Creating a National Exposome Project
The U.S. government should establish a public-private National Exposome Project (NEP) to generate benchmark human exposure levels for the ~80,000 chemicals to which Americans are regularly exposed. Such a project will revolutionize our ability to treat and prevent human disease. An investment of $10 billion over 20 years would fuel a new wave of scientific discovery and advancements in human health. To date, there has not been a systematic assessment of how exposures to these environmental chemicals (such as pesticides, solvents, plasticizers, medications, preservatives, flame retardants, fossil fuel exhaust, and food additives) impact human health across the lifespan and in combination with one another.
While there is emerging scientific consensus that environmental exposures play a role in most diseases, including autoimmune conditions and many of the most challenging neurodegenerative diseases and cancers, the lack of exposomic reference data restrains the ability of scientists and physicians to understand their root causes and manage them. The biomedical impact of creating a reference exposome would be no less than that of the Human Genome Project and will serve as the basis of technological advancement, the development of new medicines and advanced chemicals, and improved preventative healthcare and the clinical management of diseases.
Challenge and Opportunity
The Human Genome Project greatly advanced our understanding of the genetics of disease and helped accelerate a biotech revolution, creating an estimated $265 billion economic impact in 2019 alone. However, genetics has been unable to independently explain the root causes of the majority of diseases from which we suffer, including neurodegenerative diseases like Alzheimer’s and Parkinson’s and many types of cancer. We know exposures to chemicals and pollution are responsible for or mediate the 70–90% of disease causation not explained by genetics. However, because we lack an understanding of their underlying causal factors, many new medicines in development are more palliative than curative. If we want to truly prevent and cure the most intractable illnesses, we must uncover the complex environmental factors that contribute to their pathogenesis.
In addition to the social and economic benefits that would come from reducing our society’s disease burden, American leadership in exposomics would also strengthen the foundation of our biomedical innovation ecosystem, making the U.S. the premier partner for what is likely to be the most advanced health-related research field in this century.
Three key trends are converging to make now the best time to act: First, the costs of chemical sensors and the data and analytics infrastructure to manage them have fallen precipitously over the last two decades. Second, a few existing small scale exposomic projects offer a blueprint for how to build the NEP. Third, advancements in artificial intelligence (AI) and machine learning are making possible entirely new tools to make causal inferences from complex environmental data, which can inform research into treatments and policies to prevent diseases.
Plan of Action
To bring the National Exposome Project to life, Congress should appropriate $10 billion over 20 years to Department of Health and Human Services (HHS) to establish a National Exposomics Project Office within the Office of the HHS Secretary, whose director reports directly to the HHS Secretary. The NEP director should be given authority to establish partnerships with HHS agencies (National Institutes of Health, Centers for Disease Control, Advanced Research Projects Agency for Health, Food and Drug Administration) and other federal agencies (Environmental Protection Agency, Commerce, Defense, Homeland Security, National Science Foundation), and to fund and enter into agreements with state and local governments, academic, and private sector partners. The NEP will operate through a series of public-private cores that each are responsible for one of three pillars.
Recommendation 1. Create a reference human exposome
Through partnerships with industry, government, and academic partners, the NEP would generate comprehensive data on the body burden of chemicals and the corresponding biological responses in a representative sampling of the U.S. (>500,000 individuals). This would likely require collecting bio samples (such as blood, saliva, etc.) from participating individuals, performing advanced chemical analysis on the samples using technologies such as high- resolution mass spectrometry, and following up over the study with the participants to observe which health conditions emerge. Critically, bio samples will need to be collected repeatedly over time and bio-banked in order to ensure that the temporal aspect of exposures (such as whether someone was exposed to a particular chemical as a child or as an adult) is included in the final complete data set.
High-throughput toxicological data using microphysiological systems with human cells and tissues could also be generated on a priority list (~1000) of chemicals of concern to understand their potential harm or benefit.
These data would inform a reference standard for particular chemical exposures, which would contain the distribution of exposure levels across the population, the potential health hazards associated with a particular exposure level, and the potential combinations of exposures that would be of concern. This information could ultimately be integrated into patient electronic health records for use in clinical practice.
Recommendation 2. Develop cutting-edge data and analytical standards for exposomic analysis
The NEP would develop both a data standard for collecting and making available exposomic data to researchers, companies, and the public and advanced analytics to enable high-value causal insights to be extracted from these data to enable policymaking and scientific discovery. Importantly, the data would include both biochemical data collected directly as part of this project and in-field sensor data that is already being collected at individual, local, regional, national, and global levels by trusted third-party organizations, such as air/water quality. A key challenge in understanding the connections between a set of exposures and a disease state today is the lack of data standardization. The NEP’s investments in standardization and analytics could result in a global standard for how environmental exposure data is collected, cementing the U.S. as the global leader.
