MEDICAL GENETICS I
0031-3955/92 $0.00 + .20
ETHICAL ISSUES IN GENETICS Norman Fost, MD, MPH
Clinical genetics encompasses all ethical issues in medicine and health care. Geneticists, like all health care practitioners, regularly encounter problems of truth telling, paternalism, confidentiality, and rationing. In a similar way, there are no unique ethical issues in genetic practice, although some would argue that some questions about genetics cut "to a deeper level of psychological significance than do others in biomedicine."8 The facts and circumstances under which familiar ethical questions arise differ among specialties, but the underlying ethical questions cut across disciplines. For a general background on these pervasive themes the reader is referred to the many excellent collections of articles4 and theoretic texts on ethical theory. 3 The purpose of this article is to provide a review of the ethical issues that commonly arise in the clinical practice of genetics. Although the author does not share the view that there are no right or wrong answers, the limited space does not allow for a full justification of positions. Accordingly, the goal is primarily to identify common positions and justifications for various approaches as well as to identify consensus where it seems to exist. For further reading, there are collections devoted exclusively to ethical, legal, and social issues in genetics.7, 11, 17, 1R, 22
COUNSELING
There is a large and expanding amount of empiric literature on what genetic counseling is, who does it, and how effectively they do From the Department of Pediatrics and Program in Medical Ethics, University of Wisconsin, Madison, Wisconsin
PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 39' NUMBER 1· FEBRUARY 1992
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it. 9 The central ethical question is what it ought to be. The debate is over the broad question of the proper goals and purpose of genetic counseling. More specifically, the question is whether it should try to be neutral and value-free or explicitly directive. The traditional view is that the purpose of genetic counseling is to assist the client in becoming a more informed reproducer so that he or she can exercise autonomy by making free, informed choices. "It is the responsibility of the genetic counselor to adopt a neutral attitude as he provides his patients with the factual information they need to make the proper decisions according to their own conscience.""
Several criticisms have been raised against this position. First, this is not what doctors do in other settings, nor is it what patients generally expect, and it is unclear why genetic counseling should have a different standard than other doctor-patient interactions. The importance of autonomy is not seriously questioned, but part of what patients want and need to know is the doctor's opinion. Whether or not a patient should have toxic chemotherapy for cancer, for example, is among other things a moral, value-laden question, but it would be abnormal for a doctor not to express his or her personal view on the matter or for a patient not to be interested in the doctor's recommendation. Second, apart from the doctor's personal preferences, some would claim that some reproductive decisions are morally indefensible and that a physician has a duty to at least express this view. 2 , 14,25 Consider, for example, the real case of Grodin vs. Grodin, in which a woman allegedly took tetracycline while pregnant, knowing that it would stain her baby's teeth, and later encouraged a civil suit against herself on behalf of the child so that financial assets could be shifted to the child's estate to avoid excessive taxation. Few would claim that a counselor presented with such a proposal should remain neutral. A more common non genetic example would be the HIV-positive pregnant woman seeking advice about whether to terminate her pregnancy. Similarly, a woman who knows she is pregnant with a fetus affected with Tay Sachs disease or Lesch-Nyhan syndrome and asks advice would not be likely to receive value-free counseling. A second objection to the advocacy of value-free counseling is the empiric claim that it is virtually impossible to achieve and that it would be preferable for counselors to be open and direct about their biases rather than conceal them behind a cloak of apparent neutrality. This problem is illustrated by another kind of counseling commonly provided for parents of children born with birth defects, namely, whether or not to withhold life-sustaining medical treatment. Although many physicians experienced in such interactions claim that parents should make the decision, the wide variation of such parental decisions strongly suggests that they are heavily influenced by physician bias and direc-
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tive, if not distorted, counseling. Gross et al,16 for example, reported that in their referral practice, more than 50% of parents of newborns with spina bifida chose to allow their children to die. This choice for nontreatment was 5 to 10 times higher than most other reported series and is unlikely to reflect value differences among parents. Finally, some would argue that genetic counseling should not serve only the client's interests and values but that these concerns must be balanced with legitimate societal needs and wants, including the general public health. This does not distinguish genetic counseling from the rest of health care, which must necessarily include compromises between patient needs and wants on the one hand, and the larger societal needs and wants on the other, including allocation of limited resources. This point has been made emphatically in discussion of proposals for widespread population screening for carriers of the cystic fibrosis gene. At its present cost, screening all pregnant women might cost in excess of $1 billion. 31 It is unclear how many women would alter their reproductive plans if found to be at risk. If that number were small, as suggested by some studies,13 then the cost per case averted might be very high. To state the issue most starkly, suppose that all pregnant women were tested and found to be very informed reproducers, but none decided to change their reproductive plans, so that there was no public health benefit. In a society with 37 million uninsured citizens and enormous unmet basic medical needs, it would be difficult to defend the expenditure of $1 billion if the only result were more informed reproducers. An emerging issue in the genetic counselor's need to balance patient and societal interests involves the threat that genetic information poses for insurance and employment. Health and life insurance companies have long discriminated on the basis of risk of future disease or disability, either by charging differential rates or denying insurance altogether. Expanding genetic knowledge creates the potential for more sophisticated discrimination. It is not manifest that such practices differ qualitatively from the traditional techniques of "rating" applicants, whether by history, physical examination, or tests. But the increasing cost of health care and growing concern about the large number of Americans without health insurance has focused attention on the issue. Genetic counselors must consider whether to advise their clients of such risks of testing, including the opportunity to purchase extra insurance before tests that may be disqualifying. This kind of "adverse selection" is of great concern to the insurance industry. Even more controversial is the consideration of withholding stigmatizing test results from the medical record to protect the patient from adverse social consequences. Such "anonymous testing" is widely and openly practiced for HIV disease.
