The Human Genome Project

Colon cancer, perhaps, is the one that has made the most exciting impact. Here is a situation where one million people in the U.S. carry an altered copy of a gene on chromosome 2, or some of them on chromosome 3. Those genes have been identified, so at least technically it is now possible to identify those one million people, each of whom has about an 80% chance of getting colon cancer, and many of them will get that rather early, in their 40s or 50s. That's a disease we know how to cure. Those people, if offered regular colonoscopies and the ability then to identify these tumors while they're still small and benign and easily removable, ought to be spared otherwise death from metastatic colon cancer. So this is a very powerful kind of preventive medicine which comes about as a result of gene discovery.

Figure 3 Researchers use mapping and seqencing techniques to locate specific genes responsible for thousands of genetic diseases.

Let's talk about diseases such as alcoholism and manic-depressive disease. These are diseases that we don't normally think of as having a genetic origin. What impact will the Human Genome Project have on diagnosing and treating these types of diseases?
Genes that are involved in behavior and disorders of behavior, like alcoholism and manic-depressive illness, are special cases. We know from studying families and from looking at twin studies that there are genetic influences upon things of that sort, including disorders which many people would consider purely environmental, like alcoholism. There are apparently genes which predispose some individuals to that and others not.

Figure 4 Results of the Human Genome Project advance our understanding of medicine such as human gene therapy.

Now it's very important to point out that these are not predetermination genes. They are not the sort of things where you can say, "Ah-ha! That person is doomed to become an alcoholic." They are predispositions, and there's much interaction between other things that go in that person's life and their own choices that determines whether or not they actually exhibit that particular behavior. But the predispositioning genes probably do exist and ought to be mappable by the same strategies that are being applied to other disorders where the genetic influence is even stronger. To what extent will we succeed in doing that over the next few years? I suspect we probably will succeed, especially for conditions where there is a stronger genetic influence, like manic-depressive illness.

How is the Human Genome Project impacting the new molecular medicine known as gene therapy?
Gene therapy is a new field - a very exciting one - where instead of trying to treat a disease by using drugs, which modify what's going on inside a cell and hopefully point it in the direction of getting better, in this case the drug is actually a gene. You take a gene - in the simplest situation it's a gene which that cell lacks because of a genetic disease - and you add the normal copy of the gene to the cell in order to fix that problem... The Genome Project you can think of as providing the raw materials. You want to do gene therapy, you've got to have genes. And the genes are being discovered right and left in large numbers through the efforts of the Genome Project.

What do you feel are the major social, ethical, and legal issues being introduced by the Human Genome Project, and how do you think society and government should address these issues?
The most pressing issues as I see them are four. We need to do something about health insurance. In this country, health insurance is often predicated on not having a preexisting condition. Somebody, therefore, who is at risk for a genetic disease can be thought of as having a preexisting condition and have their insurance taken away. That violates my sense of fairness, and I think it does most people's, and something has to be done about that.

There are other issues as far as fairness. A second one is employment discrimination. While it is not yet happening, at least not on a large scale, it could come to pass that if somebody could be tested for, say, Alzheimer's disease and found to be at a higher than normal risk, they might not get promoted to that big, important position because a company would decide that wasn't a good investment. I don't think that is fair. I think that violates the standards of fairness that we would all subscribe to, and something needs to be done legislatively to prevent that.

Thirdly, privacy. Genetic tests are very personal. It seems to me and to most people that that ought to be something where the individual has the ability to control the dissemination of that information and not have it spread into all possible corners. That means having a medical record that doesn't leak like a sieve. At the moment, we don't have such a medical record, and real efforts need to be made, and are being made, to see how we can accomplish that.

The fourth issue is the matter of how do we decide when it is time for a new genetic test to be introduced into general medical practice. We are, in large numbers now, beginning to glimpse ways of predicting who's at risk for what. But when is it ready for the GP (general practitioner) in the office to start offering this, and who decides, and how do we make sure there is quality control in the ways that laboratories operate to be sure that if you get this result you can trust it to be right? Those issues really have to be dealt with swiftly.

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