The science of stem cells: some implications for law and policy.

• Author: Daar, Abdallah S.
• Position: Canada

Introduction

There are few areas of modem biomedical research that have aroused as much controversy as stem cells. Scientists, physicians, patients and patient advocacy groups tend to emphasize the potential therapeutic benefits. Others argue that the potential benefits of stem cells have been exaggerated. Entrepreneurs, and research scientists -- who are sometimes one and the same -- envision vast medical and financial profits from stem cell therapy. Religious leaders pronounce judgments based strictly on faith and their understanding of when life begins. Those in positions of political power are eager to remain in power and seek a position wherein the fewest number of people are offended by a given policy choice.

At first sight, the development of stem cells does not seem to be very different from other scientific developments, except that in the case of stem cells, an understanding of the scientific facts of stem cell technology per se, the embryology and the associated terminology is critically important to making ethically sound policy judgments. The facts, definitions and terminology are confusing and are liable to misuse by those who seek to further a particular position.

It is our position that a coherent discourse needs to be initiated so that regulation in this area, if undertaken, is rational, consistent and informed by a clear understanding of the science and the terminology. In this paper we provide a concise overview of the important scientific facts related to embryology and embryonic stem cells and highlight some recent scientific developments that are salient for the purpose of regulatory development in this field.

Why such Enthusiasm over Stem Cells?

Stem cells are exciting to physicians, scientists and patients because of their potential to develop into many different cell types, tissues and perhaps even organs that can possibly be used to treat large numbers of patients with a variety of diseases. (1) To scientists, stem cells offer a new way of exploring fundamental questions of biology, especially those pertaining to embryonic development. (2) In the living body, stem cells are believed to exist in small numbers in most organs including the liver, blood and brain. Stem cells have two crucial capabilities: (1) they divide repeatedly into stem cells of their own type; and (2) with appropriate stimuli they can develop or differentiate either into one particular tissue, into a small number of tissues or, as m the case of pluripotent embryonic stem cells, into potentially all types of tissue. (3)

Embryonic Stem Cells

For years, pluripotent embryonic stem cells have been viewed as the holy grail for many scientists, particularly developmental biologists. Murine embryonic stem cells were discovered about 20 years ago, but despite intense research, human embryonic stem cells have eluded scientists until recently. In 1998, almost simultaneously, two research groups in the United States (4) discovered how to purify embryonic stem cells and maintain them in culture in the laboratory. Thomson and his colleagues purified cells from spare embryos from IVF clinics. (5) Gearheart and his colleagues purified cells, functionally the same as Thomson's cells, from the gonadal ridges of early abortuses. (6) The type of cells described by Gearheart and his colleagues have been confusingly called "embryo germ cells."

Embryonic stem cells (ESCs), as they feature in much of the current debate, are those cells derived from embryos at the blastocyst stage, which is approximately five to seven days after fertilization. (7) At this stage, within the blastocyst, there is a small fluid collection (cyst) in the embryo and at one pole of the cyst a specialized clump of cells known as the inner cell mass. It is from this inner cell mass that ESCs can be obtained. (8)

Several research teams have now been able to establish cell lines in the laboratory that continue to divide into succeeding generations of daughter cells that are identical to the original ESCs. It is also well established that ESCs can, with appropriate signals, differentiate into many different cell types. (9) This capacity of ESCs to differentiate to other cell types is known as "plasticity."

Adult Stem Cells (10)

Until quite recently it was thought that stem cells found in adult tissues and organs (11) could differentiate only into the particular type of cells that make up the organ where the stem cell resides. Thus it was thought that "neuronal" stem cells could only make neurons, "hematopoietic" stem cells could only make blood cells and so on. In other words, it was thought that the cells were not "plastic" and could not "transdifferentiate" into other cell types. However, over the past few years it has been repeatedly demonstrated that stem cells originating from one organ or tissue can develop into cell types of another tissue. (12) This has been shown in both animals (13) and humans. (14)

It is this plasticity of adult stem cells that has raised hopes that they would be just as good for therapeutic purposes as ESCs. It seems obvious that if adult stem cells were ultimately proven to be as versatile as ESCs then many scientists would opt to work with adult stem cells to avoid the ethical problems associated with ESCs, whether they agree with the critics or not. At present this issue is still in dispute and the evidence is contradictory. Two recent papers have indicated that certain types of adult stem cells in animals (15) and humans (16) are quite plastic. Studies in mice have shown that cells that have transdifferentiated from another type of adult stem cell can and do function according to the new phenotype. (17) However, soon after publication of these two promising papers, reports began to appear in the literature that cast doubt on the notion that adult stem cells are as versatile as ESCs. (18)

Cloning

There is a lot of confusion surrounding use of the term "cloning," which essentially means "copying," and in this context, "making an identical (or near identical) genetic copy." Both research and service laboratories have been cloning cells for a long time without controversy. For example, human cell lines such as the HeLa cell line have been used extensively for decades. Cell lines are essentially generations of cloned cells that are maintained in-vitro. The subject of cloning became a matter of public debate and concern after the announcement of the cloning of Dolly the sheep in 1997. The public was concerned that human beings would be cloned for inappropriate purposes. In the context of the current debate we specifically need to distinguish between that which has come to be known as "reproductive cloning" and that termed "therapeutic cloning."

Reproductive Cloning

Reproductive cloning by nuclear transfer from a differentiated somatic cell, although conceptualized and developed in other species over decades of research, (19) became a reality in mammals only in 1997. Somatic cell nuclear transplant (SCNT) involves the fusion of somatic cell with an enucleated egg, or the transfer of a nucleus of a somatic cell into an enucleated egg. The somatic cell and egg may be from different individuals or from the same individual. (20)

The report announcing the cloning by SCNT and the birth of Dolly (21) made an enormous impact on the scientific community and the public because it was unexpected and because of the potential implications for human reproductive cloning. (22) While there are some who find it acceptable to clone humans beings, (23) the vast majority of commentators consider human reproductive cloning to be unethical. (24) At the international level, the United Nations has recently taken steps to draft an international treaty that would ban human reproductive cloning. (25)

Therapeutic Cloning

Where SCNT is initiated without the intention of implanting the blastocyst in a uterus, it has been termed "therapeutic cloning." (26) Although SCNT is the common starting point for both reproductive cloning and therapeutic cloning, the important distinction lies with the fact that with "therapeutic cloning" there is no intention of implanting the resultant blastocyst into a uterus of an animal or a human to create a live being. (27) Therapeutic cloning is simply used to create a blastocyst that provides a source from which ESCs can be extracted and cell lines created for research. One possible application of ESCs is to use them to make cells, tissues and/or organs that can be transplanted back into the same person who donated the somatic cell nucleus. This technology is important because it may provide a solution to the significant problem of shortage of organs for transplantation and of the rejection of transplanted organs and tissues by the recipient's immune system. (23)

Issues Relevant to Stem Cell Law and Policy

Frequently used terms require substantial clarification: "Embryo," "Fertilization" and "Conception"

Traditionally, an embryo is the result of the fusion of a sperm and an egg.(29) The single-celled entity that results from the fusion of a sperm and an egg is a "zygote." The policy implications of this are that: (1) If legislation refers to an "embryo" as the locus of legal restrictions, then this would not apply to the single celled zygote before it divides; and (2) if...