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Roeing Against the Wind and Wadeing Against the Current: Embryonic Stem Cell Research and the Abortion Debate

KARL J. STAPLES

From the Departments of ^* Pharmacology and Pathology and Laboratory Medicine, Weill Medical College of Cornell University, New York, New York.

Correspondence to: Dr Paul Lane, Department of Pharmacology, Weill Medical College of Cornell University, New York, NY 10021 (e-mail: plane{at}med.cornell.edu).

Received for publication January 12, 2003; accepted for publication January 12, 2003.

The authors opine that Roe is not pertinent to the ESC debate. Herein, we will discuss the applicable moral and legal issues relevant to ESC research as well as attempt to show that a legal framework already exists to allow a more ethical, consent-based process for continuing ESC research.

Stem Cells: Types and Utility

The adult human body is complex and composed of approximately 220 different cell types, all of which are derived from ESCs. During an embryo's development, populations of cells differentiate (become more specialized in function) into all the organs and tissues required to form a human being. Thus, the therapeutic potential of stem cells is that, once transplanted into a recipient patient, they may be able to replace damaged or destroyed cells such as insulin-producing cells of the pancreas in type I diabetes and dopamine-producing cells of the brain in Parkinson disease.

In general, stem cell lines are classified into 2 types, ESCs and adult stem cells (ASCs) (fetal, placental, or adult). ESCs are derived from the blastocyst and are pluripotent. They can be manipulated to form various types of cells (approximately 110 of the 220 cell types) (Robinson, 2001). It is their pluripotency that provides their potential therapeutic value. ASCs are more differentiated and thus have decreased utility. ASCs can only be manipulated to form a limited range of cell types. For example, stem cells from umbilical cord blood, to date, can only be induced to form other types of blood cells. However, there is a possibility in the future that ASCs may be "deprogrammed" and their pluripotency restored (Pollack, 2002). Presently, the programming process is poorly understood, and ESC research is the key to understanding this mechanism.

The Meaning of Life

Why has the stem cell debate become mired in the abortion debate? For many, it is the fact that both of these positions center on the fundamental questions of when life begins and when a life should have all the rights and privileges of being human. In the past, these questions have been relegated to religious ponderings, and yet, there seems to be no consensus among the world's major religions as to the answers. Religious views range from the Roman Catholic one that life begins at conception and that, therefore, the zygote should be treated as a human being from the fusion of egg and sperm (Congregation for the Doctrine of the Faith, 1998) to the view of Judaism, which regards a fetus as human only after it is born (Feldman, 1968; Dorff et al, 1999; Silverman and Clark, 1999). These are 2 extreme points, but there is an entire spectrum of opinions, dependent upon individual religious perspectives. For example, many Muslims believe that ensoulment (when the soul manifests in the body) renders a fetus alive, although not all sects agree as to when this occurs (Sachedina, 1999). Generally, Muslims believe that ensoulment manifests anywhere between 40 and 120 days gestation (Sachedina, 1999). Perhaps, in part, because of this widespread discord, many people today turn to science for answers to these most fundamental of questions.

Conception occurs when a female's egg cell (oocyte) is fertilized by a male's sperm cell (whether in vivo or in vitro) and the cells' 2 nuclei combine to create a human cell with a new, unique (absent an identical twin) genome (Sadler, 1995). It is at this point that Roman Catholics/Christians and others proffer that a new, unique human life has been created. From a genetic point of view, they would be correct. Once the 2 nuclei have combined, cell division occurs, creating 2 new cells. If all goes well, cell division continues for 6–7 days. The zygote is now called a blastocyst and consists of approximately 200 cells. At this stage, the blastocyst should implant into the uterine wall. Implantation itself is a crucial step in development that many blastocysts never reach and, thus, they cease growing. Indeed, this is a primary mechanism for natural abortion (miscarriage). Estimates range that from 50% to 80% of viable blastocysts never implant (Sadler, 1995; Larsen, 1997). It is at this stage (ie, that of the 200-cell blastocyst) that ESCs are harvested. Exorcising stem cells at this stage destroys the blastocyst (Thomson et al, 1998). Cells harvested prior to blastocyst formation result in nonviable cells. Cells harvested after this stage are less pluripotent because of their increased differentiation.

