Report 15 of the Council on Scientific Affairs (I-99)
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Embryonic/Pluripotent Stem Cell Research and Funding

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At the 1999 Annual Meeting, the House of Delegates adopted Resolution 526, which was introduced by the American College of Obstetricians and Gynecologists and the American Society of Reproductive Medicine delegations. It asks, "That our American Medical Association (AMA) encourage strong public support of federal funding for research involving human pluripotent stem cells (PSC)." 

This report examines the science, policy implications, and AMA initiatives and activities with regard to PSC research. The positions of those who support and those who oppose PSC research are described. AMA policy related to this issue is listed at the end of the report. 

Background

Many types of stem cells can differentiate into a number of specialized cells. A fertilized egg cell is one type of stem cell, with the potential to derive an entire human being. This potential is referred to as totipotency. A PSC is different in that it is limited in being unable to give rise to placental tissue, and thus is not able to give rise to a human being. The importance of stem cells is such that many remain with humans for their entire lifetime; for example, bone marrow stem cells, which continuously renew circulating hematopoietic cells.¹ Adult stem cells have a more limited repertoire, although their use has yet to be fully explored.^1a In this report, the subject of adult stem cells is not the main focus.

In vitro culture of cells from the inner cell mass of murine blastocysts, produces PSC.^2,3 Embryonic stem cells are derived from embryonic gondal tissue (germline cells).^4,5 These cells, which have been referred to as embryonic germ cells (EGC) or embryonic stem cells (ESC), are for the purposes of this report the same as PSCs. Such cells have been derived from primate and human embryos.^6-12

In 1998, two groups reported the successful growth of PSC in culture.^12,13 Shamblott et al¹³ derived tissue for research from gonadal tissues from abortuses. Informed consent was obtained from the donor couples after they had decided to terminate the pregnancies. Thomson et al¹² used donated embryos from in vitro fertilization (IVF) programs to derive PSC (analogous to the murine blastocysts approach). Informed consent was obtained from the donor couples. Both research programs were privately funded in accordance with federal law.¹⁴

Essential characteristics of a PSC are prolonged undifferentiated growth in vitro and the stability to develop into all three embryonic germ layers even after prolonged culture.¹² This prolonged stability is dependent on PSCs having telomerase activity. Telomerase is a ribonucleoprotein with the primary function of adding telomere repeats to chromosome ends. This maintains telomere length, which plays an important role in a cell's replicative lifespan.¹⁵ Telomerase expression is highly correlated with immortality in human cell lines. As soon as a cell ceases to make telomerase, usually at the time of differentiation, the cell begins to senesce. A third essential characteristic of a PSC line is high telomerase activity. Thomson s group has derived five independent cell lines from the inner cell masses of blastocyst cultures that have been in culture for longer than 5 months. These cell cultures express high telomerase activity. 

PSC lines have demonstrated the ability to differentiate into all three embryonic germ layers, the endoderm, mesoderm, and ectoderm. The endoderm further develops into gut epithelium; the mesoderm forms cartilage, bone, and smooth or striated muscle; and neural epithelium, embryonic ganglia, and stratified squamous epithelium are derived from the ectoderm. PSC can differentiate into the cell types of the tissue into which they are injected. Human PSC will differentiate into skin cells when injected subcutaneously into mouse recipients. No non-human primates have been studied in this manner.

Work toward potential clinical applications has already begun. Pure cultures of murine cardiomyocytes isolated through genetic manipulation of differentiating PSC are capable of forming intracardiac grafts. This approach can be used to develop many different differentiated cell grafts.¹⁶ Neural cells have been derived from PSC lines.^17-20 Snyder et al²¹ have shown that when neurological stem cells are injected into the brains of murine models of myelin neurodegeneration, a large number of diseased oligodendrocytes are replaced by normal oligodendrocytes. Similarly, hematopoiesis can be observed in murine models by grafts of PSC.²²

More research on the factors that control differentiation is necessary to realize the potential of this technology, such as factors within the blastocyst. With better understanding of the multiple factors involved, it is hoped that directed differentiation of PSC into specific cell types will be possible as well as production of large quantities of human cells, such as cardiomyocytes, neurons, or hematopoietic cells, which will be available as replacement tissue. 

