Charging that he “repeatedly or deliberately violated regulations governing the proper conduct of clinical studies” of experimental drugs, the U.S. Food and Drug Administration (FDA) has begun proceedings to disqualify Dr. James M. Wilson, the director of Penn’s Institute for Human Gene Therapy (IHGT), as a clinical investigator. If the FDA takes this step, Wilson, the John Herr Musser Professor and Chair of Cellular and Molecular Engineering, would be banned from testing new drugs on humans.
As the IHGT’s director, Wilson was in charge of a gene-therapy study in which an 18-year-old patient died on September 17, 1999. Jesse Gelsinger, who suffered from an hereditary liver disorder, died four days after being injected with a modified cold virus designed to deliver corrective genes to his liver. Penn already took steps last spring to limit the work of the IHGT, restricting the lab to animal- and cellular-model experimentation.
In its letter to the researcher, dated November 30, 2000, the FDA charged Wilson with failing to: adequately protect the safety, welfare and rights of subjects; ensure that the study was conducted according to the FDA-approved investigational plan; submit accurate reports regarding the safety of the study; and obtain informed consent from patients in accordance with regulations.
As the Gazette was going to press in early February, a University spokesperson said that Wilson had been in contact with the FDA and was planning to respond to the charges in a presentation to the agency.
Meanwhile, scientists may be closer to figuring out exactly what triggered Gelsinger’s death. According to a report in The Philadelphia Inquirer, Wilson, in a closed-door meeting with other gene-therapy researchers in January, pinpointed what Penn researchers believe may have caused the patient’s fatal immune-system response—surface proteins on the modified cold virus that was used to deliver corrective genes to his liver.
Wilson wouldn’t comment publicly on the findings until they are published in a medical journal, but the Inquirer confirmed them through other
scientists who attended that meeting. According to those scientists, Wilson explained that he injected mice and monkeys with high doses of a modified adenovirus and tagged it with a fluorescent dye to trace its path in their bodies. He discovered that most of it was absorbed by immune-system cells called macrophages, which set off the entire immune system. Though this didn’t cause problems for the mice, the monkeys receiving large doses of the virus started bleeding into their skin.
Even when they stripped the adenovirus of its genes and injected that into the monkeys, it caused an immune response, leading the scientists to believe that it is the surface proteins of the virus rather than the genes inside that are responsible for the reaction.
