Nerve agents, a class of synthetic phosphorous-containing compounds, are among the most toxic substances known. Brief exposure to the most potent variants can lead to death within minutes. Once nerve agents enter the body, they irreversibly inhibit a vitally important enzyme called acetylcholinesterase. Its normal job within the nervous system is to help brain and muscle communicate. When a nerve agent shuts down this enzyme, classes of neurons throughout the central and peripheral nervous systems quickly get overstimulated, leading to profuse sweating, convulsions and an excruciating death by asphyxiation.
US considers Nation-state efforts to develop or acquire weapons of mass destruction (WMD), their delivery systems, or their underlying technologies constitute a major threat to the security of the United States, its deployed troops, and allies. The Chemical and Biological Defense Program (CBDP) is vital to our Nation’s ability to counter current and future threats posed by chemical and biological (CB) weapons. The hazards posed by CB weapons remain real and evolving. An increased willingness to use these types of weapons either for assassinations(e.g. Russia and North Korea) or to achieve asymmetric advantages(e.g. Syria and ISIS in Iraq)indicates eroding international norms against the use of CB weapons. This paradigm shift challenges the ability of the Joint Force to operate unencumbered. The proliferation of knowledge and technology, increased ease of access, difficulty in detecting illicit activities, emerging threats, improved delivery capabilities, and our limited ability to anticipate how adversaries might employ Weapons of Mass Destruction (WMD) heighten the risk of attacks against the U.S. or its allies.
The Defense Threat Reduction Agency enables the Department of Defense, the United States Government and International Partners to counter and deter Weapons of Mass Destruction and Improvised Threat Networks. DTRA addresses WMD threats through four core functions: threat control, threat reduction, combat support, and technology development.
DOD technology requirements before deployment, are detection and monitoring of harmful agents in the intended theater of deployment for intelligence purposes and for planning exposure assessments. During a deployment, real-time detection of harmful agents will be required to ensure that mission objectives are met and for continued monitoring. The information can be archived and used to determine low levels of chemical concentrations for dose reconstruction and long-term health risk assessments. Biological samples could also be collected for studies of postdeployment health effects.
Measuring the concentration of a chemical substance can be visualized as a three-step process (NRC, 1991b). First, the medium (air, soil, water, or food) containing the chemical substance is sampled. Next, the chemical substance of interest must be separated from or otherwise distinguished from other chemical species that are present. Third, the chemical is identified.
A wide variety of measurement equipment is available to DoD. Testing kits, detectors, and monitors of varying sensitivity (lowest level detectable) and specificity (ability to distinguish the target substance from similar substances) have been developed and/or used by the armed forces to identify concentrations of harmful agents. In addition, DoD, other federal agencies (e.g., EPA), and the private sector continue to develop technologies and equipment for detecting and monitoring concentrations of TICs in multiple environmental media.
Toxic chemicals and Chemical sensors
Nerve agents, such as sarin, are among a many rarely poisonous chemical weapons. Sarin is a colourless, odourless liquid fatal even at very low concentrations. Serious sarin poisoning causes visual disturbance, vomiting, breathing difficulties and, finally, death. Sarin causes a deadly overstimulation of the nervous system that can be stopped if treated with an antidote within minutes of poisoning.
There are chemical interventions for warding off death after exposure to certain chemical weapons. Unfortunately, these interventions are costly, difficult to dose properly and are themselves quite toxic. The chemical antidotes pralidoxime and the cheaper atropine were deployed after recent attacks in Syria, but doctors in the area worry their dwindling supplies offer little protection against possible future attacks.
For a medical intervention to work after nerve gas exposure, it has to work fast. If a first responder administers a sarin-destroying molecule, each therapeutic molecule must be capable of breaking down through hydrolysis hundreds of nerve agent molecules per second, one after another. BChE is a bioscavenger prophylactic countermeasure against organophosphate nerve agents, binding nerve agent in the bloodstream before it can exert effects in the nervous system. Aside from their astonishing speed, enzymes often display an equally impressive selectivity. That is, they react with only a small number of structurally similar compounds and leave all other compounds alone.
Chemical detection finds a wide variety of applications, such as detection of toxic industrial chemicals used in industrial and manufacturing applications, law enforcement and anti-terrorist efforts, environmental and agricultural contamination monitoring, medical diagnosis, and detection of chemical warfare agents.
The usefulness of carbon nanotube (CNT) structures in the field of chemical detection has been demonstrated. CNTs are molecular-scale ‘wires’. CNTs-based sensors are capable of detecting small concentrations of gas molecules. The conductance of CNTs can be substantially increased or decreased by exposure to certain gas molecules.
While fixed sensors may utilize CNT structures to provide some amount of chemical detection, it can often be impractical to mount these sensors at locations throughout a manufacturing facility, combat zone, or other location so as to assure each worker/soldier is free from chemical exposure. Hence, what is needed is a sensor that is small and light enough to be easily carried around by a person, and yet is inexpensive enough such that a large number of workers/soldiers can be provided with one. A disposable configuration of the badge allows the user to dispose of it when contaminated with chemicals after an alarm event.
The common criteria used to evaluate individual technologies: reliability; sensitivity; selectivity (i.e., discrimination between the target substance and similar substances); speed; portability; and cost.
DTRA, DIU award $4.6M to PercuSense for development of early detection system for toxic chemical exposure
The DTRA is an agency of the Department of Defense (DoD) designed to support counters to weapons of mass destruction. It both manages and integrates DoD chemical and biological defense science and technology programs, which in turn help innovate among public health programs. The DIU helps accelerate the adoption of such commercial technology throughout the military, while similarly encouraging innovation.
