Human embryonic stem cells: research,ethics and policy

The use of human embryos for research on embryonic stem (ES) cells is currently high on the ethical and political agenda in many countries. Despite the potential benefit of using human ES cells in the treatment of disease, their use remains controversial because of their derivation from early embryos. Here, we address some of the ethical issues surrounding the use of human embryos and human ES cells in the context of state-of-the-art research on the development of stem cell based transplantation therapy.     

'New embryos' - new challenges for the ethics of stem cell research

Among the many ethical issues raised by human embryonic stem cell research (in the following all references to 'stem cells' should be read as references to human embryonic stem cells), two have gained specific prominence: (1) whether stem cell research is ethically problematic because it entails the destruction of human embryos and (2) what kind of control embryo donors should have over the stem cell lines derived from their embryos. In the present paper, I will analyse how these two issues are engaged by various attempts to derive stem cells from anomalous embryos (e.g. embryos in cleavage arrest, embryos not implanted following pre-implantation genetic diagnosis or embryos created by altered nuclear transfer) or in ways that are claimed to be non-destructive for the embryo (e.g. blastocyst or blastomere biopsy).     

Stem Cell Policy Exceptionalism: Proceed with Caution

The term "stem cell exceptionalism" has been used to characterize the policy response to controversies surrounding human embryonic stem cell research. For example, governments and funding agencies have adopted policies governing the derivation and use of human embryonic stem cell lines. These policies have effectively served to fill gaps in existing guidelines and regulations and signal that scientists are committed to a responsible framework for the conduct of research involving human embryos. Recent publications discuss whether ethical and policy issues associated with induced pluripotent cells (iPSCs) from non-embryonic sources create a need for further policy intervention. We suggest many of the issues identified by commentators may be addressed through the application of established policy frameworks governing the use of tissue, human stem cells, and research participation by human research subjects. To the extent, iPSC research intersects with hESC research (e.g. the creation of human gametes and/or embryos), the policy framework governing hESC appears sufficiently robust at this time.     

胚胎干细胞研究的伦理和心理学问题

背景：胚胎干细胞研究具有重要的医学价值,在基因治疗、组织工程学、药学等许多领域都具有广泛的应用,使人们看到了治疗疾病的新希望,而其相关研究成果也引发了许多伦理和心理学问题。 目的：综述目前胚胎干细胞研究中的伦理和心理学问题。 方法：应用计算机检索2001-01/2010-12 PubMed数据库、维普数据库及万方数据库有关干细胞研究产生的伦理和心理学问题相关文献,英文检索词“embryonic stem cells,morality,psychological”,中文检索词“胚胎干细胞,伦理学,心理学”。检索文献量总计122篇,最终纳入符合标准的文献33篇。 结果与结论：胚胎干细胞究中伦理学问题的焦点主要包括：干细胞来源的伦理学问题,干细胞“克隆”的伦理学问题,干细胞与生命的伦理学问题,干细胞研究存在和需要解决的问题及干细胞研究中伦理学规范问题。干细胞研究中的心理学问题主要是人们对干细胞研究特别是“克隆”技术的认识。相关研究多涉及造血干细胞移植患者的心理变化。胚胎干细胞的研究目前已取得了突破性成果,给医疗、卫生健康等方面带来了革命性影响。     

Ethical and Policy Issues Surrounding the Donation of Cryopreserved and Fresh Embryos for Human Embryonic Stem Cell Research

The use of human embryos in human embryonic stem cell (hESC) research raises significant ethical and policy issues associated with their donation. Recent research conducted in several countries assesses the percent of persons with cryopreserved and fresh supernumerary embryos willing to donate them for research, their reasons for considering this option, and the concerns they raise about its personal import. Such research provides new insights into rising ethical and policy questions associated with embryo donation for hESC research that should be addressed. In response to such questions, it is argued here that consent to the donation of supernumerary embryos for hESC research should be sought in two or three stages, depending on whether fresh or frozen embryos are at issue, in order to provide patients and their partners with sufficient time and information before they make a final decision. In addition, steps should be taken to support the voluntariness of their decisions by having personnel other than the treating reproductive specialist or stem cell investigators solicit their consent. Prospective embryo donors should also be given a choice about the uses to which hESCs derived from their donated embryos will be put in order to honor their ethical convictions and ensure that there are sufficient embryos for this research. The well-being and rights of those who donate embryos for this research require the sort of support and protection that can be provided by an ethical and policy framework that allows hESC investigations to move forward according to standards that are transparent and that resound with public values.     

