VX (nerve agent)

• 1. Introduction

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  VX is a nerve agent for which the estimated median lethal dose on the skin of a 70 kilogram man is only 5 to 10 milligrams. That figure is the exposure expected to kill half of a tested group. The margin is thin, because the potentially fatal dose is only slightly higher than the dose that has any effect at all. The effects also arrive so quickly that there is little time for treatment. VX is more potent than sarin, another nerve agent with a similar mechanism, and the United Nations categorizes it as a weapon of mass destruction. How did a pesticide experiment in a British laboratory turn into one of the most feared weapons of the Cold War? What does this oily liquid do inside the body to stop a person from breathing? Who has actually used it, and what did it take to destroy the stockpiles that nations built?

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• 2. Pesticide Origins

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  In 1952, two chemists at the British firm Imperial Chemical Industries, Ranajit Ghosh and J. F. Newman, discovered a new family of compounds. They were studying organophosphate esters when they found it, and in November 1952 they patented one of them, known as agent VG. Their work followed an earlier path. Gerhard Schrader, a chemist at IG Farben in Germany during the 1930s, had investigated organophosphates first. Like Schrader, Ghosh found that these compounds were very effective pesticides.

  In 1954, ICI put one of them on the market under the trade name Amiton. The company soon withdrew it, because it was too toxic for safe use. That toxicity did not go unnoticed. Samples went to Porton Down, the British government research facility in Wiltshire, and several compounds of the class became a new group of nerve agents, the V agents. Porton Down developed them further during the early 1950s. Commercial research on similar compounds ceased in 1955, when their lethality to humans was discovered.

  The best known of the V agents is VX, whose name is a contraction of the words "venomous agent X". Britain gave it the Rainbow Code name Purple Possum. The Russian V agent, called VR, comes a close second in fame, while Amiton is largely forgotten under the label VG.

  Beginning in 1959, the United States Army began volunteer testing of VX in humans. Dr. Van M. Sim underwent an intravenous infusion to establish a baseline for later experiments. About three and a half hours after the first dose, he suddenly became pale and delirious. The researchers ended the experiment immediately to preserve his life. They concluded that 2.12 micrograms per kilogram, delivered intravenously over several hours, was the maximum tolerable dose.

  The United States began producing large amounts of VX in 1961 at Newport Chemical Depot. During the Cold War its chemical weapons program concentrated on large-scale VX production, at least 4,400 tons, alongside sarin and mustard gas.

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• 3. Oily and Persistent

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  Pure VX is an amber-coloured liquid with a boiling point of 298 degrees Celsius and a freezing point of minus 51 degrees Celsius. It is oily, odorless and tasteless, and its density is close to that of water. It is also relatively hydrophobic. With a log P value of 2.047, it partitions about 100 times more into octanol than into water.

  The number that matters most is its vapor pressure of 0.09 pascals. That makes VX relatively non-volatile, so it lingers in the environment where it is dispersed. Sarin behaves differently, because VX is dangerous for its persistence rather than as a vapor hazard. Military planners therefore regard it as an area denial weapon, meant to make ground hazardous long after an attack.

  When weaponized, VX can be dispersed as a liquid or an aerosol. It can also be mixed with a thickening agent such as clay or talc.

  A second route to delivery is the binary weapon, in which two components mix in flight to form the agent just before release. Binary VX is called VX2. The Bigeye aerial chemical bomb used this approach. The XM736 8-inch projectile program pursued it too, using a liquid dimethyl polysulfide mixture known as NM, but that program was canceled.

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• 4. How It Stops Breathing

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  Every time a motor neuron fires, it releases the neurotransmitter acetylcholine into the narrow gap between the neuron and a muscle cell, called the synaptic cleft. Acetylcholine binds to nicotinic receptors at the neuromuscular junction and makes the muscle contract. To prevent constant contraction, an enzyme called acetylcholinesterase then breaks the acetylcholine down into acetic acid and choline.

  VX blocks that enzyme. Acetylcholine piles up in the gap, and the receptors are stimulated until they tire. The result is first violent contractions, then a prolonged blockade of the nerve signal. The muscles of the whole body go into flaccid paralysis, and when the diaphragm stops working the victim dies of asphyxiation. Acetylcholine also accumulates in the brain, where it causes neuronal excitotoxicity through nicotinic receptors and the release of glutamate.

