What Is the Moral Status of the Embryo?
In debates about the ethics of embryo research, the central ethical question historically has focused on the embryo’s “moral status” and whether the embryo is deserving of the same rights and protections as a child or adult person. This Committee Opinion is based on the view that although the preimplantation embryo merits respect, its moral status is not equiv- alent to that of a human being. Scientific informa- tion alone will never resolve questions about the embryo’s moral status. However, several distin- guishing features of preimplantation embryos inform the evaluation of the moral status of the embryo and, hence, the ethical arguments concern- ing embryo research. Figure 2 outlines the develop- ment of pregnancy from gamete to fetus, a path that
highlights the distinguishing characteristics of pre- implantation embryos:
1. Early embryonic cells are undifferentiated. Until the blastocyst stage, each cell is totipotent, hav- ing the capacity to differentiate into any of the cell or tissue types of the fetus or to form pla- cental and other extra-embryonic tissues. Each of the cells of the inner cell mass of the blasto- cyst is pluripotent, with the capacity to become any of the cell or tissue types of the fetus, but at this stage, these cells form a collection of undif- ferentiated cells rather than a unified organism. 2. Embryos at early stages lack individuation. This is evidenced by research demonstrating that, up to at least the 8-cell stage, one or more blas- tomeres can be removed from the embryo (eg, as for preimplantation genetic diagnosis [PGD]) and the remaining blastomeres can still produce a complete human being. Also, from the initial stages of cell division until the formation of the primitive streak, the embryo is capable of divid- ing into more than one entity (ie, twinning). Only after this period has differentiation of embryonic cells advanced to the point that sep- aration can no longer result in two or more indi- viduals (11–13).
3. The formation of the primitive streak at day 14
marks the beginning of the differentiation of cells into the various tissues and organs of the human body. Before the appearance of the
primitive streak, the cells of the embryo are undifferentiated and pluripotent. Recognizing this biologic landmark, many, now including the ACOG Committee on Ethics, have recommend- ed limiting embryo research to the first 14 days after fertilization.
4. If the preimplantation embryo is left or main-
tained outside the uterus, it cannot develop into a human being. Continuing potential for life
exists if, but only if, the embryo is transferred to the uterus for implantation (this potential will have important implications for the conduct of research and therapy involving embryos). If never implanted, development ceases. In the United Kingdom, regulations focus on implan- tation as a key to distinguishing moral status of in vitro and cloned embryos from that of an in vivo pregnancy (14). In the United States, feder- al regulations on fetal research apply from the time of implantation on (1).
Developmental Stage
Requisite or Resultant Developmental
Day Process* Cells/Structures Morphology
0 Oocyte Single germ cell
Sperm Single germ cell
1 Fertilization begins
Fertilization complete Zygote 1 cell (male and
(syngamy) after 24 hours female pronuclei)
2 Cell division begins Embryo 2 cells (nuclei)
Blastomeres (totipotential)
Genomic expression 4–8 cells
begins
Morula 8–16 cells
(compacted)
Blastocyst Multicellular
(inner cell mass and trophectoderm) 5 Implantation begins† or after 7 Differentiation begins or after
Cell division ends‡
8–9 Implantation complete§ Embryonic disc
or after
14–16 Embryogenesis begins; Primitive streak
differentiation has passed point of twinning
*Both in vivo and in vitro except as noted.
†In vivo—organizational structure as a blastocyst is requisite to beginning of implantation and persists after implantation (which may be
complete as early as 8–9 days after fertilization) until appearance of the primitive streak.
‡Cell division may end at any time in vivo or in vitro; it has not persisted in vitro beyond 6–9 days. §In vivo.
Why Pursue Embryo Research?
Most contemporary discussions about embryo research center entirely on the question of the embryo’s intrinsic moral status—whether or not the embryo meets specific criteria for moral personhood. Based on the understanding of the degree to which an embryo does or does not meet such criteria, these dis- cussions have taken a stand about the permissibility of options for embryo disposition. Bioethicist Patricia King has noted that human embryo research policy should do more than reflect mere abstract assertions about the moral status of human embryos. Rather, the moral underpinnings of human embryo research should be derived from a range of values, including the facilitation of human procreation, the advance- ment of applied scientific knowledge, the reduction of human suffering, and the protection of vulnerable persons from coercion and exploitation (15).
There can be no compelling argument for embryo research without the promise of benefit. Potential benefits of embryo research include an improved understanding of fertilization, implanta- tion, and early pregnancy biology and, with this understanding, possibly fewer undesired outcomes, such as miscarriage. For infertile couples, embryo research offers the possibility of more effective therapies: research efforts helped optimize condi- tions for intracytoplasmic sperm injection, embryo culture, and cryopreservation, for example. For oth- ers at risk for heritable genetic disease who feel pregnancy termination is undesirable or inappropri- ate, embryo research has led to the possibility of early, accurate genetic diagnosis: PGD provides diagnostic results at a point before implantation, so pregnancy termination can be avoided. In addition to these benefits of embryo research in general, stem cell research promises additional potential benefits, for such work may lead both to a better understanding of the processes leading to tissue dif- ferentiation and function and to possible therapies by creating lines that can replace diseased or non- functioning tissues. Those who donate gametes or embryos for research are offered the rewards of potentially extending scientific knowledge and, apart from any current or future hope of improving their own health, the opportunity to help others with this knowledge. Indeed, in considering the fate of excess embryos for which destruction is planned, some have argued that donation for research accords the embryo more respect than destruction alone (16, 17).