Donation of embryos for stem cell research--how many couples consent?

BACKGROUND: The huge potential of human embryonic stem cells has been a subject of wide discussion as regards the ethical and legal justification of using human embryos for establishing such cell lines. The opinions of infertile couples and their willingness to donate their supernumerary embryos for stem cell research have not been investigated earlier. METHODS: We conducted an analysis of the answers of couples who were asked to give informed consent as regards donating their embryos for stem cell research in our IVF unit in 2001-2002. RESULTS: Ninety-two percent of the couples gave informed consent as regards establishing and characterizing embryonic stem cell lines from the embryos which could not be used in their infertility treatment. Discussion in the Swedish media during May to December, 2001 regarding the importance and ethical justification of stem cell research made informing the couples easier. CONCLUSION: A high proportion, 92%, of couples who underwent infertility treatment in Sweden preferred donating their supernumerary embryos for stem cell research rather than letting them be discarded.     

Ethical Assessment of Human Embryonic Stem Cell Research According to Turkish Muslim Scholars: First Critical Analysis and Some Reflections

Background

Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.

Objective(s)

To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.

Design

Qualitative study.

Setting

Muslim scholars located in different parts of Turkey.

Methods

Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.

Results

Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.

Conclusion

Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.

     

The Procurement of Cells for the Derivation of Human Embryonic Stem Cell Lines for Therapeutic Use: Recommendations for Good Practice

The donation of human embryos for the derivation of embryonic stem cell lines that may be used in the development of therapeutic products raises more complex ethical, practical and regulatory problems than the donation of embryos for non-clinical research. This review considers these issues and offers recommendations for good practice.     

Stem cells from residual IVF-embryos - Continuation of life justifies isolation

Embryonic stem cells are undifferentiated pluripotent cells that can indefinitely grow in vitro. They are derived from the inner mass of early embryos. Because of their ability to differentiate into all three embryonic germ layers, and finally into specialized somatic cell types, human embryonic stem cells represent important material for studying developmental biology and cell replacement therapy. They are usually isolated from excess human IVF-embryos. Since many people regard isolation of human stem cells as intentional killing of the embryo, it is a very difficult ethical problem. Similar feelings concern medical or scientific use of these stem cells. Is this feeling correct, or does it arise from a sentimental view? The problem encloses two aspects: (i) use of stem cells for medical therapy and scientific research and (ii) isolation of stem cells from human IVF-embryos. Worldwide human tissues are cultured, transplanted and used for medical and scientific research. Therefore, it may be concluded that factual use of human embryonic stem cells cannot be a real ethical problem. The main key of the problem seems to be hidden in the exact definition of 'death'; in other words: is there nothing between 'death' and 'life'? Bacterial spores, lyophilised bacteria and other micro-organisms, micro-organisms stored in glycerol mixtures at -80 degrees C and tissue cultures and sperm cells stored in liquid nitrogen, they are all neither dead nor alive, but still viable. From this point it is clear that there is more than the antithesis 'dead' versus 'alive'. In addition, we think that there is still another alternative: partial death. The present view concerning isolation of stem cells implies that residual embryos and thus new human lives are killed, and that therefore these embryos must be (passively) destroyed. However, it is especially the very well planned IVF-procedure that makes that passive destruction of not-implanted embryos means intentional killing. By isolation of stem cells embryos are not fully killed: at least one embryonic cell, i.e., a stem cell, remains alive. The life of stem cells cannot be qualified as independent. Nevertheless, the embryo's life is not completely stopped and continues in a primitive way of life and consequently it is not completely dead. Against this background we feel that isolation of human embryonic stem cells is preferred instead of passive destruction.     

