This paper examines potential ethical and legal issues arising during the research, develop- ment and clinical use of a proposed strategy in personalized medicine (PM): using human induced pluripotent stem cell (iPSC)-derived tissue cultures as predictive models of individ- ual patients to inform treatment decisions. We focus on epilepsy treatment as a likely early application of this strategy, for which early-stage stage research is underway. In relation to the research process, we examine issues associated with biological samples; (...) data; health; vulnerable populations; neural organoids; and what level of accuracy justifies using the iPSC-derived neural tissue system. In relation to clinical use, we examine potential uses in pre-natal screening, and effects on clinical decision-making. Although our focus is providing recommendations for researchers developing work in this area, we identify the novel issue of deciding on an acceptable accuracy level for the system. We also emphasize an issue thus far neglected in the ethics of PM: PM tends to represent treatment decisions as though they should be directed solely by biomedical information, but this in itself could be detri- mental to best personalizing treatment decisions in the clinic. (shrink)

The discovery of induced pluripotent stem (iPS) cells in 2006 was heralded as a major breakthrough in stem cell research. Since then, progress in iPS cell technology has paved the way towards clinical application, particularly cell replacement therapy, which has refueled debate on the ethics of stem cell research. However, much of the discourse has focused on questions of moral status and potentiality, overlooking the ethical issues which are introduced by the clinical testing of iPS (...) cell replacement therapy. First-in-human trials, in particular, raise a number of ethical concerns including informed consent, subject recruitment and harm minimisation as well as the inherent uncertainty and risks which are involved in testing medical procedures on humans for the first time. These issues, while a feature of any human research, become more complex in the case of iPS cell therapy, given the seriousness of the potential risks, the unreliability of available animal models, the vulnerability of the target patient group, and the high stakes of such an intensely public area of science. Our paper will present a detailed case study of iPS cell replacement therapy for Parkinson's disease to highlight these broader ethical and epistemological concerns. If we accept that iPS cell technology is fraught with challenges which go far beyond merely refuting the potentiality of the stem cell line, we conclude that iPS cell research should not replace, but proceed alongside embryonic and adult somatic stem cell research to promote cross-fertilisation of knowledge and better clinical outcomes. (shrink)

Reprogramming of somatic cells to a pluripotent state holds huge potentials for regenerative medicine. However, a debate over which method is better, somatic cell nuclear transfer (SCNT) or induced pluripotent stem (iPS) cells, still persists. Both approaches have the potential to generate patient‐specific pluripotent stem cells for replacement therapy. Yet, although SCNT has been successfully applied in various vertebrates, no human pluripotent stem cells have been generated by SCNT due to technical, (...) legal and ethical difficulties. On the other hand, human iPS cell lines have been reported from both healthy and diseased individuals. A recent study reported the generation of triploid human pluripotent stem cells by transferring somatic nuclei into oocytes, a variant form of SCNT. In this essay, we discuss this progress and the potentials of these two reprogramming approaches for regenerative medicine. (shrink)

The recent successful conversion of adult cells into induced pluripotent stem (iPS) cells through direct reprogramming opens a new chapter in the study of disease and the development of regenerative medicine. It also provides a historic opportunity to turn away from the ethically problematic use of embryonic stem cells isolated through the destruction of human embryos. Moreover, because iPS cells are patient specific, they render therapeutic cloning unnecessary. To maximize therapeutic benefit, adult stem cell (...) research will need to be pursued in parallel with studies using iPS cells. Among the four alternative methods presented by the President’s Council on Bioethics, direct reprogram- ming is the most ethically acceptable. Nonetheless, iPS cells are tainted by their association with the human embryonic stem cell lines, derived in the past, which will be required for their validation. This concern is one that can be resolved. Human iPS cells will serve to stem the tide of human embryonic stem cell research, changing it and diverting stem cell research in a more ethical direction. (shrink)

Human induced pluripotent stem cells can be obtained from somatic cells, and their derivation does not require destruction of embryos, thus avoiding ethical problems arising from the destruction of human embryos. This type of stem cell may provide an important tool for stem cell therapy, but it also results in some ethical concerns. It is likely that abnormal reprogramming occurs in the induction of human induced pluripotent stem cells, and that the (...) class='Hi'>stem cells generate tumors in the process of stem cell therapy. Human induced pluripotent stem cells should not be used to clone human beings, to produce human germ cells, nor to make human embryos. Informed consent should be obtained from patients in stem cell therapy. (shrink)

Direct reprogramming of human skin cells makes available a source of pluripotent stem cells without the perceived evil of embryo destruction, but the advent of such a powerful biotechnology entangles stem cell research in other forms of moral complicity. Induced pluripotent stem cell (iPSC) research had its origins in human embryonic stem cell research and the projected biomedical applications of iPS cells almost certainly will require more embryonic stem cell research. Policies that (...) inhibit iPSC research in order to avoid moral complicity are themselves complicit in preventable harms to patients. Moral complicity may be unavoidable, but a Blue Ribbon Panel charged with assessing the need for additional embryonic stem cell lines may ease a transition from embryonic stem cell research to clinical applications of iPS cells. (shrink)

This year marks the tenth anniversary of the world's first transplantation of tissue generated from induced pluripotent stem cells (iPSCs). There is now a growing number of clinical trials worldwide examining the efficacy and safety of autologous and allogeneic iPSC‐derived products for treating various pathologic conditions. As we patiently wait for the results from these and future clinical trials, it is imperative to strategize for the next generation of iPSC‐based therapies. This review examines the lessons learned from (...) the development of another advanced cell therapy, chimeric antigen receptor (CAR) T cells, and the possibility of incorporating various new bioengineering technologies in development, from RNA engineering to tissue fabrication, to apply iPSCs not only as a means to achieve personalized medicine but also as designer medical applications. (shrink)

