I wrote this research essay to be submitted to my school's competitive research prize, whilst I doubt it's winning material I have thoroughly enjoyed researching such an interesting aspect of chemical warfare and hope you find some interest in reading it. Be warned it is fairly dense.
Abstract
In today’s society it is generally assumed
that nerve agents constitute yet another part of the growing international
arsenal of radical new weapons that have begun to emerge in the last one
hundred years. In reality, few people truly appreciate the menacing nature of
these agents and their potentially devastating impact upon warfare and our
everyday lives. This review aims to examine the mechanism of the action of organophosphorous
nerve agents on the human body and why this makes them an effective weapon of mass
destruction.
It is the fear of this strange and under researched
area of chemical weaponry within society that has incited me to examine the science
behind these agents in order to expose their true potency. In particular I
concentrated on the nerve agent sarin throughout my research which has
attracted media attention recently due to its impact on the Syrian conflict
during August 2013.
From synthesis to symptoms and system
disruption I have drawn research from medical textbooks, articles and journals
alike to gauge a full depiction of the effects of this poison on the human body
as well as recent and past case studies of its use in combat to identify why it
is an effective killer. It is from these
conclusions that one can begin to envisage the true effects of nerve agents and
how their use has previously and may consequently lead to devastation.
Gas! Quick
Boys! – An ecstasy of fumbling,/Fitting the clumsy helmets just in time;/But
someone still was yelling out and stumbling,/ And flound’ring like a man in
fire or lime[1]
Owen’s work poignantly illustrates that chemical
weapons are both serene and relentless in their pursuit and horrifically
violent in their attack on the human body. Seemingly unattached from the noisy
and violent artillery that goes alongside them, modern day soldiers know not to
underestimate the danger chemical warfare poses.
It was nefarious wartime rivalry between the
axis and ally powers that led to the initial production of organophosphorous nerve
agents, first developed in secrecy during the inter-war years and World War II.
Synthesis of the first organophosphorous nerve agent, tabun (commonly by its
old NATO name GA), occurred in 1936 due to the efforts of the German researcher
Gerhard Schrader at an I.G. Farbenindustrie chemical production plant, in
Wuppertal-Elberfeld.[2]
Whilst experimenting with organophosphorous insecticides, he noted the toxicity
from the Tabun vapours on himself and amongst colleagues who all experienced
mild discomfort and miosis[3]-
the exceptionally toxic nature of the compound highlighted its potential use as
an agent of warfare. Two years on and in 1938 the most prominent of all organophosphorous
nerve agents, sarin (commonly known by its old NATO name GA), was synthesised
and named with an etymology of those influential and active in its creation- Schrader, Ambros, Rudriger and van
der Linde. Shortly after this the
nerve agents VX and soman were also produced. Fortunately for allied forces the
Germans didn’t have the opportunity to utilise these resources properly before
the end of the war in 1945. [4]
Banned worldwide under the Chemical Weapon’s
Convention of 1994 nerve agents are extremely toxic both dermally[5]
and when inhaled or swallowed.[6]
The majority of nerve agents are classed within the group organophosphorous
compounds (degradable chemical compounds containing a phosphorous-carbon bond) which
also includes compounds commonly found throughout medicine and pharmacology as
well as agriculture. Examples of such include the anti-cancer drug
cyclophosphamide[7],
flame retardents such as triphenyl phosphate[8] and the
pesticide diethyl-parathion[9].
In fact all organophosphorous nerve agents have developed from and are closely
related to many of the commonly used organophosphorous insecticides examples of
which include parathion and malathion[10].
Both insecticides and nerve agents work based on the same cellular mechanisms
and inhibit the same family of enzymes, cholinesterases. Nerve agents can
however be clearly defined as distinct from insecticides as they are far more
toxic in nature. An in vitro study reveals that the nerve agent sarin has 1,000
fold more inhibitory activity on cells than the common insecticide parathion,
both however were coincidentally produced by the same company in Germany, IG
Farbenindustrie, in the 1930’s.[11]
Today in 2014, despite multiple efforts of
international powers, the armamentarium of many countries is still known or
suspected to include nerve agents though they are banned as a weapon of mass
destruction. It is indeed realistic for soldiers going into combat to prepare for
such an attack and suspect they might come face to face with chemical warfare. Whilst
nerve agents are liquid at room temperature hence the common misconception
‘nerve gas’, they can be produced as an aerosol and so contact to vapour is the
most common exposure route experienced among casualties.[12]
To comprehend the danger of nerve agents action on the body it is first key to
understand that a nerve agent is an organophosphorous compound that prevents
normal nerve transmission. On introduction to the agent the triad of the eyes,
nose and lungs begin to show progressively more intensive and dangerous
symptoms with rhinorrhea[13],
miosis and ‘tightness in the chest’ as muscular control is lost. As exposure is
prolonged a casualty may notice dim vision, profuse secretion from the nose and
mouth as well as dyspnea[14].
