Background: Organoids and organoid research

Organoid research comes with ambitious promises of revolutionizing biomedical research in the future and with it our view of the human organism and life itself. An organoid is an organized cluster of cells generated in vitro from different kinds of stem cells (either pluripotent or derived from some types of adult tissue) through the use of 3D tissue culturing methods. By using organ-specific cell types, such entities might serve as “three-dimensional culture models” mimicking the structural and functional properties of different organs, both human and non-human such as the retina, heart, brain, intestine, kidney, pancreas, liver, inner ear and skin.

Challenges: Neither a person nor a thing

Since Roman law, all entities have been categorized and regulated either as persons or as things (subjects or objects). Organoids, however, are entities, and organoid research and organoid-related technologies are examples of disruptive research and innovation that challenge this conceptual, epistemological and regulatory dualism. It involves three different kinds of uncertainty:

•  Conceptual uncertainty (ontological uncertainty): How should one conceive of entities that cannot be categorized as either persons or things? What are they? How do we know the characteristics of these entities called organoids?
   
• Epistemological and methodological uncertainty: How do we address forms of uncertainty that cannot be evaluated through the use of statistical methods, i.e. risk assessment? Epistemological uncertainty comes in two kinds, which can be categorized as qualitative, or strict, uncertainty and ignorance or non-knowledge. Qualitative or strict uncertainty is a form of uncertainty where possible positive and negative outcomes can be identified in advance but, contrary to risk assessments, the statistical magnitude of each possible outcome cannot be estimated. By contrast, ignorance or non-knowledge represents forms of uncertainty where neither possible outcomes nor the statistical magnitude of each can be identified in advance.
   
• Regulatory uncertainty: this uncertainty emerges because parts of regulatory frameworks concerning the rights and duties of persons have been merged with elements of regulation dealing with the stewardship of objects or things.

Objectives: Create new regulatory framework

HYBRIDA will address how these three kinds of uncertainties arise in organoid research and will develop a conceptual and regulatory framework consisting of: (a) Operational guidelines for the field, (b) a code of conduct (CoC) for researchers in academia and industry, (c) a set of contributions to existing ethics and normative frameworks and, if needed, (d) a supplement to the European Code of Conduct for Research Integrity (ECoC).

CFA in HYBRIDA: Co-creation and validation

CFA will be leading a central work package in HYBRIDA, which will encompass a three-stage co-creation and validation process:

• 1^st stage: Through three deliberative (mini-public) workshops, we will examine the attitudes towards organoid research of representatives of the general public, patients, donors and CSOs. Mini-publics are facilitated group deliberations fashioned to reach in-depth understandings of complex and controversial issues.
• 2^nd stage: Carry out expert interviews and co-creation workshops to map experiences and expectations of stakeholders/end-users and to identify gaps in existing ethics and normative frameworks. This stakeholder consultation will furthermore explore stakeholder views on initial elements of the guidelines, CoC and ethical frameworks produced in HYBRIDA.
• 3^rd stage: Obtain expert and professional stakeholder assessment of the guidelines, CoC and ethical framework produced in HYBRIDA. Six focus group interviews will be carried out to assess and validate the different outputs created.

Project info: Horizon 2020 project with 8 partners

HYBRIDA is a Horizon 2020 project that runs from 2021 until 2024. It involves eight partners: University of Oslo (coordinator), National Technical University of Athens, University of Manchester, Université Catholique de Louvain, Aarhus University (CFA), Leiden University Medical Center, French National Institute for Health and Medical Research, and Insubria University in Italy. The project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 101006012.