Some scientists, bioethicists and patient advocates are calling for stronger federal oversight of human gene therapy, a fledgling field of promising but unproven medicine that seeks to cure diseases by giving people new genes.
The call for closer scrutiny comes in the wake of recent revelations that biotechnology and pharmaceutical companies have been withholding information about patient deaths in gene therapy experiments, and amid concerns that an 18-year-old's death in a recent Pennsylvania gene therapy study might have been avoided with closer oversight.
"The field is being driven by companies that care about the stock market," said Abbey S. Meyers, president of the National Organization for Rare Disorders in New Fairfield, Conn., who is among those in favor of a larger federal oversight role. "But it doesn't work yet, and the companies aren't being honest about the side effects. Families with genetic disease are not being told the truth."
The renewed focus on federal regulation of gene therapy--which may climax in a showdown between federal officials and drug companies at a Dec. 8-10 meeting at the National Institutes of Health--comes three years after NIH Director Harold Varmus made the controversial decision to scale back his agency's role in reviewing proposed gene therapy studies.
That retreat, which allowed researchers to skip certain layers of scientific and ethical review, was the result of pressure from AIDS patients desperate for novel therapies, and biotechnology companies chafing under what they felt was an overly burdensome regulatory system. Both groups wanted to accelerate gene therapy's transition from a laboratory science to a medical art.
In some ways the streamlining worked: The number of new genetic therapies being tested in people increased immediately and has continued to climb steeply ever since. And while academic researchers dominated the field through the early 1990s, about 40 percent of the new studies proposed in the past three years have had industry sponsors that hope to commercialize genetic cures.
At the same time, however, the Office of Recombinant DNA Activities (ORDA), which oversees gene therapy at the NIH, suffered budgetary and staff reductions and then was given a new range of policymaking responsibilities for such difficult and controversial issues as genetic testing and cross-species organ transplants into people. That has left the office--recently renamed the Office of Biotechnology Activities, reflecting its new responsibilities--hard pressed to manage even the reduced levels of gene therapy oversight that it was left with in 1996, experts outside that office said.
For example, the office is supposed to update and manage a publicly accessible database of every gene therapy experiment in the country, including a description of side effects that researchers have encountered. But the database has not been updated since 1995 "because of a lack of money and support," said A. Dusty Miller, a gene researcher at the Fred Hutchinson Cancer Research Center in Seattle and a former member of the Recombinant DNA Advisory Committee (RAC), the panel of scientists, ethicists and others that reviewed all gene therapy protocols for ORDA before the 1996 cutback.
Now some observers are wondering whether the database might have saved the life of teenager Jesse Gelsinger, who died mysteriously in September while participating in a gene therapy experiment at the University of Pennsylvania. Only after Gelsinger's death did the Penn researchers who directed his treatment become aware that other scientists conducting similar experiments had documented serious side effects.
"It's tragic that the death of one generous young man had to be the occasion for us to see clearly the price we have paid in diminishing the RAC's power and prestige," said Erik Parens, of the Hastings Center, a bioethics think tank in Garrison, N.Y. "Perhaps one significant good that will come of this is that we will rethink the proper place and power of RAC."
James Wilson, the lead gene researcher in the Gelsinger study, was among those who wrote letters to the NIH during the summer of 1996 in favor of reducing RAC oversight--especially its power to approve or disapprove gene therapy proposals--saying the reduction was necessary "to allow continued evolution of this field in an unencumbered way."
A spokesman for Wilson said yesterday that Wilson is "still committed to the principles" behind the 1996 changes, particularly the principle that all data relevant to the safety of gene therapy should be openly shared. Wilson and his colleagues have been praised by many in the gene therapy world for their immediate disclosure of Gelsinger's death and the provision of details surrounding that tragedy.
But with the NIH database still incomplete and offline--and with some experts concerned that the informed-consent forms that spell out medical risks to gene therapy volunteers may not be getting properly reviewed since the RAC lost its power to approve them--some in Congress are wondering whether the RAC needs to be beefed up again.
Yesterday Rep. Henry A. Waxman (D-Calif.), who opposed the 1996 cutback, was preparing a letter to Varmus expressing anew his concern about the NIH's diminished standing. A spokesman for Sen. Bill Frist (R-Tenn.) yesterday said the senator was still awaiting a reply to his Nov. 4 letter to Varmus addressing similar concerns. An NIH spokesman said a response was being crafted and would be completed "very soon."
Frist's letter cited recent reports that at least seven deaths among participants in gene therapy trials in the past 20 months were not reported promptly to the RAC (some were reported later, but lacking details required by NIH); three additional deaths were reported, but the scientists or companies submitting the reports tried to keep them from becoming public.
All the deaths were reported to the Food and Drug Administration, which also reviews adverse events but which, unlike the RAC, meets behind closed doors.
Varmus said yesterday that the 1996 cutback did not change the NIH requirement that gene researchers must promptly report all significant adverse events to the RAC. "The rules are there and they're pretty clear," he said.
But some companies have said they will argue against that rule at the upcoming RAC meeting--a meeting at which Wilson will describe the results of Penn's investigation into the cause of Gelsinger's death.
CAPTION: BACKING THE TESTS (This chart was not available)
CAPTION: Jesse Gelsinger, 18, died mysteriously in September in a gene therapy test in Pennsylvania.