A yet-unresolved issue is the potential for immunological rejection of such cellular grafts. However, it is theoretically possible to genetically define and equip PSC with the autologous major histocompatibility complex antigens. Such cellular grafts would be recognized as self and not rejected. Another solution involves the potential of combining cloning technology (somatic cell nuclear transfer) with stem cell technology. In this scenario, cells would be harvested from the patient, the nucleus would be removed and placed in a "re-programmable cell," i.e., an empty (denucleated) ovum. From the subsequent blastocyst, PSC would then be isolated, directed to differentiate into the needed cell type of the diseased organ, and then injected back into that individual as an autologous transplantation. Since the replacement cells would contain the recipient's DNA, they would carry the recipient tissue's antigens and would not be recognized as foreign, thus facilitating engraftment.²³

It is likely that these scientific dilemmas will be overcome in the near future, allowing large amounts of PSC to be produced, and directed to differentiate in vitro towards many varied tissues. This will allow the replacement of damaged cells associated with certain diseases that currently are known to result from the death or dysfunction of one or a few cell types. Examples of potentially treatable diseases include juvenile-onset diabetes mellitus, myocardial infarction, neurodegenerative diseases (i.e., Parkinson's disease), spinal cord injury (regeneration of neurons in a directed fashion), and promoting hematopoietic regeneration following marrow ablation for malignancy. 

The amount of PSC that can be produced has no theoretical limit. Thus the application of PSC to new research opportunities and applications for studying pharmacology, gene-gene interactions, gene therapy, and transplantation therapy techniques will be limitless. In pharmaceutical development, use of human PSC could allow researchers to study the beneficial and toxic effects of candidate drugs in many different cell types and potentially reduce the numbers of both animal studies and human clinical trials that are currently required for drug development.²⁴   In addition to improving drug development, PSC will enhance the growing field of pharmacogenomics by the ability to develop multiple differentiated PSC lines that can be used in in vitro drug trials. Important factors involved in tissue regeneration could be further explored by use of PSC. Combining recombinant DNA technology with stem cells research will expand the potential of gene therapy by permitting the introduction of genes that are deficient in the recipient's original organ cells to the PSC, with subsequent in vitro differentiation and introduction back into the recipient to replace a diseased organ. 

Policy Implications

Use of PSC raises the morally controversial issues of whether an embryo deserves the same rights as a person. The prospect of possible cures/treatments for currently incurable and/or late onset diseases has cast a new light on this continued controversy. Anti-abortion advocates criticize using cells derived from embryos and aborted fetuses, arguing that it destroys human life and it will lead to increased demand for fetal tissue. These groups are concerned that scientists may one day produce embryo-making factories specifically for research purposes. 

There are two principal ways in which PSC may be derived; one involves the use of a living embryo. These embryos generally come from fertility clinics. The other method involves taking the cells from an already aborted fetus, which is likened to harvesting organs for transplant. As mentioned, Shamblott's¹³ research group derived tissue from aborted fetuses, whereas Thomson et al¹² obtained excess embryos donated specifically for research. Current PSC research has been funded from the private sector. 

In 1993, President Clinton and Congress lifted the eight-year ban on federal funding for fetal-tissue research. The President authorized the National Institutes of Health Revitalization Act of 1993 to end this moratorium and to begin research funding. 

Because it is legal to use federal funds to perform scientific studies on fetal tissue, stem cells derived from abortuses would not run counter to the ban on embryo research. However, the current ban on embryo research would ban the use of federal funds for the isolation of PSC from blastocysts (donated IVF embryos). The Department of Health and Human Services (DHHS) has stated that research with PSC lines is not covered under the ban. Since PSC lines are not capable of becoming a human being, nor are they organisms as defined by science, they cannot be considered embryos as defined by the law. ^25,26 The DHHS states that the ban applies only to the act of obtaining the stem cells from the embryo and does not apply to subsequent research on retrieved stem cells. The self-propagating ability of PSC means that lines used by researchers could be many generations removed from their source. 

