The death of teenager Jesse Gelsinger during an experiment at the University of Pennsylvania in September enveloped the emerging field of gene therapy in a maelstrom of controversy.
And U.S. Sen. Bill Frist '74 (R-Tenn.), a heart and lung transplant surgeon and the only physician in the Senate, is in the eye of that storm.
Frist — a University trustee who in February initiated a hearing in the Senate Subcommittee on Public Health to examine ethical issues surrounding gene therapy — charged yesterday in an interview with The Daily Princetonian that the National Institutes of Health and the Food and Drug Administration have "fallen short" in their responsibility to effectively monitor gene therapy trials.
Meanwhile, the NIH and FDA are scrambling to mend their battered images. Yesterday, they issued a joint press release detailing two new initiatives to protect participants in gene therapy experiments.
"Almost all medical ethical issues come through either my committee directly or are brought to my attention," said Frist, who had begun looking into gene therapy before Gelsinger's death.
"It became apparent to me in my conversations with FDA and NIH that the system of oversight is not working and that they had not appropriately gathered information on adverse reactions in the clinical trials underway in the field of gene therapy," he explained. "It became apparent that in this new field of gene therapy, the oversight organizations were not communicating well with each other and were not fulfilling their responsibility in providing that oversight which Congress has instructed them to do."
Outspoken
Over the last few weeks, the FDA has shut down several gene therapy trials — and others have closed voluntarily — in response to increased scrutiny and federal oversight.
Gene therapy — which attempts to modify a patient's genetic code in order to cure genetic diseases such as cancer, cystic fibrosis and Alzheimer's — has been receiving increased attention in recent months as a result of the death of Gelsinger and the outspokenness of Frist, who has helped to provoke national discussion by bringing the topic into the Senate.
In the wake of his subcommittee's hearings, Frist wrote in a letter Friday to Secretary of Health and Human Services Donna Shalala, "I remain concerned about the apparent lack of federal oversight in gene transfer trials conducted in this nation. It was clear to me from the testimony . . . that the oversight system is not adequately protecting patients."
But Frist said yesterday that he believes gene therapy research must continue, despite the spate of recent mishaps — of which the Gelsinger case was the most publicized.
"We had a balanced hearing looking at the importance of having appropriate government oversight, but at the same time we want to absolutely support scientific research and allow it to advance," he said.
"We don't halt science that I truly believe will be lifesaving in the near future, but at the same time we have to make sure of patient protection, and that has to be carried out with full consent and full disclosure, adequate reporting about the clinical trial investigators to the NIH and FDA and appropriate coordination between those agencies as well as dissemination back to the public," he added.
University bioethics professor Peter Singer took a slightly different tack than Frist in analyzing the controversy surrounding gene therapy trials.
"The key mistake in the Philadelphia case is that from the reports that I've read, there are cases of this condition in infants where it's very likely to be lethal," he said. "The reasoning is that parents would be so desperate they'd try anything. But the decision was made to experiment on people with minor forms of the illness instead of on infants. That seems to be a really misconceived idea. It should not be based on voluntary consent but on what the patient has to lose. If the patient is a young adult who has good life prospects, then he has more to lose. They do not give sufficient weight to that factor. People focus on voluntary consent rather than the reasonableness of the decision."
But Singer also agreed with Frist that gene therapy research should go on.
"I would like to see them not prohibit further research," he said.
Subcommittee hearings
Frist has informed Shalala he intends to hold a second hearing during the next few months to review the adjustments made by her department in response to the concerns that have been raised.
Testifying before Frist's subcommittee on Feb. 2, Amy Patterson, director of the Office of Biological Activities, agreed that there were serious concerns regarding her organization's handling of gene therapy treatments.
"Recent events made it clear that NIH needs to make some systemic changes to its oversight of adverse event reporting," she said, describing a system in which letters were sent to each institution stressing the responsibility to report mishaps. "Even though these reminders are explicit and targeted to each investigator, they clearly have not accomplished what we intended."
But, like Frist, she emphasized that testing should continue.
"Without clinical research, there can be virtually no new diagnostics, new treatments or new prevention strategies to improve the length and quality of our lives and the lives of our families," she said.
New steps
Today, the NIH and the FDA announced plans to create a more stringent monitoring procedure and to hold regular symposia to share medical and scientific data.
"Clinical trial monitoring and responsible reporting must be taken seriously by all parties involved in gene therapy trials," said Commissioner of Food and Drugs Jane Henney in a press release. "Our plan will help restore the confidence in the trials' integrity that is essential if gene therapy studies are to be able to fulfill their potential."
After pressure by Frist to reexamine its oversight procedures, the NIH recently admitted that 652 adverse events went unreported. Adverse events include when a patient in a trial dies, suffers a life-threatening episode or requires hospitalization or surgical intervention.
Gelsinger's death was such a case.
According to Paul Gelsinger, Jesse's father, the family was told that he might experience flu-like systems for a week, but 24 hours after receiving his first injection, Gelsinger began suffering severe effects and died soon after. The family was not told that monkeys had died in similar experiments.
"I am not against gene therapy," Gelsinger testified before Frist's subcommittee Feb. 2. "I recognize it holds so much promise for so many people. But we cannot allow what happened to Jesse to happen again. . . . I have read my son's death called by one leader in the field as 'a pot hole' on the road to gene therapy. His death was no pot hole. It was an avoidable tragedy from which I will never fully recover."
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