Monitoring Stem Cell Research

Government Report

By: President's Council on Bioethics

Date: January 14, 2004

Source: "A Report of the President's Council on Bioethics". January 14, 2004. Available online at 〈http://www.bioethics.gov/reports/stemcell/index.html〉 (accessed January 22, 2006).

About the Author: The President's Council on Bioethics was convened on November 28, 2001, to advise President George W. Bush on the bioethical concerns that have arisen around the therapeutic use of stem cells.

INTRODUCTION

Stem cells are cells that have not differentiated into one of the variety of specialized cells in the body (such as smooth muscle cells and cells of various organs). Stem cells recovered from human embryos following the deliberate or calamitous termination of pregnancy can be manipulated in the laboratory to develop into a specialized cell of choice. Less frequently, the small population of stem cells that exists in human adults can be similarly manipulated.

The ability to use stem cells to create new tissue holds the promise of organ regeneration and limb replacement. As well, stem cell replacement holds the potential to cure a variety of diseases. For example, the replacement of cells that are defective in insulin production could cure diabetes. Similarly, replacement of cells that are defective in the transport of sodium and chloride could cure cystic fibrosis. Neurologically-based illnesses such as Parkinson's disease could be a target of stem cell therapy.

Tempering this promise has been the embryonic source of cells. The potential for the deliberate termination of pregnancy, or the specific creation of embryos for the purposes of stem cell acquisition, has raised great moral and ethical concerns.

PRIMARY SOURCE

INTRODUCTION

The monitoring report has its origins in President George W. Bush's remarks to the nation on August 9, 2001. It was his first major national policy address, and the topic was unusual: federal funding of human stem cell research. In his speech, the President announced that after several months of deliberation he had decided to make federal funding available, for the first time, to finance research involving certain lines of embryo-derived stem cells. At the end of the speech the President declared his intention to name a President's Council to monitor stem cell research, to recommend appropriate guidelines and regulations, and to consider medical and ethical ramifications of biomedical innovation…. This council will keep the population informed of new developments and give the nation a forum to continue to discuss and evaluate these important issues.

In keeping with the President's intention, the Council has been monitoring developments in stem cell research, as it proceeds under the implementation of the administration's policy. Our desire has been both to understand what is going on in the laboratory and to consider for ourselves the various arguments made in the ongoing debates about the ethics of stem cell research and the wisdom of the current policy. Although both the policy and the research are still in their infancy, the council is now ready to give the President and the public an update on this important and dynamic research area.

This report is very much an "update." It summarizes some of the more interesting and significant recent developments, both in basic science and medical applications of stem cell research and in the related ethical, legal, and policy discussions. It does not attempt to be a definitive or comprehensive study of the whole topic. It contains no proposed guidelines and regulations, nor indeed any specific recommendations for policy change. Rather, it seeks to shed light on where we are now—ethically, legally, scientifically, and medically—in order that the President, the Congress, and the nation may be better informed as they consider where we should go in the future.

I. What are stem cells, and why is there contention about them?

The term "stem cells" refers to a diverse group of remarkable multipotent cells. Themselves relatively undifferentiated and unspecialized, and they can and do give rise to the differentiated and specialized cells of the body (for example, liver cells, kidney cells, brain cells). All specialized cells arise originally from stem cells, and ultimately from a small number of embryonic cells that appear during the first few days of development … all stem cells share two characteristic properties: (1) the capacity for unlimited or prolonged self-renewal (that is, the capability to maintain a pool of similarly undifferentiated stem cells), and (2) the potential to produce differentiated descendant cell types. As stem cells within a developing human embryo differentiate in vivo, their capacity to diversify generally becomes more limited and their ability to generate many differentiated cell types generally becomes more restricted.

Stem cells first arise during embryonic development and exist at all developmental stages and in many systems of the body throughout life. The best described to date are the bloodforming (hematopoietic) stem cells of the bone marrow, the progeny of which differentiate (throughout life) into the various types of red, white, and other cells of the blood. It appears that some stem cells travel through the circulatory system, from their tissue of origin, to take up residence in other locations within the body, from which they may be isolated. Other stem cells may be obtained at birth, from blood contained in the newborn's umbilical cord. Once isolated and cultured outside the body, stem cells are available for scientific investigation. Unlike more differentiated cells, stem cells can be propagated in vitro for many generations—perhaps an unlimited number—of cell-doublings.

Stem cells are of interest for two major reasons, the one scientific, the other medical. First, stem cells provide a wonderful tool for the study of cellular and developmental processes, both normal and abnormal. With them, scientists hope to be able to figure out the molecular mechanisms of differentiation through which cells become specialized and organized into tissues and organs…. Second, stem cells and their derivatives may prove a valuable source of transplantable cells and tissues for repair and regeneration. If these healing powers could be harnessed, the medical benefits for humankind would be immense, perhaps ushering in an era of truly regenerative medicine….

Why then, is there public contention about stem cell research? Not because anyone questions the goals of such research, but primarily because there are, for many people, ethical issues connected to the means of obtaining some of the cells. The main source of contention arises because some especially useful stem cells can be derived from early-stage human embryos, which must be destroyed in the process of obtaining the cells. Arguments about the ethics of using human embryos in research are not new. They date back to the mid-1970s, beginning not long after in vitro fertilization (IVF) was first successfully accomplished with human egg and sperm in 1969. A decade later, after IVF had entered clinical practice for the treatment of infertility, arguments continued regarding the fate and possible uses of the so-called "spare embryos," embryos produced in excess of reproductive needs and subsequently frozen and stored in the assisted-reproduction clinics. Although research using these embryos has never been illegal in the United States (except in a few states), the federal government has never funded it, and since 1995 the Congress has enacted an annual legislation prohibiting the federal government from using taxpayer dollars to support any research in which human embryos are harmed or destroyed.