In 1994, the National Institutes of Health (NIH) convened the Human Embryo Research panel of ethicists and researchers to study the issues of human embryo research. The panel concluded that the derivation and analysis of human PSC from embryos was ethically justifiable and merited consideration for federal funding. Congress, however, chose to pass legislation that effected a complete ban of federal monies being used for research purposes that would support the creation of human embryos for research or to perform studies in which a human embryo would be destroyed. The AMA supported the conclusions and recommendations of the NIH Human Embryo Research Panel at that time.^{27, 28a, 29a}

The NIH is developing guidelines and oversight mechanisms for this research. The scientific community, including a group of 33 Nobel laureates, has come forward in support of the value of stem cell research. There has been congressional support on both sides of the issue. Those in opposition state that, despite the legal opinion offered by DHHS counsel, funding for embryonic stem cell research "would violate both the letter and spirit of the Federal law."

In April 1999, Harold Varmus, MD, PhD, Director of the NIH, charged a Working Group of the Advisory Committee to the Director (ACD) with providing advice on the development of guidelines and oversight for this area of research. The ACD, which began crafting guidelines on April 8, 1999, is chaired by Ezra Davidson, MD, Associate Dean of Medicine and Science at Charles Drew University, and Shirley Tilghman, PhD, Life Sciences Professor at Princeton University.²⁸ The other members of the working group have backgrounds in medicine or research, as well as law, ethics, and patient advocacy.²⁹

Current draft guidelines under consideration by the NIH ACD would prohibit the injection of PSC into an existent embryo forming a chimeric embryo, containing two different individual genetic materials or from using stem cells to clone a person. Among other guidelines under consideration are the following: PSC used by federally funded researchers would be restricted to two sources; those derived from IVF treatments and those derived from fetal tissue. If PSC derived from human embryos were used, the researcher would be required to provide documentation that the embryos were originally created for an infertility treatment and that they were not created specifically for research. Investigators would have to provide documentation that the embryos were obtained through informed consent and that the donors were in no way influenced to donate spare embryos. The informed consent would have to detail that the cells derived from the embryos could lead to development of commercial products.²⁹ The NIH ACD stated that it was morally inconsistent to let scientists do research on cells they could not legally derive. Lana Skirboll, NIH Associate Director of Science Policy, indicated that it might take until Autumn 1999 for these final guidelines to be fully developed. The ACD considered and endorsed a proposal to form a Stem Cell Review Committee, which would review investigators' compliance with the developed guidelines. The Society for Developmental Biology, the American Society for Cell Biology, and the National Alliance for Aging Research are among those supporting the NIH's position. 

The ACD will then advise Dr. Varmus on implementation of the revised guidelines. The public will have 60 days to comment on draft guidelines before the topic is taken up by another high-level NIH advisory panel.³⁰ The finalized guidelines will be published in the Federal Register. The NBAC released a report in September 1999 in response to the President s request in November 1998 for it to consider the ethics of PSC research (executive summary available at: http://bioethics.gov/stemcell_exec_intro.htm ).^31,32   By majority opinion, the NBAC recommended that federal funding be allowed to permit scientists to both experiment with and derive stem cells from human embryos that were originally created for infertility treatments, as well as to conduct research on stem cells that are derived by other groups not funded by the government (i.e., the private sector). This recommendation would run counter to the current federal ban, which forbids federal support for experiments with human embryos. That federal ban will expire at the end of Fiscal Year 1999.^26,33 Alex Capron from NBAC (co-director of the Center for Health Policy and Ethics at the University of Southern California) criticizes the NIH s legal interpretation that it is permissible to use federal funds to perform research on stem cells that were derived without federal funds, and notes that it is difficult to distinguish between the derivation and the use of these cells. Furthermore, he contends that current advances in somatic cell nuclear transfer will permit the de-differentiation of somatic cells into stem cells, which justifies the continuation of the ban on embryo research.^34a

