Inadequate Models of Human Physiology
Current preclinical models of human physiology, including animals and organoids, do not fully capture the complexity of human physiology, limiting the predicting power of preclinical experiments and explaining, in part, the costly failures of drug development in clinical trials. This is especially true for complex disorders including those of aging, neurological disorders, and female reproductive biology. More systematic and representative models—including ex vivo human organ systems or even whole bodies and novel animal species—are needed to improve the predictive power of biomedical research. These technologies also have applications in addressing organ shortages, improving neonatal care, and other unmet medical needs.
Foundational Capabilities (7)
A greater variety of small animal models (along with corresponding suites of tools such as species-specific antibodies, annotated genomes, transgenics, etc.) would enable novel biological insights and could be used to develop models of complex human diseases. Additional rodent models, as well as those beyond mouse and rat would be highly enabling.
More realistic models are also critical for aging research–many diseases of aging are studied in young animals.
Analytical tools are also important to make it easier for researchers to understand a) limitations of their research models, b) be aware of superior but less commonly used models. For example, a “Maniatis” style handbook detailing which human pathophysiology is mirrored in different species.
Lab-grown 3D organ tissues have become an established additional model system to recapitulate aspects of human biology. This technology could also enable the development of functional organs for transplant.
It is also important to make tissue models that recapitulate the effects of aging, or a form of “accelerated lifetime testing”.
Develop engineering methods for cryopreserving and safely rewarming large organs or whole bodies, which could revolutionize transplantation and long-term tissue storage.
Grow human organs in animals to study disease and drug response more accurately. Use advanced stem cell technologies to grow patient-specific tissues and organs in animals for transplantation.
Human organs could also be maintained ex vivo (“in a vat”) for research purposes. Perfused organ systems (including cadaver-based models) that maintain the structure and function of human tissues ex vivo would also be enabling.
Artificial wombs could revolutionize neonatal care and reduce preterm birth complications. They are an early stage research area with various positive biomedical externalities.
High-throughput testing in a single animal would enable entire studies to be run in rare/exceptional animals, e.g. with spontaneous disease mimicking humans or species not suitable for research labs.