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).

Healing is facilitated through safety, persistence, and trust.

  • Persistence: “People did not simply progress through this sequence and experience healing. The healing journey was a recursive, back and forth process. They found helpers, used the skills/resources that those helpers provided, found other helpers that provided more resources and used those skills and resources. As this process continued, people experienced a gradual amelioration of their suffering. Although many despaired at times, all demonstrated the quality of persistence—they refused to give up.”
  • Safety & Trust: “To connect to helpers, it was essential for people to feel safe in those relationships and able to trust that the person would be a helper and not a barrier to healing. Persons whose wounds included a violation of trust were especially careful about testing the safety of new relationships.”

Resources support us as we heal. They include reframing, responsibility, and positivity. “Making connections enabled participants to acquire and refine resources and skills that were essential in their healing journey. People also brought their own personal strengths to the journey.”

  • Reframing: “A particularly important skill was the ability to reframe—that is to look at suffering through a different lens.” This does NOT mean minimizing trauma or pain, but rather it often means the opposite: understanding what happened was wrong, unfair, or uncontrollable and that we are not to blame for it.
  • Responsibility: While we don’t have control over what happened to us, we are the only ones who can help ourselves heal. “A third essential resource that people acquired or refined was the ability to take an appropriate amount of responsibility for their healing journeys. They participated actively in the process of healing. Once again, some participants already had developed this skill, and some acquired or refined it from their helpers.”
  • Positivity: “Another resource that people acquired or refined during their healing journey was choose to be positive—that is to have some optimism about their situation.” People have varying predispositions to positivity. In the study, positivity was important in helping people heal. This doesn’t mean a toxic positivity, but rather simply finding some good in life and feeling hopeful about our situations.

“Connection to others was an essential part of all the healing journeys.” Humans are social creatures, and even the most introverted of us need close relationships. Friends and family add meaning and value to life and help support us, in good times and bad. 

When we experience relational trauma, relationships can feel scary, but reestablishing safety and trust in relationships is where the healing happens. (To be clear, we do not mean reestablishing safety and trust with abusers, but rather finding other healing relationships.) 

“When safety and trust had been established, people were able to connect with helpers. The nature of the behaviours of helpers that fostered healing ranged from small acts of kindness to unconditional love.”

  • “Moving from being wounded, through suffering to healing, is possible. It is facilitated by developing safe, trusting relationships and by positive reframing that moves through the weight of responsibility to the ability to respond.”
  • “Relationships with health professionals were among these but were not necessarily any more important to the healing journey than other kinds of helpers, which included family members, friends, spirituality and their God, pets, support groups, administrators, case workers and supervisors.”

Healing probably means different things to different people, but one definition that emerged from the study is: “The re-establishment of a sense of integrity and wholeness.” 

Healing was an emergent property that resulted from each individuals’ complex healing journey, a result of bridged connections between resources and relationships. “…they gradually found relief from suffering and began to exhibit emergent characteristics: a sense of hope, self-acceptance, and a desire to help others—the immediate precursors to healing.”

 In varying degrees, “they were able to transcend their suffering and in some sense to flourish.” 

  • Helping Others: We find meaning in helping others. “Understanding that suffering gives the strength and experience to help others in similar situations.”
  • Hope: We begin to have hope that we will not always feel this bad. A Crohn’s patient said, “I think gradually I realized that I was going to feel better. I did have days when I actually didn’t vomit, when I did feel better. And I think gradually I came to believe that maybe I could have a normal life again.”
  • Self-Acceptance: We see our inherent value and understand that we are not to blame for our suffering. A participant living with HIV said, “I’m really proud of myself. I think that now I still want to live. I don’t want to die, and I really love myself a lot. I have a lot of comfort in myself.”

Suffering is the ongoing pain from wounding. 

There is some debate about whether people always experience suffering on the path to healing.

Wounding happens when we experience physical or emotional harm. It can stem from chronic illness or by physical or psychological trauma for which we do not have the tools to cope, or a combination of those factors. 

“The degree and quality of suffering experienced by each individual is framed by contextual factors that include personal characteristics, timing of their initial or ongoing wounding in the developmental life cycle and prior and current relationships.”

Characteristics: How predisposed someone may be to wounding/how many tools and resources someone may have to deal with trauma/illness.

Lifestages: Developmental timing plays an important role in the impact of trauma — young children often do not have the same resources as older adults.

Relationships: Relationships can provide solace and support for those suffering, while lack of healthy relationships can prolong suffering.