Once implantation has occurred, cell division proceeds for 2 weeks with the continued differentiation and specialization of cells into the embryo and the placenta. The next most significant event is gastrulation, the inward folding of embryonic cells to form the 3 germ layers of the embryo. This occurs during the third week of development and is the source of all fetal tissues and organs. The next 6 weeks comprise the embryonic period, when the 3 germ layers begin their metamorphosis into organs, including the heart, brain, and lungs. This stage is perhaps analogous to the earliest time some Islamic sects proclaim ensoulment occurs (40 days). As a result of embryogenesis, the major body features are discernible (Sadler, 1995).

The embryonic period gives way to the fetal period, from the third month to birth. Further maturation and differentiation of the tissues and organs and rapid growth of the body characterize this period. However, most often, a fetus remains unable to function outside the womb before approximately week 24 because the central nervous system (CNS) and respiratory system are not sufficiently developed. Nor is the coordination between the 2 systems well established (Sadler, 1995). This may be why some Islamic sects regard this as the latest period for ensoulment to occur (120 days). Having briefly outlined embryo development from conception to birth, we next discuss the influence of these findings on the Supreme Court's holding in Roe.

The Case of Roe v Wade

Roe is one of the most contentious Supreme Court decisions. Justice Harry Blackmun had carefully weighed many legal, moral, religious, and scientific facts and opinions in defining the line between when a fetus is legally regarded as a human being entitled to certain rights and privileges thereof and the parameters of a woman's right to privacy and self-determination. Ultimately, Roe legally recognized fetal development as an ongoing process. Indeed, full development of the brain does not occur until well after the fetus is born (O'Rahilly and Müller, 2001). In doing so, the Supreme Court established that a fetus' right to life depends on the gestational trimester, only out-weighing a woman's right to privacy under certain circumstances in the third trimester. Earlier legal decisions had proscribed quickening (ie, when the mother first feels the fetus move within her) as a defining point in fetal development. However, this definition was highly dependent upon the mother's accurate reporting. In Roe, the scientific basis for the third trimester decision was the fetus' potential viability outside the womb. As discussed above, fetal viability is largely dependent upon the development of the lungs and CNS, in addition to the production of surfactant by the lung epithelium, without which the lungs would collapse. None of these events occurs before the sixth month of gestation (Sadler, 1995).

While Roe is a sensible compromise in light of its polarizing subject, it is a case about the right to abort a fetus dependent upon its mother for its very life. In contrast, ESCs are derived from in vitro–fertilized blastocysts that depend upon cryogenic suspension and laboratory growth media for life. In this context, 2 of the world's major religions (Judaism and Islam) would never consider the blastocyst alive nor would they bestow human rights upon it. Furthermore, such embryos having never been implanted into a woman cannot be considered aborted. Hence, Roe is simply not pertinent to, nor is it the appropriate format for, analyzing the stem cell dilemma.

"The Life and Death Decision Has Already Been Made"

Recently, President Bush (2001) stated that federally funded research using the ca 60 ESC lines currently available should be permitted because "the life and death decision had already been made." The ramifications of this statement are far-reaching. In vitro fertilization (IVF) is an utterly inefficient process in which doctors try to maximize the number of embryos created for multiple implantation attempts (usually 3–5 embryos per attempt). Routinely, there are leftover, unused embryos. Currently, there are an estimated 100 000–1 000 000 embryos in cryostorage worldwide. What is the current fate of these unimplanted embryos if they are not used for the development of ESCs or cryopreserved for future use?

A survey of IVF facilities in the United States reported on 5 alternative fates of unimplanted embryos (Centers for Disease Control, 1999). The vast majority (>50%) are simply discarded, either actively "killed" (incineration) or allowed to "die." Some are used for training of IVF personnel, while others are donated for diagnostic purposes (genetic screening). All of these options result in the destruction of the embryo. Of those embryos not destroyed and subsequently frozen, some are donated for research, some are used for a second IVF attempt, and a minute number are donated for adoption.

