International Catholic University
The focus of this lecture is genetics. It will proceed with a bit of history about eugenics -- as a reminder of a past history tainted by eugenics programs which were egregious violations of human dignity. And it will then describe modern efforts at eugenics under the topics of genetic therapy, genetic enhancement, genetic testing and screening. The desire to improve the quality of the human race and/or the quality of individual offspring is a perennial theme in human history. Plato's Republic, one of the earliest utopian works in western philosophy, proposed selective breeding by arranging for the mating of the best men and the best women at the prime of their lives and in the most propitious seasons of the year for the good of the Politeia. There was to be no marriage and no family for these superior citizens, just coupling for the purpose of producing the best offspring for the city-state. Recall that in the Republic the activities of the individual are to be directed toward the flourishing of a well-ordered polis as the greater good.
The term "eugenics" was coined by Francis Galton in Heredity Genius his first major work which appeared in 1869. In that work, Galton, concerned about the possibility that the human species was in the process of degenerating and informed by his own research on inheritance, advocated a system of arranged marriages between carefully selected men and carefully selected women for the purpose of breeding to improve the British race. Inferior human beings were to be prevented or discouraged from reproducing.
The term "eugenics" itself, from the Greek, simply means "well born" and it connotes a sense of contributing to or improving the stock of the race or the nation. The term became one of some suspicion when the goal of genetics was embraced by various political regimes and enforced through the state's coercive power as an effective instrument for social engineering. In modern times, the first extended programs in state-sponsored eugenics were developed in the United States in the late nineteenth and early twentieth century. These eugenics programs grew from a constellation of ideas derived from evolutionary theory which embraced social Darwinism, from contemporaneous criminology encouraged by a scientific hypothesis supported by post-mortem studies of brains of criminals and the findings of the famous Jukes Report (1875) on inheritance and criminal behavior, from demographic concerns about dysgenics -- the growth of criminal population and the growth of the feeble-minded population because of their unrestrained breeding patterns -- and from surgical advances, such as vasectomy and salpingectomy, in the practice of medicine. Involuntary sterilization became the instrument of this modern attempt at eugenics. The idea of genetic sterilization, the pursuit of this end as a national goal, and the procurement of means to attain their desired result were pressed by some of the most influential families, by some of the most prestigious societies and foundations, by some powerful lawyers, judges, scientists, and physicians, and by some of the most elite universities in the United States. This central notion and clearest articulation of the goals of this movement are best recorded in the words of Mr. Justice Oliver Wendell Holmes who, writing for the majority in a 1927 United States Supreme Court decision, Buck v. Bell, found involuntary sterilization to be compatible with the guarantees found in the U.S. Constitution. Holmes concluded:
We have seen more than once that the public welfare may call upon the best citizens for their lives. It would be strange if it could not call upon those who already sap the strength of the state for lesser sacrifices, often not felt to be such by those concerned, in order to prevent our being swamped with incompetence. It is better for all the world, if instead of waiting to execute degenerative offspring for crime, or to let them starve for their imbecility, society can prevent those who are manifestly unfit from continuing their kind. The principle that sustains compulsory vaccination is broad enough to cover cutting the Fallopian tubes (Jacobson v. Massachusetts, 197 U.S. 11). Three generations of imbeciles are enough (Buck v. Bell. United States Supreme Court. Report 274, 1927).
These eugenics programs in the United States exercised considerable influence on programs in other nations. A particularly noxious combination of scientism, utopianism, and millinarianism along with German Nordic mythology, supported by the legitimating influence of practices and ideology imported from the United States, and empowered by a dictatorship spawned the eugenics excesses of the Third Reich and contributed significantly to the flourishing of the work of the German Society for Racial Hygiene. Nazi eugenics programs are often described as eugenics run amok. The Nazis began with programs which encouraged healthy families and which restructured tax laws that favored child bearing . . . both benign in themselves. However, these programs were soon followed by what were considered complementary laws, those enacted to prevent the reproduction of defective human beings. Then the notion of defect was broadened from those with physical defects and illnesses refractive of treatment to debility associated with old age to the defect of being non-German. It is estimated that between the years of 1933 and 1945, through the agency of Nazi heredity health courts, three million five hundred thousand people were sterilized -- most for no legitimate medical reason.
