From Down Syndrome to the "Human" in "Human Genetics" (2001)

 

I am deeply honored to receive the Allan Award from the American Society of Human Genetics and to join the ranks of the 38 illustrious awardees who have preceded me. The last time Arno Motulsky and I were both together on this podium, I was introducing him on his receipt of the Society’s Education Award. That was a great pleasure for me and quite appropriate, because he was the teacher and I was the student. Now, things are the other way around, and it is an even greater pleasure for the student to be introduced by his teacher.

I have been present at nearly all of the Allan Award addresses, the first one being given by Oliver Smithies as an after-dinner talk at the Society banquet in 1964. Oliver’s presentation was memorable for me because he gave us a little flute concert after concluding his talk. For a fleeting second I thought that I might emulate him and play my ’cello for you-but you will be happy to hear that I thought better of it.

There have been many other memorable talks over the years, and one that is still particularly vivid in my mind was given by Jerome Lejeune in 1969, ten years after the discovery of trisomy 21 (Lejeune 1970). The 1969 meeting, which was in San Francisco, was notable for more that Lejeune’s talk, since it had the added attraction of a San Francisco special-a gentle earthquake ! More about all of this later.

(…) I now want to return to the Allan Award lecture given by Jerome Lejeune in 1969 (Lejeune 1970). Since I was the local organizer for that meeting, I was charged with taking Lejeune to dinner. What should have been an enjoyable experience for me turned out to be less than pleasurable. I had just started the prenatal-diagnosis program at UCSF and thought that it would be a boon to genetic counseling. Lejeune, believing that human life begins at conception and strenuously opposed to abortion, thought otherwise, and he forcefully articulated his position both at dinner and the next day in his Allan Award address that turned out to be the second earthquake of the meeting. With obvious reference to those who were promoting prenatal diagnosis, he described what he called “The National Institute of Death … a new facility for research and applied eugenics” (Lejeune 1970). As stipulated in Article II.E, the function of this institute was to “destroy, delete, or decry any human condition” deemed undesirable and any embryos “not fitting standard requirements.” He concluded his talk by asking, “Should we capitulate in the face of our own ignorance and propose to eliminate those we cannot help?” It was strong rhetoric - especially since he invoked the dreaded notion of eugenics - but I was not persuaded and went on about my business.

Now, more than 30 years later, I still do not believe that we are engaged in eugenics in the sense that Lejeune implied, although it is certainly true that we seek to help people have children who are indeed well born - which is the literal meaning of “eugenic.” However, by virtue of my research on Down syndrome, I have been very much involved with volunteer organizations - the National Down Syndrome Society, in particular - that have an interest in promoting the welfare of persons with Down syndrome, and this involvement has given me personal contact with literally hundreds of people with Down syndrome, of all ages, and with their families. Furthermore, I have also dealt, in the clinic, with patients and families confronting an enormous variety of disabilities and have interacted with organizations representing their interests. Even though I do not regard abortion as the most desirable way to prevent genetic diseases, none of these encounters has dissuaded me from the belief that prospective parents should have the right to exercise the options that prenatal diagnosis makes possible.

However, I must say that, with time, I have become more sensitive to many of the concerns of Lejeune and others about the applications of modern genetics and believe that we need to be more attuned to the messages that are implicit in our various programs for the prevention of genetic disorders. The disability-rights movement asserts that the willingness to terminate a pregnancy because of fetal abnormality constitutes a rejection of those who have such an abnormality and, in the extreme, a denial of their very right to exist (Parens and Asch 1999).I do not go along with this position, but I do think that we need to listen to what is being said about how people with disabilities, genetic and otherwise, feel they are being regarded. The fact that we have state-supported maternal serum-screening and prenatal-diagnosis programs that are justified on the basis of cost : benefit calculations - dollars per trisomic fetus detected or prevented (i.e., aborted) - says a great deal about how we, as geneticists and a society, view Down syndrome and the other conditions for which we screen (Cunningham and Tomkinison 1999). As much as we talk about neutrality and nondirectiveness in genetic counseling, the message that these programs convey is that it is really not all right to give birth to a child with serious abnormalities.

Why have I have juxtaposed these troublesome thoughts about prenatal diagnosis and disability rights to a description of my research into the mechanisms by which extra chromosomes cause their deleterious effects ? My reason is quite simple: It is to remind us that the operate word in “human genetics” is “human.” Human genetics is about human beings - about humanity and humaneness.

In my Presidential Address in 1996, I described the challenge facing human geneticists as being to find the proper balance between the hopes and fears of society and the goals and interests of our science in discovering new knowledge, improving health, and curing disease (fig. 17) (Epstein 1997). The current debate over cloning and stem cells is a perfect case in point. Now I want to broaden the challenge to add a third element to the balance - the individual, the human being - whose personal interests, whether as an affected patient, a parent of an abnormal fetus, or a clinically normal person, may or may not be consonant with the interests of government, business, the genetic establishment, or society at large. With the major push toward the development and patenting and marketing of genetic tests and products, which many - certainly those who write in the business pages of the newspapers -seem to think the postgenomic era is all about, the individual already stands the risk of becoming merely grist for the mill - the consumer to be targeted. With the ever-increasing power of genomics, transgenesis, and manipulative reproductive technologies, the stakes are becoming even greater. There is no question that the potential for doing good is increasing, but so is the potential to do harm. In the end, and perhaps with greater urgency in these perilous times in which we now find ourselves, it is the human being that must be our ultimate point of reference.

Charles J. Epstein

Department of Pediatrics and Program in Human Genetics,

University of California, San Francisco

 

Publied in Am. J. Hum. Genet. 70:300–313, 2002