The rise of neurotechnologies, especially in combination with artificial intelligence (AI)-based methods for brain data analytics, has given rise to concerns around the protection of mental privacy, mental integrity and cognitive liberty – often framed as “neurorights” in ethical, legal, and policy discussions. Several states are now looking at including neurorights into their constitutional legal frameworks, and international institutions and organizations, such as UNESCO and the Council of Europe, are taking an active interest in developing international policy and governance guidelines on this issue. However, in many discussions of neurorights the philosophical assumptions, ethical frames of reference and legal interpretation are either not made explicit or conflict with each other. The aim of this multidisciplinary work is to provide conceptual, ethical, and legal foundations that allow for facilitating a common minimalist conceptual understanding of mental privacy, mental integrity, and cognitive liberty to facilitate scholarly, legal, and policy discussions.

We are sometimes unsure of the moral status of our relationships with other entities. Recent case studies in this uncertainty include our relationships with artificial agents (robots, assistant AI, etc.), animals, and patients with “locked-in” syndrome. Do these entities have basic moral standing? Could they count as true friends or lovers? What should we do when we do not know the answer to these questions? An influential line of reasoning suggests that, in such cases of moral uncertainty, we need meta-moral decision rules that allow us to either minimize the risks of moral wrongdoing or improve the choice-worthiness of our actions. One particular argument adopted in this literature is the “risk asymmetry argument,” which claims that the risks associated with accepting or rejecting some moral facts may be sufficiently asymmetrical as to warrant favoring a particular practical resolution of this uncertainty. Focusing on the case study of artificial beings, this article argues that this is best understood as an ethical-epistemic challenge. The article argues that taking potential risk asymmetries seriously can help resolve disputes about the status of human–AI relationships, at least in practical terms (philosophical debates will, no doubt, continue); however, the resolution depends on a proper, empirically grounded assessment of the risks involved. Being skeptical about basic moral status, but more open to the possibility of meaningful relationships with such entities, may be the most sensible approach to take.

Non-human animal chimeras, containing human neurological cells, have been created in the laboratory. Despite a great deal of debate, the status of such beings has not been resolved. Under normal definitions, such a being could either be unconventionally human or abnormally animal. Practical investigations in animal sentience, artificial intelligence, and now chimera research, suggest that such beings may be assumed to have no legal rights, so philosophy could provide a different answer. In this vein, therefore, we can ask: What would a chimera, if it could think, think about? Thinking is used to capture the phenomena of a novel, chimeric being perceiving its terrible predicament as no more than a laboratory experiment. The creation of a thinking chimera therefore forces us to reconsider our assumptions about what makes human beings (potentially) unique (and other sentient animals different), because, as such, a chimera’s existence bridges our social and legal expectations about definitions of human and animal. Society has often evolved new social norms based on different kinds of (ir)rational contrivances; the imperative of non-contradiction, which is defended here, therefore requires a specific philosophical response to the rights of a thinking chimeric being.

About ten years ago, reports of lab-grown “mini brains” or “brains in a dish” appeared in the media, falling somewhere between the curious and the alarming. The trigger of these reports was a new method to grow three-dimensional neural tissue from human stem cells that recapitulates, to some degree, the early development of brain tissue. Despite their relatively small size and other limitations, such model systems capture in part the structure and functions of regions of the human brain and can also be combined to form so-called assembloids.

The possibility of consciousness in human brain organoids is sometimes viewed as determinative in terms of the moral status such entities possess, and, in turn, in terms of the research protections such entities are due. This commonsense view aligns with a prominent stance in neurology and neuroscience that consciousness admits of degrees. My paper outlines these views and provides an argument for why this picture of correlating degrees of consciousness with moral status and research protections is mistaken. I then provide an alternative account of the correlation between moral status and consciousness, and consider the epistemic ramifications for research protections of this account.

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.

The risk of creating cerebral organoids/assembloids conscious enough to suffer is a recurrent concern in organoid research ethics. On one hand, we should, apparently, avoid discovering how to distinguish between organoids that it would be permissible (non-conscious) and impermissible (conscious) to use in research, since if successful we would create organoids that suffer. On the other, if we do not, the risk persists that research might inadvertently continue to cause organoids to suffer. Moreover, since modeling some brain disorders may require inducing stress in organoids, it is unclear how to eliminate the risk, if we want to develop effective therapies. We are committed to harm avoidance but hamstrung by a presumption that we should avoid research that might tell us clearly when suffering occurs. How can we negotiate this challenge and maximize the therapeutic benefits of cerebral organoid research? The author interrogates the challenge, suggesting a tentative way forward.