  Part of the extreme toxicity comes from molecular mimicry. The agent is an excellent structural copy of the transition state of acetylcholine as the enzyme handles it. VX has a very high on-rate, meaning it reacts quickly with the enzyme and forms a stable phosphorus-oxygen-carbon bond.

  A time-dependent side reaction called aging is the other half of the story. Aging removes an alkoxyl group and leaves the enzyme complex highly resistant to regeneration by any known antidote. VX ages relatively slowly compared with soman or sarin, which suggests that better antidotes might be possible.

  Researchers used X-ray crystallography to solve the enzyme's structure with VX, before and after aging, at near atomic resolution. The structures showed which parts of the molecule interact with key residues of the enzyme. They also revealed an unexpected shift in the catalytic triad, suggesting an induced fit between VX and acetylcholinesterase.

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• 5. Treatment and Detection

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  Early skin contact with VX causes local sweating and muscular twitching at the exposed spot, followed by nausea or vomiting. Exposure to the vapor brings a runny nose and tightness in the chest with shortness of breath. Pinpointing of the pupils, called miosis, can be an early sign but is not normally used as the only indicator.

  In treatment, the first priority is removing liquid agent from the skin, even before moving the person to clean air. The victim is then washed with household bleach and flushed with clean water, and contaminated clothing is removed. Where possible, decontamination is finished before the casualty goes on for medical care.

  A person known or strongly suspected to be exposed is generally given the antidotes atropine and pralidoxime, also called 2-PAM. Diazepam or a similar sedative or antiepileptic is injected if convulsions occur. Several nations issue these antidotes to soldiers in an autoinjector, such as the United States military Mark I NAAK.

  The two antidotes work differently. Atropine blocks muscarinic acetylcholine receptors, so the buildup of acetylcholine has less effect on them. Pralidoxime reactivates the enzyme by removing the phosphonate group that VX transferred onto its active site.

  Confirming exposure is a separate challenge. In controlled human studies, minimally toxic doses depressed red blood cell cholinesterase by 70 to 75 percent within several hours. In one poisoning victim, doctors measured the serum level of ethyl methylphosphonic acid, a VX breakdown product. Procedures also exist to detect breakdown products in urine and VX adducts bound to albumin in blood.

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• 6. Battlefield Reports

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  Around 1984, patients with symptoms of nerve agent exposure began appearing in hospitals in Angola. In 1988, a United Nations inquiry established that Cuba was responsible for using VX against Angolan insurgents. UN toxicologists found trace elements of VX in soil, water and plant samples from areas where Cuban troops had recently carried out counter-insurgency operations. Cuba had obtained VX during the 1980s.

  Iraq is a murkier case. Evidence suggests a combination of chemical agents, including VX, was used against the Kurds in the Halabja chemical attack in 1988 under Saddam Hussein. Hussein later told UNSCOM that Iraq had researched VX but failed to weaponize it because of production failure. After the invasion by United States and allied forces, no VX or production facilities were found. UNSCOM laboratories had, however, detected traces of VX on warhead remnants. Unconfirmed reports also say Iraqi forces used it in the Iran-Iraq War.

  The Soviet Union followed a related path. Its chemical weapons program declared production of 15,557 tons of the similar nerve agent VR, also called "Russian VX".

  In 1998, the United States bombed the Al-Shifa pharmaceutical factory in Sudan. It acted on information that the plant produced VX and that the agent was linked to both Iraq and Al Qaeda. American investigators had soil samples containing EMPTA, a chemical used in producing VX that may also have commercial uses. Chemical weapons experts later suggested that the widely used insecticide fonofos could have been mistaken for EMPTA.

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• 7. Assassination Weapon

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  On the 12th of December 1994, at 7:00 in the morning, a 28-year-old man was attacked on a street in Osaka. His name was Tadahito Hamaguchi, and the cult Aum Shinrikyo, led by Shoko Asahara, suspected him of being a spy. Tomomitsu Niimi and another member sprinkled VX on his neck. He chased them about 90 metres before collapsing into a deep coma, and he died days later without waking. Doctors suspected an organophosphate pesticide. The true cause was pinned down only after cult members arrested over the Tokyo subway sarin attack confessed. Metabolites of VX were found in samples of his blood seven months after the murder. He was the first documented VX victim anywhere in the world.

