The year is 2016. J and K meet with their pediatrician to discuss whether their 11-year-old daughter, L, should undergo a newly available course of stem cell therapy to cure her type 1 juvenile diabetes. Left untreated, L’s illness could lead to blindness, life-threatening circulation problems in her extremities, and, perhaps, early death. The therapy that L’s parents and her pediatrician are contemplating requires careful HLA (immunological compatibility) matching with one of the thousands of human embryonic stem cell (hESC) lines identified in an international registry. These were created over the previous decade from frozen human embryos remaining from infertility procedures and were donated to research or therapy by their progenitors. A matching population of specially created pancreatic stem cells could be made from one of these lines and infused into L to remedy her insulin deficit. While many parents would leap at this life-saving opportunity, J and K – and their physician – face a moral quandary. They are all devout Roman Catholics and share their church’s view that human life must be regarded as sacred from the moment of conception. They view the destruction of a human embryo for stem cell research or therapy as equivalent to killing a human being. The physician explains to J and K that the frozen human embryos used to create hESC lines were slated for destruction. Is it not better, he asks, that such embryos at least be used to save lives? But J and K are also aware of their church’s moral teaching that “one should not do evil in order that good may result.”
Any research that uses human embryonic or fetal tissues, or that implicates living human embryos or fetuses, comes under the heading of embryo or fetal research. Such research can be direct or indirect. The use of living human embryos to derive a line of embryonic stem cells is an example of direct research on the embryo, as is research on a non-viable fetus that has survived abortion or miscarriage. Research aimed at the healthcare needs of a pregnant woman that could inadvertently affect the embryo or fetus she is carrying is an example of indirect research.
Because different questions can arise depending on whether research involves embryos or fetuses, it is important to state what we mean by the fetus or embryo. For scientific purposes, the embryo is usually defined as the product of conception until eight weeks of gestation. From that point onward, the term fetus is used. However, these definitions are not pertinent to the major legal and ethical debates about research. The important distinction here is between entities produced by in vitro fertilization (IVF) and existing outside the womb and those that have implanted in a womb, where research necessarily implicates the gestational mother. Following Tauer (2004) and others (Gratton, 2002, p. 17), I will define the embryo as “the product of conception (whether produced in vitro or flushed from a uterus) as it exists in the laboratory and that has not undergone transfer to a woman.” The fetus is “the product of conception existing in a womb” and comprises both in vivo embryos and fetuses. These definitions bypass the question of the organism’s developmental stage. However, since it is not possible to culture an embryo in vitro for more than five or six days, a limit not likely to be exceeded soon, the term “embryo” as used here describes the early product of conception, a mass of largely undifferentiated cells with no bodily form or organs, while the term fetus usually refers to a more developed entity undergoing organogenesis and possessing an incipient nervous system.
A further question is when an embryo can be said to have come into being. Although many people speak of the “moment of conception,” it is now well established that conception/fertilization is not a discrete event but a process that takes places over many hours or days (President’s Council on Bioethics, 2004). There are at least several candidate “events” for conception/fertilization, ranging from sperm penetration of the egg to syngamy, the lining up of male and female pronuclei inside the egg, almost a day later. The choice among these can significantly alter our moral and legal conclusions with regard to specific research protocols. It is important to recognize that a biologically and morally informed choice is necessary here and that conception/fertilization is not the “bright line” that many people believe it is.
A different problem concerns the nature and moral status of the entities produced by nuclear transfer cloning technology. This approach, known as therapeutic cloning, is being researched for the production of immunologically compatible stem cell lines. It involves inserting a patient’s own cell into an enucleated egg, and chemically or electrically stimulating the egg to divide like one that has been normally fertilized. The resulting embryo is then disaggregated to produce a stem cell line that can be used for tissue repair or organ replacement in the original cell donor without rejection (Lanza et al., 2000). Since the entity produced in this way has never been fertilized by a sperm, some ask whether it should even be regarded as a human embryo (Kiessling, 2001). Richard Hurlbut, an opponent of human embryonic stem cell research, has also recently proposed using cloning technology combined with genetic engineering to produce an embryo incapable of developing beyond the earliest stages of growth, an approach known as “altered nuclear transfer” (President’s Council on Bioethics, 2005). Since this developmentally incompetent embryo could never become a human being, Hurlbut argues, its destruction for stem cell purposes would not be morally objectionable (Cook, 2004). Others have criticized these alternatives as definitionally inadequate or as not really eliminating the moral objections to human embryonic stem cell research (Melton et al., 2004).
