In the debates regarding the ethics of human organoid biobanking, the locus of donor autonomy has been identified in processes of consent. The problem is that, by focusing on consent, biobanking processes preclude adequate engagement with donor autonomy because they are unable to adequately recognise or respond to factors that determine authentic choice. This is particularly problematic in biobanking contexts associated with organoid research or the clinical application of organoids because, given the probability of unforeseen and varying purposes for (...) which a donor’s organoids could be employed and given the different ways in which a donor can relate to her biospecimens, a donor can value her organoids differently in different contexts and her reasons for autonomously permitting use of her cells and tissues in one case may not support an autonomous decision in another. In response, this paper has three aims: firstly, to make the case for why organoid biobanks ought to respect donor autonomy conceived as authentic choice; secondly, to explore the autonomy-respecting limits of established and widely prevalent models of biobank consent; and thirdly, to propose certain conditions that organoid biobanks ought to support or facilitate in order to respect donor autonomy. (shrink)

Organoids are three-dimensional biological structures grown in vitro from different kinds of stem cells that self-organise mimicking real organs with organ-specific cell types. Recently, researchers have managed to produce human organoids which have structural and functional properties very similar to those of different organs, such as the retina, the intestines, the kidneys, the pancreas, the liver and the inner ear. Organoids are considered a great resource for biomedical research, as they allow for a detailed study of the (...) development and pathologies of human cells; they also make it possible to test new molecules on human tissue. Furthermore, organoids have helped research take a step forward in the field of personalised medicine and transplants. However, some ethical issues have arisen concerning the origin of the cells that are used to produce organoids and their properties. In particular, there are new, relevant and so-far overlooked ethical questions concerning cerebral organoids. Scientists have created so-called mini-brains as developed as a few-months-old fetus, albeit smaller and with many structural and functional differences. However, cerebral organoids exhibit neural connections and electrical activity, raising the question whether they are or will one day be somewhat sentient. In principle, this can be measured with some techniques that are already available, which are used for brain-injured non-communicating patients. If brain organoids were to show a glimpse of sensibility, an ethical discussion on their use in clinical research and practice would be necessary. (shrink)

The advancement of and prospects for stem cell research raise a number of specific ethical issues. While navigating the ethical landscape of stem cell research is often challenging for biology researchers and biotechnology innovators, it is also difficult for the public and other persons of concern (from ethicists to policy-makers) to grasp the technicalities of a burgeoning field that develops in many directions. Organoids are one of these new biotechnological constructs that are currently eliciting a rich debate in bioethics. (...) In this guide, we argue that different types of organoids have different emerging properties with different ethical implications. Going from general properties to particular ones, we propose a typology of organoid technology and other associated biotechnology from a philosophical and ethical perspective. We point to relevant ethical issues and try to convey the sense of uncertainty peculiar to ongoing research and emerging technological objects. (shrink)

Human neural organoid research is advancing rapidly. As Greely notes in the target article, this progress presents an “onrushing ethical dilemma.” We can’t rule out the possibility that suff...

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)

Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical (...) stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to “self‐organization,” as often suggested, but rather to a process of genetically encoded self‐assembly where genetic programs encode and control the emergence of biological structures. (shrink)

Cellular 3D structures, for example, organoids, are an excellent model for studying and developing treatments for various diseases, including hereditary ones. Therefore, they are increasingly being used in biomedical research. From the point of view of safety and efficacy, recombinant adeno‐associated viral (rAAV) vectors are currently most in demand for the delivery of various transgenes for gene replacement therapy or other applications. The delivery of transgenes using rAAV vectors to various types of organoids is an urgent task, however, (...) it is associated with a number of problems that are discussed in this review. Cellular heterogeneity and specifics of cultivation of 3D structures determine the complexity of rAAV delivery and are sometimes associated with low transduction efficiency. This review surveys the main ways to solve emerging problems and increase the efficiency of transgene delivery using rAAVs to organoids. A clear understanding of the stage of development of the organoid, its cellular composition and the presence of surface receptors will allow obtaining high levels of organoid transduction with existing rAAV vectors. (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)

