Mankind’s deadliest chemicals: Nerve Agents

Featured, Health, Science 2018-03-14

Warfare. Weapons of mass destruction. Poison. Death. All four of these phrases adequately summarise nerve agents.

But what are nerve agents, how do they affect the body and what are the differences between the agents implicated in the murder of Syrian civilians, North Korean Kim Jong-Nam, and most recently implicated in the attempted murder of Sergei Skripal?

This is the scientific history behind the deadly nerve agent.

What are nerve agents?

Unlike poisons such as arsenic, chlorine gas and cyanide, nerve agents are not naturally occurring molecules or elements, concentrated into lethal doses. Instead, they must be synthesised in a laboratory. They are known as organophosphates, terminology describing the blend of composed elements including phosphorus, carbon and others. Organophosphates have one universal use in the world: they are insecticides. It is perhaps unsurprising then that nerve agents have the same effect on humans as insecticides have on insects. A chilling thought.

Nerve agents themselves are liquids at normal temperatures. They are sometimes referred to under the misnomer of nerve gases, often due to the specific method of aerosol dispersal since this has the potential to deliver a lethal dose faster. Being readily absorbed through the skin, eyes and respiratory tract, there are various methods of administration. Exposure can be achievable via vapour or gas dispersion, through contact with the skin, or even through ingestion.

As the public is now only too aware, nerve agents are lethal. The levels of toxic molecules necessary to deliver a fatal dose differ between the different modes of administration – inhalation is the deadliest. In the case of sarin, the concentration of agent that is likely to be fatal through inhalation administration is only 100 mg min m-3, whereas the concentration necessary to achieve the same effect through contact with the skin is 1700 mg min m-3. In both cases, concentration is measured through exposure and is dependent on the time exposed, the mass of compound and the area of exposure.

Furthermore, the latency period – the period before the manifestation of symptoms – varies between the agents. Some have been reported to be as short as 30 seconds, but others can last to the order of hours.

How do nerve agents affect the body?

As the name suggests, nerve agents affect the body by disrupting the central nervous system messaging channels, effectively shutting down the body’s nervous system. Cellular messaging is a key component of the nervous system, and is achieved in the body through the transmission of electrical impulses along nerves and pass from neuron to neuron via neurotransmitters. A very common neurotransmitter is Acetylcholine (ACh), which transmits these essential electrical impulses down the neuronal network and also mediates muscle contact. Once ACh has performed its role transmitting cell messages, it must be destroyed to prevent overstimulation of the nervous system. The body performs this naturally using the enzyme acetylcholinesterase (AChE) before the process begins anew.

Organophosphate nerve agents effectively disrupt this process. The compounds bind to the specific sites of the AChE enzyme rendering it ineffective. Thus, a toxic accumulation of acetylcholine occurs, resulting in the overstimulation of the nervous system.1

As the effects of nerve agent exposure increases, the victim suffers from the loss of muscular functions leading to constriction of pupils, drooling, convulsions, paralysis and respiratory arrest. Without treatment, death is inevitable.

Fortunately, these effects can be reversed using an antidote – but it must be administered rapidly. First, the bond joining the nerve agent and enzyme can be broken using specific “oxime” drugs, regenerating the enzyme for normal use. Speed is of the essence to reverse these effects; the bond “ages” over time, strengthening the link between the agent and the serine and rendering oxime drugs ineffective.

Atropine has the effect of blocking the ACh receptors, thus inhibiting the transmission possible between cells. In a healthy patient, atropine is poisonous, owing to its communication disruption. But, for patients poisoned with nerve agent, it has the potential to save their lives.

The Germany-Series

The G-Series of nerve agents were the first series of synthetic chemical weapons created. The first nerve agent dates back to 1936, when German scientist Gerhard Schrader attempted to synthesise a new insecticide that was cheaper than nicotine. What he created was more toxic than previously imagined. In fact, it is reported that the spilling of one drop in the laboratory led to Schrader and his assistant stopping work for three weeks. This would later become known as tabun.

It is perhaps no wonder then that upon the outbreak of World War II, the German military began preparing for the large-scale production of tabun as a replacement for chlorine and mustard gas, chemical weapons synonymous with World War I. It was during this process that further research resulted in more potent, deadlier weapons being discovered. Thankfully, no nerve agents were ever used during WWII, as production plants were not fully operational before the collapse of Nazi Germany. But Schrader’s research birthed the G-series of nerve agents, which have continued to be used well into the modern day.

The agents in this series includes, in order of potency: tabun (GA), sarin (GB), soman (GD) and cyclosarin (GF).

