We review recent research to introduce human brain organoids into the brains of infant rats. This research shows these organoids integrate and function to affect behaviour in rats. We argue that this raises issues of moral status that will imminently arise and must be addressed through functional studies of these new life forms. We situate this research in the broader context of the biological revolution, arguing we already have the technological power to create fully human embodied animals. This raises profound, (...) so far unaddressed ethical issues which call for urgent attention. (shrink)

In this paper, we outline how one might conduct a comprehensive ethical evaluation of human brain organoid transplantation in animals. Thus far, ethical concerns regarding this type of research have been assumed to be similar to those associated with other transplants of human cells in animals, and have therefore not received significant attention. The focus has been only on the welfare, moral status, or mental capacities of the host animal. However, the transplantation of human brain organoids introduces several new ethical (...) issues. Many of these are related to uncertainty regarding whether or not brain organoids might be conscious. While these concerns might not be immediately relevant, they warrant closer scrutiny. We discuss how various ethical issues are relevant to different stages of human brain organoid transplantation and can guide the ethical evaluation of research. Our examination would broaden the horizons of the debate on the transplantation of brain organoids. (shrink)

It would be unwise to dismiss the possibility of human brain organoids developing sentience. However, scepticism about this idea is appropriate when considering current organoids. It is a point of consensus that a brain-dead human is not sentient, and current organoids lack a functioning brainstem. There are nonetheless troubling early warning signs, suggesting organoid research may create forms of sentience in the near future. To err on the side of caution, researchers with very different views about the neural basis of (...) sentience should unite behind the “brainstem rule”: if a neural organoid develops or innervates a functioning brainstem that regulates arousal and leads to sleep-wake cycles, then it is a sentience candidate. If organoid research leads to the creation of sentience candidates, a moratorium or indefinite ban on the creation of the relevant type of organoid may be appropriate. A different way forward, more consistent with existing approaches to animal research, would be to require ethical review and harm-benefit analysis for all research on sentience candidates. (shrink)

Advances in research on human cerebral organoids (HCOs) call for a critical review of current research policies. A challenge for the evaluation of necessary research regulations lies in the severe uncertainty about future trajectories the currently very rudimentary stages of neural cell cultures might take as the technology progresses. To gain insights into organotypic cultures, ethicists, legal scholars, and neuroscientists rely on resemblances to the human brain. They refer to similarities in structural or functional terms that have been established in (...) scientific practice to validate organotypic cultures as models for brain research. In ethical discourse, however, such similarities are also used to justify assumptions about the potential risk to cause harm to HCOs. Ethicists assume that as the technology advances, organotypic cultures will increasingly resemble the human brain, raising more complex ethical issues. I argue that such reasoning is not justified given the heterogeneity of HCOs that have been modified to enable scientists to pursue their research goals. I then discuss the implications this line of thought has for advocates of the precautionary principle, focussing on those suggestions which propose adopting research regulations to the presence of bodily warning signs deemed worthy of protection. In doing so, I illustrate that the prevalent assumptions on similarity in ethical discourse ultimately risk disproportionately restricting research. I conclude that given the severe uncertainty about the technology’s future development, ethical discourse might benefit from narrowing the time frame for anticipation. (shrink)

Human brain organoids are three-dimensional masses of tissues derived from human stem cells that partially recapitulate the characteristics of the human brain. They have promising applications in many fields, from basic research to applied medicine. However, ethical concerns have been raised regarding the use of human brain organoids. These concerns primarily relate to the possibility that brain organoids may become conscious in the future. This possibility is associated with uncertainties about whether and in what sense brain organoids could have consciousness (...) and what the moral significance of that would be. These uncertainties raise further concerns regarding consent from stem cell donors who may not be sufficiently informed to provide valid consent to the use of their donated cells in human brain organoid research. Furthermore, the possibility of harm to the brain organoids raises question about the scope of the donor’s autonomy in consenting to research involving these entities. Donor consent does not establish the reasonableness of the risk and harms to the organoids, which ethical oversight must ensure by establishing some measures to mitigate them. To address these concerns, we provide three proposals for the consent procedure for human brain organoid research. First, it is vital to obtain project-specific consent rather than broad consent. Second, donors should be assured that appropriate measures will be taken to protect human brain organoids during research. Lastly, these assurances should be fulfilled through the implementation of precautionary measures. These proposals aim to enhance the ethical framework surrounding human brain organoid research. (shrink)