The collection and storage of human tissue samples has been present in medicine for centuries, however, biobanking has recently become a dedicated activity. The technological developments that have allowed the isolation, storage and long term viability of human cells ex vivo, and to obtain relevant scientific information, including genetic information, open tremendous possibilities for advancing biomedical research. At the same time, these possibilities have raised complex ethical issues regarding tissue donors, researchers using samples and society awareness of biobanking as a (...) whole. This article aims to review the operation of stem cell biobanks, related ethical issues and the legal framework in Spain. Special consideration will be given to the new but revolutionary appearance of induced pluripotent stem cells. Most of the topics discussed here will be in the framework of banking adult derived stem cells, which do not entail in themselves any significant ethical dilemma. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Comments on “Moral Complicity in Induced Pluripotent Stem Cell Research”W. Malcolm Byrnes, Ph.D. and Edward J. FurtonIn his article titled “Moral Complicity in Induced Pluripotent Stem Cell Research,” Mark T. Brown (2009) unfortunately mischaracterizes my ethical analysis of the use of induced pluripotent stem (iPS) cells for replacement therapies, or treatments (Byrnes 2008). In my paper, which Brown cites, I (...) argue that, just as it is ethically acceptable for parents to allow their children and themselves to be immunized using vaccines produced by cell lines derived from human fetuses aborted in the past, it is also acceptable for persons in the future to benefit from treatments that use iPS cells validated using human embryonic stem (ES) cell lines [End Page 202] derived in the past. The assumption I make is that iPS cells would have to be shown to be functionally equivalent to human ES cells—i.e., validated—before they could be used for cell replacement treatments. (If it turns out that this assumption is incorrect, and primate or even mouse ES cells can be used for the validation, then all residual ethical problems will disappear and there will be no ethical problems whatsoever associated with iPS cells.) I wrote:... [I]n both cases, the origin of the treatment is in a one-time event: either the one-time use of aborted fetuses to obtain cell lines (e.g., MRC-5 and WI- 38) to grow weakened virus strains for vaccine production, or the one-time destruction of human embryos to validate iPS cells, which then effectively replace embryonic stem cells. In the latter case, if no additional embryonic stem cell lines are derived, then derivation of the existing lines could be considered a “one-time” event in the past, albeit an event that extended over a several-year period(Byrnes 2008, p. 287, emphasis added).Note the phrase “if no additional embryonic stem cell lines are derived.” The derivation of ES cell lines inherently involves destruction of embryos; indeed, that is why many people, including me, are opposed to human ES cell research. In my article, I am arguing that, if no additional ES cell lines are derived, then no additional human embryos will be destroyed, and the destruction of human embryos will lie in the past. In this case, embryo destruction could be considered a past event, just as the abortion of a human fetus from which vaccine-producing cell lines were derived is a past, albeit tragic, event.In the process of building his argument that proponents of iPS cell research are morally complicit in embryo destruction, Brown (2009, p. 15) casts me as being in favor of the “derivation of new embryonic stem [cell lines].” This is the exact opposite of my position. In fact, I am opposed to further destruction of human embryos. I believe that the hundreds of ES cell lines already in existence are more than sufficient to validate iPS cells and so no additional lines need to be derived. This means that no additional human embryos will need to be destroyed.Apparently based on the misperception that I support future destruction of human embryos, Brown concludes that “Byrnes’s endorsement of ongoing iPSC validation studies would seem to implicate him and those who follow his lead in formal and material complicity in what they perceive as moral evil” (p. 16). He writes that “explicit formal complicity would attach because he [Byrnes] knowingly and intentionally recommends that embryos be killed in order to facilitate a transition to a future in which no more embryos need be destroyed” (p. 16). Additionally, my “followers” and I would be guilty of “proximate material complicity” as well as “remote material complicity” (p. 16). Unfortunately, this broad condemnation is based on a misconception of my actual position.An additional problem involves Brown’s use of a quotation he attributes to me: [End Page 203]Once embryonic stem cells are used to successfully validate iPS cells, they will no longer be needed and their association with iPS cells will lie in the past. Is there not an element of sadness and resignation in accepting something (iPS cells) associated with an unjust act (destruction of an... (shrink)

The research on stem cell-based therapies has greatly expanded in recent years. Our text attempts to seek those religious and ethical challenges that stem cell therapy and research bring into debate. Our thesis is that bioethics can defend its principle without a religious background. We will develop our argumentation on three major points: firstly, a comparison between secular ethics and religious views will clarify why stem cell therapy and research are important from a scientific point of view, (...) addressing the very center of the human being; in our view, being based on secular society, bioethics can answer the challenges of stem cell therapy and research; secondly, following Hans Jonas' perspective on experimenting on humans, we seek to understand the philosophical guidance that sciences dealing with stem cell need; thirdly, we will map the ethical guidelines for clinical translational research that have been adopted by the International Society for Stem Cell Research. . (shrink)

Personalised medicine has been discussed as a medical paradigm shift that will improve health while reducing inefficiency and waste. At the same time, it raises new practical, regulatory, and ethical challenges. In this paper, we examine PM strategies epistemologically in order to develop capacities to address these challenges, focusing on a recently proposed strategy for developing patient-specific models from induced pluripotent stem cells so as to make individualised treatment predictions. We compare this strategy to two main PM (...) strategies—stratified medicine and computational models. Drawing on epistemological work in the philosophy of medicine, we explain why these two methods, while powerful, are neither truly personalised nor, epistemologically speaking, novel strategies. Both are forms of correlational black box. We then argue that the iPSC models would count as a new kind of black box. They would not rely entirely on mechanistic knowledge, and they would utilise correlational evidence in a different way from other strategies—a way that would enable personalised predictions. In arguing that the iPSC models would present a novel method of gaining evidence for clinical practice, we provide an epistemic analysis that can help to inform the practical, regulatory, and ethical challenges of developing an iPSC system. (shrink)