Are There Alternatives to Using Preimplantation Embryos for Research?
As with all human research, research on embryos and embryonic stem cells should be engaged in only when alternative means of developing knowledge are inadequate. Whenever possible, animal models or cell and tissue culture systems should be used to advance the understanding of human biology. However, direct extrapolation of results from in vitro animal embryo studies to humans can be mislead- ing. Unfertilized oocytes also do not offer the same opportunities for investigating growth processes that embryos do.
Some have argued that obtaining or using embryonic stem cells is unnecessary because stem cells have been or can be isolated from umbilical cord blood or adult tissues, such as brain and skin. Yet such adult stem cells, in contrast to embryonic stem cells, have already progressed along the path of differentiation and lack the plasticity of embryonic stem cells. It is unlikely that once differentiated, these cells can be induced to form the range of tis- sues that can, by contrast, be produced by less-dif- ferentiated embryonic stem cells (18, 19).
Umbilical cord blood stem cells have been shown in some studies to transdifferentiate to a lim- ited extent into nonhematopoietic cells, including those of the brain, heart, liver, pancreas, bone, and cartilage, in experimental culture and animal sys- tems (20, 21). Some have speculated that, on the basis of these observations, cord blood might serve as a source of cells to facilitate tissue repair and regeneration in the distant future. Research is need- ed to clarify the role, if any, of cord blood in this field of regenerative medicine.
For those with ethical objections, recent activity in stem cell research has led to a vigorous search for alternative sources of stem cells that might obviate the need to use or destroy fresh or frozen embryos (22). Suggested techniques include 1) extrac- tion of cells from embryos already dead, 2) non- harmful biopsy of a single blastomere from a living embryo, 3) extraction of cells from artificially creat- ed nonembryonic but embryolike cellular systems (engineered to lack the essential elements of embryogenesis but still capable of some cell division and growth), and 4) dedifferentiation of somatic cells back to pluripotency. The Committee on Ethics recognizes that such techniques, if ultimately proved to be productive, would avoid some but not all of the arguments and objections that have been raised to
embryo and stem cell research. The Committee believes, however, that until such hypothetical alter- natives become realities for human tissues, their possibility should not stand as a barrier to pursuing available methods of demonstrated efficacy. Indeed, technical barriers to these proposed alternatives are not trivial, and the possibility of reprogramming adult stem cells to achieve the same potential as embryonic stem cells has been termed by experts as “exceedingly rare” (23). It also is not clear that all these suggestions are free from ethical concerns or objections (eg, distinguishing when an embryo is “dead”).
In considering embryonic stem cell research, it is also important to indicate why progress requires isolation of lines different from those already estab- lished. Federal regulations prohibit funding for investigations of the many new embryonic stem cell lines created since August 2001, some of which have been used by both international and U.S. researchers to advance the field. Yet, advocates of stem cell research note that in contrast to several of these newer lines, all lines on the National Institutes of Health (NIH) registry were cultured in contact with mouse cells and bovine serum, which limits poten- tial therapeutic applications. Furthermore, the U.S. federal guidelines prohibit federal funding of somatic cell nuclear transfer techniques (also known as SCNT techniques) and research, which may offer unique opportunities for human therapy by creating cells tailored to an individual’s genotype and thus, in theory, requiring less need for immuno- suppression if therapeutics can one day be created from such individualized cell lines.
Are There Arguments Against Embryo Research? Balanced against any potential benefits of embryo research are known and potential risks. Embryo research usually will involve destruction of embryos and, as a result, most human embryo research will not benefit the embryo that is used—enhancing nei- ther its developmental potential nor its chance of sur- vival. It is this potential harm that has led national ethics advisory committees and commissions to eval- uate the moral status of the embryo and has sharply separated the two sides of the embryo research and stem cell debate. Yet, as detailed previously, this doc- ument views destruction of in vitro embryos as dif- ferent from destruction of a human being.
Short of destruction, the manipulation of embryos that are intended for transfer to the uterus
(as with embryo biopsy for PGD) raises concern for potential manipulation-related damage in ongoing pregnancies. Some embryo research can be validat- ed scientifically and be beneficial clinically only if there is a subsequent transfer of the embryo to a woman’s uterus in an attempt to achieve pregnancy, yet until such transfer is accomplished, it remains unknown whether research interventions will enhance or reduce the prospects for healthy life.
Women and couples who either participate in research or donate gametes or embryos for research also may be at risk. If a couple decides to donate “excess” embryos for research, such as stem cell extraction, they may be at risk for psychologic harms such as uncertainty, stress, and anxiety. These potential hazards are not exclusively related to the option of donation of embryos for research purpos- es and may accompany all decisions regarding the disposition of frozen embryos. When research requires hormonal stimulation and retrieval of oocytes separate from plans for pregnancy (ie, tis- sues obtained or created for research alone), the oocyte donor faces risks similar to those involved in oocyte donation for reproductive purposes. It is essential to ensure that a woman’s or couple’s choice is free of coercion and possible exploitation and that the woman or couple gives informed consent.
