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This article reviews the evolution of ethical problems in the first generation of experimental fetal therapy and the prevailing approaches to them. The problems include: review of risks/benefits, case selection, informed consent, twin pregnancies, and refusal of proven fetal therapy. The article further discusses ethical and public policy issues in the lack of U.S. federal support for fetal diagnosis, fetal therapy, and human embryo research. An argument is made for such support, beginning with experimental gene therapy in the fetus. Ethical principles are identified that support an obligation to learn to relieve and treat such human suffering at the earliest time. Contradictions of these principles are also identified in terms of research not now supported.

The progress of genetic knowledge magnifies existing ethical problems in medical genetics. Among the most troubling types of problems -- for medicine, patients, and the larger society -- are those of privacy and disclosure. Examples of the range of problems involving privacy and disclosure are: 1) disclosure of false paternity to an unsuspecting husband; 2) disclosure of a patient's genetic make-up to his or her unknowing spouse; 3) disclosure of information, against a patient's wishes, to relatives at genetic risk; 4) disclosure of ambiguous test results; 5) disclosure of adventitious nonmedical information, e.g., fetal sex; and 6) disclosure to institutional third parties, such as employers and insurers....

The ethical attitudes of health care providers toward abortion, sex selection, and selective termination of normal and anomalous fetuses in singleton or multiple pregnancies were evaluated by questionnaires distributed to members of the American Society of Human Genetics, the International Fetal Medicine and Surgery Society, the Society of Perinatal Obstetricians, ethicists, and clergy. Demographic characteristics of respondents exhibited a preponderance of men (76%), age greater than 40 (68%), and of United States residents (82%). Seventy-nine percent of respondents were in the medical profession. Approximately half of the respondents were Protestant, the rest being evenly distributed among Catholic, Jewish, and other religions. Acceptance of abortion for social indication varied by religion and gestational age but not by religious conviction, age, country, or gender of respondent. First-trimester abortion of a normal singleton pregnancy was considered more acceptable than selective termination of normal fetuses in multifetal gestations. Sex selection was considered unethical by most respondents. Selective termination was deemed ethically appropriate in quadruplets or multifetal gestations of more than five fetuses and in multiple pregnancies bearing one anomalous fetus. In the latter situation, acceptance increased with the severity of fetal anomalies and decreased from the first to the third trimester. The medical specialty of respondents was the only independent factor strongly associated with acceptance of selective termination by trimester, indication, and number of fetuses. Acceptance of selective termination among health care professionals appears to reflect not only perceptions of procedure-related risks and benefits in the index pregnancy but also individual training and religious beliefs.

... Every hospital needs a policy statement devoted to confidentiality. This task is a good assignment for a hospital ethics committee. In drafting such a statement, one area that should not be overlooked is respect for confidentiality in cases used for teaching, patient conferences, and interdisciplinary meetings, including the teaching of clinical ethics! The University of Virginia's (UVA) Hospital Ethics Committee is considering a new policy statement on confidentiality....

A critical analysis is undertaken of the ethical debate on two general classes of research activities that bear on the future of human gene therapy: (i) the human fetus and (ii) the preimplantation human embryo after in vitro fertilization (IVF). The conclusion is that the hope of human gene therapy and of other clinical applications of the human genome initiative is in danger because of the obstacles to research in reproductive biology and human genetics in the federal sector.

We will set the stage for our analysis by reviewing selected medical aspects of anencephaly, outlining the history of the use of anencephalics as organ sources, and summarising the results of an important study recently completed at Loma Linda University. We will then employ some of the arguments and justifications underlying the Uniform Determination of Death Act (UDDA) to claim that anencephaly is morally equivalent to brain death, i.e., the reasons for considering brain-dead patients to be dead also apply to anencephalics. Finally, we will critique our proposal and discuss its implications.

Assisted reproductive technologies have aided thousands of couples, but complications have resulted in multifetal pregnancies creating a bitter irony for infertility patients. In an effort to increase the rate of intact survival, we have successfully performed transabdominal first-trimester selective termination procedures on 22 pregnancies including one octuplet, five quintuplet, twelve quadruplet, and four triplet gestations. There have been eight sets of twins, and two singletons delivered, seven twin pregnancies are ongoing, and one early and four late losses of pregnancies. With experience we now counsel as to a high likelihood of a technically successful procedure, but we still have concerns for late losses. We have tried to balance the arguments about the direct harms of performing selective termination and the obstetric risks of not performing selective termination. We believe that selective termination should not be considered a "social" procedure. Our data do not yet make clear whether one, two, or three is the optimal number of embryos to leave. Therefore, on the basis of both current obstetric risk factors and ethical reasoning we will continue to support our protocol of optimally leaving twins.