  The VX itself came from Masami Tsuchiya, who synthesized 100 to 200 grams of it in December 1994 and January 1995. Other targets survived. A man helping dissident cult members was attacked on the 28th of November and the 2nd of December 1994 and was hospitalized for 45 days. On the 4th of January 1995, Hiroyuki Nagaoka, head of the Aum Shinrikyo Victim's Group, was hospitalized for several weeks. In February 1995, Ryuho Okawa, leader of the Institute for Research into Human Happiness, was targeted after criticizing the group, and he suffered no ill effects. Unlike sarin, VX was not used by the cult for mass murder.

  On the 13th of February 2017, Kim Jong-nam, half-brother of North Korean leader Kim Jong-un, died after an assault at Kuala Lumpur International Airport in Malaysia. Many believe his brother ordered it. Authorities said VX was found on his face, and that one of the women suspected of applying it showed symptoms of VX poisoning. He died within fifteen minutes of exposure. A director of a non-proliferation research program at the Middlebury Institute of International Studies at Monterey observed that VX fumes would have killed the attackers even in gloves. That suggests the agent was applied as two non-lethal components that mixed into VX only on the victim's face.

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• 8. Destroying the Stockpiles

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  On the 15th of June 1967, the steamship Cpl. Eric G. Gibson was loaded with 7,380 VX rockets and scuttled in 7200 feet of water off Atlantic City, New Jersey. The operation, CHASE 8, was part of a United States Army disposal program whose name stood for Cut Holes And Sink 'Em. In 1969, the American government cancelled its chemical weapons programs, banned VX production and began destroying stockpiles. A Defense Department study released in fiscal year 2008 found that between 1969 and 1970 the country had dumped at least 124 tons of VX into the Atlantic. The dumping was off New York, New Jersey and Florida. It included nearly 22,000 M55 rockets, 19 bulk containers of 1400 pounds each, and one M23 chemical landmine.

  Incineration of VX began in 1990 at Johnston Atoll in the North Pacific. Plants followed at Deseret Chemical Depot, Pine Bluff Arsenal, Umatilla Chemical Depot and Anniston Army Depot. The last VX at these sites was destroyed on the 24th of December 2008. The Army Chemical Materials Agency finished its incineration work in March 2012.

  Newport Chemical Depot took a different route. From 2005 it neutralized VX with concentrated caustic solution, shipping the waste off-site, and it finished in August 2008.

  The Chemical Weapons Convention of 1993 bans VX, outlawing production and stockpiling above 100 grams per year. The only exception is for "research, medical or pharmaceutical purposes outside a single small-scale facility in aggregate quantities not exceeding 10 kg per year per facility". When the convention entered force in 1997, parties declared worldwide stockpiles of 19,586 tonnes of VX. By December 2015-98 percent had been destroyed.

  The last American stockpile sat at the Blue Grass Army Depot in Kentucky. It held 101,764 warheads and canisters with a total of 523 tons of chemical agents. Destruction there began in 2019, at a pilot plant plagued by repeated cost overruns and schedule slippages. The last VX rocket was destroyed on the 19th of April 2022, and the Centers for Disease Control and Prevention announced it in September 2022. The final American chemical weapon was destroyed on the 7th of July 2023, and President Biden issued a statement the same day. The United States was the last of the eight signatory countries to finish, and it missed the treaty deadline, according to the account, by following higher safety protocols than other countries.

  In Russia, the Nunn-Lugar Global Cooperation Initiative helped convert a former chemical weapons depot at Shchuchye, Kurgan Oblast, into a destruction facility. It opened in May 2009 to eliminate nearly 5950 tons of nerve agents. Yet that site held only about 14 percent of Russian chemical weapons, which were spread across seven sites.

  Destroying VX does not end chemical weapons. Syria deployed chlorine gas during its civil war, and Russia has used chemical agents for assassinations.

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