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SCREENING
Screening usually refers to a search for occult disease in a large population, typically under government auspices. The term testing is used when a decision is made to search for a disorder as a result of an individual decision between a physician and a patient. The terms overlap, because even government-sponsored or mandated screening programs, such as newborn screening for phenylketonuria, may require informed consent and may therefore resemble individual decisions in actual practice. Similarly, testing can become so routine, often with little attention to informed consent, that it can effectively result in widespread population screening. The ethical and social problems in mass population screening are similar, regardless of whether the disorder being sought is genetic. Thus, the concerns and guidelines that emerge for screening for infectious diseases such as HIV19 closely resemble guidelines for genetic screening. 12, 26 Screening can be done for any of three purposes: to identify patients who may benefit from pre symptomatic treatment; to identify persons at risk for having an affected child and who therefore have an interest in counseling; or for purposes of research, such as enumeration, natural history studies, or recruitment of patients into experimental treatment protocols, Screening is a ubiquitous and increasing part of health care, and examples abound of screening programs and practices that, in retrospect, exposed patients to unconsented harms without compensating benefits. When the purpose is treatment, the common pitfalls include the following: 1. Failure to recognize the heterogeneity of the disorder. The early
days of phenylketonuria screening falsely labeled infants with high blood phenylalanine levels as having the disease phenylketonuria, before it was realized that most such infants were not destined to be retarded. As a result, some infants were started on a diet with no benefit, which in some cases caused retardation because of delayed appreciation of hazards of inadequate phenylalanine intake. 2. Failure to test the efficacy of the intervention with properly designed and peer-reviewed pilot studies. Newborn screening for cystic fibrosis preceded assessment of the efficacy of early intervention, and the only prospective controlled study has not yet shown any benefit after 5 years of comprehensive treatment. 23 3. Failure to inform prospective patients or their parents that the program is experimental; i.e., bypassing of the usual institu-
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tional checks on human experimentation, including review by an institutional review board, and inadequate attention to traditional standards of informed consent. Screening programs for the purpose of reproductive counseling have encountered a somewhat different set of problems: 1. Failure to dearly establish the goals of the program. Government-sponsored sickle cell screening programs commonly failed to distinguish individual goals-allowing clients to make informed, free choices-from public health goals, such as reduction in the incidence of sickle cell disease. 2. Inadequate education and counseling, so that clients were unable to make informed choices because of inability to understand the basic facts. Worse, some programs had extraordinarily high levels of confusion and irrational decisions. 29 3. Inadequate appreciation of adverse psychosocial effects of being identified as being at risk for producing children with severe genetic disease. Many people identified as sickle carriers discovered too late that they had lost employment and insurance opportunities. In summary, there has been a strong consensus for at least 15 years on the essential components of an ethically defensible mass screening program. 12, 26 The key ingredients include: 1. Clear statement of purpose and goals. 2. Peer-reviewed pilot studies showing that the stated goals can be achieved with acceptable costs and adverse effects. 3. Education of the target population. 4. Attention to traditional standards of informed consent. This implies avoiding mandatory programs except where there is a compelling argument for doing so. 5. Respect for confidentiality of potentially stigmatizing information. These standards are not impossible to realize, although the difficulty varies with the target population and the disorder in question. There have been well-documented highly successful mass screening programs with wide community acceptance, effectiveness in achieving stated goals, and minimum adverse effects. 5, 20 The rapidly growing number of new genetic tests, particularly for common genetic disorders such as cystic fibrosis, threatens to create pressures to implement widespread screening before adequate pilot studies can be done and before the development of sufficient resources to provide services that will meet the requirements for ethically defensible mass screening. 31
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CONFIDENTIALITY
The principle of confidentiality is one of the oldest and most basic ethical principles in medicine. It is based on two notions: (1) a utilitarian concern that the public health is best served if patients feel comfortable in seeking health care, and in confiding all information to the doctor that is essential in arriving at the proper course of action. (2) Because patients depend so much on the assumption that potentially embarrassing information will not be revealed, the very existence of a doctorpatient relationship is assumed to include a promise that the doctor will not disclose information without explicit consent, or will do so for generally accepted purposes such as collection of third-party payments or when he or she is legally required to report to a state health department. Unconsented disclosure therefore constitutes the breaking of an implied promise, which is prima facie wrong regardless of the consequences. Like all principles, confidentiality cannot claim absolute dominion over all other ethical obligations. Certain cases attract widespread support for breaching the principle. These cases typically involve situations in which there is a high probability that a third party will suffer serious physical harm, which can be prevented in no other way. Familiar examples include child abuse, for which there is widespread support for disclosing stigmatizing information about a parent to protect a child from serious injury. In psychiatry, the Tarasoff Rule, adopted in many state court decisions, requires a therapist to warn a third party when the therapist is convinced that his or her client intends to cause serious injury to the unsuspecting victim. Genetic counseling situations do not commonly rise to this standard. Warning a relative that he or she is at risk of conceiving a child with hemophilia, for example, raises questions about whether there is even a third party to protect. The potential person does not exist at the time the question of disclosure arises. And whether or not that potential person would be better served by never being born is a question of extreme complexity. Finally, contemporary treatment of hemophilia makes it a condition that does not seem as severe a burden as child abuse or homicide. Given these ambiguities, it is not surprising that there is no consensus among surveyed geneticists regarding disclosure in this situation. 30 In contrast, there was strong consensus for not disclosing unsuspected paternity, perhaps because the consequences of non-disclosure were primarily psychosocial, not involving a high likelihood of serious physical harm. Although practitioners and ethicists disagree about the appropriate boundaries of confidentiality, there would seem to be a duty for those who can anticipate breaches to include their policies in obtaining
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consent for genetic testing. If, for example, a client is tested for Huntington's disease with the usual assumptions of no unconsented disclosure, and the counselor's policy is to inform relatives at risk over the client's objection, there would seem to be a duty to advise the client before the testing is done. To proceed otherwise would be to add deception to the list of ethical problems.
