GENE THERAPY: New Findings in Death Raise Suspicions

      Federal investigators have discovered startling new findings that indicate "serious problems" in the gene therapy experiment that killed Arizona teenager Jesse Gelsinger, the Washington Post reports. New evidence concerning the September death suggests that, at the time of the experiment, Gelsinger's liver was not functioning at the minimum level required by federal regulators for participation in the gene therapy study -- in which UPenn researchers infused Gelsinger's liver with "trillions of genetically altered viruses." FDA officials also discovered that researchers failed to alert the agency to serious side effects suffered by two experiment volunteers prior to Gelsinger's infusion. According to rules established by FDA and scientists governing the study, the adverse effects were serious enough to put an immediate moratorium on the experiment. Also, UPenn researchers did not inform federal officials about results of preliminary animal experiments that may have "influenced the agency's judgement of the study's safety," regulators said. Researchers failed to alert the FDA about a significant change in the language of the study's consent form -- which omitted information about the deaths of four monkeys from a similar gene therapy. The new findings, the first from an ongoing federal investigation into Gelsinger's death, resurrect questions about the conduct of UPenn scientists. The information "stands in stark contrast" to a public statement made last week by UPenn researchers that claimed "no 'human error'" contributed to the fatality. UPenn researchers responded to the FDA findings by stating, "We are disappointed by the FDA's release to certain media outlets of its preliminary findings about our gene therapy clinical trial ... prior to completing their report or communicating these finding to us."

New Evidence, New Suspicions
      UPenn scientists released a statement yesterday responding to the FDA study, arguing that Gelsinger's liver functioned at the acceptable level when he was enrolled in the experiment. FDA regulators do not dispute this, but rather suggest that Gelsinger was not well enough to participate at the time of his infusion. But FDA Director of the Center for Biologies Evaluation and Research Kathryn Zoon indicated that "Gelsinger's acceptance into the study is one of 'a number of different areas that [FDA officials] have concerns about.'" Zoon explained that at least two earlier participants receiving lower dose infusions than Gelsinger received suffered "Grade 3" liver damage, which should have halted the UPenn study. The FDA, however, was never alerted to the events. Following Gelsinger's death, UPenn lead researcher James Wilson told the Washington Post that no study participants -- other than Gelsinger -- had suffered adverse effects from the treatment. Wilson later recanted, acknowledging one of the two liver damage cases. On Thursday, UPenn researchers and FDA officials will present the initial results of their separate investigations into Gelsinger's death -- the first believed to be caused by gene therapy. The presentation will occur at a special three-day meeting at NIH, during which biotech industry representatives are expected to petition for "reduced federal oversight" of gene therapy studies (Weiss/Nelson, 12/8).

Other Gene News
      Scandals in the world of gene therapy have not dissuaded all proponents of the benefits of genetic research. On the heels of last week's news of the discovery of chromosome 22, U.S. Rep. Louise Slaughter (D-NY) announced yesterday that she is introducing legislation to help communities bring the benefits of genetic research home. Slaughter's legislation, the Genetics and Public Health Services Act, would establish two federal-state grant programs aimed at funneling information gleaned from genetic research into "practical public health strategies." Slaughter stated, "With the passage of this legislation, we will be able to embark on some truly exciting public health research and prevention activities. ... There is a chance to affect not only a single disease or a family of illnesses, but virtually every disorder known to humanity." Sen. Edward Kennedy (D-MA) has introduced a companion Senate proposal, S.1981, which would authorize $100 million for FY 2000 through FY 2009 (Slaughter release, 12/7).