Recent developments in biotechnology allow for the generation of increasingly complex products out of human tissues, for example, human stem cell lines, synthetic embryo-like structures and organoids. These developments are coupled with growing commercial interests. Although commercialisation can spark the scientific and clinical promises, profit-making out of human tissues is ethically contentious and known to raise public concern. The traditional bioethical frames of gift versus market are inapt to capture the resulting practical and ethical complexities. Therefore, we propose an (...) alternative approach to identify, evaluate and deal with the ethical challenges that are raised by the increasing commercialisation of the exchange of sophisticated human tissue products. We use organoid technology, a cutting-edge stem cell technology that enables the cultivation of ‘mini-organs’ in a dish, as an example. First, we examine the moral value of organoids and recognise them as hybrids that relate to persons and their bodies as well as to technologies and markets in ambiguous ways. Second, we show that commercialisation of organoids is legitimised by a detachment of the instrumental and commercial value of organoids from their associations with persons and their bodies. This detachment is enacted in steps of disentanglement, among which consent and commodification. Third, we contend that far-reaching disentanglement is ethically challenging: (1) Societal interests could be put under pressure, because the rationale for commercialising organoid technology, that is, to stimulate biomedical innovation for the good of society, may not be fulfilled; (2) The interests of donors are made subordinate to those of third parties and the relational moral value of organoids may be insufficiently recognised. Fourth, we propose a ‘consent for governance’ model that contributes to responsible innovation and clinical translation in this exciting field. (shrink)

Certain organoid subtypes are particularly sensitive. We explore whether moral intuitions about the heartbeat warrant unique moral consideration for newly advanced contracting cardiac organoids. Despite the heartbeat’s moral significance in organ procurement and abortion discussions, we argue that this significance should not translate into moral implications for cardiac organoids.

Brain organoid research raises ethical challenges not seen in other forms of stem cell research. Given that brain organoids partially recapitulate the development of the human brain, it is plausible that brain organoids could one day attain consciousness and perhaps even higher cognitive abilities. Brain organoid research therefore raises difficult questions about these organoids' moral status – questions that currently fall outside the scope of existing regulations and guidelines. This paper shows how these gaps can be addressed. (...) We outline a moral framework for brain organoid research that can address the relevant ethical concerns without unduly impeding this important area of research. (shrink)

Human cerebral organoids (HCOs) are three-dimensional in vitro cell cultures that mimic the developmental process and organization of the developing human brain. In just a few years this technique has produced brain models that are already being used to study diseases of the nervous system and to test treatments and drugs. Currently, HCOs consist of tens of millions of cells and have a size of a few millimeters. The greatest limitation to further development is due to their lack of (...) vascularization. However, recent research has shown that human cerebral organoids can manifest the same electrical activity and connections between brain neurons and EEG patterns as those recorded in preterm babies. All this suggests that, in the future, HCOs may manifest an ability to experience basic sensations such as pain, therefore manifesting sentience, or even rudimentary forms of consciousness. This calls for consideration of whether cerebral organoids should be given a moral status and what limitations should be introduced to regulate research. In this article I focus particularly on the study of the emergence and mechanisms of human consciousness, i.e. one of the most complex scientific problems there are, by means of experiments on HCOs. This type of experiment raises relevant ethical issues and, as I will argue, should probably not be considered morally acceptable. (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)

Organoids are quickly becoming an accepted model for understanding human biology and disease. Pluripotent stem cells (PSC) provide a starting point for many organs and enable modeling of the embryonic development and maturation of such organs. The foundation of PSC‐derived organoids can be found in elegant developmental studies demonstrating the remarkable ability of immature cells to undergo histogenesis even when taken out of the embryo context. PSC‐organoids are an evolution of earlier methods such as embryoid bodies, taken (...) to a new level with finer control and in some cases going beyond tissue histogenesis to organ‐like morphogenesis. But many of the discoveries that led to organoids were not necessarily planned, but rather the result of inquisitive minds with freedom to explore. Protecting such curiosity‐led research through flexible funding will be important going forward if we are to see further ground‐breaking discoveries. (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)