Thousands of embryos are created every year for the purpose of IVF. Presently, the apex for these excess embryos is implantation, destruction, or perpetual cryopreservation. In short, because the life and death decision has already been made, we must ask, is it more ethical to incinerate these embryos or to use them for potentially life-saving research? What of future ESC lines created in the private sector using nonfederal money: will these cell lines be available for use by National Institutes of Health (NIH)-funded researchers? Estimates of the number of ESC lines required for tissue matching with transplant recipient patients are generally in the range of 200–2000 (Studer, 2002). The embryos currently slated for destruction would alone yield an abundance of cell lines above this need. The free and unfettered availability of numerous ESC lines would enable researchers to realize the full potential of stem cell technology without resorting to the more contentious techniques of embryo cloning or the creation of embryos solely for research. Hard-line Christians must realize that, to paraphrase the Pope, there is no morally tenable way with which to deal with frozen embryos. If the life and death decision must be made, then surely it is more moral and more ethical to do this in a manner that may save other lives in the future.

The Genie Is Out of the Bottle—Now Give Me My 3 Wishes

"Its prelude was a proud mastery of science over nature—irreversible. Its sequel was violence and death on a horrible scale. In the minute that the new light spread across that sky, humans became fantastically powerful and fantastically vulnerable" (James Gleick in reference to Trinity, the first atomic bomb test [Gleick, 1992]).

The progress of science has traditionally trodden a path of controversy, walking the fine line between the potential benefit to mankind and the potential harm that may be inflicted by its misuse. The atom bomb is a devastating weapon. Some may say that the bombings of Japan were the pointless extinction of tens of thousands of lives, while others may say its use to end the war saved lives, as a prolonged invasion of Japan would have resulted in far greater loss of human life. Both are valid arguments. Power demands great responsibility. Despite the horrors of Nagasaki and Hiroshima, we now live in a nuclear world because knowledge cannot be undiscovered, the mastery of science over aspects of nature is irreversible, and our only hope is in the responsible application of such technology. Dr Stan Pelofsky, President of the American Association of Neurological Surgeons, when asked by President Bush for his opinion on the issue of stem cells, stated, "The genie is out of the bottle." Having rubbed the lamp, is it now appropriate, or even possible, to replace the stopper without getting our wishes? Stem cells have the potential to be a panacea in the fight against disease. We can grow and manipulate stem cells. This knowledge cannot be unlearned. Therefore, society must ensure an ethical and responsible application of stem cell technology.

The compromise plan implemented by President Bush introduces several problems, the greatest of which is the lack of governmental oversight of the production of new stem cell lines. By his refusal to allow federal funds to be used for the development of new ESCs, he gave up the easiest mechanism for close federal monitoring of ESC research. The only places where this kind of research can now be carried out in the United States are in the private sector or at independently funded research facilities. Already, scientists using nonfederal funding have created embryos specifically for the harvesting of stem cells; these embryos were created using sperm and eggs obtained from paid donors (Lanzendorf et al, 2001). More alarmingly, Advanced Cell Technology, a private-sector biotechnology company, has successfully cloned human embryos for the sole purpose of creating ESC lines (Cibelli et al, 2002). Throughout the stem cell debate, cloning and embryo creation solely for ESC line development are generally condemned. However, forcing the development of ESCs into the private sector creates issues of ESC ownership, access, and availability. In addition, if any legal rights were extended to embryos, as recently suggested in the remit of the Secretary's Advisory Committee on Human Research Protections (Check, 2002), this would drive any ESC research outside US borders, denying Americans any access to the debate, much less any ownership in the intellectual property or the availability of derived therapies. Federally funded research would provide the best of both worlds by making ESC lines freely available to all scientists while still imposing ethical constraints on their research. It will never be possible to fully satisfy all sides in such a contentious debate, but it is obvious that the current governmental position is far from ideal and mired in religious dogma. The authors believe a consent-based donation system would render irrelevant some of the ethical issues and religious arguments strangling ESC research.

All Donations Gratefully Received

Once again, the abortion conundrum is not the correct paradigm for evaluating research employing ESCs. In this last section, we will propose an alternative paradigm, one based on consent and presently exercised in analogous situations. The established moral and legal framework governing the organ donation of a decedent's corpse and tissues is equally appropriate and efficacious for distilling the stem cell debate while stripping it of its religious distractions.