Eugenic sterilization, including non-voluntary genetic sterilization, in the United States reached in apogee in the 1930s and continued until 1973. It has been reported that between the years of 1907 and 1963, there were eugenic sterilization programs in thirty states and in those programs combined more than sixty thousand persons were sterilized. It is interesting to note that eugenic sterilization programs in the United States continued even after the Nuremberg Trials. It was not until 1973, that the debate over eugenic non-voluntary sterilization became a public debate in the United States. What forced the public debate was the public disclosure of the sterilization of young poor African American women and even some little girls in a family planning clinic located in Alabama and funded by the Department of Health, Education and Welfare, and the public disclosure of programs of routine sterilization of retarded men institutionalized as wards of the state. In 1978, HEW put into place a set of rigorous guidelines to protect minors and mentally incompetent persons from sterilization and to protect, with an elaborate consent mechanism, those competent persons, who are dependent on public funds, from coercive sterilization.
So while forced sterilization is no longer a respectable means to accomplish a eugenic vision (at least not in developed and developing, free nations), the eugenic vision continues. Advances in science, including the unraveling of the DNA structure of the human gene, the mapping of the human genome, and the development of technologies that allow the alteration of human genes, present amazing opportunities for humanity. As with all new knowledge and technology, there are also possibilities for misuse in the violation of human dignity, of human rights, and of the ordered good of society. Eugenics now has at its disposal the sophisticated tools of genetic engineering -- whose possibilities seem endless once the human genome map is completed in the understanding of the function and interaction of the genes. The anatomy of the human genome will provide both a new basis for biological study such as evolution and comparative anatomy and a new anatomical model for application in medical treatment.
There are four types of genetic engineering. They are, in order of potential medical and scientific implication and ethical seriousness, designated types I, II, III, and IV. Type I is somatic cell gene therapy; type II is germ cell gene therapy; type III is somatic cell gene enhancement and type IV is germ cell gene enhancement. Type I is therapeutic, genetic engineering and is directed to the cure and prevention of disease which has its source in somatic cells such as blood, bone, nerve, cells specific to solid organs. Type I therapy is limited in scope to the specific individual receiving the therapy. Type II is also therapeutic. It is genetic engineering that is directed to the cure and prevention of disease that has its locus in germ cells -- the gametes essential for reproduction. This type of therapy has the potential to affect future human beings -- offspring born of the person whose germ cells were modified. Type III and type IV are not, strictly speaking, therapy. They are attempts to manipulate genes in order to enhance some desired capabilities or some desired traits. Type III is somatic gene enhancement; the effect of the manipulation is limited to the individual. Type IV is germ-line gene enhancement; it has the potential to affect future generations and perhaps, at its farthest reach, to alter the human species.
While much of genetic engineering remains a promise, there has been some success in type I somatic cell gene therapy. In 1990, a four-year-old girl, who suffered from a rare genetic disease -- SCID -- a severe combined immune deficiency, became the first patient to undergo gene therapy. SCID is caused by the absence of an enzyme required for the proper function of the immune system. People suffering from this disease are required to live a restricted life in a sterile environment -- recall David the bubble boy. Physicians from the National Institutes of Health used a vector to insert autologous lymphocyte cells, cells taken from the patient, with the desired gene that produces the enzyme adenosine deaminase to compensate for the defective gene. The corrected lymphocytes were returned to the child by intravenous infusion. The child was being treated with PEG-ADA, a version of the ADA enzyme, but this treatment had not been sufficient to restore immune function to desired levels. The new treatment was successful and it, in combination with PEG-ADA, continued for the child. With her immune system strengthened, she was able to attend school. Four years after the inception of this new protocol, the child weathered chicken pox with no more difficulty than that experienced by any other child with chicken pox.
This success was followed by the development of gene marker and therapy protocols. Within five years of the first treatment of a patient with gene therapy, there were more than a hundred protocols either up and running or in the process of review. The use of recombinant DNA techniques to treat diseases involving missing or impaired genes seems unproblematic. Its use to treat such diseases as SCIDs, cystic fibrosis, types of anemia, some types of cancers seems an appropriate human good and an intervention that allows human beings to exercise a providential role for the created world. It appears to be little different from any other curative measure practiced in the realm of medicine. And it may offer better options for patients who suffer from severe illness. Cystic fibrosis provides a clear example of the potential benefit of somatic cell gene therapy. As the disease progresses, lung transplantation becomes the treatment of last resort. If lungs become available, a very big if, the patient is required to undergo an invasive surgical procedure and is required to ingest immuno-suppressant drugs for a lifetime. A further and not inconsequential aspect of the lung transplantation is the considerable cost. It is hoped that as somatic cell gene therapy develops it will prove to be less invasive; it will be immune to rejection; it will be cost-effective costs; and finally, it will cure or regulate the disease to permit normal or close to normal human function.
