Tracking Down Killer Genes

By J. MADELEINE NASH ANN ARBOR Francis Collins

Q . You just found the gene for neurofibromatosis, often confused with Elephant Man's disease. A year ago, you were instrumental in finding the gene that triggers cystic fibrosis. How will such discoveries affect the practice of medicine?

A. They will transform medicine in ways we can't even predict. I'm sure that a hundred years from now, people will look back on this era and shake their heads in disbelief in the same way that we look back on arsenic treatments for syphilis in the previous century. But that's in the long run. It's sort of a paradox. Here we have a field of research that I believe will totally change the face of medicine. The timetable is going to be slow enough that to the average person it won't seem like a revolution at all.

Q. But how will it be different?

A. There is going to be a shift away from a therapeutic sort of medicine, where you treat someone who is already ill, to a medicine where you identify the risks a particular individual has for developing certain diseases and then try to prevent that person from ever becoming ill. Ironically, one of the first consequences of a better understanding of genetics will be an emphasis on altering the environmental contribution to disease because that's a lot easier to change. If you know you are at high risk for lung cancer, your motivation to stop smoking will increase.

Q. You are both a scientist and a physician. Does seeing patients affect your research?

A. It adds a sense of urgency. The cystic fibrosis gene has been found now for a year, and in that year 1,000 people have died, including people I knew personally. That is both troubling and motivating. You can't sit back and treat what you do as an intellectual exercise when the mere mention of a disease brings to your mind the faces of people you care about. That's why it's important to have a certain percentage of people working in this field who are comfortable with both basic science and clinical medicine. If we don't, we are going to miss out on opportunities to apply this new information.

Q. Many people find the notion of genetic testing scary. Should they?

A. When you go to your doctor and have your cholesterol measured, what's really being measured is your genes. We as a society seem quite comfortable with screening for cholesterol and then using that information to alter behavior. No one would argue that testing for cholesterol is opening a Pandora's box. So we have already started down this path. Like it or not, we have opened the door and walked through.

Q. Surely you must have some concerns?

A. Here we are, poised on the threshold of widespread genetic screening that should be beneficial to people. Yet we are talking about carrying this out on a population that is largely uninformed about genetics. Those of us involved in genetic counseling are appalled by the scale of the problem.

Q. What kinds of things might go wrong?

A. We have the disturbing example of sickle-cell anemia to prove to us that if we don't include explanations and education and counseling in a screening program, we will end up doing more harm than good. An awful lot of people were found to be sickle-cell carriers, with no significant risk to their own health, but they wound up believing that eventually they would become ill. Insurers canceled policies. It is terrifying to look back on this experience, and a good reason to go slow on screening for cystic fibrosis.

Q. Couldn't genetic screening also be misused by affluent individuals to create superior children, thereby increasing social inequalities?

A. The notion of yuppie couples' picking the child with the highest IQ out of the 10 or 12 possibilities they might be able to generate through, say, in vitro fertilization is not worth spending a lot of time on. Intelligence is very complex. We can't even define it. It is not at all clear to me that a $ real grasp of the genes responsible for intelligence is going to come about, certainly not during the next hundred years. Athletic ability? That's even worse. Are we talking physical strength or height or quickness, and what do those traits mean? We should be focusing on scenarios that are closer to home.

Q. Such as?

A. It is important to make a distinction between a life-threatening disease and a trait. In our society, prenatal diagnosis followed by pregnancy termination has been deemed acceptable when the consequences to the unborn child are devastating disease and early death. But now we come to sex selection. Sex is not a disease. Yet it is possible, using simple diagnostic techniques, to determine the sex of an unborn child well before the time when pregnancy termination is no longer allowable. There are certainly instances in genetics clinics where couples come in with just that idea in mind. Legally there is nothing criminal about what these couples are proposing. But to me, and I suspect to the majority of the American population, this is troubling, even repugnant. It affronts me.

Q. What about diseases that may not strike until late in life, or that vary in severity?

A. This is where it gets muddy, and everyone is going to draw the line differently. Consider the situation with manic-depressive illness, a reasonably common disorder. It is clearly genetically influenced, though not in a simple way. Now, manic-depressive illness can be a terrible cross to bear. The swings into depression are awful, and the highs can be very destructive. Yet a substantial number of highly creative people have suffered from this disease. Suppose we find the gene responsible for manic depression. If every couple has a prenatal test to determine if a fetus is at risk for manic depression, and if every time the answer is yes that fetus is done away with, then we will have done something troubling, something with large consequences. Is this what we want to do?

Q. Where do you draw the line?

A. Because of my own religious background ((Baptist)), I will be on one end of the spectrum arguing against the use of this information too broadly for fetal selection. And that really highlights that we're not talking about a scientific issue. Scientists have the capacity to understand and explain what it is possible to do. But they are not in a unique position to be saying what is proper, moral and ethical to do. We are in an awkward situation right now because those who have the most experience in philosophical and religious spheres are not well informed about the scientific facts. We need to get ourselves together and teach each other something.

Q. Personally you do not approve of abortion. How do you handle this in a clinical setting?

A. It is a sacred and unbreakable rule that genetic counselors avoid imposing their own value systems. If a patient struggling with a terrible decision asks me, what would I do, I don't answer. I must not answer. The consequence of taking that rather hard-line view is that I can tell you of situations where couples have taken information I have helped them get, and then done with that information things that horrify me.

Q. When will gene therapy start providing couples with better options?

A. It's conceivable that we'll have effective treatments for some of these diseases in the next 10 to 15 years, but I couldn't swear to it. The problem is, we're just starting down this path, feeling our way in the dark. We have a small lantern in the form of a gene, but the lantern doesn't penetrate more than a couple of hundred feet. We don't know whether we're going to encounter chasms, rock walls or mountain ranges along the way. We don't even know how long the path is.