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)

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)

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...

Recent advances in stem cell-derived human brain organoids and microelectrode array (MEA) tech- nology raise profound questions about the potential for these systems to give rise to sentience. Brain organoids are 3D tissue constructs that recapitulate key aspects of brain development and function, while MEAs enable bidirectional communication with neuronal cultures. As brain organoids become more sophisticated and integrated with MEAs, the question arises: Could such a system support not only intelligent computation, but subjective experience? This paper (...) explores the philosophical implications of this thought experiment, considering scenarios in which brain organoids exhibit signs of sensory awareness, distress, preference, and other hallmarks of sentience. It examines the ethical quandaries that would arise if compelling evidence of sentience were found in brain organoids, such as the moral status of these entities and the permissibility of different types of research. The paper also explores how the phenomenon of organoid sentience might shed light on the nature of consciousness and the plausibility of artificial sentience. While acknowledging the speculative nature of these reflections, the paper argues that the possibility of sentient brain organoids deserves serious consideration given the rapid pace of advances in this field. Grappling with these questions proactively could help set important ethical boundaries for future research and highlight critical avenues of scientific and philosophical inquiry. The thought experiment of sentient brain organoids thus serves as a valuable lens for examining deep issues at the intersection of neuroscience, ethics, and the philosophy of mind. (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)

Reaching back more than a century, suspension cultures have provided major insights into processes of histogenesis; e.g., cell communication, distinction of self/nonself, cell sorting and cell adhesion. Besides studies on lower animals, the vertebrate retina served as excellent reaggregate model to analyze 3D reconstruction of a complex neural laminar tissue. Methodologically, keeping cells under suspension is essential to achieve tissue organisation in vitro; thereby, the environmental conditions direct the emergent histotypic particulars. Recent progress in regenerative medicine is based to a (...) large extent on human induced pluripotent stem cells (hiPSCs), which are cultured under suspension. Following their genetically directed differentiation into various histologic 3D structures, organoids provide excellent multipurpose in vitro assay models, as well as tissues for repair transplantations. Historically, a nearly fully laminated retinal spheroid from avian embryos was achieved already in 1984, foreshadowing the potential of culturing stem cells under suspension for tissue reconstruction purposes. (shrink)

The post-genomic era raises questions about neo-Darwinian genetic determinism. Instead, open aspects of macroevolution become intelligible by Evo-Devo research. At all developmental levels, self-organization acts robustly towards “wholeness”, as exemplified by organoid technologies. In retinal reaggregates histotypical features are reached along different formative routes. Thus, tissue formation is not merely gene-directed, but channeled by unpredictable external conditions. These insights restrict conceptions of onto- and phylogenesis. Neither is characterized by unlimited randomness nor by finite genocentrism. A re-examination of Driesch´s drive to (...) wholeness, i.e., robustness and intentionality, appears timely, while his teleologic ­ postulates remain undecidable by reductionist reasoning. (shrink)

Growing awareness of the ethical implications of neuroscience in the early years of the 21st century led to the emergence of the new academic field of “neuroethics,” which studies the ethical implications of developments in the neurosciences. However, despite the acceleration and evolution of neuroscience research on nonhuman animals, the unique ethical issues connected with neuroscience research involving nonhuman animals remain underdiscussed. This is a significant oversight given the central place of animal models in neuroscience. To respond to these concerns, (...) the Center for Neuroscience and Society and the Center for the Interaction of Animals and Society at the University of Pennsylvania hosted a workshop on the “Neuroethics of Animal Research” in Philadelphia, Pennsylvania. At the workshop, expert speakers and attendees discussed ethical issues arising from neuroscience research involving nonhuman animals, including the use of animal models in the study of pain and psychiatric conditions, animal brain-machine interfaces, animal–animal chimeras, cerebral organoids, and the relevance of neuroscience to debates about personhood. This paper highlights important emerging ethical issues based on the discussions at the workshop. This paper includes recommendations for research in the United States from the authors based on the discussions at the workshop, loosely following the format of the 2 Gray Matters reports on neuroethics published by the Presidential Commission for the Study of Bioethical Issues. (shrink)

