Nerve agent

Nerve agents (also known as nerve gases, though these chemicals are liquid at room temperature) are a class of phosphorus-containing organic chemicals (organophosphates) that inhibit the acetylcholinesterase enzyme in animals. As a chemical weapons, they are classified as weapons of mass destruction by the United Nations according to UN Resolution 687, and their production and stockpiling was outlawed by the Chemical Weapons Convention of 1993; the Chemical Weapons Convention officially which took effect in 1997.

Poisoning by a nerve agent leads to contraction of pupils, profuse salivation, convulsions, involuntary urination and defecation, and eventual death by asphyxiation as control is lost over respiratory muscles. Nerve agents can be absorbed through the skin, requiring that those likely to be subjected to such agents wear a full body suit in addition to a gas mask.

Biological effects

As their name suggests, nerve agents attack the nervous system of the human body. All such agents function the same way: by interrupting the breakdown of the neurotransmitters that signal muscles to contract, preventing them from relaxing.

Initial symptoms following exposure to sarin (and other nerve agents) are a runny nose, tightness in the chest and dilation of the pupils. Soon after, the victim will then have difficulty breathing, and will experience nausea and drooling. As the victim continues to lose control of his or her bodily functions, he or she will involuntary vomit, defecate and urinate. This phase is followed by twitching and jerking, and ultimately the victim will become comatose and suffocate as a consequence of convulsive spasms.

The effects of nerve agents are very long lasting and cumulative (increased successive exposures), and survivors of nerve agent poisioning almost invariably suffer chronic neurological damage.

Mechanism of action

When a normally funtioning motor nerve is stimulated it releases the neurotransmitter acetylcholine, which transmits the impulse to a muscle or organ. Once the impulse is sent, the enzyme acetylcholine esterase immediately breaks down the acetylcholine in order to allow the muscle or organ to relax.

Nerve agents disrupt the nervous system by inhibiting the enzyme acetylcholine esterase by forming a covalent bond with the site of the enzyme where acetylcholine normally undergoes hydrolysis (breaks down). The results is that acetylcholine builds up and continue to act so that any nerve impulses is continually transmitted, and muscle contractions do not stop.

This same action also occurs at the gland and organ levels, causing uncontrolled resulting in drooling, tearing of the eyes (lacrimation), and excess production of mucous from the nose (rhinorreah).

Antidotes

Atropine and related anticholinergic drugs act as antidotes to nerve agent poisoning because they block acetylcholine receptors, but they are poisonous in their own right. While they will save the life of a person affected with nerve agents, that person may be incapacitated briefly, or for an extended period of time, depending on the amount of exposure. Atropine for field use by military personnel is often loaded in an autoinjector, for ease of use in stressful conditions.

Pralidoxime chloride, also known as 2-Pam chloride, is also used as an antidote. Rather than counteracting the initial effects of the nerve agent on the nervous system like atropine, while pralidoxime chloride actually neutralizes the nerve agent in the bloodstream. Though safer to use, it takes a longer time to have an effect.

Different nerve agents

There are two main classes of nerve agents. The members of the two classes share similar properties, are are given both a common name (such as sarin), and a two character NATO identifier (such GB).

G-Series

The G-series, thus named because German scientists first synthesized them. All of the compounds in this class were discovered and synthesized during or soon after World War II, led by Dr. Gerhard Schrader.

This series is the first and oldest family of nerve agents. The first nerve agent ever synthesised was was GA (tabun) in 1936. GB (sarin) was discovered next in 1938, followed by GD (soman) in 1944 and finally the more obscure GF (cyclosarin) in 1949.

V-Series

The V-series is the second family of nerve agents, and also contains four members: VE, VG, VM, VX. The most studied agent in this family, VX, was invented in the 1950s at Porton Down in England. The other agents in this series have not been studied extensively, and information about them is limited. It is known, however, that the V-series agents are about 10 times more toxic than the G-agent sarin (GB).

All of the V-agents are persistent agents, meaning that these agents do not degrade or wash away easily, and can therefore remain on clothes and other surfaces for long periods. The consistency of these agents is similar to oil; as a reults, the contact hazard for V-agents is primarily - but not exclusively - dermal.

