Civilian research on chemical medical countermeasures

The increasing risk of a terrorist attack in the United States involving toxic chemicals has created new challenges for many programs across the federal government. Threat agents, including toxic industrial chemicals and pharmaceuticals (e.g. synthetic opioids) as well as traditional chemical warfare agents, have become of more and more concern because of their recent use in terrorist incidents, warfare, and individual poisonings. The severe toxicity of these chemicals can be difficult to manage because of their often-rapid modes of action, causing severe injury or death within minutes. Although several medical countermeasures (MCMs) are already fielded for a few specific chemical threats, the U.S. government continues to support research on improvement and optimization of the nation’s medical response capabilities, as well as treatment for the many as-yet unaddressed chemical threats.

In 2006, the U.S. Congress appropriated funds to the National Institutes of Health (NIH) to implement the National Strategic Plan and Research Agenda for Medical Chemical Countermeasures. The NIH Countermeasures Against Chemical Threats (CounterACT) program is led by the National Institute of Neurological Disorders and Stroke (NINDS) and is part of a larger biodefense effort led by the National Institute of Allergy and Infectious Diseases (NIAID). The program has a dual and complementary mission: to support basic research focused on understanding chemical toxicities and to use that knowledge to identify novel targets and develop promising candidate therapeutics for treating exposures that lead to mass casualties. In this regard, the program serves as a science and technology base for the larger federal research enterprise and supports more advanced translational research with promising lead compounds that would be eligible for transition to the Biomedical Advanced Research and Development Authority (BARDA) within the Office of the Assistant Secretary for Preparedness and Response in the U.S. Department of Health and Human Services (HHS) (Biomedical Advanced Research and Development Authority, 2019).

The NIH CounterACT program is a trans-NIH effort that utilizes expertise from several other NIH institutes including the National Eye Institute, NIAID, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Child Health and Human Development, National Institute of Environmental Health Sciences, National Institute on Drug Abuse, NINDS, National Library of Medicine, and other important resources at NIH. The program funds a comprehensive network of Research Centers of Excellence, individual co-operative research projects, small business innovation research grants, contracts, and interagency agreements with the Department of Defense laboratories. At NIH, a broad research community that otherwise would not be involved in chemical weapons research is being engaged to take advantage of its critical expertise in areas of scientific endeavor relevant to the civilian and military research programs.

The NIH program works in concert with the Chemical Medical Countermeasures program at BARDA. BARDA provides an integrated, systematic approach supporting development and acquisition of the necessary vaccines, treatments, diagnostics and other medical devices for public health emergencies, including many MCMs emerging from the basic research and preclinical development activities sponsored by NIH CounterACT.

The 2017–2018 Public Health Emergency Medical Countermeasures Enterprise Strategy and Implementation Plan emphasizes the need to develop effective medical countermeasures to protect the civilian population against chemical threats (Office of the Assistant Secretary for Preparedness and Response 2017). The great size and breadth of the US civilian population combined with the unpredictable nature of the threat present unique challenges to preparedness. For instance, children, the elderly, and individuals with preexisting medical conditions may be particularly vulnerable to the toxic effects of chemical exposure, and deployment of emergency medical countermeasures may involve some delay. The mission of the HHS Chemical MCM program thus is to improve health outcomes for all victims of chemical exposure through improved standards of care (including efficient and effective decontamination) and improved therapeutic interventions.

The overriding goal of the BARDA program is to develop MCMs that are easily accessible to first responders and local public health authorities for use in a mass casualty situation and that are safe and effective for adults, children, and the elderly. This goal is being addressed both through enhancement of the emergency MCMs forward-deployed in the CHEMPACK program of the Strategic National Stockpile and through label expansion of commonly available drugs. Injuries caused by toxic chemicals can share many similarities with conventional clinical disease states; therefore, clinically used drugs can be used to treat chemical casualties. For instance, the benzodiazepine drug Midazolam (Seizalam®) was recently approved for a status epilepticus indication and is slated to replace diazepam as a component of the three-drug regimen used to treat nerve agent intoxication (CDER 2018).

Developing MCMs for use in a response to a civilian chemical emergency, whether terrorist or accidental in nature, presents several challenges for researchers and drug developers. Use characteristics of MCMs must be clearly relevant to use in emergencies with potentially large numbers of casualties. Drugs must have a route of administration consistent with their concept of the use in a mass casualty event. For example, drugs that are only effective when administered intravenously may not be ideal if they need to be given as soon as possible after exposure, in a pre-hospital setting (since many patients would need to be treated at once), but drugs designed to treat later-arising conditions (such as pulmonary edema) could utilize more complex routes in the hospital setting. Drugs must be safe and effective for use in children, the elderly, and other at-risk populations. Careful planning is necessary to ensure that MCMs are available when and where they are needed, either through stockpiling and forward deployment strategies or by leveraging drugs that are already commonly available in pharmacies and hospital formularies. The NIH and BARDA programs together strive to take a holistic approach to MCM development, using basic and translational research to understand mechanisms of chemical toxicity to identify candidate therapeutics as well as best practices in advanced drug development taking in order to provide effective and accessible chemical medical countermeasures for the American people.

Disclosure statement

This report does not represent the official view of the National Institute of Neurological Disorders and Stroke (NINDS), the National Institutes of Health (NIH), the Office of the Assistant Secretary for Preparedness and Response, or any part of the US Federal Government. No official support or endorsement of this article by the NINDS, NIH, or HHS is intended or should be inferred. No potential conflict of interest was reported by the authors.