Dr. Koenig, an anthropologist who studies contemporary biomedicine, is Executive Director and Senior Research Scholar at the Stanford University Center for Biomedical Ethics. Prior to her move to Stanford, she served as the west coast research coordinator for The Hastings Center, a bioethics organization located in New York, and she was also on the faculty of the University of California, San Francisco.
Dr. Koenig has a long-standing interest in the cultural context of biomedical innovation. With Stanford Center for Biomedical Ethics colleagues, she recently established the Stanford Program in Genomics, Ethics, and Society (PGES), an endeavor devoted to multidisciplinary research, as well as policy analysis, of the clinical challenges engendered by molecular genetics research. Koenig serves as Co-Director of PGES. The PGES group has conducted an in-depth analysis of the social, ethical, and legal implications of DNA testing for the recently identified breast cancer genes BRCA1 and BRCA2, and, this year, has looked at genetic testing for predisposition to Alzheimer's disease.
Would you say something about the work you're doing this year in the area of Alzheimer's?
When I came to Stanford five years ago in January, I tried to think of what kind of work we should do at the fairly newly-established Stanford Center for Biomedical Ethics. It immediately became apparent to me that because of the scientific strengths at Stanford in molecular genetics and genetic science that this was an important area for us to begin working in. So, with colleagues I established the Stanford Program in Genomics, Ethics and Society (PGES). This program is meant to use scholars from throughout Stanford and the surrounding community to really look at the impact of advancing knowledge in molecular genetics and genomics.
And we decided to be very concrete -- to try and chose problems that were important, that were just on the verge of being clinically relevant and then to establish working groups with individuals to write reports, to reflect on the issues, and to do a thorough investigation of all the social, ethical and legal implications of particular scientific innovations. So, in the first year of the existence of the PGES, we did work on genetic testing for breast and ovarian cancer susceptibility.
In the second year we wanted to take on an illness that was quite different than breast cancer and which had other characteristics and it seemed to us that Alzheimer's disease genetic testing was ripe for study. There'd been a little work in a few other centers, but for a number of reasons -- the genetics are very complex -- there are a number of genes that are involved that potentially convey some kind of an increased risk, but it is more complicated in general than the breast cancer situation, or in other genetic disease. How clearly having a particular genotype, such as one form of the APOE gene, predicts the later development of Alzheimer's disease is not well established. There is a lot of uncertainty because all that is conveyed by having a particular APOE genotype is an increased risk and we don't yet know about what pushes people over from just having this theoretical risk into actually developing the disease. The predictive value of this information is quite low.
So if someone was told they had, and these aren't the real numbers, a 25% elevated risk over the general population risk of developing Alzheimer's disease, how would they understand that? And what would the meaning of that number be? So one of the reasons we chose Alzheimer's to work on was because it seemed to us to be a good paradigm case for other genetic illnesses in the future where the value of tests will likely not be straightforward. There will be considerable uncertainty about what "the numbers" mean or the predictive certainty of the text may be real but low. For example, will people experience an increase from 10% to 30% as meaningful?
In technical terms, the penetrance of the gene may be low, and this is in contrast to classic genetic illnesses like Huntington's disease where having the genetic defect is essentially the equivalent of having the disease -- there is a very high predictive value or high penetrance if you have the mutation in the Huntington's gene. That's not the case with Alzheimer's, particularly for the more common genes like the APOE genes that are currently being studied.
Now the one exception to that rule, is that there are a small number of situations of familial Alzheimer's disease with relatively early onset, where the genetics is much more comparable to Huntington's, but those families are quite rare and they tend to have multiple individuals in their families with Alzheimer's disease and to know who they are. In those situations, the whole dynamics of whether one would want to avail oneself of a genetic test will be quite different. You have to consider the issues for each kind of testing in a very different way because the implications will be quite different; balancing the benefits and burdens of testing would be quite different.
What do you see as the key ethical issues for the individual to consider in these instances?
For the individual -- in the small number of very very high risk families, I would argue that there may be some justification for testing, although again, it's going to be a very complex individual decision because the problem is that even if you can identify someone as being at risk, there is not anything definitive that one can do to prevent the onset of a condition like Alzheimer's disease. The problem is that, although there are a lot of hypothetically useful agents, for example, taking estrogen, that may help lower the likelihood that the disease will develop, none of those have been proven with any high degree of certainty. And certainly they haven't been studied in families with these high penetrance diseases.
