3—
Handle With Care:
Race, Class, and Genetics

Arthur L. Caplan

Race, Ethnicity, Class, and Genetics—a Grim and Dismal History

Discussions of the consequences of increased knowledge concerning the composition and structure of the human genome for public policy often leave those involved with research or clinical care in the domain of human genetics surprised and angry. They are often taken aback by the high level of ethical concern expressed about their work. Why is it, they wonder, that knowledge of human heredity so often becomes the center of controversy and protest? Why is it that in some nations, such as Germany,^[1] talk of genetic engineering or gene therapy elicits heated political protests, strict legislative controls, and sometimes outright bans on certain types of research? There can be no disputing the fact that the subject of genetics evinces a great deal of concern and worry. The reason why this is so is to be found in the past.

Human genetics has a problematic history, and sadly, minorities and the poor have not fared well in that history. Genetics, race, and ethnicity have sometimes proven to be an explosive and even fatal mixture. In Germany, for example, racial and ethnic minorities paid with their lives when developments in genetics were used in the service of a science of racial hygiene whose leaders gave enthusiastic and vocal support to Nazism.^[2] Groups such as Jews, Gypsies, and Slavs were targeted for extermination on the grounds that their genes posed a threat to the overall health and reproductive well-being of the German people.

Some dismiss Nazi science as merely mad science or bad science,^[3]

but the involvement with Nazism by many mainstream authorities and leaders in medicine, public health, and science in a technologically and scientifically advanced nation cannot be dismissed as merely "fringe" or "peripheral." The road to Dachau and Auschwitz runs too straight through the eugenic institutes and genetic courts of pre–World War II Germany to be considered nothing more than an inexplicable detour.^[4]

Obviously, there is no inherent connection between the science of genetics and a public policy of murder and euthanasia based upon race hygiene. Nazism or genocidal policies cannot be deduced or inferred from facts about human heredity, and it would be dangerous to suggest otherwise. But genetics, at least in the form that prevailed in Germany during the 1920s and 1930s, served as a powerful source, tool, and buttress for racist ideology—an ideology that took a terrible toll in human lives.

It is worth noting that the majority of biologists, social scientists, and physicians who used their beliefs about human heredity to support the Nazi cause were not forced to do so. Some had arrived at racist conclusions long before the Nazi party came to power.^[5] They lent their support because they believed their scientific beliefs were consistent with Nazism and not because the Nazis demanded that they fit their science to suit an ideological purpose.^[6] Neither biomedical science in general nor genetics in particular were responsible for the rise of the Third Reich or the Holocaust, but some scientists and physicians used their skills and authority to create a "scientific" foundation for the racism that was a pivotal factor in legitimating Nazism and bringing about the Holocaust.^[7]

The case for the tie between mainstream genetics and racist social policy is bolstered by the fact that efforts to link genetics and social policy were not confined to Germany. For example, in the United States for much of the first half of this century, the mentally ill, the retarded, alcoholics, recent immigrants, and those thought to be sexually promiscuous, especially if they were members of minority groups and poor, became the object of government-sponsored sterilization efforts aimed at preventing the spread of "bad" genes to future generations.^[8] Restrictive immigration laws, forced sterilization, and prohibitions on interracial marriage were in part a legacy of mixing genetics, race, and class in the United States and many other countries.

The use of genetic information to guide American social policy continued through the 1960s and 1970s with mixed results. Attempts to conduct mass screening programs to detect carriers for such diseases as sickle cell, thalassemia, and Tay–Sachs led to much confusion, misunderstanding, and stigma.^[9] One state considered enacting a law requiring any child found to be a carrier of the sickle cell gene to be vaccinated before admission to public school even though this would have no possible prophylactic effect! Companies and government agencies such as the Department of Defense enacted discriminatory policies that excluded African-Americans from jobs or promotions based on flawed and confused misunderstandings about the genetic basis of disease.^[10] Efforts to create mass screening programs aimed at particular groups in an atmosphere of uncertainty about the meaning of genetic information as well as prejudice and bias resulted in a great deal of harm.

