During yet another day of new revelations of problems in a fatal University of Pennsylvania gene therapy experiment, researchers apologized for their lapses while parents of sick children pleaded with federal regulators not to slow the pace of research on inherited diseases.
In an unusually emotional meeting of regulators and scientists in a crowded auditorium at the National Institutes of Health in Bethesda, federal investigators revealed additional evidence that Jesse Gelsinger, the Arizona teenager who died from the treatment, should not have undergone the experimental treatment in September.
They also made public for the first time that the Penn researchers changed the rules for inclusion in the study without the required approval of the Food and Drug Administration. And they provided details of deaths of monkeys getting a treatment similar to the one Gelsinger got--deaths that according to FDA regulations should have been reported within 15 days, but which did not get reported until after Gelsinger died, more than a year later.
Those problems stand in addition to previous findings of improprieties, including that Gelsinger was too sick to meet the criteria for participating in the study and that scientists failed to halt the experiment and notify federal officials as required in two instances when volunteers suffered serious toxic reactions before Gelsinger was enrolled.
All three of the principal researchers apologized for the growing list of deficiencies cited by the FDA this week as part of its ongoing investigation into Gelsinger's death.
"We could have done better . . . and we apologize," said Mark Batshaw of the Children's National Medical Center in the District.
"I really regret" the oversights, said Penn gene researcher James Wilson.
"We now recognize we should have contacted FDA," said Penn surgeon Steven Raper.
Their conciliatory comments marked a rhetorical shift from the single brief statement that Wilson made Wednesday, in which the scientist indicated the team had been in compliance with federal regulations.
The Penn researchers also said for the first time that none of the volunteers definitively improved from the treatment. The "corrections" the team had previously reported in three patients were not statistically significant, meaning the small improvements seen on some laboratory tests could have been caused by chance alone.
The new information came out at a public, three-day meeting of an NIH gene therapy oversight committee, which ends today.
The experiment, which has now been halted, called for the infusion of trillions of gene-altered viruses known to be capable of triggering liver failure and death. The treatment was designed to treat a rare liver disorder that Gelsinger inherited.
The 18-year-old Gelsinger died Sept. 17, four days after getting his infusion, from multiple organ failure that the researchers acknowledge was caused by the treatment. His death is the first to be attributed directly to gene therapy, an unproved approach to treating cancer and other diseases.
In the midst of a mostly scientific and regulatory discussion about Gelsinger's death, parents of children who have the liver disorder or whose children have already died of the disease delivered passionate pleas for the research to go forward.
"There are children alive today who might possibly become adults if this treatment works," said Tish Simon of Union, N.J., her voice quavering with emotion. Simon lost her 14-year-old son in 1996 to the liver disease--ornithine transcarbamylase deficiency.
Claudia Mickelson, head of the Recombinant DNA Advisory Committee (RAC), which sponsored the meeting, choked up as she told parents that the committee had no intention of slowing research unnecessarily. But there is no point in conducting studies that are poorly designed or carried out, she said, since they could jeopardize the health of volunteers without generating any useful information.
The FDA reported that Gelsinger was the second volunteer to get the highest dose even though the protocol required that the first two participants at each new dose be women since they are less severely affected. In addition, researchers changed the protocol to allow the inclusion of volunteers with greater liver dysfunction than approved by the agency.