With severe exposure a casualty is most likely to fall unconscious immediately
and experience intense bronchial spasms; this can lead to death by
asphyxiation.[15] On
a basic cellular level, nerve agents act by inhibiting the action of enzymes in
the cholinergic nervous system, this being all nerve tissue where the molecule
acetylcholine acts as a neurotransmitter. In vertebrae the cholinergic nervous
system comprises all neuromuscular junctions, where signals cross a synapse
from the central nervous system to muscle fibres. [16]
Nerve agents are grouped under the class
cholinesterase inhibitors, which also includes insecticides and herbicides.
Working like many other well known poisons, nerve agents inhibit the action of
an enzyme by binding to it and irreversibly changing its shape. This prevents
the enzyme from being able to perform its function of catalysing a metabolic
reaction and the molecule which is meant to be broken down by the enzyme builds
up in excess. It is the excess endogenous acetylcholine neurotransmitter which
leads to the toxic effects of the nerve agent on the body. Under normal
conditions the enzyme acetylcholinesterase works by hydrolysing the
neurotransmitter acetylcholine thus terminating its activity at the receptor
site so that it may only very briefly transit a signal across the synapse. Without
the action of this enzyme the levels of acetylcholine build up at the
postsynaptic cleft, continuing to send impulses to the receptor, triggering a
continual response and causing muscle spasm. This leads to loss of control over
breathing and potential death by asphyxiation.[17]
One clear example of the effects of a nerve agent can be seen in the 1995
victims of the Tokyo subway terrorist bombings. Victims reported that they
thought an eclipse had occurred on leaving the station, this was owing to the
uncontrollably contraction of the pupils due to exposure to sarin gas and
consequently an inability to allow light to enter the eye. This clearly
demonstrates the loss of muscular control exposure to nerve agents so famously produces.[18]
The
organpophosphorous nerve agent sarin inhibits the enzyme acetylcholinesterase
by phosphorylating (adding a phosphate group) to the active site causing it to
denature. In fig.1 we see how sarin reacts by breaking the bond of the alkyl
group attached to the acetylcholinesterase molecule and forming a covalent bond
to the active site. Sarin is an irreversible inhibitor so cannot diffuse in and
out of the active site but will permanently inhibit the activity of this
enzyme.
Nerve agents attack on a microscopic scale. They are inescapable and practically impossible to impede; no amount of rigorous training can protect a soldier from the assault on his cholinergic nervous system that comes from these acetylcholinesterase inhibitors.[20] The recent chemical attacks on the Ghouta agricultural belt outside the Syrian capital of Damascus resulted in an estimated number of 1,000 deaths last year on the night of the 21st of August. This marks the first major chemical attack in 25 years since the Halabaj poison gas attacks in 1988. The attack saw the deadly nerve agent sarin launched into suburban areas in rockets[21] and begins to resurrect fears and questions among communities and governments concerning chemical warfare. This is a prime example of a nerve agent’s use as a weapon of mass destruction. Not only did the sarin attack result in the death of 1,000 civilians but it displaced thousands of people from their homes and produced copious numbers of casualties, treatment for which required atropine injection.[22] This is a relatively expensive drug and creates additional strain for the limited medical services already in demand across the region. In addition those who witnessed the actions of the agent may show signs of PTSD and depression throughout their life as well as the obvious grief that comes from the loss of a loved one. Across the state any sense of security among the population has been eliminated by this atrocious act of warfare.