PRENATAL DIAGNOSIS
Some would claim that prenatal diagnosis is linked so closely with abortion that it is necessary to assume the acceptability of patient choice regarding abortion to even consider the possibility of participating in prenatal diagnosis. Against this view, however, is the observation that most prenatal diagnostic tests result in normal findings, encouraging the client to continue the pregnancy to term. For some conditions, such as Tay Sachs disease, the availability of prenatal diagnosis almost certainly reduces the incidence of abortion, because couples at risk prefer to terminate all pregnancies rather than risk having an affected child. It has been argued by some, therefore, that prenatal diagnosis can be justified, at least in some circumstances, by those who believe abortion is immoral. In addition, some clients may find benefits in prenatal diagnosis even when abortion is not a consideration, whether for relief of anxiety, preparation for the birth of an abnormal child, consideration of placement for adoption at the time of delivery, or preparation for medical interventions that may be needed at the moment of delivery. Even for those who are tolerant or supportive of abortion, a number of ethical issues arise. Whether or not unanticipated results should be disclosed seems to arouse less controversy than in earlier times, and a majority of surveyed geneticists believe such information should be shared. 30 This is consistent with the general increase in respect for patient autonomy and the trend away from paternalism in medical practice. There are also utilitarian arguments against concealing information, because subsequent discovery by the patient is not rare and may lead to general distrust, not to mention potential legal claims. A major current controversy involves questions regarding the use of prenatal diagnosis for conditions other than the traditional risks of advanced maternal age and its association with chromosomal abnormalities or the identification of specific genetic disorders in patients with a positive family history. Less well accepted are requests for gender identification, unrelated to sex-linked disorders, or testing to assess the fetus' potential as a source for bone marrow transplantation for a relative. 1, 6
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Prenatal diagnosis for the sale purpose of selecting the gender of a live-born child has been opposed on several grounds. First, because there is no claim of disease or disability, this practice does not seem the proper function of the medical care system. In opposition, advocates point out the many examples of support for medical services that serve "mere" psychological or social needs, independent of diseases. Second, widespread gender selection could have undesirable implications for population policy. Studies suggest that a majority of clients would prefer that a first-born child be a boy. This could lead to imbalances in male-female ratios as well as inequality of opportunity if there were systematic differences in the accomplishments of first-born children. Proponents point out that the number of persons requesting this service is currently small, and that until the number becomes large, population issues are remote and theoretic. Finally, the strongest argument against offering this service for mere gender selection is based on concerns about justice and fair allocation of limited resources. Specifically, in a country in which hundreds of thousands of women cannot afford prenatal care or cannot find an obstetrician even when financing is available, it seems an unacceptable luxury to provide gender selection to those who are already well served by the health care system. More recently, public controversy erupted over the reports of families who conceived for the purpose of creating a baby who could serve as a bone marrow donor, usually for a sibling. Geneticists have been asked to facilitate human leukocyte antigen testing of such fetuses, with the intention of aborting fetuses who were not genetically suitable as organ donors. Whereas the initial professional and public reactions were generally not supportive,lO others have argued that many, if not most, infants are conceived for more selfish reasons, or no reason at all, and many are considerably more likely to be born into families in which their prospects for adequate nurturing are poor. This view is critical of the inconsistency in singling out a small number of families whose motives for procreation must be subjected to judgment because of their need for medical assistance.
GENETIC THERAPY
Treatment of genetic disorders includes all the modalities used to treat nongenetic diseases, including pharmaceutical products, blood products, enzymes, organ transplantation, and life-prolonging machinery. Ethical issues raised by such therapies are no different when the disease is of genetic origin. The possibility of specific gene replacement, in contrast, has been believed to raise new issues, depending on whether the proposed treatment is aimed at somatic or germ cells. 28
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Somatic cell therapy, such as the effort to insert the gene that would correct adenosine deaminase deficiency, 1 does not seem to raise ethical questions different from other manipulations of somatic cells and tissues. As Rosenberg has argued, "there is little difference between inserting a normal beta-globin gene into the marrow cells of a patient with sickle cell anemia and replacing that patient's marrow cells with normal cells by transplantation."2s As with all experimental treatments, various complex ethical issues must be addressed, including the following: 1. Whether to restrict initial efforts to patients with the capacity to consent. 2. Whether to do the first trials on patients with end stage disease who have little to lose, or patients early in their course who have the greatest potential for a favorable outcome. 3. Whether to try treatments that could prolong the life of patients with severe neurologic impairment, possibly without affecting their neurologic status. There is no clear consensus on these issues, except for the growing view that they are not uniquely genetic issues and therefore raise no new reasons for resisting or regulating somatic genetic therapies. In contrast, inserting genes into fertilized eggs affects not only the life of that individual, but the potential of all of his or her progeny. If the insertion is successful (replacing a harmful gene with a normal version) there is little cause for alarm. The potential for affecting untold generations, it is claimed, raises more serious ethical questions, however, particularly because the actual effects of such experiments are unpredictable. Although the potential for harm to future generations should arouse special caution, it is not clear that genetic therapy is new in that regard or even the most serious threat to the well-being of future persons. A wide range of social and environmental policies pose more immediate threats to the health and well-being of future persons, than do nongenetic therapies. The ability to prolong the lives of patients with diabetes and hemophilia, for example, has presumably resulted in higher fertility rates for affected individuals and an increase in the incidence of affected individuals in subsequent generations. Without such therapy, some of these individuals would not have been born. Such discussions quickly become mired in complex philosophic questions of whether the person born with a genetic disease has actually been harmed, because that particular person would not have been born at all had his or her ancestors died before reproducing. It is beyond the point of this article to probe deeper into these complexities. The central point is that they are not unique to germ cell therapy, so that although such possible consequences should be taken extremely seri-
