Andrew J. Barnhart

Unresponsive Wakefulness Syndrome (UWS), a condition characterized by wakefulness without awareness, presents significant medical and moral uncertainties, particularly in end-of-life decision-making. Digital Brain Twins (DBTs), virtual replicas of patients’ brains driven by advanced artificial intelligence, offer the potential to alleviate medical uncertainties by providing precise diagnoses, prognoses, and experimental platforms for treatment testing. This paper provides a theoretical contribution by examining the potential ethical impact of these technologies in the context of UWS. We argue that, while DBTs promise greater diagnostic accuracy, personalized predictions of recovery, and non-invasive tools for exploring therapeutic interventions, they do not necessarily resolve the moral uncertainties faced by proxy decision-makers. Decisions about withdrawing or continuing life-sustaining treatment are fundamentally moral and value-laden, often extending beyond empirical evidence provided by DBTs. Factors such as cognitive biases, emotional distress, and subjective interpretations of best interest further complicate these decisions. While DBTs represent a breakthrough in precision medicine, their role in navigating the ethical complexities of UWS is limited, emphasizing the need for integrated approaches that combine technological innovation with ethical and psychological support for proxies.

In precision medicine, digital twins—virtual models of patients created using personalized data and advanced machine learning—are potentially changing healthcare by predicting health outcomes and guiding medical decisions. However, their use raises complex ethical questions, particularly concerning their relationship to human dignity. Patients often regard dignity as central to their healthcare experience, and failing to incorporate this principle into the design and application of digital twins risks undermining personal autonomy, misusing sensitive data, eroding patient–provider trust, and creating broader ethical challenges. This paper argues that digital twins are not mere data sets or predictive tools, but symbolic extensions of the dignity of the individuals they represent. Using David Kirchhoffer's multidimensional framework of human dignity, this study examines how digital twins engage with both absolute (inherent) and contingent (socially constructed) dimensions of dignity. The analysis begins by exploring the multidimensional concept of human dignity, followed by a discussion of how digital twins embody these dimensions, illustrated through examples such as digital brain twins, posthumous digital representations, and disability contexts. Finally, the paper addresses the ethical implications of these findings, emphasizing the moral responsibilities of researchers, developers, and clinicians to treat digital twins as representations of patient dignity, thereby ensuring these technologies advance healthcare without compromising the fundamental respect owed to every individual.

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.

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.

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.