The evolving ethics of anatomy: Dissecting an unethical past in order to prepare for a future of ethical anatomical practice

Anatomical practice has arguably one of the most ethically challenging histories in the medical sciences. Among the oldest scientific disciplines in medicine, dissection of the human body for scientific purposes occurred as early as the third century Before the Common Era. Throughout the history of anatomical practice, human dissection has occurred in ways that cross the line from progressing medical science to violating the sanctity of the human body. The dissection of the human body creates ethical dilemmas which stem from the need for anatomical science to gain medical knowledge in juxtaposition with prevailing religious and moral views surrounding anatomy as a threat to the sanctity of the human body. This article examines the unethical history of human dissection throughout the ages and explores the rationale behind the unethical practices. In addition, this article explores imperative modern day ethical standards in anatomy including, the ethical handling of human bodies, respecting human life, and ensuring informed consent for dissection of bodies that are donated. Finally, this article explores the question of which ethical prism we should use when dealing with anatomy collections or works of the past. Learning both the history of unethical practices in anatomy and the rationale behind them is imperative so that the discipline can prepare for an ethical, diverse, and inclusive future. This article provides a foundation for understanding the evolution of ethics in anatomical practice and is a valuable resource for students and anatomists alike.     

The new stem cell biology: something for everyone.

The ability of multipotential adult stem cells to cross lineage boundaries (transdifferentiate) is currently causing heated debate in the scientific press. The proponents see adult stem cells as an attractive alternative to the use of embryonic stem cells in regenerative medicine (the treatment of diabetes, Parkinson's disease, etc). However, opponents have questioned the very existence of the process, claiming that cell fusion is responsible for the phenomenon. This review sets out to provide a critical evaluation of the current literature in the adult stem cell field.     

The subsidiarity principle in the context of embryonic stem cell research

Embryonic stem cell research is regulated by different forms of the subsidiarity principle, i.e. research on embryos should only be conducted if no suitable alternatives exist. Four types are discussed: animal versus human material, adult versus embryonic stem cells, affected or at risk embryos versus healthy embryos, and supernumerary versus research embryos. Three major arguments regarding the subsidiarity principle are discussed: the necessity argument, the least offensive moral approach and the 'nothing is lost' argument. It is proposed that the burden of proof should be shifted onto those who oppose embryonic research. When the freedom of research and the moral obligation to relieve human suffering is taken seriously, the opponents of this research should first demonstrate that embryonic stem cells do not work or that adult stem cells work better.     

Deriving morally uncontroversial human pluripotent stem cell lines: obligation or election?

At present, the American public debate over the moral status of the human embryo has stalemated, and perhaps intractably so. On one side of the discussion, all or most of the stem cell research community (together with as many as two-thirds of the American public*) conclude that, because the human embryo is not a member of the human community, the creation and destruction of human embryos are far outweighed by the good end of developing prospective cures. On the other side of the debate, a very small number of scientists/clinicians and roughly one-third of Americans conclude that, because the human embryo is a member of the human community and, therefore, enjoys the same rights as mature human beings, the good end of embryonic stem cell research (ESCR) (therapies for those suffering from degenerative diseases) does not validate its unjust means (creation/destruction of embryonic human beings). The impasse in the status-of-the-humanembryo debate is mirrored in the deadlock over federal funding. Investigators interested in pursuing ESC-derived therapies have applied for private and state funding. But they are lobbying, at the same time, for legislation that would appropriate federal monies for research using spare IVF embryos. In contrast, those with moral objections to ESCR have rallied behind postnatal (or adult) stem cell initiatives, insisting that these are the only research projects worthy of their state and federal tax dollar support. ESC researchers respond by reminding their detractors that, even though adult stem cells may be effective in treating some kinds of degenerative conditions, only ESCs possess the stable pluripotency and plasticity needed to treat the entire spectrum of degenerative diseases. Acknowledging both the debate gridlock and the unique therapeutic power of ESCs, people on both sides of these issues have begun to ask, "Would there be a way to derive human pluripotent stem cells (hPSCs)-the functional equivalent of hESCs-without destroying human embryos?" In other words, "Is it possible to offer all Americans the prospective benefits of pluripotent stem cell derived therapies without provoking the moral disdain of a sizable minority?"     