To provide a basis for international discussion of ethical problems, we studied responses of medical geneticists in 18 countries to questionnaires about 14 clinical cases and five screening situations. Of 1,053 asked to participate, 677 (64%) responded. There was greater than or equal to 75% consensus on five cases involving (1) disclosure of (1) conflicting diagnostic findings, (2) disclosure of ambiguous results, (3) disclosure of controversial interpretations, (4) protection of mother's confidentiality in cases of false paternity, and (5) nondirective counseling about 45,X and XYY syndrome. A majority (51%-60%) would disclose the diagnosis to relatives at risk for Huntington disease or hemophilia A, against the patient's wishes; would disclose which parent carries a translocation causing Down syndrome; and would disclose XY genotype in a female. As reproductive options for patients with disorders not diagnosable prenatally, 84% would discuss artificial insemination by a donor, 66% would discuss in vitro fertilization with donor egg, and 46% would discuss surrogate motherhood. In all, 85% would perform prenatal diagnosis for (or would refer) parents who refuse abortion, 75% for maternal anxiety, and 42% for selection of fetal sex. Screening questions showed that 72% believed that workplace screening should be voluntary and that results should be confidential.

Ethical issues generally evolve through four stages: threshold, open conflict, extended debate, and adaptation. The history of the ethical debate on human gene therapy is examined. The threshold was the Nirenberg appeal in 1967. The open conflict centered around two early controversial cases: those of Rogers and Cline. The extended debate has lasted from 1980 to the present, but now adaptation, i.e., a public policy, for somatic cell gene therapy is emerging.

The federal moratorium on fetal tissue transplantation research is creating an ever growing wall of separation between public and private research. This federal policy is based on undocumented psychological assumptions about what motivates women to have abortions, neglects to consider the suffering that could be prevented by allowing such research, disregards the fact that other forms of fetal research are performed at federal expense, infringes on the scientific freedom of federally employed scientists and compromises the federal government's ability to control the quality of research. Efforts must be made to legally dismantle this wall before it further impedes the goals of medical research.

The approaches of 295 medical geneticists in the United States to 14 clinical problems and 3 screening situations that required a moral choice are summarized. These data are part of a survey of 682 geneticists in 19 nations. Of 490 U.S. geneticists asked to participate, 295 (60%) returned anonymous detailed questionnaires. There was strong (greater than 75%) consensus that preserving the mother's confidentiality overrides disclosure of true paternity; that conflicting test results, new/controversial interpretations of results, and ambiguous/artifactual results should be disclosed; that artificial insemination by donor, adoption, taking chances, contraception, sterilization, and in-vitro fertilization with a donor egg should be presented as reproductive options to carriers of disorders not diagnosable prenatally; that prenatal diagnosis should be performed for patients who refuse abortion and for maternal anxiety in the absence of medical indications; that screening in the workplace should be voluntary. There was no consensus about disclosure of a diagnosis of Huntington disease or hemophilia A to relatives at risk, against the patient's wishes, or about disclosure of parental translocations. Geneticists in the U.S. differed from 18 other nations in presenting surrogate motherhood as an option (67%); willingness to perform prenatal diagnosis for sex selection or refer (62%); and disclosure of XY genotype in a female (62%). Men were more likely than women to say that they would give directive counseling. Women were more likely than men to say that they would perform prenatal diagnosis for maternal anxiety or for sex selection.

As the potential for the first human trials of somatic cell gene therapy nears, two ethical issues are examined: problems of moral choice for members of institutional review boards who consider the first protocols, for parents, and for the clinical researchers, and the special protections that may be required for the infants and children to be involved, and ethical objections to somatic cell therapy made by those concerned about a putative inevitable progression of genetic knowledge from therapy to mass genetic engineering in human reproduction. The author's viewpoint is that a consensus exists on the required moral approach to somatic cell therapy, but that no moral approach yet exists for experiments beyond this level, especially in the germline cells of human beings.

