Like every medical revolution before it, the field of gene therapy began with the vision of a brighter future. Researchers promised to cure such hereditary disorders as cystic fibrosis, muscular dystrophy and sickle-cell anemia, not with conventional medicine but with the magic of genetic engineering, supplanting defective genes with their normal counterparts. Patients dreamed of a life free of the diseases they had inherited. Venture capitalists dreamed of untold riches and backed the leading researchers in the field with millions of dollars of seed money.
But turning visions into reality has always been the trickiest step in conducting a successful revolution. Five years after the first approved experiments on humans in the U.S., there are now 600 Americans enrolled in 100 clinical trials. Yet after all the tests and all the hype, there is still no unambiguous proof that gene therapy has cured--or even helped--a single patient.
No one denies that gene therapy holds extraordinary promise or that it will eventually yield results. But critics have grown increasingly concerned that the initial excitement led to a premature rush to get unproved gene therapies out of the laboratory and into human patients. Researchers are still not sure which are the best methods to transport genes into affected cells. Nor have they figured out how to stop people's own immune systems from rejecting what are, in effect, microscopic transplants of foreign material.
Even more troubling are signs that financial considerations may have replaced scientific rigor in determining how and when to use gene therapy. Nearly every investigator currently running a clinical trial has a relationship of one sort or another with a biotechnology firm. Some critics charge that businessmen are pushing researchers too hard in order to get a quick return on their investment, and that some doctors have been too hasty, launching clinical trials early in hopes of "cashing out" when a large drug company buys their firm.
Now comes word of major technical snags in two areas of gene therapy that had been regarded as among the farthest along. Reporting in separate articles in the New England Journal of Medicine last week, researchers concluded that the most commonly used genetic treatments for cystic fibrosis and muscular dystrophy had run into a dead end. In both cases, scientists inserting normal genes into patients with defective ones were not able to elicit corrective changes in their patients' bodies.
Quick to put the best face on the discouraging results, investigators pointed out that they have other research paths to pursue. "You don't usually hit a home run the first time," says Dr. Michael Knowles, the University of North Carolina researcher who led the cystic fibrosis trial. "You usually make incremental steps forward, and that's what this study did."