Insecticides

A number of insecticides, such as dichlorvos, malathion and parathion are nerve agents. The metabolism of insects is sufficiently different from mammals that these compounds are considered innocuous for humans and their food animals; but there is considerable concern about the effects of long-term exposure to these chemicals by farm workers and animals alike.

History

The discovery of nerve agents

This first class of nerve agents, the so-called "G-Series", was accidentally discovered in Germany on December 23, 1936 by a research team headed by Dr. Gerhard Schrader. Since 1934, Schrader had been in charge of a laboratory in Leverkusen to develop new types of insecticides for IG Farben. While working toward his goal of improved insecticide, Schrader experimented with numerous fluorine-containing compounds, eventually leading to the preparation of tabun.

In experiments, tabun was extremely potent against insects: as little as 5 ppm of tabun killed all the leaf lice he used in his initial experiment. In January 1937, Schrader observed the effects of nerve agents on human beings first-hand when a drop of tabun spilled onto a lab bench. Within minutes he and his laboratory assistant began to experience miosis (contraction of the pupils of the eyes), dizziness, and severe shortness of breath. It took them three weeks to recover fully.

In 1935 the Nazis leadership had passed a decree that required all inventions of possible military significance to be reported to the Ministry of War, so in May of 1937 Schrader sent a sample of tabun to the chemical warfare (CW) section of the Army Weapons Office in Berlin-Spandau. Dr. Schrader was summoned to the Wehrmacht chemical lab in Berlin to give a demonstration, after which Schrader's patent application and all related research was classified. Colonel Rüdiger, head of the CW section, ordered the construction of new laboratories for the further investigation of tabun and other organophosphate compounds, and Schrader soon moved to a new laboratory at Wuppertal-Elberfeld in the Ruhr valley to continue his research in secret throughout World War II.

Three of the most widely known agents, sarin (GB), soman (GD), and tabun (GA) were also developed during this period for use as chemical warfare agents, but were not used in combat. Cyclosarin (GF) was developed somwhat later, in 1949, by the same team.

The Nazi mass production of tabun

In 1939, a pilot plant for tabun production was set up at Munster-Lager, on Luneberg heath near the German Army proving grounds at Raubkammer. In January 1940, construction began on a secret plant, code named "Hochwerk", for the production of tabun at Dyernfurth-am-Oder (now Brzeg Dolny in Poland), on the Oder River 40 km (24.9 miles) from Breslau (now Wroclaw) in Silesia.

The plant was large, covering an area of 2.4 by 0.8 km (1.5 by 0.5 miles), and was completely self-contained, synthesizing all intermediates as well as the final product, tabun. The factory even had an underground plant for filling munitions, which were then stored at Krappitz (now Krapowice) in Upper Silesia. The plant was operated by Anorgana GmbH, a subsidiary of IG Farben, as were all other chemical weapon agent agent production plants in Germany at the time.

Because of the plant's deep secrecy and the difficult nature of the production process, it took from January 1940 until June 1942 for the plant to become fully operational. Many of tabun's chemical precursors were so corrosive that reaction chambers not lined with quartz or silver soon became useless. Tabun itself was so hazardous that the final processes had to be performed while enclosed in double glass-lined chambers with a stream of pressurized air circulating between the walls.

3,000 German nationals were employed at Hochwerk, all equipped with clothing and respirators constructed of a poly-layered rubber/cloth/rubber sandwich that was destroyed after the tenth wearing. Despite all precautions, there were over 300 accidents before production even began, and at least 10 workers were killed during the 2.5 years of operation. Some incidents cited in A Higher Form of Killing: The Secret History of Chemical and Biological Warfare are as follows:

• Four pipe fitters had liquid tabun drain onto them; they died before their rubber suits could be removed.
• A worker had 2 liters of tabun pour down the neck of his rubber suit; he died within 2 minutes.
• Seven workers were hit in the face with a stream of tabun of such force that the liquid was forced behind their respirators; only two survived despite heroic resuscitation measures.