Recommendation 3. Catalyze biomedical innovation and entrepreneurship
A NEP could bolster new entrepreneurial ecosystems in advanced diagnostics, medicines, and clinical services. With access to a core reference exposome as a foundation, the ingeniousness of American entrepreneurs and scientists could result in a wellspring of innovation, creating the potential to reverse the rising incidence rates of many intractable illnesses of our modern era. One can imagine a future where exposomic tests are a part of routine physicals, informing physicians and patients exactly how to prevent certain diseases from emerging or progressing, or one where exposomic data is used to identify novel biological targets for curative therapeutics that could reverse the course of an environmentally caused disease.
The Size of the Prize
The National Exposome Project offers great potential to catalyze biomedical entrepreneurship and innovation.
First, the high-quality reference levels of exposures generated by the NEP could unlock significant opportunities in medical diagnostics. Already, great work is being done in diagnostics to understand how environmental exposures are driving diseases from autism to congenital heart defects in newborns. NEP would accelerate such work, enabling the early detection and monitoring of conditions that today have limited diagnostic approaches.
Second, a deeper understanding of exposures could lead to the faster development of new medicines. One way the NEP data set could do this would be by enabling biologists to identify novel molecular targets for medicines that might otherwise be overlooked—for example, the NEP data might reveal that certain exposures are protective and beneficial for patients with a given disease, a finding that could be more deeply examined at the molecular level to identify a novel therapeutic strategy. In addition, we know that genetics is unable to explain the hundreds of failed drug trials. Exposomics could rescue many drugs that failed testing due to environmentally related nonresponse by identifying the causative agents.
Finally, we expect that the NEP would likely result in significant advances in the physical hardware and instrumentation that is used for large-scale chemical analysis and research, and in the AI-driven computational approaches that would be necessary for the data analysis. These advancements would set the U.S. up to be the leader in exposomic sequencing and analysis, much in the same way that the Human Genome Project established the U.S. as the leader in genetic sequencing. Furthermore, these technical advances would likely be useful in many domains outside of human health where chemical analysis is useful in developing new products—such as in the agriculture, industrial chemical, and energy industries.
Conclusion
To catalyze the next generation of biomedical innovation, we need to establish a national network of exposome facilities to track human exposure levels over time, accelerate efforts to create toxicological profiles of these chemicals, develop advanced analytical models to establish causal links to human disease, and use this foundational knowledge to further the development of new medicines and policies to reduce harmful exposure. This knowledge will transform our biomedical and healthcare industries, as well as provide a path for an improved chemical industry that creates products that are safer by design. The result will be longer health spans, reductions in mortality and morbidity, and economic development associated with spurring new startups that can create new therapies, technologies, and interventions.
This action-ready policy memo is part of Day One 2025 — our effort to bring forward bold policy ideas, grounded in science and evidence, that can tackle the country’s biggest challenges and bring us closer to the prosperous, equitable and safe future that we all hope for whoever takes office in 2025 and beyond.
Anyone concerned with large government initiatives may object to the proposed budget for this project. While we acknowledge the investment needed is substantial, the upside to the public is enormous, borne out both in direct economic development benefits in new exposomic industries created as a result and in the potential demystification of a large portion of currently unexplained diseases that afflict us.
Industries responsible for manufacturing products that potentially expose populations to suspected harmful chemicals may also push back on this effort. As a response, we believe that there is abundant misinformation fueled by underpowered or poorly designed studies on chemicals, including those with more harmful reputations than data supports. A more systemic data set and a newly created industry that gives people more complete, personalized, and real-time data on exposure can not only support debunking myths but also expand the set of possible actions to mitigate exposure, taking us out of a continued cycle of finger-pointing. Indeed, such a systematic approach should reveal many positive associations with modern chemicals and health outcomes, such as preservatives reducing food-borne illness or antibiotics reducing microbial-based disease.
Governance and accountability will be critical to ensure proper stewardship of taxpayer dollars and responsible engagement with the complex set of stakeholders across the country. We therefore propose creating an external advisory committee made up of community members, industry representatives, and key opinion leaders to provide oversight over the project’s design and execution and advice and recommendations throughout all stages to the NEP director.
The first steps to realizing this vision have actually already begun. ARPA-H, the agency responsible for high-risk, high-reward research and development for health, has begun to fund some foundational exposomic work. National Institutes of Health’s All of Us program has also set a foundation for what might be possible in regards to large-scale bio-banking studies. However, to have the needed impact at scale, the NEP needs to be launched on a much bigger scale, outside of existing programs, and focus on spurring economic development and the creation of new industries.
Some of the most important factors that determine success of ambitious efforts like this are the specifics of the legislative authority, the leadership/governance structure, and how much appropriations can be made available upfront. Further, while collaboration across agencies is clear, establishing clear decision-making structure with the proper oversight is critical. This is why we believe creating a dedicated program office, with a clear leader who reports directly to a member of the cabinet, endowed with the necessary authorities including Other Transactions Authority, is key to success.
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