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ously in contemplating human experimentation, they do not appear to raise new issues calling for new rules. In a similar way, concerns have arisen that genetic therapy may lead to desires and demands to mold offspring according to parental expectations. Such desires have existed for millennia and have been effectively practiced through various techniques including careful selection of mates, orthodontia, hair bleaches and dyes, cosmetic surgery, treatment with growth hormone, and an endless search for ways to improve the intelligence of children. Genetic therapy may prove more effective than some of these interventions, but the issues raised would seem quantitative rather than qualitative. IS References 1. Anderson F: Rx of ADA deficiency. 2. Arras J: AIDS and reproductive decisions: Having children in fear and trembling. Milbank Quarterly 68:353--382, 1990 3. Beauchamp TL, Childress JE: Principles of Biomedical Ethics, ed 2. New York, Oxford Press, 1983 4. Beauchamp TL, Walters L: Contemporary Issues in Bioethics, ed 3. Belmont, Wadsworth Publishing Co, 1989 5. Cao A, Furbetta M, Galanello R, et al: Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia. Am J Hum Genet 33:592605, 1981 6. Caplan A, Kearney W: Parity for donation of bone marrow: Ethical and policy considerations. In Blank R, Bonnicksen A (eds): Emerging Issues in Biomedical Policy. New York, Columbia University Press, 1992 7. Capron AM, Lappe M, Murray RM, et al: Genetic Counseling: Facts, Values and Norms. New York, Alan R. Liss Inc, 1979 8. Capron AM: Unsplicing the Gordian knot: Legal and ethical issues in the "New Genetics." In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 9. Childs B: Genetic counseling: A critical review of the literature. In Cohen BH, Lilienfeld AM, Huang PC (eds): Genetic Issues in Public Health and Medicine. Springfield, Charles C Thomas, 1978 10. Clark RD, Fletcher J, Petersen G: Conceiving a fetus for bone marrow donation: An ethical problem in prenatal diagnosis. Prenatal DiagnOSis 5:329-334, 1989; Retraction. Prenatal Diagnosis 10:549, 1990 11. Cohen BH, Lilienfeld AM, Huang PC: Genetic Issues in Public Health and Medicine. Springfield, Charles C Thomas, 1978 12. Committee for the Study of Inborn Errors of Metabolism: Genetic Screening: Programs, Principles and Research. Washington DC, National Academy of Sciences, 1973 13. Erbe R: Reproductive choices of couples at risk for CF [abstract]. Am J Public Health, 1991 14. Fletcher J: The Ethics of Genetic Control: Ending Reproductive Roulette. Garden City, NY, Doubleday, 1974 15. Fost N: Regulating genetic technology: Values in conflict. In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 16. Gross RH, Cox A, Tatyrek R, et al: Early management and decision making for the treatment of myelomeningocoele. Pediatrics 72:450-458, 1983 17. Hilton B, et al: Ethical Issues in Human Genetics. New York, Plenum Press, 1983 18. Holtzman N: Proceed With Caution: Predicting Genetics Risks in the Recombinant DNA ERA. Baltimore, Johns Hopkins Press, 1989
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19. 10M Committee on Perinatal HIV Screening. In Hardy L (ed): HIV Screening of Pregnant Women and Newborns. Washington, National Academy Press, 1991 20. Kaback MM, Zeiger RS: The Johns Kennedy Institute Tay Sachs Program: Practical and ethical issues in an adult genetic screening program. In Condliffe P, Callahan D, Hilton B (eds): Ethical Issues in Genetic Counseling and the Use of Genetic Knowledge, New York, Plenum Press, 1972 21. Karp L: Genetic Engineering: Threat or Promise. Chicago, Nelson-Hall Inc, 1976 22. Milunsky A, Annas GJ: Genetics and the Law III. New York, Plenum Press, 1985 23. Farrell PM, Mischler EH: Newborn screening for cystic fibrosis. Advances in Pediatrics, 1992, in press 24. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research: Splicing Life. Washington DC US Government Printing Office, 1982 25. Purdy LM: Genetic diseases: Can having children be immoral? In Buckley JJ (ed): Genetics Now: Ethical Issues in Genetic Research. Washington DC University Press of America, 1978 26. Research Group, Institute of Society, Ethics, and the Life Sciences: Ethical and social issues in screening for genetic disease. New Engl J Med 286:1129-1132, 1972 27. Robertson JA: Genetic alteration of embryos: The ethical issues. In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 28. Rosenberg LE: Can we cure genetic disorders. In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 29. Stamatoyannopoulos G: Problems of screening and counseling in the hemoglobinopathies. In Motulsky AG, Lenz W (eds): Birth Defects Proceedings of the 4th International Conference. Amsterdam Excerpta Medica, 1974 pp 268--276 30. Wertz DC, Rosenfield JM, Janes SR, et al: Attitudes toward abortion among parents of children with cystic fibrosis. Am J Public Health 81:992-996, 1991 31. Wilfond BS, Fost N: The cystic fibrosis gene: Medical and social implications for heterozygote detection. JAMA 263:2777-2783, 1990 Address reprint requests to
Norman Fost, MD, MPH Clinical Genetics Center, Room 353 University of Wisconsin 1500 Highland Avenue Madison, WI 53706
0031-3955/92 $0.00 + .20
ETHICAL ISSUES IN GENETICS Norman Fost, MD, MPH
Clinical genetics encompasses all ethical issues in medicine and health care. Geneticists, like all health care practitioners, regularly encounter problems of truth telling, paternalism, confidentiality, and rationing. In a similar way, there are no unique ethical issues in genetic practice, although some would argue that some questions about genetics cut "to a deeper level of psychological significance than do others in biomedicine."8 The facts and circumstances under which familiar ethical questions arise differ among specialties, but the underlying ethical questions cut across disciplines. For a general background on these pervasive themes the reader is referred to the many excellent collections of articles4 and theoretic texts on ethical theory. 3 The purpose of this article is to provide a review of the ethical issues that commonly arise in the clinical practice of genetics. Although the author does not share the view that there are no right or wrong answers, the limited space does not allow for a full justification of positions. Accordingly, the goal is primarily to identify common positions and justifications for various approaches as well as to identify consensus where it seems to exist. For further reading, there are collections devoted exclusively to ethical, legal, and social issues in genetics.7, 11, 17, 1R, 22