Stem cell research and the ethics of transparency

Stem cell research represents a field of scientific inquiry subject to intense public and political attention and debate worldwide. There are several reasons for this. First, it is a research endeavor surrounded by great expectations of future therapeutic benefits. Some of these expectations seem to be well founded, while others originate from adult and embryonic research enthusiasts having hyped their case. A second reason why this represents a field of public and political attention relates to deeply felt concerns regarding the moral justifiability of sacrificing potential human lives for research. The aim of this paper is to discuss different ways of making the performance of international embryonic stem cell research more transparent, and of unveiling the need for more open-minded dialog concerning the ethical costs of this research endeavor.     

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.     

Sustained interaction: the new normal for stem cell repositories?

Stem cell repositories, similar to many areas in human scientific research, must balance the interests of the individuals who donate their time and samples to science with the interests of scientific progress. This article seeks to explore how sustained interaction with stem cell donors can advance key donor interests (autonomy and privacy) while also increasing the scientific utility of stem cell lines. The ability to trace stem cell lines to their respective donors - underpinned by robust informed consent - enables donors to gain access to information regarding research outcomes and the uses of their biological samples, while also supporting basic and clinical research by providing a means for quality and safety controls. Measures to recontact donors and also to enable donors to withdraw from research should be well designed to ensure donors' preferences are respected while mitigating negative consequences resulting from limited data availability or compromised sample quality. To guarantee the integrity of research while respecting donors' autonomy and preferences, stem cell repositories require a prospective approach to informed consent.     

Exploring common ground in the stem cell ethical debate—A perspective for scientists

The purpose of this special issue of Stem Cell Reviews is to address some of the most difficult ethical debates surrounding the derivation of pluripotent stem cell lines. The possible benefits of stem cells are widely discussed, but the scientific community is particularly aware that research in this area is still at an early, but essential, stage of development. With this research at such an early stage, it is noteworthy that the media, the public, religious leaders, politicians, policy makers, and regulators have had as much interest in stem cell research as for any other area of scientific inquiry. The central issue that has made this area so controversial has been the use of the human embryo for deriving stem cell lines.     

表皮干细胞：治疗难愈性皮肤创面的种子细胞

难愈性皮肤创面是指在期望的时间内不能正常愈合的皮肤组织创面。本文以表皮干细胞（ESC）为靶点,对其在难愈性皮肤创面愈合中的研究和应用进行综述。首先介绍ESC的解剖位置和对创面愈合的调节作用。其次,总结难愈性皮肤创面的特点及共同的病理学机制。最后,归纳ESC在难愈性皮肤创面愈合中的作用：直接修复损伤皮肤组织;作为组织工程学构建人工皮肤的种子细胞;以及其基因修饰治疗用于皮肤创面修复。     

Stem Cell Research in the Greater Middle East: The Importance of Establishing Policy and Ethics Interoperability to Foster International Collaborations

While fossil fuel reserves have strengthened the economies of numerous countries in the Greater Middle East (GME) for decades, multiple nations within this region are now increasingly investing in internal science and engineering programs as a mechanism to develop more extensive knowledge-based economies. One of these newly pursued disciplines is stem cell research. Nations such as Saudi Arabia and Qatar have founded nascent programs while Iran, Turkey, and Israel are more established in the field. The extent to which these investments have been productive, as measured by publication quantity and impact, remains unknown. Here we assess the state of stem cell research in the GME, report on the policy and ethical considerations facing the region, and determine the impact of international research collaborations in this area. In the majority of the region, there is no legal framework regulating stem cell research. Instead, scientists often rely on religious decrees outlining acceptable practices. These guidelines do not provide the necessary structure to foster international collaborations with nations that have enacted formal laws recognized worldwide. Our results illustrate that international collaborations in the GME produce publications of greater impact despite the fact that political tensions and issues unrelated to science have the potential to dramatically hinder cross-border relationships in the region. Overall, we conclude that the national governments of countries within the GME have the unique opportunity to establish stem cell research policies which confer interoperability between nations to foster crucial international collaborations throughout the region.     