This paper reviews past, present and future social and ethical considerations of screening carriers of autosomal disorders and other heterozygotes. A body of ethical and social guidance has evolved in the 1970's and 1980's for screening. The values of voluntaristic participation and informed consent are high. The goal of programs should be to provide couples, families, and individuals with knowledge respecting their reproductive choices. The dangers are coercive strategies, stigmatization, and careless communication of risk information. It is assumed that the number of autosomal carrier states that are screenable will undoubtedly increase as will states of heterozygosity that cause susceptibility to common diseases. Before the end of the century, something approaching a "biopsy of the human genome" will be a practical reality. To balance the potential for harmful psychological and social effects of so much new genetic knowledge, new efforts must be made to find treatments for progeny affected by recessive disorders. Maternal and paternal screening, prenatal diagnosis and treatment will be increasingly linked in the future. This paper will report on a case of fetal therapy for congenital adrenal hyperplasia as a paradigm for the future. The argument will be made that society ought to put a higher priority on prenatal care and prevention of disorders of prematurity than genetic disorders with a low frequency, lest genetic screening be distorted by unfounded concern about eugenics.

The argument of this paper is that sex selection, except to avoid sex-linked disorders, is unethical. Two reasons are given: 1) Prima facie examination of any argument for sex selection cannot overcome the unfair and sexist basis of a choice to select the sex of a child. The desire to control the sex of a child is not rational, since any claim that is made for the parents' preference for one sex can be demonstrated to be provided also by the other sex. 2) On an examination of the consequences of sex selection, if it were practiced by parents in significant numbers, the harmful consequences would far outweigh the few fleeting beneficial consequences. The hypothesis that sex selection might reduce population in less developed or overpopulated nations cannot be demonstrated without violation of ethical principles of fairness and beneficence. The paper clarifies and, to an extent, revises a position taken earlier by the author on sex selection by amniocentesis. In an effort to argue that the motives of parents who desire to choose the sex of their child should not be singled out for harsh judgment in societies that allow abortion, the author's position about the ethics of sex selection itself was not directly stated. This paper attempts to strengthen the ethical content of the author's views and recommends a policy for physicians who receive requests from parents to assist them in sex selection.

Decisions not to start or to stop life-sustaining technologies raise the most frequent ethical problems in clinical and long-term care settings in the United States. At the University of Virginia Hospitals, 66% of the requests for ethics consultation concern decisions to forego treatment. The decision is especially hard in cases when death is the only alternative to starting or stopping treatment that is costly in pain and suffering as well as resources. The author presents five maxims, fitting five common dilemmas, to help guide the physician in making such decisions.

In order to provide a basis for international discussion of ethics among geneticists, we surveyed the responses of medical geneticists to a questionnaire describing 14 hypothetical cases that posed ethical dilemmas. The cases were selected through discussions with leading geneticists in 12 nations, as representative of the most difficult problems of moral choice experienced in practice. Six cases involved indications for prenatal diagnosis or disclosure of information. All medical geneticists in each of 18 nations were included. Of 1053 asked to participate, 677 (64 per cent) responded. A large majority (83 per cent) would perform prenatal diagnosis for parents who oppose abortion but request the service. A smaller majority (63 per cent) would do so for maternal anxiety, and a minority (25 per cent) would perform for sex selection in the absence of X-linked disease. Most would disclose conflicting controversial, or ambiguous test results, and two-thirds would disclose colleagues' differences of opinion.

Unless present trends change, in the next few years the public will see earlier and safer methods of prenatal diagnosis combined with more efficacious methods of fetal therapy. For some time to come, the power to diagnose will far outstrip the power to treat, but with sufficient research and resources, the 2 activities of fetal medicine will assume more balance. The effect of conjoining therapy to diagnosis will bring about a more ethical balance between the immediate risks and benefits of prenatal diagnosis. Abortion will not cease to be a controversial issue in the context of fetal medicine, but the ability to offer treatment to more affected fetuses will create more assurance that progress in diagnosis and treatment will not be halted due to legal and constitutional efforts to protect the life of the fetus. At the same time, special attention should be paid to the mother, father and extended family of the fetus diagnosed for a treatable disorder. Careful discussion and clear communication may prevent misunderstandings and surface family problems that could arise at the last minute to complicate the mother's consent to treatment. When the risks are significant for the mother and the benefits of treatment are unclear, there should be no suggestion or appearance of pressure on her to agree. The same principle should apply even when the risks to the mother are minimal and the benefits to the future child are unclear.