COUNSELING
There is a large and expanding amount of empiric literature on what genetic counseling is, who does it, and how effectively they do From the Department of Pediatrics and Program in Medical Ethics, University of Wisconsin, Madison, Wisconsin
PEDIATRIC CLINICS OF NORTH AMERICA VOLUME 39' NUMBER 1· FEBRUARY 1992
79
80
FaST
it. 9 The central ethical question is what it ought to be. The debate is over the broad question of the proper goals and purpose of genetic counseling. More specifically, the question is whether it should try to be neutral and value-free or explicitly directive. The traditional view is that the purpose of genetic counseling is to assist the client in becoming a more informed reproducer so that he or she can exercise autonomy by making free, informed choices. "It is the responsibility of the genetic counselor to adopt a neutral attitude as he provides his patients with the factual information they need to make the proper decisions according to their own conscience.""
Several criticisms have been raised against this position. First, this is not what doctors do in other settings, nor is it what patients generally expect, and it is unclear why genetic counseling should have a different standard than other doctor-patient interactions. The importance of autonomy is not seriously questioned, but part of what patients want and need to know is the doctor's opinion. Whether or not a patient should have toxic chemotherapy for cancer, for example, is among other things a moral, value-laden question, but it would be abnormal for a doctor not to express his or her personal view on the matter or for a patient not to be interested in the doctor's recommendation. Second, apart from the doctor's personal preferences, some would claim that some reproductive decisions are morally indefensible and that a physician has a duty to at least express this view. 2 , 14,25 Consider, for example, the real case of Grodin vs. Grodin, in which a woman allegedly took tetracycline while pregnant, knowing that it would stain her baby's teeth, and later encouraged a civil suit against herself on behalf of the child so that financial assets could be shifted to the child's estate to avoid excessive taxation. Few would claim that a counselor presented with such a proposal should remain neutral. A more common non genetic example would be the HIV-positive pregnant woman seeking advice about whether to terminate her pregnancy. Similarly, a woman who knows she is pregnant with a fetus affected with Tay Sachs disease or Lesch-Nyhan syndrome and asks advice would not be likely to receive value-free counseling. A second objection to the advocacy of value-free counseling is the empiric claim that it is virtually impossible to achieve and that it would be preferable for counselors to be open and direct about their biases rather than conceal them behind a cloak of apparent neutrality. This problem is illustrated by another kind of counseling commonly provided for parents of children born with birth defects, namely, whether or not to withhold life-sustaining medical treatment. Although many physicians experienced in such interactions claim that parents should make the decision, the wide variation of such parental decisions strongly suggests that they are heavily influenced by physician bias and direc-
ETHICAL ISSUES IN GENETICS
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tive, if not distorted, counseling. Gross et al,16 for example, reported that in their referral practice, more than 50% of parents of newborns with spina bifida chose to allow their children to die. This choice for nontreatment was 5 to 10 times higher than most other reported series and is unlikely to reflect value differences among parents. Finally, some would argue that genetic counseling should not serve only the client's interests and values but that these concerns must be balanced with legitimate societal needs and wants, including the general public health. This does not distinguish genetic counseling from the rest of health care, which must necessarily include compromises between patient needs and wants on the one hand, and the larger societal needs and wants on the other, including allocation of limited resources. This point has been made emphatically in discussion of proposals for widespread population screening for carriers of the cystic fibrosis gene. At its present cost, screening all pregnant women might cost in excess of $1 billion. 31 It is unclear how many women would alter their reproductive plans if found to be at risk. If that number were small, as suggested by some studies,13 then the cost per case averted might be very high. To state the issue most starkly, suppose that all pregnant women were tested and found to be very informed reproducers, but none decided to change their reproductive plans, so that there was no public health benefit. In a society with 37 million uninsured citizens and enormous unmet basic medical needs, it would be difficult to defend the expenditure of $1 billion if the only result were more informed reproducers. An emerging issue in the genetic counselor's need to balance patient and societal interests involves the threat that genetic information poses for insurance and employment. Health and life insurance companies have long discriminated on the basis of risk of future disease or disability, either by charging differential rates or denying insurance altogether. Expanding genetic knowledge creates the potential for more sophisticated discrimination. It is not manifest that such practices differ qualitatively from the traditional techniques of "rating" applicants, whether by history, physical examination, or tests. But the increasing cost of health care and growing concern about the large number of Americans without health insurance has focused attention on the issue. Genetic counselors must consider whether to advise their clients of such risks of testing, including the opportunity to purchase extra insurance before tests that may be disqualifying. This kind of "adverse selection" is of great concern to the insurance industry. Even more controversial is the consideration of withholding stigmatizing test results from the medical record to protect the patient from adverse social consequences. Such "anonymous testing" is widely and openly practiced for HIV disease.
