Ethical and Legal Issues of Fetal Research: History and Background1
Ethics and Fetal Research: Past, Present, and Future
JOHN C. FLETCHER
Center for Biomedical Ethics, University of Virginia Charlottesville, Virginia
Fetal research has been the dominant conflict in research ethics since the early 1970s. Fetal research can be categorized as therapeutic or investigative, involving a possibly viable or a nonviable fetus. The most controversial area, which has influenced all aspects of the debate, involves research affecting the fetus in elective abortion.
Beginning with the deliberations of the Peel Commission in the United Kingdom in 1972, and the United States National Commission for the Protection of Human Subjects from 1973 to 1974, three distinct ethical positions arose:
Selectively higher research risks are permitted when abortion has been elected than when the fetus is wanted, based on the moral view of the pregnant woman as the primary decision maker in elective abortion, whose consent is required for research related to scientific and medical goals of benefit to society.
Opposition to all investigative research in the context of abortion, based on the premise of the fetus as child: if the research will not benefit the child directly, the child is being exploited and the research is not morally justified.
A "Golden Rule" position, adopted in the United States, based on the concept of equal protection of wanted and unwanted fetuses, with research limited to "minimal risks" and exceptions permitted only after review by an Ethics Advisory Board (EAB) and a waiver of restrictions by the Secretary of Health and Human Services.
Up to 1980, the role of the U.S. government in relation to research ethics was primarily that of patron of public discourse. During the 1980s, in a political climate influenced by antiabortion sentiment, the government dismantled most of the public process for debate and resolution, including the EAB. Federal support of fetal tissue transplant research was placed under an "indefinite moratorium" (lifted by President Clinton in 1993). As a consequence, there has been essentially no federally funded embryo or in vitro fertilization research.
Every major question related to fetal research in the United States (and many aspects of research with other vulnerable populations such as children, prisoners, and the mentally ill or impaired) needs reexamination and new policy parameters. A critical question for the future of research is whether selectively greater investigative risks are justified in instances of elective abortion, especially in the first trimester of pregnancy. Up to the present time, National Institutes of Health researchers have not been permitted to investigate the causes of cancer in human embryos obtained after in vitro fertilization (IVF). Yet, experiments with living children involving more than minimal risk, without prospect of direct benefit to the subjects but with the possibility of deriving greater knowledge about their disorders, have been allowed. The ability to transfer genes into fetal cells for therapeutic trials calls for new studies of the natural history of genetic diseases, including genetic causes of cancer. An Ethics Advisory Board to the Secretary of Health and Human Services should be restored to serve as an ongoing resource in an overall reevaluation of research ethics, beginning with fetal research.
FEDERAL AND STATE REGULATIONS OF FETAL RESEARCH: A CURRENT PERSPECTIVE2
LORI B. ANDREWS
American Bar Foundation, Chicago, Illinois
In 1971, medical investigators in Massachusetts undertook an experiment to learn how pregnant women metabolize certain antibiotics and whether the antibiotics cross the placenta. The research involved women planning to abort, who had consented to administration of the drugs. Specific consent had not been requested, however, for subsequent analyses of the aborted fetuses to determine
the effects of the antibiotics. After the study was published, an indictment was brought against the scientists under an 1814 grave-robbing statute. Although the criminal prosecution was later dismissed, the fact that it was brought at all indicates how politically charged the area of fetal research has become in the wake of Roe v. Wade, with significant consequences at the state level.
In addition to federal laws governing research on the unborn, 24 states have widely varying laws concerned with one or more of the following considerations:
Purpose: Is the research intended to benefit the fetus, the mother, an infertile progenitor, or a tissue recipient, or is its purpose to acquire general scientific or medical knowledge?
Effect: Does the research impose a risk to the life or health of the fetus? If so, what are the likelihood and the seriousness of risk?
Relation to abortion: Does the research involve a fetus before, during, or after an induced abortion?
Fetal location: Is the fetus in the womb or outside it?
Stage of development: Has the fetus reached the stage at which it has acquired characteristics that warrant specific protection, such as the capacity for experiencing pain?
Who in fact is the beneficiary of research is a significant question often ignored by federal regulations and state statutes. Possible beneficiaries range from the pregnant woman or the fetus, to a couple, a fetal tissue transplant recipient, or the public at large. Particularly difficult issues arise when pregnant women are treated for illnesses with treatments that, although not experimental for the women, have unknown effects on the fetus and may, thus, be considered experimental for the fetus. Nine states define in utero research so broadly as to include just such a circumstance. Ironically, the research necessary to determine the fetal effects of many "standard" treatments has simply not been permitted. Roe v. Wade upheld the primacy of a woman's concern for her life and health, including her psychological health. Nonetheless, federal regulations regarding research (as opposed to therapeutic interventions) say that, even if an intervention may benefit the woman, it is permissible only if risk to the fetus is minimal.
