Human tissues in a dish: The research and ethical implications of organoid technology

Ethics of organoid research Growing functional human tissues and organs would provide much needed material for regeneration and repair. New technologies are taking us in that direction. In addition to their use in regenerative medicine, stem cells that grow and morph into organ-like structures known as organoids can be used in drug development and toxicology testing. The potential developments and possibilities are numerous and affect not only biomedicine but also areas of ongoing ethical debate, such as animal experimentation, research on human embryos and fetuses, ethics review, and patient consent. Bredenoord et al. review how organoids affect existing ethical debates and how they raise novel ethical dilemmas and professional responsibilities. Science, this issue p. 10.1126/science.aaf9414 BACKGROUND Organoids are stem cell–derived structures generated in vitro that display the three-dimensional architecture and physiology of intact organs. They offer unique possibilities for modeling and studying normal development and disease processes and open up innovative approaches to medical research, drug discovery, and toxicology testing. Together with reprogramming technology and gene editing methods, organoids hold the promise to influence the innovation cycle in biomedical research, including fields that historically have been the subject of intense ethical debate. In this Review, we discuss the ethical implications of organoid technology and the impact on biomedical research. ADVANCES Owing to their great potential, organoids are likely to affect ongoing ethical debates over subjects ranging from the role of animal experiments and the use of human embryos and tissues in biomedical research to precision medicine, stem cell transplantation, and gene therapy. Most societies have formulated public policies to balance the advancement of biomedical science with the various concerns regarding the use of animals and human embryos and tissues for biomedical research. Organoids may necessitate a recalibration of these ethical and legal policies. However, they should not be presented as a simple solution that can abrogate controversial technologies. We suggest that the use of organoids is complementary to, rather than in competition with, these classical research methodologies. In addition, organoids should not be seen as a morally neutral alternative. They are grown from cells and tissues obtained from human individuals, and establishing the moral and legal status of human organoids requires ethical discussion and empirical research, particularly for sensitive cases such as brain organoids. The storage and use of organoids in so-called living biobanks raise ethical and governance challenges—for example, questions about the type of donor consent and ethics review needed for long-term storage and use and for feedback of clinically relevant findings to the patient. Personalized drug testing in organoids may close the gap between preclinical drug development and clinical trials. It will further blur the line between research and care and will challenge policies for drug reimbursement by insurance companies. Cautious ethical approaches are needed for the first clinical transplantations of organoids, particularly when organoid technologies are combined with gene editing. Last, the strong public interest in organoids, together with the immature nature of the field, requires particular attention regarding public (media) communication to avoid inaccurate or incomplete representations and excessive expectations. OUTLOOK Organoid research holds considerable potential for investigating human development and disease and for advancing precision and regenerative medicine. Despite these promising applications, there are several layers of complexity, not only in a technological sense, but also with regard to the ethical introduction in research, clinical care, and society. By engaging scientists, clinicians, patients, ethicists, policy-makers, and the public in constructive interdisciplinary collaborations and dialog around the challenges discussed in this Review, we strive for responsible research and innovation and long-term acceptance of this exciting technology. Ethical considerations of organoid models. Organoids are likely to affect policies for research using animals and human embryos. They also have implications for biobanking and patient consent policies and require particular responsibility in communicating results to the public. Credit: K. Sutliff/SCIENCE The ability to generate human tissues in vitro from stem cells has raised enormous expectations among the biomedical research community, patients, and the general public. These organoids enable studies of normal development and disease and allow the testing of compounds directly on human tissue. Organoids hold the promise to influence the entire innovation cycle in biomedical research. They affect fields that have been subjects of intense ethical debate, ranging from animal experiments and the use of embryonic or fetal human tissues to precision medicine, organoid transplantation, and gene therapy. However, organoid research also raises additional ethical questions that require reexamination and potential recalibration of ethical and legal policies. In this Review, we describe the current state of research and discuss the ethical implications of organoid technology.