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SCREENING
Screening usually refers to a search for occult disease in a large population, typically under government auspices. The term testing is used when a decision is made to search for a disorder as a result of an individual decision between a physician and a patient. The terms overlap, because even government-sponsored or mandated screening programs, such as newborn screening for phenylketonuria, may require informed consent and may therefore resemble individual decisions in actual practice. Similarly, testing can become so routine, often with little attention to informed consent, that it can effectively result in widespread population screening. The ethical and social problems in mass population screening are similar, regardless of whether the disorder being sought is genetic. Thus, the concerns and guidelines that emerge for screening for infectious diseases such as HIV19 closely resemble guidelines for genetic screening. 12, 26 Screening can be done for any of three purposes: to identify patients who may benefit from pre symptomatic treatment; to identify persons at risk for having an affected child and who therefore have an interest in counseling; or for purposes of research, such as enumeration, natural history studies, or recruitment of patients into experimental treatment protocols, Screening is a ubiquitous and increasing part of health care, and examples abound of screening programs and practices that, in retrospect, exposed patients to unconsented harms without compensating benefits. When the purpose is treatment, the common pitfalls include the following: 1. Failure to recognize the heterogeneity of the disorder. The early
days of phenylketonuria screening falsely labeled infants with high blood phenylalanine levels as having the disease phenylketonuria, before it was realized that most such infants were not destined to be retarded. As a result, some infants were started on a diet with no benefit, which in some cases caused retardation because of delayed appreciation of hazards of inadequate phenylalanine intake. 2. Failure to test the efficacy of the intervention with properly designed and peer-reviewed pilot studies. Newborn screening for cystic fibrosis preceded assessment of the efficacy of early intervention, and the only prospective controlled study has not yet shown any benefit after 5 years of comprehensive treatment. 23 3. Failure to inform prospective patients or their parents that the program is experimental; i.e., bypassing of the usual institu-
ETHICAL ISSUES IN GENETICS
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tional checks on human experimentation, including review by an institutional review board, and inadequate attention to traditional standards of informed consent. Screening programs for the purpose of reproductive counseling have encountered a somewhat different set of problems: 1. Failure to dearly establish the goals of the program. Government-sponsored sickle cell screening programs commonly failed to distinguish individual goals-allowing clients to make informed, free choices-from public health goals, such as reduction in the incidence of sickle cell disease. 2. Inadequate education and counseling, so that clients were unable to make informed choices because of inability to understand the basic facts. Worse, some programs had extraordinarily high levels of confusion and irrational decisions. 29 3. Inadequate appreciation of adverse psychosocial effects of being identified as being at risk for producing children with severe genetic disease. Many people identified as sickle carriers discovered too late that they had lost employment and insurance opportunities. In summary, there has been a strong consensus for at least 15 years on the essential components of an ethically defensible mass screening program. 12, 26 The key ingredients include: 1. Clear statement of purpose and goals. 2. Peer-reviewed pilot studies showing that the stated goals can be achieved with acceptable costs and adverse effects. 3. Education of the target population. 4. Attention to traditional standards of informed consent. This implies avoiding mandatory programs except where there is a compelling argument for doing so. 5. Respect for confidentiality of potentially stigmatizing information. These standards are not impossible to realize, although the difficulty varies with the target population and the disorder in question. There have been well-documented highly successful mass screening programs with wide community acceptance, effectiveness in achieving stated goals, and minimum adverse effects. 5, 20 The rapidly growing number of new genetic tests, particularly for common genetic disorders such as cystic fibrosis, threatens to create pressures to implement widespread screening before adequate pilot studies can be done and before the development of sufficient resources to provide services that will meet the requirements for ethically defensible mass screening. 31
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CONFIDENTIALITY
The principle of confidentiality is one of the oldest and most basic ethical principles in medicine. It is based on two notions: (1) a utilitarian concern that the public health is best served if patients feel comfortable in seeking health care, and in confiding all information to the doctor that is essential in arriving at the proper course of action. (2) Because patients depend so much on the assumption that potentially embarrassing information will not be revealed, the very existence of a doctorpatient relationship is assumed to include a promise that the doctor will not disclose information without explicit consent, or will do so for generally accepted purposes such as collection of third-party payments or when he or she is legally required to report to a state health department. Unconsented disclosure therefore constitutes the breaking of an implied promise, which is prima facie wrong regardless of the consequences. Like all principles, confidentiality cannot claim absolute dominion over all other ethical obligations. Certain cases attract widespread support for breaching the principle. These cases typically involve situations in which there is a high probability that a third party will suffer serious physical harm, which can be prevented in no other way. Familiar examples include child abuse, for which there is widespread support for disclosing stigmatizing information about a parent to protect a child from serious injury. In psychiatry, the Tarasoff Rule, adopted in many state court decisions, requires a therapist to warn a third party when the therapist is convinced that his or her client intends to cause serious injury to the unsuspecting victim. Genetic counseling situations do not commonly rise to this standard. Warning a relative that he or she is at risk of conceiving a child with hemophilia, for example, raises questions about whether there is even a third party to protect. The potential person does not exist at the time the question of disclosure arises. And whether or not that potential person would be better served by never being born is a question of extreme complexity. Finally, contemporary treatment of hemophilia makes it a condition that does not seem as severe a burden as child abuse or homicide. Given these ambiguities, it is not surprising that there is no consensus among surveyed geneticists regarding disclosure in this situation. 30 In contrast, there was strong consensus for not disclosing unsuspected paternity, perhaps because the consequences of non-disclosure were primarily psychosocial, not involving a high likelihood of serious physical harm. Although practitioners and ethicists disagree about the appropriate boundaries of confidentiality, there would seem to be a duty for those who can anticipate breaches to include their policies in obtaining
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consent for genetic testing. If, for example, a client is tested for Huntington's disease with the usual assumptions of no unconsented disclosure, and the counselor's policy is to inform relatives at risk over the client's objection, there would seem to be a duty to advise the client before the testing is done. To proceed otherwise would be to add deception to the list of ethical problems.