To recognize sarin’s capability as a weapon of mass destruction it is vital to question why offensive forces in Syria chose to propel sarin rockets into the Ghouta region in preference to other chemical agents suspected to be within their arsenal. The usage of sarin over other chemical weapons such as the blister agent mustard gas is attributed to its odourless and colourless state as well as its immediate effect on casualties. Sarin begins to act on the body within seconds of inhalation, however ill-effects attributed to mustard gas exposure may not be seen for up to 6 hours after contact. This provides a greater opportunity for medical personnel to intervene and take remedial action before serious injury occurs. Consequently sarin’s immediate assault upon its victim makes it a more perilous weapon with a higher capacity for devastation. In addition, other nerve agents such as soman and tabun are less toxic in nature and have faintly fruity odours making them more detectable than the agents sarin and VX meaning they would be unsuitable for an attack of a covert nature.[23]
Sarin has seen active use in conflict around the world in the Tokyo subway terrorist attacks and more recently in Syria. Of all the organophosphorous nerve agents sarin is the second most lethal after VX but is still more widely used. An in vitro study reveals that the aerosol exposure required to cause death in 50% of the population for VX is 10mg/min/m3 whilst this value is 100mg/min/m3 for sarin vapour and four times as much for Tabun[24]. VX’s increased toxicity is due to its low volatility of 10.5mg/m3 at 25°C compared to sarin’s higher volatility of 22,00mg/m3at 25°C, which is just below that of water.[25] This increases the potentially lethal nature of VX as it will remain on a tissue’s surface for longer so is likely to cause more disruption to our nervous system, this also means it is harder to decontaminate an area from VX.
Whilst VX is a more effective weapon of mass destruction the nerve agent sarin is more frequently used within conflict because of its less enduring character. As sarin is more volatile than VX it will evaporate more readily, this reduces the danger of an area still being contaminated by the agent in the weeks ensuing an attack and also reduces the risk of aerosols of sarin being propelled by winds away from a target area and potentially against friendly forces. However with developments in technology and more intensive and outrageous conflicts developing worldwide we could see VX usage more commonly in the theatre of war.
Chemical warfare is made up of seven different groups of agents which all act in different devastating ways to cause turmoil in the body. Common agents such as the lachrymatory agents tear gas and pepper spray, used for riot control, are the only chemical agents legally accessible to civilians in some countries and are frequently used across the world. Whilst these weapons are accessible to militia and terrorists their potency is unlikely to cause any grievous or permanent harm to one’s health and their toxicity is incomparable to that of a nerve agents, thus in terms of chemical warfare they are far less effectual. Other chemical agents which have gained fame through their use in warfare include mustard gas, which is a blister agent famous for its catastrophic use in the World War I trenches and Agent Orange, famous for its use in Vietnam.[26] Mustard gas is far more gradual in its onslaught of our health than a nerve agent and so as a weapon of mass destruction it is less valuable. Agent Orange, designed as a herbicidal agent of warfare, caused major health problems among the Vietnamese population as exposure to the herbicide caused permanent mental and physical disabilities as well as cleft palate. Whilst the effects of Agent Orange caused shock among the American public this agent only affected around 20% of Vietnamese exposed to it and so would never intentionally be used as a chemical weapon when resources of other more potent compounds are available. Organophosphorous nerve agents have yet to gain the fame of these agents but nerve agents immediate and effective nature as a weapon and their extremely toxic effect on our bodies suggests they will play an influential role in future conflicts.
It is clear that nerve agents’ irreversible inhibition of acetylcholinesterase in the cholinergic nervous system poses a major threat to any casualtie’s health and it is only through early diagnosis of the primary symptoms and a thorough understanding of these poisons that an antidote such as atropine and thorough decontamination may lead to recovery. Whilst the biological mechanisms behind this process are relatively simple and mirrored by other everyday poisons, a nerve agent’s ability to cause rapid deterioration should still never be undervalued. Comparison of physical and chemical properties between the different organophosphorous nerve agents reveals why only two have seen major usage and also advocates that we may see VX’s appearance in theatre over the more commonly used sarin as weaponry systems develop. With the recent civil wars in Libya and Syria militaries have seen rises in a fraudulent and guerrilla style of warfare that points towards the possible increased usage of banned weapons such as nerve agents in the future. As a weapon of mass destruction we know these agents are extremely destructive and their characteristics make them favourable by militia over other agents such as mustard gas or indeed mortar or missiles which induce no chemical threat.
Chemical warfare instils a horror that conventional warfare cannot mimic, by contrast to artillery and small arms, death from a chemical attack is immoral, often drawn out, painful and undignified. Barack Obama himself stated that chemical warfare was the ‘red line’ that should not be crossed. Rather than reduce numbers the actions of governments seems to have flared terrorists and armies worldwide to dare to cross the ‘red line’. Whilst warfare is by its very nature unpredictable and temptuous we’re undoubtedly going to see nerve agents play an instrumental role in the conflicts of tomorrow.
