Penn hit with suit over gene therapy


The family of Jesse Gelsinger argued that risks were not disclosed. He died last fall during the program.

Jesse Gelsinger died four days after getting an experimental gene drug to try to correct a inherited liver disorder. By Huntly Collins

The family of an Arizona teenager who died last fall during a gene-therapy experiment at the University of Pennsylvania yesterday sued Penn and others involved in the controversial procedure, which aimed to correct an inherited liver disorder.

The suit, filed in Philadelphia Common Pleas Court, follows the first anniversary of the death of Jesse Gelsinger, 18, of Tucson, Ariz., who died here Sept. 17, 1999, four days after getting an experimental gene drug in a trial for which he had volunteered.

But in their complaint, Gelsinger's father, Paul Gelsinger, of Tucson, and his uncle, John Gelsinger, of Medford, N.J., allege that the patient consent form signed by Gelsinger and other trial volunteers deliberately underplayed the risks of the procedure, which shot trillions of disarmed cold viruses directly into patients' livers.

Penn officials yesterday described the Gelsinger family's complaint as "only one version of a very complicated and painful story." They said they would respond to the specific allegations "in due course," declining to do so yesterday.

The suit also contends that the three doctors who conducted the trial should never have enrolled Gelsinger because his ammonia levels were higher than those specified in the trial protocol.

It also alleges that Penn's experiment was fraught with conflicts of interest - including was the financial stake of James M. Wilson, the Penn doctor in charge of the experiment - which were not sufficiently explained to Gelsinger and other patients.

Arthur Caplan, the Penn ethicist who advised Wilson's team to conduct the experiment on relatively healthy adults rather than sick babies, is also named as a defendant.

Alan Milstein, a Moorestown lawyer representing the Gelsinger family, said he would seek maximum monetary damages allowable under the law. He said the timing of the suit was not coincidental.

"Paul thought it was appropriate that we file action at the anniversary of his son's death," Milstein said. "This is something that still affects him. He wants to get to the truth, and he wants those accountable to be held responsible."

In a statement, Penn officials said the first anniversary of Gelsinger's death - which they believe was a tragic accident - was "a sobering moment" for the university.

"Our deepest sympathy is with the Gelsinger family at this very difficult time," university officials said.

Penn officials said they were trying to correct weaknesses at the school's Institute for Human Gene Therapy but argued that those weaknesses - which prompted federal regulators to shut down the program's human trials - did not contribute to Gelsinger's death.

Penn also said it "categorically rejects" the complaint's charge that financial gain "played any part in any aspect" of the trial.

Gelsinger was the 17th patient to get the experimental gene drug, which used modified adenoviruses - a type of cold virus - to deliver corrective genes to people suffering from a liver disorder known as ornithine transcarbamylase (OTC) deficiency.

He is believed to be the first person to die as a direct result of gene therapy, a highly experimental field that holds out the promise of correcting underlying genetic disorders, not just treating the disorders.

Although the precise cause of Gelsinger's death is not yet known, Penn doctors believe he had a massive immune response to the adenoviruses used to deliver the corrective genes, prompting his natural defense system to attack his own organs.

Gelsinger's death has prompted widespread internal reviews of gene-therapy programs at universities and in private industry, led to intensified monitoring by federal agencies, and stirred Congress to call for even more stringent regulations.

Penn's gene-therapy program has been put on hold by the U.S. Food and Drug Administration, which found numerous violations of federal guidelines during an on-site investigation conducted there after Gelsinger's death.

Besides Wilson and Caplan, the other individuals named in the suit are Steven Raper, the Penn physician in charge of Gelsinger's daily care; Mark Batshaw, a physician at Children's National Medical Center in Washington and an OTC expert who also oversaw the trial; and William Kelley, former dean of Penn's medical school.

Besides Penn, the suit names two other institutions as defendants - Children's National Medical Center and Children's Hospital of Philadelphia. Batshaw, now at the Washington hospital, used to work at Children's Hospital in Philadelphia, which reviewed the consent forms for the OTC trial.

Although Gelsinger freely signed such a form, the plaintiffs allege that the risk of toxic effects from the viral vectors were understated; that the form did not mention that monkeys injected with a similar vector got sick or died; and that several patients treated before Gelsinger suffered serious side effects.

The suit also alleges that Penn may have given the green light for human trials of the OTC therapy based on a "defective product" used in testing the approach on animals. The viral vectors given to the animals had been sitting on lab shelves for 25 months before they were administered to animals, likely making them less potent than the freshly grown viruses used in the human trial, the suit says.

Milstein declined comment yesterday on whether he was involved in efforts to reach an out-of-court settlement with Penn. But in its statement, Penn said representatives of the Gelsinger family "had initiated discussions with the university and the other institutional defendants, and we will respond." The statement did not elaborate.

Gelsinger family members could not be reached for comment yesterday. Officials at the children's hospitals here and in Washington declined comment. Caplan said his lawyers would not allow him to comment. Wilson, Raper and Batshaw did not return calls seeking comment.