Frontiers in medical countermeasures against CBRN agents

From nerve agent antidotes to radiation sickness treatments, medical countermeasures against CBRN threats remain an oft-overlooked corner of defence spending. This piece examines the current state of play and identifies where the most urgent capability gaps lie.

Military medicine has always been worried about how to treat injuries and illnesses caused by chemical, biological, radiological, and nuclear (CBRN) agents and materials. Medical countermeasures to CBRN threats are useful in a military context because soldiers’ lives can be saved, injuries and illnesses can be reduced in intensity or duration, and disability can be alleviated. In a civil protection context, harm to the public can be reduced if useful medical treatments and diagnostics are available. In a broader political and economic context, reducing the lifetime expenses to society in terms of disability pensions or lost labour is a public good, even if it is a cynical calculation at times.

The phrase ‘medical countermeasures’ is a decades-old term that appears to have come out of the Pentagon as a logical phrase to describe a budget category. What is and isn’t covered by the term varies from country to country, but I will try to take a balanced approach. From a medical perspective, protective clothing and respiratory protection equipment could be considered preventive medicine or occupational health, but are generally covered elsewhere. Likewise, decontamination is vital in many kinds of medical circumstances but, aside from some very specialist aspects, decontamination is dealt with as its own CBRN subject. Broadly, we can consider prophylaxis, diagnostics, and various types of post-exposure interventions as the core of medical countermeasures.

When considering CBRN medical countermeasures from the standpoint of defence journalism, three factors emerge. First, this is a conceptual space and a market segment that is an afterthought from both the defence perspective and the broader medical and pharmaceutical industry perspective. Even the largest possible contract is small in the context of global healthcare. Second, progress, especially in the form of new products or technologies is slow, and on any given day there is not all that much new to report. Third, many of the technologies, techniques, procedures, and products used to treat CBRN casualties are generic, usually with more non-CBRN uses than specialist CBRN purposes. Oxygen and ventilation are still oxygen and ventilation, whether it is a phosgene victim or a person suffering a heart attack. For these reasons, a more thoughtful approach to defence journalism is to look at where the current gaps are. Where are the obvious and not-so-obvious areas for improvement?

Prevention and prophylaxis

Obviously, preventing exposure to CBRN materials is the best way to prevent eventual illness, injury, or disability. Many of the approaches to doing that are things like respiratory protection, protective clothing, detection, and intelligence collection that do not fall under the rubric of medical countermeasures are preventive measures. But in the medical sphere, we are talking about things like vaccines and prophylactic medicines.

Vaccination has a long history in biological defence, and one not without controversy. Mandatory use of anthrax vaccination in military forces engendered some hesitancy that pre-dates modern civilian-sector ‘anti-vax’ activism and conspiracist nonsense. However, vaccination is an effective way to prevent death from anthrax. A fair bit of biodefence research over the past decades has been devoted to improving existing vaccines and developing new vaccines. For example, numerous countries have sunk time and money into better anthrax vaccines, with an aim to reduce the number of doses needed. As an example, a 2019 article in Nature described a new single-dose vaccine for anthrax, the DPX-rPA vaccine, in the USA. Other efforts have been devoted to processes for rapidly developing new vaccines in times of crisis. The world’s experience with COVID-19 shows that novel vaccines can be rapidly fielded; CBRN warfare would require even faster development.

The other medical approach is prophylaxis. This already works with many biological threats. If you take enough of the right antibiotics, for example, you will not catch anthrax or bubonic plague. But for decades, research into chemical warfare agent prophylaxis and radioprotectants has not been completely wasted. There has been promising work on nerve agent ‘bioscavengers’ – chemicals such as enzymes, that can circulate in the bloodstream having been administered ahead of time. Such bioscavengers have, in theory, been shown to reduce harm from nerve agent exposure for periods of time. Radioprotectants are drugs that reduce the harm to the body from exposure to ionising radiation. For example, it has been demonstrated that high doses of vitamin E have temporary radioprotectant value. Such courses of action, of course, require procedures in place, logistics, and decisions based on intelligence.

