Green Light

By Philip Elmer-DeWitt

The goal is grand -- and maddeningly difficult to achieve. Ever since Watson and Crick first deciphered the structure of DNA in 1953, doctors have had visions of treating disease not from the outside, with drugs or scalpels, but from the inside, by altering the primal instructions tucked in the nucleus of living cells.

Now, after years of debate about the ethics of genetic engineering and lengthy tests in animals, the first human trials are about to begin. Last week two experimental techniques passed a major regulatory hurdle, winning approval from the National Institutes of Health's Recombinant DNA Advisory Committee. The official go-ahead from the director of the NIH, as well as a nod from the Food and Drug Administration, is expected to follow within a few months for at least one of the experiments, clearing the way for human gene treatments as early as this fall. "This is the first step toward what will probably be a medical revolution," said Dr. W. French Anderson, one of the scientists whose proposal was approved. "Millions of patients are going to be helped by this in the future."

The two experiments rely on a technology that has evolved over the past 12 years. Each uses a virus to act as a kind of biological taxi to transport a desired gene into the nucleus of human blood cells. In one experiment, a team led by Dr. Steven Rosenberg proposes to treat malignant melanoma, a form of skin cancer, with blood cells that have been genetically altered to transform them into tiny factories for a tumor-killing protein.

The experiment proposed by Dr. Anderson is more controversial. He would use gene therapy to treat children who lack a key immune-system enzyme called adenosine deaminase (ADA), leaving them vulnerable to every passing germ. Some researchers question the wisdom of performing a novel -- and potentially dangerous -- therapy on children, especially since there is already an effective drug treatment. "There are a lot of other diseases without therapies," says Duke University's Dr. Michael Hershfield, an expert on ADA deficiency. "And they're in adults who can make decisions for themselves."

Thousands of inherited diseases may be linked to the malfunctioning of specific genes. In addition, researchers are discovering that nearly every disorder has a genetic component. Last week the National Cancer Institute published two studies suggesting that susceptibility to lung cancer may be associated with a single gene.

But there is no guarantee that gene therapy will be effective against any of these illnesses. Some genes are too big to fit inside the viral taxi. And things could go wrong. The new genes might not "turn on" inside the body, or they might get misplaced in the gene sequence and rather than fight cancers, start triggering them instead. Ultimately, the only way to see what happens is with carefully designed experiments. As Dr. Anderson puts it, "Now we can find out if gene therapy is really going to work."

CHART: NOT AVAILABLE

CREDIT: TIME Chart by Steve Hart

CAPTION: THE PLAN OF ATTACK

With reporting by Dick Thompson/Washington