While the development of somatic cell gene therapy presents great hope for those suffering from serious disease, there always lies the possibility of unanticipated consequences. A graver physical danger might be the eventual outcome rather than the hoped for good. So careful risk/benefit analysis must be considered. With this possibility in mind, great care must be taken that the approved steps for developing therapeutic medical treatments be carefully adhered to and there be no rush to embrace "miracle" cures. Another possible danger lies in the current reductionism that is a consequence of a narrow focus on a single gene. The risk here is the potential failure to understand how the gene operates in relation to other genes and in the whole person. A final concern is that of the distribution of the therapy. Because it is therapy, not research or enhancement, its end is to serve sick people. Procedures for distribution must aspire to be just and must be public. With these caveats in mind, it seems appropriate to go forward with the additional caution in regard to possible harms which lie in the potential to misallocate the energy of science and the resources that medical science has available for medical relief. The excitement of the new fangled thing -- the WOW technology -- can be the occasion of forgetfulness of the need to supply basic medicine such as vaccination to the children of the world.
Type II therapy, germ line therapy, has not yet been performed because of its complexity -- science does not yet know how to do it successfully -- and because of the serious ethical issues involved. The risk of type II germ-line genetic therapy lies in its potential effects on future generations. The unlocking of the anatomy -- both mapping and function -- of the human genome combined with sophisticated assisted reproductive techniques would allow for new level of genetic screening, genetic diagnosis, and treatment. These effects could be could be good or they could be bad. A possible good effect is cure of the disease or defect in the individual and in subsequent offspring. The possible deleterious effects are all the same as the ones listed for somatic cell therapy. However, an addition possible bad effect may be the destruction of nascent human life if the screening is done after that life begins. The direct destruction of defective genes is not problematic; the direct destruction of defective human beings is problematic.
Type III and type IV are not strictly speaking, medical interventions. They are human desires for enhancements of some characteristic or trait. Now enhancement of itself is not problematic. Think of all the ways human life is enhanced in the contemporary world: better nutrition has made us stronger and, combined with disease control, increased the span of our lives; vitamins even before birth delivered through the mother across the placenta give human beings a healthy start in life, laser surgery to improve vision and to eliminate glasses. On the other hand, we express disdain for those whose athletic performances were enhanced by chemicals; we tend to judge these as unfair. So we do draw lines. And we ought to draw lines, but when we draw lines we must be able to defend the placement of the line, that is, it must be for such important reasons as grave harm or uncertainty for the future or misuse of resources. In a developed and affluent society in which choice and power to effect that choice control the direction of science and technology, some of the concerns are: the reason for the enhancement, the degree of enhancement, and the means of enhancement. In developed and developing nations there is a normal progression of enhancement of human life and human living. This normal progression might even be designated natural. One example is the "Flynn Effect," the progression of IQ over time. The studies by James Flynn, taken from a variety of sources from twenty countries over sixty years and supported by significant and reliable data, show steadily increasing IQs. If there is a natural progression of improvement, might it be possible to use that as a model to guide enhancement -- an incremental progression of enhancement. The important concerns in regard to genetic enhancement in addition to why, what degree, and by what means, are concerns of the distribution of the good of enhancement, the direction of financial resources toward enhancement and away from cure -- think of the millions of dollars spent in developed nations on cosmetic surgery -- and the possible change of perception of normal versus disabled human being with a consequence of increased discrimination against those who are not enhanced and decreasing sensitivity toward those who are perceived as less than perfect.
Type IV germ cell genetic enhancement has all the potential problems as somatic cell enhancement and the additional risk of "made for order" children and the destruction of those who, when examined before birth, do not live up to the specifications.
Every year when I teach the issues of gene therapy and gene enhancement, my students raise the question as to what human emotion might be lost, if there were no persons with disabilities to draw forth sympathy, compassion, and finally love. What kind of society might we have then? An important question to ponder. In response, I always ask them if they had a child with a disability and they had the opportunity to correct that disability, would they? And there the issue is joined.
