How do scientists model humanness? A qualitative study of human organoids in biomedical research.

We investigate how changes in biotechnology are transforming the pursuit of human-specific models of disease and development. Our case study focuses on scientists who make human organoids. Organoids are stem cell-based three-dimensional multicellular living systems, made in labs, that mimic the function of human organs. Organoids create new opportunities for human health research, but we know little about how researchers understand the relationship between these model systems and the humans they are meant to represent. By analysing 25 interviews, complemented by observation and documentary research conducted in 2020-2022, we identify and discuss four themes that characterize how researcher's model humanness in organoids. For scientists, organoids are powerful tools to approximate the biology of human beings because they represent the closest thing to undertaking experiments on living humans, not previously possible. As laboratory tools, human organoids may replace the need for experimentation on animals, potentially contributing to the 3Rs of animal research (replacement, reduction, and refinement). Humanness is partly operationalized by modelling different human characteristics within organoids, such as male and female, different disease states, age, and other attributes. We find that human organoids are opening up previously closed spaces of experimentation and modelling in biomedicine. We argue that the humanness of organoid model systems are not a given but are enacted with and through a variety of scientific practices. These practices require critical attention from social scientists as the enactments of humanness being modelled in organoids have the potential to shape what and who counts as human in biomedical research.

Clarifying the Ethics and Oversight of Chimeric Research.

This article is the lead piece in a special report that presents the results of a bioethical investigation into chimeric research, which involves the insertion of human cells into nonhuman animals and nonhuman animal embryos, including into their brains. Rapid scientific developments in this field may advance knowledge and could lead to new therapies for humans. They also reveal the conceptual, ethical, and procedural limitations of existing ethics guidance for human-nonhuman chimeric research. Led by bioethics researchers working closely with an interdisciplinary work group, the investigation focused on generating conceptual clarity and identifying improvements to governance approaches, with the goal of helping scholars, funders, scientists, institutional leaders, and oversight bodies (embryonic stem cell research oversight [ESCRO] committees and institutional animal care and use committees [IACUCs]) deliver principled and trustworthy oversight of this area of science. The article, which focuses on human-nonhuman animal chimeric research that is stem cell based, identifies key ethical issues in and offers ten recommendations regarding the ethics and oversight of this research. Turning from bioethics' previous focus on human-centered questions about the ethics of "humanization" and this research's potential impact on concepts like human dignity, this article emphasizes the importance of nonhuman animal welfare concerns in chimeric research and argues for less-siloed governance and oversight and more-comprehensive public communication.

Composite Animals: Then and Now.

Since the early twentieth century, the term "chimera" has been used to describe many experimental composite plants and animals. Composite animals and embryos, involving the transfer of cells from different species to make chimeras, continue to be a fundamental cornerstone of biomedical research. However, the twenty-first century appears to be offering a new role for composite animals. Over the last fifteen to twenty years, composite animals and embryos have taken on a different form of life-an institutional life. With this institutional life, I argue, comes an opportunity to recast differences between humans and other animals and to reconsider how research on human health is governed.

Developing a Collaborative Agenda for Humanities and Social Scientific Research on Laboratory Animal Science and Welfare.

Improving laboratory animal science and welfare requires both new scientific research and insights from research in the humanities and social sciences. Whilst scientific research provides evidence to replace, reduce and refine procedures involving laboratory animals (the '3Rs'), work in the humanities and social sciences can help understand the social, economic and cultural processes that enhance or impede humane ways of knowing and working with laboratory animals. However, communication across these disciplinary perspectives is currently limited, and they design research programmes, generate results, engage users, and seek to influence policy in different ways. To facilitate dialogue and future research at this interface, we convened an interdisciplinary group of 45 life scientists, social scientists, humanities scholars, non-governmental organisations and policy-makers to generate a collaborative research agenda. This drew on methods employed by other agenda-setting exercises in science policy, using a collaborative and deliberative approach for the identification of research priorities. Participants were recruited from across the community, invited to submit research questions and vote on their priorities. They then met at an interactive workshop in the UK, discussed all 136 questions submitted, and collectively defined the 30 most important issues for the group. The output is a collaborative future agenda for research in the humanities and social sciences on laboratory animal science and welfare. The questions indicate a demand for new research in the humanities and social sciences to inform emerging discussions and priorities on the governance and practice of laboratory animal research, including on issues around: international harmonisation, openness and public engagement, 'cultures of care', harm-benefit analysis and the future of the 3Rs. The process outlined below underlines the value of interdisciplinary exchange for improving communication across different research cultures and identifies ways of enhancing the effectiveness of future research at the interface between the humanities, social sciences, science and science policy.