the pharmaceutical industry. As the financial pressure to recruit subjects quickly has escalated, so has the amount of money available to subjects. Today it is not uncommon to see recruitment advertisements offering subjects $5,000 for an inpatient, Phase 1 clinical trial, or even more if the study lasts several weeks or requires invasive procedures, such as biopsies or endoscopies. Some testing sites offer subjects bonuses if they persuade a friend to participate. A few even offer money to children.

Yet while testing sites offer enough money to persuade poor people to enroll, they do not offer much else. If a subject is injured in a study, for example, chances are that they will have to pay for their medical care themselves. Only 16% of academic health centers provide free care to injured subjects. None pay for pain and suffering or lost wages. (No systematic data is available for private sponsors, but the situation is unlikely to be much different.) Poor subjects are also less likely to get access to the drugs whose safety they are testing once the drugs are approved, because they are often unemployed and thus unlikely to be insured. As Bob Helms, a former guinea pig pro, says, "I’m not going to get the benefit of the health care that is developed by this research because I am not in the economic class to get health insurance."  Two years after Bloomberg Markets reported that SFBC International, a contract research organization, was paying poor immigrants in Miami to test drugs under ethically dubious conditions in a converted motel -- one that was later demolished for fire and safety violations -- regulators have still taken no action to ensure that subjects are not being exploited elsewhere.

Yet it also took a while for Pappworth's book to have an effect. It did not help that one of the unethical studies cited by Pappworth had been conducted by Franz Ingelfinger, the powerful editor of The New England Journal of Medicine, who was not pleased to be named. In an angry response, "The Unethical in Medical Ethics," Ingelfinger derided Pappworth's muckraking style as "a paradigm of a practice that, if carried out in an unrestrained and overly zealous fashion, may in itself be questionably ethical--this is the cavalier and often imitative disposition to cry, 'J'accuse.'"

Today, Ingelfinger's complaint sounds almost quaint -- a relic of an earlier time when doctors actually felt threatened by medical ethicists. The world is different now. Most ethicists have abandoned the muckraking approach of Pappworth and Beecher for a more judicious, analytical style of writing -- the kind that will secure NIH grants and tenure in a medical school. Ethicists too feel the maniacal impulse to publish research papers, promotion and success depending on it. And the honorable job of being a pestilential nuisance has been left behind.

Carl Elliott teaches at the University of Minnesota, where he is Professor in the Departments of Pediatrics and Philosophy and in the Center for Bioethics.  A native South Carolinian, Elliott trained as a doctor before earning a PhD in philosophy.  He has taught in medical schools in Scotland, New Zealand, South Africa and Canada.  In 2003-04, he led a year-long faculty seminar on bioethics at the Institute for Advanced Study in Princeton, New Jersey.  His articles have appeared in publications such The New Yorker, The Atlantic Monthly, The Believer, Slate.com, The London Review of Books, The American Prospect, The Wilson Quarterly and the op-ed page of The New York Times, as well as The Lancet and The New England Journal of Medicine.  His current work is supported by a grant from the National Institutes of Health.  He is the author or editor of six previous books, including Better than Well: American Medicine Meets the American Dream (Norton, 2003). His new book, White Coat, Black Hat, will be published by Beacon Press in 2009.

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