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Word count (excluding abstract, quotes, footnotes and bibliography) – 2496
Bibliography
Books (4)
- Owen, W (1994). The Poems of Wilfred Owen. Ware, Hertfordshire: Wordsworth Editions Limited
- Sidell, F (1997). Medical Aspects of Chemical and Biological Warfare. Borden Institute: Office of The Surgeon General
- Gilman, A et al (1982). Organophosphorous Compounds. Bartholomew Press, Dorking: Adlard and Son Ltd
- Haruki, M (2001). Underground: The Tokyo Gas Attack and the Japanese Psyche. USA: Vintage Books
Journals (2)
- Grob, D, Harvey, J. (1957). Effects in Man of the Anticholinesterase Compound Sarin (Isopropyl Methyl Phosphonoflouridate). Journal of Clinical Investigation
- Wills, J. (1954). A Statistical Study of the Adamek Report. Medical Laboratory Special Report.
Internet Articles (6)
- Katz, K. (2013). Organophosphate Toxicity. Available at: http://emedicine.medscape.com/article/167726-overview#a0101
- Ivarsson, U. (1992). Types of Chemical Weapons: Nerve Agents. Available: http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/nerve-agents/
- Soderberg, T. (2012). 12.4C: Enzymatic ester hydrolysis: acetylcholinesterase and sarin nerve gas. Available: http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/Chapter_12%3A_Acyl_substitution_reactions/Section_12.4%3A_Esters
- Bowen, J (2014). Syria Crisis: Damascus-area sarin attack, one year on. Available: http://www.bbc.co.uk/news/world-middle-east-28891307
- British Armed Forces. (2014). UK Industry’s Chemical, Biological, Radiological and Nuclear Defence Special Interest Group. Available: http://www.cbrn-uk.com/about-us/
- Jacobs, S. (2013). Chemical Warfare, From Rome to Syria. A Time Line. Available: http://news.nationalgeographic.com/news/2013/08/130822-syria-chemical-biological-weapons-sarin-war-history-science/ Last accessed 28th August 2014.
Visits (1)
- Visit to the RAF Henlow Centre of Aviation Medicine CBRN unit (chemical, biological, radiological and nuclear)
[1] Owen, W (1994). The Poems of Wilfred Owen. Ware, Hertfordshire: Wordsworth Editions Limited. pp.60
[2] Sidell, F (1997). Medical Aspects of Chemical and Biological Warfare. Borden Institute: Office of The Surgeon General. pp.130
[3] Contraction of the pupil
[4] Sidell pp. 130-131
[5] To come into contact with the skin’s surface
[6] Sidell pp.142-147
[7] Gilman, A et al (1982). Organophosphorous Compounds. Bartholomew Press, Dorking: Adlard and Son Ltd. pp.146
[8] Gilman, A pp.269
[9] Katz, K. (2013). Organophosphate Toxicity. Available: http://emedicine.medscape.com/article/167726-overview#a0101 Last accessed 1st September 2014.
[10] Katz, K
[11] Grob, D, Harvey, J. (1957). Effects in Man of the Anticholinesterase Compound Sarin (Isopropyl Methyl Phosphonoflouridate). Journal of Clinical Investigation, pp.350-368.
[12] Sidell pp. 142
[13] More commonly known as a runny nose
[14] Shortness of breath
[15] Ivarsson, U. (1992). Types of Chemical Weapons: Nerve Agents. Available: http://www.opcw.org/about-chemical-weapons/types-of-chemical-agent/nerve-agents/ Last accessed 28th August 2014.
[16] Sidell pp. 132
[18] Haruki, M (2001). Underground: The Tokyo Gas Attack and the Japanese Psyche. USA: Vintage Books p. 30-45
[19] Soderberg, T. (2012). 12.4C: Enzymatic ester hydrolysis: acetylcholinesterase and sarin nerve gas. Available: http://chemwiki.ucdavis.edu/Organic_Chemistry/Organic_Chemistry_With_a_Biological_Emphasis/Chapter_12%3A_Acyl_substitution_reactions/Section_12.4%3A_Esters Last accessed 29th August 2014.
[20] Sidell p. 131
[21] Bowen, J (2014). Syria Crisis: Damascus-area sarin attack, one year on. Available: http://www.bbc.co.uk/news/world-middle-east-28891307 Last accessed 29th August 2014.
[22] Sidell pp. 159
[23] Sidell pp. 141-142
[24] Wills, J. (1954). A Statistical Study of the Adamek Report. Medical Laboratory Special Report. (54).
[25] Sidell p. 141
[26] Jacobs, S. (2013). Chemical Warfare, From Rome to Syria. A Time Line. Available: http://news.nationalgeographic.com/news/2013/08/130822-syria-chemical-biological-weapons-sarin-war-history-science/ Last accessed 28th August 2014.
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