Although the arguments about embryo research had been going on for twenty-five years, they took on new meaning in 1998, when the current stem cell controversy began. It was precipitated by separate publications, by two teams of American researchers, about methods for culturing cell lines derived respectively from: (1) cells taken from the inner cell mass of very early embryos, and (2) the gonadal ridges of aborted fetuses. (In this report, we shall generally refer to the cell lines derived from these sources as, respectively, embryonic stem cells [or "ES cells"] and embryonic germ cells [or "EG cells"].) This work, conducted in university laboratories in collaboration with and with financial support from Geron Corporation, prompted great excitement and has already led to much interesting research, in the US and abroad. It has also sparked a moral and political debate about federal support for such research: Is it morally correct to withhold support from research that holds such human promise? Is it morally permissible to pursue or publicly support (even beneficial) research that depends on the exploitation and destruction of a nascent human life?

People interested in the debate should note at the outset that ES and EG cells are not themselves embryos; they are not whole organisms, nor can they be made (directly) to become whole organisms. Moreover, once a given line of ES or EG cells has been derived and grown in laboratory culture, no further embryos (or fetuses) need be used or destroyed in order to research with cells from that line…. Thus, there is a continuing scientific interest in developing new embryonic stem cell lines, and the existence of large numbers of stored cryopreserved embryos in assisted-reproduction clinics provides a potential source for such additional derivations. Complicating the debate has been another group of stem cells, commonly called "adult stem cells," are derived not from embryos but from the many different tissues in the bodies of adults or children—sources exempt from the moral debate about obtaining ES and EG cells. For this reason, we often hear arguments about the relative scientific merits and therapeutic potential of embryonic and adult stem cells, arguments in which the moral positions of the competing advocates might sometimes influence their assessments of the scientific facts. Further complicating the situation are the large commercial interests already invested in stem cell research and the competition this creates in research and development not only in the United States but throughout the world. The seemingly small decision about funding stem cell research may have very large implications.

SIGNIFICANCE

"Monitoring Stem Cell Research" provided a forum for discussion on stem cell research, with the diverse concerns of those who see the therapeutic value of stems cells and those who are concerned about the moral and ethical considerations of the research. The report revealed the deep divide that currently exists over the rights of the pre-embryonic collection of dividing cells that, depending on one's viewpoint, has the potential to develop into a human being or is already a human being.

Stem cells exist in sources other than embryonic cells. For example, hematopoieic stem cells, which form blood cells, are found in the blood, in bone marrow, and in umbilical cord blood. Retrieval of these cells is less ethically contentious. Blood can be withdrawn or umbilical cord blood collected after birth. Currently, these cells are used for transplantation; their use as the source of cells for organ and tissue replacement is still years in the future.

The process of directed differentiation of a stem cell into the desired cell (for example, a kidney cell) is still not clearly understood and is even more difficult to achieve. Without stem cell research, the necessary research may be slowed down, at least in countries such as the United States. Elsewhere in the world, such as in Singapore and South Korea, stem cell research has been embraced.

The zeal to advance knowledge of stem cells, and to reap resulting personal career rewards, has led one South Korean researcher to falsify data. In the early years of this century, Hwang Woo Suk, a veterinarian and prominent stem cell researcher in South Korea, had reported stunning success in cultivating stem cells in the laboratory. Unfortunately, in late 2005, after months of suspicion, he admitted that most of the data was fraudulent.

Whether this dampens enthusiasm of legislators in the United States and elsewhere to support stem cell research is as yet unclear. What is clear and real is the potential that stem cells offer for tissue replacement.

FURTHER RESOURCES

Books

Holland, Suzanne, Karen Lebacqz, and Laurie Zoloth, eds. The Human Embryonic Stem Cell Debate: Science, Ethics, and Public Policy (Basic Bioethics). Cambridge: MIT Press, 2001.

Novartis Foundation. Stem Cells: Nuclear Reprogramming and Therapeutic Applications. New York: John Wiley & Sons, 2005.

Parson, Ann B. The Proteus Effect: Stem Cells and Their Promise for Medicine. Washington, D.C.: Joseph Henry Press, 2004.

Snow, Nancy E., ed. Stem Cell Research: New Frontiers in Science and Ethics. Bloomington, Ind.: University of Notre Dame Press, 2004.

Periodicals

Golden, F. "The Man Who Brought You Stem Cells/Stem Winder." Time no. 7 (2001): 27-28.

Lanza, R. "The Stem Cell Challenge." Scientific American no. 6 (2004): 92-99.

Web sites

Embryonic Stem Cells: Research at The University of Wisconsin-Madison. "Stem Cells in Culture." 〈http://www.news.wisc.edu/packages/stemcells/es_gpt.html〉 (accessed April 24, 2005).

NIH Stem Cell Information. "Frequently Asked Questions." 〈http://stemcells.nih.gov/info/faqs.asp〉 (accessed April 24, 2005).

PBS—Nova "Stem Cells/Watch the Segment." 〈http://www.pbs.org/wgbh/nova/sciencenow/3209/04.html〉 (accessed April 24, 2005).