After the commercialisation of induced pluripotent stem cells (IPSCs) in 2007, the pressure to commercialise women's eggs for stem cell research could have been expected to lessen. However, the pressure to harvest human eggs in large quantities for research has not diminished; rather, it has taken different directions, for example, in germline mitochondrial research. Yet there has been little acknowledgement of these technologies' need for human eggs, the possible risks to women and the ethical issues concerning (...) potential exploitation. Rather, there has been a renewed campaign to legalise payment for eggs in research, although the actual scientific advances are at best modest. This article shows why a market in women's eggs is ethically problematic in terms of the doctor's duty to do no harm and the limitations of informed consent. (shrink)

Ford, Norman Many people think that the Catholic Church is morally opposed to all research and therapeutic use of stem cells. This is far from the truth. The Church is rightly morally opposed to all destructive use of human embryos to obtain pluripotent embryonic stem cells, but it is not opposed to pluripotent stem cells ethically derived from adult cells.

It is argued that the use of induced pluripotent stem cells for regenerative therapy may soon be ethically practicable and could sidestep the various objections pertaining to other types of stem cell (human embryonic stem cells, and stem cells obtained by altered nuclear transfer or somatic cell nuclear transfer).

Stem cell science is advancing at an unprecedented rate, with thousands of research papers being published every year and many clinical trials for a wide range of conditions underway as registered on ClinicalTrials.gov. This rapidly expanding and alluring field has brought with it ever more complex and multifaceted ethical issues, many of which require new guidelines, consent protocols and even change in legislation, since they do not fit comfortably in the existing bioethical regulations and protocols. Keeping up with the (...) ethical implications of stem cell research is daunting to the expert and non-expert. We review the various types of stem cells and then focus on multipotent and pluripotent cell types, since it is these cell types that bring with them the greatest research and therapeutic potential, while concurrently delivering novel ethical conundrums. Certain key considerations are currently lacking and what is needed is how to obtain permission from individuals who donate their biological material for both scientific inquiry and eventually, for their potential therapeutic utility. (shrink)

Recent advances in reprogramming technology do not bypass the ethical challenge of embryo sacrifice. Induced pluripotent stem cell (iPS) research has been and almost certainly will continue to be conducted within the context of embryo sacrifice. If human embryos have moral status as human beings, then participation in iPS research renders one morally complicit in their destruction; if human embryos have moral status as mere precursors of human beings, then advocacy of iPS research policy that is inhibited (...) by embryo sacrifice concerns renders one morally complicit in avoidable harms to persons. Steps may be taken to address these complicity concerns, but in the final analysis there is no alternative to achieving clarity with respect to the moral status of the human embryo. (shrink)

Machine generated contents note: Introduction. -- Acknowledgments. -- The Author. -- 1 Ethical Theories and Bioethics in a Global Perspective. -- Theories of Ethics. -- Are Theories of Ethics Global? -- Can Theories of Ethics Encourage People to Do the Right Thing? -- 2 Autonomy and Informed Consent in Global Perspective. -- Ethical Principles and Practical Issues of Informed Consent. -- Does Informed Consent Really Matter to Patients? -- Is Informed Consent a Universal Principle or (...) a Cultural Value? -- 3 Withholding or Withdrawing Treatment and Physician-Assisted Suicide. -- Withholding or Withdrawing Treatment at the End of Life. -- Assisting Patients in Committing Suicide. -- 4 Ethical Issues in Reproductive Health. -- Ethics of Abortion in Different Times, Places, and Cultures. -- Current Ethical Issues in Abortion. -- Assisted Reproductive Technology and Stem Cell Research. -- Emergency Contraception. -- Ethics of Imposing Conditions on Funding. -- 5 Ethical Issues of Female Genital Mutilation. -- The Facts About FGM. -- FGM as a Challenge to Ethical Relativism. -- Ethics of FGM for Adult Women. -- 6 Ethical Issues of Research with Human Subjects. -- Background Information and the Belmont Report. -- Autonomy and Voluntary Informed Consent. -- Beneficence and Cost-Benefit Analysis. -- Issues of Justice and Fairness for Human Subjects. -- 7 The Right to Health Care, and Ethical Obligations to Provide Care. -- Is There an Ethical Right to Health Care? -- Ethical Obligations of Health Care Professionals. -- Ethical Obligations of for-Profit Health Care Providers. -- 8 Ethical Issues in Rationing and Allocation of Limited Resources. -- Levels of Allocating Resources. -- Methods of Rationing Health Resources. -- Comparative Effectiveness Research and Cost-Effectiveness Analysis. -- 9 Ethical Issues of Health Insurance and Health System Reform. -- Ethical Issues in Financing Health Services and Designing Insurance Systems. -- Fundamental Values of Health Systems. -- 10 Ethical Issues in the Movement of Patients Across National Borders. -- Ethical Duties to Provide Health Care to Undocumented Aliens. -- Ethical Issues in Medical Tourism. -- 11 Ethical Issues in the Movement of Health Care Professionals Across National Borders. -- Ethical Issues in the Migration of Health Professionals. -- Proposed Solutions and Their Ethical Implications. -- Fair Treatment of Health Care Workers from Other Countries. -- 12 Corruption and Informal Payments in Health Systems. -- Payment of Informal Fees by Patients and Their Families. -- Is Corruption Bad for Your (and Other People's) Health? -- References. -- Index. (shrink)

