Ricin

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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.^[1] It is considered to be twice as deadly as cobra venom. The 2007 Guinness World Records Book considers ricin the world's most potent plant toxin.^{[citation needed]}.

Contents 1 Toxicity and manufacture 2 Potential medicinal use 3 Use as a chemical/biological warfare agent 4 Patented extraction process 5 Detected ricin incidents 5.1 Assassination of Bulgarian Dissident Georgi Markov, London 1978 5.2 Related arrests in Britain in 2003 5.3 In South Carolina 5.4 In Washington, D.C. 5.5 In Richmond, VA 5.6 In Austin, Texas 6 In popular culture 7 See also 8 Notes and references 9 External links

[edit] Toxicity and manufacture

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.^[2] Symptomatic and supportive treatment is available. Long term organ damage is likely in survivors. Ricin causes severe diarrhea and victims can die of shock. (See abrin).

According to the National Library of Medicine: "Ingestion of seeds of the castor oil plant is rare, and may cause toxicity but rarely death. The presumed toxic component is ricin, a highly potent cellular poison. We report the case of a young adult who ingested a large number of the seeds, causing initial toxicity, but with subsequent full recovery. The management of such ingestions and the apparent discrepancy between the extreme toxicity of ricin and the generally milder toxicity of ingested seeds are discussed."[1]

Although the highly toxic nature of castor bean (ricinis communis) is well recognized, reports of human toxicity in the English medical literature are scarce. The potentially lethal doses reported for children and adults are three beans and eight beans respectively. Recent experience with two cases provides added insight into the expected course of toxicity. In both cases, repeated vomiting, diarrhea, and transiently elevated serum creatine occurred. Dehydration was much more pronounced in the second case. Both patients recovered uneventfully. Other reported manifestations of castor bean toxicity, such as hepatic necrosis, renal failure, erythrocyte hemolysis, convulsions, and shock, did not occur. [2]

A 21-year old student ingested thirty ricin seeds in a suicidal attempt, some of which were masticated. Three hours later he developed severe diarrhea with vomiting and abdominal cramps, followed by extracellular dehydration and circulatory collapse. He recovered following symptomatic treatment by infusion of saline and glucose solutions. [3]

Commonly used references present a very gloomy prognosis for castor seed ingestion. This is not in concordance with actual experience when actual case experience is sought out and examined in detail. [4]

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

• Ricin A is an N-glycoside hydrolase that specifically removes an adenine base from ribosomal RNA, resulting in an inhibition of protein synthesis.
• Ricin B is a lectin that binds galactosyl residues and 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

Ricins 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.

Therapeutically, ricin is used in magic bullets to specifically target and destroy cancer cells.[5]

[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.^[3]

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.^[4]

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] Patented extraction process

The process for creating ricin is well-known, and for example described in a patent.^[5] The described extraction method is very similar to the preparation of soy protein isolates. Modern extraction plants might use membrane filtration to make highly purified ricin isolates.^{[citation needed]}

The patent was removed from the United States Patent and Trademark Office (USPTO) database sometime in 2004, but is still available online through international patent databases.^[6] Modern theories of protein chemistry cast doubt on the effectiveness of the methods disclosed in the patent.^[7]

[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.

[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 South Carolina

In 2003, a package and letter sealed in a ricin-contaminated envelope was intercepted in Greenville, South Carolina, at a United States Postal Service processing center.^[8]

[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.^[9][10]

[edit] In Austin, 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.^[11][12] News reports on 25 February report that further testing has indicated that the substance found is not, in fact, ricin.^[13] 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.
• A killer used ricin to murder Travis McGee's girlfriend in 1979's The Green Ripper
• 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"^[14] comic at toothpaste for dinner^[15]
• 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: Crime Scene Investigation Series 2 Episode 7.^[16]
• In Hour 1 of 24: The Game, terrorists plan to release ricin into Los Angeles Harbor.
• The Umbrella-gun pellet assassination incident was featured in Mythbusters.
• Ricin was one of the poisons used to exact terrorism in the 2004 book, "3rd Degree" by James Patterson
• In Episode 15 of Season 2 in The Unit, Ricin is used in a bomb inside the United Nations building.
• Ricin-laced hot chocolate was the weapon used to kill a private school history professor in J. D. Robb's 2007 novel, "Innocent in Death".
• Ricin is mentioned as being dispersed in Dirty Bombs across LA in one site the viral marketing campaign for the new nine inch nails album, "Year Zero".^[17]

[edit] See also

• 2001 anthrax attacks

[edit] Notes and references

[edit] External links

• UK Department of Health ricin information
• Cornell University ricin information
• Castor bean information
• Medical research on ricin
• Army Chemical Review
• [http://www.bt.cdc.gov/agent/ricin/ CDC Ricin - Emergency Preparations[

• Links to external chemical sources