Spring 2001; Volume 2, Number 1
Implications of Policy Decisions on Human Embryonic Stem Cell Research in the United States
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Although research with human embryonic stem cells was recognized as one of the most promising fields in science by Science, in 1991 (Bloom, 1999), the issue of public funding remains a powerful determinant in the future of stem cell research.
Because federal law prohibits the use of public funding for any research that harms a human embryo, research projects in this area are so far exclusively conducted by the private sector. Recently, promising scientific results have been achieved in this field, and applications in tissue engineering and transplantation are now clearly envisioned. These techniques could have a major impact on the treatment of a variety of still incurable diseases (see below).
While a number of very insightful experiments have been conducted with mammalian embryonic stem cells, clinical research will ultimately require the use of human embryonic stem cells. However, ethical issues linked to the production of human embryonic stem cells solely for research purposes pose a challenge to policy makers. Despite numerous promising applications, a significant fraction of the general public is strongly opposed to any research involving human embryonic stem cells. Policy makers therefore must weigh the potential life-saving benefit of this research for the patient versus public concerns and reservations.
In order to balance the advancement of science in this field with ethical concerns, the National Institutes of Health (NIH) revised their funding guidelines. According to the new guidelines issued on August 23, 2000, federal funding is now available for fetal stem cell research and derivation of these cells. Derivation of embryonic stem cells is still not federally funded and research with embryonic stem cells is only funded if these cells are derived in compliance with the NIH guidelines (Vogel, Science 289 (2000), 1442-1443).
This research paper aims to analyze the scientific background that provides a solid basis for policy recommendations. After describing the current status of funding and regulation of human embryonic stem cell research, recommendations will be proposed to establish a persuasive regulatory framework.Scientific Background
Recent scientific advances regarding the isolation and successful culturing of human pluripotent stem cell lines have generated great excitement and promise major benefits for public health. Scientific studies have demonstrated that embryonic stem cells can be made to differentiate into any specific cell type, ultimately allowing the generation of tissue that can be used for transplantation therapy without causing any adverse immunological reaction. Such research could also contribute to the understanding of complex events that occur during human development, facilitating gene discovery and drug development.
Although recent experimental success has raised expectations for the clinical potential of human stem cells, most experts believe that healthcare benefits will not be realized until after several years of research. They are concerned that during this time the credibility of the field could be damaged by over-optimism and suggest restraint in making exaggerated claims.
In order to provide a solid background for political decision-makers, scientific terms must first be explained and clarified. There are essentially three different types of stem cells that are currently employed in scientific research:
Embryonic stem cells can develop into any kind of tissue. Because of this fact they are termed totipotent. Embryonic germ cells are more specialized stem cells, which eventually give rise to the gonads of the embryo. Adult stem cells and embryonic germ cells occur in later stages of development. Adult stem cells, such as blood stem cells, are found in human adults and can develop into more specialized cell types, such as red blood cells.
Both adult stem cells and embryonic germ cells are pluripotent, which means that they can give rise to many but not all of the cell types necessary for fetal development. Thus, pluripotent cell types cannot develop into a fetus when placed into a woman's uterus (NIH: Stem Cells - a Primer, 2000).
To distinguish between a fetus and an embryo, an embryo in this context is defined as existing in "the period from after the long axis appears until all major structures are represented. In humans, this is from about two weeks after fertilization to the end of the seventh or eighth week."
A fetus, on the other hand, is "a developing human offspring in the postembryonic period, from seven or eight weeks after fertilization to the time of birth" (Harcourt Dictionary of Science).
Recent success in the field of stem cell research has triggered the hope of many scientists to eventually be able to treat a number of diseases, which are so far either entirely incurable or curable only in conjunction with the significant disadvantages of organ transplantation. Apart from the dearth of organ-donations being very scarce, the patient has to endure a life-long suppression of the immune system to avoid graft-host reactions.
A solution to this problem could be posed by advances in stem cell research: a number of cell types (see below) can be developed from undifferentiated stem cells. With tissue derived from these cells, all the diseases in Table 1 might eventually be cured without fear of graft-host reaction because the transplanted tissues being immunologically identical to the patient's own cells.
While stem cells are necessary during early human development, pluripotent stem cells are found in children and adults. However on the way to specialization, the potential of pluripotent stem cells to differentiate into other cell types decreases substantially.
