The vision of precision medicine in organoid and organ-on-chip research

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Submission Summary
Precision medicine is motivated by the insight that patients and their problems show great variability and ideally should be treated in way that accounts for the individual’s biology and context. Realizing this vision rests on the development of new model systems that can recapitulate the physiological context beyond genomics and account for relevant characteristics of individual patients. Organoids are 3D cell cultures derived from stem cells or dissociated primary tissue (e.g., a tumor), sometimes combined via microfluidics into a so-called organ-on-chip model. Organoids and organ-on-chip models are hoped to present new opportunities for direct translation from bench to bedside, by bridging the gap between in vitro models and specific in vivo targets. These models are in the scientific literature described as “miniature organs”, “diseases in a dish”, “patients-on-chips”, and are envisioned to lead to a new “one-patient paradigm” in medicine. The aim of this paper is to provide an empirically informed philosophical analysis of what is expressed in such concepts and visions for the future. Through a qualitative content analysis and ethnographic field work, we unpack what the “vision of precision” entails in organoid and organ-on-chip research and analyze the ontological and epistemic implications of different versions of this vision. We then examine an application that has already been implemented in some clinical contexts, namely the use of tumor organoids for patient-specific drug screening. By allowing for “real-time” testing targeted treatments on organoids developed from a specific patient’s cancer cells, these personalized models challenge traditional understandings of preclinical models and clinical trials. In exploring the potentials and challenges of the new model systems, we uncover underlying assumptions about what characterizes disease and constitutes evidence when the scope of preclinical models narrows down to specific patients. We show how epistemic uncertainties about translational inferences from bench to bedside relate to ontological uncertainties about how fine-grained disease categories should be understood. Moreover, we show how epistemic and ethical implications intersect when cancer patients become urgently dependent on ongoing laboratory research.
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University of Copenhagen
University of Oslo
University of Copenhagen

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