It was what the New York Times headlined a biotech death. Eighteen-year-old Jesse Gelsinger died four days after receiving gene therapy for a rare metabolic disorder. It was also the first death associated with gene therapy. As details of the experiment and the death unfolded, with often contradictory information, the field of gene experimentation appeared neither orderly nor well regulated.
Gelsinger had a rare metabolic disorder called ornithine transcarbamylase deficiency, which prevents the normal breakdown of ammonia. Children born with the condition often die a quick death, but Gelsinger had a mild form, controlled by drugs and a rigorous low-protein diet. Nonetheless, the diet and drugs were tough on a teenager striving to lead a normal life. As it happened, the University of Pennsylvania was working on a protocol in which volunteers with forms of the OTC deficiency similar to Gelsinger's would receive a healthy copy of the OTC gene, delivered via adenovirus. Gelsinger signed up for the gene therapy study, and it shut down his organs one by one, and killed him.
Twelve days after Gelsinger's death, the Washington Post got wind of the story and began uncovering a series of ethically questionable features of the protocol. The Recombinant DNA Advisory Committee had discussed the experiment at a meeting in 1995 and eventually approved it. But the Post discovered that a member of the committee had expressed concern about trying such a novel treatment on people who were not critically ill. The decision to work with adults who were relatively well rather than with infants who had the quickly fatal form of the disease turned out to be the result of the university's own ethics committee. The committee had ruled that parents could not possibly make a rational decision about the risks of the experiment.
Also, the RAC had recommended that the genetic material be delivered via an intravenous line rather than a catheter into the liver, as the researchers had planned. Only after Gelsinger's death did RAG members learn that the Penn researchers, in consultation with the Food and Drug Administration, had used the catheter route after all, in an effort to avoid side effects.
There were other perhaps even more egregious problems. Monkeys that had received a similar adenovirus had died of blood and liver complications, and while the consent form shown to reviewers had mentioned this fact, it did not appear on the form signed by Gelsinger. Further, FDA officials said that on the day before the injection, Gelsinger's ammonia levels had risen above the maximum allowed by the protocol. …