The chief themes of this discussion are as follows. First, we need a theory of the grounds of moral status that could guide practical considerations regarding how to treat the wide range of potentially conscious entities with which we are acquainted – injured humans, cerebral organoids, chimeras, artificially intelligent machines, and non-human animals. I offer an account of phenomenal value that focuses on the structure and sophistication of phenomenally conscious states at a time and over time in the mental (...) lives of conscious subjects. Second, we need to map a theory of moral status onto practical considerations. I prefer the precautionary framework proposed by many, and fruitfully precisified recently by Birch. I have suggested that in addition to further discussion surrounding the evidential bar for attributing consciousness to different types of entities, more discussion is needed regarding how value and moral status may vary across different entity-types, and regarding the sources of value in an entity’s mental life. (shrink)

Ontologies of living things are increasingly grounded on the concepts and practices of current life science. Biological development is a process, undergone by living things, which begins with a single cell and (in an important class of cases) ends with formation of a multicellular organism. The process of development is thus prima facie central for ideas about biological individuality and organismality. However, recent accounts of these concepts do not engage developmental biology. This paper aims to fill the gap, proposing the (...) lineage view of stem cells as an ontological framework for conceptualizing organismal development. This account is grounded on experimental practices of stem cell research, with emphasis on new techniques for generating biological organization in vitro. On the lineage view, a stem cell is the starting point of a cell lineage with a specific organismal source, time-interval of existence, and ‘tree topology’ of branch-points linking the stem to developmental termini. The concept of ‘enkapsis’ accommodates the cell-organism relation within the lineage view; this hierarchical notion is further explicated by considering the methods and results of stem cell experiments. Results of this examination include a (partial) characterization of stem cells’ developmental versatility, and the context-dependence of developmental processes involving stem cells. (shrink)

Das letzte halbe Jahrhundert hat einen unvergleichlichen Siegeszug der Molekularbiologie erlebt, zu dem die Genomik, die molekulare Zell- und Entwicklungsbiologie, die Epigenetik sowie Erkenntnisse der Stammzellbiologie als tragende Säulen beigetragen und die Biowissenschaften insgesamt in die sogenannte postgenomische Ära geführt haben. Anstelle eines verengten Blicks in den Kern der Zelle und seiner DNA hat sich das Visier von Biologen auf eine sich dynamisch verändernde Zellumgebung hin geöffnet. Wechselwirkungen zwischen molekularen, zellulären, organismischen bis hin zu ökologischen Hierarchieebenen, stets aufwärts und abwärts (...) interagierend (bottom-up und top-down), bestimmen das Bild post-genomischer Naturbetrachtung. Dieses erweiterte Gesichtsfeld führte einerseits weg von einem strikten Gen-gesteuerten Determinismus hin zu Systemdenken und zur Systembiologie. Zum anderen rückten auf diesem Weg wieder Lücken in der klassischen neodarwinistischen Lehre in den Fokus, die nach einer erweiterten Synthese der Standardlehre der Evolution rufen. So hat das neue Forschungsfeld Evo-Devo (Akronym für Evolutionary Developmental Biology) erstmals molekulare Mechanismen für die sprunghafte Entstehung von Merkmalen aufgezeigt, die die Grundlage für die Entstehung neuer Baupläne (Makroevolution) bildeten. (shrink)

Das letzte halbe Jahrhundert hat einen unvergleichlichen Siegeszug der Molekularbiologie erlebt, zu dem die Genomik, die molekulare Zell- und Entwicklungsbiologie, die Epigenetik sowie Erkenntnisse der Stammzellbiologie als tragende Säulen beigetragen und die Biowissenschaften insgesamt in die sogenannte postgenomische Ära geführt haben. Anstelle eines verengten Blicks in den Kern der Zelle und seiner DNA hat sich das Visier von Biologen auf eine sich dynamisch verändernde Zellumgebung hin geöffnet. Wechselwirkungen zwischen molekularen, zellulären, organismischen bis hin zu ökologischen Hierarchieebenen, stets aufwärts und abwärts (...) interagierend (bottom-up und top-down), bestimmen das Bild post-genomischer Naturbetrachtung. Dieses erweiterte Gesichtsfeld führte einerseits weg von einem strikten Gen-gesteuerten Determinismus hin zu Systemdenken und zur Systembiologie. Zum anderen rückten auf diesem Weg wieder Lücken in der klassischen neodarwinistischen Lehre in den Fokus, die nach einer erweiterten Synthese der Standardlehre der Evolution rufen. So hat das neue Forschungsfeld Evo-Devo (Akronym für Evolutionary Developmental Biology) erstmals molekulare Mechanismen für die sprunghafte Entstehung von Merkmalen aufgezeigt, die die Grundlage für die Entstehung neuer Baupläne (Makroevolution) bildeten. (shrink)