Heal Thyself or Die Trying

The rigor scared Stephen Hoffman. He had felt irritable and feverish all morning in his hotel room. Then, in the midst of a presentation at a meeting of the American Society for Clinical Investigation, he began to shake uncontrollably. Ironically, the subject of that presentation was whether the antibodies elicited by the vaccine he had helped develop would prevent malaria. To prove it would work, he and six of his coworkers took the vaccine and then exposed themselves to the bites of malaria-infected mosquitoes. Five people contracted the disease. Hoffman immediately went to the University Hospital in San Diego, but the parasite could not be found in his blood. He suffered for 36 hours until a parasitologist finally spotted Plasmodium falciparum parasites in his blood, and Hoffman took the chloroquine that ended the chills and fever. Since then, Hoffman has gone on to develop a more effective vaccine based on T cell-mediated immunity, and he has exposed himself to the malaria parasites multiple times, all without infection developing. Formerly at Rockville, Md.-based Celera Genomics, Hoffman has formed his own biotechnology startup, Sanaria (Latin for healthy air, as opposed to malaria, for bad air) to develop the vaccine for marketing. "I have no regrets about doing it," Hoffman says of his self-induced illness. "Somebody had to. Why not one of the people who helped develop the vaccine?" Isaac Newton did it. Marie Curie did it. The practice of self-experimentation has mostly died out thanks to an increased emphasis on the investigator's detachment, as well as the rising income and social status of scientists. But a few passionate, or poor, scientists keep self-experimentation alive. THE RISKS AND REWARDS The practice can offer enormous monetary and career rewards. One of the more famous cases of self-experimentation is that of Barry Marshall, who, as a young professor in Australia, swallowed a beakerful of Helicobacter pylori to prove that it led to ulcers. Later he was given his own institute at the University of Virginia, and he is often spoken of as a candidate for the Nobel Prize. These days, it's much more difficult to use yourself as a subject in your own research than it was in the time of Newton or Curie. Most studies must pass through an ethics panel or institutional review board (IRB), which often balks at the inclusion of researchers in their own studies, especially when there is potential danger involved. "There would be very little scientific yield," says Moira Keane, a member of the University of Minnesota's IRB. "I would have to be completely convinced that the person's judgment wasn't clouded in any way." That's not to say the practice should be avoided altogether, Keane says. "If it's something benign like testing a new instrument with your own blood sample, I see no problem," she explains. "As long as there's no invasive procedure or danger, it's usually not a problem." Other institutions' IRB members agreed, although none contacted by The Scientist stated that they had written guidelines on the issue. Alison Wichman, deputy director of the NIH Office of Human Subjects Research, says the only written NIH policy regarding self-experimentation involves rules against employees double-billing the agency for both research work and study-subject work. "We require that if a member of the research team is going to be a subject, the IRB must be notified, but then it's up to the IRB to decide on a case-by-case basis," Wichman says. One ethical quandary is whether investigators can ensure that their biases won't affect the results of the study. "From a scientific perspective, when [researchers are] the subject of their own research, any risk of bias becomes incredibly important," says Michael Kalichman, director of the Research Ethics Program at University of California, San Diego. "They may feel the drug works because they want it to work." HISTORIC SELF-TESTING The concept of self-experimentation is built into the ethical basis of scientific research. Early scientists often used themselves as guinea pigs. More recently, the Nuremberg Code of ethics was drawn up in the aftermath of the Nuremberg trials of Nazi doctors who, in the course of their studies, experimented on and killed concentration camp inmates. The code explicitly states that only scientists willing to be subjects in trials should run them on humans. "Some people define that in a literal sense, but I see it as a moral floor," says Minnesota's Keane. "In other words, you have to ask yourself that question when designing a study and if your answer is no, don't do the study." Yet, even the Nazi doctors were involved in self-experimentation. Nazi principal investigators were the first subjects when a hypobaric chamber was brought to Dachau to test people's ability to survive a simulated ejection from an airplane at high altitudes. "They determined where they started to feel uncomfortable, and then they began using the inmates at that pressure level," says Jonathan Moreno, director of the University of Virginia's Center for Biomedical Ethics, who studied the transcripts of the trial. "It shows that just because you're involved as a subject doesn't automatically whitewash the whole enterprise." Some bioethicists do consider scientists' self-experimentation to be prerequisite to human trials, though. In his classic 1969 paper entitled, "Philosophical Reflections on Experimenting with Human Subjects,"1 Hans Jonas, a founder of the field of bioethics, called for the "conscription" of scientists into their own studies as a defense against abuse of subjects. Of course, the ethics of self-experimentation take on a different light when scientists use themselves as control subjects, assuming that the participant cannot subjectively alter the results. But a thicket of problems arises when other staff members want to enroll. "The term coercion is used, but it's almost never a case of coercion. It's a matter of undue influence," says Holly Taylor of Johns Hopkins University's Phoebe R. Berman Bioethics Institute. That's not to say that postdocs, technicians, and grad students should be banned from being control subjects, says Taylor, but such a practice needs to be executed according to strict guidelines. For instance, a principal investigator (PI) should never personally ask a staff member to participate in a study. Instead, the request should be posted and staff members should be asked to give samples only when the PI is not present. Also, a PI shouldn't publicly announce that he or she is a voluntary subject. "If it slips out once, I could understand," Taylor says. "But if it's heard in the lab over and over again, you're getting close to an environment of coercion." Self-experimentation policies can vary widely. Some institutions, such as Baylor College of Medicine in Houston, have banned staff altogether from participation as test subjects. Others carefully regulate certain groups of staff. For instance, Harvard University has restrictions on medical students participating in studies, for fear of undue influence. With all the legal liabilities, official naysaying, and bureaucratic hurdles in place, self-experimentation is certainly on the decline. But has research lost something else in the process? "Science values detachment more than passion, and that has an effect on how it interacts with society," Virginia's Moreno says. Moreno thinks that if more scientists were the subjects of their own experiments, they may bring a little fun to the profession. "If people saw it as being part of the adventure of science, it wouldn't discourage them," Moreno says. "It might make the whole business of science as romantic as it once was." Sam Jaffe can be contacted at samjaffe@the-scientist.com. 1. H. Jonas, "Philosophical reflections on experimenting with human subjects," Daedalus, 98:219-47, 1969. Please indicate on a 1 - 5 scale how strongly you would recommend this article to your colleagues? Not recommended 1 2 3 4 5 Highly recommended Please register your vote

Heal Thyself or Die Trying

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Sam Jaffe

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July 2003

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