Ethical, legal and social aspects of human cerebral organoids and their governance in Germany, the United Kingdom and the United States.

Human cerebral organoids (HCOs) are model systems that enable researchers to investigate the human brain in ways that had previously been impossible. The emergence of HCOs was accompanied by both expert and layperson discussions concerning the possibility of these novel entities developing sentience or consciousness. Such concerns are reflected in deliberations about how to handle and regulate their use. This perspective article resulted from an international and interdisciplinary research retreat "Ethical, Legal and Social Aspects of Human Cerebral Organoids and their Governance in Germany, the United Kingdom and the United States", which took place in Tübingen, Germany, in August 2022. The retreat focused on whether HCO research requires new ethical and regulatory approaches. It addressed epistemic issues around the detection and theorisation of consciousness, ethical concerns around moral status and research conduct, difficulties for legislation and guidelines managing these entities, and public engagement.

Ethical Issues in Cerebral Organoid Research.

About ten years ago, reports of lab-grown "mini brains" or "brains in a dish" appeared in the media, falling somewhere between the curious and the alarming. The trigger of these reports was a new method to grow three-dimensional neural tissue from human stem cells that recapitulates, to some degree, the early development of brain tissue. Despite their relatively small size and other limitations, such model systems capture in part the structure and functions of regions of the human brain and can also be combined to form so-called assembloids.

Initial heritable genome editing: mapping a responsible pathway from basic research to the clinic.

Following the Second Summit on Human Gene Editing in Hong Kong in 2018, where the birth of two girls with germline genome editing was revealed, the need for a responsible pathway to the clinical application of human germline genome editing has been repeatedly emphasised. This paper aims to contribute to the ongoing discussion on research ethics issues in germline genome editing by exploring key issues related to the initial applications of CRISPR in reproductive medicine. Following an overview of the current discussion on bringing germline genome editing into clinical practice, we outline the specific challenges associated with such interventions and the features that distinguish them from conventional clinical testing of new medical treatments. We then review proposed ethical requirements for initial heritable genome editing, such as the absence of reasonable alternatives, the existence of sufficient and reliable preclinical data, appropriate informed consent, requirements related to safety, and long-term follow-up.

The Moral Status of Cognitively Enhanced Monkeys and Other Novel Beings.

The discussion about the moral status of novel beings tends to focus on artificial intelligence, robots, and other man-made systems. We should, however, also consider a likelier kind of novel beings: animals that are genetically modified to develop human-like cognitive capabilities. This paper focuses on the possibility of conferring human characteristics on nonhuman primates (NHPs) in the context of neuroscientific research. It first discusses the use of NHPs for neuroscientific research and then, second, describes recent developments that promise to revolutionize the field and how that may lead to NHPs attaining human-like cognitive capabilities. Third, an account of moral status is developed to ground the central claim, that making the NHP brain more human-like is unproblematic as long as the NHPs do not become persons. In conclusion, this paper discusses the implications for the moral status of cognitively enhanced NHPs, as well as the implications for other novel beings.

The Emergence and Development of Animal Research Ethics: A Review with a Focus on Nonhuman Primates.

The ethics of using nonhuman animals in biomedical research is usually seen as a subfield of animal ethics. In recent years, however, the ethics of animal research has increasingly become a subfield within research ethics under the term "animal research ethics". Consequently, ethical issues have become prominent that are familiar in the context of human research ethics, such as autonomy or self-determination, harms and benefits, justice, and vulnerability. After a brief overview of the development of the field and a discussion of relevant theoretical ethical frameworks, I consider two of these issues, namely autonomy and self-determination on the one hand, and harms and benefits on the other hand. My concern is with philosophical and ethical issues, rather than animal research oversight. I focus my discussion on nonhuman primates, as the most plausible nonhuman candidates for this approach. I conclude that the approach, although promising, depends strongly on the moral status of nonhuman research subjects.

Objections still fail: a response to Faria.

In her reply to my critical assessment of objections to the Weatherall report's justification of non-human primate (NHP) research, Catia Faria focuses on three objections which she entitles 'the disanalogy', 'the utilitarian calculus' and 'species overlap'. Faria finds my assessment unconvincing, butI argue that the objections still fail.

The ethical justification for the use of non-human primates in research: the Weatherall report revisited.

The Weatherall report on the use of non-human primates in research was published in 2006. Its main conclusion was that there is a strong scientific case for the use of non-human primates in some cases, but the report stressed the importance of evaluating each case in the light of the availability of alternatives. In addition to arguing for the scientific necessity of using non-human primates in research, the report also provided an ethical justification. As could be expected, the report was harshly criticised by animal rights groups, but in the academic literature, only two critical replies appeared. In what follows, I will describe the ethical justification for non-human primate research as it is laid out in the Weatherall report and then consider the criticism in the academic literature. I conclude that the report's ethical justification for the use of non-human primates in research, in particular in basic neuroscientific research, has not been convincingly challenged by its critics. Since the criticism of the report is limited and represents only a small part of the academic discussion about the use of non-human primates in research, and a still smaller part of the ethical discussion about animal research, it is important that the discussion continue both at the academic and social level.

Synthetic Biology between Self-Regulation and Public Discourse: Ethical Issues and the Many Roles of the Ethicist.

This article discusses the roles of ethicists in the governance of synthetic biology. I am particularly concerned with the idea of self-regulation of bioscience and its relationship to public discourse about ethical issues in bioscience. I will look at the role of philosophical ethicists at different levels and loci, from the "embedded ethicist" in the laboratory or research project, to ethicists' impact on policy and public discourse. In a democratic society, the development of governance frameworks for emerging technologies, such as synthetic biology, needs to be guided by a well-informed public discourse. In the case of synthetic biology, the public discourse has to go further than merely considering technical issues of biosafety and biosecurity, or risk management, to consider more philosophical issues concerning the meaning and value of "life" between the natural and the synthetic. I argue that ethicists have moral expertise to bring to the public arena, which consists not only in guiding the debate but also in evaluating arguments and moral positions and making normative judgments. When ethicists make normative claims or moral judgments, they must be transparent about their theoretical positions and basic moral standpoints.

On balance: weighing harms and benefits in fundamental neurological research using nonhuman primates.

One of the most controversial areas of animal research is the use of nonhuman primates for fundamental research. At the centre of the controversy is the question of whether the benefits of research outweigh the harms. We argue that the evaluation of harms and benefits is highly problematic. We describe some common procedures in neurological research using nonhuman primates and the difficulties in evaluating the harm involved. Even if the harm could be quantified, it is unlikely that it could be meaningfully aggregated over different procedures, let alone different animals. A similar problem arises for evaluating benefits. It is not clear how benefits could be quantified, and even if they could be, values for different aspects of expected benefits cannot be simply added up. Sorting harms and benefits in three or four categories cannot avoid the charge of arbitrariness and runs the risk of imposing its structure on the moral decision. The metaphor of weighing or balancing harms and benefits is inappropriate for the moral decision about whether to use nonhuman primates for research. Arguing that the harms and benefits in this context are incommensurable, we suggest describing the moral consideration of harms and benefits as a coherent trade-off. Such a decision does not require commensurability. It must be well-informed about the suffering involved and the potential benefits, it must be consistent with the legal, regulatory and institutional framework within which it is made, and it must cohere with other judgments in relevant areas.