The seventh-floor pulmonary ward at the National Institutes of Health in Bethesda, Maryland, looks much like any normal hospital ward. But if you look above the door to Room 7S-255, you'll see some unusual ductwork; beside the door you'll see a pressure gauge. The room has been modified so that the pressure inside is lower than the pressure in the rest of the building. Air can easily flow into the room, but it can leave only through a series of filters that trap even the smallest floating viruses.
In that room, on Sunday, April 18, 1993, pulmonary specialist Ron Crystal and his colleagues at the NIH dripped a virus into the lungs of a person with cystic fibrosis. The virus was carrying a normal version of the gene that's defective in CF patients; the researchers hoped that the virus would infect the lungs' cells and drop off the new gene, and that the new gene would, in turn, cure the cells by correcting their genetic defect. The filters and ducts were in place to ensure that no one else was exposed to these genetically altered bugs. "It was very much like Neil Armstrong and his colleagues coming back from the moon," recalls Crystal.
With that experiment, the researchers took their first, albeit tentative, step toward bringing gene therapy to these desperately ill people. In this early stage of testing, the scientists are more concerned with showing that the therapy is safe than with showing that it can cure. That will have to wait until the next few rounds. But while the experiment is far from over, and its outcome is anything but clear, already it's being considered one of the most important gene therapy experiments to date.
Gene therapy is one of the biggest potential payoffs from the past decade's explosion of research in molecular biology. Until now, however, its hype has far exceeded its accomplishments. In September 1990, researchers from the NIH performed the first gene therapy experiment, on a young girl with a rare but lethal immune system disorder called severe combined immunodeficiency, or SCID. They took blood from the child, then established a culture of her white blood cells, which were genetically unable to manufacture a crucial enzyme; next they inserted a new gene into the white cells; finally they transfused back into the patient her own, modified cells. The process required weeks of labor, not to mention thousands upon thousands of dollars, to treat one patient, one time. Since then, experiments have begun on 18 other diseases. So far, however, not one has resulted in a complete cure.
Crystal and other CF researchers think their strategy may finally allow gene therapy to reach that goal. For one thing, it's much less labor- intensive: the virus does all the work of delivering the genes to the cells, and does it quickly; the other therapies require that at least some cells be removed and cultured so that genes can be placed into them. The new approach is also simple. All the researchers have to do is drip a liquid containing the genetically altered virus into a patient's lungs. If the technique works, the procedure could one day be performed in a doctor's office or even in the patient's home.
