Ricin

Image:Castorbeans.jpg The protein ricin (pronounced rye-sin) is a poisonmanufactured from the castor bean(Ricinus communis). Its name comes from the seed's resemblance to the tick. Ricin can be extractedfrom castor beansand is known to have an average lethal dosein humans of 0.2 milligrams(1/5,000th of a gram), though some sources give higher figures [1]. It is considered to be twice as deadly as cobravenom.

Toxicity and manufacture

Ricin is poisonous if inhaled, injected, or ingested, acting as a toxin by the inhibition of protein synthesis. There is no known antidote; only symptomaticand supportive treatment is available. Long term organdamage 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 diarrheaand victims can die of shock. (See abrin).

Although the castor bean planthas long been noted for its toxicity, ricin was first isolatedand named in 1888by Hermann Stillmark. Modern feed-making techniques break down the ricin in castor beans by heating at 140 degrees Celsiusfor 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. [2]. 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 cocks and ducks.[3]

Ricin consists of two distinct proteinchains (almost 30kDaeach) that are linked to each other by disulfide bond:

• Ricin A is toxic to the cellby interfering with Ribosomes, responsible for proteinsynthesis
• 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 if and only if the B chain is not present.

Ricin is easily purifiedfrom castor-oil manufacturing waste. The seed-pulpleft 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.

As little as one castor bean, about 0.5 grams, may be fatal in a child.

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

Potential medicinal use

Ricin may have therapeutic use in the treatment of cancer. Ricin could be linked to a monoclonal antibodyto 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 antigensinto cells thus greatly increasing their immunogenicity. Use of ricin as an adjuvanthas potential implications for developing mucosal vaccines

Use as a chemical/biological warfare agent

The United Statesinvestigated 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 coated bullets and shrapnel. The dust cloud concept could not be adequately developed, and researchers believed the coated bullet/shrapnel concept was unethical. The War ended before it was weaponized.

During the Second World Warthe United States and Canadaundertook 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 warfarewas by the Soviet Union's KGBduring the Cold War. In 1978, the Bulgariandissident Georgi Markovwas assassinated by Bulgarian secret policewho surreptitiously 'shot' him on a Londonstreet with a modified umbrella using compressed gas to fire a tiny pellet contaminated with ricin into his leg. He died in hospital a few days later; the pellet was discovered by chance during an autopsyand the poison linked back to the KGB. Earlier, Soviet dissident Aleksandr Solzhenitsynalso suffered (but survived) ricin-like symptoms after a 1971 encounter with KGB agents (D.M. Thomas, Alexander Solzhenitsyn: A Century in His Life, 368-378).

Despite ricin's extreme toxicityand utility as an agent of chemical/biological warfare, it is extremely difficult to limit the production of the toxin. Under both the 1972Biological Weapons Conventionand the 1997Chemical Weapons Convention, ricin is listed as a schedule 1controlled 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 [4].

In August of 2002, USofficials asserted that the Islamic militant group Ansar al-Islamtested ricin, along with other chemicaland biologicalagents, in northern Iraq.

To put ricin used as weaponinto perspective, it is worth noting that as a biological weaponor chemical weapon, ricin may be considered as not very powerful, if only in comparison with other poisons such as botulinumor 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 casualities 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 Spiegelthat he judges it rather reassuring that Al Qaedaexperimented with ricin as it suggests their inability to produce botulin or anthrax.)

Pure ricin could be dispersed through the air, however it would tend to be oxidized and rendered harmless by ozone, nitrogen oxides, and other pollutants in a matter of hours. 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 magnitudeless toxic than botulinumor tetanustoxins, but those are more difficult to obtain.

Ricin patent

Image:Ricin process.png The process for creating ricin is well-known, in part because a patent was granted for it in 1952. The inventors named in US Patent3,060,165 (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 onlinethrough international patent databases.

Ricin extraction process

The extraction of ricin from castor beans is very similar to the prepartion of soy protein isolates. Modern extraction plants might use membrane filtrationto make highly purified ricin isolates

Ricin is initially extracted from defatted castor beans by aquous 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 sulfatewith 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 extranious nitrogenoussubstances. 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 aerosolpowder may be prepared by spray dryingor air grinding the purified ricin using cold air.

Ricin-related arrests in Britain in 2003

It was widely reported in the media that traces of ricin were detected by British police in a flat in Wood Green, North Londonafter a raid on a suspected ring of terrorists on 5 January, 2003. Media reports stated that a group was suspected of intending to use the poison in an attack on the London Underground. However at the trial of Kamel Bourgass in 2005 it became apparent that within a few days of the raid the leader of the Biological Weapon Identification Group at the Porton DownDefence Science and Technology Laboratoryhad concluded that ricin was not present at Wood Green [5] [6]. Some acetone, 22 castor beans, and poor recipes for ricin and other poisons copied from the Internet were found. It appears that an individual conducting amateur research on poisons was found in this raid.

A little later several arrests were made in France and a bottle of something that tested positive for ricin was found. Further analysis identified the material as ground wheat germ. The analytic confusion was caused by the similarity of many plant proteins to one of the ricin components, which suggests that higher quality (better specificityand sensitivity) analytic tests for ricin are needed.

Six more suspects were arrested in Bournemouthin England in connection with the investigation into the alleged ricin incident in London. They were not convicted of any poisons related crime.

Three more suspects were arrested in Manchesterin England in connection with the investigation of the alleged ricin found in London, following a raid carried out pursuant to an investigation into immigration issues. A Special Branchpoliceman, DC Stephen Oake, was fatally stabbed during the arrests, and three other officers were also injured, one seriously.

On January 20, 2003 Finsbury Park mosquewas raided by police, apparently as part of the investigation into the alleged discovery of ricin in Wood Green. A number of men who were apparently living at the mosque were arrested.

On February 5, 2003, U.S. Secretary of StateColin Powellpresented those arrested as the "UK Poison Cell" of a global terrorist network in making the case for military intervention in Iraqto the UN Security Council[7].

In April 2005 31-year-old Kamel Bourgasswas jailed for 17 years after being convicted of conspiracy to commit a public nuisance"by the use of poisons and explosives to cause disruption, fear or injury". He was also jailed for life following a conviction for murderingthe Special Branch policeman who went to arrest him. All others accused in connection with the Wood Green flat were acquitted on all counts.

Ricin in Washington, D.C.

Ricin was detected in the mail at the White Housein 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.

Ricin 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.[8][9]

Ricin in popular culture

Ricin was the poison used in the Agatha ChristieTommy and TuppencewhodunnitThe House of Lurking Death in a 1929collection of short stories called Partners in Crime.

Ricin was used as the poison of choice of the murderer in the 1962comedy film Kill or Cure.

Ricin was mentioned in the "call me the prankster"comic at toothpaste for dinner

The Penn and Tellerbook How To Play With Your Food (ISBN 0679743111) includes a "gimmicks envelope" of small objects related to the tricks inside the book. One of these is a sticker reading "With all-natural ricin!". The book explains that ricin is a poison.

See also

• 2001 anthrax attacks

External links

• UK Department of Health ricin information
• Cornell University ricin information
• Castor bean information
• Medical research on ricinde:Rizin

fr:Ricine he:ריצין it:Ricina (proteina) ja:リシン (毒物) nl:Ricine pl:Rycyna sv:Ricin

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It uses material from the http://en.wikipedia.org/wiki/Ricin Wikipedia article Ricin.