In any hospital, many critically ill patients are kept alive by ventilators. Despite physicians' best efforts, death occurs, although many organs continue to function by receiving oxygen via life-support machines. Death in this context is defined as brain death: "the irreversible cessation of all functions of the entire brain, including the brain stem" (National Conference of Commissioners on Uniform State Laws, 1980). The result is the inability to respire without the aid of a life-support machine and should not be confused with a deep coma. Once a physician has declared a person brain-dead, the decedent's next of kin can turn off the life-support machine and have the intact body interred in a manner commensurate with their religious beliefs (see the Uniform Anatomical Gift Act, 1987). Alternatively, life support may be continued until a suitable organ recipient is identified or until the body is donated to science. It is the next of kin (eg, the parent(s) of a minor, a spouse, or the closest surviving relative) who are legally vested with decisional capacity over the decedent's body (Fuller v Marx, 1984). Therefore, with deference to the fundamental legal tenant of stare decisis, the next of kin should have similar decisional authority over embryos created for IVF that are not going to be implanted. Under this analysis, a blastocyst would be classified as brain-dead, as it has no neural tissue whatsoever. Indeed, as previously discussed, neural tissue does not develop until the third week of development and is dependent upon successful implantation of the embryo into the uterine wall. Furthermore, neural activity has not been detected in an embryo before the sixth week of gestation (O'Rahilly and Müller, 2001). Thus, the blastocyst is technically brain-dead, and storage media and cryopreservation mimic life-support machines. Therefore, the next of kin or gamete contributors of the embryo(s) should have similar decisional capacity: destroy the embryo (switch off the life support); donate the cells (organs?) for transplant; or donate the cells (body) for medical research. While this scheme may remain unpalatable to those who regard conception as the beginning of life, such a schemata allows the individuals with the greatest nexus to exercise their moral and religious beliefs without imposing their ideology on others. As long as there is fully informed consent by the legally appropriate person(s), is there any need for further legislation or moralizing?

So what is the legality of giving parents the power to choose what the fate of their embryos will be? Current legal precedent states that the next of kin have a "quasiproperty" right in a corpse for the purposes of possession, preservation, and burial (or other disposition) (Fuller, 1984). Similarly, frozen preembryos have previously been ruled to be "quasiproperty," and disposition of the embryos was decided to be a matter for the parties contributing the gametes (York v Jones, 1989). Furthermore, the Uniform Anatomical Gift Act (1987) allows either parent of the decedent to make an anatomical gift of all or part of a decedent's body for donation. Thus, as can be seen, the decisional power of parents already resides within the American legal system.

Fearing a slide down the well-greased slippery slope, some may argue that this paradigm could be stretched to allow the creation of new embryos from donor eggs and sperm. However, as previously discussed, the authors strongly refute the necessity of creating new embryos for ESC research because there exists a large surplus of unused, IVF-created embryos sufficient for current research purposes (Lanzendorf et al, 2001). Moreover, the reservoir of not-to-be-used embryos continues to grow as the number of persons seeking assistance in reproducing increases. Furthermore, should research on ESCs using stored embryos lead to the realization of the mechanisms of "deprogramming" ASCs for therapeutic purposes, then cloning human embryos for the purpose of creating individualized ESC lines also becomes unnecessary. Additionally, ESC research may lead to more efficient IVF processes, thereby ultimately reducing the number of un-implanted embryos and consequently those that are destroyed. In conclusion, federal funding for ESC research should be authorized under the aforementioned restraints and, by doing so, ethically and responsibly embrace the boundless potential of ESC technology while releasing the research from the costs and coveting of the private sector.

The entire stem cell debate hinges on whether ESCs can live up to the hype: in this matter, only the science will be important for determining the facts, as ideology has a peculiar habit of dissolving when the fate of you, or a loved one, is at stake. The high-profile nature of the debate has created a double-edged sword, raising both public awareness and expectation. The public will eventually demand federal funding for ESC research but will also demand results. However, in truth, stem cell research is at a very seminal stage, and derived therapies, if ever developed, will not be available for many years. The public, fueled by sensationalistic reporting of scientific discoveries by the general (ie, nonscientific) media, may in the future wonder what all the fuss was about and treat all scientific discoveries with disdain should their expectations go unrealized.

Footnotes

^* Journal of Andrology welcomes letters to the editor regarding "Forum" articles and other ethical and legal issues of interest in your own practice or research. We also invite you to suggest topics that deserve attention in future issues. Papers appearing in this section are not considered primary research reports and are thus not subjected to peer review. Unsolicited manuscripts are welcome, and will be reviewed and edited by the Section Editor. All submissions should be sent to the Journal of Andrology Editorial Office.

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