Eight Years after Jesse's Death, Are Human Research Subjects Any Safer?

It has been more than eight years since Jesse Gelsinger, Paul's son, died in a gene therapy clinical trial. But despite the press exposure and public outcry that followed, no progress has been made in fixing the broken system of protections for human research subjects. These people are no safer today than they were eight years ago—they are still at serious risk of exploitation and harm.

Many things stand in the way of better protection, but perhaps the greatest obstacle is the lack of adequate federal oversight. Not all human research is subject to federal regulations, since the regulations apply only to studies that are federally funded or that involve new drugs and devices for which applications have been filed with the Food and Drug Administration. An estimated 30 percent of studies are not covered. In contrast, each and every experiment involving animals is regulated by the federal government under the Animal Welfare Act.

Further, the federal oversight that does exist offers minimal protection. Last year, a report by the inspector general of the Department of Health and Human Services found that the FDA, the agency responsible for overseeing most clinical trials, inspected just 1 percent of study sites. Small wonder, since it has a mere two hundred investigators and there are 350,000 sites.¹ When the FDA detects a problem, it typically does so long after the research is completed. Proactive oversight of the safety of human subjects is extremely limited.

Given the lack of oversight, it is no surprise that adverse events are underreported. According to the only comprehensive study on the subject, just eight deaths and 386 adverse events were reported to the Office of Human Research Protections of the Department of Health and Human Services from 1990 to 2000. Yet we would have expected several hundred deaths and tens of thousands of adverse events in a ten-year period.²

Paul Gelsinger gained an intimate understanding of the underreporting of adverse events after his son died. Jesse, who was eighteen years old, was participating in a phase I safety study of a gene transfer therapy for ornithine transcarbamy-lase deficiency (OTCD), a rare metabolic condition. He had a mild form of the disorder and knew that he would get no medical benefit from the trial. But he enrolled in the study, which was conducted at the University of Pennsylvania, because it seemed safe enough. The consent form did not mention any serious reactions in humans, and conversations with the doctors led Paul and Jesse to believe the therapy was safe. And the trial could possibly benefit people with severe forms of OTCD. Paul encouraged his son to participate.

As it happened, Jesse received the maximum dose of the gene transfer infusion. Within a day, he experienced a massive immune response to the adenoviral vector. Four days later, on September 17, 1999, he had multiple organ failure and died.

Paul set out to discover what had gone wrong. He confronted the doctors involved in the study. Meanwhile, Adil Shamoo and members of his organization, Citizens for Responsible Care and Research, a nonprofit dedicated to improving the protection of humans in research, were also asking questions. Two months after Jesse's death, Paul and CIRCARE learned that the FDA had not created a system for tracking gene therapy patients and disseminating information about serious adverse reactions. Further digging led to the minutes of a 1995 meeting of the Recombinant DNA Advisory Committee of the National Institutes of Health, which oversees gene therapy research. In the minutes, an FDA representative admitted under pressure that one reason that the FDA did not create this tracking system was that his superiors "answer to industry." ³ The drug companies were using their influence with the FDA to prevent the dissemination of adverse reaction information on the grounds that it was proprietary. It did not seem to matter that withholding this information endangered the lives of those participating in research.

The FDA's own investigation into Jesse's death found that the researchers were responsible because they...