Gene therapy: the splice of life.

• Author: Ward, Darrell E.

IN CONCORD, CALIF., a healthy 11-year-old boy rolls up his sleeve for his after-dinner injection of genetically engineered human growth hormone. His parents hope to "cure" their child of something most people don't think of as a disease--below-average height.

The therapy is unproven, costs $150,000 per year, and will take 10 years to complete. Nevertheless, the boy wants it--at 4'11" tall, he's four inches below average, and he's tired of being called "shrimp" at school--and his parents want it for him. His father, a bank vice president, justified the injections in the New York Times Magazine (June 16, 1991), saying, "You want to give your child that edge no matter what. I think you'd do just about anything."

Compare that boy to a four-year-old girl in Bethesda, Md., who received a transfusion of her own white blood cells in September, 1990. She had been born with a defective gene, leaving her without a critical enzyme and with a severely crippled immune system. To counter the hereditary defect, the child's doctors stitched copies of a normal gene into a group of her white cells in the laboratory. The modified blood cells were cultured until they numbered in the millions before being returned to her body. There, the physicians hoped, the normal gene would produce enough of the missing enzyme to relieve the symptoms of her disease, Adenosine Deaminase (ADA) Deficiency. That young girl had become a medical pioneer, the first human being in history to be treated by gene therapy.

These children are examples of a biological revolution made possible by recombinant DNA technology, which is the ability to locate, cut, alter, add, and even manufacture individual genes--flecks of DNA smaller than most viruses. "Gene manipulation gives us the ability to identify genetic problems and find simple, cheap, available-to-everyone remedies for them," explains Dana Wrensch, a geneticist and associate professor of entomology, Ohio State University. Because of it, "the day will likely come when no one has to be sick from a genetic disease or susceptible to cancer." Researchers also are investigating its use to treat heart disease, diabetes, AIDS, and cancers of the breast, bladder, and colon.

While gene manipulation holds promise, it also presents a wide spectrum of ethical issues and possible social perils. These range from invasion of privacy and misuse of information to further devaluing of the elderly and handicapped and designing babies to suit society's needs.

"This technology could be used very, very beneficially and improve the quality of life--if we spot these ethical problems now," notes Wrensch, who is a member of a bioethics discussion group at Ohio State. "We've been manipulating life for our benefit since prehistoric times by taking plants and making pastes that we apply to injuries. Antibiotics made it possible to get a wound and not die of gas gangrene. But now we've got something different. We're not just taking what nature has given us, massaging it a little, and using it. Now we have the ability to engineer life forms."

That ability to engineer life forms made it possible to isolate the gene for human growth hormone and transplant it into bacteria that churn out the stuff by the batch. Previously, the drug had to be extracted painstakingly from the pituitary glands of cadavers.

Simply put, healthy children now can use human growth hormone to "combat" normal shortness for the same reason that mountain climbers scale Mount Everest--because it's there. Such potions are tempting for parents, who of course want as many advantages and as few disadvantages as possible for their offspring.

Today, eliminating disadvantages begins in the womb or even earlier in the egg or sperm. These problems take the form of genetic birth defects--such as ADA deficiency--that arise due to damage to one or more genes. While most hereditary diseases are rare in terms of their incidence in the population (which also means they receive less attention by researchers), they bring incalculable suffering to the afflicted and untold sorrow and guilt to the unsuspecting parents who transmit them. They cost society billions of dollars annually and are responsible for nearly half of all pediatric hospital admissions, 20% of all infant deaths, half of all miscarriages, and 80% of mental retardation. Most are incurable and many are untreatable.

There are some 5,000 genetic diseases on the books. Many of these can be detected in the laboratory, 100 of them by direct study of DNA. "But that number could go up with the next issue of Science, Nature, or Cell," indicates Judith Westman, a clinical assistant professor of pediatrics at Ohio State University and a clinical geneticist with Children's Hospital, referring to three prominent scientific journals. The work is moving so fast that researchers talk in terms of the "gene of the week." When someone asks her if a test is available for a particular gene, Westman...