By COL Paul Kassebaum, Commander, U.S. Army Medical Research Institute of Chemical Defense (MRICD), and Dr. James Dillman, Chief Science Officer, MRICD, USA.
The U.S. Army Medical Research Institute of Chemical Defense continues to advance military and civilian medical chemical defense with next-generation diagnostics, therapeutics, and decontamination products.
For over 100 years, scientists at Edgewood, Maryland have researched chemical weapon medical countermeasures. Through iterations as the Medical Research Division, the Medical Research Laboratory, the U.S. Army Biomedical Laboratory, and the U.S. Army Medical Research Institute of Chemical Defense (MRICD), research has steadfastly progressed towards eliminating suffering in the world caused by chemical threats. Key contributions include nerve agent treatments, increased understanding of vesicating agents and neurotoxins, skin decontamination products, diagnostics, and clinical training on chemical casualty care. Today MRICD is the nation’s center of excellence for medical chemical defense, conducting medical research and education out of a new, state-of-the-art facility occupied in 2015.
Since 1917, U.S. Army scientists have developed medical solutions for chemical threats. That legacy is carried on today by the U.S. Army Medical Research Institute of Chemical Defense (MRICD) at Aberdeen Proving Ground-South in Edgewood, Maryland. MRICD traces its origins to components of the Army Medical Department responsible for defense against chemical weapons during World War I. In October 1922, the Medical Research Division was organized at Edgewood Arsenal to study the pharmacological actions of chemical threat agents, to develop treatments for exposed casualties, and to provide the information generated to Army Medical Corps personnel. During this period, Edgewood Arsenal became the center for chemical defense research, development, and testing operations.
During World War II, emphasis on treating chemical casualties continued and increased when nerve agents developed by the Germans were discovered at the end of the war. Atropine was studied as a primary antidote for treating nerve agent exposure, and in the mid-1950s reactivators of acetylcholinesterase, the toxic target of nerve agents, were synthesized and studied. The oxime reactivator 2-PAM was demonstrated to be effective as an antidote. Both atropine and 2-PAM were eventually formulated for use in autoinjector systems, first in the Mark I Nerve Agent Antidote Kit (NAAK) as two separate injectors and then combined together into the Antidote Treatment Nerve Agent Autoinjector (ATNAA).
Second half of the XX century
MRICD, known then as the Medical Research Laboratory, moved into a new clinical research and headquarters building in 1968. The laboratory was re-designated the U.S. Army Biomedical Laboratory in 1971. In 1979, the laboratory added a veterinary medicine building housing modern facilities for all aspects of animal care. Also in 1979, the U.S. Army Surgeon General became the Executive Agent for medical chemical defense, and the U.S. Army Medical Research and Development Command assumed oversight. As a result, the Institute was given its current name in 1981 and designated the lead laboratory for medical chemical defense technology base programs.
In the late 1970s and throughout the 1980s the pace of research at MRICD increased in response to a renewed concern about chemical threat agents as well as rapid developments in biotechnology. Advancements in therapy for nerve agent exposure continued, and there was a shift in emphasis in the research program to treatments for vesicating agents, primarily sulfur mustard. In the late 1980s, program activities expanded to include basic research on neurotoxins.
Diazepam, an anticonvulsant, was shown to control nerve agent-induced seizures and reduce brain injury in animal models. Because diazepam was effective and also approved by the FDA for treatment of status epilepticus, diazepam was adopted by the U.S. military as the drug for immediate anticonvulsant treatment of nerve agent casualties in the field. In addition, pyridostigmine bromide, a drug approved by the FDA since 1952 for the treatment of myasthenia gravis, was shown to improve the effectiveness of the standard nerve agent treatments when used as a pretreatment.
In the early 1990s the U.S. military issued several products researched at MRICD – autoinjectors containing diazepam (Convulsive Antidote, Nerve Agent, or CANA), pyridostigmine for pretreatment of nerve agent exposure, and the M291 skin decontamination kit. In addition, a barrier skin cream intended to augment physical protection, termed skin exposure reduction paste against chemical warfare agents (SERPACWA), was submitted to the FDA in 1994 under an investigational new drug application and was approved in 2000. In addition to research, the institute had a long history of delivering world-class medical training for chemical casualty care. The Chemical Casualty Care Division was established in 1997 to provide remote and onsite training.
