Threat of costly lawsuit looms

Since the September 1999 death of Jesse Gelsinger during his participation in a Penn gene therapy trial, all eyes have been on the University and its research practices. But those same eyes have also been on Gelsinger's parents -- and the possibility of a huge lawsuit. Such a suit could have tremendous repercussions for not only Penn's Institute for Human Gene Therapy -- which conducted the clinical trial -- but for the U.S. Food and Drug Administration as well. The FDA admitted last fall to not enforcing patient-safety monitoring rules for gene therapy researchers, and to having never inspected Penn's lab until after Gelsinger's death. Shortly after his son's death, Paul Gelsinger said he felt blame should be placed mostly on the FDA for their inability to properly monitor gene therapy research at the IHGT. "I told the FDA they had dropped the ball in overseeing Jesse's case," Paul Gelsinger said at a December 1999 National Institutes of Health hearing, while at the same time defending the IHGT. "[The Penn team] has told me everything. I want them to continue their work. That's what Jesse would want." But Paul Gelsinger's support of the IHGT began to waver when the FDA suspended Penn's entire gene therapy program in January, citing 18 violations of federal research protocol. Alan Milstein, Paul Gelsinger's attorney, said, "Many of the observations made by the FDA suggest Jesse should not have taken part in that experiment at that time." He said his client will make a decision on whether to file a suit when all of the information surrounding the case has been received and processed. The most serious of the violations against the Institute's researchers were those regarding patient consent forms and the IHGT's failure to report significant findings to the FDA. Many of the patient consent forms were improperly filled out, sometimes with no witness signature. Some patients were also allowed to take the consent forms home with them, with witnesses signing after the fact. The consent forms themselves failed to mention sizable risks involved in the research, including negative reactions experienced by prior patients and the deaths of two monkeys exposed to a treatment similar to Gelsinger's. And so, when Paul Gelsinger testified before a U.S. Senate subcommittee in January, he claimed he and his son had not been aware of the risks involved in the trials. Paul Gelsinger said he was comfortable sending his son to Philadelphia with the information he had at the time. But, he added, "Looking back, I can see that I was fairly naive to have been as trusting as I was." In addition to problems with consent forms, the FDA alleged that Jesse Gelsinger was not eligible to participate in the study due to his blood ammonia levels. While the IHGT claimed that Gelsinger's blood ammonia levels had been acceptable before testing began, the FDA alleged that they had risen and should have been tested again before research could proceed. And in July, the FDA attacked Penn again with a 15-page warning letter claiming the IHGT researchers had used outdated, expired viruses to test the toxicity of material used in their research. Whether all of this information will be enough to win a lawsuit, though, is another matter. Bioethicist and Boston University Professor of Health Law George Annas said, "It's very unusual to see a lawsuit come out of any research program." He went on to say that in the Gelsinger case, it will be difficult to prove that patients were not told of things that did not appear on the consent forms. Annas pointed to a recent article by U.S. Secretary of Health and Human Services Donna Shalala in the American Journal of Medicine which describes this case as very unique. Shalala wrote that the incident caused a complete turn-around in the field of gene therapy, where many more regulatory steps will now be taken -- meaning that the Gelsingers would be more likely to win than most if they filed a lawsuit. After Gelsinger's death, other cases were revealed in which patients had experienced severe negative reactions to treatment or even died, but Annas said only a handful of lawsuits are likely because of the slim chance of successfully suing researchers. The last piece of the responsibility puzzle rests with the organizations that fund gene therapy research. Anne Thomas of the National Institutes of Health, which funds gene therapy research projects, said that organizations like hers cannot be held accountable for what goes on during research. What the NIH required were "adverse events reports" if something serious occurred in a gene therapy program, but these were not supplied to the NIH by the FDA before or after Gelsinger's death. Annas agreed that funding agencies can only be held accountable if they know in advance that on-going research is unlawful. For this reason, IHGT Director James M. Wilson's private company Genovo -- which provided 20 percent of IHGT's funding but has since been bought out by Targeted Genetics Corporation -- will probably also be blame-free in the event of a lawsuit. University General Counsel Peter Erichsen said he could not speculate about the possibility of a lawsuit from the Gelsingers.