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)

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)

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)

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)

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)

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. (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)

The article “Consciousness in a Bioreactor? Science and Ethics of Potentially Conscious Human Cerebral Organoids” (Zillo and Lavazza 2023) presents a thoughtful discussion on the potential ethical...

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 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. (shrink)

Sietske A.L. van Till and Eline M. Bunnik (2024) have recently expressed a concern about science miscommunication regarding human brain organoids. They worry that the mereological fallacy is often being committed when the possibility of brain organoid psychological capacities such as consciousness and intelligence are considered, especially by bioethicists discussing the moral status of human brain organoids. Focusing specifically on one psychological capacity, namely consciousness, this article begins with a brief introduction to van Till and Bunnik’s concern about (...) the mereological fallacy as it relates to brain organoids. It is then shown that whether the mereological fallacy is being committed depends on commitments in philosophy of mind about how consciousness relates to the brain and its neural mechanisms. This is demonstrated by appealing to two different example views about the ontology of consciousness embraced by J.J.C. Smart’s type identity theory and a version of hylomorphism. The article ends with a discussion of how neurobiological theories of consciousness can be intertwined with ontological commitments about consciousness that have significant implications for HBOs. An awareness of this can yield a philosophically informed application of neurobiological theories to the topic of whether HBOs could be conscious. (shrink)

Human brain organoids (HCOs) are laboratory-grown biological entities that have been added to the catalog of living entities for just over a decade. How they are formed and may continue to develop for some time is not irrelevant, given their peculiarity, which is that they mimic the human brain with a high degree of similarity. Revolving around this key issue is the discussion on our target article (Zilio and Lavazza 2023), for which we are grateful to all the commentators.

Recent developments in 3D cultures exploiting the self‐organization ability of pluripotent stem cells have enabled the generation of powerful in vitro systems termed brain organoids. These 3D tissues recapitulate many aspects of human brain development and disorders occurring in vivo. When combined with improved differentiation methods, these in vitro systems allow the generation of more complex “assembloids,” which are able to reveal cell diversities, microcircuits, and cell–cell interactions within their 3D organization. Here, the ways in which human brain (...) class='Hi'>organoids have contributed to demystifying the complexities of brain development and modeling of developmental disorders is reviewed and discussed. Furthermore, challenging questions that are yet to be addressed by emerging brain organoid research are discussed. (shrink)

In this interesting paper, Lavazza and Massimini draw attention to a subset of the ethical issues surrounding the development and potential uses of cerebral organoids. This subset concerns the possibility that cerebral organoids may one day develop phenomenal consciousness, and thereby qualify as conscious subjects—that there may one day be something it is like to be an advanced cerebral organoid. This possibility may feel outlandish. But as Lavazza and Massimini demonstrate, the science of organoids is moving fast, (...) and I agree that the ethical issues now deserve careful scrutiny. The ethical issues are not entirely separate from epistemological issues concerning how certain we could ever be (a) that an organoid is conscious or (b) that regarding any conscious state or process, an organoid is capable of tokening that state or undergoing that process. Lavazza and Massimini’s approach is theory-based—they claim that ‘we need a general theory of consciousness that attempts to explain what experience is and what type of physical systems can have it’. I am not convinced, however, that a theory of consciousness is what we need. Nor am I convinced that detecting the presence of consciousness is the most important moral issue. Let me say a word regarding theories of consciousness first. In general, to the extent that pervasive disagreement characterises expert discussion of some phenomenon P, one should modify one’s credence downward regarding any theory of the nature of P. In my view, this is the case regarding expert discussion of consciousness. Although most philosophers are confident that consciousness is an entirely physical phenomenon, a …. (shrink)

