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 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)

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)

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)

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)

In his interesting commentary, Joshua Shepherd raises two points—one related to epistemology, the other to ethics—about our article on human cerebral organoids.1 2 From the epistemological standpoint, he calls into question the need for a theory of consciousness. A theory of consciousness, for him, is not necessary because of the lack of consensus about the very nature of consciousness. Shepherd suggests that ‘given widespread disagreement, applying a theory of consciousness may not be helpful when attempting to diagnose the presence of (...) consciousness in cerebral organoids’. In Shepherd’s view, it would be better to transfer ‘concepts already under development in work on the presence and structure of consciousness in difficult marginal cases involving traumatic brain injury’.2 We could not agree more on this last point; detecting a minimal capacity for consciousness in the brain of comatose patients is a very similar challenge to inferring the presence of consciousness in cerebral organoids. Every day, as a by-product of saving many lives, intensive care medicine artificially produces thousands of brains that may remain isolated, split or fragmented; in the worst case, cortical islands, or an archipelago of islands, may survive while being disconnected from the outside world. Can these islands host some form of consciousness? That is, does it feel like anything to be a large piece of human cortex? Addressing this difficult question requires the development of general, objective brain-based indices of consciousness that are independent of sensory processing, executive functions and motor outputs.3 Consider, for example, a patient showing reflexive spontaneous behaviour, no response to command and no ability to communicate. In her brain, afferent pathways are damaged, thereby impairing the recruitment of cortical areas in response to sensory stimulation; basal ganglia, as well as other frontal structures supporting executive functions, are impaired. However, resting metabolism and significant electroencephalography …. (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)

Hank Greely’s target article, “Human Brain Surrogates Research: The Onrushing Ethical Dilemma” reviews the manifold scientific and ethical questions surrounding models of human brains used i...

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)

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)

What consciousness exactly is remains an unsettled issue among both philosophers and biologists. Three aspects of consciousness are generally recognized: awareness consciousness (through connection...

This paper examines potential ethical and legal issues arising during the research, develop- ment and clinical use of a proposed strategy in personalized medicine (PM): using human induced pluripotent stem cell (iPSC)-derived tissue cultures as predictive models of individ- ual patients to inform treatment decisions. We focus on epilepsy treatment as a likely early application of this strategy, for which early-stage stage research is underway. In relation to the research process, we examine issues associated with biological samples; data; health; vulnerable (...) populations; neural organoids; and what level of accuracy justifies using the iPSC-derived neural tissue system. In relation to clinical use, we examine potential uses in pre-natal screening, and effects on clinical decision-making. Although our focus is providing recommendations for researchers developing work in this area, we identify the novel issue of deciding on an acceptable accuracy level for the system. We also emphasize an issue thus far neglected in the ethics of PM: PM tends to represent treatment decisions as though they should be directed solely by biomedical information, but this in itself could be detri- mental to best personalizing treatment decisions in the clinic. (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)

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)

In their latest target article, Zilio and Lavazza (2023) major claim is that research on human cerebral organoids (HCOs) must take into account whether they can acquire sentience or a primitive for...

The moral status of human brain organoids (HBOs) has been debated in view of the future possibility that they may acquire phenomenal consciousness. This study empirically investigates the moral sensitivity in people’s intuitive judgments about actions toward conscious HBOs. The results showed that the presence/absence of pain experience in HBOs affected the judgment about the moral permissibility of actions such as creating and destroying the HBOs; however, the presence/absence of visual experience in HBOs also affected the judgment. These findings suggest (...) that people’s intuitive judgments about the moral status of HBOs are sensitive to the valence-independent value of phenomenal consciousness. We discuss how these observations can have normative implications; particularly, we argue that they put pressure on the theoretical view that the moral status of conscious HBOs is grounded solely in the valence-dependent value of consciousness. We also discuss how our findings can be informative even when such a theoretical view is finally justified or when the future possibility of conscious HBOs is implausible. (shrink)

The convergence of human and artificial intelligence is currently receiving considerable scholarly attention. Much debate about the resulting _Hybrid Minds_ focuses on the integration of artificial intelligence into the human brain through intelligent brain-computer interfaces as they enter clinical use. In this contribution we discuss a complementary development: the integration of a functional in vitro network of human neurons into an _in silico_ computing environment. To do so, we draw on a recent experiment reporting the creation of silico-biological intelligence as (...) a case study (Kagan et al., 2022b ). In this experiment, multielectrode arrays were plated with stem cell-derived human neurons, creating a system which the authors call _DishBrain_. By embedding the system into a virtual game-world, neural clusters were able to receive electrical input signals from the game-world and to respond appropriately with output signals from pre-assigned motor regions. Using this design, the authors demonstrate how the _DishBrain_ self-organises and successfully learns to play the computer game ‘Pong’, exhibiting ‘sentient’ and intelligent behaviour in its virtual environment. The creation of such hybrid, silico-biological intelligence raises numerous ethical challenges. Following the neuroscientific framework embraced by the authors themselves, we discuss the arising ethical challenges in the context of Karl Friston’s Free Energy Principle, focusing on the risk of creating synthetic phenomenology. Following the _DishBrain’s_ creator’s neuroscientific assumptions, we highlight how DishBrain’s design may risk bringing about artificial suffering and argue for a congruently cautious approach to such synthetic biological intelligence. (shrink)