USAMRICD adapted to the ever-changing nature of chemical threats
From the 1990’s into the 2000’s efforts turned to the development of next generation nerve agent treatments. The anticonvulsant midazolam was shown in several studies at MRICD to be more potent and rapid in stopping nerve-agent induced seizures compared to diazepam. Work that began in the late 1980s and continued into the 2000s demonstrated that a naturally occurring enzyme, butyrylcholinesterase, could prophylactically act as a scavenger and bind nerve agent in the bloodstream. Other naturally occurring enzymes that rapidly break down nerve agent were also studied during this time and continue to be researched today. In 2004 the joint services established an operational requirement for an effective skin decontaminant. Critical studies conducted at MRICD led to the selection of Reactive Skin Decontamination Lotion (RSDL), which was subsequently approved by the FDA, replacing the M291 kit. In 2005, as a result of the Base Realignment and Closure Act, the Institute became the nation’s center of excellence for medical chemical defense and in 2009, ground was broken for a new 526,000-square-foot facility.
Into the 2010s, the development of a broader research portfolio took shape in response to concerns about civilian medical chemical defense. Concerns about synthetic opioids resulted in research efforts to develop treatments for opioid exposure. In 2015 the new MRICD facility was opened. This significantly enhanced MRICD’s research mission and provided a state-of-the-art venue for the three chemical casualty care courses for pre-hospital care, hospital care, and medical facility management of mass casualty events. A clinical simulation center, virtual environment capability, and a field training site support these courses. Research into new diagnostics for use by soldiers on the battlefield developed ChemDx, a handheld device that identifies presymptomatic nerve agent exposure with a single drop of blood in 20 seconds. Robotic screening platforms, synthetic and medicinal chemistry facilities, and a humanized mouse model developed at MRICD that more closely replicates nerve agent exposure in humans supported research on acetylcholinesterase reactivators.
Current efforts
In 2022, MRICD continues to deliver solutions for medical chemical defense. The ChemDx device transitioned to its next milestone in December 2021. MRICD research supported FDA approval and fielding in 2022 of a new 10 mg naloxone autoinjector to treat opioid exposure. The research portfolio has expanded to include work in CBRN battlefield medicine, specifically the development of models combining traumatic injury and chemical exposure for testing therapeutics and clinical practice guidelines to treat traumatic injuries in a chemically contaminated environment. Repurposing FDA-approved therapeutics for treatment of chemical exposure has also become part of the research portfolio. A Wound Decontamination Research Pipeline seeks to identify a next-generation decontamination product for wounds and eyes. MRICD has also established and maintains the DOD’s only certified clinical laboratory for testing medical samples to confirm chemical agent exposure.
“Moving into the future, MRICD is poised to leverage partnerships across the DOD, the interagency, academia, and industry as the institute continues to drive innovation towards a new era of medical chemical defense”
Moving into the future, MRICD is poised to leverage partnerships across the DOD, the interagency, academia, and industry as the institute continues to drive innovation towards a new era of medical chemical defense. Early-stage efforts in nanoparticle drug delivery, decontamination products, therapeutics, and novel chemistries supporting new diagnostics all focus on the development of innovative solutions for military and civilian medical chemical defense. Remaining ready to address emerging threats by applying capabilities in new ways pushes MRICD into new areas of research to eliminate suffering in the world caused by chemical threats.
*The views expressed in this article are those of the author(s) and do not reflect the official policy of the Department of Army, Department of Defense, or the U.S. Government. MRICD would like to thank the Defense Threat Reduction Agency-Joint Science and Technology Office, the Joint Program Executive Office for Chemical and Biological Defense, and the National Institutes of Health for funding and support.
About the Authors:
Colonel Paul Kassebaum is Commander, MRICD. He has served in the U.S. Army as an active-duty pharmacy officer for nearly 20 years.
Dr. James Dillman is the Chief Science Officer, MRICD. He has worked in the field of medical chemical defense for the past 22 years.
