Monika Piotrowska

Depression is a widespread and debilitating disorder, but developing effective treatments has proven challenging. Despite success in animal models, many treatments fail in human trials. While various factors contribute to this translational failure, standardization practices in animal research are often overlooked. This paper argues that certain standardization choices in behavioral neuroscience research on depression can limit the generalizability of results from rodents to humans. This raises ethical and scientific concerns, including animal waste and a lack of progress in treating human patients. To address these issues, animal ethics committees can establish reasonable expectations for preclinical research and highlight the impact of standardization on generalizability. Such efforts can help improve translation from animal models to human patients and ultimately benefit those suffering from depression.

Translation failure occurs when a treatment shown to be safe and effective in one type of population does not produce the same result in another. We are currently in a crisis involving the translatability of preclinical studies to human populations. Animal trials are no better than a coin toss at predicting the safety and efficacy of drugs in human trials, and the high failure rate of drugs entering human trials suggests that most of the suffering of laboratory animals is futile, creating no commensurate benefit for human patients. Here, I argue that animal ethics committees have a role to play in getting us out of this crisis. Inadequate representation is a known contributor to translation failures and is a matter of both scientific and ethical concern. Ethical review committees have the authority to address it by reprioritising the values already enshrined in their guiding principles.

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.

Human embryo models formed from stem cells—known as embryoids—allow scientists to study the elusive first stages of human development without having to experiment on actual human embryos. But clear ethical guidelines for research involving embryoids are still lacking. Previously, a handful of researchers put forward new recommendations for embryoids, which they hope will be included in the next set of International Society for Stem Cell Research guidelines. Although these recommendations are an improvement over the default approach, they are nonetheless unworkable, because they rely on a poorly conceived notion of an embryoid’s ‘potential’ to trigger stringent research regulations.

New discoveries are improving the odds of human cells surviving in host animals, prompting regulatory and funding agencies to issue calls for additional layers of ethical oversight for certain types of human–animal chimeras. Of interest are research proposals involving chimeric animals with humanized brains. But what is motivating the demand for additional oversight? I locate two, not obviously compatible, motivations, each of which provides the justificatory basis for paying special attention to different sets of human–animal chimeras. Surprisingly, the sets of animals that actually get flagged for special scrutiny by research and funding guidelines do not correlate with either of the sets of animals that arise when we think about what is motivating additional oversight. What this shows is that existing research policies and funding guidelines are disconnected from their motivation: the rationale for flagging certain types of human–animal chimeras as requiring special oversight is ignored in execution.

Research ethics committees must sometimes deliberate about objects that do not fit nicely into any existing category. This is currently the case with the “gastruloid,” which is a self-assembling blob of cells that resembles a human embryo. The resemblance makes it tempting to group it with other members of that kind, and thus to ask whether gastruloids really are embryos. But fitting an ambiguous object into an existing category with well-worn pathways in research ethics, like the embryo, is only a temporary fix. The bigger problem is that we no longer know what an embryo is. We haven’t had a non-absurd definition of ‘embryo’ for several decades and without a well-defined comparison class, asking whether gastruloids belong to the morally relevant class of things we call embryos is to ask a question without an answer. What’s the alternative? A better approach needs to avoid what I’ll refer to as “the potentiality trap” and, instead, rely on the emergence of morally salient facts about gastruloids and other synthetic embryos.

Media reporters often announce that we are on the verge of bringing back the woolly mammoth, even while there is growing consensus among scientists that resurrecting the mammoth is unlikely. In fact, current “de-extinction” efforts are not designed to bring back a mammoth, but rather adaptations of the mammoth using close relatives. For example, Harvard scientists are working on creating an Asian elephant with the thick coat of a mammoth by merging mammoth and elephant DNA. But how should such creatures be classified? Are they elephants, mammoths, or both? Answering these questions requires getting clear about the concept of reproduction. What I hope to show is that with an appropriate notion of reproduction—one for which I will argue—resurrecting a member of Mammuthus primigenius is a genuine possibility.