There may be some potential negatives to getting the information in terms of one's ability to get, say long-term care insurance or perhaps other forms of health insurance. Although, since Alzheimer's disease tends to have a late onset as opposed to familial breast cancer, many people may still be covered by Medicare at the point that they get the disease.
Now that of course doesn't cover any of the long-term care that's required, but at least it doesn't leave the individual with the possibility of having to compete in a private market for health insurance. Also, because of the late onset of some forms of Alzheimer's disease, the issues surrounding employability may not be as important as for other forms of genetic illness.
But I think it's still a very emotionally sensitive issue within families. If you can imagine, there is an enormous emotional component to making this decision that involves multiple people in the family and the whole issue of how you'll make that decision, who should be involved, how you'll evaluate the risk, whether you think its useful or not -- is going to be very individual. Each individual--and each family-- will have to think about it very carefully. In the case of the genetic susceptibility that might possibly be conveyed by a particular APOE genotype, there are very few benefits to testing at this point in time. Our group at Stanford is actually recommending that predictive use of APOE testing at this point in time is quite premature. It has so many negatives associated with it that there would be few positives.
On the issue of more global societal impacts, you touched on the issues of employability and insurability as being those two factors of discrimination -- what have you seen in terms of the trends in that area and the protections that are afforded?
Well, in terms of health insurance, the Kennedy-Kassebaum Bill which passed last summer has improved the situation somewhat, but it hasn't solved all the problems, because it didn't deal with the fundamental issue of affordability. So, although it was called the Health Insurance Portability Act and does make it easier for individuals who are employed to move and hold onto health insurance, it still doesn't deal with the huge problem in America of the large number of people who have no health insurance altogether. And it certainly doesn't guarantee that insurance be offered at an affordable price.
At the state level, California has passed legislation to try to minimize the impact of discrimination, but not every state has passed consumer protections. Although it is not my area of expertise, my understanding is that the California laws are quite comprehensive and do prohibit discrimination based on genetic predisposition and also it extends that same protection to information that's just derived from family history.
Taking the longer view, in terms of the Human Genome Project and the rate at which discoveries are being made in this area, can the ethical considerations and discussions keep pace with the speed of what scientific discovery seems to be moving in at this point?
No. This is a very complex time and I think we have plenty of evidence that often the scientific possibilities of what we CAN do move quickly ahead of reasoned reflection about what we OUGHT to do. That's one of the unfortunate byproducts of the scientific quest for knowledge. I don't think that's necessarily a bad thing and it may be inevitable. This is another deeply cultural issue because it's particularly difficult in the U.S. for people to sort of sit on their hands and say, "OK, we now know a little bit about this gene, let's wait until we know more about it before we do anything." So we tend to try to rush ahead. Sometimes that works, sometimes it doesn't.
Sometimes it may just be a short period of time when there's a real lag between what we know about a condition and the ability to treat it and in other situations that can be very long and I think that it's not accurate to assume that just because we made a particular discovery in molecular genetics that that's going to lead quickly and inevitably to a solution. Some of these problems are enormously complex biologically (and in terms of interactions between genetics and the environment). I think we need to be careful not to base our actions simply on naive hope and strong belief in scientific progress. The reality is that it's often quite a long period of time between the discovery of a genetic link, say, with a condition and any real ability to intervene in the course of the disease.
Where are the discussions of genetics and ethics being held outside of the realm of academic discussions? Where are the public forums?
We have made an effort to try to include people who are affected in their day to day life in our projects to the extent possible. Sometimes it's hard for people to make the kind of commitment to participate, but I think that organizations like yours are a wonderful forum for these kinds of discussions to take place -- hopefully your conference will move these issues forward.
I think there has been a lot of activity in the legislature. In California there have been a lot of public hearings -- I've gone to testify myself. And as you probably know there was recently a public television special that included Alzheimer's issues, so I think that all those things will move the public debate. One of the problems is the general level of scientific education and understanding. We sometimes joke that many people learned more about DNA by watching the movie Jurassic Park than they did in school.
My Center does, as I'm sure FCA does, a fair amount of work on education And the reality is that in this area in particular even physicians are not educated. All of the data show that the average practicing physician simply doesn't have the basic knowledge of genetics to answer all these questions when someone goes to a physician's office, because it's so specialized and constantly changing. At Stanford we are working on a CD ROM program in genetics, including ethical issues, that practicing physicians can use. The technology makes it possible for the program to be constantly updated with the most recent information.
While there's good availability of genetic counseling, it's also quite costly and not all health plans cover it. So it's just a real dilemma in terms of people having adequate resources and knowledge to respond to these very complex scientific questions and choices.
Interview Date: November 1997
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