Experts debate FDA charges' impact

The FDA decision to halt gene therapy at Penn may have larger repercussions. The shockwave of the federal government's decision to halt all gene therapy research at Penn has been felt by researchers across the country, leaving many scientists wondering what the allegations against the University -- if substantiated --will mean for the decade-old research field. Along with the moratorium, which was announced on Friday, the U.S. Food and Drug Administration issued a list of 18 possible protocol violations by Penn researchers involved in the Institute for Human Gene Therapy clinical study that cost 18 year-old Jesse Gelsinger his life. Among the violations are that at least one of the patients enrolled in the study was ineligible to participate, that researchers did not report the deaths of monkeys in test trials until after Gelsinger's death and that patient consent forms were poorly documented. Wilson and his researchers have yet to respond to the list of infractions , or to the FDA's subsequent letter which put all eight gene therapy clinical studies -- only five of which were active -- at the Institute on hold. University spokesman Ken Wildes said that the IHGT will respond to these allegations within a few days. While gene therapy researchers acknowledge the seriousness of the FDA's charges, most are reserving judgement on the IHGT and its founder and director James M. Wilson, a renowned pioneer in the field of gene therapy, who led the study. "The biggest question in my mind is how strong the evidence was," said John Lantos, the director of the MacLean Center for Clinical Medical Ethics at the University of Chicago. "If the researchers knew there were problems and didn't tell people, that's a problem." Dusty Miller, a researcher and professor at the Fred Hutchinson Cancer Research Center in Seattle agreed, saying patients have the right to know what they're getting into. "The informed consent issues -- if they're true -- are surprising," Miller said. Among the FDA's allegations were numerous examples of discrepancies between witness and patient signature dates on consent forms -- the agency claimed that some forms lacked witness signatures altogether. Jeffrey Kahn, director of the University of Minnesota's Center for Bioethics, agreed that patients need to be adequately informed by investigators before taking part in clinical trials. "Then it's up to the individual," he said. But the three researchers stressed that the potential protocol violations are only allegations against the IHGT team of researchers at this point. "Jim is a conscientious guy. I respect his work," Miller said. "Now [he] has a chance to defend himself." Wilson, who once served as president of the American Society for Gene Therapy, founded the IHGT in 1993. The Institute has since become one of the leading gene therapy research institutions in the country. The FDA allegations levied against the IHGT are a setback that will be felt throughout the scientific community, Kahn said. "It's not just a story about gene therapy," he noted. "It's a wakeup call for all clinical research. It's very unusual for a subject to die? from the therapy that's being researched." Yet other scientists are unsure about how the FDA's action at Penn will impact gene therapy. "It's very hard to judge what it actually means," said Michael Blaese, the chief scientific officer of Kimeragen, a Newtown, Pa.-based biotechnology firm that conducts gene therapy trials. Before 1996 it was clearer, Blaese explained, because the Recombinant DNA Committee (RAC) of the National Institutes of Health had authority over what gene therapy trials could be performed. But when Harold Varmus, the former director of the NIH, took authoritative power away from the RAC, that power was divided between the FDA and the Institutional Review Boards of the individual research institutions. That created much confusion among researchers, Blaese noted, because there were several levels of review that researchers had to go through. He thinks the outcome of Friday's FDA decision will ultimately be to make the regulatory process simpler. "There will be clarity," he said. "In that sense [the FDA action at Penn] will probably be positive." Dusty Miller thinks gene therapy has tremendous potential, but he recognizes that, like the space program, it has risks. "There's no sense sending people up on firecrackers if you want to be safe," he said. "The bottom line is this is an experimental process." Miller said he thinks patient safety needs to be of the foremost concern, but he hopes that the FDA action at Penn will not halt research in the young field. "It's like the Challenger disaster. You spend two years soul-searching, and I think people are missing the point," Miller said. "The point is that gene therapy will have some benefit." On Friday, University President Judith Rodin asked Provost Robert Barchi to form a committee of scientists unaffiliated with the University to recommend ways the IHGT can achieve FDA compliance. The committee, which is expected to be formed this week, will likely release its final recommendations in six to eight weeks, Rodin said on Tuesday.