A Cure That May Cost Us Ourselves

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. Treatment of a number of genetic diseases, such as hemophilia, appears promising as well. There has also been significant progress in the use of gene therapy to deliver vaccines for protection against AIDS and several types of cancer. Most physicians expect that in the first 10 years of the new millennium we will see an explosion of gene-therapy treatments for many maladies that have been a scourge to human health. Genetic engineering should allow people to lead healthier, happier lives and add decades to our life span.

But there is also a more worrisome side to this story. For one thing, this technology is not risk-free. Although toxicity has been extremely low during 400 or so clinical trials in the past nine years, the recent unexpected and unexplained death of a gene-therapy patient in a University of Pennsylvania clinical trial underscores how little we still understand about human bodies and how our bodies respond to potent treatments.

There is also a broader danger. Unlike small-molecule therapy--which can be considered a "smart drug" strategy--gene therapy alters an individual's genetic blueprint. Once we have the ability to give a patient any gene we want in order to treat a disease, then we will also have the ability to give a human being genes for any purpose besides therapy. The downside of this powerful technology? Eugenics could be practiced on a scale far larger than any "selective breeding" policy could accomplish. Just a few weeks ago, a gene was discovered that seems to make mice more intelligent. Human genes have been identified that appear to influence behavior: an affinity for risk-taking, intelligence and even sexual preference. We've known for years which genes influence body size and muscle mass. The temptation to try to use genes such as these to "improve" ourselves is very strong--maybe even irresistible.

Already the first indications of potential abuse are surfacing. For example, one company is developing a treatment for the hair loss that occurs as a result of chemotherapy for cancer. It has already developed a salve that can transfer a functional gene into the hair follicles in human skin. Now the company is searching for a growth-factor gene that would stimulate hair growth. No one would object to preventing the psychologically traumatic side effect of hair loss caused by cancer therapy. But the real motivation is to sell the product to the millions of healthy men who are naturally going bald. Is this bad? Not necessarily, but it does start us down a slippery slope of using human genetic engineering for cosmetic purposes. Where does one draw the line? If hair growth, then hair color? If hair color, then skin color? If skin color, then other "racial" features? Where would the re-engineering of the human body end?

Society faces a real danger. In the name of minor "improvements" that we see as conveniences, we might start using human genetic engineering to attempt to change ourselves and then our children. Engineering the human germ line would result in permanent changes in the gene pool. We as a society have yet to end discrimination, including its most virulent expression, "ethnic cleansing." What would happen if we add intentional genetic enhancement to the mix? In the 1997 movie "GATTACA," only the genetically enhanced can hold good jobs. "Love children," who were produced by natural means and have a natural set of genes with all their weaknesses, are relegated to the bottom of the social and economic ladder.

Our only protection is to accept clear stopping points. And the only way to achieve those is to make sure that society is informed and can recognize the dangers and prevent misuses before it is too late. If such crucial decisions are left to the marketplace, might we ultimately engineer ourselves to the point where we are no longer human beings? We cannot dictate to the people of 100 years from now what they should do. They will care as little about our opinion as we care about the mandates of our 19th-century forebears. They might want to engineer their genes as routinely as we take vitamins. But what they do is not our responsibility. Our duty is to go into the era of human genetic engineering as respectfully as possible. That means that we should not use human genetic engineering for any other purpose than the treatment of serious disease, no matter how tempting it might be.

Far horizons: Our 2000 baby will live longer than his mother and father--the average boy will live to be 73 years old, and the average girl will reach 82.