Gene therapy patient dies under HUP care

Gene therapy, a growing field of medical research that holds promise in curing ailments from heart disease to cancer, may come under closer scrutiny following the death of an 18-year-old during an experiment at the University of Pennsylvania, bioethicists said yesterday. ''It certainly should cause us to pause and reflect,'' said Jeffrey Kahn, director of the Center for Bioethics at the University of Minnesota. ''It's a very difficult thing for us to confront, especially when the death is attributed to the research.'' Doctors still do not know why Jesse Gelsinger died September 17, four days into an experiment in which researchers placed healthy genes in his liver to combat a disease that inhibits the body's ability to rid itself of ammonia, a by-product of the processing of protein. Most victims of the disorder -- known as ornithine transcarbamylase deficiency, or OTC -- die as infants. The Tuscon, Ariz., teenager, who had a mild form of the disease that he kept in check with medications and low-protein foods, volunteered for the study to help other OTC sufferers, his father Paul Gelsinger said. A genetically altered version of a cold virus was used as a vehicle to deliver the genes. Gene therapy studies usually involve people whose diseases are so advanced that traditional treatment does not work, but the Penn experiment included OTC sufferers with less severe symptoms. ''There's a good reason, therapeutically, to do gene therapy before people are so sick it can't help them. But if the person is relatively healthy and the research poses a significant risk of harm or death, it poses a difficult dilemma,'' Kahn said. ''When do you engage in what could be quite risky research when the individual could live a long time?'' In gene therapy, working genes are inserted to compensate for genetic flaws such as the ones that lead to OTC, the rare disease Gelsinger was diagnosed with at age 2. ''Research is a risky business,'' said John Lantos, associate director of the MacLean Center for Clinical Medical Ethics at the University of Chicago. ''Often, experimental interventions are themselves dangerous. The hope is they're less dangerous than the disease.'' Some wonder if gene therapy has moved too quickly from lab animals to the thousands of humans who have taken part in gene therapy trials nationwide, but Kahn disagrees. ''I think it's a very hard case to make [that] this has been a quick journey,'' Kahn said. ''Lots of very smart people have thought about [gene therapy] for a very long time and it has been very closely scrutinized.'' Penn's experiment involving 18 patients has been halted until researchers can determine why Gelsinger died. Officials at the University's Institute for Human Gene Therapy said his case will be closely reviewed and an autopsy will be conducted to determine the cause of death. ''This death will certainly fuel the debate about how fast and how far gene therapy has come,'' Kahn said. ''But that's a general question we need to ask, and do ask, about all kinds [of medical research]. These questions are not unique to gene therapy.''