Eight years after the heart-bypass operation that saved his life, Floyd Stokes was in deep trouble again. His angina had returned with a vengeance. He was gulping nitroglycerine tablets and was virtually incapacitated, unable to do simple chores on his Seminole, Texas, ranch. Too far gone for another bypass, he had a choice, as he puts it, of "just waiting for death or trying to do something about it."
Stokes chose to survive. He volunteered to take part in a novel clinical trial about to be conducted on heart patients by Dr. Jeffrey Isner at the St. Elizabeth Medical Center in Boston. To his surprise, he was accepted. Last May he flew to Boston, where a solution containing billions of copies of a gene that triggers blood-vessel growth was injected directly into his heart.
Within three weeks, Stokes was feeling better and now, at 58, he is back at work on a normal, nitroglycerine-free routine. "I ride horses and I run tractors," he says. "You have to be in pretty good shape to do what I do." As it turned out, all 16 heart patients in Isner's trial showed improvement, and six are entirely free of pain.
The St. Elizabeth clinical trial is one of some 300 similar types of procedures being performed today on more than 3,000 patients around the world. These numbers reflect a growing optimism that gene therapy, a medical discipline that emerged with great fanfare in the early 1990s but fell out of favor during its adolescence, is finally coming of age. "Twenty years from now gene therapy will have revolutionized the practice of medicine," predicts Dr. W. French Anderson, director of gene therapy at the University of Southern California medical school, who is perhaps the most outspoken champion of this slowly maturing medical art. "Virtually every disease will have gene therapy as one of its treatments."
Gene therapy, simply defined, is the placement of beneficial genes into the cells of patients. By introducing the gene and consequently the protein it produces, says Inder Verma, a professor at the Salk Institute in La Jolla, Calif., "you either eliminate the defect, ameliorate the defect, slow down the progression of the disease or in some way interfere with the disease."
The initial goals of gene therapists were to cure relatively straightforward genetic disorders, such as Huntington's disease and sickle-cell anemia, that are caused by a single defective gene. The strategy was simple: substitute a normal gene for a faulty one. But scientists quickly realized that adding genes to cells could also impart new functions to those cells. That may lead to the genetic treatment of a host of other disorders, including heart disease and many forms of cancer.
But how do you get a new gene into the nucleus of a cell? The trick, researchers discovered early on, is to take advantage of the infectious power of viruses; burrowing into cells is second nature to them. A virus is nothing more than a tiny strip of DNA or RNA crammed into a protein envelope. Using the tools of molecular biology, scientists render the virus harmless by deleting some or all of its genes, splicing the therapeutic gene into the remaining genetic material and, in a laboratory Petri dish, mixing it with human cells. The altered virus, now called a carrier or vector, can deliver the therapeutic gene into the nucleus with great dispatch.