The generation of three-dimensional cerebral organoids from human-induced pluripotent stem cells (hPSC) has facilitated the investigation of mechanisms underlying several neuropsychiatric disorders, including stress-related disorders, namely major depressive disorder and post-traumatic stress disorder. Generating hPSC-derived neurons, cerebral organoids, and even assembloids (or multi-organoid complexes) can facilitate research into biomarkers for stress susceptibility or resilience and may even bring about advances in personalized medicine and biomarker research for stress-related psychiatric disorders. Nevertheless, cerebral organoid research does not come without (...) its own set of ethical considerations. With increased complexity and resemblance to in vivo conditions, discussions of increased moral status for these models are ongoing, including questions about sentience, consciousness, moral status, donor protection, and chimeras. There are, however, unique ethical considerations that arise and are worth looking into in the context of research into stress and stress-related disorders using cerebral organoids. This paper provides stress research-specific ethical considerations in the context of cerebral organoid generation and use for research purposes. The use of stress research as a case study here can help inform other practices of in vitro studies using brain models with high ethical considerations. (shrink)

Pluripotent stem cells have gained special attraction because of their almost unlimited proliferation and differentiation capacity in vitro. These properties substantiate the potential of pluripotent stem cells in basic research and regenerative medicine. Here three types of in vitro‐cultured pluripotent stem cells (embryonic carcinoma, embryonic stem and induced pluripotent stem cells) are compared in their historical context with respect to their different origin and properties. It became evident that tumourigenicity (...) is an inherent property of pluripotent cells based on p53 down‐regulation, expression of tumour‐related genes and high telomerase activity that allow unlimited proliferation. In addition, culture‐adapted genetic and epigenetic changes may induce tumourigenicity of pluripotent cells. The use of stem cells in regenerative medicine, however, requires non‐malignant cell types and strategies that circumvent stages of malignancy. Reprogramming strategies of adult somatic cells that avoid the tumourigenic state of pluripotency may offer alternatives for future biomedical application. (shrink)

Novel therapies resulting from regenerative medicine and tissue engineering technology may offer new hope for patients with injuries, end-stage organ failure, degenerative disorders and many other clinical issues. Currently, patients suffering from diseased and injured organs are treated with transplanted organs. However, there is a shortage of donor organs that is worsening yearly as the population ages and new cases of organ failure increase. Scientists in the field of regenerative medicine and tissue engineering are now applying the principles (...) of cell transplantation, material science, and bioengineering to construct biological substitutes that can restore and maintain normal function in diseased and injured tissues. In addition, the stem cell field is a rapidly advancing part of regenerative medicine, and new discoveries in this field create new options for this type of therapy. For example, new types of stem cells, such as amniotic fluid and placental stem cells, that can circumvent the ethical issues associated with embryonic stem cells have been discovered. The process of somatic cell nuclear transfer and the creation of induced pluripotent cells provide still other potential sources of stem cells for cell-based tissue engineering applications. While stem cells are still in the research phase, some therapies arising from tissue engineering endeavors that make use of autologous, adult cells have already entered the clinical setting, indicating that regenerative medicine holds much promise for the future. (shrink)

Ethical guidelines commonly state that research subjects should have a right to withdraw consent to participate. According to the guidelines we have studied, this right applies also to research on biological samples. However, research conducted on human subjects themselves differs in important respects from research on biological samples. It is therefore not obvious that the same rights should be granted research participants in the two cases. This paper investigates arguments for and against granting a right to (...) withdraw consent to research on biobank samples. We conclude that (1) there are no explicit arguments for such a right in the guidelines we have studied, (2) the arguments against such a right are inconclusive, (3) considerations of autonomy, privacy, personal integrity, and trust in medical research provide sufficient reasons for granting a right to withdraw consent to research on biobank samples, (4) in certain cases, research participants should be allowed to waive this right. (shrink)

According to the judgement of the European Court of Justice in 2014, human parthenogenetic stem cells are excluded from the patenting prohibition of procedures based on hESC by the European Biopatent Directive, because human parthenotes are not human embryos. This article is based on the thesis that in light of the technological advances in the field of stem cell research, the attribution of the term ‘human embryo’ to certain entities on a descriptive level as well as the attribution (...) of a normative protection status to certain entities based on the criterion of totipotency, are becoming increasingly unclear. The example of human parthenotes in particular demonstrates that totipotency is not at all a necessary condition for the attribution of the term ‘human embryo’. Furthermore, the example of hiPSC and somatic cells particularly shows that totipotency is also not a sufficient condition for the attribution of a normative protection status to certain entities. Therefore, it is not a suitable criterion for distinguishing between human embryos worthy of protection and human non-embryos not worthy of protection. Consequently, this conclusion has repercussions for the patenting question. The strict delineation between an ethically problematic commercial use of human embryos and the concomitant patenting prohibition of hESC-based procedures and an ethically unproblematic commercial use of human non-embryos and the therefore either unrestrictedly permitted or even unregulated patenting of procedures based on these alleged alternatives becomes increasingly blurred. (shrink)

Stem cell research. Drug company influence. Abortion. Contraception. Long-term and end-of-life care. Human participants research. Informed consent. The list of ethical issues in science, medicine, and public health is long and continually growing. These complex issues pose a daunting task for professionals in the expanding field of bioethics. But what of the practice of bioethics itself? What issues do ethicists and bioethicists confront in their efforts to facilitate sound moral reasoning and judgment in a variety of venues? Are (...) those immersed in the field capable of making the right decisions? How and why do they face moral challenge -- and even compromise -- as ethicists? What values should guide them? In The Ethics of Bioethics, Lisa A. Eckenwiler and Felicia G. Cohn tackle these questions head on, bringing together notable medical ethicists and people outside the discipline to discuss common criticisms, the field's inherent tensions, and efforts to assign values and assess success. Through twenty-five lively essays examining the field's history and trends, shortcomings and strengths, and the political and policy interplay within the bioethical realm, this comprehensive book begins a much-needed critical and constructive discussion of the moral landscape of bioethics. (shrink)

