Nova ARPA-H eLetter Published in Science

(In response to Policy Forum piece: ARPA-H: Accelerating biomedical breakthroughs)

ARPA-H: biomedical solutions to the health crisis require an integrated exposome approach

Bold new approaches are urgently needed to overcome the mounting health crisis (1). The proposed Advanced Research Projects Agency for Health (ARPA-H) within the National Institutes of Health provides a promising opportunity to achieve this, through a vision that considers entire ecosystems and all populations, with vulnerable groups in mind (2). 

While new technologies for earlier detection and more effective treatment are critical, we urge equal attention to the wider (physical, emotional, social, political, and economic) environmental ecosystems driving the noncommunicable disease (NCD) crisis in the first place. No matter how innovative, a “downstream” targeted focus on disease will ultimately fail if not considered in tandem with the “upstream” total lived experience (the exposome), which determines vulnerabilities of individuals and communities over time (3, 4).

The “omics” revolution offers new opportunities for truly personalized approaches that consider not only optimal pharmacological interventions but also measures of personal ecology (3, 5) and strategies to buffer adversity and promote flourishing (6). 

This means considering environmental factors (positive and negative) that influence individual ecology, including microbiomes (5, 7) to differentially determine disease risk and treatment response. It should address racial and socio-economic health inequities, reflected in unequal access to healthy food, safe green spaces, clean air and water, employment, and financial security—highlighted by the COVID-19 pandemic (8). Critically, as life expectancy (and NCD risk) are strongly determined by early life environments, ARPA-H should invest in early interventions as a matter of effectiveness and social justice.

Critically, this calls for an integrated, cross-sectoral vision that spans the interwoven connections affecting health across the scales of people, places, and planet. Initiatives like ARPA-H are uniquely placed to build this broader exposome perspective, which will not only enhance the quest for health equity through personalized, precision medicine but encourage cross-sectoral partnerships—as human health ultimately depends on addressing our social and environmental challenges (4).


Brian Berman*
Nova Institute for Health (formerly The Institute for Integrative Health), Baltimore, MD 21231, USA
Family and Community Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA


Susan L. Prescott
School of Medicine, University of Western Australia, Nedlands 6009, Western Australia, Australia
Family and Community Medicine, University of Maryland School of Medicine, Baltimore MD 21201, USA
Nova Institute for Health (formerly The Institute for Integrative Health), Baltimore, MD 21231, USA 


Steven Woolf
Family Medicine and Population Health, Virginia Commonwealth University, Richmond, VA 23284, USA
Nova Institute for Health (formerly The Institute for Integrative Health), Baltimore, MD 21231, USA 


* Corresponding author: 

  1. A. S. Venkataramani, R. O’Brien, A. C. Tsai, Declining life expectancy in the United States: The need for social policy as health policy. JAMA 325, 621-622 (2021).
  2. F. S. Collins, T. A. Schwetz, L. A. Tabak, E. S. Lander, ARPA-H: Accelerating biomedical breakthroughs. Science 373, 165-167 (2021).
  3. H. Renz et al., An exposome perspective: Early-life events and immune development in a changing world. J Allergy Clin Immunol 140, 24-40 (2017).
  4. R. T. Emeny, D. O. Carpenter, D. A. Lawrence, Health disparities: Intracellular consequences of social determinants of health. Toxicol Appl Pharmacol 416, 115444 (2021).
  5. S. L. Prescott, A. C. Logan, Each meal matters in the exposome: Biological and community considerations in fast-food-socioeconomic associations. Econ Hum Biol 27, 328-335 (2017).
  6. T. J. VanderWeele, E. McNeely, H. K. Koh, Reimagining Health-Flourishing. JAMA 321, 1667-1668 (2019).
  7. M. A. Schachtle, S. P. Rosshart, The microbiota-gut-brain axis in health and disease and its implications for translational research. Front Cell Neurosci 15, 698172 (2021).

8. S. H. Woolf, R. K. Masters, L. Y. Aron, Effect of the covid-19 pandemic in 2020 on life expectancy across populations in the USA and other high income countries: simulations of provisional mortality data. BMJ 373, n1343 (2021).