Author: Jon Merz
Date: 02-10-05 08:46
Source: Philadelphia Inquirer
URL: http://www.philly.com/mld/philly/news/10860057.htm?1c
Date published: February 10th 2005
Penn to pay $517,000 in gene therapy death
By Susan FitzGerald and Virginia A. Smith
Inquirer Staff Writers
More than five years after the death of a teenager in a gene therapy experiment at the University of Pennsylvania, federal law enforcement officials yesterday announced a $517,000 settlement with Penn and said research restrictions would be placed on three doctors involved in the case.
The U.S. Department of Justice said that before the September 1999 death of Jesse Gelsinger, 18, of Tucson, Ariz., false statements and claims were made to federal regulators about the gene therapy trial, including the misrepresenting of information that would have halted the experiment.
Gelsinger's death was the first caused by gene therapy and greatly slowed a burgeoning field of medicine that seemed to hold great promise for treating and even curing dozens of diseases. But so far, success has been limited.
The case raised questions of whether scientists had acted too quickly to move gene therapy experiments from animals into people, and whether patient volunteers were fully informed about the risks of unproven therapies.
In the settlement announced yesterday by U.S. Attorney Patrick L. Meehan, the government said that James M. Wilson, the Penn researcher who headed the gene therapy trial, would have restrictions placed on his human research for five years, but that he would not be barred from doing research on people.
The government said Wilson would not be allowed to lead any trials regulated by the Food and Drug Administration for five years, and for three years must have a designated monitor for any human research.
The government also said Wilson must be retrained in how to conduct trials and cannot do more than one human study at a time. Wilson also will be required to have a monitor for animal research that could influence the safety of human research.
Wilson, 49, has not been involved in human research since January 2000, according to the government. He was considered one of the brightest stars in the gene therapy field when Gelsinger died after being infused with a batch of viruses genetically engineered to deliver genes to correct a liver disorder.
In its settlement, the government placed three-year research restrictions, including some monitoring, on Steven E. Raper, a Penn gastrointestinal surgeon, and on Mark L. Batshaw, chief academic officer at Children's National Medical Center in Washington, who also helped conduct the trial.
The medical center agreed to pay the government $514,000 to settle the case. That payment, with Penn's, is double the amount of federal funding that the researchers received for the gene therapy trial, the government said.
Jesse Gelsinger's father, Paul Gelsinger of Tucson, yesterday criticized the settlement, saying there was no "public accountability of what happened here."
Paul Gelsinger wanted the government to demand a public apology from Wilson and order the release of all documents in the case. "These doctors were blinded by the money and blinded by the prestige of what they were doing, and they lost their perspective," he said.
Gelsinger, who settled a suit against Wilson, Penn and others in 2000, also had hoped for an FDA apology. "The FDA was caught flat-footed, and they know it by what happened to Jesse," said Gelsinger, vice president of an advocacy group, Citizens for Responsible Care and Research.
The government said that before Jesse Gelsinger's participation, "the study had produced toxicities in humans that should have resulted in termination, but the study continued."
It said that patient consent forms did not disclose all possible dangers.
Under the settlement, Penn, Children's National Medical Center, and the three researchers did not admit to the government's allegations and contended "that their conduct was at all times lawful and appropriate."
"Reaching this agreement means that I can continue to devote myself fully and without restriction to my laboratory research and that I may conduct clinical research when it would be appropriate for scientific advancement," Wilson said in a written statement yesterday.
As part of the settlement, Wilson will publish a "lessons learned" article, and the Gelsinger family has the right to add comments.
Penn spokeswoman Lori Doyle said the university would allow Wilson to return to human research.
"As this investigation closes, we reaffirm our commitment to the safe conduct of research, strengthening our resolve to continue to set the highest standards possible in this important area," Penn said in a statement.
Children's National Medical Center said in a statement that Batshaw had learned from his role in the gene therapy experiment, and that he and the hospital had conducted themselves properly.
Batshaw, the former physician in chief at Children's Seashore House in Philadelphia, is a leading authority on the liver disorder targeted by the gene therapy experiment, a condition called ornithine transcarbamylase (OTC) deficiency, which causes a dangerous buildup of ammonia in the body. The disease is treated with diet and drugs, but the hope was that gene therapy could provide a long-lasting fix.
Gelsinger, who had a mild form of OTC, died Sept. 17, 1999, from what doctors believe was a massive revolt by his immune system against the disarmed cold viruses used to shuttle the corrective genes into his liver.
After Gelsinger's death, the FDA ordered Penn to halt all the gene therapy experiments at its Institute for Human Gene Therapy, which Wilson directed. An FDA investigation into the Gelsinger case found that researchers recruited patients who may have been too sick to participate; underreported side effects; and kept FDA regulators and university monitors in the dark about critical changes in the study.
The FDA notified Wilson in November 2000 that it was moving to permanently bar him from human research.
Wilson was also criticized for potential conflicts of interest because he was the founder of a biotechnology firm set up to take gene therapy from the laboratory to the marketplace. His company, Genova Inc., provided about a quarter of the budget for Penn's gene therapy institute. When Genova was sold in 2000 to Seattle-based Targeted Genetics Corp., Wilson was to receive one million shares, then worth about $13.5 million.
In the years since Jesse Gelsinger died, the nation's top medical schools have instituted tough conflict-of-interest guidelines requiring researchers to disclose any financial interest they have in patient studies.
Penn, among its other reforms, started an Office of Human Research to help ensure patients' safety.
The National Institutes of Health, which this year will spend about $8.7 billion on research, including gene therapy, has increased the independent-oversight and reporting requirements for all clinical trials and has improved language guidelines for patient consent forms.
Wilson came to Penn in 1993 to lead the university's push into gene therapy. At the time of Gelsinger's death, the gene institute was overseeing eight trials.
Wilson stepped down in 2002 as director of the institute, which is now defunct, and concentrates on teaching and laboratory and animal research.
He is working on developing new viral "vectors," which shuttle corrective genes into the body. He is also working on the development of vaccines against HIV, SARS and Ebola virus.
Penn, which has three gene trials under way, is not as heavily vested in gene therapy as it once was.
"I still believe that the wise scientific view is that this is a field with great potential," said Glen Gaulton, Penn's vice dean for research and research training. "But... it has to be very carefully controlled, so it progresses slowly."
Katherine A. High, president of the American Society of Gene Therapy, said the Gelsinger case caused researchers to slow down out of concern that "there are things maybe we haven't anticipated in the animal data."
High, a gene therapy researcher in hemophilia at Children's Hospital of Philadelphia, has done research with Wilson.
Amy Patterson, director of the office of biotechnology activities at the National Institutes, sees the slowdown as a sign that the gene therapy field has matured. "Gone are the days of a lot of hype," she said. "Now there's a focus on careful monitoring and careful science."
Contact staff writer Susan FitzGerald at 215-854-2780 or sfitzgerald@phillynews.com. Online: Read a release about the terms of the settlement at http://go.philly.com/genetherapy
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