The US National Conference of Catholic Bishops (represented by Richard Doerflinger) strongly opposes the plan to fund stem cell research, stating that federal officials are wrong to make a distinction between embryos and stem cells derived from embryos, and doing research on either destroys human life. Paradoxically, at fertility centers embryos are routinely created for implantation to treat infertility, and those that are not implanted into a uterus are destroyed if not donated to research or to other couples.³⁰

Countering Doerflinger's position is Roger A. Pedersen, PhD, a well-respected stem cell researcher. He argues that the derivation of stem cells from the blastocyst stage, with removal of the outer cellular layer of the blastocyst, means the placenta cannot form, which is a requisite for implantation in the uterus and the beginning of fetal development.^31a

Other opponents of stem cell research are promoting expansion of the legal restrictions already in force on the use of fetal tissue and fetal tissue transplantation to stem cells. Scientists doing research on stem cells would be responsible for assuring that proper informed consent had been obtained for the tissue, even though they may be quite removed from original site of the donation. The informed consent for embryos that are donated to research by couples seen in fertility clinics would not necessarily be available to the basic scientists, nor would the informed consent meet research requirements. In addition, requiring the stem cell researcher to verify the informed consent could be viewed as a violation of privacy and confidentiality of those patients. Such increased stringency would put stem cell researchers in an impossible position to comply in order to receive federal funding.

The American Association for the Advancement of Science and the Institute for Civil Society in their August 1999 report acknowledge that PSC research raises ethical and policy concerns, and support educating and informing the public about these issues. They believe that existing federal regulatory and social control mechanisms provide a sufficient framework for oversight of PSC research. This joint committee supports federal funding for stem cell research to promote investment, encourage sound public policy, and foster public confidence in PSC research. This committee endorses both public and private research on PSC derived from all sources including embryonic, fetal, and adult tissues in order to keep up with the rapidly advancing technology.³⁴

Nobel laureate Paul Berg, PhD (1980, Chemistry), Stanford University, stated during an April 28, 1999, House Appropriations/HHS Subcommittee hearing that any PSC research oversight process to monitor funding should apply to both the public and private sector to standardize research use and the generation of PSC. It is felt that without federal funding to support embryo research the research will continue in the private sector without appropriate review or oversight from any public or government body.

Stem cell research has become a political issue. During the first week of July 1999, Sen. Sam Brownback (R-KS) denounced NIH s decision to fund experiments with stem cells derived from human embryos, arguing that the federal law which forbids NIH from supporting work with the embryos also applies to embryonic "byproducts." This position has wide support, including former Surgeon General C. Everett Koop, MD, and Edmund D. Pellegrino, MD, Kennedy Institute of Ethics, Georgetown University. 

In addition to the scientific community, a coalition of patient advocacy groups, CURe (the Patients' Coalition for Urgent Research), is publicly supporting stem cell research. The main battle is expected to be the Fiscal Year 2000 appropriations bill for the NIH, which for the past few years has included a legislative rider forbidding the NIH from supporting research in which "embryos are destroyed, discarded, or knowingly subjected to risk of injury or death." However, neither side has revealed a strategy for achieving their aims. 

Opponents to NIH's legal interpretation of the current ban that would allow NIH funding of human PSC research do admit that NIH's position that PSC are not embryos would be difficult to overturn in court. A strategy to re-word the current ban to specifically mention PSC would essentially concede that NIH's position is correct and would also fail. Another option is to await the final NIH guidelines, which will outline the process by which federal funds would be available and then attack that language, by applying specific riders to NIH appropriation legislation that would in effect prevent federal funding.³⁵

The White House, in response to the NBAC final report in July 1999, stated that it would not act on the NBAC recommendation to fund derivation of stem cells from donated embryos but would support public funding for stem cell research. The White House stated that no other legal actions were deemed necessary at this time. 