Research directed primarily at the health needs of fertile or pregnant women is likely to implicate a developing fetus. In such cases, it is necessary to balance possible risks and benefits for the woman with risks or benefits to the fetus. This consideration has long made fetal research an important area of ethical inquiry, leading to regulations in many jurisdictions that seek to balance maternal and fetal claims. Direct research on the fetus has also been pursued in the effort to reduce the incidence of miscarriages or birth defects. Specific health problems affecting embryos or fetuses, such as the impacts of drugs, diagnostics, nutrition, or regimens of prenatal care have required direct fetal research with its attendant ethical questions. Recently, in utero fetal surgery for spina bifida has raised questions concerning how we should balance maternal and fetal claims in a research or clinical context (Howe, 2003; Bliton, 2005).
Fetal tissue transplantation research has also long been an object of medical interest. Fetal neural tissue has been used, with mixed results, in the treatment of Parkinson disease and other neurological disorders (Freed et al., 2001). With the discovery that fetal germ cells are able to differentiate into a variety of other tissues (Shamblott et al., 1998), the issues raised by fetal tissue transplantation research have reappeared in connection with embryonic stem cell research.
Today, the most intensely debated issues arise in connection with human embryonic stem cell research. The creation of stem cell lines for use in regenerative medicine research currently requires the destruction of human embryos. This raises questions about the moral status of the early human embryo and when, if ever, nascent human life may be sacrificed for the medical benefit of children and adults. Research is underway on non-destructive methods of stem cell derivation (Chung, 2006), and, as mentioned above, some theorists have offered controversial proposals for alternative ways of generating stem cells that they believe could reduce or eliminate the moral issues raised by embryo destruction (President’s Council on Bioethics, 2005). However, the availability of tens of thousands of frozen embryos remaining from infertility treatments as a resource for stem cell research suggests that this issue will not go away. In addition, researching some of these alternatives may require the destruction of human embryos.
Three distinct research areas come under the heading of fetal research: (i) direct research on the fetus itself, (ii) research directed toward pregnant women or the condition of pregnancy (for which the fetus is an indirect subject of research), and (iii) fetal tissue transplantation research. For each of these research areas, current US regulations identify the major moral issues involved and, with one or two exceptions, also reflect the international moral consensus on these issues (Green, 2002a).
Where direct research on the fetus itself is concerned, the US Code of Federal Regulations distinguishes between research of medical benefit to a particular fetus and research not to its benefit. In the former case, the risks must be “the least possible for achieving the objectives of the research” (US Department of Health and Human Services, 2005). In the latter case, institutional review boards can approve a protocol if the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means. Examples are minor changes in maternal diet or the use of ultrasonography.
Regulations in the USA, and most other nations, do not distinguish between a fetus destined for abortion and one meant to be carried to term. At first sight, it might seem reasonable to permit some degree of increased risk when the termination of the pregnancy is in prospect and when useful research can be done. An example is an experiment to see whether an agent likely to cause birth defects passes through the placenta. However, endangering the fetus in such cases will either limit a woman’s freedom to change her mind about the abortion or will result in harm to a born child if she should choose to continue the pregnancy. The unacceptability of either of these alternatives counsels a standard of similar treatment of all fetuses.