Ethical deliberations are unfolding for potentially controversial organoid‐entities such as brain organoids and embryoids. Much of the ethical deliberation centers on the questionable moral status of such organoid‐entities. However, while such work is important and appropriate, ethical deliberations may become too exclusively rooted in moral status and potentially overshadow other relevant moral dilemmas. The ethical discussion on organoid models can benefit from insights brought forth by both Judith Jarvis Thomson and Don Marquis in how they attempted to advance the (...) abortion debate. To discuss other abortion ethical issues more fully, both Thomson and Marquis assumed differing moral status positions of the conceptus and followed lines of reasoning based on these moral status assumptions. We suggest a similar approach with controversial organoid‐entities like brain organoids and embryoids. To avoid overshadowing or overlooking other relevant ethical issues, ethicists ought to first assume an organoid‐entity moral status position (such as a high moral status or no moral status) and explore any possible arguments that may result from such a position. While we ought not to copy the content of Thomson and Marquis' arguments exactly for organoid‐entities, it is worthwhile to translate their arguments' overarching structures. This paper explores the relevant insights of Thomson and Marquis, how they can be translated into the organoid ethics debate, and what possible lines of inquiry may be worth exploring based on particular moral status assumptions. (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)

Alongside in vitro studies, researchers are increasingly exploring the transplantation of human brain organoids (HBOs) into non-human animals to study brain development, disease, and repair. This paper focuses on ethical issues raised by such transplantation studies. In particular, it investigates the possibility that they might yield enhanced brain function in recipient animals (especially non-human primates), thereby fundamentally altering their moral status. I assess the critique, raised by major voices in the bioethics and science communities, according to which such concerns (...) are premature and misleading. I identify the assumptions underlying this skeptical critique, and mention some objections against them, followed by some possible replies. I proceed to argue that the skeptical position is ultimately implausible, because it presupposes an unreasonably high standard of full moral status. My argument appeals to David DeGrazia’s idea of a “borderline person”, and to the need for consistency with existing animal research regulations. I outline the practical implications of my view for the conduct of studies that might result in the development of full moral status in a transplanted animal. I also discuss some of the ethical implications of animal enhancement (particularly of rodents) below the threshold associated with full moral status. I conclude that far from being premature, further debate on these issues is urgently needed to help clarify the prospects that a neural chimera might attain full moral status in the foreseeable future, and the level of quality of life required to make it acceptable to knowingly create such a being via HBO transplantation. (shrink)

This study aims to provide a comprehensive review of the ethical, legal and social issues in human brain organoid research, with a view to different types of research and applications: in vitro research, transplantation into non-human animals, and biocomputing. Despite the academic and societal attention on the possibility that human brain organoids may be conscious, we have identified diverse issues in human brain organoid research and applications. To guide the complex terrain of human brain organoid research and applications, a (...) multidisciplinary approach that integrates ethical, legal, and social perspectives is essential. (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)

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)