In conclusion, it is clear that stem cell research brings the controversial ethical issues of embryo research back to fore. It is interesting that the prospect of stem cell research impacting tremendously on the potential for cures for adult-onset disorders represents a counterbalance to the previous context of embryo research, mainly the abortion issue. There does appear to be a consensus that federal funds should not be used to create embryos for stem cell research. The continuing controversy will be the issue of public scrutiny of this research, which holds so much potential for advancing medical care and understanding basic mechanisms of developmental biology. How to apply public scrutiny and the use of federal funds to effect public oversight will require continued vigilance to this area of biomedical research. 

AMA Initiatives and Activities

The AMA has followed the issue of PSC very carefully. The AMA has been a signatory to two letters addressed to members of Congress calling for support of stem cell research, and one advertisement that appeared in the Congressional Quarterly. There is significant relevant AMA policy on embryo and fetal research (detailed below).

On February 19, 1999, the AMA was a signatory on a letter to Sen. Arlen Specter (R-PA), entitled "Stem Cell Letter Sent to All Members of Congress," which was written by the Association of American Medical Colleges in collaboration with many other medical, health, and science-related societies. The letter supports research utilizing human PSCs and supports the NIH's plan to develop clear guidelines to address the specifics of funding, as well as scientific, legal, and ethical issues. A copy of this letter appears in    Appendix I. 

A follow-up letter, dated July 29, 1999, to Rep. John Edward Porter (R-IL), Chairman, Subcommittee on Labor, Health and Human Services, Education and Related Agencies, Committee on Appropriations, United States House of Representatives reiterated the AMA s support for federal funding of PSCs, and urged the Chairman to allow this research to move forward (see    Appendix II).  The letter addresses the fact that the NIH is producing guidelines, and notes that a public opinion poll showed 74% of those polled favor funding of stem cell research by the NIH.

Relevant AMA Policy [Editor's Note:  The following represents AMA policy at the time this report was written (December 1999).] 

H-5.985 Fetal Tissue Research

The AMA reaffirms its position in support of the use of fetal tissue obtained from induced abortion for scientific research. (Res. 540, A-92). 

H-5.992 Fetal Tissue Transplantation Research

The AMA (i) supports continued research employing fetal tissue obtained from induced abortion, including investigation of therapeutic transplantation; (ii) demands that adequate safeguards be taken to isolate decisions regarding abortion from subsequent use of fetal tissue, including the anonymity of the donor, free and non-coerced donation of tissue, and the absence of financial inducement; and (iii) urges restoration of federal funding for continued research utilizing tissue from induced abortion to provide therapeutic transplantation for diabetes mellitus, neurodegenerative disorders, including Parkinson's disease, and for other disabling and fatal disorders. (Res. 170, I-89; Reaffirmed by Res. 91, A-90). 

H-5.994 Use of Fetal Tissue for Legitimate Scientific Research

The AMA supports (i) the concept of the use of fetal tissue for legitimate scientific research, including transplantation; and (ii) continued federal funding for such research. (Res. 26, I-88, Reaffirmed: Res. 91, A-90). 

H-140.982 Frozen Pre-Embryos

The AMA recommends as follows: (1) primary authority for frozen pre-embryos rests with the two gamete providers, and they must agree to any disposition of the pre-embryos; (2) agreements by the gamete providers for the future disposition of their pre-embryos should generally be enforceable. However, either gamete provider should be able to show that changed circumstances make enforcement of the agreement unreasonable. The gamete providers should not be required to enter into an agreement that will govern the future disposition of their pre-embryos; and (3) frozen pre-embryos may be used by the gamete providers, donated for use by other parties, or donated for research. The frozen pre-embryos also may be allowed to thaw and deteriorate. (BOT Rep. OO, I-89)

H-460.937 Human Embryo Research

The AMA supports the conclusions and recommendations of the Human Embryo Research Panel of the National Institutes of Health. (BOT Rep. 13, A-95)

H-460.940 Support for Federal Funding of Early-Stage Embryo Research

The AMA supports federal funding of biomedical research which promises significant human and scientific benefits. (Res. 242, I-94)

E-2.10 Fetal Research Guidelines 

The following guidelines are offered as aids to physicians when they are engaged in fetal research:

1. Physicians may participate in fetal research when their activities are part of a competently designed program, under accepted standards of scientific research, to produce data which are scientifically valid and significant.  
2. If appropriate, properly performed clinical studies on animals and nongravid humans should precede any particular fetal research project.   
3. In fetal research projects, the investigator should demonstrate the same care and concern for the fetus as a physician providing fetal care or treatment in a non-research setting.   
4. All valid federal or state legal requirements should be followed.   
5. There should be no monetary payment to obtain any fetal material.   
6. Competent peer review committees, review boards, or advisory boards should be available, when appropriate, to protect against the possible abuses that could arise in such research.   
7. Research on the so-called "dead-fetus," macerated fetal material, fetal cells, fetal tissue, or fetal organs should be in accord with state laws on autopsy and state laws on organ transplantation or anatomical gifts.   
8. In fetal research primarily for treatment of the fetus: (a) voluntary and informed consent, in writing, should be given by the gravid woman, acting in the best interest of the fetus;  and (b) alternative treatment or methods of care should be carefully evaluated and fully explained. If simpler and safer treatment is available, it should be pursued.  
9. In research primarily for treatment of the gravid female: (a) voluntary and informed consent, in writing, should be given by the patient; (b) alternative treatment or methods of care should be carefully evaluated and fully explained to the patient. If simpler and safer treatment is available, it should be pursued; and (c) if possible, the risk to the fetus should be the least possible, consistent with the gravid female's need for treatment.  
10. In fetal research involving a fetus in utero, primarily for the accumulation of scientific knowledge: (a) voluntary and informed consent, in writing should be given by the gravid woman under circumstances in which a prudent and informed adult would reasonably be expected to give such consent; (b) the risk to the fetus imposed by the research should be the least possible; (c) the purpose of the research is the production of data and knowledge which are scientifically significant and which cannot otherwise be obtained; and (d) in this area of research, it is especially important to emphasize that care and concern for the fetus should be demonstrated. (Issued March 1980; updated June 1994 [I, III, V])

E-2.14 In Vitro Fertilization

The technique of in vitro fertilization and embryo transplantation enables certain couples previously incapable of conception to bear a child. It is also useful in the field of research directed toward an understanding of how genetic defects arise and are transmitted and how they might be prevented or treated. Because of serious ethical and moral concerns, however, any fertilized egg that has the potential for human life and that will be implanted in the uterus of a woman should not be subjected to laboratory research.

All fertilized ova not utilized for implantation and that are maintained for research purposes shall be handled with the strictest adherence to the Principles of Medical Ethics, to the guidelines for research and medical practice expressed in the Council's opinion on fetal research, and to the highest standards of medical practice. (Issued June 1983 [I, V, VII])

E-2.141 Frozen Pre-Embryos

The practice of freezing extra pre-embryos harvested during the in vitro fertilization process (IVF) has enhanced the ability of infertile couples to preserve embryos for future implantation. This practice has also posed a number of ethical and legal dilemmas, including questions regarding decision making authority over the pre-embryos and appropriate uses of pre-embryos.

This country's cultural and legal traditions indicate that the logical persons to exercise control over a frozen pre-embryo are the woman and man who provided the gametes (the ovum and sperm). The gamete providers have a fundamental interest at stake, their potential for procreation. In addition, the gamete providers are the parties most concerned with the interests of a frozen pre-embryo and most likely to protect those interests.

Gamete providers should be able to use the pre-embryos themselves or donate them for use by other parties, but not sell them. In addition, research on pre-embryos should be permitted as long as the pre-embryos are not destined for transfer to a woman for implantation and as long as the research is conducted in accordance with the Council's guidelines on fetal research. Frozen pre-embryos may also be allowed to thaw and deteriorate.

Gamete providers should have an equal say in the use of their pre-embryos and, therefore, the pre-embryos should not be available for use by either provider or changed from their frozen state without the consent of both providers. The man and woman each has contributed half of the pre-embryo's genetic code. In addition, whether a person chooses to become a parent and assume all of the accompanying obligations is a particularly personal and fundamental decision. Even if the individual could be absolved of any parental obligations, he or she may have a strong desire not to have offspring. The absence of a legal duty does not eliminate the moral duty many would feel toward any genetic offspring.

