In this conversation, four experts in animal research oversight—Christopher Stodgell, Lori Hill, Robert Kesterson, and Angelika Rehrig—discuss the complexities of stem cell-based chimeric animal experiments, especially in relation to traditional animal welfare practices. Each expert shares their experiences and suggestions for how best to conduct chimeric animal research, including discussing the importance of communication and collaboration between experts in animal behavior and welfare and the investigators conducting or proposing chimeric research studies.

Human brain research is moving into a dilemma. The best way to understand how the human brain works is to study living human brains in living human beings, but ethical and legal standards make it d...

The burgeoning field of biomedical research involving the mixture of human and animal materials has attracted significant ethical controversy. Due to the many dimensions of potential ethical conflict involved in this type of research, and the wide variety of research projects under discussion, it is difficult to obtain an overview of the ethical debate. This paper attempts to remedy this by providing a systematic review of ethical reasons in academic publications on human-animal chimera research. We conducted a systematic review of (...) the ethical literature concerning human-animal chimeras based on the research question: “What ethical reasons have been given for or against conducting human-animal chimera research, and how have these reasons been treated in the ongoing debate?” Our search extends until the end of the year 2017, including MEDLINE, Embase, PhilPapers and EthxWeb databases, restricted to peer-reviewed journal publications in English. Papers containing ethical reasons were analyzed, and the reasons were coded according to whether they were endorsed, mentioned or rejected. Four hundred and thirty-one articles were retrieved by our search, and 88 were ultimately included and analyzed. Within these articles, we found 464 passages containing reasons for and against conducting human-animal chimera research. We classified these reasons into five categories and, within these, identified 12 broad and 31 narrow reason types.15% of the retrieved passages contained reasons in favor of conducting chimera research, while 85% of the passages contained reasons against it. The reasons against conducting chimera research fell into four further categories: reasons concerning the creation of a chimera, its treatment, reasons referring to metaphysical or social issues resulting from its existence and to potential downstream effects of chimera research. A significant proportion of identified passages fell under Category C. We hope that our results, in revealing the conceptual and argumentative structure of the debate and highlighting some its most notable tendencies and prominent positions, will facilitate continued discussion and provide a basis for the development of relevant policy and legislation. (shrink)

In this paper I explore some of the moral issues that could emerge from the creation of human–nonhuman chimeras capable of human gamete production and human pregnancy. First I explore whether there is a cogent argument against the creation of HNH-chimeras that could produce human gametes. I conclude that so far there is none, and that in fact there is at least one good moral reason for producing such types of creatures. Afterwards I explore some of the moral problems that (...) could emerge from the fact that a HNH-chimera could become pregnant with a human conceptus. I focus on two sets of problems: problems that would arise by virtue of the fact that a human is gestated by a nonhuman creature, and problems that would emerge from the fact that such pregnancies could affect the health of the HNH-chimera. (shrink)

What types of human-animal interspecific entities are used in biomedical research? Is creating such entities morally wrong? And what do interspecifics tell us about the moral significance of species? This thesis offers an introduction to the field of human-animal interspecifics from a bioethical perspective, with a special focus on the question of speciesism.

The prospect of using cell-based interventions to treat neurological conditions raises several important ethical and policy questions. In this target article, we focus on issues related to the unique constellation of traits that characterize CBIs targeted at the central nervous system. In particular, there is at least a theoretical prospect that these cells will alter the recipients' cognition, mood, and behavior—brain functions that are central to our concept of the self. The potential for such changes, although perhaps remote, is cause (...) for concern and careful ethical analysis. Both to enable better informed consent in the future and as an end in itself, we argue that early human trials of CBIs for neurological conditions must monitor subjects for changes in cognition, mood, and behavior; further, we recommend concrete steps for that monitoring. Such steps will help better characterize the potential risks and benefits of CBIs as they are tested and potentially used for treatment. (shrink)