Alternative sources of pluripotent stem cells: scientific solutions to an ethical dilemma

Stem cell researchers in the United States have faced a quagmire of uncertainty due to multiple factors: the ethical divide over the use of embryos for research, the lack of clarity in federal guidelines governing this research, the restrictive patent situation surrounding the generation of new human embryonic stem (HES) cell lines; and the limits on types of research eligible for federal funding. In this commentary, we describe how recent advances in derivation of hES cell-like lines may allow at least some of these uncertainties to be resolved. More importantly, we suggest that the derivation of hES cell-like lines by morally acceptable methods would not only avoid the corrosive effects of a protracted ethical debate over stem cell research, but would also allow U.S. researchers to access federal funds and compete on a more level international playing field.     

Diversity in Public Views Toward Stem Cell Sources and Policies

Studies of public views on stem cell research have traditionally focused on human embryonic stem cells. With more recent scientific research on developing other stem cell sources, a series of focus group studies was undertaken with Canadian adults to examine their views on different stem cell sources (adult, umbilical cord blood, human embryonic stem cells, somatic cell nuclear transfer or SCNT, and interspecies nuclear transfer, or iSCNT). Views on three different policy models—a permissive, middle-of-the-road and restrictive policy approach—were also explored. Participants were recruited from several different social groups including patients, young adults, seniors, members of two ethnic communities, and a mixed group of adults. Participants were generally supportive of the use of adult stem cell sources. While there was also majority support for the use of hESC and SCNT, this was conditional on strict regulatory oversight. There was also majority support for a permissive policy which allows research on hESC and SCNT. General themes that cut across different groups included the potential cost of new technologies to the health care system, issues around who would gain access to these technologies, and trust in the scientific establishment and regulatory systems. A diversity of viewpoints was found as participants justified their positions on stem cell sources and policy approaches, showing more complexity and nuance than has been generally portrayed. The authors acknowledge support for this study from the project “Towards the clinic: ethical, legal, and social issues relevant to emerging stem cell therapies” funded by the Stem Cell Network of Canada.     

An ethical analysis of alternative methods to obtain pluripotent stem cells without destroying embryos

Although few ethical concerns exist regarding the use of adult stem cells, the field of embryonic stem cell research is fraught with moral qualms. Several alternative sources of pluripotent stem cells have recently been presented that try to sidestep the destruction of human embryos. The goal of these new proposals is to avoid embryo destruction, the main objection to embryonic stem cell research and thus introduce a type of stem cell research that would gain widespread approval and support. This article suggests that most embryo-saving alternatives fail to reach this goal given the concessions they require with regard to the speed of progress, technical complexity, safety and security of applications, degree of dependence on limited resources and extent of the field of application. The second part of the article identifies and analyses the two main strategies that alternative sources of pluripotent stem cells are based on and points out their shortcomings.     

The status of human nuclear transfer

Human therapeutic cloning is a recently emerged application of somatic cell nuclear transfer (SCNT), which is currently being performed to produce patient-specific stem cell lines for future stem cell therapies. The advantages in producing human nuclear transfer (NT) embryos to derive NT stem cell lines are that these can be tailor-made (i.e., are autologous in nature) for the patient and may overcome the need to administer life-long immunosuppression following stem cell transplantation. Although the rationale for using NT embryos is not for reproductive purposes, human NT remains clouded in ethical, moral, and religious controversies. The recent retraction of high-impact factor publications in the field of human NT from a research group in South Korea has placed stem cell research in a delicate situation. These heavily publicized issues may hinder the progress of this research and may threaten to bring current research to a complete halt. This review outlines the recent status of human NT, its continuing progress and the difficulties the field faces. Of most concern are the ethical issues, which surround obtaining human oocytes for research. Recent evidence suggests that failed-to-fertilize oocytes are poor sources for human SCNT, but obtaining fresh, viable oocytes may be even more problematic. The current status of human SCNT is outlined in this review with particular reference made to, lessons learnt from animal research, the oocyte dilemma and optimization of human NT.     

Regulation of Human Stem Cell Research in Australia

Australia is currently well placed to contribute to the global growth of human stem cell research. However, as the science has progressed, authorities have had to deal with the ongoing challenges of regulating such a fast moving field of scientific endeavour. Australia’s past and current approach to regulating the use of embryos in human embryonic stem cell research provides an insight into how Australia may continue to adapt to future regulatory challenges presented by human stem cell research. In the broader context, a number of issues have been identified that may impact upon the success of future human stem cell research in Australia.     