The Evolution of Policy Issues in Stem Cell Research: An International Survey

Stem cell research remains a tremendously promising yet controversial field of study. It continues to attract considerable public interest and generate discussion and debate. However, while the high profile of this field has endured, the tone and nature of the discourse that drives this profile appears to be changing. In order to get a better sense of how these potential shifts are perceived by individuals directly embedded in the field, we conducted an international internet survey of members of the stem cell research community. Our participants included individuals publishing on both scientific and ethical, legal and social issues topics. We explored the degree to which participants perceived that key policy issues were becoming more or less contentious over time. We queried views regarding the effect of regulatory frameworks on emerging stem cell research technologies and the extent to which participants experience pressure related to clinical translation. We also explored participants?? relationships with industry, experience with patents and perceptions regarding the emphasis placed on the potential economic benefits of stem cell research. Our results suggest that while traditional debates such as those surrounding the moral status of the embryo remain, other issues more closely associated with clinical translation and commercialization are perceived as becoming increasingly contentious. This survey provides useful insight into the perspectives of a sample of active researchers working in countries around the world as well as an opportunity to reflect on the likely direction of future stem cell policy debates.     

Mass preparation of size-controlled mouse embryonic stem cell aggregates and induction of cardiac differentiation by cell patterning method

Embryonic stem cells (ESCs) are promising cell sources for cell-based therapy. It has been established that the formation of ESC aggregates promotes their differentiation into the derivatives of all three germ layers. ESC aggregates are generally prepared via the formation of suspended spherical aggregates called embryoid bodies (EBs). Because the differentiation efficiency depends on the size of EBs, it becomes one of the research topics how to prepare size-controlled EBs in a scalable manner for reproducible and high-throughput experiments. Here, we have developed a novel culture method that enables simple mass preparation of size-controlled ESC aggregates on a culture surface instead of floating EBs. We developed a maskless photolithography device that enabled rapid fabrication of micropatterned surfaces. Utilizing this device, we fabricated the culture substrates the surfaces of which comprised arrays of cell-adhesive circular micro-domains (100–400 μm in diameter) and the rest of non-cell-adhesive domains. We seeded mouse ESCs on this substrate and prepared size-controlled ESC aggregates on the micro-domains. We analyzed cardiac differentiation in the ESC aggregates and found that the optimal diameter of micro-domains was 200 μm. The present method is useful for the simple and reproducible mass preparation of ESC-derived differentiated cells and high-throughput assays.     

Pilot assessment of HIV gene therapy-hematopoietic stem cell clinical trial acceptability among minority patients and their advisors

Clinical trials involving technologically involved novel treatments such as gene therapy delivered through hematopoietic stem cells as human immunodeficiency virus (HIV) treatment will need to recruit ethnically diverse patients to ensure the acceptance among broad groups of individuals and generalizability of research findings. Five focus groups of 47 HIV-positive men and women, religious and community leaders and health providers, mostly from African American and low-income communities, were conducted to examine knowledge about gene therapy and stem cell research and to assess the moral and ethical beliefs that might influence participation in clinical trials. Three themes emerged from these groups: (1) the need for clarification of terminology and the ethics of understanding gene therapy-stem cell research, (2) strategies to avoid mistrust of medical procedures and provider mistrust, and (3) the conflict between science and religious beliefs as it pertains to gene therapy-stem cell research.     

Do We Have a Workable Clinical Protocol for Differentiating Lympho‐Hematopoietic Stem Cells from the Source of Embryonic Stem Cells and Induced Pluripotent Stem Cells in Culture?

In recent years, many researchers are focusing on deriving lympho‐hematopoietic stem cells (L‐HSC) from human embryonic stem cells (ESC) and/or induced pluripotent stem cells (iPSC) in culture as alternative sources for transplantation. Two protocols are available for research purposes: mouse stroma cell line coculture system and embryoid bodies (EBs) suspension culture system. However, due to the lack of human stroma cell line, which could support the derivation of L‐HSC in culture, the generation of therapeutic lympho‐hematopoietic cells for clinical purpose can only be achieved using EBs suspension culture system. In this short communication/review, the results of EBs suspension culture system using mouse and human ESC/iPSC are summarized and the potential clinical application is discussed.     

