A Cure That May Cost Us Ourselves: SOCIETY: One of the Pioneers of Human Genetic Engineering Predicts That within 30 Years, There Will Be a Gene-Based Therapy for Most Diseases. but He Fears the Profound Dangers of His Own Work

Article excerpt

A revolution is sweeping medicine--only the fourth one since Hippocrates argued, some 2,400 years ago, that the workings of the body can be explained by the laws of nature rather than the supernatural. The first revolution occurred soon after British surgeon John Snow discovered, in 1854, that cholera is spread by contaminated water: this led to sanitation systems that protected people from the devastating infections that had habitually plagued mankind. The second revolution, surgery with anesthesia, came at about the same time, allowing doctors to readily fix ailments such as appendicitis and bowel obstruction. The third revolution was the introduction of vaccines and antibiotics: many infectious diseases could finally be prevented or cured. But aside from remedying infectious diseases and some surgical problems, we physicians do not actually "cure" anything. Our medicines just help the body heal itself. Our treatments relieve symptoms but do not correct the underlying problems. Human genetic engineering--the fourth medical revolution--will profoundly change the practice of medicine over the next 30 to 40 years. But more than that, its effects will be felt far beyond medicine. It will influence every aspect of our culture. Used carefully, it will increase health and human happiness. But if used unwisely, the genetic engineering of human beings could endanger everything we value--including who and what we are.

Human genetic engineering, also known as gene therapy, is based on the premise that our genes are the defense and healing system of our body. It is our genes that protect our body from the assaults of nature; it is our genes that repair the damage caused by disease and restore us to health; it is our genes that, when they function abnormally, bring on not only such traditionally understood "genetic" diseases as sickle cell anemia and Huntington's disease, but also contribute to cancer, heart disease, Alzheimer's and mental illness. If we want to cure a disease, therefore, we must do it at the level of the genes.

There are two primary ways that genes can be used to treat disease. The first is gene therapy, in which one or more genes are injected into the patient to replace those that are absent or not working properly. This approach has been used to treat rare enzyme disorders, including one known as ADA deficiency, and clinical trials have employed gene therapy against a broad range of disorders: heart disease, many forms of cancer, arthritis, AIDS, hemophilia, cystic fibrosis and muscular dystrophy. The second way to exploit genes to treat disease is known as small-molecule therapy. In this approach, a small molecule (that is, a drug) is given to the patient to modify the function of one or more genes in the body. Pharmaceutical and biotech companies are investing heavily in both of these approaches.

As the Human Genome Project identifies all of the 70,000 to 130,000 human genes and, in time, teaches us what they do, we will rapidly develop the ability to screen for defects or weaknesses in all of our genes. By "weaknesses" I mean genes that do not function optimally for the environment in which the individual lives, which may be unusually stressful because of diet, toxins, radiation or some other factor and therefore will result in the patient's developing a disease. Once a defective or poorly functioning gene is discovered, we will be able to give the individual a more effective gene to replace the "weak" one. Or if the gene is making a normal product but just too much or too little of it, a small molecule (drug) can be given to regulate production. Thirty years from now, essentially every disease will have gene-based therapy as a treatment option.

Gene therapy is still too inefficient to be helpful in most cases. But progress is rapid, and the first treatments are expected to be available to the public over the next five years. The greatest success so far has been in stimulating new blood-vessel growth in the heart to treat heart failure or in the limbs to correct faulty circulation. …