In the debates regarding the ethics of human organoid biobanking, the locus of donor autonomy has been identified in processes of consent. The problem is that, by focusing on consent, biobanking processes preclude adequate engagement with donor autonomy because they are unable to adequately recognise or respond to factors that determine authentic choice. This is particularly problematic in biobanking contexts associated with organoid research or the clinical application of organoids because, given the probability of unforeseen and varying purposes for which (...) a donor’s organoids could be employed and given the different ways in which a donor can relate to her biospecimens, a donor can value her organoids differently in different contexts and her reasons for autonomously permitting use of her cells and tissues in one case may not support an autonomous decision in another. In response, this paper has three aims: firstly, to make the case for why organoid biobanks ought to respect donor autonomy conceived as authentic choice; secondly, to explore the autonomy-respecting limits of established and widely prevalent models of biobank consent; and thirdly, to propose certain conditions that organoid biobanks ought to support or facilitate in order to respect donor autonomy. (shrink)

Much of the current research in regenerative medicine concentrates on stem-cell therapy that exploits the regenerative capacities of stem cells when injected into different types of human tissues. Although new therapeutic paths have been opened up by induced pluripotent cells and human mesenchymal cells, the rate of success is still low and mainly due to the difficulties of managing cell proliferation and differentiation, giving rise to non-controlled stem cell differentiation that ultimately leads to (...) cancer. Despite being still far from becoming a reality, these studies highlight the role of physical and biological constraints (e.g., cues and morphogenetic fields) placed by tissue microenvironment on stem cell fate. This asks for a clarification of the coupling of stem cells and microenvironmental factors in regenerative medicine. We argue that extracellular matrix and stem cells have a causal reciprocal and asymmetric relationship in that the 3D organization and composition of the extracellular matrix establish a spatial, temporal, and mechanical control over the fate of stem cells, which enable them to interact and control (as well as be controlled by) the cellular components and soluble factors of microenvironment. Such an account clarifies the notions of stemness and stem cell regeneration consistently with that of microenvironment. (shrink)

In the October edition of theJournal of Medical Ethics, Akabayashi and colleagues state that ’to establish a heterogeneous [induced pluripotent stem cell] iPSC bank covering roughly 80% of Japan’s population…the Japanese government decided to invest JPY110 billion (US$ 1.1 billion) over 10 years in regenerative medicine research; a quarter of this was to be allocated to the iPSC stock project'. While they claim this amount of money to be an unfair distribution of state resources, we believe (...) their assessment is based on a misunderstanding of the facts. Similarly, other criticisms by them are based on mistaken interpretations. This article is a rebuttal to the arguments that form the basis of Akabayashi and colleagues’ five criticisms by explaining their misinterpretations. (shrink)

The right to withdraw from research without penalty is well established around the world. However, it has been challenged in some corners of bioethics based on concerns about various harms—to participants, to scientific integrity, and to research bystanders—that may stem from withdrawal. These concerns have become particularly salient in emerging debates about the ethics of controlled human infection (CHI) studies in which participants are intentionally infected with pathogens, often in inpatient settings with extensive follow‐up. In this article, (...) I provide support for preserving the right to withdraw from research without penalty and demonstrate that it is also typically justified in the specific context of CHI studies. The right is well aligned with individual freedoms outside the research setting, where autonomous individuals are permitted to engage in behaviors that will foreseeably cause them harm; where they cannot be compelled to satisfy contracts for their services, nor penalized for failure to do so; and where their behavior is not constrained by public health authorities except in extreme circumstances. These freedoms are supported by U.S. law, as well as by ethical analysis that is more globally relevant. The problems associated with the right to withdraw, however, remain. The best approach to addressing them is not to restrict the right but rather to avoid initiating research when withdrawal would be especially problematic. If research proceeds, steps can still be taken to minimize participant withdrawal without infringing the right. Investigators can avoid participant surprise through informed consent focused on a study’s most burdensome aspects and promote study completion through financial incentives. Should participants nonetheless seek to withdraw, investigators may attempt to persuade them not to do so by encouraging consideration of the range of potential harms that may result. Researchers conducting CHI studies and other research from which withdrawal might be especially problematic should prepare for the possibility of participant withdrawal, respect participant requests to withdraw without penalty, and incorporate various measures to avoid such requests. (shrink)

The obligation to maintain the privacy of patients and research participants is foundational to biomedical research. But there is growing concern about the challenges of keeping participant information private and confidential. A number of recent studies have highlighted how emerging computational strategies can be used to identify or reidentify individuals in health data repositories managed by public or private institutions. Some commentators have suggested the entire concept of privacy and anonymity is “dead”, and this raises legal and ethical questions about (...) the consent process and safeguards relating to health privacy. Members of the public and research participants value privacy highly, and inability to ensure it could affect participation. Canadian common law and legislation require a full and comprehensive disclosure of risks during informed consent, including anything a reasonable person in the participant or patient’s position would want to know. Research ethics policies require similar disclosures, as well as full descriptions of privacy related risks and mitigation strategies at the time of consent. In addition, the right to withdraw from research gives rise to a need for ongoing consent, and material information about changes in privacy risk must be disclosed. Given the research ethics concept of “non-identifiability” is increasingly questionable, policies based around it may be rendered untenable. Indeed, the potential inability to ensure anonymity could have significant ramifications for the research enterprise. (shrink)

The demonstration that pluripotent stem cells could be generated by somatic cell reprogramming led to wonder if these so-called induced pluripotent stem (iPS) cells would extend our investigation capabilities in the cancer research field. The first iPS cells derived from cancer cells have now revealed the benefits and potential pitfalls of this new model. iPS cells appear to be an innovative approach to decipher the steps of cell transformation as well as to screen the activity (...) and toxicity of anticancer drugs. A better understanding of the impact of reprogramming on cancer cell-specific features as well as improvements in culture conditions to integrate the role of the microenvironment in their behavior may strengthen the epistemic interest of iPS cells as model systems in oncology. (shrink)