Anxiety level, perception of control over illness, stage of cognitive development, and stage of reasoning about illness were examined in pediatric oncology, obese, and healthy children and adolescents. Among the groups, there were no mean differences with regard to any of these measures. Older participants in the higher stages of cognitive development were higher on stage of reasoning about illness in general and their own illness than were younger and less cognitively mature participants. In the pediatric oncology and obese groups, participants higher on perception of control over illness were higher on stage of reasoning about illness in general and their own illness, in particular, than those lower on perception of control. Anxiety level was not related to stage of reasoning about illness, but participants higher on anxiety were lower on perception of control over illness. Clinical implications of the findings are discussed.

This article presents data from a study of 295 qualified medical geneticists in the United States. The study's objective was to determine the degree of consensus and variation among practicing medical geneticists about the major ethical problems of prenatal diagnosis. Based on the data presented, the argument has been made that most medical geneticists share a dominant moral approach on three major problems: abortion choices, controversial indications for fetal diagnosis, and problems in disclosure of ambiguous or disputed results. Ethical problems in selective termination in high-risk twin and multiple pregnancies need more study. A preliminary evaluation of the strengths and weaknesses of prevailing standards in prenatal diagnosis was also made. Three weaknesses were noted: neglect of the demands for fairness in access to and distribution of prenatal diagnosis in the United States, unpreparedness for society's growing concerns about developing trends in human genetics, and need for changes in non-directive counseling in order to appreciate the complexities that will accompany the introduction of proven new treatments for genetic disorders.

Of 1,053 medical geneticists in 18 nations 677 (64%) returned questionnaires on their views on the importance of seven goals of genetic counseling, the appropriateness of five directive/nondirective approaches to counseling, and their choices of action in four situations involving directive/nondirective counseling. The majority (92%-94%) regarded nondirective approaches as appropriate; their views on both goals and approaches were similar to those reported in an earlier survey of 205 genetic counselors in the United States. In clinical situations involving presentation of reproductive options to carriers of disorders not diagnosable prenatally, 74%-85% would present contraception, sterilization, taking one's chances, artificial insemination donor (AID), or adoption as options even if not asked; 66% would present in vitro fertilization (IVF) with a donor egg; and 46% (67% in the United States) would present surrogate motherhood. In regard to three situations involving fetuses with low-burden disorders (Turner syndrome, XYY, and a possible small neural tube defect), 84%-88% would counsel nondirectively. Stepwise logistic regression analyses on professional and personal background variables showed that gender was related, cross-nationally, to self-reported directiveness in counseling, with men more likely than women to regard directive approaches as appropriate, more likely to give advice about fetuses with low-burden disorders, and more likely to present either IVF with donor egg or surrogate motherhood as options. Social and ethical implications of this widespread acceptance of nondirective counseling are discussed.

21-Hydroxylase deficiency results in congenital adrenal hyperplasia and leads to masculinization of the external genitalia of affected females. This complication could be avoided if fetal adrenal gland function were suppressed. A woman with mild 21-hydroxylase deficiency whose previous female child had classic congenital adrenal hyperplasia with masculinization was given dexamethasone beginning at the tenth week of gestation. Maternal estriol and cortisol values indicated rapid and sustained fetal and maternal adrenal gland suppression. At 39 weeks' gestation, the patient was spontaneously delivered of a female neonate with normal external genitalia. Postnatal tests indicated the infant was a single heterozygote for 21-hydroxylase deficiency. This study demonstrates prolonged suppression of the fetal adrenal gland with dexamethasone and suggests it might prevent abnormal masculinization in fetuses with severe congenital adrenal hyperplasia.

A survey on mass screening was sent to 1,053 medical geneticists in 18 nations, of whom 677 responded. Three theoretical screening situations were proposed, screening in the workplace for genetic susceptibility to work-related disease, carrier screening for cystic fibrosis, and presymptomatic testing for Huntington disease. Of the respondents, 72 percent thought screening in the workplace should be voluntary, and 81 percent said employers should have no access without the worker's consent, including 22 percent who believed that employers should have no access at all. There was strong consensus in all but one nation that insurance companies should have no access to test results without the worker's consent, and strong consensus in two countries that they should have no access at all. Most (82 percent) believed that screening for cystic fibrosis should be applied to the entire population, but 18 percent believed that it should be applied primarily to Caucasians. In all, 66 percent of respondents believed that individuals at risk for Huntington disease should be told their test results only if they say that they wish to know, recognizing a "right not to know" whether they will develop the disease in later life. Twelve percent thought that spouses should have access to test results if they asked, and 26 percent thought that spouses should be informed of results even if they did not ask. Geneticists in all nations were vividly aware of the potential damage from third party access to results, especially access by insurance companies. They had little sympathy with insurers' needs to assess actuarially accurate premiums.