Inquiry into behaviors such as criminality, intelligence, aggressiveness, homosexuality, altruism, and mathematical skill and their prevalence in various ethnic or racial groups have been and continue to be the source of heated debate within and outside the scientific community in the United States and many other nations. While careful inquiry into these subjects is certainly appropriate, it is also the case that the results of such inquiries must be handled with great caution since racism and prejudice are still with us. For example, many women continue to this day to have abortions upon learning that the fetus they are carrying is 47XYY, a condition that some geneticists maintained more than a decade ago was causally responsible for criminal conduct. While the evidence for the "criminal chromosome" has proven weak, the consequences for procreative decisions have proven to be very resilient. There are many genetics screening programs in India, Canada, and other nations that provide prenatal screening and testing services to couples seeking to abort any fetus that is female, no questions asked.^[11] There is no evidence from the realm of genetics that being female is a disease. Nonetheless, genetic information can have direct and indirect consequences for female fetuses if it is simply dumped into the public arena where bias and prejudice are allowed to mix with information about heredity.

Racism, prejudice, and genetics have made for a socially combustible and often deadly mix. The mixture has proven so toxic that a strong case can be made that applying knowledge from the realm of

human genetics to public policy has led to far more misery, confusion, and suffering in the twentieth century than it has to human betterment. History suggests that there are real reasons for concern about the impact a rapid increase in knowledge about human heredity might have on current and future social policy. This is especially true in light of the fact that those who proudly espouse racism continue to invoke the terminology of genetics to support their views.^[12]

But is it really fair to assess the implications for human groups and populations of the human genome project solely on the basis of history? After all, Nazi racial hygiene, while accepted by many scientists of that era as valid, is understood today to be invalid. And the genetics reflected in Nazi social policy is simply an instance of biomedical information being applied in a political state gone mad. The eugenic dreams of some biologists and physicians concerning prophylactic sterilization that led to government-sponsored programs of coercive surgery in many regions of the United States combined what we now recognize as fallacious science with overt prejudice. Why should we let the errors of the past be our guide to the ethical implications of current work in genetics when we are no longer bound by crude knowledge concerning human heredity, the yoke of totalitarian ideologies or the scurrilous prejudices of our parents and grandparents?

Ironically, the only way to understand the significance of the past with respect to justice and genetics in thinking about the implications of the human genome project for various groups and subpopulations may be to look forward into the future. By trying to imagine how our own (hypothetically) more sophisticated (at least hypothetically), more humane (at least arguably), and tolerant values (at least hypothetically) might combine with new, less error-laden (at least hypothetically) genetic knowledge to produce a range of consequences for various groups thirty or fifty years from now, we might be in a better position to evaluate the lessons taught by historical experiences of the past.

Future Implications of the Genome Project for Minorities and Groups

Imagine that the year is 2030. It is ten years after the completion of the complete genome maps for human beings, fruit flies, slime molds, carp, the roundworm, the Norway rat, the dog, the chim-

panzee, and a large number of viruses and bacteria. Much work has been done to try to analyze the connections between structure and function in these genomes and to examine how the information contained in the genome interacts with the environment to mediate ontogenesis across a whole range of characteristics and behaviors. Not only are a large number of archetypal maps on hand for a large number of animal and plant species but a large number of regional maps, called demic maps , have also been compiled. These provide an overview of key areas of the genome in various races and subpopulations—demes —in animal species and in various racial and ethnic groups in the human population. The maps provide information about the precise degree of variation that exists within subpopulations at certain key loci. The X and Y chromosomes have been analyzed down to the finest detail. What sorts of policies and issues might have evolved by this point in time? What sorts of implications would this knowledge have for equity, fairness, and justice? Consider six possible case scenarios that might be occupying the attention of bioethicists of the twenty-first century.

Case 1. Who Is a Jew?

A certain Avram Kaplan has decided to immigrate from his home in Minnesota to Israel. He can no longer stand the sterile, artificially controlled climate of his home state and wants to go back to a land that has been preserved in a relatively pristine, natural, and peaceful state by international accords. He knows that, as a Jew, he has the right to return to Israel as a citizen. But he faces the problem that his grandmother on his mother's side was not Jewish.

The Orthodox rabbinate in Israel, who sets policy on matters regarding the law of return, insists that every person invoking the law of return to enter Israel as a citizen undergo genetic testing. The Israeli government maintains a large computerized registry of demic maps obtained from the genomes of Jews from various parts of the world. Whenever an immigrant arrives, a tissue sample is taken and the genetic material from the cells is used to cross-check claims of Jewish identity with the deme maps in the registry. By examining the X chromosome, it is possible to identify markers that show whether a man did or did not have a "Jewish" mother or is of Jewish matrilineal descent.

