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)

ObjectiveTo present the ethical issues, moral arguments, and reasons found in the ethical literature on organoid models.DesignIn this systematic review of reasons in ethical literature, we selected sources based on predefined criteria: The publication mentions moral reasons or arguments directly relating to the creation and/or use of organoid models in biomedical research; These moral reasons and arguments are significantly addressed, not as mere passing mentions, or comprise a large portion of the body of work; The publication is peer-reviewed and published (...) in an academic article, book, national-level report, working paper, or Ph.D. thesis; The publications collected are in English.AnalysisEach article was read in-depth for identifiable moral reasons, arguments, and concerns. These were then inductively classified and synthesized to create broader categories of reasons, and eventually an overarching conceptual scheme was created.ResultsA total of twenty-three sources were included and analyzed out of an initial 266 collected sources. Five themes of ethical issues and arguments were found: Animal Experimentation; Clinical Applications and Experiments; Commercialization and Consent; Organoid Ontology and Moral Status; and Research Ethics and Research Integrity. These themes are then further broken down into sub-themes and topics. Given the extensive nature of the topics found, we will focus on describing the topics that comprised of more in-depth reasons and arguments rather than few, passing mentions or concerns.ConclusionsThe ethics of organoids requires further deliberation in multiple areas, as much of the discussions are not presented as in-depth arguments. Such sentiments are also echoed throughout the organoid ethics literature. (shrink)

Slightly modified excerpt from the section 13.4 Zusammenfassung und Ausblick (translated into englisch): This chapter is based on an analysis of ethical debates on epigenetics and genome editing, debates, in which ethical arguments relating to future generations and justice play a central role. The analysis aims to contextualize new developments in genetic engineering, such as genome and epigenome editing, ethically. At the beginning, the assumptions of "genetic determinism," on which "genetic essentialism" is based, of "epigenetic determinism" as well as "genetic" (...) and "epigenetic exceptionalism" are analyzed and critically discussed. The remarks on the ethical discourse on epigenetics show that the notion of "epigenetic determinism" can sometimes be discerned not only in popular scientific discourse but also in ethical discourse. Ethical debates on epigenetics, however, have distanced themselves from this deterministic understanding. As a result, the focus in the ethical discourse on epigenetics shifts from responsibility for one's own health and that of subsequent generations to justice. What is meant here is justice, for example, in terms of access to healthy environmental conditions, regardless of whether these contribute to health with or without epigenetic agency. An analysis of the discourse on genome editing reveals that it is primarily germline interventions that are being ethically examined, with a concentration on the aspect of inheritance. The question is whether this is accompanied by an implicit "genetic determinism" or even a "genetic essentialism": the determinism could lie in the centrality of the aspect of heritability, since only genetic information is inherited. Does the aspect of heritability and genome modification play a more decisive role in debates on genome editing than the safety issue? Is the problem of embryos and their potential offspring not being able to consent to germline intervention given such a high priority because it is a genetic intervention? Under such a premise of "strong genetic determinism" supplemented by "epigenetic determinism," not only genome editing but also epigenome editing would be ethically relevant precisely because it too would have an influence on the genome. How this influence of genome editing and epigenome editing is ethically evaluated in each case therefore depends initially on whether the assumptions of "genetic" and "epigenetic determinism" are advocated. These assumptions are increasingly viewed critically in ethical discourse because they cannot be confirmed from a scientific perspective. In popular scientific debates in particular, however, they seem to persist, which ultimately also influences the public discussion. Since a broad public discussion is required especially on genome editing, a reflective approach to the various "-isms" analyzed in this chapter is central. DOI: 10.5771/9783748927242. (shrink)

In 2008, researchers created human three-dimensional neural tissue – known as the pioneering work of “brain organoids.” In recent years, some researchers have transplanted human brain organoids into animal brains for applicational purposes. With these experiments have come many ethical concerns. It is thus an urgent task to clarify what is ethically permissible and impermissible in brain organoid research. This paper seeks (1) to sort out the ethical issues related to brain organoid research and application and (2) to propose future (...) directions for additional ethical consideration and policy debates in the field. Toward (1), this paper first outlines the current state of brain organoid research, and then briefly responds to previously raised related ethical concerns. Looking next at anticipated scientific developments in brain organoid research, we will discuss (i) ethical issues related to in vitro brain organoids, (ii) ethical issues raised when brain organoids form complexes or have relationships with other entities, and (iii) ethical issues of research ethics and governance. Finally, in pursuit of (2), we propose research policies that are mindful of the ethics of brain organoid research and application and also suggest the need for an international framework for research and application of brain organoids. (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)

This article proposes a methodological schema for engaging in a productive discussion of ethical issues regarding human brain organoids, which are three-dimensional cortical neural tissues created using human pluripotent stem cells. Although moral consideration of HBOs significantly involves the possibility that they have consciousness, there is no widely accepted procedure to determine whether HBOs are conscious. Given that this is the case, it has been argued that we should adopt a precautionary principle about consciousness according to which, if we are (...) not certain whether HBOs have consciousness—and where treating HBOs as not having consciousness may cause harm to them—we should proceed as if they do have consciousness. This article emphasizes a methodological advantage of adopting the precautionary principle: it enables us to sidestep the question of whether HBOs have consciousness and, instead, directly address the question of what kinds of conscious experiences HBOs can have, where the what-kind-question is more tractable than the whether-question. By addressing the what-kind-question, we will be able to examine how much moral consideration HBOs deserve. With this in mind, this article confronts the what-kind-question with the assistance of experimental studies of consciousness and suggests an ethical framework which supports restricting the creation and use of HBOs in bioscience. (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)

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)

Carrying out research on brains is important for medical advances in various diseases. However, such research ought not be carried out on human brains because the benefits do not outweigh the potential risks. A possible alternative is the use of brain surrogates. Nevertheless, some scholars who uphold a threshold account of moral status suggest the possibility that, with technological advances in the near future, more advanced brain surrogates will have very similar features to humans. This may suffice for these having (...) the same moral status as humans, and as a result, the situation may have implications for brain research, indeed, leading to the implication that this ought also not to be carried out upon brain surrogates. In this article, we present a relational approach to moral status which upholds that brain surrogates do not have the same moral status as human beings. Hence, brain research ought not be rejected on the grounds of equality of moral status between humans and brain surrogates. (shrink)

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)

Brain Organoids in their current state of development are patentable. Future brain organoids may face some challenges in this regard, which I address in this contribution. Brain organoids unproblematically fulfil the general prerequisites of patentability set forth in Art. 3 (1) EU-Directive 98/44/ec (invention, novelty, inventive step and susceptibility of industrial application). Patentability is excluded if an invention makes use of human embryos or constitutes a stage of the human body in the individual phases of its formation and development. Both (...) do not apply to brain organoids, unless ES-cells are used. Art. 6 (1) EU-Directive 98/44/ec excludes patentability for inventions “the commercial exploitation of which would be contrary to ordre public or morality”. While there is no conceivable scenario, in which the commercial application of current brain organoids violates the ordre public, the same is not necessarily true for future brain organoids. Keeping in mind that a development of consciousness-like abilities in future brain organoids cannot be excluded and that an ability for both physical and psychological suffering has been theorized, both of which are aspects of the ordre public, certain applications of future brain organoids may constitute a violation of the ordre public and therefore lead to an exclusion of patentability. (shrink)

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. (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)

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)

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. (shrink)