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AbstractAlthough chemical and radiological agents cause toxicity through different mechanisms, the multiorgan injuries caused by these threats share similarities that convene on the level of basic biological responses. This publication will discuss these areas of convergence and explore “multi-utility” approaches that could be leveraged to address common injury mechanisms underlying actions of chemical and radiological agents in a threat-agnostic manner. In addition, we will provide an overview of the current state of radiological and chemical threat research, discuss the US Government’s efforts toward medical preparedness, and identify potential areas for collaboration geared toward enhancing preparedness and response against radiological and chemical threats. We also will discuss previous regulatory experience to provide insight on how to navigate regulatory paths for US Food and Drug Administration (FDA) approval/licensure/clearance for products addressing chemical or radiological/nuclear threats. This publication follows a 2022 trans-agency meeting titled, “Overlapping Science in Radiation and Sulfur Mustard Exposures of Skin and Lung: Consideration of Models, Mechanisms, Organ Systems, and Medical Countermeasures,” sponsored by the National Institute of Allergy and Infectious Diseases (NIAID), a part of the National Institutes of Health (NIH). Discussions from this meeting explored the overlapping nature of radiation and chemical injury and spurred increased interest in how preparedness for one threat leads to preparedness for the other. Herein, subject matter experts from the NIAID and the Biomedical Advanced Research and Development Authority (BARDA), a part of the Administration for Strategic Preparedness and Response (ASPR), summarize the knowledge gained from recently funded biomedical research, as well as insights from the 2022 meeting. These topics include identification of common areas for collaboration, potential use of biomarkers of injury to identify injuries caused by both hazards, and common and widely available treatments that could treat damage caused by radiological or chemical threats.

AbstractPurpose:To summarize presentations and discussions from the 2022 trans-agency workshop titled “Overlapping science in radiation and sulfur mustard (SM) exposures of skin and lung: Consideration of models, mechanisms, organ systems, and medical countermeasures.”Methods:Summary on topics includes: (1) an overview of the radiation and chemical countermeasure development programs and missions; (2) regulatory and industry perspectives for drugs and devices; 3) pathophysiology of skin and lung following radiation or SM exposure; 4) mechanisms of action/targets, biomarkers of injury; and 5) animal models that simulate anticipated clinical responses.Results:There are striking similarities between injuries caused by radiation and SM exposures. Primary outcomes from both types of exposure include acute injuries, while late complications comprise chronic inflammation, oxidative stress, and vascular dysfunction, which can culminate in fibrosis in both skin and lung organ systems. This workshop brought together academic and industrial researchers, medical practitioners, US Government program officials, and regulators to discuss lung-, and skin- specific animal models and biomarkers, novel pathways of injury and recovery, and paths to licensure for products to address radiation or SM injuries.Conclusions:Regular communications between the radiological and chemical injury research communities can enhance the state-of-the-science, provide a unique perspective on novel therapeutic strategies, and improve overall US Government emergency preparedness.

Over the past 20+ years, the U.S. Government has made significant strides in establishing research funding and initiating a portfolio consisting of subject matter experts on radiation-induced biological effects in normal tissues. Research supported by the National Cancer Institute (NCI) provided much of the early findings on identifying cellular pathways involved in radiation injuries, due to the need to push the boundaries to kill tumor cells while minimizing damage to intervening normal tissues. By protecting normal tissue surrounding the tumors, physicians can deliver a higher radiation dose to tumors and reduce adverse effects related to the treatment. Initially relying on this critical NCI research, the National Institute of Allergy and Infectious Diseases (NIAID), first tasked with developing radiation medical countermeasures in 2004, has provided bridge funding to move basic research toward advanced development and translation. The goal of the NIAID program is to fund approaches that can one day be employed to protect civilian populations during a radiological or nuclear incident. In addition, with the reality of long-term space flights and the possibility of radiation exposures to both acute, high-intensity, and chronic lower-dose levels, the National Aeronautics and Space Administration (NASA) has identified requirements to discover and develop radioprotectors and mitigators to protect their astronauts during space missions. In sustained partnership with sister agencies, these three organizations must continue to leverage funding and findings in their overlapping research areas to accelerate biomarker identification and product development to help safeguard these different and yet undeniably similar human populations – cancer patients, public citizens, and astronauts.