PRENATAL DIAGNOSIS
Some would claim that prenatal diagnosis is linked so closely with abortion that it is necessary to assume the acceptability of patient choice regarding abortion to even consider the possibility of participating in prenatal diagnosis. Against this view, however, is the observation that most prenatal diagnostic tests result in normal findings, encouraging the client to continue the pregnancy to term. For some conditions, such as Tay Sachs disease, the availability of prenatal diagnosis almost certainly reduces the incidence of abortion, because couples at risk prefer to terminate all pregnancies rather than risk having an affected child. It has been argued by some, therefore, that prenatal diagnosis can be justified, at least in some circumstances, by those who believe abortion is immoral. In addition, some clients may find benefits in prenatal diagnosis even when abortion is not a consideration, whether for relief of anxiety, preparation for the birth of an abnormal child, consideration of placement for adoption at the time of delivery, or preparation for medical interventions that may be needed at the moment of delivery. Even for those who are tolerant or supportive of abortion, a number of ethical issues arise. Whether or not unanticipated results should be disclosed seems to arouse less controversy than in earlier times, and a majority of surveyed geneticists believe such information should be shared. 30 This is consistent with the general increase in respect for patient autonomy and the trend away from paternalism in medical practice. There are also utilitarian arguments against concealing information, because subsequent discovery by the patient is not rare and may lead to general distrust, not to mention potential legal claims. A major current controversy involves questions regarding the use of prenatal diagnosis for conditions other than the traditional risks of advanced maternal age and its association with chromosomal abnormalities or the identification of specific genetic disorders in patients with a positive family history. Less well accepted are requests for gender identification, unrelated to sex-linked disorders, or testing to assess the fetus' potential as a source for bone marrow transplantation for a relative. 1, 6
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Prenatal diagnosis for the sale purpose of selecting the gender of a live-born child has been opposed on several grounds. First, because there is no claim of disease or disability, this practice does not seem the proper function of the medical care system. In opposition, advocates point out the many examples of support for medical services that serve "mere" psychological or social needs, independent of diseases. Second, widespread gender selection could have undesirable implications for population policy. Studies suggest that a majority of clients would prefer that a first-born child be a boy. This could lead to imbalances in male-female ratios as well as inequality of opportunity if there were systematic differences in the accomplishments of first-born children. Proponents point out that the number of persons requesting this service is currently small, and that until the number becomes large, population issues are remote and theoretic. Finally, the strongest argument against offering this service for mere gender selection is based on concerns about justice and fair allocation of limited resources. Specifically, in a country in which hundreds of thousands of women cannot afford prenatal care or cannot find an obstetrician even when financing is available, it seems an unacceptable luxury to provide gender selection to those who are already well served by the health care system. More recently, public controversy erupted over the reports of families who conceived for the purpose of creating a baby who could serve as a bone marrow donor, usually for a sibling. Geneticists have been asked to facilitate human leukocyte antigen testing of such fetuses, with the intention of aborting fetuses who were not genetically suitable as organ donors. Whereas the initial professional and public reactions were generally not supportive,lO others have argued that many, if not most, infants are conceived for more selfish reasons, or no reason at all, and many are considerably more likely to be born into families in which their prospects for adequate nurturing are poor. This view is critical of the inconsistency in singling out a small number of families whose motives for procreation must be subjected to judgment because of their need for medical assistance.
GENETIC THERAPY
Treatment of genetic disorders includes all the modalities used to treat nongenetic diseases, including pharmaceutical products, blood products, enzymes, organ transplantation, and life-prolonging machinery. Ethical issues raised by such therapies are no different when the disease is of genetic origin. The possibility of specific gene replacement, in contrast, has been believed to raise new issues, depending on whether the proposed treatment is aimed at somatic or germ cells. 28
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Somatic cell therapy, such as the effort to insert the gene that would correct adenosine deaminase deficiency, 1 does not seem to raise ethical questions different from other manipulations of somatic cells and tissues. As Rosenberg has argued, "there is little difference between inserting a normal beta-globin gene into the marrow cells of a patient with sickle cell anemia and replacing that patient's marrow cells with normal cells by transplantation."2s As with all experimental treatments, various complex ethical issues must be addressed, including the following: 1. Whether to restrict initial efforts to patients with the capacity to consent. 2. Whether to do the first trials on patients with end stage disease who have little to lose, or patients early in their course who have the greatest potential for a favorable outcome. 