Institutional ethics consultation services for biomedical scientists have begun to proliferate, especially for clinical researchers. We discuss several models of ethics consultation and describe a team-based approach used at Stanford University in the context of these models. As research ethics consultation services expand, there are many unresolved questions that need to be addressed, including what the scope, composition, and purpose of such services should be, whether core competencies for consultants can and should be defined, and how conflicts of interest should (...) be mitigated. We make preliminary recommendations for the structure and process of research ethics consultation, based on our initial experiences in a pilot program. (shrink)

Human-nonhuman chimeric research—research on nonhuman animals who contain human cells—is being used to understand human disease and development and to create potential human treatments such as transplantable organs. A proposed advantage of chimeric models is that they can approximate human biology and therefore allow scientists to learn about and improve human health without risking harms to humans. Among the emerging ethical issues being explored is the question of at what point chimeras are “human enough” to have human rights and thus (...) be owed higher standards of research protection than that currently afforded to nonhuman animals. However, this question and other related questions assume that the ethics of experimenting on nonhuman animals have been settled, which they have not. In this essay, we argue that it is imperative to give adequate attention to familiar questions about nonhuman animal research as well as new questions about chimera research and that failure to do so will result in a distorted understanding of the ethics of chimera research. (shrink)

Animal models of human diseases are often used in biomedical research in place of human subjects. However, results obtained by animal models may fail to hold true for humans. One way of addressing this problem is to make animal models more similar to humans by placing human tissue into animal models, rendering them chimeric. Since technical and ethical limitations make neurological disorders difficult to study in humans, chimeric models with human neural tissue could help advance our understanding of neuropathophysiology. In (...) this article, we examine whether the introduction of human neural tissue and any consequent cognitive change is relevant to the way we ought to treat chimeras. We argue that changes in cognitive abilities are morally relevant to the extent that they increase the capacities that affect the moral status of any entity, including awareness, autonomy, and sociability. We posit that no being, regardless of species, should be treated in a way that is incommensurate with its moral status. Finally, we propose a framework that can be used to guide ethical assessment of research involving chimeras with advanced cognitive capacities. We advance this framework as a useful tool for bringing relevant considerations to the forefront for those considering the ethical merit of proposed chimeric research. In doing so, we examine concepts relevant to the question of how any entity may be treated, including moral status, dignity, and capacities. (shrink)

Human–nonhuman chimeras have been the focus of ethical controversies for more than a decade, yet some related issues remain unaddressed. For example, little has been said about the relationship between the origin of transferred cells and the morally relevant capacities to which they may give rise. Consider, for example, a developing mouse fetus that receives a brain stem cell transplant from a human and another that receives a brain stem cell transplant from a dolphin. If both chimeras acquire morally relevant (...) capacities as a result of transplantation, and if those capacities are indistinguishable, should the difference in cell origin matter to how we classify these creatures? I argue that if morally relevant capacities are easy to detect, cell origin is irrelevant to how the chimera ought to be treated. However, if such capacities are hard to detect, cell origin should play a role in considerations about how to treat the chimera. (shrink)

Institutional ethics consultation services for biomedical scientists have begun to proliferate, especially for clinical researchers. We discuss several models of ethics consultation and describe a team-based approach used at Stanford University in the context of these models. As research ethics consultation services expand, there are many unresolved questions that need to be addressed, including what the scope, composition, and purpose of such services should be, whether core competencies for consultants can and should be defined, and how conflicts of interest should (...) be mitigated. We make preliminary recommendations for the structure and process of research ethics consultation, based on our initial experiences in a pilot program. (shrink)

The discussion by Greely et al. (2007) of the Stanford advisory committee's deliberations regarding whether to pursue research involving the transfer of human brain stem cells to fetal mice not onl...

