Physiology and Medicine

Clinical trial designs are often inefficient, resulting in high costs, lengthy timelines, and suboptimal patient outcomes. Innovative trial designs and decision-support tools are required to streamline the clinical evaluation process and accelerate therapeutic development.

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.

Current in-vivo delivery systems (viral vectors, nanoparticles, microchips) face challenges such as off-target accumulation and inefficiency, particularly in delivering therapies to the brain. Novel delivery approaches are needed to improve targeting and performance.

A comprehensive understanding of human health over time is hindered by the lack of longitudinal data from cohorts that are diverse and globally representative. Such datasets are essential to track developmental, nutritional, and environmental influences on long-term health outcomes.

Our understanding of human physiology and disease remains incomplete. In the last century, we have developed cures for many diseases with well-defined root causes (polio, smallbox, cholera, SMA, cervical cancer, etc.). However, a wide array of conditions still eludes cures and treatments. We have yet to fully decipher the dynamic interplay between brain and peripheral systems, the bioenergetic processes underlying chronic conditions, and the multifactorial pathways that drive aging. The biological mechanisms driving complex diseases and the aging process are multifactorial, involving multiple interacting pathways.  Although we understand some individual aging mechanisms, we do not yet have line of sight to comprehensively rejuvenating mammals or extending lifespan. To overcome these challenges, we need combinatorial approaches that can modulate multiple mechanisms simultaneously, allowing us to measure multi-system impacts and develop effective interventions.

Drug development is often hampered by failures related to absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox). Improved predictive models for molecular interactions are essential for designing safer, more effective drugs, as well as evaluating the impact of environmental chemicals. Additionally, there is a significant gap in our knowledge of what exactly is present in foods and how these components affect human biology. A comprehensive mapping of the “foodome” and studies on food component functionality are needed to advance nutrition science and personalized dietary interventions.