The social interface between reproductive medicine and embryonic stem cell research has been investigated in a pilot study at a large IVF clinic in central China. Methods included observation, interviews with hospital personnel, and five in-depth qualitative interviews with women who underwent IVF and who were asked for their consent to the donation of embryos for use in medical (in fact human embryonic stem cell) research. This paper reports, and discusses from an ethical perspective, the results of an (...) analysis of these interviews. The participants talked of extreme social pressure to become pregnant. Once they had a baby, ‘spare’ embryos lost practical significance due to the Chinese one-child policy. In the context of decision making about donating embryos to research, the women used the clinical distinctions between ‘good and bad quality’ embryos and also between frozen and transferred embryos, as guiding moral distinctions. In the absence of concrete information about what sort of research their embryos should be used for, the women interviewed either refused consent (for fear that the embryo would be given to another couple) or accepted, expressing motives of solidarity with other women in a similar situation. This reveals that they filled the knowledge gap with an image of research improving fertility treatment. (shrink)

Like most bioethical discussion, examination of human biobanks has been largely framed in terms of research subjects’ rights, principally informed consent, with some gestures toward public benefits. However, informed consent is for the competent, rights-bearing individual: focussing on the individual, it thus neglects social, economic and even political matters; focussing on the competent rights-bearer, it does not serve situations where consent is plainly inappropriate (eg, the young child) or where coercion can obviously be justified (the criminal). Using the (...) British experience of large-scale biobanking, I argue that the focus on consenting individuals distorts our ways of thinking about biobanks and has serious practical ramifications. This becomes clear if we contrast the case of adult biobanks intended for medical research with two other forms of biobanking. Thus child cohort studies – vital for sound scientific investigation of the interplay of genetics and environment in health – have been very badly funded next to adult studies. On the other hand, forensic databases have attracted massive investment, but little debate – partly owing to a sense that here, at least, is a case where consent is not relevant. Contrasting these central types of biobanking, I will suggest that there are powerful factors at work in limiting ‘ethics’ to individual rights. Projects of this size should direct our attention to more overtly political questions concerning priority setting and organisation of medical research. (shrink)

In 2006, Shinya Yamanaka and colleagues discovered how to reprogram terminally differentiated somatic cells to a pluripotent stem cell state. The resulting induced pluripotent stem cells (iPSCs) made a paradigm shift in the field, further nailing down the disproval of the long‐held dogma that differentiation is unidirectional. The prospect of using iPSCs for patient‐specific cell‐based therapies has been enticing. This promise, however, has been questioned in the last two years as several studies demonstrated intrinsic epigenetic (...) and genomic anomalies in these cells. Here, we not only review the recent critical studies addressing the genome integrity during the reprogramming process, but speculate about the underlying mechanisms that could create de novo genome damage in iPSCs. Finally, we discuss how much an elevated mutation load really matters considering the safety of future therapies with cells heavily cultured in vitro. (shrink)

Korean biobanks are now adapting to integrate the new paradigm of precision medicine into their fundamental role of promoting health technology. Since the enactment of Bioethics and Safety Act in 2004, the Republic of Korea has developed a regulatory framework that reflects ethical principles. However, the existing regulation of biobanks has recently proven to be limited in responding to newer ethical and legal issues that have arisen. First, as there is an emerging trend for human biospecimens to be stored, managed (...) and distributed as digitalized data, the current role of the Distributive Review Committee may become less important compared to the Data Access Committee. Second, even if public health data is anonymized, the risk of identifiability is growing. This makes a third point relevant, informed consent is crucial to respect the autonomy of patients and research subjects, but current consent rules need to change to reflect the interactive and dynamic communication process, in which information and communication technology plays an increasingly prominent role. Fourth, even though data sharing for research is expected to be altruistic and the sale of human biospecimens and genome data remains prohibited, data sharing practices have become more complicated and are closer to commercial use and commercialization. Given these challenges, there is a pressing need for continuing and deeper deliberation in order to develop a more comprehensive and responsive governance framework. (shrink)

Advances in medical technology and information have facilitated clinical practices that favourably affect the success rates of treatment for diseases. Regenerative medicine has been the focus of the recent medical agenda, to the extent of fundamentally changing treatment paradigms. Stem cell practices, their efficacy, and associated ethical concerns have been debated intensively in many countries. Stem cell research is carried out along with the treatment of patients. Thus, various groups affected by the practices inevitably participate in the (...) discussions. In addition to discussions based on avoiding any harm, providing benefits and respecting personal autonomy and justice, problems arise owing to the lack of legal regulations for stem cell research and practice. The dimensions of the problems vary in the developing countries, with widespread use of advanced medical technology but with lack of sources allocated for healthcare, dominance of paternalistic physician–patient relationships and failure to achieve a sufficient level of awareness of patients’ rights. This article discusses the current situation of stem cell practices within the context of regenerative medicine in Turkey and ethical concerns about some of the legal regulations, such as the Regulation for Umblical Cord Blood Banking and Guidelines for Non-embryonic Stem Cell Study for Non-clinical Purposes directing the research on this issue. (shrink)

Advances in medical technology and information have facilitated clinical practices that favourably affect the success rates of treatment for diseases. Regenerative medicine has been the focus of the recent medical agenda, to the extent of fundamentally changing treatment paradigms. Stem cell practices, their efficacy, and associated ethical concerns have been debated intensively in many countries. Stem cell research is carried out along with the treatment of patients. Thus, various groups affected by the practices inevitably participate in the (...) discussions. In addition to discussions based on avoiding any harm, providing benefits and respecting personal autonomy and justice, problems arise owing to the lack of legal regulations for stem cell research and practice. The dimensions of the problems vary in the developing countries, with widespread use of advanced medical technology but with lack of sources allocated for healthcare, dominance of paternalistic physician–patient relationships and failure to achieve a sufficient level of awareness of patients’ rights. This article discusses the current situation of stem cell practices within the context of regenerative medicine in Turkey and ethical concerns about some of the legal regulations, such as the Regulation for Umblical Cord Blood Banking and Guidelines for Non-embryonic Stem Cell Study for Non-clinical Purposes directing the research on this issue. (shrink)