Cerebral organoid models in-of-themselves are considered as an alternative to research animal models. But their developmental and biological limitations currently inhibit the probability that organoids can fully replace animal models. Furthermore, these organoid limitations have, somewhat ironically, brought researchers back to the animal model via xenotransplantation, thus creating hybrids and chimeras. In addition to attempting to study and overcome cerebral organoid limitations, transplanting cerebral organoids into animal models brings an opportunity to observe behavioral changes in the animal itself. Traditional animal ethics frameworks, such as the well-known three Rs (reduce, refine, and replace), have previously addressed chimeras and xenotransplantation of tissue. But these frameworks have yet to completely assess the neural-chimeric possibilities. And while the three Rs framework was a historical landmark in animal ethics, there are identifiable gaps in the framework that require attention. The authors propose to utilize an expanded three Rs framework initially developed by David DeGrazia and Tom L. Beauchamp, known as the Six Principles (6Ps). This framework aims to expand upon the three Rs, fill in the gaps, and be a practical means for assessing animal ethical issues like that of neural-chimeras and cerebral organoid xenotransplantation. The scope of this 6Ps application will focus on two separate but recent studies, which were published in 2019 and 2020. First, they consider a study wherein cerebral organoids were grown from donors with Down syndrome and from neurotypical donors. After these organoids were grown and studied, they were then surgically implanted into mouse models to observe the physiological effects and any behavioral change in the chimera. Second, they consider a separate study wherein neurotypical human embryonic stem cell-derived cerebral organoids were grown and transplanted into mouse and macaque models. The aim was to observe if such a transplantation method would contribute to therapies for brain injury or stroke. The authors place both studies under the lens of the 6Ps framework, assess the relevant contexts of each case, and provide relevant normative conclusions. In this way, they demonstrate how the 6Ps could be applied in future cases of neural-chimeras and cerebral organoid xenotransplantation.

This paper will ask whether the legal status presently afforded to nonhuman animals ought to influence regulatory debates concerning human cerebral organoids. The New York Courts recently refused to grant a writ of habeas corpus to Happy the Elephant as she was property rather than a legal person while at the same time accepting that she is a moral patient deserving of rights protection. An undesirable situation has therefore arisen in which the law holds a being with moral status to be incapable of benefitting from legal redress due to their legal status as property.

The author argues that this is something that we ought to avoid when designing the regulatory framework which will govern the use of human cerebral organoids. Yet, a difference exists in that, whereas the judges already accept Happy is a moral patient, there is presently no consensus around the moral status of organoids. This paper will consider whether human cerebral organoids have passed the moral threshold of sentience. If they have, or are close to doing so, regulators ought to consider their legal status in advance so as to ensure that adequate limitations are placed on this usage so as to avoid unethical practices.

Human brain organoids (HBOs) are three-dimensional biological entities grown in the laboratory in order to recapitulate the structure and functions of the adult human brain. They can be taken to be novel living entities for their specific features and uses. As a contribution to the ongoing discussion on the use of HBOs, the authors identify three sets of reasons for moral concern. The first set of reasons regards the potential emergence of sentience/consciousness in HBOs that would endow them with a moral status whose perimeter should be established. The second set of moral concerns has to do with an analogy with artificial womb technology. The technical realization of processes that are typically connected to the physiology of the human body can create a manipulatory and instrumental attitude that can undermine the protection of what is human. The third set concerns the new frontiers of biocomputing and the creation of chimeras. As far as the new frontier of organoid intelligence is concerned, it is the close relationship of humans with new interfaces having biological components capable of mimicking memory and cognition that raises ethical issues. As far as chimeras are concerned, it is the humanization of nonhuman animals that is worthy of close moral scrutiny. A detailed description of these ethical issues is provided to contribute to the construction of a regulative framework that can guide decisions when considering research in the field of HBOs.

The complexity of the human brain creates a spectrum of sophisticated behavioral repertoires, such as language, tool use, self-awareness, symbolic thought, cultural learning, and consciousness. Understanding how the human brain achieves that has been a longstanding challenge for neuroscientists and may bring insights into the evolution of human cognition and disease states. Human pluripotent stem cells could differentiate into specialized cell types and tissues in vitro. From this pluripotent state, it is possible to generate models of the human brain, such as brain organoids. The recent observation that brain organoids can spontaneously develop complex neural network activity in a dish can help one understand how neural network oscillations evolve and vary between normal and disease states. Moreover, this finding can be leveraged to other applications outside medicine, including engineering and artificial intelligence. However, as the brain model technology becomes more complex, it raises a series of ethical and moral dilemmas. This article discusses the status of this technology, some of its current limitations, and a vision of the future.

Pekka Louhiala crosses disciplines and decades to present a remarkably detailed review of the existing literature on placebos, placebo effects, and related concepts. The problem at hand—and Louhiala does aptly frame it as a problem—is a striking lack of consensus among researchers, scholars, and clinicians regarding virtually all aspects of the placebo topic. In capturing the complexity of this problem, Louhiala expertly compiles an extensive catalog of placebo literature that effectively gives the reader both a map of the territory and a legend to decipher it. He does not, however, give us clear directions to find our way out of the conceptual maze. The focus is often more on the problems than their solutions, which is simultaneously the most notable weakness and the greatest strength of the book.