Aug. 4, 2000 (Washington) -- Just like any other tourist in Washington, D.C., Paul Gelsinger seemed lost as he tried to navigate his family through the city's formidable subway system last week. But even though he was on vacation, Gelsinger eagerly shifted the focus of conversation from sightseeing in the nation's capitol to the fate of his son Jesse.
Since last September, when 18-year-old Jesse Gelsinger became the first patient to die as a result of a gene therapy experiment, his father has emerged as a symbol of a tragedy that has shaken the scientific community, government regulators, and patients in need of a miracle treatment. "You can't imagine what it's like," Gelsinger tells WebMD of Jesse's death.
The elder Gelsinger says that some sort of legal action against the University of Pennsylvania, which administered the treatment for Jesse's rare liver disorder, is imminent. However, it's not clear that the matter will wind up in court.
"We're certainly not anywhere near settling the case," Alan Milstein, Paul Gelsinger's lawyer, tells WebMD. Milstein says that Paul Gelsinger will ultimately be asking the university for millions of dollars in damages for the "wrongful death" of his son.
In the meantime, the FDA shut down all the University of Pennsylvania's gene therapy programs in January, and in May officials at the university said the institution would no longer conduct gene therapy experiments on people. The lead researcher at the university's Institute for Human Gene Therapy, James Wilson, MD, did not respond to requests for comments.
Aside from one family's grief, the Jesse Gelsinger tragedy has triggered a number of federal investigations as well as a national rethinking of the risks and benefits of gene therapy.
Other programs under scrutiny by the FDA included a tumor vaccine study in which young cancer patients might have been accidentally exposed to deadly viruses. The research was underway at St. Jude's Children's Research Hospital in Memphis and at Baylor College of Medicine in Houston.
But pediatric oncologist Laura Bowman, MD, of St. Jude's, says the problem was only a "false positive" lab test, and there was no vaccine contamination. "Our vaccine program is up and running full stream," Bowman tells WebMD. But she also says coverage of the issue caused a "lot of pain for the families."
The vaccine program at Baylor remains on hold, and patients who participated are being carefully followed, says a spokeswoman.
In March, the FDA shut down a gene therapy study aimed at growing new blood vessels in patients with severe heart disease at Boston's St. Elizabeth's Hospital. The issue still being negotiated is whether the researchers properly reported two patient deaths to the FDA, according to a hospital spokeswoman there.
And in July, the newly created Office for Human Research Protections, established to help the government oversee all human clinical trials, stopped federally funded medical research at the University of Oklahoma College of Medicine in Tulsa over concerns about the safety of a vaccine to treat melanoma. An audit revealed a number of manufacturing flaws in the product, raising questions about whether patients with the deadly skin cancer understood the risks involved in the trial.
Not long after, the dean of the College of Medicine resigned, along with two other high-ranking officials involved with the institution's research program. Termination proceedings are underway against the vaccine's lead investigator, Michael McGee, MD, and his research has been restricted.
"We felt like it was a very serious problem and obviously one that needed to be addressed," Ken Lackey, president of the University of Oklahoma Tulsa programs, tells WebMD. The rapid action may signal a new mentality in the research community.
"All agencies have been jolted. They all are now proactive," Inder Verma, PhD, president of the American Society of Gene Therapy, tells WebMD. "They're all becoming more active in making sure that there are preventive measures before anything reaches that point."
Verma says that the University of Pennsylvania's Wilson was probably running more trials than he could reasonably handle but that the field of gene therapy will be stronger because of Jesse Gelsinger's death. "The expectations have been high. The delivery has been low, and, therefore, the field suffered ... a backlash," says Verma.
And that backlash may be at the detriment of both the field and those who could benefit from its progress. Recent reports indicate that some trials are now having a hard time recruiting patients in the midst of all the negative publicity about gene therapy. While the news media have been enthralled by the story of a much-ballyhooed technology in trouble, the pieces often miss the point, according to medical ethicist Arthur Caplan, PhD, of the University of Pennsylvania.
Caplan tells WebMD that even though some researchers have financial interests in gene treatments, money is not the main issue, as some news coverage suggests. "Ambition, arrogance, laziness, hubris are all much more important, and so is the drive to succeed and win -- be the first," says Caplan.
Some of the reform efforts, which typically involve more regulations and more federal oversight, no matter how well intended, are also off the mark, says Caplan. "Oddly enough, it's the ethics of the scientist that count, [and] you can't be there in the lab -- you can't be there with every patient," says Caplan.
One major issue for scientists is the multiple layers of regulation. Before human trials can begin, the investigators must win approval from local institutional review boards (IRBs), the safety boards that monitor human trials at individual institutions, then get an approval from the FDA, and in many cases, the National Institutes of Health.
And that's just the tip of the iceberg. "There are four reviews that go on for every study before [an IRB] ever sees the trial, and then it's reviewed by 35 [IRBs] around the country at each of our sites before a human subject ever enters a trial," Robert Schooley, MD, head of infectious diseases at the University of Colorado School of Medicine, tells WebMD of his AIDS research.
Schooley says it takes thousands of hours to assemble the paperwork necessary to get a major study off the ground. Just last year, Schooley says the FDA shut down the entire research program at the University of Colorado for about 5 months over some alleged discrepancies in paperwork. Thousands of studies were halted, and investigators could not enroll new subjects until the matter was resolved.
"Patients with HIV infection in Colorado who wanted access to state-of-the-art clinical trials had no access for 6 to 8 months by the time all the studies were rereviewed," says Schooley. "It's bad for patients and bad for progress." A spokeswoman for the FDA declined to comment on the case.
One solution, says Schooley, is the creation of data safety monitoring boards, which are capable of gathering and reviewing data from different sites all over the country. The board would theoretically be able to spot problems that isolated review boards might miss.