Death Now Blamed Directly on Gene Therapy
by
Jennifer Brown,
Associated Press Writer

4:36 PM EST; December 2, 1999; Philadelphia, PA (AP) -- In a setback for one of the most exciting fields of medical research, investigators confirmed that a young man who died during a gene therapy experiment in September was killed by the treatment. The preliminary report on the death of Mr. Jesse Gelsinger of Tucson, AZ found that an infusion of corrective genes, encased in a weakened cold virus, triggered an extreme immune-system reaction that caused multiple organ failure, said James M. Wilson, Director of the University of Pennsylvania Institute for Human Gene Therapy. Mr. Gelsinger, 18, is believed to be the first person to die as a direct result of gene therapy.

The case has stirred debate over using patients in gene-therapy experiments who are not close to death. Gelsinger had a severe gene disorder controlled by drugs and diet but was relatively healthy when he began the therapy. In addition, the results could delay experiments that use viruses to transport the corrective genes into the body -- currently the most common treatment method. In the Penn trial, the corrective genes were encased in a "weakened cold virus," which researchers had thought was safe for humans since even a full-blown cold virus usually causes no damage.

"People say, 'I have a disease, and I want gene therapy; I don't care about the risks.' Then someone dies and everyone says, 'How could you let this happen?'" bioethicist Prof. Arthur Caplan of the University of Pennsylvania said Thursday. "It will slow it for a while, then the pressures will build again, and it will get going even faster."

Gelsinger died September 17th, four days after researchers injected the modified cold virus andengineered genes into an artery leading into his liver. He suffered from Ornithine Transcarbamylase Deficiency, a genetic disorder that leaves the body unable to produce enzymes that remove ammonia from the body -- a byproduct of protein processing. Most victims of the rare disorder die as infants. Gelsinger had a mild form that he kept in check with medications and low-protein foods. Researchers said they still do not understand precisely why Gelsinger died. Seventeen other patients had been through the procedure without ill effects; and "none of the studies on animals indicated that there would be an immune reaction such as the one that killed Gelsinger," Wilson said. "The preliminary investigation suggests that the cold virus should not be injected into the bloodstream or liver the way it was done in Gelsinger's case," Wilson said. "But it has caused no problems in other patients."

Gelsinger's father, Paul, has said his son knew there was a chance he could die from participating in the study, but he accepted the odds because he wanted to help himself and others. In gene therapy, working genes are inserted to compensate for genetic flaws. It is a growing field of research that holds promise in curing ailments from heart disease to cancer. After Gelsinger's death, the university study was stopped, and the Food and Drug Administration ordered a halt in the enrollment of new patients in two experiments by Schering-Plough to use gene therapy to treat liver cancer and colorectal cancer. Those studies, like the Penn experiment, used relatively high doses of the cold virus to pass new genes into the liver.

Several clinical trials are also under way that directly inject corrected genes into a person's organs -- so-called naked-DNA infusions. Naked DNA does not carry the added risks of using a virus. The Penn researchers are to present their preliminary, 337-page report on Gelsinger's death to Federal officials on December 9th.