 

Diagnostics: Knowing that you have a problem

There are several large inter-related problems lurking in the CBRN medical field. They are latency, generic symptoms, cumulative effects, and low-level toxicity. Latency is a period of time between exposure and the onset of signs and symptoms in the victim. For example, someone may have a very large exposure to phosgene gas, but might not show any real effects of it for many hours. The latency problem is such that it is not a useful technique to look for obvious or painful signs and symptoms as a means of detecting a CBRN attack; this problem also drives much of the requirement for CBRN detection.

The ‘generic symptom problem’ is that many of the signs and symptoms caused by CBRN materials are shared with other causes. There are CBRN agents that cause nausea and difficulty breathing, but there are myriad non-CBRN causes that do likewise. Six men in a platoon with a bad cough that came on suddenly could have a lot of different causes. Some CBRN threats, such as nerve agents and many types of radiation exposure, have cumulative effects. In other words, small asymptomatic exposures could add up over time to cause problems. The ‘low-level toxicity problem’ is that, actually, many types of CBRN materials could be causing long-term damage even though there are no immediately noticeable acute symptoms. Relying on acute symptoms to know that there has been an exposure to CBRN materials is a deficient course of action. This point is reinforced by the growing body of medical evidence pointing to low-level nerve agent exposure as one of the possible causes, even the main cause, of so-called ‘Gulf War Illness/Syndrome’ (see ‘Toxic legacies of warfare: Burn pits and other health hazards’, in ESD 07/08-25).

Relying on people to have noticeable effects from CBRN materials should not be a primary component of defensive doctrine, and is one of the reasons why detection and contamination avoidance exist as fields of endeavour in military CBRN defence. However, detection has many limitations, both practical and theoretical. What can and should supplement CBRN detection is the availability of good medical diagnostics.

There is a capability gap in cheap, easily-used, accurate medical diagnostics that can be used in field conditions to determine whether people have been exposed to various kinds of CBRN materials. For decades, science has hypothesised whether ‘biodosimetry’ (measurement of dose received) is feasible. In other words, can something like a blood sample yield a reasonable estimate of how much radiation or a toxic substance someone has received? Are there subtle biomarkers that indicate a low-level exposure to nerve agents? What physiological processes are underway in the human body in the latent period between phosgene or anthrax exposure and onset of symptoms, and can they be rapidly detected in the field? In a like mode, are there sprays we can put on a person’s skin to show that they have been exposed to a slow-acting blister agent or a Novichok-series nerve agent? After all, it took several hours for the Skripals to collapse after their encounter with a door handle contaminated with a Novichok agent. Is a soldier’s cough or fever benign or a biological attack?

There will not be easy answers to all of these questions, and some of the answers will not be amenable to small, quick, easy field diagnostic devices on the order of a COVID test kit. But some almost certainly will be addressable problems if enough money and intellect are devoted to them. Field diagnostics are probably the area where the easiest gains could be had in the field of CBRN medical countermeasures, partly because, unlike vaccines or drugs, there are fewer safety considerations and regulatory hurdles to overcome. A key example in the diagnostics arena that has emerged out of development is the BioFire Defense (Utah, USA) ‘BioFire Warrior Panel’, which is a quick field laboratory product for rapid detection of six different biological warfare threat agents from blood, sputum, or blood culture samples. It was licensed by the US authorities in March 2025.

Treatment

Treatments do exist for a wide variety of CBRN-related injuries and illnesses. For some of the most immediately dangerous CBRN threats, there are existing treatments that do work, some of the time at least. Rather a lot of work has been devoted to improving existing medical countermeasures. Nerve agents have long had reliable countermeasures in the form of atropine and various oxime drugs, used in combination. Nerve agents cause harm by interfering with the delicate balance of chemicals the human nervous system uses to send signals. Atropine (or its rival drug scopolamine) directly counteract the build-up of acetylcholine, a neurotransmitter. This build-up of acetylcholine is the principal adverse mechanism of harm by nerve agents. Oxime drugs, such as HI-6, obidoxime, or pralidoxime, work to reverse the binding action of nerve agents, freeing up the enzyme acetylcholinesterase to do its original job, which is to counteract the acetylcholine.

