Ethical Implications in Making Use of Human Cerebral Organoids for Investigating Stress—Related Mechanisms and Disorders

Abstract

The generation of three-dimensional cerebral organoids from human-induced pluripotent stem cells (hPSC) has facilitated the investigation of mechanisms underlying several neuropsychiatric disorders, including stress-related disorders, namely major depressive disorder and post-traumatic stress disorder. Generating hPSC-derived neurons, cerebral organoids, and even assembloids (or multi-organoid complexes) can facilitate research into biomarkers for stress susceptibility or resilience and may even bring about advances in personalized medicine and biomarker research for stress-related psychiatric disorders. Nevertheless, cerebral organoid research does not come without its own set of ethical considerations. With increased complexity and resemblance to in vivo conditions, discussions of increased moral status for these models are ongoing, including questions about sentience, consciousness, moral status, donor protection, and chimeras. There are, however, unique ethical considerations that arise and are worth looking into in the context of research into stress and stress-related disorders using cerebral organoids. This paper provides stress research-specific ethical considerations in the context of cerebral organoid generation and use for research purposes. The use of stress research as a case study here can help inform other practices of in vitro studies using brain models with high ethical considerations.

Brain organoids and organoid intelligence from ethical, legal, and social points of view

“…An interdisciplinary framework incorporating scientific, philosophical, ethical, legal, and public perspectives can steer organoid research toward responsible translation. Lavazza and Reichlin (2023) called for the extended scientific community, neuroethicists, and other relevant experts to contribute to the development of this ethical framework, in dialog with society and policymakers (Bassil and Horstkötter, 2023;Capps, 2023). Creative governance solutions and proactive engagement fostering mutual understanding between scientists and publics will be key.…”

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

“…They can be distinguished from specific ethical issues that are related to different types of organoid research design which will be briefly touched upon here. There are ethical questions regarding the complexity of experimental systems such as assembloids (Munsie et al, 2017) or the use of HCOs and chimeras for studying stress-related disorders (Bassil and Horstkötter, 2023). Living biobanking encompasses ethical issues associated with the scope of consent, governance, genetic relationships and privacy, and what to do with actionable results (Boers et al, 2016).…”

Human Brain Organoids: Why There Can Be Moral Concerns If They Grow Up in the Lab and Are Transplanted or Destroyed

“…As was appropriately pointed out, "chimeric cerebral organoid animals … if somehow 'brain enhanced' … might experience the stress exposure even more seriously than typical experimental animals." 101 The point of interest here, however, is not the protection of animal models used in experiments, which is certainly an issue of great importance. Our interest focuses on the moral concerns that may arise from interspecies hybridization between HBOs and nonhuman animals.…”