The NIH Stem Cell Guidelines
by Sanyin Siang
Posted September 15, 2000 · Issue 86
The recently released NIH Guidelines for Research Involving Human Pluripotent Stem Cells adds fuel to an already fiery debate between patient advocacy and scientific organizations and right-to-life groups. In this article, the author explores political, ethical, and scientific issues surrounding the use of human embryonic stem cells in research and medicine.
On August 23, 2000, after incorporating comments from two draft guidelines and recommendations by the National Bioethics Advisory Commission, the National Institutes of Health (NIH) released its Guidelines for Research Involving Human Pluripotent Stem Cells (HpSC). Under the new plan, a researcher can apply for NIH funds to support research on stem cells derived from fetal tissue or human embryos.
The news fueled an already fiery debate between patient advocacy groups and scientific organizations and right-to-life groups regarding the ethics of research involving cells extracted from embryos. The controversial issue pervades the political arena and has gained primacy in the presidential campaigns. Both Republican nominee Governor George W. Bush and Democratic candidate Vice President Al Gore issued strong statements - the former condemning the use of HpSC and the latter praising it.
The NIH plan elicited applause from key patient advocacy groups and scientific organizations, including the American Association for Cancer Research, the American Medical Association, and the Memorial Sloan-Kettering Cancer Center, who believe in the tremendous potential medical benefits of HpSC. Scientists can coax these undifferentiated cells to grow into various types of cells for repairing damaged tissue or organs. Hence, they can "grow" nerve cells for stroke or Parkinson's disease victims, insulin-secreting cells for diabetics, and spinal cord cells for paraplegics. Furthermore, in contrast with privately funded research, publicly funded research would give some assurance that the treatments developed will be available to those who would not otherwise be able to pay for it.
The use of stem cells derived from embryos evokes strong opposition from those who maintain that embryos deserve full human status. Opponents fear that the reasoning for the research will lend justification to practices that destroy embryos, as with abortions, and will lead to other, unforeseen, ethical ramifications. Senator Sam Brownback (R-KS), who believes that federal funding of human embryonic stem cell research is "illegal, immoral, and unnecessary," has compared research in this area to that performed on Holocaust victims by the Nazis.
One focus of the debate is whether HpSC research is necessary given the capabilities of adult stem cells. The viewpoints were revisited at a hearing by the U.S. Senate Committee on Appropriations Subcommittee on Labor, Health & Human Services, Education two weeks following the guidelines' release. Committee chair Senator Arlen Specter (R-PA) believes that the NIH guidelines are too restrictive; he intends to move his bill, Stem Cell Research Act of 2000, S. 2015, to the Senate floor this year.
Opponents of HpSC research tout adult stem cells and those gleaned from umbilical cords and placentas as viable and more desirable alternatives to the use of embryonic or fetal-tissue derived stem cells. HpSC might run the risk of uncontrolled differentiation into tumors or other tissues. Furthermore, if clinicians retrieve cells from the patient, they can forego the risks of transplant rejection, a potential problem with the use of embryonic stem cells.
"There is a wealth of references on the use of stem cells as an adjunct in the treatment of numerous types of cancer, including brain tumors, ovarian cancer, various solid tumors, multiple myeloma, breast cancer, and non-Hodgkin's lymphoma. The adult stem cells are purified from bone marrow or circulating blood, preferably from the patient, and, after treatment to destroy the cancer cells, the patient is given back their own purified stem cells," noted hearing witness David Prentice, professor of life sciences at Indiana State University and a researcher on adult stem cells. "Adult stem cells have also been used successfully to treat several autoimmune diseases such as multiple sclerosis, systemic lupus, juvenile rheumatoid arthritis, and rheumatoid arthritis, as well as anemias."
Prentice cited several recent findings and breakthroughs to bolster his case. In August, a report noted one of the first uses of an adult neural stem cell line for treatment of stroke. Two reports detailed the use of corneal stem cells to restore vision. In July, two groups from the United States and the United Kingdom found that bone marrow stem cells, one of the most versatile and accessible of adult stem cells, could form liver cells. Prentice cited an August report that indicated that the bone marrow stem cells could be changed into neurons that proliferate in cell culture.
While proponents of federally funded HpSC research support the study of adult stem cells, they argue that there is insufficient knowledge regarding differences and similarities between the two types of stem cells and that comparisons cannot be made until research progresses on embryonic stem cells as well.
"In terms of adult stem cells, there is new evidence that they have more versatility. In terms of our goals, we have to think in terms of every disease range possibility. Embryonic stem cells have been shown to be able to treat every kind of disease. The adult stem cells may be successful in treating these areas, but certainly not every area," stated Gerald Fischbach, director of the National Institute of Neurological Disorders and Stroke, at the Senate hearing. "I think the notion that stem cells in bone marrow might be useful for repairing nerve cells is a hope that we all share. The publication referred to demonstrates a small first step. It will take years to translate that into useful therapy. Studies of embryonic stems cells are much closer to that goal, but both efforts should be pursued. I don't know any case in which an adult stem cell has formed a nerve cell that will reverse the effects of Parkinson's. That may change along the years."
