Ricin

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Image:Castor beans.jpg The protein ricin (pronounced [ˈraɪsɪn]) is a toxin from the castor bean (Ricinus communis). Ricin can be extracted from castor beans and is known to have an average lethal dose in humans of 0.2 milligrams (1/5,000th of a gram), though some sources give higher figures<ref name="http://www.bt.cdc.gov/agent/ricin/facts.asp">http://www.bt.cdc.gov/agent/ricin/facts.asp</ref>. It is considered to be twice as deadly as cobra venom.

1 Toxicity and manufacture
2 Potential medicinal use
3 Use as a chemical/biological warfare agent
4 Patent
- 4.1 Extraction process
5 Detected ricin incidents
6 In popular culture
7 Notes and references
8 See also
9 External links

[edit] Toxicity and manufacture

Image:Ricin structure.jpg Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. While there is no known antidote, the US military has developed a vaccine.<ref>http://www.dcmilitary.com/army/standard/12 18/local news/36813-1.html</ref> Symptomatic and supportive treatment is available. Long term organ damage is likely in survivors. In small doses, such as the typical dose contained in a measure of castor oil, ricin causes digestive tract cramps. Ingested in larger doses, ricin causes severe diarrhea and victims can die of shock. (See abrin).

Although the castor bean plant has long been noted for its toxicity, ricin was first isolated and named in 1888 by Hermann Stillmark. Modern feed-making techniques break down the ricin in castor beans by heating at 140 degrees Celsius for 20 minutes, although some studies suggest that residual toxic effects may linger. Although one seed contains enough ricin to kill an adult human, they may pass harmlessly through the digestive system if swallowed whole.<ref name="http://www.ansci.cornell.edu/plants/castorbean.html">http://www.ansci.cornell.edu/plants/castorbean.html</ref>. Typically 2.5–20 raw seeds can kill an adult human; 4 a rabbit, 5 a sheep, 6 an ox, 6 a horse, 7 a pig, 11 a dog, but 80 for chickens and ducks.<ref name="http://www.hort.purdue.edu/newcrop/duke_energy/Ricinus_communis.html">http://www.hort.purdue.edu/newcrop/duke energy/Ricinus communis.html</ref> As little as one castor bean, about 0.5 grams, may be fatal in a child.

Ricin consists of two distinct protein chains (almost 30kDa each) that are linked to each other by disulfide bond:

Ricin A is toxic to the cell by interfering with ribosomes, responsible for protein synthesis
Ricin B is important in assisting ricin A's entry into a cell by binding with a cell surface component.

Many plants such as barley have the A chain but not the B chain. Since people do not get sick from eating large amounts of such products, ricin A is of extremely low toxicity as long as the B chain is not present.

Ricin is easily purified from castor-oil manufacturing waste. The seed-pulp left over from pressing for castor oil contains on average about 5% by weight of ricin. Since 0.2 mg of purified Ricin constitutes a fatal dose, this is a considerable amount of ricin.

In the United States, a person caught manufacturing or possessing ricin may be sentenced to up to 30 years in prison.

[edit] Potential medicinal use

Ricin may have therapeutic use in the treatment of cancer. Ricin could be linked to a monoclonal antibody to target malignant cells recognized by the antibody. Genetic modification of ricin is believed to be possible to lessen its toxicity to humans, but not to the cancer cells. A promising approach is also to use the non-toxic B subunit as a vehicle for delivering antigens into cells thus greatly increasing their immunogenicity. Use of ricin as an adjuvant has potential implications for developing mucosal vaccines.

[edit] Use as a chemical/biological warfare agent

The United States investigated ricin for its military potential during the First World War. 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. The War ended before it was weaponized.

During the Second World War 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 (LD50 <30 mg.min.m^–3). Ricin was given the military symbol W.

