PROJECT SUMMARY Efforts to understand the mechanisms of brain-based disease have been hindered by the limited ability of animal models to reflect the full complexity of human brain and behavior. Brain organoids represent a potential solution, allowing scientists to model human neurodevelopmental and disease processes in-vitro. These multicellular, three-dimensional tissue structures are derived from induced pluripotent stem cells and self-organize to recapitulate aspects of human cortical development. Brain organoids are linked to their original human donor through shared DNA, and also through what they can reveal about individual-specific patterns of brain development and dysfunction. Given the central role the brain plays in personal identity, it is critical to understand what human donors think and feel about brain organoids grown from their cells, and consider whether organoid models of the brain deserve unique moral status compared to, for example, lung or kidney organoids. The proposed research seeks to engage participants and other stakeholders to explore ethical issues in brain organoid research, and thus addresses a core principle of BRAIN Initiative: considering the ethical implications of neuroscience research. In Aim 1, qualitative interviews with current participants will be conducted to explore their perspectives towards brain organoid research including beliefs about meaning, moral status, and permissible uses of organoid tissue. In Aim 2, an educational video that describes brain organoids will be imbedded into an online survey and used to measure attitudes in larger groups of stakeholders who represent future participants in brain organoid research. In Aim 3, insights learned from participants and stakeholders about preferences for brain organoid research will be compared to current research practices and modifications to guide the field going forward will be proposed. The long-term goal is to ensure that brain organoid research can achieve its scientific potential and proceed in accordance with donor beliefs and values. The proposed research and training plan will leverage expertise of an interdisciplinary team of mentors and strong bioethics/neuroethics research environment across the University of Washington Center for Neurotechnology and the Treuman Katz Center for Pediatric Bioethics at Seattle Children’s. During the mentored phase of the award, the applicant will gain new content knowledge in the basic science of brain organoids, learn new skills for neuroscience communication, and complete a master’s degree in bioethics. This additional training will equip the applicant with the skills necessary to conduct the proposed research and transition into an independent faculty position.

PROJECT NARRATIVE Scientists have developed the ability to coax cells from human donors to grow into miniature pieces of neural tissue known as “brain organoids”. These organoids express genes and recapitulate aspects of neurodevelopment that are shared with their human donors, allowing insight into individual-specific disease processes and potential treatments. This project seeks to understand how human donors feel and think about brain organoids grown from their cells, with the ultimate goal to ensure that future brain organoid research is conducted in accordance with donor values.