There has been much criticism of the idea within and outside of Israel that there are ideal or "typical" maps for different races or groups, but since these same maps are widely used in molecular anthropology, forensic biopsychology, and biological archeology, it is difficult to argue that the systematics used in those fields are of no utility in the realm of public policy. Many governments and the United Nations have sanctioned the use of genomic archetypes to help resolve land conflicts and ancestral ownership claims among Tibetans and Chinese, Azeris and Armenians, and Serbs and Croats, as well as those in Poland, Russia, and the Ukraine who claim German citizenship on the grounds that they are ethnic Germans. The secular law in many nations including the United States has long recognized archetypical and demic matching as legitimate techniques for establishing individual identity.

Is it fair for genetic testing to be used for the purpose of identifying who is and is not a "real" or "true" member of a racial group? Should those doing tests agree to do them for nonmedical, non-health-related reasons? Should religious authorities in nations where ancestry is seen as relevant to the religious or social standing of a person be discouraged or encouraged to use genetic testing to remove uncertainties?

Case 2. Affirmative Action

Sally Hightower was thrilled to learn that the U.S. government had started a new program to encourage Native American people to enter the field of philosophy. The demand for teachers of philosophy had escalated dramatically with the shift in demographics toward a much older society. Sally was certain she could qualify for the scholarship since she had long been active in her tribe. She was on the tribal council, had participated in numerous interviews with anthropologists and oral historians seeking to record Native American ways of life, and was one of only a handful of people remaining fluent in her tribe's language. She had long had an interest in ethics and was eager to take advantage of the opportunity to go to college.

Federal regulations required sequence matches on at least six key marker areas of one of the Native American subpopulation maps in order to qualify for the program. All applicants were required to

submit a blood sample for use in determining eligibility for affirmative action programs such as this one.

When Sally's DNA was extracted from the refrigerated blood sample she sent to the Bureau of Indian Identity and Affairs, it failed to achieve the requisite number of matches. Unbeknown to her, she had quite a bit of white ancestry. The government was uncertain about what to do with respect to her application since it would be politically difficult to turn down a person as prominent in Native American affairs as Sally on the grounds that she failed to satisfy the biological test requirements federal law mandated to be classified as a Native American. Sally would also be uncertain as to what to make of these test results. Should she resign her position on the tribal council? Was she deceiving her closest friends if she chose not to reveal her white ancestry?

Is it fair to use information about the genetic makeup or composition of a population to establish membership in a racial, ethnic, or tribal group? Should social policy allow people to define themselves on the basis of culture and behavior as belonging to a particular group, or is biological inheritance a key element of membership as well? Should such tests be required for the purposes of determining eligibility for affirmative action or equal opportunity programs? Would such evidence be admitted or even required in discrimination suits?

Case 3. The Real Scoop on Jimmy Carter

By the turn of the century, so many scientists, conspiracy theory buffs, biographers, and media organizations were seeking samples of tissue of former U.S. Presidents for genetic analysis at the Smithsonian Institution that the National Presidential Tissue Sample Registry had been established with strict rules governing access, disclosure of findings, and the collection of new materials. Some samples, such as those of Lincoln and Kennedy, were of enormous interest. Others, such as those of Chester A. Arthur and Franklin Pierce, drew very little attention.

The registry had a number of thorny issues to contend with concerning the control of information about public figures. The discovery of the source of Gerald Ford's lack of balance as resulting from a congenital neurological defect had created such a stir among his

descendants that the museum felt it could no longer honor every request for cells or tissues. The earlier decision by George Bush not to permit a tissue sample to be kept in the registry to protect his and his family's privacy had led the Smithsonian to call for legislation guaranteeing a fifty-year ban following the death of the source of tissues before they would be made available to the general public for analysis.

But now the museum faced a very tough problem. A researcher at Emory medical school who was interested in the genetics of the pancreatic cancer that had ultimately caused Jimmy Carter's death had inadvertently found a marker on a segment of Carter's DNA that suggested he might have had a distant relative who was African-American. Should the general public be told? How should unintentionally acquired information about race or ethnicity be handled in terms of privacy, confidentiality, and disclosure?

