Nine months later, Ellen Roche, a Bayview employee who had volunteered for Togias' study, was dead of respiratory failure—a direct result of having breathed hexamethonium. As in Oklahoma, the government shut down federally funded trials, and the OHRP and the hospital began their investigations. And as in Oklahoma, there were violations on several levels. For one thing, using subcommittees to pre-review applications is a violation of federal policy: minority views on a study's safety expressed at the subcommittee level might have a harder time being heard by the full committee.

For another, there was evidence in the literature that hexamethonium might be unsafe. Togias did a search and didn't turn that up, but after-the-fact searches using different search engines and databases did turn up references to the potential risks to humans. The FDA also raised questions about the informed-consent forms that Roche and two other subjects had signed. On them, hexamethonium is referred to as a "medication" and as "(having) been used as an anesthetic"—giving subjects a false sense that it was an FDA-approved medicine and therefore safe. An outside review board commissioned by the hospital noted in a report, "The consent form is not meant to reassure the subject, quite the contrary, it is meant to raise every possible concern that might be relevant to the subject's participation."

Another criticism: Togias failed to report that his first subject (Roche was the third) had developed a cough. It went away, and Togias assumed it had to do with a viral infection making the rounds at Bayview at the time. To be safe, he added a buffer solution to the hexamethonium—but without informing the irb, which he should have done. That omission may be a reflection of the prevailing sentiment at many hospitals: that the irb and its review process are a bureaucratic pain in the neck, not a clinical necessity.

In the end, nobody could say that strict compliance would have saved Roche. But even the possibility haunts everyone involved. "If all things leading up to doing that study had been perfect and she had died, it still would have been a horrible event," says Dr. Edward Miller, dean and ceo of Johns Hopkins Medicine, "but I would have felt better about the fact that we had done everything humanly possible to prevent it."

Johns Hopkins' response to the crisis, as in Oklahoma and at the University of Pennsylvania, was to rereview all its clinical trials and completely restructure its institutional review system; Johns Hopkins also brought in an outside irb to evaluate all new applications until the process is complete. The University of Oklahoma, for its part, is spending hundreds of thousands of dollars to create a model system for human- subject protection—including requiring its researchers to become certified in subject safety. And last July, Penn instituted a new policy on financial conflicts of interest: any potential conflict, whether it involves funding or financial stakes in the outcome of the trial, must be reviewed by both the irb and by a separate, university-wide panel of experts from the law school and ethics departments.

But the U.S. can't afford to wait for every research institution to react to its own lapses. That's the impetus for a sweeping overhaul of the OHRP, designed by director Greg Koski—with advice from a newly motivated Johns Hopkins—to make the agency more aggressive in protecting human subjects. It's also behind legislation that will soon be moving through both houses of Congress. Representative Diana DeGette of Colorado will introduce a bill this week that is aimed at finally giving humans the same legislative protections that animals receive; the rules will apply to all research on humans, not just federally funded or FDA-regulated research. Her bill gives the OHRP more auditing responsibility and enforcement options, including the ability to punish individual researchers without shutting down an entire institution—something that office has long wanted. And her bill will lay down new rules that address financial conflicts of interest. In the Senate, Edward Kennedy plans to hold a hearing next week at which Mathias, among others, will testify, and will introduce his own bill soon after.

Both DeGette and Kennedy endorse the idea of accrediting IRBS. But they are split on whether accreditation should be mandatory. So far, Kennedy is saying yes. DeGette, who has championed patient protection in part because the University of Colorado was severely sanctioned by OHRP in 1999, thinks a voluntary system would, paradoxically, protect patients better. "The whole point of accreditation," says DeGette, "is to encourage research institutions to reach for a higher bar, to go above and beyond the minimum requirements."

Critics of the current system have all sorts of ideas about how hospitals and research labs could go beyond the minimum. One is the notion of subject advocates—independent consultants whose sole function would be to look out for the best interests of the subjects, not the scientists. Argues George Annas: "You cannot rely on the conscience of the individual investigator, because he has an inherent conflict of interest. He has to enroll subjects in his study."

Many critics also point to the consent forms people sign when they join a clinical trial. Even when the risks are clearly spelled out—and they frequently aren't—patients tend to misunderstand what's actually going on. The truth is that less than 5% of subjects in Phase I trials, which measure the toxicity of a new drug, will receive any health benefit whatsoever. Yet when a 1995 University of Chicago study quizzed patients about why they enrolled in their Phase I cancer trials, fully 85% answered, "Possible therapeutic benefit."

In another study of cancer patients, at Harvard Medical School, nearly 75% of the subjects did not understand that the trial was investigating a treatment that was not standard. Two-thirds said they did not know they might face additional pain or discomfort. Says Annas: "These trials involve a great deal of mutual self-deception. Patients really want to believe it's treatment, and doctors really want to believe they are curing somebody."

Insisting that patients be given the unvarnished truth about clinical trials might scare many away. But that doesn't bother Alan Milstein, an attorney who has represented Jesse Gelsinger's family, as well as many of the participants in McGee's study. "The biggest myth out there," Milstein says, "is that every one of these studies is essential to the advancement of medicine. That's just nonsense. Most have to do with the advancement of the researcher himself." If it were just a lawyer talking, that sentiment might be easy to dismiss. But Marcia Angell expresses a similar criticism: "We have floods of me-too drugs," she complains. "So much research is trivial duplication."

But no matter what regulations, what standardized forms, what oversight committees the government and institutions end up putting in place, in the end, it's still up to the researcher to treat his subjects with dignity and care. In fact, argues University of Virginia bioethicist Jonathan Moreno, there's a downside to stronger protectionism: "When you take away the discretion of scientists, it's possible they'll shrug their shoulders and say, 'Protecting subjects isn't my job. Someone else will have to take care of it.' And if we don't have a morally responsible community of investigators, then nothing we do will make a difference."

That said, everyone involved in an experiment has the duty to put the subjects' interests first. Says Duke's Sugarman: "The moral responsibility for the protection of patients lies with the investigator, the sponsors, the people who carry out the research: nurses, assistants, technicians, research pharmacists. You can't just say, 'The irb said it was O.K.'"

Luckily for many of the patients in Dr. Michael McGee's vaccine trial, Cherlynn Mathias already had that attitude—though she has paid a price for her action. Facing nasty criticism from many of her colleagues at the University of Oklahoma and worried she would not be able to get decent medical treatment in Tulsa, she finally moved to Texas last August. Sometimes she wonders whether she did the right thing by sending that letter to the OHRP, but she is proud of the way the university responded.

She doesn't say the same for her former boss, though. "What hurt me so much was that McGee allowed some of the patients to believe that the only reason they were dying was that they had been forced to stop taking his drug. Many of them died," she says, "believing I was responsible for their deaths." The truth is that she was responsible only for shattering their illusions.

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