March 2000

High Stakes for Gene Therapy

After a decade of disappointment and a teenager's death, this experimental treatment faces a crucial test. Can it cure hemophilia?

By Ken Garber

Kathy High doesn't sleep well these days. A chronic insomniac, the University of Pennsylvania hematologist now gets even less rest than usual. The reason? Stress. High does gene therapy.

These are not easy times for High and other researchers trying to cure patients with DNA. A few hundred yards down the road from High's Children's Hospital of Philadelphia office, over in Penn's main hospital, 18-year-old Jesse Gelsinger died last September after receiving gene therapy for a rare liver disorder. The teenager's death prompted highly public soul-searching by the gene-therapy community and intense scrutiny by the Food and Drug Administration. In January, the FDA put all of the human trials run out of Penn's Institute for Human Gene Therapy, including the one Gelsinger had volunteered for, on indefinite hold.

More quietly, and beginning even before Gelsinger's death, once-enthusiastic private companies have been backing off from gene therapy. Swiss drug firm Novartis pulled the plug on its flagship gene-therapy project, for brain tumors, in 1998. Biotech powerhouse Chiron virtually eliminated new in-house gene-therapy research last year. Of 14 biotech firms sponsoring gene-therapy trials in 1995, half no longer exist as independent companies, and the stock prices of most of the survivors have languished.

Driven by the logic of the bottom line, many companies have decided it's more sensible to invest in proven drug strategies than in a highly experimental treatment that has so far yielded no definitive cures. At a conference last November, the Salk Institute's Inder Verma-a prominent researcher in the field-characterized gene therapy's successes to date as "almost nonexistent." But Verma, High and many of their colleagues have chosen to persevere despite public scrutiny and industry's chilly feet. One motivation: They are working on genetic treatments for hemophilia and they believe that this disease may well be the first to be cured by gene therapy.

For the field of gene therapy, there's a lot riding on the outcome of the hemophilia research. If there is a cure, the bloom-and the corporate investments-might come back. If it's a bust, the entire enterprise moves one step closer to a dead end. Speaking to a small group of fatigued colleagues during the annual American Society for Gene Therapy meeting last June, then-president Jim Wilson, director of Penn's Institute for Human Gene Therapy, captured the mood of the moment. "The stakes are incredibly high," Wilson said. "For once I may say what I really think: I hope to God this works."