3. Whether to try treatments that could prolong the life of patients with severe neurologic impairment, possibly without affecting their neurologic status. There is no clear consensus on these issues, except for the growing view that they are not uniquely genetic issues and therefore raise no new reasons for resisting or regulating somatic genetic therapies. In contrast, inserting genes into fertilized eggs affects not only the life of that individual, but the potential of all of his or her progeny. If the insertion is successful (replacing a harmful gene with a normal version) there is little cause for alarm. The potential for affecting untold generations, it is claimed, raises more serious ethical questions, however, particularly because the actual effects of such experiments are unpredictable. Although the potential for harm to future generations should arouse special caution, it is not clear that genetic therapy is new in that regard or even the most serious threat to the well-being of future persons. A wide range of social and environmental policies pose more immediate threats to the health and well-being of future persons, than do nongenetic therapies. The ability to prolong the lives of patients with diabetes and hemophilia, for example, has presumably resulted in higher fertility rates for affected individuals and an increase in the incidence of affected individuals in subsequent generations. Without such therapy, some of these individuals would not have been born. Such discussions quickly become mired in complex philosophic questions of whether the person born with a genetic disease has actually been harmed, because that particular person would not have been born at all had his or her ancestors died before reproducing. It is beyond the point of this article to probe deeper into these complexities. The central point is that they are not unique to germ cell therapy, so that although such possible consequences should be taken extremely seri-
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ously in contemplating human experimentation, they do not appear to raise new issues calling for new rules. In a similar way, concerns have arisen that genetic therapy may lead to desires and demands to mold offspring according to parental expectations. Such desires have existed for millennia and have been effectively practiced through various techniques including careful selection of mates, orthodontia, hair bleaches and dyes, cosmetic surgery, treatment with growth hormone, and an endless search for ways to improve the intelligence of children. Genetic therapy may prove more effective than some of these interventions, but the issues raised would seem quantitative rather than qualitative. IS References 1. Anderson F: Rx of ADA deficiency. 2. Arras J: AIDS and reproductive decisions: Having children in fear and trembling. Milbank Quarterly 68:353--382, 1990 3. Beauchamp TL, Childress JE: Principles of Biomedical Ethics, ed 2. New York, Oxford Press, 1983 4. Beauchamp TL, Walters L: Contemporary Issues in Bioethics, ed 3. Belmont, Wadsworth Publishing Co, 1989 5. Cao A, Furbetta M, Galanello R, et al: Prevention of homozygous beta-thalassemia by carrier screening and prenatal diagnosis in Sardinia. Am J Hum Genet 33:592605, 1981 6. Caplan A, Kearney W: Parity for donation of bone marrow: Ethical and policy considerations. In Blank R, Bonnicksen A (eds): Emerging Issues in Biomedical Policy. New York, Columbia University Press, 1992 7. Capron AM, Lappe M, Murray RM, et al: Genetic Counseling: Facts, Values and Norms. New York, Alan R. Liss Inc, 1979 8. Capron AM: Unsplicing the Gordian knot: Legal and ethical issues in the "New Genetics." In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 9. Childs B: Genetic counseling: A critical review of the literature. In Cohen BH, Lilienfeld AM, Huang PC (eds): Genetic Issues in Public Health and Medicine. Springfield, Charles C Thomas, 1978 10. Clark RD, Fletcher J, Petersen G: Conceiving a fetus for bone marrow donation: An ethical problem in prenatal diagnosis. Prenatal DiagnOSis 5:329-334, 1989; Retraction. Prenatal Diagnosis 10:549, 1990 11. Cohen BH, Lilienfeld AM, Huang PC: Genetic Issues in Public Health and Medicine. Springfield, Charles C Thomas, 1978 12. Committee for the Study of Inborn Errors of Metabolism: Genetic Screening: Programs, Principles and Research. Washington DC, National Academy of Sciences, 1973 13. Erbe R: Reproductive choices of couples at risk for CF [abstract]. Am J Public Health, 1991 14. Fletcher J: The Ethics of Genetic Control: Ending Reproductive Roulette. Garden City, NY, Doubleday, 1974 15. Fost N: Regulating genetic technology: Values in conflict. In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 16. Gross RH, Cox A, Tatyrek R, et al: Early management and decision making for the treatment of myelomeningocoele. Pediatrics 72:450-458, 1983 17. Hilton B, et al: Ethical Issues in Human Genetics. New York, Plenum Press, 1983 18. Holtzman N: Proceed With Caution: Predicting Genetics Risks in the Recombinant DNA ERA. Baltimore, Johns Hopkins Press, 1989
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19. 10M Committee on Perinatal HIV Screening. In Hardy L (ed): HIV Screening of Pregnant Women and Newborns. Washington, National Academy Press, 1991 20. Kaback MM, Zeiger RS: The Johns Kennedy Institute Tay Sachs Program: Practical and ethical issues in an adult genetic screening program. In Condliffe P, Callahan D, Hilton B (eds): Ethical Issues in Genetic Counseling and the Use of Genetic Knowledge, New York, Plenum Press, 1972 21. Karp L: Genetic Engineering: Threat or Promise. Chicago, Nelson-Hall Inc, 1976 22. Milunsky A, Annas GJ: Genetics and the Law III. New York, Plenum Press, 1985 23. Farrell PM, Mischler EH: Newborn screening for cystic fibrosis. Advances in Pediatrics, 1992, in press 24. President's Commission for the Study of Ethical Problems in Medicine and Biomedical and Behavioral Research: Splicing Life. Washington DC US Government Printing Office, 1982 25. Purdy LM: Genetic diseases: Can having children be immoral? In Buckley JJ (ed): Genetics Now: Ethical Issues in Genetic Research. Washington DC University Press of America, 1978 26. Research Group, Institute of Society, Ethics, and the Life Sciences: Ethical and social issues in screening for genetic disease. New Engl J Med 286:1129-1132, 1972 27. Robertson JA: Genetic alteration of embryos: The ethical issues. In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 28. Rosenberg LE: Can we cure genetic disorders. In Milunsky A, Annas GJ (eds): Genetics and the Law III. New York, Plenum Press, 1985 29. Stamatoyannopoulos G: Problems of screening and counseling in the hemoglobinopathies. In Motulsky AG, Lenz W (eds): Birth Defects Proceedings of the 4th International Conference. Amsterdam Excerpta Medica, 1974 pp 268--276 30. Wertz DC, Rosenfield JM, Janes SR, et al: Attitudes toward abortion among parents of children with cystic fibrosis. Am J Public Health 81:992-996, 1991 31. Wilfond BS, Fost N: The cystic fibrosis gene: Medical and social implications for heterozygote detection. JAMA 263:2777-2783, 1990 Address reprint requests to
Norman Fost, MD, MPH Clinical Genetics Center, Room 353 University of Wisconsin 1500 Highland Avenue Madison, WI 53706
