Medicine: Jesse and the Wayward Gene

Jesse Gelsinger, 18, had good reasons not to sign up for experimental gene therapy. Though the Tucson, Ariz., teen was born with a rare genetic disorder that partly disabled his liver, his course of drugs and diet was working. The Phase I trial at the University of Pennsylvania, where doctors would pump a modified cold virus into his system to correct genetic flaws, promised nothing in the way of a cure.

But Jesse was determined to become a guinea pig. “It made him feel good as a person,” says his father Paul. “He said, ‘Hey, this may be good for me, and I’ll be helping newborn infants.’ You know teenagers. They think they’re going to live forever.”

Jesse died on Sept. 17 in Philadelphia, just months after his father told him he was a hero and put him on a plane to the university. He could be the first patient to die because of gene therapy, although the only thing certain is that he died of multiple organ failure. Doctors immediately began an internal analysis. “I consider this trial over,” says Dr. James Wilson, director of the University of Pennsylvania’s Institute for Human Gene Therapy.

Gene therapy is a promising but unproved field of medicine, currently undergoing some 230 clinical trials. Since viruses are so good at hacking into the human body, scientists figure they can be used as packaging material for whatever gene the patient lacks. In Jesse’s study, all 18 participants had the same disease: ornithine transcarbamoylase (OTC) deficiency, which slows the liver’s ability to metabolize nitrogen and releases deadly ammonia into the bloodstream. So Wilson’s team harnessed the adenovirus (a cause of the common cold), neutralized harmful elements and used the virus to send in normal copies of the gene that was defective in Jesse.

What is still puzzling is why Jesse’s body reacted so violently. Was his an isolated case, or is there a problem with the way this virus was delivered–injected into the bloodstream? Is it a safe technique? Is the liver too sensitive? Should this particular kind of gene-therapy research be stopped altogether?

Not according to Mindy Rosen, co-president of the National Urea Cycle Disorders Foundation, which deals with Jesse’s disease. “This is our hope,” she says. “It is our dream for our children.”

For Paul Gelsinger, there is no anger or blame over the loss of his selfless son. “The way he went about this thing demonstrated to me a love we should all emulate,” he says. “It changed my life, to be sure.”

–By Chris Taylor. With reporting by William Dowell/New York and David Schwartz/Tucson