Under a $4.6 million contract with the Defense Threat Reduction Agency (DTRA) and Defense Innovation United (DIU), PercuSense has been tapped to develop a continuous biosensor system for early detection of potential toxic chemical exposure among soldiers and first responders. PercuSense, a biosensor and digital health company, has already created a continuous monitoring platform. Building off of that, the goal for this system is to be deployable on-person and capable of rapidly identifying chemical exposure in real-time. Beyond situational awareness, the partners hope this will reduce threats and drive treatment interventions.
“We are grateful to be recognized by DTRA for our cutting-edge technology, our experienced team, and our history of solutions-oriented development,” Brian Kannard, CEO of PercuSense, said. “This award will support our mission to be the leading biosensor company, providing simple solutions to monitor critical biomarkers for a variety of diseases, environments, and conditions. This support will enable us to expand our sensing platform and make a positive impact on military service members and first responders with rapid identification of exposure to toxic chemicals.”
Money from the pair will go toward developing sensing electrodes capable of identifying the consumption of toxins like nerve agents, opioids, and mustard agents. “Since its founding, PercuSense has been focused on developing sensing technology aimed at continuously and simultaneously measuring physiological relevant molecules through a novel minimally invasive sensor system,” Rajiv Shah, founder and chairman of PercuSense, said. “We are thrilled to be collaborating with DTRA and DIU to leverage this technology to support development of a wearable sensor capable of detecting the early signs of toxic chemical exposure. The project is especially gratifying when looking at the opportunity to protect the men and women of the military who are tasked with protecting all of us.”
UNMC Awarded 1.9M to Develop Nerve Agent Countermeasure
In 2015, The Defense Threat Reduction Agency (DTRA) has awarded a $1.9 million grant to researchers at the University of Nebraska Medical Center (UNMC) to develop a new therapy to protect service members from nerve agent exposure. Nerve agents affect nerve impulses that can cause death by making it impossible to breath. Nerve agents are made up of the same chemicals as insecticides, but are delivered in an activated form designed to kill or cause illness.
Over two and a half years, researchers will develop a formulation of a molecule called Butyrylcholinesterase (BChE) into an intramuscular injection, and prove its safety, effectiveness and dosing in animal models. They also will demonstrate its ability in dried form to retain activity for at least two years, and produce the substance for other research studies. BChE, which is found in human plasma, is a bioscavenger and when it finds nerve agent in the blood, it deactivates it. “The idea is military troops would administer the medication two to four hours before going into an area where nerve agents may be used,” Dr. Hinrichs said. “The medication would protect against nerve agents for up to two weeks.”
Dr. Lockridge has been studying BChE for 40 years and is the world’s leading expert on the subject. She has developed a method to extract and purify BChE as a pre-emptive therapy. “We know how to purify it and dry it down to a powder, so it’s stable for years. And it works,” Dr. Lockridge said. “You don’t need a lot to protect you. It’s very potent but has no side effects.”
Squid Enzymes Could Help Neutralize Chemical Weapons
Researchers at the University of Tennessee at Knoxville (UT) are a step closer to creating a prophylactic drug that would neutralize the deadly effects of the chemical weapons and nerve toxins. Through a joint effort between scientists at UT, Oak Ridge National Laboratory (ORNL), and a French national laboratory in Grenoble, the research focuses on engineering enzymes—called bioscavengers—that catalyze the hydrolysis of nerve agents as a prophylactic approach to diminishing their toxic effects.
“Enzymes exist that can potentially chew up nerve agents and render them useless before they’ve had time to act, but they need to be improved to work faster,” said Jeremy Smith, UT-ORNL Governor’s Chair and an expert in computational biology. The researchers are using neutron scattering and computational sciences to study these nerve agent bioscavengers. Neutron scattering allows the scientists to get a detailed three-dimensional view of the enzymes. Computer simulation then uses this view to understand how the enzymes break down the nerve agents. “The simulations produced an unexpected result,” Smith said. “The enzymes break down sarin in an unusual way. Now we can use that result to engineer them rationally.”
RFI – Bioscavenger Medical Countermeasures
The U.S. Department of Defense is seeking information from organizations on their capability to support advanced development of human butyrylcholinesterase (HuBChE) as a medical countermeasure. Overseen by the Joint Product Manager – Medical Countermeasure Systems (JPM-MCS) and executed by the prime contractor Dynport Vaccine Company LLC (DVC), a subcontractor is sought to perform half maximal inhibitory concentration (IC50) determinations for Guinea Pig, Rhesus Macaque and Human Erythrocyte-associated Acetylcholinesterase (AChE) exposed to organophosphate nerve agents (GD and VX). Respondents must have appropriate safety practices in place to handle organophosphate nerve agents; demonstrated ability to perform in vitro enzyme inhibition studies.
New drug against nerve agents in sight
Nerve agents destroy the function of a very important protein in the nervous system called acetylcholinesterase. As long as the nerve agent is bound to the protein, the breakdown of an important signal substance is prevented. The antidote HI-6 removes the nerve agent and restores the function of the nervous system. Drugs against nerve agent poisoning have been used for a long time, still it has been unclear how they actually work.
After years of hard work, chemists from FOI and Umeå University are now presenting a three-dimensional structure that depicts the HI-6 moments before the bond between the nerve agent and the protein is broken. The structure gives a high-resolution image that, in detail, describes the individual positions of atoms and provides an understanding of how the bond breaks. The scientific breakthrough was enabled by combining three-dimensional structural depictions with advanced calculations and biochemical experiments.
“After seven years of work using many different techniques, we have finally been able to bring this to a successful close and can show a uniform picture of how HI-6 approaches sarin. It opens up for new opportunities in finding antidotes to sarin and other nerve agents by structure-based molecular design,” says Anders Allgardsson.