With an increasing number of ways to ‘assist’ reproduction, some bioethicists have started to wonder what it takes to become a genetic parent. It is widely agreed that sharing genes is not enough to substantiate the parent–offspring relation, but what is? Without a better understanding of the concept of reproduction, our thinking about parent–offspring relations and the ethical issues surrounding them risk being unprincipled. Here, I address that problem by offering a principled account of reproduction—the Overlap, Development and Persistence account—which I believe best captures the meaning of ‘genetic parenthood’.

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

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.

Extrapolation from a well-understood base population to a less-understood target population can fail if the base and target populations are not sufficiently similar. Differences between laboratory mice and humans, for example, can hinder extrapolation in medical research. Mice that carry a partial or complete human physiological system, known as humanized mice, are supposed to make extrapolation more reliable by simulating a variety of human diseases. But what justifies our belief that these mice are similar enough to their human counterparts to simulate human disease? I argue that, unless three requirements are met in the process of humanizing mice, very little does. My requirements are not meant to provide necessary and sufficient conditions that guarantee a particular outcome. Instead, they serve as a heuristic for guiding scientific judgments involving extrapolation. In developing each requirement, I engage with philosophical issues concerning the nature of model-based science and the mechanistic approach (and its limits) to making generalizations in the life sciences

The book is divided into four sections, and contains two central arguments. The goal of the first argument is to show that generally accepted concepts in moral theory have an irreducibly second-personal character and that it is impossible to fully understand many central moral ideas without it. Here, by evaluating a broad range of literature in moral theory and articulating the second-personal aspect of each, Darwall elaborates on the interpersonal nature of moral obligation. The detailed discussion presents some well-known moral theories, and while emphasizing the Deontological perspective, highlights the second-personal character of all moral theories; a perspective that has, in the past, gone unnoticed. However, as Darwall himself acknowledges, the first argument cannot vindicate the very ideas it analyzes. He thus dedicates the second part of the book to a reverse-strategy: instead of arguing for the existence of a second-person foundation in moral theory, Darwall sets out to show that the presuppositions of the second-person standpoint include the moral law in them. In this second argument, Darwall explains that the second-personal standing can only be justified within a circle of four interrelated ideas (claim, accountability, second-personal reason, and second-personal authority), and that this circle necessarily excludes instances of coercion.

Comparative genomicists seem to be convinced that the unit of measurement employed in their studies is a gene that drives the function of cells and ultimately organisms. As a result, they have come to some substantive conclusions about how similar humans are to other organisms based on the percentage of genetic makeup they share. I argue that the actual unit of measurement employed in the studies corresponds to a structural rather than a functional gene concept, thus rendering many of the implications drawn from comparative genomic studies largely unwarranted, if not completely mistaken. †To contact the author, please write to: Department of Philosophy, University of Utah, 215 South Central Campus Drive, Carolyn Tanner Irish Humanities Building, 4th Floor, Salt Lake City, UT 84112; e‐mail: [email protected].

I begin with a description of the benefits and limits of DNA barcoding as presented by its advocates not its critics. Next, I argue that due to the mutually dependent relationship between defining and delimiting species, all systems of classification are grounded in theory, even if only implicitly. I then proceed to evaluate DNA barcoding in that context. In particular, I focus on the barcoders’ use of a sharp boundary by which to delimit species, arguing that this boundary brings along additional theoretical commitments inconsistent with the way taxonomists conceive of species, viz., as entities that have vague boundaries and that cannot be defined by any single attribute other than ancestry. Given these inconsistencies, I conclude that even if groupings based on DNA barcodes match those of an existing taxonomy, the two systems of classification are not necessarily tracking the same entities, i.e., species.

What’s the basis for considering an egg donor a genetic parent but not a mitochondrial donor? I will argue that a closer look at the biological facts will not give us an answer to this question because the process by which one becomes a genetic parent, i.e., the process of reproduction, is not a concept that can be settled by looking. It is, rather, a concept in need of philosophical attention. The details of my argument will rest on recent developments in biological technology, but the persuasiveness of my argument will turn on the history of another biological concept, death. Given some important similarities between the two concepts, the way in which ‘death’ evolved in the recent past can provide guidance on how we should think about ‘reproduction.’