Advance agreements are recommended for deciding the disposition of frozen pre-embryos in the event of divorce or other changes in circumstances. Advance agreements can help ensure that the gamete providers undergo IVF and pre-embryo freezing after a full contemplation of the consequences but should not be mandatory. (Issued March 1992 based on the report "Frozen Pre-Embryos," issued December 1989; Updated June 1994 [I, III, IV, V])

RECOMMENDATIONS

The following statements, recommended by the Council on Scientific Affairs, were adopted by the AMA House of Delegates as AMA policy in December 1999.

1. The AMA ncourages strong public support of federal funding for research involving human pluripotent stem cells (PSC);   
2. The AMA supports the recommendations of the National Bioethics Advisory Commission (NBAC) report, Ethical Issues in Human Stem Cell Research, September 1999, which include: (a)research involving the derivation and use of human embryonic germ cells (EGC) from fetal tissue cadavers should continue to be eligible for federal funding; (b) research involving the derivation and use of human embryonic stem cells (ESC) [ie, PSC] from embryos remaining after infertility treatments should be eligible for federal funding; (c) federal agencies should not fund research involving the derivation or use of human ESC from embryos made either solely for research purposes using IVF, or made using somatic cell nuclear transfer into oocytes; (d) prospective donors of embryos remaining after infertility treatments should receive timely, relevant, and appropriate information to make informed and voluntary choices; (e) in federally funded research involving embryos remaining after infertility treatments, researchers may not promise donors that ESC derived from their embryos will be used to treat patient-subjects specified by the donors; (f) embryos and cadaveric fetal tissue should not be bought or sold; (g) DHHS should establish a National Stem Cell Oversight and Review Panel to ensure that all federally funded research involving the derivation and/or use of human ESC/EGC is conducted in conformance with the ethical principles and recommendations contained in the NBAC report; (h) protocols involving the derivation of human ESC and EGC should be reviewed and approved by an institutional review board (IRB) or by another appropriately constituted and convened institutional review body prior to consideration by the Oversight and Review Panel (i) for privately funded research projects that involve ESC or EGC that would be eligible for federal funding, private sponsors and researchers are encouraged to adopt voluntarily the applicable recommendations of the report;  and (j) the National Stem Cell Oversight and Review Panel should be chartered for a fixed period of time, not to exceed five years.

3. The AMA will continue to monitor PSC research and update AMA policies as required with reference to advances in this field.

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APPENDIX I

Stem Cell Letter Sent to All Members of Congress 

February 19, 1999

The Honorable Arlen Specter 
United States Senate 
711 Hart Senate Office Building 
Washington, D.C. 20510

Dear Senator Specter:

The undersigned organizations applaud the determination by the Department of Health and Human Services that current law permits the use of federal funds to support research utilizing human pluripotent stem cells.

Human pluripotent stem cells have the ability to give rise to other more specialized types of cells, such as muscle, skin, nerve, pancreas or blood cells. This ability to produce specialized cells opens a tremendous avenue of research with enormous potential for the treatment of many diseases. For example, human stem cells could be used to produce different kinds of specialized cells and tissues for use in transplantation to treat many diseases and conditions, including neurological disorders such as Parkinson's and Alzheimer's diseases, heart disease and stroke, diabetes, osteoarthritis, rheumatoid arthritis, and spinal cord injury. Stem cell research also offers great promise for use in drug development and testing, to evaluate and understand both the beneficial and toxic effects of drugs on different human cell types, thus potentially reducing the need for animal studies and enabling fewer and more sharply focused human clinical trials. Research on human stem cells will open exciting new pathways by which to strengthen the understanding of normal human cell and tissue development. This, in turn, will accelerate our insights into the mechanisms of abnormal growth and development, and could lead to the discovery of radically new approaches to the prevention and treatment of birth defects and cancer. 