Research on human-animal chimeras have elicited alarms and prompted debates. Those involving the generation of chimeric brains, in which human brain cells become anatomically and functionally intertwined with their animal counterparts in varying ratios, either via xenografts or embryonic co-development, have been considered the most problematic. The moral issues stem from a potential for “humanization” of the animal brain, as well as speculative changes to the host animals’ consciousness or sentience, with consequential alteration in the animal hosts’ moral status. However, (...) critical background knowledge appears to be missing to resolve these debates. Firstly, there is no consensus on animal sentience vis-à-vis that of humans, and no established methodology that would allow a wholesome and objective assessment of changes in animal sentience resulting from the introduction of human brain cells. Knowledge in interspecies comparative neuropsychology that could allow effective demarcation of a state of “humanization” is also lacking. Secondly, moral status as a philosophical construct has no scientific and objective points of reference. Either changes in sentience or humanization effects would remain unclear unless there are some neuroscientific research grounding. For a bioethical stance based on moral status of human-animal brain chimera to make meaningful contributions to regulatory policies, it might first need to be adequately informed by, and with its arguments constructed, in a manner that are factually in line with the science. In may be prudent for approved research projects involving the generation of human-animal brain chimera to have a mandatory component of assessing plausible changes in sentience. (shrink)

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human‐nonhuman chimeric research. Led by bioethics researchers working closely with an (...) interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human‐nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics’ previous focus on human‐centered questions about the ethics of “humanization” and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less‐siloed governance and oversight and more‐comprehensive public communication. (shrink)

We have arrived at an inflection point, a moment in history when the sentience, conscious- ness, intelligence, agency, and even the moral agency of many nonhuman animals can no longer be questioned without ignoring centuries of accumulated scientific knowledge. Nowhere is this more true than in our understanding of nonhuman primates (NHPs). A neu- roethics committed to probing the ethical implications of brain research must be able to respond to and anticipate the challenges ahead as brain projects globally prepare to (...) increase the use of NHPs in research. This requires adopting a less anthropocentric focus that includes nonhuman animals within its scope. But the Neuroethics Roadmap represents a missed opportunity to critically examine the future direction of research with NHPs in an ethically-responsive neuroscience. (shrink)

Human‐animal chimeras—creatures composed of a mix of animal and human cells—have come to play an important role in biomedical research, and they raise ethical questions. This article focuses on one particularly difficult set of questions—those related to the moral status of human‐animal chimeras with brains that are partly or wholly composed of human cells. Given the uncertain effects of human‐animal chimera research on chimeric animals’ cognition, it would be prudent to ensure we do not overlook or underestimate their moral status. (...) However, to assess moral status, we first need to determine what kinds of capacities are morally relevant. The standard view holds that it matters, morally, if chimeric animals develop uniquely human cognitive capacities. I argue that this view is mistaken, highlighting three problems with it: that we can think of examples of uniquely human cognitive capacities that are not morally significant, that we can think of examples of morally significant cognitive capacities that are not uniquely human, and that evidence that some cognitive capacity is shared with nonhuman animals does not undermine claims that this capacity is morally significant. We need a better framework for thinking about the moral status of part‐human beings. (shrink)

The American Journal of Bioethics, Volume 12, Issue 9, Page 26-28, September 2012.

The American Journal of Bioethics, Volume 12, Issue 9, Page 34-35, September 2012.

To be made aware of bioethical issues related to their disciplines, undergraduate students in biology and pharmaceutical sciences at the University of Basel are required to enroll in the bioethics course called “Introduction to Bioethics”. This article describes the chances and challenges faced when teaching a large number of undergraduate biology and pharmaceutical sciences students. Attention is drawn to the relevance and specific ethical issues that biology and pharmaceutical sciences students may be confronted with and to how these could be (...) integrated into ethics curricula. Results from a survey addressing the knowledge and opinion of students taking the course in spring semester 2012, 2013, and 2014 are presented and discussed. Finally, we describe the lessons learned and how we have improved the course based on students’ feedback throughout the following years. (shrink)