Any attempt at consciousness assessment in organoids requires careful consideration of the theory of consciousness that researchers will rely on when performing this task. In cognitive neuroscience and the clinic, there are tools and theories used to detect and measure consciousness, typically in human beings, but none of them is neither fully consensual nor fit for the biological characteristics of organoids. I discuss the existing attempt relying on the Integrated Information Theory and its models and tools. Then, I revive the (...) distinction between global theories of consciousness and local theories of consciousness as a thought-provoking one for those engaged in the difficult task of adapting models of consciousness to the biological reality of brain organoids. The “microconsciousness theory” of Semir Zeki is taken as an exploratory path and illustration of a theory defending that minimal networks can support a form of consciousness. I suggest that the skepticism prevailing in the neuroscience community regarding the possibility of organoid consciousness relies on some assumptions related to a globalist account of consciousness and that other accounts are worth exploring at this stage. (shrink)

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. (shrink)

Human cerebral organoids are three-dimensional biological cultures grown in the laboratory to mimic as closely as possible the cellular composition, structure, and function of the corresponding organ, the brain. For now, cerebral organoids lack blood vessels and other characteristics of the human brain, but are also capable of having coordinated electrical activity. They have been usefully employed for the study of several diseases and the development of the nervous system in unprecedented ways. Research on human cerebral organoids is proceeding at (...) a very fast pace and their complexity is bound to improve. This raises the question of whether cerebral organoids will also be able to develop the unique feature of the human brain, consciousness. If this is the case, some ethical issues would arise. In this article, we discuss the necessary neural correlates and constraints for the emergence of consciousness according to some of the most debated neuroscientific theories. Based on this, we consider what the moral status of a potentially conscious brain organoid might be, in light of ethical and ontological arguments. We conclude by proposing a precautionary principle and some leads for further investigation. In particular, we consider the outcomes of some very recent experiments as entities of a potential new kind. (shrink)

Neural organoids are laboratory-generated entities that replicate certain structural and functional features of the human brain. Most neural organoids are disembodied—completely decoupled from sensory input and motor output. As such, questions about their potential capacity for consciousness are exceptionally difficult to answer. While not disputing the need for caution regarding certain neural organoid types, this paper appeals to two broad constraints on any adequate theory of consciousness—the first involving the dependence of consciousness on embodiment; the second involving the dependence of (...) consciousness on representations—to argue that disembodied neural organoids are not plausible candidates for consciousness. (shrink)

1. 1.1. Suffering is bad. This is why, ceteris paribus, there are strong moral reasons to prevent suffering. Moreover, typically, those moral reasons are stronger when the amount of suffering at st...

Organoids and specifically human cerebral organoids (HCOs) are one of the most relevant novelties in the field of biomedical research. Grown either from embryonic or induced pluripotent stem cells, HCOs can be used as in vitro three-dimensional models, mimicking the developmental process and organization of the developing human brain. Based on that, and despite their current limitations, it cannot be assumed that they will never at any stage of development manifest some rudimentary form of consciousness. In the absence of behavioral (...) indicators of consciousness, the theoretical neurobiology of consciousness being applied to unresponsive brain-injured patients can be considered with respect to HCOs. In clinical neurology, it is difficult to discern a capacity for consciousness in unresponsive brain-injured patients who provide no behavioral indicators of consciousness. In such scenarios, a validated neurobiological theory of consciousness, which tells us what the neural mechanisms of consciousness are, could be used to identify a capacity for consciousness. Like the unresponsive patients that provide a diagnostic difficulty for neurologists, HCOs provide no behavioral indicators of consciousness. Therefore, this article discusses how three prominent neurobiological theories of consciousness apply to human cerebral organoids. From the perspective of the Temporal Circuit Hypothesis, the Global Neuronal Workspace Theory, and the Integrated Information Theory, we discuss what neuronal structures and functions might indicate that cerebral organoids have a neurobiological capacity to be conscious. (shrink)

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. (shrink)

An ethical and legal framework is needed to regulate the rapidly developing human brain organoid research field properly. However, considering the legal issues involved in human brain organoid research remains underdeveloped and scattered. This article reviews the legal issues of human brain organoid research, grouping them into the following five broad themes: (1) consciousness, (2) legal status, (3) consent, (4) ownership, and (5) transplantation. The issues in each topic include both the urgent (e.g., appropriate forms of consent) and the speculative (...) (e.g., protection of conscious human brain organoids). Therefore, we have attempted to be as explicit as possible about the timescale within which each issue will be realized and to prioritize each. Examining these issues has revealed legal issues specific to human brain organoid research and issues common to research in other fields. Further discussion of human brain organoid research from a legal perspective is needed in the future, considering discussions in related fields. (shrink)