Case 4. Immigration and Human Disease Vectors

North American immigration authorities did not like the policy that forbids those of Haitian ancestry to enter the United States and Canada, but they enforced it. Five years earlier, it had been found using genome maps and genetic autopsies that poor Haitians of African descent were especially likely to be carriers of mitochondrial prions, which had long been implicated in the transmission of degenerative diseases such as multiple sclerosis, some forms of arthritis, some cancers, and lupus. At that time, governments all around the world restricted the rights of Haitians to visit or immigrate freely. The policy required a quick-scan genetic screen to be run on all nonwhites living outside North America to establish racial and ethnic identity and ancestry. This took time, was costly, and led to a large number of fights and arguments between immigration authorities and would-be immigrants.

The immigration authorities were not wild about having to handle and risk contact with infected or potentially infected tissue specimens. Also, it was not clear that the level of risk or danger to the public health would justify restrictions on freedom of movement for various groups and subpopulations within American society. Nor was there any consensus about when public health officials, technicians, doctors, police, or other government officials could be forced to

come into contact with individuals suspected of being "biologically dangerous." Since these groups did not have to interact with those deemed biologically dangerous by court order except on a voluntary basis, it was difficult to find a legal basis to compel interaction in the face of prior risk.

Is it possible that certain groups of people could find themselves labeled as dangerous to others by dint of their biological makeup? What would be the legacy of current disputes about the duties of health care providers and others to interact with people infected with HIV when advances in genetics allow very precise determinations as to who is and is not likely to transmit disease?

Case 5. Public Health and Good Mating Practices

The newest virtual reality tapes (VRs) on marriage and childbearing from the Minnesota Department of Health and Procreation were ready for distribution.^[13] They warned young people about the economic consequences for the state and for themselves of reproducing without a genome test. The public service VRs made a very persuasive case that certain groups known to be at high risk of bringing children into the world with disabling and costly disorders and defects, such as diabetes, gout, deafness, migraines, panic disorders, and allergies, should get a complete genetic analysis before mating and procreating. Strong reinforcement stimuli introducing subliminal messages were used to urge young couples to get an embryo biopsy before sending their offspring off for incubation at the fetal nursery.

Many civil libertarians were aghast at the idea that the state could coerce reproductive behavior. While no one disagreed about the importance of using genetic information to encourage responsible parenting, to many people it seemed wrong for the state to try to compel such behavior. Yet, since there had been no effort to create a right to privacy following the dismantling of Roe v. Wade in the mid-2010s, it was almost impossible to find a basis to protect procreative liberty against the interests of the state in protecting the public good. Mandating the provision of information about who was at risk of procreating a child having a problem and the financial consequences of an unfortunate pregnancy outcome seemed the only way to handle ethically the question of individuals and groups at risk of passing on deleterious genes.

When should the state be allowed to encourage or require genetic testing, screening, or counseling? What conditions merit such activities? And what bases will individuals and families have to assert their rights to reproduce in the face of an overwhelming state interest in minimizing the burden of disease and disability on the community?

Case 6. Mass Screening for Bad Blood

The National Health Insurance program announced its intent to create a screening program to detect genetic markers associated with especially high risk for high blood pressure. The burden imposed by illnesses related to high blood pressure, such as diabetes and stroke, was such that the program sought to screen all groups believed to be at higher than average risk for the disorder. Broad screening would permit early intervention using psychological as well as pharmacological methods. But the program had limited funds to carry out screening, counseling, and follow-up interventions. Since it had been established in the 1970s that African-Americans were at especially high risk of high blood pressure,^[14] the program intended to make this group the first population targeted for screening and intervention.

The federal insurance program was built on a two-step strategy. The program would provide information on stress management, relaxation, and free medications that could lower blood pressure with only minimal risks of side effects. Higher premiums would be charged to those identified at high risk who failed to manage their blood pressure responsibly.

Would it be ethical to target a particular racial group, whose membership is defined by culture and history, for genetic screening? Should such programs be undertaken if there are penalties attached for noncompliance? What will greater information about the risks created by one's genetic makeup do to our understanding of the concepts of personal responsibility and voluntary choice?