Various improvements to nerve agent treatment have either been fielded or are in some stage in the development pipeline, mainly but not exclusively driven by US government funding. Nerve agents get much attention, for the obvious reason that they are, in many ways, an ideal class of chemical for use in chemical warfare. Novichok exposure is particularly resistant to oxime treatment. There is certainly scope for investigation into alternative biochemistry which could re-activate the necessary chemicals in the human body to cope with nerve agent poisoning or even promote the body’s own production of extra enzymes.

Some efforts are more practical than theoretical and involve improved delivery of medicines that are already well-established in the pharmacopeia. Sublingual or nasally-administered atropine for treatment of nerve agents have been explored for scenarios when injection is not the best course of action. Autoinjectors designed for paediatric (or small-sized adult) patients are now a viable product, filling a gap that was identified in the sector. The firm Kaleo (USA) has been awarded a contract to produce a reconstituted atropine (mixed very quickly from dry component and a solvent) autoinjector that greatly improves both storage characteristics in varied temperature conditions and shelf-life for nerve agent antidotes. Kaleo was awarded a 39 million USD contract in 2023 for this product. Further research into scopolamine, a rival to atropine, has been undertaken. There have been research efforts on the subject of sedatives like midazolam, which act in some ways to prevent permanent neurological damage in nerve agent poisonings. If such sedatives can be administered safely very quickly after a serious nerve agent exposure, there may be improved outcomes. In 2022 the US Food and Drug Administration (FDA) approved a midazolam autoinjector for this purpose, intended to phase out a long-standing diazepam autoinjector.

There have been worries about fentanyl and other synthetic opiates being weaponised as lethal or severely incapacitating warfare agents. This phenomenon has seen the development and fielding of military-standard naloxone auto-injectors similar to those already in use in the civilian emergency medical sector. Again, Kaleo has done work in this area, as have other companies around the world. But the fact that military budgets are going into such items shows that concerns about fentanyl and related agents being used as weapons are being realised in practical ways.

 

Other ideas are further upstream but show some promise. A number of interesting ideas have been put into the development pipeline in the USA and other places. The US government’s Biomedical Advanced Research and Development Agency (BARDA) is openly asking for ideas to fund in the areas of antivirals and antitoxins. This includes smallpox antivirals (actual treatment of smallpox rather than merely a vaccine to prevent it), anthrax antitoxin (medicines that counteract the toxins made by anthrax bacteria in the human body, a necessary but missing adjunct to antibiotics), therapies for filo-viruses (Ebola and its ilk), and improved botulism antitoxins. Nerve agent bioscavengers, already mentioned previously, may have some utility in post-exposure treatment as well.

The R and N in CBRN has often been the backwater of CBRN medical countermeasures. Treatment of acute radiation sickness has improved, partly in conjunction with research on cancer. Two drugs, filgrastim and pegfilgrastim, have received approval from the USA’s FDA for treatment of radiation exposure. Both work by stimulating the human body’s production of neutrophils, a form of the body’s white blood cells. Depression of white blood cell count is one of the major mechanisms of harm in acute radiation sickness, which is the primary means of direct harm from radiation after a nuclear incident. Getting normal white blood cells back into circulation improves the survival prospects of a radiation sickness victim.

Future Prospects?

None of these ideas are going to progress forward without both money and intention. On the one hand, re-arming of Europe shows a lot of funding going into defence; some will end up in CBRN as part of a ‘rising tide lifts all boats’ phenomenon. Thus far, little movement specific to CBRN medicine has been seen. In the US, chaos and confusion with regards to health, science, and defence priorities makes this correspondent a bit sceptical that new efforts will be launched. Many existing efforts may need to fight a rear-guard action to stay alive. However, the areas mentioned earlier will be key things to watch in the next five years.

Dan Kaszeta