Background Human brain organoids are a valuable research tool for studying brain development, physiology, and pathology. Yet, a host of potential ethical concerns are inherent in their creation. There is a growing group of bioethicists who acknowledge the moral imperative to develop brain organoid technologies and call for caution in this research. Although a relatively new technology, brain organoids and their uses are already being discussed in media literature. Media literature informs the public and policymakers but has the (...) potential for utopian or dystopian distortions. Thus, it is important to understand how this technology is portrayed to the public. Methods To investigate how brain organoids are displayed to the public, we conducted a systematic review of media literature indexed in the Nexis Uni database from 2013–2019. News and media source articles passing exclusion criteria (_n_ = 93) were scored to evaluate tone and relevant themes. Themes were validated with a pilot sample before being applied to the dataset. Thematic analysis assessed article tone, reported potential for the technology, and the scientific, social, and ethical contexts surrounding brain organoids research. Results Brain organoid publications became more frequent from 2013 to 2019. We observed increases in positively and negatively toned articles, suggesting growing polarization. While many sources discuss realistic applications of brain organoids, others suggest treatment and cures beyond the scope of the current technology. This could work to overhype the technology and disillusion patients and families by offering false hope. In the ethical narrative we observe a preoccupation with issues such as development of artificial consciousness and “humanization” of organoid-animal chimeras. Issues of regulation, ownership, and accuracy of the organoid models are rarely discussed. Conclusions Given the power that media have to inform or misinform the public, it is important this literature provides an accurate and balanced reflection of the therapeutic potential and associated ethical issues regarding brain organoid research. Our study suggests increasing polarization, coupled with misplaced and unfounded ethical concern. Given the inhibitory effects of public fear or disillusion on research funding, it is important media literature provides an accurate reflection of brain organoids. (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)

Recent scientific and technological developments enable the generation of increasingly sophisticated organoids: three-dimensional, lab-grown stem cell-based entities that model human organs anatomi...

Due to their contested ethical and legal status, human cerebral organoids (HCOs) have become the subject of one of the most rapidly expanding debates in the recent bioethics literature. There is no...

In terms of ethical implications, Boers, van Delden and Bredenoord have made an interesting step forward with their model of organoids as hybrids, which seeks to find a balance between subject-like value and object-like value. Their framework aims to introduce effective procedures not to exploit donors and to increase their engagement, but it does not seem to take sufficient account of how organoids are used and how donors and society as a whole may want to act about such (...) uses. I will concentrate my remarks on three points that I consider relevant. The first comment concerns the so-called mini-brains. The second one is related to the issue of consent and long-term ‘control’ over the organic material granted by donors. The last comment focuses on ‘genetic minorities’. (shrink)

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)

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...

This article investigates a critical yet underexplored structural aspect of consciousness in the context of the practical ethics of neural organoid research: the unity of consciousness. We advocate for the necessity of the unified field, which has garnered substantial support from both philosophical and empirical standpoints, although the debate remains unresolved. We highlight the brainstem as a potential source of the unified conscious field, a structure already under scrutiny in neural organoid research in relation to conditions such as Parkinson’s disease (...) and post-COVID-19 syndromes. We argue that if unity is a necessary feature of consciousness, consciousness is contingent upon a specific biological system without which consciousness cannot arise, thereby narrowing the range of neural organoids of ethical concern. Furthermore, the transplantation of neural organoids into animals has emerged as a practical concern, with ethical implications varying based on the necessity of the unity of consciousness. We argue that transplantation evades a significant ethical dilemma if unity is necessary and if the organoids to be transplanted lack the neural basis for the unified field of consciousness. (shrink)

Human brain organoids (HBOs) are novel entities that may exhibit unique forms of cognitive potential. What moral status, if any, do they have? Several authors propose that consciousness may hold the answer to this question. Others identify various _kinds of_ consciousness as crucially important for moral consideration, while leaving open the challenge of determining whether HBOs have them. This paper aims to make progress on these questions in two ways. First, it proposes a framework for thinking about the moral (...) status of entities other than paradigmatic persons. This framework identifies four qualities that ground moral status: evaluative stance, self-directedness, agency, and other-directedness. Second, we speculate on ways in which these qualities are relevant to dimensions of conscious experience that have been, or could be, identified in nonhuman animals. We further explore how these approaches could be adapted for use in HBOs, and argue that such studies, or something similar to them, will have to be performed if we wish to have empirical indications that HBOs have consciousness of a morally significant kind. We end by proposing that in our current scientific and epistemic situation, it is too soon to attribute any moral status to HBOs, but that this might change in the future. (shrink)

In the last two decades, stem cell-based brain organoids have been developed to study disease mechanisms in various neurological, psychiatric, and developmental disorders. Simultaneously, there hav...