The Federal government has an important role in funding and in overseeing the conduct of this research so that the talent and creativity of the nation's scientists -- both privately and federally funded -- can be applied to this valuable line of research. Federal involvement creates a more open research environment, promoting the free exchange of ideas and data among scientists, and ensuring greater public engagement and the protections of federal regulatory oversight. Federal support will also increase fiscal resources and expand the pool of well-trained investigators engaged in this area of research, both of which will speed the pace of scientific discovery.

We concur with the National Institutes of Health's plans to move forward to develop clear guidelines to address the special scientific, legal, and ethical issues surrounding this research. We are confident that this process will have appropriate public input, as well as the advice of the National Bioethics Advisory Commission and NIH's newly established Council of Public Representatives. NIH has made clear that it will not support any research using human pluripotent stem cells until the appropriate guidelines have been developed and disseminated and an oversight process is in place.

Given the tremendous promise this research holds for millions of Americans, indeed all humankind, we strongly urge you to work with the NIH to ensure that this research can move forward with the support and oversight of the Federal government.

Stem Cell Letter to House and Senate Appropriations Committees 

July 29, 1999

The Honorable John Edward Porter,Chairman
Subcommittee on Labor, Health and Human Services, 
Education and Related Agencies 
Committee on Appropriations 
United States House of Representatives 
2373 Rayburn House Office Building 
Washington, D.C. 20515-1310

Dear Mr. Chairman:

This past February we wrote to you regarding our support for federal funding of research using human pluripotent stem cells. With the Appropriations process progressing we write now to reiterate that support and to urge you to allow this research to move forward.

Human pluripotent stem cells have enormous potential for treatment of disease because they have the ability to form into any type of cell in the body. But only a fraction of the work that will be necessary to transform this potential into reality has yet begun, and only a fraction of the biomedical research community has been able to participate because the federal government has not yet funded any of this work. The National Institutes of Health are in the process of completing guidelines that will permit and govern the use of these cells by federally funded investigators. Only when these guidelines are in place will it be possible to unleash the full capability of the biomedical research workforce toward bringing the remarkable potential of human pluripotent stem cells to fruition. 

It is also clear that the American public supports federal funding of this research. A recent nationwide survey conducted by Opinion Research Corporation International has found that 74% of those polled favor funding of stem cell research by the NIH. 

Some have argued that "adult" stem cells will be sufficient in our pursuit of treatments or cures of various diseases. While we believe that research in the area of adult stem cells is vital to the research effort, we are concerned that to restrict work to that area alone will prove insufficient and would be a grave mistake. The prospect of cutting off an avenue of research as promising as that with embryonic stem cells at this very early stage of discovery deeply troubles those of us who conduct and promote health research. Such a prohibition could delay possible treatments for diseases like diabetes, cancer, Alzheimer's and Parkinson's by years. Past work on animals has shown us that it is the embryonic stem cells that hold the greatest potential in their ability to be manipulated for treatments of disease. 

We are also concerned by the argument that embryonic stem cell research can be left to the private sector. While it is clear that a few privately funded centers are working on pluripotent stem cell research, it is not generally the practice of private companies to conduct this kind of basic research into fundamental developmental processes. That is why it has been and remains the role of the federal government to make the lion's share of the investment in basic research, which has then been used by biotechnology and pharmaceutical companies to develop products used for treating diseases. And that is why we cannot rely on private industry to conduct the kind of basic research necessary to move the field of stem cell research from the laboratory bench to the clinic. 

Our intent is simply to ensure that research on stem cell lines is not unduly restricted. With appropriate ethical safeguards, such as those being developed by the National Institutes of Health, we believe that a balance can be achieved, which respects both the moral status of the embryo and the public's sensitivity to this issue while ensuring progress in critical medical research. As we have said before, the government can play an important role of oversight so that our nation's federally funded scientists can conduct this critical work. Federal support will also increase the financial resources directed to this area of research, which will speed the pace of scientific discovery.

With the great hope pluripotent stem cell research provides to patients ailing or dying from devastating diseases, we urge the Congress to allow this research to move forward with federal support.