What Is a "Race" and Who Are Its Members?

A number of issues concerning justice, fairness, and equity for minority groups arise from the previous six cases. Emerging knowledge about human heredity will have enormous implications for the use

of genetic information to classify human beings and for understanding the reality and legitimacy of racial and ethnic classification schemes, the purposes for which testing and screening are done, the selection of traits to screen, and the need to protect privacy and confidentiality. The extent to which beliefs about heredity and human genetics have been used, abused, and misused in the past indicates how important it is that discussion begin now about the normative and prescriptive stand that is appropriate for shaping social policy in the light of rapidly expanding knowledge of the genome in the future.

Perhaps no question is more pressing from the viewpoint of ethnic and racial minorities than understanding the ways in which new genetic knowledge will shape their self-understanding and social standing. Should knowledge generated by the genome project be used to identify, classify, or label racial or ethnic groups or to establish the boundaries of their membership? When screening programs are undertaken for groups, should the traditional cultural and political definitions of race and ethnicity prevail or will—and to what extent can—biological definitions be used? Will the information generated by the genome project be used to draw new, more "precise" boundaries concerning membership in existing groups? Will individuals who have tried to break their ties with ethnic or racial groups be forced to confront their biological ancestry and lineage in ways that clash with their own self-perception and the lives they have built with others?

It might be argued that it is morally acceptable to use genetic information to classify groups of human beings for scientific purposes, but perhaps not for use solely in the service of social, community, or public policy goals. However, since there may be very real benefits associated with the compilation of information about the medical or psychological needs of certain groups, a better principle might be to avoid testing except when it is undertaken with the goal of benefitting the individual being tested or the group of which that person might be a member. Health professionals in particular will need to be cautious about allowing themselves to be cast into the role of using genetic information for purely social purposes if they hope to retain the trust of minority group members.

While it is possible that the genome project will reveal huge amounts of variation and difference among the genotypes of those

persons who are currently lumped together as being in the same ethnic or racial group based upon their phenotypes, it is also likely that some genetic information will be found to be unique or prevalent among the members of certain groups. If this is so, then the temptation to cluster groups in the light of this information may well be unavoidable. Those taking genetic tests may have to be fully informed about the possible threat to self-image and sense of personal identity that this testing may pose. Warnings—genomic informed consent—about the possible impact of genetic testing and screening for individuals in terms of their self-worth, self-esteem, and sense of personal security may have to become commonplace in the not-so-distant future.

Because of the many possible invidious uses of genome profiling, the principles of autonomy and informed voluntary choice will have to be used to regulate the collection and use of genetic information for the purposes of classification. If individuals have a right to their genetic privacy, then new genetic knowledge should not be used to classify those who do not wish to be classified, including children from what we now term "mixed" marriages, potential donors of organs or tissues, or those who for personal reasons do not want their ancestry known to others. Nor should genetic information be used for social policy purposes unless it is shown to be absolutely necessary as a precondition for expanding opportunities or benefits to the members of certain groups and then only if the information is obtained and used with the express permission of the source of the genetic material. The lessons of history count as stern cautions in favor of these broad recommendations. One shudders to think what the use of genetic information based upon the genome might have meant in terms of social policy in Alabama in 1890, Germany in 1939, or South Africa in 1970.

Some attempt must be made to decide what purposes justify genetic screening and the storage of genetic information targeted toward specific racial or ethnic groups. One possible moral stance is that those in biomedical science and health care will not screen groups or populations unless it is for the future benefit of those in the group or other members of the same group. Nontherapeutic testing and screening must be approached with great caution, especially in the light of the historical abuse of genetic information by those responsible for social policies in the past and the potential for

abuse that will be possible in the not-so-distant future. Those involved in public health will need to understand their duty to protect the interests, dignity, and rights of individuals against the desire of the community or the state to obtain information that could be used to enact social or financial policies that might be advantageous to many but with a great cost to a few.

The selection of traits, behaviors, and properties to identify, screen, and classify should be driven by a concern to identify what is incapacitating, disabling, or damaging to the members of groups rather than merely what is characteristic, distinctive, or typical of a group. The classification of human beings into groups, races, subgroups, and ethnic groups must be undertaken with great care. The ethics of human systematics that will emerge is likely to become one of the greatest moral challenges to face those involved with the human genome project.