G-series nerve agents

G-series nerve agents, tabun, sarin, soman and cyclosarin (left to right)

Sarin is perhaps the most widely recognised agent from this class. Named after the scientists behind its discovery, Schrader, Ambros, Ritter & Van der Linde, it is the most volatile of the G-series, which makes dispersal as a gas easier.

G-series agents are also reported as being non-persistent. This is an expression of the duration of chemical effect, which impacts the ease and feasibility of decontamination methods. Common decontamination methods of sarin include simply washing exposed area with copious amounts of water to dilute the agent.

The Venomous-series

After WWII, pesticide research continued, and, ironically, more lethal nerve agents were again developed from attempts to synthesise an effective insecticide. It was here in the UK, at Imperial Chemical Industries (ICI), where amiton was created. This insecticide eventually had to be removed from sale due to its toxicity. However, this research was continued at Porton Down Chemical Weapons Research Centre, near Salisbury, where amiton was given a new name: VE.

Between 1952 and 1955, other V-series nerve agents were synthesised at Porton Down, most notably VX. Often cited as a colourless or amber-coloured liquid, the V-series agents have lower volatilities than other agents such as sarin. This low volatility means the primary method of dispersal is through skin contact since aerosol dispersion is difficult. What sets the V-series apart from their G-series brethren is their toxicity. VX is many times more toxic than sarin or tabun, with the lethal concentration being around 10-15 mg min m-3 for both skin contact and inhalation. Compare this to the lethal concentration of sarin, at 100 and 1700 mg min m-3 for inhalation and skin contact respectively, VX is clearly a deadly chemical.

VX

VX nerve agent

The V-series are also persistent agents, due to their low volatility and reactivity. Bleach and alkali are effective means of decontaminating any exposed area, and often a mix of water and bleach is used.

The Novichok agents

The most recent example of nerve agent use, in the poisoning of Sergei Skripal, has now been identified as belonging to the Novichok class of nerve agents.

The Novichok, or N-series, nerve agents are a secretive class of chemicals that, prior to leaks made in the 1990’s by Russian defectors, were unknown to the world. The spotlight has now been shone on these agents, but very little is still known. What is known is that they were developed in the Soviet Union in the 1970’s or 80’s, and various sources, including a compendium of chemical warfare agents, has estimated that the Novichok agents are around 10 times more lethal than VX.

When have nerve agents been used?

Thankfully, usage has been largely absent from warfare.

VX itself has itself been used on multiple occasions. In 1968, the accidental discharge of VX during military testing resulted in the death of over 3000 sheep in Dugway, Utah. But, VX has been implicated in two assassinations. The first was committed by members of the Japanese Aum Shinrikyo cult in 1994 to assassinate a former cult member in Osaka (this cult was also responsible for the Tokyo subway station sarin release in 1995 in which 13 people died). Until recently, this was the only confirmed human fatality attributed to VX. That changed following in 2017 with the murder of Kim Jong-Nam, the half-brother of North Korean leader Kim Jong-un, alleged to have been caused by the smearing of VX across his face.

Turning to the darker side of history, sarin has unfortunately been used to inflict mass indiscriminate carnage. The oldest documented use was in March 1988 by Saddam Hussein; it is believed that he used sarin against Kurdish citizens in Halabja, leaving 5000 people dead. There have been two other documented uses of sarin, alongside other chemical weapons such as mustard and chlorine gases, during the Syrian civil war in 2013 and 2017.

Fortunately, due to the serious nature of these chemicals, their synthesis requires expertise, facilities, equipment and funding. It is therefore unlikely that individual terrorist organisations or rogue chemists would be capable of their synthesis without extensive assistance. Furthermore, the Chemical Weapons Convention, which came into effect in 1997, outlawed the stockpiling and production of nerve agents, including sarin or VX. Enacted by 192 countries, part of the treaty is the commitment to the disposal of agents. In November 2017, a pivotal goal was reached as it was announced over 96% of global chemical weapons have been destroyed.

Self-made monsters

There are few words that I can offer that adequately summarise nerve agents. They can kill or injure indiscriminately. Throughout my research, I was both amazed and terrified by the lethality and potency of what scientists have created over the years. Nerve agents are weapons of war, synonymous with lethality, suffering, pain and death, and are without a doubt amongst the worst of mankind’s self-made monsters.

References:

  1. Anders Allgardsson et al., PNAS, 2016, 113, 5514-5519. (Link)

I wish to thank the following publications, all accessed on 14/03/2018 for the information that constitutes the bulk of this article, so I encourage the reader to visit the following articles.

Furthermore, facts were found and corroborated from the following websites.

Due to the constant stream of updated information, all data and facts published here are correct at the time of writing.