Developments in genetic testing and screening, coupled with the possible new genetic therapies to cure defects or illness, holds out great promise for human beings. But, as with all human progress, there is the possibility for abuse. First there is a distinction to be made. Genetic testing refers to the determination of the genetic status of a particular individual thought to be at risk, either because of clinical symptoms or family history for inherited disease. Genetic screening is the evaluation of populations or groups of people independent of known risk for inherited disease. Both genetic testing and genetic screening must be done without traversing basic human goods.
Genetic screening is not new. Its first application was the development of a test for phenylketonuria (PKU), an error in the metabolism of phenylalanine, that unless treated by diet restriction, results in mental retardation. PKU testing is essentially testing for the presence of a disease or disability in a situation where there is a relatively simple way of ameliorating the condition. Since then the advances have been rapid. There are at least ten genetic disorders for which newborns are routinely screened. The ethical requirements for such screening are: (1) there is a clear indication of benefit for the child; (2) a system is in place to confirm the diagnosis; and (3) treatment for the disease is available.
Genetic testing wedded to reproduction is now becoming routine for those considering reproduction whose medical history or genetic background indicates an increased risk for fetal genetic disorder. Three types of prenatal testing are now available: carrier testing, testing of the preimplantation embryo, and in utero testing. Carrier testing is the evaluation of the prospective parents before conception to evaluate the likelihood of conceiving a child with a particular disease. Some population groups and communities, who are susceptible for serious inherited diseases, such as Jews of eastern European ancestry who have a higher incidence of Tay-Sachs, encourage testing before marriage to alert men and women who would be parents of the potential risks for their children. Evaluation of the preimplantation embryo is part of the process of in vitro fertilization and is done prior to transfer to the uterus of the woman. In utero testing, such as ultrasonography, amniocentesis, fetoscopy, and chorionic villus sampling, is used to evaluate the condition of the fetus. Genetic evaluation combined with counseling affords couples the opportunity to know and understand the risks for the child they might conceive. It allows the couple to make a prudential judgment as to whether or not the possible harms for the child are greater than the benefit of existence for that child. Evaluation of the preimplantation embryo or the fetus, by any means available, allows for the possibility of treatment prior to birth, if treatment is available, or allows the parents to make plans for appropriate treatment, if their child has a problem for which there is no medical remedy at this time, or allows the medical team that will care for the mother and child to prepare for problems that might attend the birth of the child or allows the parents to rejoice in the knowledge that their child is well as they wait in joyful anticipation and the expectation of a safe birth. Evaluation of the preimplantation embryo and evaluation of the fetus that permits the destruction of the embryo or the fetus is an act of directly killing a vulnerable developing human being. The fact that the killing is done in a hospital by those whose profession commits them to protect human life and done with the consent of the mother . . . or the mother and father . . . does not change the nature of the act.
Genetic testing of children for the possibility of genetic disease represents a particularly difficult decision. The ethical principles that have been operative in the testing of newborns provides some guidance here. The difficulty is compounded when the child is asymptomatic and there is no cure for the disease and/or no amelioration of its course. In general, genetic testing should not be done on children unless there are serious reasons for the testing. Symptoms of illness or a familial history of a treatable disease are cogent reasons for limited testing. Presymptomatic testing of children for diseases such as Huntington's chorea whose clinical manifestations occur later in life and for which there is no cure ought not to be pursued. At this time the risk/benefits ratio is too great. Despite pleas of parents for the information as a way of preparing for their child's future, clinical observations of the social and psychological risks to the child are too grave. The future for any human being is not guaranteed. The child upon achieving adulthood may choose, for serious reasons, to have that information as a way of planning for their own life or for marriage and children.
Genetic testing of adults has a set of potential benefits and burdens that must be weighed carefully. Among the potential benefits are: knowledge of diagnosis or risk, intervention for prevention or treatment, risk for members of family, guidance for reproductive decisions, and facilitation of economic planning decisions. Among the potential harms are psychological and emotional harm, economic harm including exclusion from insurance and employment, stigmatization, and serious physical harm.
In summary genetic testing should be done only when there are compelling reasons for the testing; only when the burdens-to-benefit ratio is favorable; only after careful scrutiny of the vulnerability of the person in the case of serious negative outcomes; and only if there is a caring and compassionate well-informed family or network in place.