Investigated by Jesse Gelsinger Gene Therapy Death / Penn Medicine
Investigated Food and Drug Administration
Start Date 1999-00-00
Notes This is an archived page. Report a problem Hide header banner toolbar December 9, 1999 F.D.A. Officials Fault Penn Team in Gene Therapy Death Related Articles A Death Puts Gene Therapy Under Increasing Scrutiny (Nov. 4, 1999) Patient's Death Stops Gene Therapy Studies (Oct. 12, 1999) Patient Dies While Undergoing Gene Therapy (Sep. 29, 1999) Forum Join a Discussion on Health in the News By SHERYL GAY STOLBERG BETHESDA, Md. -- Officials of the Food and Drug Administration said Wednesday that Jesse Gelsinger, the 18-year-old Arizona man who lost his life in a gene therapy experiment in September, was ineligible for the clinical trial and should not have been treated because his liver was not functioning well enough before doctors infused him with a dose of corrective genes. 'Deviations' in a highly regarded research program. In announcing the preliminary results of their inquiry into Gelsinger's death, the officials also said the University of Pennsylvania scientists running the study had violated F.D.A. requirements by failing to report immediately information about two patients who, long before the death, had experienced serious side effects. And they said the informed-consent form that the investigators gave patients deviated from one the agency had approved, in that it omitted information about the death of monkeys that had received treatment similar to that given Gelsinger, although much more powerful. "We don't know what the impact of these deviations are" on Gelsinger's death, said Dr. Kathryn Zoon, director of the agency's Center for Biologics Evaluation and Research, which monitors gene therapy studies. But "they're important," she said, adding that when the agency concludes its inquiry, it will take "appropriate action." She declined to say what that action might be. In response, Dr. James Wilson, the lead scientist for the Penn study, vigoriously defended his conduct. In interviews, Dr. Wilson, who directs one of the most respected academic gene therapy programs in the country, has said repeatedly that there was no evidence from either animal or human testing that could have foretold Gelsinger's death. In a brief statement he read to reporters today, Dr. Wilson maintained that at the time Gelsinger was enrolled in the study -- three months before he was treated -- blood tests showed that his liver was functioning within the study's parameters. "We remain fully comfortable with the clinical decision" to treat him, Dr. Wilson said. While he acknowledged that he had not telephoned the F.D.A. immediately with information about the other patients' side effects -- highly elevated enzyme levels -- Dr. Wilson said the agency had been given "comprehensive data" in writing about those effects eight months before Gelsinger died. He did not address the issue of the informed-consent form, and he did not take questions. The dispute over Gelsinger's treatment, aired in dueling news conferences, lent a bizarre, circuslike air to the first day of a three-day session of the Recombinant DNA Advisory Committee, the National Institutes of Health panel that oversees gene therapy research. The meeting room here was packed with scientists, reporters and others, including Paul Gelsinger, Jesse's father, who sat in the back and quietly took notes on a yellow legal pad. In an interview, Gelsinger said he remained supportive of the scientists at Penn. "These guys didn't do anything wrong," he said. The panel is not scheduled to hear formal presentations from Dr. Wilson and the F.D.A. until Thursday. Inside the meeting room, today's session stuck strictly to the agenda, as a parade of gene therapy researchers reported about the safety and toxicity of adenovirus, the weakened cold virus that was used as a "vector" to deliver healthy DNA to Gelsinger and the 17 other patients treated in the Penn study. Outside the meeting, Dr. Wilson, trailed by press aides and a lawyer, scrambled to respond to the F.D.A.'s accusations, first reported today by The Washington Post. The debate is likely to intensify concern over the conduct of researchers in gene therapy, a nine-year-old field that has enjoyed few treatment successes but, until the Penn study, never experienced the death of a patient. Officials at the advisory committee have complained that beyond Dr. Wilson, some gene therapy researchers have failed to make their safety data public, as guidelines of the National Institutes of Health require. On Friday, the committee will discuss new rules that would force greater openness. One reason the Penn study has generated so much controversy is that Jesse Gelsinger was not sick before he died. He suffered from a relatively mild form of ornithine transcarbamylase, or OTC, deficiency -- a rare hereditary metabolic disorder in which the liver is unable to process ammonia, a toxic breakdown product of protein. When ammonia builds up in the blood, it can travel to the brain, causing coma and death; Gelsinger's ammonia levels were kept in check through diet and drugs, although he had slipped into a coma for a time eight months before he was treated in the study. The study was not designed to benefit people like Gelsinger; it was to test the safety of a treatment for babies with a fatal form of his disorder. Acting on the advice of medical ethicists, the Penn scientists decided it was not proper to test the treatment on babies. So their study called for stable adults, including female carriers of the defective OTC gene and men, like Gelsinger, who had what scientists call a "partial enzyme deficiency," to receive the treatment: an infusion of trillions of particles of weakened adenovirus, each with the OTC gene tucked inside it. The infusion was given through the hepatic artery, which leads directly to the liver. Scientists and doctors who specialize in genetic disorders, including some who reviewed the experiment for the Recombinant DNA Advisory Committee, raised questions about the study's safety from the outset, and those questions are now being raised anew. In an interview today, Dr. Holmes Morton, an expert in metabolic diseases who runs the Clinic for Special Children in Strasburg, Pa., said there had been enough evidence about the side effects of adenovirus to raise serious doubts about the wisdom of giving it to someone with OTC deficiency. Gene therapy experts have known for some time that adenovirus provokes an immune system response that frequently includes high fevers. Gelsinger's temperature rose to 104.5 degrees the night he received his gene infusion. After the fever, he experienced jaundice, then a blood clotting disorder. His ammonia levels began to rise uncontrollably; he then suffered kidney failure, lung failure and brain death. Dr. Morton said high fevers were particularly dangerous for someone with Gelsinger's disorder, and might have caused the subsequent reactions. "Any time a patient with that disorder is stressed by illness, and in particular any time they develop a fever, their underlying disease becomes not only unstable but life-threatening," Dr. Morton said. "That, in a sense, is a quite predictable problem." But Dr. W. French Anderson, the scientist who conducted the first gene therapy experiment, and who is regarded as the father of the field, said he was convinced that it had been reasonable to proceed with the experiment. Dr. Anderson added that in a busy laboratory like Dr. Wilson's, "sometimes things fall through the cracks." "What this meeting is doing," he said, "is to tighten everything up." Home | Site Index | Site Search | Forums | Archives | Marketplace Quick News | Page One Plus | International | National/N.Y. | Business | Technology | Science | Sports | Weather | Editorial | Op-Ed | Arts | Automobiles | Books | Diversions | Job Market | Real Estate | Travel Help/Feedback | Classifieds | Services | New York Today Copyright 1999 The New York Times Company
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