My paper builds on the conceptual tools from three interrelated philosophical debates that—as I believe—may help structure important if chaotic discussions about surrogates for living human brains and resolve some practical issues related to regulatory matters. In particular, I refer to the discussions about the “moral precautionary principle” in research ethics (Koplin and Wilkinson 2019); about normative uncertainty in ethics (MacAskill, Bykvist, and Ord 2020), and about the inductive risk problem for animal welfare scientists (Birch 2018). I elucidate upon the (...) possible meanings of the phrase “a too good human brain surrogate” used by Henry T. Greely (2021), and I demonstrate that the evaluation of the practical and regulatory implications of the “goodness” of such surrogates created for research purposes should be sensitive to the possible consequences of two types of errors: the under-attribution and over-attribution of moral status to such beings. Many authors writing about this topic (including Greely 2021, but see also, e.g., Koplin and Savulescu 2019) concentrate only on the first type of error, neglecting the negative consequences of the second type, i.e., over-attribution. (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)

Consciousness scientists have not reached consensus on two of the most central questions in their field: first, on whether consciousness overflows reportability; second, on the physical basis of consciousness. I review the scientific literature of the 19th century to provide evidence that disagreement on these questions has been a feature of the scientific study of consciousness for a long time. Based on this historical review, I hypothesize that a unifying explanation of disagreement on these questions, up to this day, is (...) that scientific theories of consciousness are underdetermined by the evidence, namely, that they can be preserved “come what may” in front of (seemingly) disconfirming evidence. Consciousness scientists may have to find a way of solving the persistent underdetermination of theories of consciousness to make further progress. (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)

This introductory chapter attempts to clarify the philosophical, empirical, and theoretical bases on which a cognitive neuroscience approach to consciousness can be founded. We isolate three major empirical observations that any theory of consciousness should incorporate, namely (1) a considerable amount of processing is possible without consciousness, (2) attention is a prerequisite of consciousness, and (3) consciousness is required for some specific cognitive tasks, including those that require durable information maintenance, novel combinations of operations, or the spontaneous generation of intentional (...) behavior. We then propose a theoretical framework that synthesizes those facts: the hypothesis of a global neuronal workspace. This framework postulates that, at any given time, many modular cerebral networks are active in parallel and process information in an unconscious manner. An information becomes conscious, however, if the neural population that represents it is mobilized by top-down attentional amplification into a brain-scale state of coherent activity that involves many neurons distributed throughout the brain. The long-distance connectivity of these `workspace neurons' can, when they are active for a minimal duration, make the information available to a variety of processes including perceptual categorization, long-term memorization, evaluation, and intentional action. We postulate that this global availability of information through the workspace is what we subjectively experience as a conscious state. A complete theory of consciousness should explain why some cognitive and cerebral representations can be permanently or temporarily inaccessible to consciousness, what is the range of possible conscious contents, how they map onto specific cerebral circuits, and whether a generic neuronal mechanism underlies all of them. We confront the workspace model with those issues and identify novel experimental predictions. Neurophysiological, anatomical, and brain-imaging data strongly argue for a major role of prefrontal cortex, anterior cingulate, and the areas that connect to them, in creating the postulated brain-scale workspace. (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...

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)

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)

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...

Different types of consent are used to obtain human biospecimens for future research. This variation has resulted in confusion regarding what research is permitted, inadvertent constraints on future research, and research proceeding without consent. The National Institutes of Health Clinical Center's Department of Bioethics held a workshop to consider the ethical acceptability of addressing these concerns by using broad consent for future research on stored biospecimens. Multiple bioethics scholars, who have written on these issues, discussed the reasons for consent, the (...) range of consent strategies, and gaps in our understanding, and concluded with a proposal for broad initial consent coupled with oversight and, when feasible, ongoing provision of information to donors. This article describes areas of agreement and areas that need more research and dialogue. Given recent proposed changes to the Common Rule, and new guidance regarding storing and sharing data and samples, this is an important and tim.. (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)

Uncovering the neural basis of consciousness is a major challenge to neuroscience. In this Perspective, Tononi and colleagues describe the integrated information theory of consciousness and how it might be used to answer outstanding questions about the nature of consciousness.

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 brain research is moving into a dilemma. The best way to understand how the human brain works is to study living human brains in living human beings, but ethical and legal standards make it d...

The International Society for Stem Cell Research (ISSCR) has recently released the 2021 update of its guidelines. The update includes detailed new recommendations on human–animal chimera research. This paper argues that the ISSCR recommendations fail to address the core ethical concerns raised by neurological chimeras—namely, concerns about moral status. In minimising moral status concerns, the ISSCR both breaks rank with other major reports on human–animal chimera research and rely on controversial claims about the grounds of moral status that many people (...) will rightly reject. A more robust framework for regulating human–animal chimera research still needs to be developed. (shrink)

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...