Concise review: Deciphering the mechanism behind induced pluripotent stem cell generation

Regenerative medicine using spluripotent/multipotent stem cells holds a great promise in developing therapies for treating developmental abnormalities, degenerative disorders, and aging-related illness. However, supply and safety of the stem cells are two major problems with today's regenerative medicine. Recent development of induced pluripotent stem cells (iPSCs) has overcome the supply shortages by allowing the reprogramming of patients' body cells to embryonic stem cell (ESC)-like pluripotent cells. Still, the potential tumorigenicity of iPSCs remains as an obstacle. During early embryogenesis ESCs can be generated without tumor formation; therefore, understanding the mechanisms underlying ESC generation may help us to prevent iPSC tumorigenicity. Previous studies have shown that an ESC-enriched noncoding RNA, miR-302, induces somatic cell reprogramming (SCR) to form iPSCs, suggesting its pivotal role in stem cell generation. Recent research further revealed that miR-302-induced SCR involves an epigenetic reprogramming mechanism similar to the natural zygotic reprogramming process in the two- to eight-cell-stage embryos. These findings indicate that miR-302, as a cytoplasmic gene silencer, inhibits the translation of multiple key epigenetic regulators, including AOF1/2, methyl-CpG binding proteins 1 and 2, and DNA (cytosine-5-)-methyltransferase 1, to induce global DNA demethylation, which subsequently triggers the activation of the previously defined factors Oct4, Sox2, and Nanog to complete the reprogramming process. The same mechanism was also found in the event of somatic cell nuclear transfer. Based on these advanced understandings, this review describes the currently established SCR mechanism--as compared to the natural process of early ESC formation--and demonstrates how stem cell researchers may use this mechanism to improve iPSC generation.     

The search for alternative sources of human pluripotent stem cells

Human embryonic stem cells (ESCs), stable, pluripotent, and self-renewing, are today of tremendous interest, both to scientists seeking to better understand human development and to clinicians hoping to use them to replace and restore cells that have been damaged by disease or injury. As of this writing, alas, it is impossible to obtain new lines of human ESCs without destroying human embryos. Whether it is ethical to do so is a subject of sharp and persistent controversy. On one side is the potentially great (though as yet unrealized) promise of these cell lines to advance knowledge and to relieve human suffering; on the other side is the respect (and protection) many Americans feel is owed to nascent human life. As both sides of the argument have something vital to defend, a national consensus seems elusive for the time being. In the absence of such a consensus, embryodestructive stem cell research is likely to remain legal in the United States, but the eligibility of such research for federal funding will be politically contentious for years to come. As long as human ESC research remains entangled in legal, ethical, and political conflict, neither side in the national debate is likely to be satisfied, and conciliation seems out of the question.     

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.     

Stem cell research: cloning, therapy and scientific fraud

Stem cell research has generated intense excitement, awareness, and debate. Events in the 2005-2006 saw the rise and fall of a South Korean scientist who had claimed to be the first to clone a human embryonic stem cell line. From celebration of the potential use of stem cells in the treatment of human disease to disciplinary action taken against the disgraced scientists, the drama has unfolded throughout the world media. Prompted by an image of therapeutic cloning presented on a South Korean stamp, a brief review of stem cell research and the events of the Woo-suk Hwang scandal are discussed.     

Credentialed Persons, Credentialed Knowledge

The vast experimental literature on human error agrees with history of medicine, folklore, and superstition In discrediting knowledge claims based solely on anecdotal impressions. Since clinical experience consists of anecdotal impressions by practitioners, tt Is unavoidably a mixture of truths, half-truths, and falsehoods. The scientific method is the only known way to distinguish these, and it is both unscholariy and unethical for psychologists who deal with other persons' health, careers, money, freedom, and even life itself to pretend that clinical experience suffices and that quantitative research on diagnostic and therapeutic procedures is not needed. Disputes about philosophy of science (e.g., logical positivism) are irrelevant to this issue, which is simply one of distinguishing knowledge claims that bring reliable credentials and others that do not.