In order to study early human development while avoiding the burdens associated with human embryo research, scientists are redirecting their efforts towards so-called human embryo-like structures (hELS). hELS are created from clusters of human pluripotent stem cells and seem capable of mimicking early human development with increasing accuracy. Notwithstanding, hELS research finds itself at the intersection of historically controversial fields, and the expectation that it might be received as similarly sensitive is prompting proactive law reform in many jurisdictions, including the (...) Netherlands. However, studies on the public perception of hELS research remain scarce. To help guide policymakers and fill this gap in the literature, we conducted an explorative qualitative study aimed at mapping the range of perspectives in the Netherlands on the creation and research use of hELS. This article reports on a subset of our findings, namely those pertaining to (the degrees of and requirements for) confidence in research with hELS and its regulation. Despite commonly found disparities in confidence on emerging biotechnologies, we also found wide consensus regarding the requirements for having (more) confidence in hELS research. We conclude by reflecting on how these findings could be relevant to researchers and (Dutch) policymakers when interpreted within the context of their limitations. (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)

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

Many think that a specific aspect of phenomenal consciousness—valenced or affective experience—is essential to consciousness’s moral significance (valence sentientism). They hold that valenced experience is necessary for well-being, or moral status, or psychological intrinsic value (or all three). Some think that phenomenal consciousness generally is necessary for non-derivative moral significance (broad sentientism). Few think that consciousness is unnecessary for moral significance (non-necessitarianism). In this paper, I consider the prospects for these views. I first consider the prospects for valence sentientism in (...) light of Vulcans, beings who are conscious but without affect or valence of any sort. I think Vulcans pressure us to accept broad sentientism. But I argue that a consideration of explanations for broad sentientism opens up possible explanations for non-necessitarianism about the moral significance of consciousness. That is, once one leans away from valence sentientism because of Vulcans, one should feel pressure to accept a view on which consciousness is not necessary for well-being, moral status, or psychological intrinsic value. (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)

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...

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)

Consciousness-based approaches to non-human moral status maintain that consciousness is necessary for (some degree or level of) moral status. While these approaches are intuitive to many, in this paper I argue that the judgment that consciousness is necessary for moral status is not secure enough to guide policy regarding non-humans, that policies responsive to the moral status of non-humans should take seriously the possibility that psychological features independent of consciousness are sufficient for moral status. Further, I illustrate some practical consequences (...) of calling consciousness-based views into question. (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)

Sawai et al. (2022) provide a good summary of the bioethical debate about brain organoids with an eye toward future directions. Like many contemporary texts in bioethics, they call for engagement w...

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)

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)

Human brain organoids (HBOs), three-dimensional neural tissues derived from human pluripotent stem cells, are at the forefront of biomedical research, provoking intricate ethical quandaries (Sawai...

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

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

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

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)

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)

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)

Organoids, in general, have become an established theme in bioethics. However, brain organoids are almost unique due to the vital and symbolic nature of the organ they reproduce, albeit partially,...

In his paper “Non-human moral status: problems with phenomenal consciousness,” Joshua Shepherd emphasized an objectivist understanding of welfare to establish the moral status of non-human entities...

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)