GENE THERAPY: New Report Reveals Side Effects in Trials
New documents released Saturday reveal that several participants in gene therapy trials for liver cancer suffered serious side effects, including changes in liver functioning and blood cell count, nausea, mental confusion and stroke. The New York Times reported that the discovery comes six weeks after the FDA placed a hold order on two liver cancer gene therapy trials being conducted by the Schering-Plough Corp. The report, released by the NIH's Office of Recombinant DNA Research (ORDA), is drawing significant attention, primarily due to the fact that the Schering-Plough studies use methods similar to those employed by a University of Pennsylvania study in which 18-year-old Jesse Gelsinger died in September. Since Gelsinger's death, ORDA -- the NIH department that oversees gene therapy research -- has been collecting data from gene therapy trials that use adenovirus as a means to deliver DNA. Both University of Pennsylvania and Schering-Plough researchers used adenovirus. After Gelsinger died, the FDA prohibited new patients from enrolling in the Schering-Plough trials. Schering-Plough spokesperson Robert Consalvo declined to comment specifically about the side effects; he noted, however, that these are "late-stage patients [in the trials] who are very sick and have other illnesses and problems. Many of these side effects, although serious, are not unexpected in this patient population." Both UPenn researchers -- who continue to investigate the cause of Gelsinger's death -- and Schering-Plough representatives are expected to speak at the December ORDA advisory meeting (Stolberg, 11/20).
So far, University of Pennsylvania researchers have discovered little insight into Gelsinger's death, which is believed to be the first from gene therapy. But the Washington Post reports that a closer look into the UPenn laboratory provides "a rare snapshot of that subtle scientific and ethical landscape known as the cutting edge of medicine." Gelsinger's death was caused by a "rare and irreversible" blood reaction to the DNA; researchers, however, had witnessed the same reaction in laboratory monkeys treated in the same way. Despite the deaths and complications in animal research trials, the UPenn team forged ahead with human experiments. Now many critics are wondering if the UPenn scientists overlooked safety precautions "out of eagerness to win a nine-year-old race to produce the world's first gene-based cure." Also in question are the financial motives behind the UPenn study and other gene therapy trials; corporate investors, too, were anxious to see returns on tens of millions of dollars invested in the UPenn Lab, as well as a private company founded by lead UPenn researcher James Wilson. Wilson denies financial influences in his decision-making process, saying, "To suggest that I acted or was influenced by money is really offensive to me." But such ties between corporate entities and university researchers are a point of contention with gene therapy ethicists, who question the objectivity of scientists who stand to make millions from being the first to successfully use gene therapy. Moreover, Gelsinger's death has refueled criticism that gene researchers are experimenting on "too many people too soon." More than 3,000 have participated in gene therapy studies since 1990, without a successful treatment among them. Experts warn that moving ahead with human trials -- and risking patients' lives -- could ultimately undermine public trust in gene therapy, a field already rich in controversy due to its goal of altering people's genetic makeup. Berlin-based Humboldt University genetic researcher Guenter Cichon said, "People will say [the researchers] cannot cure patients and now they're killing them" (Nelson/Weiss, 11/21).