Direct research on the fetus can also take place on the fetus outside the womb following a spontaneous or induced abortion. A viable fetus is treated by existing US regulations as a premature infant and comes under the protections of regulations governing research on children or newborns. A non-viable fetus (or neonate) may be involved in research only if (i) the vital functions of the neonate will not be artificially maintained, (ii) the research will not terminate the heartbeat or respiration of the neonate, (iii) there will be no added risk to the neonate resulting from the research, and (iv) the purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means (US Department of Health and Human Services, 2005).
Since fetuses normally have male and female progenitors, the question arises as to whose consent is required for such research. The need for the mother’s consent is evident and is recognized in all jurisdictions. Perhaps reflecting heated debates in the USA on maternal–paternal consent for abortion, the father, as co-progenitor, is also required to consent on behalf of the fetus. However, federal regulations permit three exceptions to this rule: if the father is unavailable, incompetent or temporarily incapacitated, or the pregnancy resulted from rape or incest (US Department of Health and Human Services, 2005).
Research directed at women who are pregnant can also indirectly affect the fetus. The US federal regulations specify that no pregnant woman may be involved as a research subject unless either (i) the purpose of the activity is to meet the health needs of the mother, and the fetus will be placed at risk only to the minimum extent necessary to meet such needs; or (ii) the risk to the fetus is minimal (US Department of Health and Human Services, 2005). Since some procedures, drugs, or dosage levels may enhance maternal outcomes while increasing fetal risk, these regulations can require institutional review boards to weigh the mother’s welfare against that of the fetus.
Fetal transplantation research is currently allowed in many jurisdictions, including the USA and UK. Since the mid 1990s, a strong international consensus has emerged about the conditions for good clinical practice regarding this (de Wert et al., 2002). These aim at separating the motives and timing for the abortion decision from the decision to donate fetal tissue, and they preclude commercialization of the tissue. There are voices that entirely reject this international consensus on the grounds that fetal tissue transplantation either encourages abortion or involves wrongful complicity in it. The Roman Catholic Church and some conservative Protestant groups hold these views (de Wert et al., 2002).
Public debate about embryo research began in earnest in 1978 with the birth of Louise Brown, the world’s first “test tube” baby. The development of IVF made the early, ex utero embryo a possible research “subject,” but, additionally, the rapid growth of infertility medicine created demand for more successful and less risky infertility treatments, intensifying the demand for embryo research (Green, 2001). The development of the first human embryonic stem cell lines by James Thomson and John Gearhart in 1998 (Thomson et al., 1998; Shamblott et al., 1998) opened up new uses for human embryos in the area of regenerative medicine research.
Unlike fetal research, where the welfare of born children and women complicates matters, embryo research unavoidably raises the question of how much protection nascent human life deserves. Two main ethical answers to this question have been proposed. One, strongly associated with the views of conservative religious groups, holds that human life deserves full moral protection from conception onward. This places the earliest embryo (and fetus) on a plane of equality with child and adult subjects and rules out embryo research that is not medically to the benefit of the embryo under study (Sacred Congregation for the Doctrine of the Faith, 1974; Pontifical Academy for Life, 2000).
Opposing this position is a range of views that can be termed “gradualist” or “developmental.” Some views stress the moral importance of qualities like sentience, brain activity, the presence of substantial bodily form, or the ability to survive independently of the mother (viability). Others emphasize not one but a variety of considerations that, taken together, compel us to extend protections (NIH Human Embryo Research Panel, 1994; Warren, 1997). What all these views have in common is the belief that the moral weight of the embryo and fetus is not established once and for all, but rather it increases over the course of a pregnancy as additional morally significant features make their appearance. Most who hold this view are willing to permit embryo research, including research that destroys the embryo, up to 14 days of development. At that time, the primitive streak appears, organ formation begins, and further morally significant developmental events cannot be ruled out.