The secret gets out

After World War II, the Allies recovered German artillery shells containing the three German nerve agents of the day, prompting further research into nerve agents by the former Allies. In 1952, researchers in Porton Down, England invented the VX nerve agent, but soon abandoned the project. In 1958 the British government traded their VX technology with the United States of America in exchange for information on thermonuclear weapons; by 1961 the US was producing large amounts of VX, and performing its own nerve agent research. This research produced three more agents; the four agents (VE, VG, VM, VX) are collectively known as the "V-Series" class of nerve agents.

Nerve agents in Nazi Germany

In mid-1939, sarin was invented, and the formula for the agent was passed to the Chemical Warfare section of the German Army Weapons Office, which ordered that it be brought into mass production for wartime use. A number of pilot plants were built, and a high-production facility was under construction (but was not finished) by the end of World War II. Estimates for total sarin production by Nazi Germany range from 500 kg to 10 tons.

During that time, German intelligence believed that the Allies also knew of these compounds, assuming that because these compounds were not discussed in the Allies' scientific journals information about them was being suppressed. Though sarin, tabun and soman were incorporated into artillery shells, Germany ultimately decided not to use nerve agents against Allied targets, fearing a potentially devastating Allied retaliatory nerve agent deployment (in actuality, the Allies didn't learn about these agents until shells filled with them were captured near the end of the war.) This is detailed in Joseph Borkin's book The Crime and Punishment of IG Farben:

Speer, who was strongly opposed to the introduction of tabun, flew Otto Ambros, I.G.'s authority on poison gas as well as synthetic rubber, to the meeting. Hitler asked Ambros, "What is the other side doing about poison gas?" Ambros explained that the enemy, because of its greater access to ethylene, probably had a greater capacity to produce mustard gas than Germany did. Hitler interrupted to explain that he was not referring to traditional poison gases: "I understand that the countries with petroleum are in a position to make more [mustard gas], but Germany has a special gas, tabun. In this we have a monopoly in Germany." He specifically wanted to know whether the enemy had access to such a gas and what it was doing in this area. To Hitler's disappointment Ambros replied, "I have justified reasons to assume that tabun, too, is known abroad. I know that tabun was publicized as early as 1902, that Sarin was patented, and that these substances appeared in patents. (...) Ambros was informing Hitler of an extraordinary fact about one of Germany's most secret weapons. The essential nature of tabun and sarin had already been disclosed in the technical journals as far back as 1902, and I.G. had patented both products in 1937 and 1938. Ambros then warned Hitler that if Germany used tabun, it must face the possibility that the Allies could produce this gas in much larger quantities. Upon receiving this discouraging report, Hitler abruptly left the meeting. The nerve gases would not be used, for the time being at least, although they would continue to be produced and tested.

Since World War II

To date, nerve agents have not been used in warfare on a large scale. Iraq briefly used chemical weapons, including nerve agents, during the Iran-Iraq war of 1981-1988; the Kurdish village of Halabja was exposed to nerve agents, and controversy still rages as to whether this was a deliberate or accidental act. Nerve agents were not used by Iraq in the Gulf War, despite widespread fears to the contrary. However, the widespread use of anticholinergic drugs as a prophylaxis against nerve gas attack has been proposed as a possible cause of Gulf war syndrome.

One of the most widely publicised uses of nerve agents was the 1995 terrorist attack in which operatives of the group Aum Shinrikyo released sarin into the Tokyo subway system (see Sarin gas attack on the Tokyo subway).

References

• Clarke, Robin (1968). We All Fall Down: The Prospects of Biological and Chemical Warfare. Penguin Press. 1968. ASIN 0140211217
• E-Medicine. (June 29, 2004). CBRNE - Nerve Agents, V-series: Ve, Vg, Vm, Vx. Retrieved Oct. 23, 2004.
• E-Medicine. (June 30, 2004). CBRNE - Nerve Agents, G-series: Tabun, Sarin, Soman. Retrieved Oct. 23, 2004.
• Mitretek Systems. (May 2004). Short History of the Development of Nerve Gases. Retrieved Oct. 23, 2004.
• Paxman, J.; Harris, R. (2002). A Higher Form of Killing: The Secret History of Chemical and Biological Warfare (2002 Rando edition). Random House Press. ISBN 0812966538.
• United States Senate, 103d Congress, 2d Session. (May 25, 1994). The Riegle Report. Retrieved Nov. 6, 2004.