Guinea Pig Nation

Personality both affects and is affected by physiology. In studies of presumably normal students, those with the "healthiest" MMPI scores or the most dominant personalities had more active immune systems. A stronger system could increase resistance to disease or boost the response to vaccines, affecting the outcome of certain clinical trials.

Many volunteers in the three-drug confinement study lied to researchers about their health, their history of drug use, and other life events, suggesting a tendency to "purposefully conceal or distort." It was not the first study to show a tendency of NHRVs to provide fraudulent personal information, particularly about drug or alcohol use. In one such study, 45 of 282 volunteers who said they didn't smoke actually tested positive for tobacco use. Volunteers may be telling investigators what they think the investigators want to hear, rather than what they are genuinely experiencing. Perhaps they are doing the same about matters directly under study, such as drug side effects.

In It for the Money?

Yes, indeed, most healthy volunteers do it for the money, or because they can't afford routine medical care. Dollars prove a "significant motivator" for 50 to 93 percent of volunteers, Tishler and Bartholomae found. Recruits answer ads and notices in newspapers and magazines, on TV, on Web sites such as clinicaltrials.gov, centerwatch.com, and clinicalconnection.com. They also respond to flyers with messages like "Smoke Pot, Get Paid! Legal Studies." Bioethicists Trudo Lemmens of the University of Toronto and Carl Elliott of the University of Minnesota call attention to studies like one in Scotland that paid healthy volunteers £600 to drink orange juice laced with pesticides.

In 1996, Robert Helms, a former Philadelphia union organizer and long-time study volunteer, launched a now defunct publication called Guinea Pig Zero for those who, like himself, rented themselves out as human research subjects. In vivid detail, volunteers described what the clinical language of research protocols never did: the pain and bruising from botched blood draws, the indignity of prostate exams or induced hallucinations, as well as all manner of bad behaviors and irksome habits—from aggression to snoring to rudeness—among fellow volunteers. Helms openly labeled the volunteers "medical meat-puppets" and "brain sluts." What made those notes from the guinea pig underground so revealing, says ethicist Elliott, is that Helms "assumed that nobody in his right mind would enroll in a study for anything but the money."

There is, today, hot competition for recruits to clinical trials. The number of people enrolled in trials around the U.S. is estimated to have tripled between 1991 and 2001, and many hundreds of new-drug applications are filed each year with the Food and Drug Administration. Evaluating these drug candidates requires healthy volunteers for early phases of testing. In the absence of standards that limit how much volunteers can be paid, fees can be increased where recruitment is slow-going. Some for-profit companies and university-based investigators play the "everybody has their price game," say Tishler and Bartholomae, a practice that could lead to undue inducement and seems likely to attract volunteers who are different in psychological makeup and economic circumstance from non-volunteers.

Ethicists fear that many advertisements for clinical trials downplay the very real risks involved. Consider a now-infamous ad for a leukemia drug trial, posted to the Web in early 2006 by a private company contracting with drug makers to test new medicines. "You'll be paid for your time and inconvenience," it read, emphasizing the free medical care and free food, and added: "You'll have plenty of free time to read or study, or just relax—with digital TV, pool table, video games, DVD player and now FREE Internet access!" Yet this trial had rare, disastrous results that sent a shudder through the medical community. Six healthy men volunteered to take the new drug in London for £2,000 each (about $3,500), most of them immigrants. All six ended up in intensive care shortly after receiving the drug, in intense pain and with multi-organ failure—the result of immune overreaction.

Still, most volunteers deny that money is the only reasonable motivator. "I was a scientist and understood the need as a public service," says Kusinitz, now the senior science communications advisor at the FDA. "Yeah, I made about $600 in the malaria study and $20 to get nasal washes that felt like waterboarding. I was a single dad and the money was nice, and I got on Oprah when I got malaria, but believe me I didn't risk getting malaria for the money or my 10 minutes of fame." A panel that looked into the 2001 death of Ellen Roche, a serial research volunteer who died during a lung function challenge study at Johns Hopkins, concluded that she was drawn to participate for a variety of reasons: altruism and admiration for the principal investigators (her employers), in addition to the $365 offered.

A Mixture of Motives

The fact is, most repeat volunteers are like the rest of us—complex human beings who defy easy categorization with respect to background and motives. And although money is part of it, it isn't all of it by a long shot.