Transforming our Understanding of Health through Precision Medicine 2.0

Medicine is in the midst of an unprecedented transformation. Known broadly as Precision Medicine –disease and health are being redefined by their molecular characteristics. Such characterization enables the sub-grouping of patient populations and the development of targeted interventions. Somewhat ironically, these Personalized Medicine interventions are developed without consideration of sex differences, differences between populations, individual life history, and social circumstances.

As the Precision Medicine paradigm has advanced it has revealed that the mechanisms of disease are remarkably complex. The emerging health challenges of the 21st century are not simple. The health burdens that confront both developed and developing countries are shifting to chronic, multifactorial diseases such as cancer, cardiovascular, psychiatric, and neurodegenerative disease. Diseases of Westernization, including those considered ‘lifestyle diseases’ of affluence and excess, such as obesity and cardiovascular disease, are of increasing significance worldwide. Immune-related diseases, in the form of autoimmunity and allergies, are a growing driver of international morbidity and mortality.

Health is modified by individuals’ economic and environmental contexts. Underappreciated is the role that social influences such psychosocial stress play on health and disease risk. Independent of economic status and environmental exposures, these social influences are shown to result in measurable differences in metabolic homeostasis via neuroendocrine and immunological processes. This suggests that the underlying etiology of disease may be different within different social contexts and that interventions that are developed in different social contexts may have differing efficacy.

Addressing the emerging diseases of the 21st century calls for a Precision Medicine 2.0. Precision Medicine 2.0 is characterized by certain key insights. First is the recognition that Disease is Complex – a “system” with interactions among multiple physiological, psychological, and environmental components resulting in emergent properties – that is, a whole more than the sum of the parts. Second, in addition to the host, the system includes an encompassing ecosystem with which the host interacts and resides. Due to this ecosystem, Context Matters. This system is dynamic and has capabilities that adjust in response to change. As such, mechanisms that produce health in one context manifest disease in others. Third, interdependence of factors means that comparative advantages for one trait have concomitant trade-offs and compromises with others – hence, Health is a Compromise. This insight also explains the adverse events often observed in targeted therapeutics. Fourth, Health is a Continuum – the changing ecologies that an individual experiences within a lifetime and that a species faces over evolutionary time shape phenotypes and “life history strategies” – the age-specific patterns and timing of life events.

Precision Medicine 2.0 requires transdisciplinary teams examining multidimensional data that include longitudinal health records, metabolic measures, hormonal assessment, immune profiles, and state-of-the-art genomic characterizations. Disease risk varies at both the global and local level. Insight is gained from contrasting populations drawn from different contexts and different ancestry including pre-industrial populations and disparate Western, Educated, Industrialized, Rich, and Democratic (WEIRD) populations within the United States and across the world. For example, some populations in the Amazon don’t appear to get cardiometabolic diseases, while marathoners in the U.S. that have equitable exercise and healthy diets do.

Arizona State University’s Center for Evolution and Medicine is pioneering Precision Medicine 2.0. The Center is an exemplar of ASU’s New American University. The Center’s innovative research agenda is focused on today’s health problems with the goal of translation to practice. Its focus on Precision Medicine 2.0 blends academic disciplines and bridges medicine and public health.