All current studies regarding HpSC are from privately funded research, which raises uneasiness regarding what happens "behind closed doors." Federal funding for the research would subject the science to public scrutiny and government oversight. "It will make the research more open, more published, and more diverse," noted Fishbach. "I think NIH sets a standard for the field and the world."
"In the end, in a real sense, the question we are grappling with here is not a scientific question. We've heard evidence on both sides on the promise of both types of cells. In the end, this is a moral and ethical issue. In my opinion, it is never acceptable to sacrifice one human life for another," said Prentice.
"What greater morality exists than doing all we can to help those individuals whose lives are embattled by disease and disability?" said Nobel Laureate Paul Berg at an American Society for Cell Biology press briefing following the issuance of the guidelines. "We can ill afford the luxury of proceeding with these promising technologies in series. We owe it to those who are in need to explore all possible avenues that could lead to a cure."
To address concerns from HpSC research opponents and to comply with a congressional amendment prohibiting use of federal funds on embryo research, the guidelines impose several restrictions on the source of stem cells used in research. The stem cells will be supplied by privately funded sources, and the embryos used must be excesses from fertility clinics that have been slated for destruction. To ensure that women will not create fresh embryos for research purposes, only frozen embryos may be used, and reimbursement for donation is prohibited. The guidelines also preclude "research in which HpSCs are combined with an animal embryo."
Furthermore, the federally funded HpSC research will come under oversight of a newly created NIH HpSC Review Group. The group will hold public meetings as new funding requests arise. The committee is scheduled to review its first case in December and grants are not expected to be awarded until late in 2001. According to Allen M. Spiegel, hearing witness and director of the National Institute of Diabetes and Digestive and Kidney Diseases, several dozen investigators have already expressed interest in pursuing research in HpSC.
The use of federal funding is still in limbo considering that political action by Congress or the new administration can stall its progress. The next administration could issue an executive order that would stop the research, or research opponents may invoke the right to sue the NIH. In Congress, Representative Jay Dickey (R-Ark) is already garnering support for opposition to the new guidelines.
The U.S. guidelines are still conservative when compared with the policy direction that the British are taking. Britain currently allows for research on embryos donated by clinics, as long as the embryos are destroyed within 14 days, the time from which the nervous system begins development. An August report issued by the U.K. Department of Health on the potential of stem cell research and cell nuclear replacement to benefit human health condoned the conditioned use of embryos cloned from patients. The report stipulates that cloning is an alternative if no other means of conducting the research exists. If the British Parliament passes the recommendations into policy, it will make Britain's liberal policy on the use of embryos for research the most radical internationally.
"Great Britain has already approved the use of HpSCs and is considering what is not permitted by the NIH Guidelines, i.e., allowing researchers to create embryos for the purposes of establishing pluripotent stem cell lines. Are the English less moral or ethical than we? Are they less sensitive of the sanctity of life? I think not. They have chosen to use sources for stem cells that are sanctioned by law and medical practice in order to save lives and reduce suffering of the living," commented Berg.
Sanyin Siang works on a variety of issues at the intersection of science, ethics, and law at the Directorate for Science Policy Programs of the American Association for the Advancement of Science.
Julia Kuhl has done illustrations for the New Yorker and the New York Times, among others. She now lives in Heidelberg, Germany, with her neurobiologist husband and is working on a comic book - a Fulika atra (coot) version of Shakespeare's Hamlet.
Constructing Immortalized Human Cell Lines - a review of recent advances in methods for culturing human stem cells. From Current Opinion in Biotechnology. Full text from BioMedNet.
The National Institutes of Health - offers several pages related to stem cell research including the Stem Cell Information page, Stem Cells: A Primer, and What Would You Hope to Achieve from Human Pluripotent Stem Cell Research?
Stem Cell Research & Applications - provides information on many scientific and ethical issues surrounding stem cell research. From the American Association for the Advancement of Science.
Ethical Issues in Human Stem Cell Research - a downloadable document from the National Bioethics Advisory Committee's Publications Section.
Stem Cells - an international, peer-reviewed journal of stem cell research. This journal contains a great series of concise reviews of literature in the field and provides abstracts and full text of articles.
Stem Cell Research News - a biweekly report that covers research, legislation, government oversight, and commercialization of stem cell research. This site requires a subscription, but short summaries of recent news are available at no charge.
Can Old Cells Learn New Tricks?, Researchers Get Green Light for Work on Stem Cells, and Intimations of Immortality - several recent articles from Science. (Paid subscription required for access.)
Stem Cell News & Press Releases - links to reports in mainstream media about stem cell research from the Stem Cell Research Organization, a group ethically opposed to embryonic stem-cell research.
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