Penn's gene therapy program suspended

Lower Merion High School '98

Bala Cynwyd, Pa.

Penn's gene therapy program found itself under fire this year after a patient's death during a clinical trial drew national attention as the first death directly attributed to the high-profile gene therapy field.

Eighteen-year-old Jesse Gelsinger, of Tucson, Ariz., died on September 17, 1999, after receiving experimental gene therapy. His death was the first known fatality from the experimental medical treatment that seeks to cure people by replacing their genes, and the case quickly sparked national controversy.

And after an investigation by the Food and Drug Administration into the case revealed many instances where Penn's Institute for Human Gene Therapy violated various federal regulations, the U.S. government suspended Penn's entire gene therapy program, which until then was one of the largest and most respected in the nation.

Gelsinger died just four days after receiving an infusion of genes intended to treat the disorder he suffered from, known as ornithine transcarbamylase (OTC), which prevents the body from breaking down ammonia, a by-product of protein digestion.

Though IHGT Director James M. Wilson and other IHGT researchers had long maintained that Gelsinger's death had not been due to human error, media reports suggested that the OTC team had ignored preliminary animal studies.

Among the allegations made by the FDA was that patients were not adequately informed about the risks involved in the trial, that Gelsinger was ineligible to participate in the study and that the adverse reactions experienced by patients prior to Gelsinger should have been reported in a timely manner.

The FDA also questioned why animal study data, including the deaths of monkeys in trials similar to the OTC trial, were not reported to federal regulators on time.

Wilson and the lead investigators of the trial admitted that they should have notified the FDA earlier about previous patient reactions, but they insisted that those decisions did not lead to Gelsinger's death.

Gelsinger's family -- in particular his father, Paul -- remained steadfast supporters of the Penn researchers, instead blaming the FDA for a lack of oversight in the trial.

But in January that support began to waver when the FDA suspended all gene therapy at the University. In a letter sent to the IHGT, federal regulators cited 18 "serious deficiencies" in the Institute's oversight and monitoring of the OTC trial that prompted the moratorium.

Following the announcement of the moratorium, University President Judith Rodin pledged the University's cooperation with the FDA investigation and directed the IHGT to respond to the allegations. She also convened a committee of scientists unaffiliated with the University to perform a review of the Institute's research procedures.

A separate committee, chaired by Provost Robert Barchi, was formed to look into human testing procedures all across the University.

Days after the FDA imposed its gene therapy moratorium, Paul Gelsinger testified before a U.S. Senate subcommittee that he and his son were unaware of the dangers associated with the clinical trial.

"With the knowledge I had at that time, I was comfortable enough to send my son... to Philadelphia alone," Gelsinger explained. "Looking back, I can see that I was fairly naive to have been as trusting as I was."

The gene therapy program remains under suspension.

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