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NIH Committee Suggests Changes Following Fatal Gene Therapy Experiment

Dec. 9, 1999 (Washington) -- A federal committee charged with overseeing the safety of gene therapy is recommending a series of changes in the wake of a patient death that has attracted national attention.

After two days of hearings focused on gene therapy, which uses a disabled common cold virus to deliver a gene that corrects a liver enzyme problem, the National Institutes of Health's Recombinant DNA Advisory Committee suggested the need for better standards as well as more communication between the researchers, the FDA, and NIH.

Specifically, the panel, comprised of members from a number of government agencies, wants to see greater uniformity in the use of these viruses since the potency and the dosages of these powerful biologic agents vary widely. In addition, the committee, known as the RAC, wants to develop a database so that gene therapy researchers as well as regulators can compare their results.

"We have no interest in stopping human gene therapy, none whatsoever. We are very interested in ensuring that the quality of the trials and the quality of the science are worth the investment of the patient," Claudia Mickelson, PhD, chairwoman of the NIH panel, tells WebMD.

The hearings revolved around the fatal result of an experimental gene therapy given to 18-year-old Jesse Gelsinger on Sept. 13. It was apparently the first time a patient has died directly as a result of gene therapy. Gelsinger suffered from ornithine transcarbamylase deficiency, an inherited liver disorder that allows ammonia to build up to dangerous levels. The condition is often fatal.

The FDA was critical of the researchers, led by James Wilson, MD, director of the Institute for Human Gene Therapy at the University of Pennsylvania, saying that they shouldn't have given Gelsinger the therapy because his ammonia levels were too high immediately prior to the treatment. The agency says that some of the other 17 patients in the trial also had liver "toxicities" and also should have been disqualified.

FDA officials say they should have been notified about these issues, as well as the results of animal studies using a similar therapy that preceded Jesse's treatment. The FDA's Anne Pilaro says 11 monkeys developed liver toxicity and that five of them died. That information came to the agency after Jesse died, but a spokeswoman for the University of Pennsylvania insists that no primates got the same treatment as Jesse. A formal investigation is underway.

Wilson, who has refused to respond to media questions, defends the treatment, but he did apologize for holding back on some information about his experiment. "If we could do it over again, it would have been very easy to go ahead and disclose that to the RAC, and it was an oversight," Wilson told the committee.