Ethical issues in stem cell research.

• Author: Balint, John A.

INTRODUCTION

Human stem cell research and its possible connection to human cloning (i.e., somatic cell nuclear transfer) has been the subject of much debate recently. Significant confusion exists, however, in the public discourse on this topic--about what an embryo is, as well as about the ethical, religious, and legal issues involved. The aim of this essay is to clarify these issues and lay out as impartially as possible some of the ethical, religious, and scientific questions surrounding these complex matters, in the hope of stimulating and facilitating informed public debate.

Professor A.V. Hill in 1923, a future Nobel laureate, in an address to the Royal Philosophical Society of Glasgow, urged scientists to take a broad view. (1) He said:

The chief trouble I see with Science is that it is often not philosophical enough; so many of its apostles cultivate some little corner of it so intensively that they never find time or inclination to go up to the top of the neighboring hill in order to see their own little patch in its proper proportions, and to enjoy the romance of the larger landscape. (2) I hope to outline in this essay some of this broader landscape--the ethical, scientific, religious, and public policy issues within which we need to think about human stem cell research.

DEFINITIONS

Gametes--that is, ova and spermatozoa--carry one half of the genetic material, i.e., the DNA, of the female and male putative parents. When a spermatozoon enters an ovum and its DNA is introduced into the nucleus of the ovum, this DNA pairs up with the corresponding DNA already in the nucleus of the ovum, reconstituting its total genetic material in forty-six chromosomes. A fertilized ovum or zygote is thus formed. This can occur in the female genital tract (usually in the fallopian tube) as part of normal sexual reproduction, or in vitro fertilization (IVF) in the case of assisted fertility. In both instances the zygote starts to divide if conditions are favorable; first to form a blastomere of eight, then sixteen cells, and ultimately to form around day five a blastocyst. The blastocyst consists of 120 to 150 cells, some of which are the stem cells that can develop into all forms of normal human tissue. These are called totipotent. It is important to remember that at this stage the blastocyst, which is an early embryo, can divide into two or more living entities that can then develop into normal embryos. Thus, blastocysts are not individuals or unique entities. They are twinnable.

At fourteen days of development, a structure known as the primitive streak appears. This represents the primitive central nervous system. From this point on, the embryo is a unique individual and is no longer twinnable. As I shall discuss later, some authorities regard this developmental stage as critical in their thinking about when human, as contrasted to simply biological, life begins.

Finally, I wish to define the process of cloning. Based on the work of Ian Wilmut in producing Dolly the sheep, (3) this process involves removing the nucleus of an ovum and replacing it with the nucleus of an adult cell taken from the egg donor or another adult. This is known as somatic cell nuclear transfer (SCNT). This is a difficult task attended by a high failure rate. It took over 250 tries to get Dolly. (4) Using a fetal or embryonic cell as a nuclear donor is an easier way to achieve cloning. Such cloned cells are then induced to divide and develop into embryos.

SOURCES OF STEM CELLS

Totipotent stem cells can be obtained from blastocysts or other forms of early embryos. These are considered the most likely to be able to be grown into any organ of the human body or to be used for cell transplantation to help injured human tissues recover from injury.

Germ line cells from early fetuses, derived from terminated pregnancies, are almost as useful as embryonic stem cells. However, it is not clear whether they are fully capable of forming all types of tissue. They are regarded as being pluripotent.

Stem cells have now been isolated from a number of tissues of adult humans. These include bone marrow stem cells used in some forms of bone marrow transplantation. Stem cells have also been identified in adipose (fat) tissue, the central nervous system, and the liver. Their full potential has yet to be determined.

POSSIBLE FATES OF EMBRYOS IN VITRO

When an infertile couple turns to IVF for help in having a baby, more embryos are usually created than needed since it is likely that some of the embryos placed into the mother's uterus will not implant and will be lost. The availability of multiple embryos permits repeat efforts at implantation without the need for repeated egg retrieval. However, once success is attained, the remaining embryos are no longer needed by the parents. The possible fate of these "extra" embryos could include donation to another couple for implantation, donation to an institution for research, or destruction of the embryos. In some countries, such as the United Kingdom, unused embryos must be destroyed after five years of storage. (5)

Before we can determine whether human embryonic or fetal stem cells can be used within an ethical framework, it is critical that we define the efficacy and safety of using such stem cells for medical purposes. Current experience with human hematopoietic stem cells derived from bone marrow indicates that such cells are indeed safe and effective as autografts in reconstituting a patient's bone marrow weakened by the high doses of radiation and chemotherapy used to treat some forms of malignancy. (6) There is currently no data available for human embryonic stem cells. (7)

A sampling of a variety of recent publications indicates a split of opinion regarding the potential of embryonic stem cells: high hopes on the one hand (8) and serious warnings and questions on the other. (9) These reports show the potential of stem cells to survive in culture, but some find they differentiate spontaneously. There are also concerns about control of gene expression in these cells. Furthermore, the high level of telomerase activity, necessary for ongoing cell division, raises questions of a potential tendency to carcinogenesis. These diverse findings bolster the argument for more basic research and suggest the need for a more diverse group of cell lines for this purpose.

ETHICAL ISSUES

The ethical challenges in human stem cell research and the associated issues related to research on human embryos will be considered from several different points of view. There is generally very little concern about research with non-human embryonic or adult stern cells and there are few ethical concerns regarding plans for research with human stem cells obtained from adults. Some have expressed a concern, however, about the lack of defined limits regarding the extent of such research. (10) For example, they ask how far should society allow work on gene transfer to go? Are germ line gene modifications acceptable? John C. Fletcher quotes Hans Jonas, who wrote, "the erosion of ... moral values ... by too ruthless a pursuit of scientific progress would make its most dazzling triumphs not worth having." (11) This essay addresses issues arising from this particular area of ethical inquiry.

The first set of critical issues involves defining when human life begins and determining the rights and privileges of an early human embryo (sometimes called a pre-embryo). An embryo is a living entity whether or not it is endowed with human qualities. Therefore, its destruction for the purpose of retrieving stem cells is absolutely unacceptable to some, (12) but acceptable and even mandatory to others, within certain boundaries. (13) There is general agreement that a human embryo, because it is a living entity and a potential human, deserves respect. (14) But some have questioned how this can be achieved if the embryo is in fact destroyed. (15) The proposals by Michael Meyer and Lawrence Nelson, who suggest that there is a hierarchy of respect due to living entities and conclude that an in vitro embryo comes low in this hierarchical scheme, are not entirely persuasive. (16) They argue that an embryo implanted in the uterus, and therefore intended to become a human, is higher in the hierarchical order than an embryo in vitro, and that such an in vitro embryo's status diminishes as the likelihood that it will be implanted declines. (17) This approach leaves a great deal to the discretion of individual researchers' and would likely not be useable as the basis of national policy. Nevertheless, many agree that if research on human embryonic stem cells is allowed, or supported by federal funds, researchers should follow strict guidelines for responsible scientific enquiry. Such guidelines are laid out in the September 1999 report of the National Bioethics Advisory Commission (NBAC); (18) these were developed after the NBAC heard testimony from both opponents and supporters of human embryo research. (19) These debates, however, do...