ricin that may be present. the remaining spent crushed seeds, called variously the "cake", "oil cake", and "press cake", can contain up to 5% ricin. while the oil cake from coconut, peanuts, and sometimes cotton seeds can be used as cattle feed or fertilizer, the toxic nature of castor beans precludes their oil cake from being used as feed unless the ricin is first deactivated by autoclaving. accidental ingestion of ricinus communis cake intended for fertilizer has been reported to be responsible for fatal ricin poisoning in animals. deaths from ingesting castor plant seeds are rare, partly because of their indigestible seed coat, and because some of the ricin is deactivated in the stomach. 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". 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. swallowing castor beans rarely proves to be fatal unless the bean is thoroughly chewed. the survival rate of castor bean ingestion is 98%. in 2013 a 37-year-old woman in the united states survived after ingesting 30 beans. victims often manifest nausea, diarrhea, fast heart rate, low blood pressure, and seizures persisting for up to a week. blood, plasma, or urine ricin or ricinine concentrations may be measured to confirm diagnosis. the laboratory testing usually involves immunoassay or liquid chromatography-mass spectrometry. therapeutic applications although no approved therapeutics are currently based on ricin, it does have the potential to be used in the treatment of tumors, as a "magic bullet" to destroy targeted cells. because ricin is a protein, it can be linked to a monoclonal antibody to target cancerous cells recognized by the antibody. the major problem with ricin is that its native internalization sequences are distributed throughout the protein. if any of these native internalization sequences are present in a therapeutic agent, the drug will be internalized by, and kill, untargeted non-tumorous cells as well as targeted cancerous cells. modifying ricin may sufficiently lessen the likelihood that the ricin component of these immunotoxins will cause the wrong cells to internalize it, while still retaining its cell-killing activity when it is internalized by the targeted cells. however, bacterial toxins, such as diphtheria toxin, which is used in denileukin diftitox, an fda-approved treatment for leukemia and lymphoma, have proven to be more practical. a promising approach for ricin is to use the non-toxic b subunit (a lectin) 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. regulation in the us, ricin appears on the select agents list of the department of health and human services, and scientists must register with hhs to use ricin in their research. however, investigators under the control of less than 1000 mg are exempt from regulation. ricin is classified as an extremely hazardous substance in the united states as defined in section 302 of the us emergency planning and community right-to-know act (42 u.s.c. 11002), and is subject to strict reporting requirements by facilities that produce, store, or use it in significant quantities. chemical or biological warfare agent a metal vial containing ricin from the 2003 ricin letters 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 ... o employ poison or poisoned arms". world war i ended before the united states weaponized 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 ~10 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 us army chemical corps began a program to weaponize sarin. the soviet union also possessed weaponized ricin. the kgb developed weapons using ricin which were used outside the soviet bloc, most famously in the markov assassination. in spite of ricin's extreme toxicity and utility as an agent of chemical/biological warfare, production of the toxin is 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. 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 tons (1,100,000 short tons) 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 or likely to cause as many casualties as other agents. ricin is easily denatured by temperatures over 80 °c (176 °f) meaning many methods of deploying ricin would generate enough heat to denature it. once deployed, an area contaminated with ricin remains dangerous until the bonds between chain a or b have been broken, a process that takes two or three days. in contrast, anthrax spores may remain lethal for decades. jan van aken, a german 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. developments a biopharmaceutical company called soligenix, inc. licensed an anti-ricin vaccine called rivax from vitetta et al. at ut southwestern. the vaccine was found safe and immunogenic in mice, rabbits, and humans. two successful clinical trials were completed. soligenix was issued a us patent for rivax. the ricin vaccine candidate was granted orphan drug status in the us and the eec and, as of 2019, was in clinical trials in the us. grants from the national institute of allergy and infectious diseases and the us food and drug administration supported development of the vaccine candidate. synthesis the first isolation of ricin is attributed to the baltic-german microbiologist peter hermann stillmark (1860–1923) in 1888. terrorist use ricin has been involved in a number of actual or planned attacks on individuals. in 1978, the bulgarian dissident georgi markov was assassinated by bulgarian secret police who surreptitiously shot him on a london street with what was later found to have been a modified umbrella using compressed gas to fire a tiny pellet containing 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 defence 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 that 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 later confirmed the kgb's involvement. soviet dissident aleksandr solzhenitsyn had (but survived) ricin-like symptoms after an encounter in 1971 with kgb agents. ten days before the attack on georgi markov another bulgarian defector, vladimir kostov, survived a similar attack. kostov was standing on an escalator of the paris metro when he felt a sting in his lower back above the belt of his trousers. he developed a fever, but recovered. after markov's death the wound on kostov's back was examined and a ricin-laced pellet identical to the one used against markov was removed. several terrorist individuals and groups have experimented with ricin or planned to use it. there have been incidents of the poison being mailed to us politicians. for example, on 29 may 2013 two anonymous letters sent to new york city mayor michael bloomberg contained traces of it. another was sent to the offices of mayors against illegal guns in washington, d.c. a letter containing ricin was also reported to have been sent to american president barack obama at the same time. shannon richardson, an actress, was later charged with the crime, and pleaded guilty that december; she sentenced to 18 years in prison plus a restitution fine of us$367,000. on 2 october 2018, two letters suspected of containing ricin were sent to the pentagon, one addressed to secretary of defense james mattis, and the other to chief of naval operations, admiral john richardson. a letter was received on 23 july 2019 at pelican bay state prison in california which claimed to contain a suspicious substance. authorities later confirmed it contained ricin; no detrimental exposures were identified. in 2020, some media in the czech republic reported, based on intelligence information, that a person carrying a russian diplomatic passport and ricin had arrived in prague with the intention of assassinating three politicians. russian president vladimir putin denied the reports. the targets were said to have been zdeněk hřib, the mayor of prague (capital of the czech republic), who was involved in renaming a square in prague, "pod kaštany", where the russian embassy is situated, to the square of boris nemtsov, an opposition politician assassinated in the kremlin in 2015; ondřej kolář, the mayor of prague 6 municipal district, who was involved in removing the controversial statue to the soviet-era marshal konev; and pavel novotný, the mayor of prague's southwestern řeporyje district. they all received police protection. czech president miloš zeman later described the police protection of zdeněk hřib as an attempt by an insignificant politician to gain attention. zeman also confused ricin with non-poisonous laxative castor oil. in 2018 and 2023 german police thwarted attempted ricin attacks by people supporting islamist terrorist organisation daesh (also calling itself islamic state, is), after tip-offs believed to have come from the us fbi. in popular culture ricin has been used as a plot device, such as in the television series breaking bad. the popularity of breaking bad inspired several real-life criminal cases involving ricin or similar substances. kuntal patel from london attempted to poison her mother with abrin after the latter interfered with her marriage plans. daniel milzman, a 19-year-old former georgetown university student, was charged with manufacturing ricin in his dorm room, as well as the intent of " the ricin on another undergraduate student with whom he had a relationship". mohammed ali from liverpool, england, was convicted after attempting to purchase 500 mg of ricin over the dark web from an undercover fbi agent. he was sentenced, on 18 september 2015, to eight years imprisonment. in the 2013 movie the good mother, a mother injects and feeds her daughters with ricin in a case of munchausen by proxy; she is caught after a daughter dies. in the 2014 movie the interview, a transdermal strip carrying ricin is used in a cia plot to assassinate north korean dictator kim jong-un via handshake.