When the toxin ricin was discovered in the office of Senate Majority Leader Bill Frist in February, prompting three Senate office buildings to be closed, most of the coverage concerning the incident mentioned the strange case of Georgi Markov. And almost all the reporters got a key fact about that case wrong. Following a version stated in many textbooks and references, they claimed that Markov was murdered by ricin, but the means of Markov's death never was established.
In the 1970s, Markov, a Bulgarian novelist and playwright, was living in London and producing anti-Communist radio broadcasts for Radio Free Europe and the BBC. On Sept. 7, 1978, he felt a jab in the back of his right thigh, apparently from an umbrella, while waiting for a bus on Waterloo Bridge. Within hours he became ill, and was admitted to hospital the next day with high fever, leukocytosis (WBC=33,000), and hypotension. Despite treatment for presumed septicemia and shock, he did not respond and died on the third day.
At autopsy, a very small platinum sphere, 1.52 mm in diameter, was found in the subcutaneous tissue of Markov's right thigh. Two tiny perpendicular holes had been bored through the sphere, possibly by a high-tech laser, creating a central cavity able to contain 0.28 cubic mm of toxin. Scientists from the Government Chemical Defense Establishment examined the autopsy specimens. Although government experts felt that ricin was the most likely explanation for Markov's death, they were never able to demonstrate that it was actually present in his body or on the sphere (Brit Med J 1979;1:350).
In fact, if we put aside the Markov affair, there has never been a reported case in all of history of murder by ricin. This is somewhat remarkable because theoretically ricin is extremely powerful. It is often called the most dangerous substance in the plant world, and described as several times more toxic by weight than the nerve agent VX. It also is easy to acquire, at least in crude form.
Ricin is contained in the castor bean plant (Ricinus communis), a shrub native to Africa but now grown in many areas of the world. The toxin is most concentrated in the plant's beans, which have a thick brown mottled shell and are often used to make decorative necklaces and bracelets. Large amounts of castor beans also are processed by industry to make lubricants (e.g., Castrol motor oil), paints and varnishes, synthetic fabrics, and medicinal products. Ricin can be isolated from the fibrous mash that remains after oil is extracted from the beans.
Route of Exposure
The structure of ricin — two peptide chains linked by a disulfide bridge — is similar to those of diphtheria toxin and botulinin. The A peptide is the active toxin that enters into cells, and kills them by shutting down protein synthesis. The B peptide binds to receptors on cell surfaces. Expected clinical syndromes that might be seen after exposure would depend on the route of entry.
Ingestion could produce symptoms similar to severe gastroenteritis, inhalation exposure would produce significant respiratory distress, and parenteral exposure would lead to local necrosis followed by multi-organ failure. (See table.) Because the A peptide enters cells relatively slowly, there may be a delay of up to eight hours between exposure and symptom onset. Fortunately, there are virtually no data concerning human exposure to ricin. It has never been successfully deployed as a biological weapon. Even animal studies are scarce. Workers in plants processing castor beans have become ill after exposure to powder from bean products, but in many cases this may not have been from ricin toxicity. The castor bean also contains a powerful allergen that can cause a range of allergic manifestations, including contact dermatitis, rhinitis, hives, wheezing, and anaphylaxis.
Although the individual emergency physician is not likely to encounter toxicity from exposure to pure ricin in his clinical career, it is not at all rare to see a child who has ingested one or more castor beans or an adult who has chewed and swallowed a number of beans in a suicide attempt. Because intact castor beans are nontoxic, clinical manifestations will depend in part on the number of beans ingested and the extent to which they have been chewed. After a delay of four to eight hours, these patients can present with gastrointestinal symptoms — nausea, vomiting, diarrhea, abdominal pain, and volume depletion.
As with ricin, the severity of exposures to castor beans is frequently overstated. Many references claim that ingestion of one castor bean can be fatal to a young child, although there is actually no such case on record. A recent review identified 424 cases of castor bean ingestion, with 14 deaths from hypovolemic shock. Most of these fatal cases occurred before 1930, with the last death reported in 1950 (Ann Emerg Med 1990;19:1177). This was before the era of modern intensive care and fluid resuscitation.
Because interventions carried out before death in some of these cases included the administration of cocaine, strychnine, ouabain, camphor, calomel, digitalis, and “nutrient enemas,” it is not unreasonable to assume that the treatment itself may have been responsible for some of the fatalities. A brilliant paper by Rauber and Heard critically reappraised the hazards of castor bean ingestion in light of historical experience and modern medical capabilities, and concluded that virtually all of these cases will do well with observation and fluid support (Vet Hum Toxicol 1985;27:498).
Patients who present after castor bean ingestion should be given one dose of activated charcoal and observed for eight hours. Gastric lavage is not justified, even if the patient presents early, because these are virtually never life-threatening situations. In pediatric cases, partially chewed beans may not fit through the holes in a lavage tube. Asymptomatic patients can be medically cleared after eight hours, with discharge instructions to return if any gastrointestinal symptoms occur.