The best-known documented use of ricin as an agent of biological warfare was by the Soviet Union's KGB during the Cold War. 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; the body of Georgi Markov was passed to a special poison branch of the British MOD who discovered the pellet during an autopsy. The main suspect was the Bulgarian secret police; this was because Georgi Markov had defected from Bulgaria several years prior to the incident and was wanted for writing many controversial books on the communist government at the time, however, it was believed at the time that Bulgaria would not have been able to produce the poison, 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 a 1971 encounter with KGB agents.<ref>D.M. Thomas, Alexander Solzhenitsyn: A Century in His Life, 368-378</ref>

Despite ricin's extreme toxicity and utility as an agent of chemical/biological warfare, it is extremely difficult to limit the production of the toxin. 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 metric tonnes of castor beans are processed each year, and approximately 5% of the total is rendered into a waste containing high concentrations of ricin toxin.<ref name="http://www.ansci.cornell.edu/plants/toxicagents/ricin/ricin.html">http://www.ansci.cornell.edu/plants/toxicagents/ricin/ricin.html</ref>

In August of 2002, US officials asserted that the Islamic militant group Ansar al-Islam tested ricin, along with other chemical and biological agents, in northern Iraq.

To put ricin used as weapon into perspective, it is worth noting that as a biological weapon or chemical weapon, ricin may be considered as not very powerful, if only in comparison with other poisons such as botulinum or anthrax. Hence, a military willing to use biological weapons and having advanced resources would rather use either of the latter instead. Ricin is easy to produce, but is not as practical nor likely to cause as high casualties as other agents. Ricin denatures (ie, the protein changes structure and becomes less dangerous) much more readily than anthrax spores, which may remain lethal for decades. (Jan van Aken, an expert on biological weapons explained in an interview with the German magazine Der Spiegel that he judges it rather reassuring that Al Qaeda experimented with ricin as it suggests their inability to produce botulin or anthrax.)

Pure ricin could be dispersed through the air, but ozone, nitrogen oxides, and other pollutants would oxidize it within a few hours, rendering it harmless. Since it acts as an enzyme, catalyzing destruction of ribosomes, even a single oxidation is likely to render the ricin molecule harmless. Presumably it could be sealed inside some sort of dust particle that would dissolve in water, but this would be difficult.

The major reason it is dangerous is that there is no specific antidote, and that it is very easy to obtain (the castor bean plant is a common ornamental, and can be grown at home without any special care). Ricin is actually several orders of magnitude less toxic than botulinum or tetanus toxin, but those are more difficult to obtain.

[edit] Patent

The process for creating ricin is well-known, in part because a patent was granted for it in 1952. The inventors named in U.S. Patent 3,060,165 (granted October 23, 1962) "Preparation of Toxic Ricin", assigned to the U.S. Secretary of the Army, are Harry L. Craig, O.H. Alderks, Alsoph H. Corwin, Sally H. Dieke, and Charlotte Karel. The patent was removed from the United States Patent and Trademark Office (USPTO) database sometime in 2004, but is still available online<ref name="http://v3.espacenet.com/origdoc?DB=EPODOC&IDX=US3060165&QPN=US3060165">Harry L. Craig, O.H. Alderks, Alsoph H. Corwin, Sally H. Dieke, and Charlotte Karel, US Patent 3,060,165, "Preparation of Toxic Ricin", granted October 23 , 1962</ref> through international patent databases. Modern theories of protein chemistry cast doubt on the effectiveness of the methods disclosed in the patent.<ref name="http://www.globalsecurity.org/org/nsn/nsn-040723.htm">http://www.globalsecurity.org/org/nsn/nsn-040723.htm</ref>

[edit] Extraction process

The extraction method described in the patent is very similar to the preparation of soy protein isolates. Modern extraction plants might use membrane filtration to make highly purified ricin isolates.

Ricin is initially extracted from defatted castor beans by aqueous extraction at pH 3.8 to yield a leachate containing solubilized ricin. The leachate is filtered to remove insoluble matter and the crude ricin then precipitated by the addition of a 12% solution of sodium sulfate with a pH of 7.0-8.0. After precipitation, the crude ricin cake is washed with a 16.7% solution of sodium sulfate to remove extraneous nitrogenous substances. The precipitated ricin may be reextracted once to further purify it.

The final ricin precipitate is dried and then purified by floatation in carbon tetrachloride. An aerosol powder may be prepared by spray drying or air grinding the purified ricin using cold air.