With regard to the fetus itself, federal regulations distinguish between therapeutic and nontherapeutic activities, but six states do not, thereby potentially prohibiting innovative therapies even to save the fetus's life.
Research beneficial to the couple includes techniques for initiating pregnancy or for gathering information about the fetus. Such research has led to prenatal diagnostic techniques to detect the presence of genetic disorders (e.g., chorionic villi sampling, developed through research on patients planning first trimester abortion), now widely used to help a couple to decide whether or not to continue a pregnancy. Yet, seven states have laws that prohibit experimental prenatal diagnostic procedures on the fetus. Although in vitro fertilization is no longer considered experimental, some of its adjuncts are, including cryopreservation of
embryos for subsequent implantation or embryo donation to an infertile recipient. State laws that interfere with a couple's reproductive decisions by banning prenatal screening or infertility treatments, or that constrict the treatment options of a pregnant woman, have been struck down as unconstitutional by federal courts in Louisiana and Illinois.
The abortion controversy has had tremendous impact on the debate over fetal tissue transplantation research. Specific concerns include the fear that women will conceive and abort in order to donate tissue for treatment of an ailing loved one. To address this concern, an advisory panel of the National Institutes of Health (NIH) has recommended prohibition of the sale of fetal tissue or designation of a specific tissue recipient.
During the moratorium, one proposal was to establish a fetal tissue bank with tissue obtained from spontaneous abortions. Even in this circumstance, however, federal regulations defer to state law with regard to research on dead fetuses. Of 14 states that have dealt with this issue, nine allow such research with certain provisions for parental consent; four states permit only pathological examination or autopsy. Other states have regulations that echo the NIH recommendations. In states without specific regulations, decisions are based on the state's interpretation of the Uniform Anatomical Gifts Act.
Some of the greatest controversy occurs when the potential beneficiary of fetal research is less identifiable, especially the public at large. Although much information of medical relevance can be obtained through animal research, human research is ultimately necessary. Humans differ from animals. In rubella vaccination trials in monkeys, the vaccine did not cross the placenta; in human trials it did, and was therefore deemed unsafe for use with pregnant women. Many of the data that confirmed the efficacy and safety of amniocentesis were obtained from research involving fetuses prior to abortion. Of the 24 states with fetal research statutes, 12 either prohibit or seriously restrict general scientific research in utero and 18 prohibit it ex utero.
In the focus on federal research policies and funding mechanisms it is often overlooked that the legality of research involving embryos and fetuses has fallen mainly under the domain of state laws. These laws are not finely tuned and generally do not take into consideration the varied policy concerns that might be raised, based on the nature of the research and its intended beneficiary. The distinction, however, cannot be ignored by those directly involved in the research enterprise, regardless of their sources of support. For some researchers, the state in which they work will ultimately determine what experiments they may and may not undertake.
OPEN DISCUSSION PERIOD
The discussion began with an overview of the present state of regulation of fetal research in the United Kingdom. The Governmental Human Fertilization
Embryology Act allows British researchers a large degree of freedom in line with the first ethical position, based on the moral view of the pregnant woman as the primary decision maker. To aid research, the Medical Research Council maintains a tissue bank to collect and prepare fetal tissue for research.3
It is unclear where initiative for change in the United States will come from, but discussants agreed that the public is generally receptive to the goals of fetal research to lessen or alleviate serious health problems. It was further argued that scientists have a responsibility to interact with legislators and the public to help create the conditions for meaningful change. The difficulty of achieving such change, however, can be seen in the current state of organ transplantation. Repeated surveys have shown overwhelming public approval of organ transplantation. Yet, there are still no effective procedures for obtaining an adequate supply of organs, a problem that would be even more difficult for fetal tissue transplantation. Another special characteristic of fetal tissue banks is quality. In recently established tissue banks that are limited to spontaneously aborted fetuses, the material is frequently found to be abnormal or infected and, consequently, of little value for therapy or research. A necessary, but fundamental, change would be to establish tissue banks for the storage of normal, therapeutically useful tissue from elective abortions.
It was clear from the discussion that many ethical questions will reemerge. For example, does a woman seeking an abortion have the right to know everything that will be done to her fetus in a research project, based on the possibility that particular kinds of research might be objectionable to her? With the federal funding mechanisms for fetal research being reconstituted, it appears that such questions will again become the grist for public debate.