This article develops a model of informed consent for fresh oöcyte donation for stem cell research, during in vitro fertilisation (IVF), by building on the importance of patients’ embodied experience. Informed consent typically focuses on the disclosure of material information. Yet this approach does not incorporate the embodied knowledge that patients acquire through lived experience. Drawing on interview data from 35 patients and health professionals in an IVF clinic in Australia, our study demonstrates the uncertainty of IVF (...) treatment, and the tendency for patients to overestimate their chances of success prior to the experience of treatment. Once in active treatment, however, patients identify their oöcytes as both precious and precarious. We argue that it is necessary to formally include embodied experience as a source of knowledge in informed consent procedures, both for gratuitous donation and for egg-sharing regimes. We recommend that at least one full cycle of IVF be completed before approaching women to divert eggs away from their own fertility treatment. (shrink)

BackgroundBiobanks are considered primary means+ of supporting contemporary research, in order to deliver personalized and precise diagnostics with public acceptance and participation as a cornerstone for their success.AimsThis study aims to assess knowledge, perception, and attitudes towards biomedical research and biobanking among students at the University of Jordan.MethodologyAn online questionnaire was designed, developed, and piloted. It was divided into 5 sections that included questions related to issues of biomedical research and biobanking as well as factors influencing the decision to participate.ResultsResponses (...) from 435 students revealed that 52.9% previously heard of biobanks. There was an overwhelming acceptance for participation in biomedical, genetic, and biobanking research. A blood sample was the most preferred for donation. Protection of privacy, informed consent prior to donation, approval of an ethics committee, and trust towards researchers were the most important factors associated with willingness to participate. On the other hand, the vagueness of the type of research performed on the biospecimens and the unavailability of general research results to the donor had a negative connotation. There was no clear agreement on the type of informed consent preferred by students, but to be contacted and informed of research results was preferred by the majority. Students also preferred the disposal of biospecimens and information when deciding to withdraw from participation.ConclusionThere is strong enthusiasm among students to participate in biomedical research and biobanking with all rights reserved thus providing hope for a very promising future in Jordan. (shrink)

Informed consent is a central topic in contemporary biomedical ethics. Yet attempts to set defensible and feasible standards for consenting have led to persistent difficulties. In Rethinking Informed Consent in Bioethics Neil Manson and Onora O'Neill set debates about informed consent in medicine and research in a fresh light. They show why informed consent cannot be fully specific or fully explicit, and why more specific consent is not always ethically better. They argue that consent needs distinctive (...) communicative transactions, by which other obligations, prohibitions, and rights can be waived or set aside in controlled and specific ways. Their book offers a coherent, wide-ranging and practical account of the role of consent in biomedicine which will be valuable to readers working in a range of areas in bioethics, medicine and law. (shrink)

Two groups of scientists have just announced what is being described as a leap forward in human stem cell research.1–3 Both have found ways of producing what are being called “induced pluripotent cells” , stem cells that they hope will demonstrate the same key properties of regeneration and unrestricted differentiation that human embryonic stem cells possess, but which are derived from skin cells not from embryos. In simple terms, these scientists have succeeded in reprogramming skin (...) cells to behave like hESCs.Stem cell research has been hailed as one of the most important and exciting areas of science, because it is believed that these types of cells will not only play an important part in regenerative medicine, but also yield valuable scientific information. These latest developments in cell reprogramming represent a milestone for stem cell science. No longer does the paradigm of irreversible cell specialisation hold true; instead, almost any type of cell might have the potential to become any other.The advent of techniques for producing these iPCs has also been hailed as an ethical breakthrough. Up until now, the production of hESCs has required a process which involves the destruction of embryos. Many of these embryos are available as by-products of IVF; but in addition, the process of somatic cell nuclear transfer to produce cloned embryonic stem cells requires a supply of human oocytes, which must currently be harvested from female donors at no insignificant cost. In a nutshell, iPCs seem to enable us to produce “embryo-free” human pluripotent stem cells, and in a “gender-neutral” way—that is, without the need for human oocytes.The response from the scientific community, ethical commentators and the public has, however, reflected an inherent confusion over the ethical significance of this research. The anti-embryo …. (shrink)

The right to refuse medical intervention is well established, but it remains unclear how best to respect and exercise this right in life support. Contemporary ethical guidelines for critical care give ambiguous advice, largely because they focus on the moral equivalence of withdrawing and withholding care without confronting the very real differences regarding who is aware and informed of intervention options and how patient values are communicated and enacted. In withholding care, doctors typically withhold information about interventions (...) judged too futile to offer. They thus retain greater decision-making burden and face weaker obligations to secure consent from patients or proxies. In withdrawing care, there is a clearer imperative for the doctor to include patients in decisions, share information and secure consent, even when continued life support is deemed futile. How decisions to withhold and withdraw life support differ ethically in their implications for positive versus negative interpretations of patient autonomy, imperatives for consent, definitions of futility and the subjective evaluation of benefits and burdens of life support in critical care settings are explored. Professional reflection is required to respond to trends favouring a more positive interpretation of patient autonomy in the context of life support decisions in critical care. Both the bioethics and critical care communities should investigate the possibilities and limits of growing pressure for doctors to disclose their reasoning or seek patient consent when decisions to withhold life support are made. (shrink)

