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Expand chemical defense to include chemical exposures—detecting, neutralizing, and remediating toxins before they cause chronic disease.
Key Insight: Federal chemical defense has been built around acute crises and military exposures, leaving chronic environmental threats largely unaddressed.
The federal government's responses to chemical exposures are generally critical incidences, including military-related exposures. For combat exposures, the U.S. military administered the largest prophylaxis treatment to 250,000-300,000 American troops in the Gulf War to protect against the effects of the nerve agent Soman. The treatment, pyridostigmine bromide (PB), which reversibly binds to AChE, is the only approved pharmacological prophylaxis for military use by the U.S. FDA to reduce lethality following nerve agent poisoning. Unfortunately, there is speculation that the PB pretreatment is causally associated with Gulf War illness [1]. For diseases like GWI, along with exposure to Agent Orange and burn pits, the Veterans Affairs Department has been tasked with developing interventions to mitigate the long term effects. In addition, there has been minimal efforts to track the health of affected civilian populations after pollutive events (e.g., Love Canal, Camp Lejeune, Deepwater Horizon), as the EPA is commissioned to projects on environmental remediation.
Influxes of federal funds have been allocated in disparate programs to advance the protection of military members and civilians against chemical toxicity. Since 2006, NIAID has been tasked with distributing funds at the top of the funnel of innovation via the Chemical Countermeasures Research Program/CounterACT program for academic researchers, small companies, large contractors (e.g., Battelle) and interagency agreements with the U.S. Army Medical Research Institute of Chemical Defense. Discovery and early development research has been focused on basic mechanisms of toxicity, identification and validation of targets, and pre-clinical experiments.
The Biomedical Advanced Research and Development Authority (BARDA) under the Department of Health and Human Services, has fueled R&D for defense against biological, chemical, and radioactive hazards to the public. BARDA has carved out their Chemical Medical Countermeasures Program specifically for exposures such as nerve agents, chlorine, and opioids, with the goal of securing national stockpiles of potential treatments to a broad spectrum of acute exposures. Additionally, BARDA's Repurposing Drugs In Response to Chemical Threats (ReDiRECT) program has focused on FDA-approved or late-stage drugs for chemical emergencies. The CMC coined "treat the injury, not the agent," modeling an approach that is flexible and dynamic given the unpredictability of exposures, which could be applied to longer term chronic environmental exposures. The same pipeline that has been devised to enable clinical trials, studies for investigative new drug applications, and faster FDA approval (often via Animal Rule) could be expanded for a broader suite of common, cumulative environmental exposures.
Passive biological surveillance in the U.S., another important component of detecting environmental threats, has had limited effects in translating findings of associations into meaningful impact. The CDC's National Health and Nutrition Examination Survey (NHANES) or California's biomonitoring program are solely to examine high-level trends, reference ranges, and associations. These retrospective, cross-sectional studies do not include the same analytes from each collection period. While the data from these efforts have been useful for academic researchers' pursuits, the results have done little to sway regulations, industry practices or consumer behavior with respect to individual exposures (beyond supporting the lead phase-out in the 1980s and 90s). During the same period, the National Children's Study was well underway to catalogue environmental exposures during early-life development in attempts to explain chronic conditions in later life. Yet the program was shutdown in 2014 after 14 years of spending $1.3B due to poor management and execution. Despite these setbacks, nationwide longitudinal sampling for environmental pollutants would be a cornerstone of a strategy to define mechanisms of environmental exposure, as recommended by researchers calling for a National Exposome Project.
Key Insight: New programs like TERP and existing cohort infrastructure are creating the foundation for intervention studies against environmental pollutants.
Recently there has been more momentum in developing therapeutic targets to exposures of pollution. In 2021, the Congressionally Directed Medical Research Program, which funds high-risk, high-gain biomedical research, established a new Toxic Exposure Research Program (TERP) with the goal of filling a gap in funding of exposures that are typical for deployed military, families living on bases and the general public. Topics ranged from repurposed candidate drugs for clearance of PFAS from the body to novel detection methods.
Over two hundred researchers in the fields of neurotoxins, Gulf War Illness, airborne hazards and other military service-related exposures gave expert opinions on funding prioritization, consistently favoring foundational research (>40%) and diagnosis/treatment (>20%) over prevention, epidemiology, etiology, and survivorship across topic areas. The respondents also emphasized their need for more clearly defined exposure profiles, access to samples/specimens, funding for a broader array of exposures, and incentivizing collaborative research. While the program was designated $30M per year for the first three years, the budget was reduced to $15M for FY25. TERP combined several initiatives that had been housed under CDMRP for the past 20+ years and exemplified bipartisan support for this prolonged research effort at the intersection of environmental health and pipelines for biotech interventions.
Several existing large and ongoing cohorts could be a starting place for broad scale intervention studies to determine best approaches to protect populations against the harms of environmental pollutants. In lieu of the National Children's Study, the NIH established the Environmental influences on Child Health Outcomes (ECHO) Program. This consortium of cohorts includes standardized protocols of sample collection methods and data analysis as well as a centralized data repository. Additional ongoing cohorts include the Children's Health and Development Studies, which is a three generational cohort of families and over 60,000 patients tracked to examine early life exposures in relation to adverse outcomes. Several of these longitudinal studies are well-poised to include treatments that could reduce body burdens of exposure; the ECHO Program already has clinical trials in progress for low-risk interventions for asthma as well as in utero exposure to opioids and cannabinoids.
Given the interdisciplinary and interagency coordination required for implementation of these programs, organizational government models that arose during the pandemic could be an appropriate path for quickly moving forward chemoprevention and countermeasure interventions:
Key Insight: Verified chemical exposure treatments would enable faster disaster response and real-time biomonitoring networks for both routine and emergency scenarios.
The broader defense response ecosystem could expand and benefit from including environmental chemical threats. With verified treatments for chemical exposures, there would be faster deployment of detection methods after environmental disasters. Members of Homeworld have been on site in the aftermath of two such manmade disasters, the East Palestine train derailment of 2023 and the Moss Landing Battery Fire of 2025. The team has proposed follow-up cohort studies in partnership with prominent direct-to-consumer healthtech startups, ImYoo (for immune blood cell biomarkers) and Million Marker (for biomonitoring of pollutants) to measure long-term effects of hazardous exposures on local populations. Both ImYoo and Million Marker exemplify the cutting-edge technology needed to fuel a broader National Early Health Warning and Response Network that could enable real-time exposure monitoring after chemical (or other) incidents.
Premier researchers in the field of protein binding, like Prof. Pranam Chatterjee at University of Pennsylvania, have begun building the in silico/in vitro combined infrastructure for peptide treatments that expedites the process. The lab's Metallorian model generates de novo peptides that chelate heavy metals—including cadmium, lead, and mercury—with user-defined specificity. These computationally designed peptide chelators could enable both bioremediation applications and clinical interventions. The Chatterjee lab's multi-objective framework ensures designed chelators maintain favorable solubility and reduced toxicity alongside high binding affinity.
Roadmap: A decade-long plan to build national chemical defense infrastructure from working groups to operational networks.