Most legal jurisdictions permit carefully regulated direct or indirect research on the human fetus and many also permit fetal tissue transplantation research. The legal treatment of human embryo research is much more diverse. In 1990, the British Parliament passed the Human Fertilisation and Embryology Act, which led to the establishment of the Human Fertilisation and Embryology Authority, an official government agency that provides oversight and guidance for clinical and research programs in infertility medicine. In its current activities, the agency oversees and licenses all clinical infertility programs in the UK, as well as research on human embryos. Regulations in the UK are at once the most comprehensive and the most permissive in the world. Embryo research is permitted for a wide variety of reasons (Human Fertilisation and Embryology Authority, 2003), and therapeutic cloning research is allowed.
The situation in the USA is very different. Federal funding for any research requiring the destruction of human embryos is prohibited by law (Green, 2001). At the same time, except for some restrictive state laws, private sector research on embryos in the US is unregulated, unlike the UK where all research falls under the authority of the government agency. Despite this relative research freedom, the absence of federal support for human embryo research in the USA, a country with over 450 infertility programs, has contributed to the inefficiency and high cost of IVF (Neumann et al., 1994; Chambers et al., 2006). It has also increased the risks to women undergoing these procedures (Rossing et al., 1994; Rebar, 2002) and the children produced by them (Jones and Schnom, 2001; Kovalesky et al., 2003; Powell, 2003). The US regulations have blocked most federal funding for human embryonic stem cell research and slowed the pace of that research (Dreifus, 2006).
Similar diversity of legislation is also evident on the international scene. Some nations (for example, Israel, Singapore, China, and India) permit or even fund embryonic stem cell research, while others (Ireland, Italy, and Germany) forbid it (Hoffman, 2004). Religion is a driving force in these differences. Nations with large Roman Catholic or evangelical Christian populations tend to oppose human embryonic stem cell research, whereas nations with non-Christian populations or fewer conservative Protestants or Catholics tend to be more supportive (Walters, 2004).
Since it is unlikely that moral positions on fetal or embryo research will change in the near future, a resolution of these debates may partly hinge on a series of science and technology policy determinations. Among these is the possibility of developing alternatives to the use of human embryos or fetuses in regenerative medicine research. This might include the use of adult stem cells or alternatives to the derivation of stem cells from spare human embryos. Recently, there has been considerable debate about the viability of these alternatives as a way of bypassing the current stem cell impasse and, in the USA, legislation has been proposed to encourage these directions (Hulse, 2006).
A second policy issue raised by embryo research concerns which considerations should guide public policy. Is it possible to separate one’s personal moral or religious views from the question of what should be appropriate public policy in a democratic society where citizens hold very different moral beliefs?
Finally, those who oppose research involving the destruction of embryos or fetuses will have to determine the extent to which they are prepared to benefit from the fruits of this research. Are they prepared to use stem cell lines derived from human embryos or vaccines made with fetal tissues? At what point does use become complicity and how does one form public policy in this area (Green, 2002b)? Germany and Italy currently ban the derivation of embryonic stem cell lines, but permit the clinical or research use of lines created before the dates that these bans went into effect. Although US President George Bush opposes research destroying human embryos, he authorized the use of stem cell lines created before the imposition of his restrictive policy. These and other cases reveal how complex are the issues raised by morally controversial but potentially beneficial research.
Now that embryonic stem cells have demonstrated curative potential, J and K and their physician will have to re-examine the bases of their opposition to the medical uses of human embryonic stem cells. Does the privileging of early embryos over more developed human beings really make sense? The pediatrician can also play a useful role by making clear how pervasive and difficult is the question of the extent to which we are prepared to help ourselves or others by using the fruits of deeds we morally oppose. For example, versions of the polio vaccine, which most citizens hailed as a major advance in human health, were prepared from cell cultures grown on the tissues of aborted fetuses. Each individual must determine where he or she will draw the line between benefiting from wrongful deeds and complicity in them.
This chapter is adapted from: Green, R. M. (2008). Research with fetuses, embryos, and stem cells. In The Oxford Textbook of Clinical Research Ethics, ed. E. J., Emanuel, G., Grady, R., Lie, F., Miller, and D. Wendler. New York: Oxford University Press, in press.