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Other genetics experts argue that the time has come to re-evaluate the approach taken by most gene therapists, and perhaps even to redirect their efforts. Last spring Dr. Harold Varmus, head of the National Institutes of Health, appointed an independent committee of scientists to look into how the NIH spends its gene-therapy research dollars (some $200 million a year) and whether the government is getting its money's worth. "I've been a bit concerned that we weren't fulfilling the promise of gene therapy in any obvious way at this point," Varmus explains. "My intuition tells me that we need to emphasize more basic aspects of gene-therapy research."
Scientists are, after all, working counter to millions of years of evolution. The basic goal of gene therapy is to take bits of DNA that did not originate in patients' bodies, insert them into the patients' tissue and somehow get them to turn on or, in the jargon of the field, "express" themselves. Yet this is precisely the sort of biological action that the body's immune system interprets as a threat and is primed to fight.
Furthermore, it is not just the immune system that scientists must outwit. They also have to get the cells that are targeted for treatment to open their molecular locks and allow the foreign genes inside. As Dr. James Wilson, director of the Institute for Human Gene Therapy at the University of Pennsylvania, points out, "The basic principles necessary to make gene therapy successful are only beginning to be defined."
If real clinical benefits have been slow to materialize, however, that has not stopped large pharmaceutical firms from buying up the gene-therapy concerns that seem to show the most promise. "Many, many companies have scrambled to get into the race," notes Ed Hurwitz, an analyst for Robertson, Stephens & Co. The list of recent mergers, as Hurwitz ticks them off, reads like a Who's Who of biotechnology: "Sandoz buys Genetics Institute. Chiron buys Viagene. Bristol Myers makes a big investment in Somatix. Merck makes a big investment in Vical. Rhone-Poulenc invests in Applied Immune Sciences and several other gene-therapy companies."
Some of this is unavoidable. Even the NIH's Varmus acknowledges the legitimate role commercial investment plays in moving gene therapy forward. The danger is that overreliance on commercial investors could change the kind of science that gets done. "The involvement of privately funded companies is already moving the focus away from rare genetic disorders," says Doris Zallen, a member of the NIH advisory panel that reviews gene-therapy trials for safety. Private investors tend to be more interested in diseases that affect large numbers of potential customers.