Ethics and embryonic stem cell research

There are important ethical issues that can be raised about embryonic stem cell research. One large ethical issue that has unfortunately arisen recently has to do with the falsification of scientific results and how, if at all, the scientific community can protect itself from such a thing. Regarding all medical research, and indeed, regarding everything having to do with health care policy, there are important ethical issues about who bears the burdens and reaps the benefits in a health care system that is fundamentally unjust, inhumane and inadequate to the needs of the growing segment of our population that is economically disadvantaged. Who is going to own this technology? Who is going to reap the economic benefits from it? How are the medical benefits going to be distributed? Yet another ethical issue is about how properly to obtain informed consent from women who volunteer to donate eggs for embryonic stem cell research, since there are some risks, but no direct benefits, to the donor.     

Ethical aspects of tissue engineering: a review

Tissue engineering (TE) is a promising new field of medical technology. However, like other new technologies, it is not free of ethical challenges. Identifying these ethical questions at an early stage is not only part of science's responsibility toward society, but also in the interest of the field itself. In this review, we map which ethical issues related to TE have already been documented in the scientific literature. The issues that turn out to dominate the debate are the use of human embryonic stem cells and therapeutic cloning. Nevertheless, a variety of other ethical aspects are mentioned, which relate to different phases in the development of the field. In addition, we discuss a number of ethical issues that have not yet been raised in the literature.     

Stem Cells in Amniotic Fluid as New Tools to Study Human Genetic Diseases

In future, the characterization and isolation of different human stem cells will allow the detailed molecular investigation of cell differentiation processes and the establishment of new therapeutic concepts for a wide variety of diseases. Since the first successful isolation and cultivation of human embryonic stem cells about 10 years ago, their usage for research and therapy has been constrained by complex ethical consideration as well as by the risk of malignant development of undifferentiated embryonic stem cells after transplantation into the patient’s body. Adult stem cells are ethically acceptable and harbor a low risk of tumor development. However, their differentiation potential and their proliferative capacity are limited. About 4 years ago, the discovery of amniotic fluid stem cells, expressing Oct-4, a specific marker of pluripotent stem cells, and harboring a high proliferative capacity and multilineage differentiation potential, initiated a new and promising stem cell research field. Inbetween, amniotic fluid stem cells have been demonstrated to harbor the potential to differentiate into cells of all three embryonic germlayers. These stem cells do not form tumors in vivo and do not raise the ethical concerns associated with human embryonic stem cells. Further investigations will reveal whether amniotic fluid stem cells really represent an intermediate cell type with advantages over both, adult stem cells and embryonic stem cells. The approach to generate clonal amniotic fluid stem cell lines as new tools to investigate molecular and cell biological consequences of human natural occurring disease causing mutations is discussed.     

Human embryonic stem cells: the real challenge for research as well as for bioethics is still ahead of us

Research on human embryonic stem cells (ESCs) has aroused a lot of controversy for years. Stimulated by recent work on mammalian embryology and new developments in stem cell research, an International Symposium entitled 'Stem Cell Research: A Challenge for Embryology, Regenerative Medicine and Bioethics' was held in Bonn (Germany) in 2006, bringing together embryologists, stem cell researchers and ethicists interested in human ESC research and the ensuing ethical debate. Two contributions to this Symposium are being published in Cells Tissues Organs, and the present paper aims to provide an introduction to these as well as personal impressions of the author about the perspectives that surfaced at the meeting, confronting them with relevant reports about stem cell research published recently. This paper highlights discussions about the mechanisms of specification of the main body axes during development, the role of extrinsic or intrinsic signals, and about the remarkable potential of ESCs to develop a basic body plan (individuation capacity) resembling properties of early embryonic cells (as shown by the formation of embryoid bodies and entire embryos if tetraploid complementation is performed). Another topic is 'alternative sources for human ESCs' recently proposed by the US President's Council on Bioethics ('organismically dead embryos', biopsied blastomeres or 'biological artifacts', e.g. created by 'altered nuclear transfer' and reprogramming of somatic cells). The possibility to rescue such (epi)genetically handicapped cells shows that this is not a way leading out of the ethical cul-de-sac. Recent reports about reprogramming somatic cells (fibroblasts) to gain ES-like potential highlight again the importance of focusing on the developmental potentiality as the major challenge for ethical considerations. Such a change of focus may be the only way out of the ethical impasse.