Research with human–animal chimera raises a number of ethical concerns, especially when neural stem cells are transplanted into the brains of non-human primates . Besides animal welfare concerns and ethical issues associated with the use of embryonic stem cells, the research is also regarded as controversial from the standpoint of NHPs developing cognitive or behavioural capabilities that are regarded as “unique” to humans. However, scientists are urging to test new therapeutic approaches for neurological diseases in primate models as they better (...) mimic human physiology than all current animal models. As a response, various countries have issued reports on the topic. Our paper summarizes the ethical issues raised by research with human–animal brain chimeras and compares the relevant regulatory instruments and different recommendations issued in national reports from three important European research nations: Germany, Switzerland and the United Kingdom. We assess and discuss the focus and priorities set by the different reports, review various reasons for and perspectives on the importance of the brain in chimera research, and identify critical points in the reports that warrant further specification and debate. (shrink)

Research that involves the creation of animals with human-derived parts opens the door to potentially valuable scientific and therapeutic advances, yet invokes unsettling moral questions. Critics and champions alike stand to gain from clear identification and careful consideration of the strongest ethical objections to this research. A prevailing objection argues that crossing the human/nonhuman species boundary introduces inexorable moral confusion (IMC) that warrants a restriction to this research on precautionary grounds. Though this objection may capture the intuitions of many who (...) find this research unsettling, it relies on mistaken views of both biology and moral standing, ultimately distorting the morally relevant facts. We critically examine IMC, identify mistaken essentialist assumptions, and reframe ethical concerns. The upshot is a stronger line of objection that encourages a more inclusive and productive ethical discourse. (shrink)

Much bioethical discussion has been devoted to the subject of human enhancement through various technological means such as genetic modification. Although many of the same technologies could be, indeed in many cases already have been, applied to non-human animals, there has been very little consideration of the concept of “animal enhancement”, at least not in those specific terms. This paper addresses the notion of animal enhancement and the ethical issues surrounding it. A definition of animal enhancement is proposed that provides (...) a framework within which to consider these issues; and it is argued that if human enhancement can be considered to be a moral obligation, so too can animal enhancement. (shrink)

In this work I present a detailed critique of the dignity-related arguments that have been advanced against the creation of human–nonhuman chimeras that could possess human-like mental capacities. My main claim is that the arguments so far advanced are incapable of grounding a principled objection against the creation of such creatures. I conclude that these arguments have one, or more, of the following problems: they confuse the ethical assessment of the creation of chimeras with the ethical assessment of how such (...) creatures would be treated in specific contexts, they misrepresent how a being could be treated solely as means towards others’ ends, they fall short of demonstrating how humanity’s dignity would be violated by the creation of such entities, and they fail to properly characterise the moral responsibilities that moral agents have towards other moral agents and sentient beings. (shrink)

In this conversation, three researchers from the fields of developmental biology and stem cell science—Ali Brivanlou, Lorenz Studer, and May Schwarz—speak about the importance of conducting chimeric animal experiments. The scientists describe some of the stem cell-based chimeric research being conducted in the United States, responsibilities they have in using modified animals for experiments, and things they would like the public to understand about this research. This conversation illuminates not only what chimeric animal researchers are doing in the lab but (...) also how their work may benefit society and where this science might go in the future. (shrink)

When Mrs. Frederick C. Little's second son was born, everybody noticed that he was not much bigger than a mouse. (E. B. White, 1945, 1.) In every somatic and morphological detail Stuart Little was...

According to Haber and Benham (2012), a sufficient condition for full moral consideration is that a creature bears a genealogical relation to the Homo sapiens lineage. Since part-humans do not bear such a relation, they are not due full moral consideration on that basis. Given this argument, my aim in this commentary is twofold. First, I want to challenge its soundness by showing that it is possible for part-humans to bear a genealogical relation to the H. sapiens lineage. Second, I (...) want to argue that Haber and Benham's attempt at avoiding moral confusion by reframing ethical concerns about part-humans doesn’t work. (shrink)