Race, Class, and Genetics in the Here and Now

The hypothetical case studies raised earlier present obvious challenges to the ways in which new knowledge about heredity will impact public policy, our notions about race, and the ethics of health care. But one need not await new knowledge about genetics to see how information about biological differences influences and shapes the distribution and allocation of resources to the members of racial and minority groups. The allocation of organ and tissue transplants is currently extremely sensitive to the nature of group-based biological differences in ways that raise important questions about the ethics of using emerging genetic information concerning human populations.

Study after study has appeared in recent years showing that access to cadaver kidneys for transplants for those with renal failure does not reflect the actual need for kidney transplants in the general population in the United States.^[15] African-Americans are underrepresented relative to the percentage of whites with renal failure who receive transplants. Many explanations have been advanced as to why the difference in rates of kidney transplantation exists between blacks and whites, including differences in the age of onset of renal failure, differences in the type and severity of the illnesses causing renal failure, and socioeconomic differences that are thought to correlate with compliance and thus with the efficacy of kidney transplantation.

However, one key reason for the difference in rates between the races is the reliance of many programs on antigen matching in determining who will have priority for receiving available kidneys.

Certain crucial biological markers have been identified in key components of the immune system—the lymphocytes—that are fairly predictive of whether or not an organ from a particular person will trigger a strong immunological reaction in the recipient. When a cadaver is identified and permission is given to procure a kidney, surgeons remove the kidneys and, if possible, lymph nodes in order to maximize the changes of obtaining a sample of healthy lymphocytes to allow for the identification or "typing" of antigens. Standard classification systems have evolved for categorizing characteristic markers found on well-mapped areas of these antigens. Many transplant surgeons look for the best possible match between donor and recipient on the A, B, and Dr loci even though these are not the only areas governing immunological resistance. By mixing lymphocytes with various known forms of human sera, it is possible to determine the degree of biological similarity between donor and recipient on these important loci.

The reliance on tissue typing is believed by many to correlate with increased changes for successful engraftment in kidney and other forms of transplants.^[16] Many studies show that significant differences, between five and ten percent, in outcomes at one year and five years of survival can be shown for kidneys transplanted between donors and recipients who are biologically similar to one another. Full matches at the A, B, and Dr loci, which rarely occur due to the enormous variation that exists among the immune systems of human beings, have such marked success in terms of graft survival that the current national health systems for distributing organs in the United States and Europe mandate that a cadaver kidney always be made available to a recipient who is a full match for it.

In terms of equitable distribution of kidneys among blacks and whites, the use of antigen matching as a critical factor in allocating kidneys means those who are members of minority groups have a lower probability of receiving a transplant. Since the antigens are closely linked to race and ethnicity, it is much easier to find a biological match among people with similar ethnic and racial backgrounds than it is among any two randomly selected individuals. On the basis of tissue matching, organs from blacks will almost always go to blacks

and organs from whites will almost always go to whites. Blacks, however, have a much higher incidence of kidney failure than whites. But since whites significantly outnumber blacks in the American population, there are still large numbers of whites waiting for organs. There are so many, in fact, that nearly every white donor is matched to a white recipient. Blacks and other minorities must rely on a much smaller pool of kidneys. The situation for potential black kidney transplant recipients is made even worse by the fact that blacks have a lower rate of cadaver organ donation than do whites. So there is a disproportionately small share of black cadaver kidneys available for a disproportionately large group of blacks in need of kidney transplants. By deciding to use biology in the name of efficiency and, it must be added, fairness, whites wind up with a much larger number of kidney transplants than do blacks relative to the incidence of renal failure in both groups.

The reality of the dilemma that exists between being guided by considerations of efficacy and equity in the allocation of cadaver kidneys for transplantation today is likely to become all too familiar as new knowledge about genetics points the way toward the more efficacious use of medical resources tomorrow. The challenge societies will face is deciding to what extent the values of equal opportunity and fairness justify modifications in policies aimed at the maximization of effectiveness when it is biology that influences the chances for success. Whatever the answer offered in response to situations in which biology points in one direction but notions of equal opportunity and fairness point in another, it is important that the answer be formulated publicly so that those whose interests are at issue can demand accountability from those who must ultimately decide.