March 10, 2000 (Bethesda, Md.) -- At the end of a grueling three-day meeting here, and without taking a formal vote, an advisory committee on gene therapy turned down a proposal Friday that would have halted gene treatments except for patients in life-or-death situations.
The move is not a direct affirmation of the controversial type of research. But allowing it to continue sends the message that there still is value in this type of study -- even when no one is sure of its benefits or what it might cost to achieve them.
"What we don't want is another Jesse Gelsinger," activist Jeremy Rifkin told the committee. Rifkin's group, the Foundation on Economic Trends, has been a long-time critic of gene research. Gelsinger, the 18-year-old who died after suffering a severe reaction to an experimental gene therapy last September, captured headlines and shocked researchers who had touted the gene therapy's relative safety for the last decade. It was the first death attributed to genetic treatment. The FDA halted the trial in January.
Rifkin's original letter to the Recombinant DNA Advisory Committee (RAC) last November asked that the RAC "impose an immediate moratorium on the consideration of any future human ... gene therapy ... except where the protocol can legitimately be considered a treatment of last resort for a life-threatening illness."
Committee members, however, argued against stopping gene research on people, fearing such action also would stop some useful, but low-risk, research. "I think [a moratorium] comes perilously close to saying that terminally ill subjects are expendable," panelist Nancy King, JD, of the University of North Carolina, told the committee.
In a surprise move, Jesse Gelsinger's father, Paul, appeared before the RAC earlier in the day and made a plea for a national center to protect patients' rights. He told the RAC he thought his son was doing everything right. However, the senior Gelsinger later came to believe that the researchers at the University of Pennsylvania who performed the treatment to correct an inherited liver disorder glossed over the experiment's risks. Those risks proved to be fatal.
"I had no idea there were 38 trillion viral particles being put into my son. All I knew is it was the maximum dose allowed by the FDA," said Gelsinger. He also complained he should have seen a detailed description of the experimental protocol, and that he should have known more about the lead researcher's financial interest in the treatment.
"It is a national issue, and I think it's something that should be done by the National Institutes of Health. It is that important," said Gelsinger. A source, who did not want to be identified, indicated Gelsinger is likely to take some kind of legal action against the University of Pennsylvania.
Rising to support Gelsinger, Rifkin called it "shameful" that the committee had waited until a patient death before finally coming to grips with key safety issues. "You're just getting around to asking questions you should have asked 10 years ago. You're just beginning to look at what ... appropriate protocols should be put in place to make sure there are no problems," said Rifkin.
On Wednesday, the RAC discussed the shutdown of another gene therapy experiment, this one involving Allovectin-7 -- a treatment for melanoma. Researchers at the University of South Florida suspended the study after a patient's death in 1999 was reclassified as "probably" caused by the treatment.
While the main focus for the meeting was safety, the committee also was pushed to endorse new treatments for desperately ill patients. On Thursday, Roger Karlin, MD, and his wife, Helene, who holds a doctorate in psychology, watched anxiously as the RAC debated a new type of gene therapy for Canavan's disease -- a devastating brain disorder affecting children. Their 5-year-old daughter Lyndsay has the disease and previously had been given a gene treatment called apaspartoacylase (ASPA).
However, researchers from Thomas Jefferson University in Philadelphia now believe that a new type of delivery system called an adeno-associated virus would produce better results, and they were asking the RAC for an endorsement of the approach.
Withholding the treatment would amount to giving her daughter a "death sentence," Helene Karlin told the committee. Roger Karlin, an internist practicing in New Fairfield, Conn., worked with the gene researchers as they developed their approach, and the couple even established a foundation to help the estimated one in 10,000 who contracts this deadly illness.
Still, after considerable discussion, RAC panelists insisted that the scientists provide more data about how this new treatment delivery system would work in animals and whether the replacement gene would really function correctly. The situation proved particularly frustrating for the Karlins, because they feel they know the risks and the benefits as well as anyone.
Ironically, the Karlins believe Jesse Gelsinger's death may have created an environment that is endangering their daughter. "Unfortunately, the bureaucratic element often interferes in these protocols, and what happens is that the ethical rights of these children ... [are] violated," says Helene Karlin.
Though the Karlins say they hope that their daughter will get started in a new gene trial in a couple of months, the process has made them angry. "Death doesn't wait for meetings, and that's what we object to," says Helene Karlin.
In spite of the pressure to come up with new procedures to publicize adverse events from gene trials, the committee couldn't reach a consensus on how much information researchers should report and when, even though it was a top priority of the meeting.
"We'll pound it until we come to agreement, and the things to agree on initially are, 'What will we do with the data and what purpose will it serve?'" RAC chairwoman Claudia Mickelson, PhD, tells WebMD.
But for Paul Gelsinger, the wait for answers about what happened to his son has already been agonizing. "I think it's remarkable that they don't have real answers yet," he tells WebMD. "That to me is totally amazing."