[edit] Detected ricin incidents

[edit] Assassination of Bulgarian Dissident Georgi Markov, London 1978

On September 7, 1978 the Bulgarian dissident Georgi Markov was shot in the leg in public on Waterloo Bridge in the middle of London by a man using a weapon built into an umbrella. The weapon embedded a small pellet in Markov's leg which contained ricin. Markov died three days later.

Image:Ricin plot Daily Mirror.jpg

Daily Mirror front page, part of a media frenzy in the United Kingdom when the ricin plot news was released.

[edit] Related arrests in Britain in 2003

Main article: Wood Green ricin plot

On 5 January, 2003 the Metropolitan Police raided a flat in north London and arrested six Algerian men whom they claimed were manufacturing ricin as part of a plot for a poison attack on the London Underground. No ricin was recovered as a result of this raid.

[edit] In Washington, D.C.

Ricin was detected in the mail at the White House in Washington, D.C. in November of 2003. The letter containing it was intercepted at a mail handling facility off the grounds of the White House, and it never reached its intended destination. The letter contained a fine powdery substance that later tested positive for ricin. Investigators said it was low potency and was not considered a health risk. This information was not made public until February 3, 2004, when preliminary tests showed the presence of ricin in an office mailroom of U.S. Senate Majority Leader Bill Frist's office. There were no signs that anyone who was near the contaminated area developed any medical problems. Several Senate office buildings were closed as a precaution.

[edit] In Richmond, VA

In January 2006, ricin was found in a home in the suburbs of Richmond, VA. It was in the form of mashed castor beans. Although the suspect, Chetanand Sewraz, was allegedly isolating the toxin to kill his estranged wife, and not for some form of bioterrorism, it nonetheless highlighted the ease with which ricin toxin can be made.<ref name="http://wtvr.com/Global/story.asp?S=4457615">http://wtvr.com/Global/story.asp?S=4457615</ref>^,<ref name="http://wtvr.com/Global/story.asp?S=4457626">http://wtvr.com/Global/story.asp?S=4457626</ref>

[edit] In Austin, Texas

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FBI confirms that ricin was not found at the University of Texas

On 23 February 2006, a student in the Moore-Hill dormitory at the University of Texas at Austin found a strange powder in a roll of quarters she was using to do laundry. The University Environmental Health and Safety department immediately sanitized the affected rooms. Lab results (returned the following Friday) indicated ricin. The source of the powder remains unknown, with both the university and Joint Terrorism Task Force investigating. The student and her roommate were being treated for potential exposure to the poison, although neither has exhibited symptoms. After cleansing and reinspection of the affected rooms (completed at 2:30am), the dorm reopened.<ref>"Ricin discovered in dormitory", Austin-American Statesman, 25 February 2006</ref>^,<ref>"Powdered substance reported by student in Moore-Hill Dormitory", Official UT Austin Press Release, 24 February 2006</ref> News reports on 25 February report that further testing has indicated that the substance found is not, in fact, ricin.<ref>"Tests: No ricin in UT student from Pearland", Houston Chronicle, 25 February 2006</ref> The identity of the powder has yet to be determined.

[edit] In popular culture

Ricin was the poison used in the Agatha Christie "Tommy and Tuppence" whodunnit, The House of Lurking Death in a 1929 collection of short stories called Partners in Crime.
Ricin was used as the poison of choice of the murderer in the 1962 comedy film Kill or Cure.
Ricin was the poison used in Agatha Raisin and the Wizard of Evesham by M.C.Beaton, published in 1999.
Ricin was mentioned in the "call me the prankster"<ref name="http://www.toothpastefordinner.com/061505/call-me-the-prankster.gif">"call me the prankster"</ref> comic at toothpaste for dinner<ref name="http://www.toothpastefordinner.com">toothpaste for dinner</ref>
The Penn and Teller book How To Play With Your Food (ISBN 0-679-74311-1) includes a "gimmicks envelope" of small objects related to the tricks inside the book. One of these is a sticker reading "Contains all-natural ricin," intended to be placed on food as a joke. The book explains that ricin is a poison.
Ricin appears in CSI Series 2 Episode 7<ref name="http://www.imdb.com/title/tt0534662/">CSI Series 2 Episode 7</ref> , consumed accidentally.
In Hour 1 of 24: The Game, terrorists plan to release ricin into Los Angeles Harbor.