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease, primarily leading to the degeneration of motor neurons. The traditional focus on motor neuron‐centric mechanisms has recently shifted towards understanding the contribution of non‐neuronal cells, such as microglia, in ALS pathophysiology. Advances in induced pluripotent stem cell (iPSC) technology have enabled the generation of iPSC‐derived microglia monocultures and co‐cultures to investigate their role in ALS pathogenesis. Here, we briefly review the insights gained from these studies into the role of (...) microglia in ALS. While iPSC‐derived microglia monocultures have revealed intrinsic cellular dysfunction due to ALS‐associated mutations, microglia‐motor neuron co‐culture studies have demonstrated neurotoxic effects of mutant microglia on motor neurons. Based on these findings, we briefly discuss currently unresolved questions and how they could be addressed in future studies. iPSC models hold promise for uncovering disease‐relevant pathways in ALS and identifying potential therapeutic targets. (shrink)

In lieu of an abstract, here is a brief excerpt of the content:Kennedy Institute of Ethics Journal 14.1 (2004) 97-114 [Access article in PDF] Stem Cell Research in the U.S. after the President's Speech of August 2001 Cynthia B. Cohen On 9 August 2001, in a nationally televised speech, President Bush addressed the contentious question of whether to provide federal funds for human embryonic stem cell research (White House 2001).1 This research involves taking the primordial cells found in (...) embryos and transforming them into certain specialized cells, such as those of the heart, nerves, and muscles, with the ultimate goal of transferring these cells into patients to repair damaged cells and tissues. In his remarks, the President authorized funding for research only on stem cells already harvested from remaining embryos at in vitro fertilization (IVF) centers as of 9 August 2001, the date of the speech. In a "Fact Sheet" about embryonic stem cell research, he added the ethical requirements that (1) the donors of embryos gave informed consent to the derivation of stem cells from their embryos, (2) the embryos were created solely for reproductive purposes, and (3) no financial inducements were given to the embryo donors. The President also prohibited federally funded research on embryonic stem cells derived from embryos after 9 August 2001, as well as the creation of embryos for research purposes and the cloning of human embryos for both reproductive and research purposes. He did not seek to ban the pursuit of embryonic stem cell research with private funds. "This allows us to explore the promise and potential of stem-cell research without crossing a fundamental moral line by providing taxpayer funding that would sanction or encourage further destruction of embryos," the President stated (White House 2001).The President's speech stirred intense controversy. Many applauded the new policy because it allowed some embryonic stem cell research to proceed, thereby raising hope that treatments might be developed for those suffering from such conditions as Parkinson's disease, Alzheimer's disease, and diabetes. Others supported it on grounds that it would discourage the future destruction of embryos in stem cell research. They maintained that although it was wrong to have derived stem cells from embryos, this wrong was no longer remediable and it therefore was justifiable to allow research using such embryos to proceed. Some, however, objected to the new policy because they held that it unduly limited the [End Page 97] number of embryonic stem cells available for federally funded research. Still others opposed it on grounds that it made the federal government complicit in what they took to be the wrongful destruction of human embryos that had taken place prior to 9 August 2001. The President established the President's Council on Bioethics by executive order in November 2001 and charged it, among other tasks, with monitoring stem cell research and recommending guidelines and regulations for biomedical innovations.Questions about the moral status of human embryos have so captured public attention since the President issued his remarks that other significant ethical and policy issues raised about stem cell research inside the Beltway have remained in the shadows. A number of individuals and organizations—legislators, scientists, patient groups, the President's Council on Bioethics, ethicists, religious task forces, and social commentators—have attempted to bring these other issues to legislative and public attention. They also have revisited the more publicly prominent question of what sorts of protections we owe to human embryos. In response, Congress has attempted to address several of these newly emerging issues at hearings and in legislation. I review these efforts, consider developing issues and arguments, and conclude by exploring possible future directions for federal and private sector stem cell policy. The Availability of Embryonic Stem Cell Lines to Federally Funded Researchers President Bush, in developing his stem cell research policy, accepted a distinction between the "derivation" and the "use" of embryos enunciated by the General Counsel of the Department of Health and Human Services toward the end of the Clinton administration. This distinction was adopted to avoid contravening the Dickey-Wicker Amendment (added... (shrink)

The ability to convert human somatic cells into induced pluripotent stem cells (iPSCs) is allowing the production of custom‐tailored cells for drug discovery and for the study of disease phenotypes at the cellular and molecular level. IPSCs have been derived from patients suffering from a large variety of disorders with different severities. In many cases, disease related phenotypes have been observed in iPSCs or their lineage‐specific progeny. Several proof of concept studies have demonstrated that these phenotypes can (...) be reversed in vitro using approved drugs. However, several challenges must be overcome to take full advantage of this technology. Here, we highlight recent advances in the field and discuss the main challenges associated with this technology as it applies to disease modelling. (shrink)

The rise of precision medicine has led to an unprecedented focus on human biological material in biomedical research. In addition, rapid advances in stem cell technology, regenerative medicine and synthetic biology are leading to more complex human tissue structures and new applications with tremendous potential for medicine. While promising, these developments also raise several ethical and practical challenges which have been the subject of extensive academic debate. These debates have led to increasing calls for longitudinal governance arrangements between (...) tissue providers and biobanks that go beyond the initial moment of obtaining consent, such as closer involvement of tissue providers in what happens to their tissue, and more active participatory approaches to the governance of biobanks. However, in spite of these calls, such measures are being adopted slowly in practice, and there remains a strong tendency to focus on the consent procedure as the tool for addressing the ethical challenges of contemporary biobanking. In this paper, we argue that one of the barriers to this transition is the dominant language pervading the field of human tissue research, in which the provision of tissue is phrased as a ‘donation’ or ‘gift’, and tissue providers are referred to as ‘donors’. Because of the performative qualities of language, the effect of using ‘donation’ and ‘donor’ shapes a professional culture in which biobank participants are perceived as passive providers of tissue free from further considerations or entitlements. This hampers the kind of participatory approaches to governance that are deemed necessary to adequately address the ethical challenges currently faced in human tissue research. Rather than reinforcing this idea through language, we need to pave the way for the kind of participatory approaches to governance that are being extensively argued for by starting with the appropriate terminology. (shrink)