Gene therapy team facing allegations

The FDA alleges that the Penn scientists violated researvh protocols. Top officials from the University of Pennsylvania Health System and its Institute for Human Gene Therapy will confront accusations today from the federal government that researchers improperly led a study that left an 18-year-old man dead. IHGT Director James M. Wilson, the lead researcher in the controversial study, and officials from the U.S. Food and Drug Administration will separately present their preliminary findings to officials from the National Institutes of Health in Bethesda, Md., on what caused the September 17 death of Jesse Gelsinger, a patient in a gene-therapy experiment. In the first day of a three-day conference, FDA officials yesterday charged that the Penn team committed serious research misconduct. The specific accusations included that scientists ignored important test results and reactions in early study participants, failed to mention on patient consent forms that a monkey died after receiving the gene therapy and that they withheld information from federal regulators. The allegations were announced yesterday after a daylong hearing before an NIH advisory committee investigating the death and looking at safety issues in gene therapy. The hearing, before a packed auditorium, will resume today. Wilson issued a statement yesterday defending his methods, but declined to comment further, promising a full discussion of the case today. Gelsinger, a Tucson, Ariz., native had ornithine transcarbamylase (OTC) deficiency, a genetic disorder that left him unable to digest ammonia, a poisonous by-product of protein metabolism. Since he had a mild form of the disease, his symptoms had been kept in check with drugs and a low-protein diet. Gelsinger died four days after being infused with genetically altered viruses that would bring functioning genes to his liver, where they would theoretically produce the missing enzyme. But the FDA is alleging that Gelsinger's liver was not functioning effectively enough for him to be infused with the modified cold virus. As recently as last week, the research team -- consisting of Wilson, Mark Batshaw of Children's National Medical Center in Washington, D.C., and Penn physician Steven Raper -- insisted that no human error contributed to Gelsinger's death. Instead, they said in a 337-page report that the modified virus triggered an immune response that eventually led to lung failure. Gelsinger's father, Paul, said he blamed the FDA for not supervising the experiment more closely. "I told the FDA that they had dropped the ball in overseeing Jesse's case," he said. "[The Penn team] has told me everything. I want them to continue their work. That's what Jesse would want." According to Jeffrey Kahn, director of the Center for Bioethics at the University of Minnesota, the allegations "uncover a fair amount of concerning information," especially the possibility that the researchers overlooked certain recruitment and treatment criteria. "We should ask whether it's an isolated case and what it means for safety for all patients in research," he said. And the findings, he said, should serve as a "wake-up call" to federal regulators who oversee this research. Gelsinger's death -- the first reported death related to gene therapy -- rocked the nine-year-old field that holds the promise of curing diseases ranging from cancer to cystic fibrosis and raised questions about its continued viability. The Penn experiment had caused controversy even before it began, with concerns about the use of relatively healthy patients and the infusion of the virus directly into the liver. Since Gelsinger's death, media reports have suggested that the team ignored serious side effects in preliminary animal studies and revealed that Wilson may have had a financial stake in the success of the study. In addition to the Penn and FDA presentations, comments will also be made by the Recombinant DNA Advisory Committee, an NIH panel that advises the FDA on issues relating to gene therapy research. The forum started yesterday, with a symposium on the use of the adenovirus in gene therapy. And tomorrow, the guidelines for reporting "adverse events"-- deaths or serious illnesses related to gene therapy -- will be reviewed. This has become increasingly important in light of recent information that researchers in New York and Boston did not tell the NIH about deaths and side effects in gene-therapy patients. It has been speculated that knowledge of some of these studies could have prevented Gelsinger's death. Kahn said he thinks the forum will "force a close look at the way protocols are carried out." "There's a fine line between the protection of proprietary information and protecting the safety of the subjects," he said, adding that "fuller" disclosure of adverse events is necessary. The Associated Press contributed to this article.

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