A number of critics of embryonic stem cell research favor the use of cells in later stages of human development, such as embryonic germ cells or adult stem cells, mostly for ethical reasons. However, stem cells from adults may not have the same capacity to proliferate as younger cells do. Additionally, adult stem cells do not exist in all tissues of the body, are often present in small quantities, are difficult to isolate and purify, and their numbers may decrease further with age. In addition, adult stem cells may contain more DNA abnormalities than embryonic stem cells, caused by long term exposure to sunlight and toxins as well as by errors made during DNA replication over the lifetime of the cell. Adult stem cells could also be disadvantaged when compared to embryonic stem cells with respect to their shortened telomeres (the ends of chromosomes). These phenomena might trigger undesirable responses such as apoptosis (programmed cell death) which would undermine the potential utility of adult stem cells in research and medical treatment.
Research on the early stages of cell specialization may also not be possible with adult stem cells since they appear to be farther along the developmental pathway than pluripotent stem cells. In order to determine the best source of the specialized cells and tissues of the body for new treatments and even cures, it will be important to study the developmental potential of adult stem cells and compare it to that of pluripotent stem cells (Aldhous, 2000).
Embryonic germ cells on the other hand are obtained from fetal tissue after miscarriage or abortion and thus carry a lesser ethical burden than the use of embryonic stem cells. Even though embryonic germ cells have some potential to develop into different types of tissue, these cells have led to abnormalities when introduced into embryos (McLaren, 2000). In addition, scientists have not been able to culture these stem cells for more than 21 days, a fact that clearly limits their use in scientific research.
It is crucial that relevant distinctions between the different cell types are made clear to both the public and to political decision-makers by disclosing possible consequences for stem cell research and future applications.The NIH Guidelines
In compliance with federal law, the newly revised NIH guidelines state that NIH-funded scientists are allowed to work with pluripotent stem cells. The cell lines used in this research have to be derived by private companies from frozen embryos discarded after fertility treatment. The donor of the embryo must have expressed informed consent and cannot accept any compensation. The NIH guidelines also seek to ensure that embryos are not created specifically for this purpose and that embryonic stem cells are not combined with animal cells. In addition, any attempts of reproductive cloning and the use of stem cells to create human embryos are strongly opposed. The NIH guidelines therefore prohibit public funding to be utilized for any of the above mentioned purposes (Vogel, Science 289: 2000, 1442).
In determining which types of embryonic stem cell research should be eligible for funding, a number of points are worth considering. First, it is possible that the creation of research embryos will provide the only means by which to conduct certain kinds of research, such as research into the process of human fertilization. Second, as in vitro fertilization techniques improve, it is likely that the supply of embryos for research from this source will decline. Nevertheless, the NIH has concluded that, from a scientific and an ethical perspective, there is no compelling reason at this time to provide federal funding for the creation of embryos for research. According to the NIH, cadaveric fetal tissue and embryos remaining after infertility treatment provide an adequate supply of research resources for federal research projects.
Currently, the derivation of human embryonic stem cells is only permitted in privately funded laboratories. Once a cell line is obtained, the stem cells could be passed on to federally funded scientists.
Researchers on federal grants are however concerned that privately funded scientists will gain important insights and advantages through derivation and experimental manipulation of stem cells. NIH-funded researchers will be limited to the cell lines provided by private firms and will not be able to create and tailor cell lines to meet their specific needs.
Most scientists and their supporters do not view the derivation and use of embryonic stem cells as ethically distinct activities and believe that it is important that federal funding be made available for protocols to derive such cells. Researchers using human embryonic stem cell lines hope to obtain substantial scientific benefits from a detailed understanding of the process of embryonic stem cell derivation and argue that the methods of derivation may affect the properties of the embryonic stem cells. Those dissatisfied with the current funding policy of the NIH emphasize the close connection in practical and ethical terms between both derivation and use of embryonic stem cells.Oversight and Review of Human Stem Cell Research
To ensure that the research involving stem cells is delivering the anticipated benefits and to identify any concerns that may arise, federal oversight at the local, national and institutional level is crucial to assure the public that this research is being undertaken in a controlled and legal manner.
When applying for NIH funding, scientists therefore have to submit their research proposals to four separate review bodies. In addition, the newly founded Human Pluripotent Stem Cell Review Group (HPSCRG) seeks to ensure compliance with the NIH guidelines. Despite the promise of the federal agency to work quickly, this process might however impose bureaucratic hurdles and delay research (Davis, 2000).
Another problem could arise if the embryonic stem cell lines currently used in federally funded research are not approved for further research according to the new guidelines because the process of their derivation did not occur in compliance with the new guidelines. In such cases some research projects could be substantially impeded and deferred or would have to be abandoned altogether (Kennedy, 2000).
Anonymous donation of embryonic stem cells to ensure privacy and informed consent of the donor might also conflict with the requirement of the NIH guidelines to trace back and document the precise origins of the cells (Marshall, 1999).page 1 | page 2 | references
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