Recognizing such risks, some have expressed concern regarding the potential to exploit women as oocyte donors. In part to answer such concerns, some guidelines such as those proposed by the National Academy of Sciences recommend no com- pensation for oocyte donation for research other than for out-of-pocket expenses (24). Such restric- tions, however, seem inappropriate to the ACOG Committee on Ethics and are inconsistent with pol- icy and practice concerning compensation both to oocyte donors for reproductive purposes and women participating in other types of research protocols. Compensation for oocyte donation for reproductive purposes is supported by ASRM (25) and is custom- ary in the United States, and there is no strong argu- ment for distinguishing this practice from donation in the research context. The risks to the woman and the need to protect against potential abuses are sim- ilar in the two situations. Payment to an oocyte donor should be understood to be compensation for the woman’s time, effort, risk, and discomfort and not as payment for the eggs that may be recovered. The level of compensation should be consistent with ASRM guidelines intended to preclude payment lev-
els that might be construed as exerting undue influ- ence on the donor (25). In providing advice to those seeking oocyte donors, ASRM guidelines also high- light the importance of protecting vulnerable popu- lations and providing compensation commensurate with the time and effort involved.
Who Should Give Permission for Embryos to Be Used for Research?
Individuals will differ in their beliefs about morality of and appropriate limits for embryo research. This is true for individuals or couples creating embryos as part of infertility treatment and later making deci- sions regarding frozen embryos, as well as for gamete donors, who may in some cases be different from the individuals for whom the embryos were created (26, 27). In considering the question of who should give consent for research using preimplanta- tion embryos, it is important to recognize that such research may occur long after gametes have been donated and embryos created, and in addition, the details of future research questions and protocols are unlikely to be known at the time of donation. In many cases, of course, those supplying the egg and sperm will be the same as those for whom the embryo is created, and these circumstances present the easiest conditions for obtaining appropriate, informed consent for research. In such cases, cou- ples may indicate at the time the embryos are frozen that they would be willing to consider future dona- tion for research, but specific permission needs to be obtained at the later time when custody is trans- ferred to the research team. If details of the research protocol are known at the time embryos are frozen, couples should be so informed. Alternatively, some couples will be willing to donate unused embryos to an appropriate party (eg, those operating the labora- tory or storage facility) for use in future research projects as yet unformulated at the time of donation. If such work includes projects in stem cell research, this should be specifically discussed and the details of stem cell research (eg, creation of immortal cell lines) described insofar as they are known at the time of donation. If both members of the couple have not previously given consent at the time custody is trans- ferred, embryos should not be used for research.
If gamete donors are different from those for whom embryos were created, research should pro- ceed only if gamete donors have been made aware of the option of embryo research and have given their consent to such research. Given the emotions and
discussion surrounding stem cell research, potential research projects should be described as much as possible. However, gamete donors need to recognize that the details of future research projects are unlike- ly to be available at the time of gamete donation, and therefore donors need to be comfortable consenting to research that is described only in general terms (28). Abandoned embryos, as defined by the ASRM Ethics Committee (29, 30), should not be accepted for research.
When embryo research is conducted in anticipa- tion of transfer (for example, PGD research), the intended parents and, if different, the gamete donors must be provided with adequate information regard- ing the nature of the research, the risks to the embryo, and the chances for a successful pregnancy resulting in the birth of a healthy child, and they must provide their informed consent (31). If research is to be done on an embryo that is to be transferred eventually to a third party (a gestational carrier’s uterus), this indi- vidual also should give informed consent for the research.
Finally, choices should be made in circum- stances free of financial or other coercion. Full infor- mation should, therefore, include assurance that consent to donation of embryos for research is not a condition for receiving services and that fee scales are not contingent on consent to research. Moreover, donors of embryos should understand that they will receive no compensation for their donation of excess embryos. The consent process also should cover any possible identifiers that will be maintained with the tissue to link it back to the donors, access to current and future health information from donors, willing- ness of donors to be contacted in the future, owner- ship, patent rights, and commercial uses of stem cell lines that may be developed from the embryo. All providing consent also should understand that they may withdraw their consent up to the time that the donated tissues actually are used in research.
In the scenarios of adults donating gametes for the creation of embryos solely for research and adults donating somatic cells for somatic cell nuclear transfer, special considerations must be taken into account. The information provided to donors for embryonic stem cell research must acknowledge that the process of obtaining the embryonic stem cell line from the inner cell mass of the blastocyst will result in the destruction of the embryo and also should indicate that the derived stem cell lines may be propagated indefinitely. The
consent process also should cover the same elements as consent obtained when unused embryos are donated for research. A woman wishing to donate oocytes for research must be informed of possible risks to her in the process of controlled ovarian hyperstimulation and retrieving oocytes, and egg donor programs should set up medical and psycho-