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Ricin (pron.: /ˈraɪsɪn/), from the castor oil plant Ricinus communis, is a highly toxic, naturally occurring protein. A dose the size of a few grains of table salt can kill an adult human. The median lethal dose (LD50) of ricin is around 22 micrograms per kilogram (1.78 mg for an average adult, around 1⁄228 of a standard aspirin tablet/0.4 g gross) in humans if exposure is from injection or inhalation. Oral exposure to ricin is far less toxic and a lethal dose can be up to 20–30 milligrams per kilogram.

Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. That is,

It prevents the cell from assembling various amino acids into protein according to the messages it receives from RNA. This process, conducted by the cell's ribosome – literally a protein-making machine – is the most basic level of cell metabolism, essential to all living cells and thus to life itself. Ricin is resistant, but not impervious, to digestion by peptidases. By ingestion, the pathology of ricin is largely restricted to the gastrointestinal tract where it may cause mucosal injuries; with appropriate treatment, most patients will make a full recovery. Because the symptoms are caused by failure to make protein, they emerge only after a variable delay from a few hours to a full day after exposure. An antidote has been developed by the UK military, although it has not yet been tested on humans. Another antidote developed by the U.S. military has been shown to be safe and effective in lab mice injected with antibody-rich blood mixed with ricin, and has had some human testing. Symptomatic and supportive treatment are available.

Long term organ damage is likely in survivors. Ricin causes severe diarrhea and victims can die of shock. Death typically occurs within 3–5 days of the initial exposure. The ingestion of Ricinus communis cake used as fertilizer has been responsible for fatal ricin poisoning in animals. Deaths from ingesting castor plant seeds are rare, partly because of their indigestible capsule, and because the body can, only with difficulty, digest ricin.  The pulp from eight beans is considered dangerous to an adult. Rauber and Heard have written that close examination of early 20th century case reports indicates that public and professional perceptions of ricin toxicity "do not accurately reflect the capabilities of modern medical management".

Overdose

This section requires expansion. (April 2013) Most acute poisoning episodes in humans are the result of oral ingestion of castor beans, 5–20 of which could prove fatal to an adult. Victims often manifest nausea, diarrhea, tachycardia, hypotension and seizures persisting for up to a week.[10] Blood, plasma, or urine ricin concentrations may be measured to confirm diagnosis

Manufacture

Ricin is easily purified from castor oil manufacturing waste. The aqueous phase left over from the oil extraction process is called waste mash. It would contain about 5–10% ricin by weight, but heating during the oil extraction process denatures the protein, making the resultant seed cake safe for use as animal feed. Ricin can be isolated from fresh seed by chromatographic techniques similar to those routinely used for purification of many other plant proteins. Patented extraction process A process for extracting ricin has been described in a patent. The described extraction method is very similar to that used for the preparation of soy protein isolates. The patent was removed from the United States Patent and Trademark Office (USPTO) database sometime in 2004. Modern theories of protein chemistry cast doubt on the effectiveness of the methods disclosed in the patent.

Potential military and terrorist use

The United States investigated ricin for its military potential during World War I. At that time it was being considered for use either as a toxic dust or as a coating for bullets and shrapnel. The dust cloud concept could not be adequately developed, and the coated bullet/shrapnel concept would violate the Hague Convention of 1899 (adopted in U.S. law at 32 Stat. 1903), specifically Annex §2, Ch.1, Article 23, stating "... it is especially prohibited ... [to employ poison or poisoned arms". World War I ended before the United States weaponised ricin. During World War II the United States and Canada undertook studying ricin in cluster bombs. Though there were plans for mass production and several field trials with different bomblet concepts, the end conclusion was that it was no more economical than using phosgene. This conclusion was based on comparison of the final weapons, rather than Ricin's toxicity (LCt50 ~40 mg·min/m3). Ricin was given the military symbol W or later WA. Interest in it continued for a short period after World War II, but soon subsided when the U.S. Army Chemical Corps began a program to weaponise sarin. The Soviet Union also possessed weaponised ricin. There were speculations that the KGB used it outside the Soviet bloc; however, this was never proven. In 1978, the Bulgarian dissident Georgi Markov was assassinated by Bulgarian secret police who surreptitiously "shot" him on a London street with a modified umbrella using compressed gas to fire a tiny pellet contaminated with ricin into his leg.He died in a hospital a few days later; his body was passed to a special poison branch of the British Ministry of Defense (MOD) that discovered the pellet during an autopsy. The prime suspects were the Bulgarian secret police: Georgi Markov had defected from Bulgaria some years previously and had subsequently written books and made radio broadcasts which were highly critical of the Bulgarian communist regime. However, it was believed at the time that Bulgaria would not have been able to produce the pellet, and it was also believed that the KGB had supplied it.

The KGB denied any involvement although high-profile KGB defectors Oleg Kalugin and Oleg Gordievsky have since confirmed the KGB's involvement. Earlier, Soviet dissident Aleksandr Solzhenitsyn also suffered (but survived) ricin-like symptoms after an encounter in 1971 with KGB agents.Given ricin's extreme toxicity and utility as an agent of chemical/biological warfare, it is noteworthy that the production of the toxin is rather difficult to limit. The castor bean plant from which ricin is derived is a common ornamental and can be grown at home without any special care, and the major reason ricin is a public health threat is that it is easy to obtain. Under both the 1972 Biological Weapons Convention and the 1997 Chemical Weapons Convention, ricin is listed as a schedule 1 controlled substance. Despite this, more than 1 million tonnes of castor beans are processed each year, and approximately 5% of the total is rendered into a waste containing negligible concentrations of undenatured ricin toxin. Ricin is several orders of magnitude less toxic than botulinum or tetanus toxin, but the latter are harder to come by. Compared to botulinum or anthrax as biological weapons or chemical weapons, the quantity of ricin required to achieve LD50 over a large geographic area is significantly more than an agent such as anthrax (tons of ricin vs. only kilogram quantities of anthrax). Ricin is easy to produce, but is not as practical nor likely to cause as many casualties as other agents. Ricin is inactivated (the protein changes structure and becomes less dangerous) much more readily than anthrax spores, which may remain lethal for decades. Jan van Aken, a Dutch expert on biological weapons, explained in a report for The Sunshine Project that Al Qaeda's experiments with ricin suggest their inability to produce botulinum or anthrax.[49] A biopharmaceutical company called Soligenix, Inc. has developed a vaccine called RiVax™ that is currently in trials. Incidents involving ricin Main article: Incidents involving ricin Ricin has been involved in a number of incidents, including the high-profile assassination of Georgi Markov in 1978 using a weapon disguised as an umbrella. Several terrorists and terrorist groups have experimented with ricin, and several incidents of the poison being mailed to U.S. politicians have occurred in the 21st century.