GENE THERAPY

February 2, 2000
		As gene therapy trials come under fire for underreporting harmful side effects, Congress begins investigating the proper balance between regulation and research. Susan Dentzer reports on developments in controversial gene therapy treatments. The Health Unit is a partnership with the Henry J. Kaiser Family Foundation.

Health Spotlight on Gene Therapy Dec. 8, 1999: Controversial Therapy Dec. 2, 1999: Breaking the Code Nov. 30, 1999: Medical Errors Focus: Internet Rx Browse the NewsHour's coverage of health.   American Society of Gene Therapy Dr. W. French Anderson	SUSAN DENTZER: The promise of gene therapy has long seemed spectacular: Prevent or cure illness by injecting healthy copies of defective or missing genes into the body. But the death of a teenager last fall in a controversial gene therapy clinical trial focused a harsh spotlight on the ways these experiments are being carried out and monitored. That was the subject of a senate subcommittee hearing today chaired by Republican Senator William Frist of Tennessee. SEN. WILLIAM FRIST: If we ask patients to participate in moving science forward, then we must be assured that gene therapy clinical trails are safe. I hope that today's hearing will be a thoughtful discussion and provide a thorough review of the oversight mechanisms that are in place. There is absolutely no room, no place for mistakes that compromise patient safety.
	A sudden breakthrough
	SUSAN DENTZER: The death of the teenager, 18-year-old Jesse Gelsinger, who suffered from a rare liver disorder, occurred during an experiment at the university of Pennsylvania. Gelsinger was injected with special viruses designed to carry healthy copies of a gene into his body. His father, Paul Gelsinger, told Senators today that his son's disease was actually under control, but that he agreed to participate in the clinical trial to help other sufferers from the disease. PAUL GELSINGER: Jesse was doing exceptionally well on his medications, and nothing should have prevented him from living a full and happy life. He believed, after discussions with representatives from Penn, that the worst that could happen in the trial would be that he would have flu-like symptoms for a week. He was excited to help. SUSAN DENTZER: 17 other patients had preceded Jesse into the trial and were apparently treated with few ill effects. But Gelsinger's case quickly turned to tragedy soon after he was injected with genes carried by the viral messenger, known as a vector. PAUL GELSINGER: Less than 24 hours after they injected Jesse with the vector in the amount that only one other person had ever been given, Jesse's entire body had been reacting adversely. He went into a coma before I could get to Philadelphia and see him, and died two days after my arrival, directly as a result of that gene therapy experiment.
	A safe procedure?
	SUSAN DENTZER: Precisely how the gene therapy and viral messenger precipitated Gelsinger's death is still unclear. But last month, the federal Food and Drug Administration shut down the University of Pennsylvania experiment, charging that investigators at the university had violated federal research regulations and failed to adequately protect the lives of patients. Then, earlier this week, officials at the National Institutes of Health disclosed that they had recently received delayed reports of more than 600 other serious adverse events. Those had occurred in similar gene therapy trials under way since 1993. SEN. BILL FRIST: The events of the past few months involving gene therapy have given all of us, our government and our society, reason to pause. If we learn that the appropriate systems and guidelines are in place on paper, we must then ask, are they working in reality? I suspect they're not. SUSAN DENTZER: Today's hearing focused on three main issues. Perhaps the foremost was whether patients like Jesse Gelsinger are adequately informed of the risks before they enter gene therapy experiments, especially from the special viral messengers, called adenoviruses, that are commonly used to transport genes into the body. In the University of Pennsylvania case, the FDA's preliminary findings suggest much information was withheld from patients, including the fact that monkeys had died from similar procedures, and that earlier human volunteers in the study had suffered serious side effects. PAUL GELSINGER: We were also unaware of the severity of liver injury incurred by several of the patients prior to Jesse. I learned that a pharmaceutical company had conducted experiments similar to the one Jesse was in and had obtained adverse results, which if disclosed, would have fully informed Jesse and me of the real risks in this procedure. I had very close contact with the doctors involved until December 10, 1999, immediately following the RAC meeting. Looking back, I can see that it was very naive to have been as trusting as I was. SUSAN DENTZER: Next, the Senators questioned officials from the FDA and NIH about delays in reporting to federal agencies on adverse events in other trials. Federal guidelines require that both the FDA and NIH be informed about these events under strict time limits, in part so that the agencies can share the information with researchers in other clinical trials. But in the case of the NIH, that apparently wasn't happening, says Dr. Amy Patterson. She directs the NIH office that oversees gene therapy research. DR. AMY PATTERSON: We recently became aware that there was widespread noncompliance with NIH's requirements for reporting adverse events. We're actively analyzing the extent of this noncompliance and the possible contributing factors for this noncompliance. Investigators have violated the federal guidelines. SUSAN DENTZER: Finally, Senators today questioned whether there were too many gaps in federal oversight of gene therapy research. There was broad agreement that such gaps needed to be plugged so that gene therapy research could safely proceed. Otherwise, patients could lose out on the enormous potential benefits. Eric Kast is a patient with cystic fibrosis, a crippling lung disease, who has participated in earlier gene therapy research. ERIC KAST: We can continue with the appropriate oversight and the caution that we require, or we can let the fear paralyze us into inaction. One of my greatest fears is that, if we delay greatly, that I may die just a year or two before a cure is found for CF. If that happens, my wife, Sherry, is going to have to live the rest of her life knowing that if I had just survived or made it one more year, we may have lived happily together for the next 30, 40, even 50 years. We really are that close, and we've really come that far. SUSAN DENTZER: The NIH And FDA are now developing proposals to improve oversight that are likely to be topics of further discussion in Congress later this year.