Section C: Ricin
Stephen Traub
RICIN
Ricin is a toxin found in castor beans, which are the seeds of the plant Ricinus communis. Ricin poisons mammalian ribosomes, that part of the cell responsible for protein synthesis. It is extraordinarily potent, with a lethal dose of 500 to 700 micrograms for the average human adult when inhaled or injected. The U.S. Centers for Disease Control (CDC) classifies ricin as a Class B biological terrorism threat (1, 2), identifying it as an agent that can be disseminated with moderate ease and that would be expected to cause significant morbidity.
The processing of castor beans to castor oil, a commonly available consumer product, produces a residue that is rich in ricin. This residue is then heated to deactivate the toxin and used for agricultural purposes. It is conceivable that the residue could be diverted before heating, however, and purified for terrorist purposes.
Ricin is toxic by oral, injected, and inhaled routes. Should ricin ever be used as a weapon of mass destruction, it would most likely be disseminated by aerosolization.
THEORETICAL AND SCIENTIFIC BACKGROUND
MOLECULAR BASIS OF RICIN TOXICITY
Ricin toxin is composed of two protein chains, A and B, which are joined together by a chemical linkage of two sulfur atoms. The ricin A chain produces the biochemical changes that produce cellular toxicity, whereas the ricin B chain governs the entrance of ricin into susceptible cells.
Ricin binds through the B chain to cell surface carbohydrates. These cell surface carbohydrates are ubiquitous within the human body, and thus ricin can bind to and subsequently enter many different types of cells. The exact mechanism by which ricin enters the cell is not completely understood and may involve several different pathways (3).
Once ricin enters the cell, the chemical linkage between the A and B chain is broken. The free A chain then acts as an enzyme that chemically alters mammalian ribosomes (4), rendering them dysfunctional. Because the A chain is an enzyme, which promotes a destructive chemical reaction but is not consumed by it, each ricin A chain molecule is capable of inactivating over 1,000 ribosomes. This, in part, is responsible for ricin’s potency because a single molecule can disrupt the protein-synthesis machinery of a cell.
Because ribosomes are crucial to normal protein synthesis, their deactivation by ricin disrupts normal cellular function. Cells incapable of producing the proteins crucial to their survival soon die, producing the cascade of symptoms seen in ricin poisoning.
TECHNICAL CONSIDERATIONS REGARDING RICIN AS A WEAPON OF MASS DESTRUCTION
Contamination of food or water supplies could produce epidemic oral ricin poisoning. This mode of attack would likely be less appealing to terrorists, however, because ricin is several orders of magnitude less toxic when administered by the oral route. Inhalation would likely be the route by which bioterrorists would deliver ricin because it can be stored as a powder, aerosolized without losing its biological activity, and is extremely potent when delivered in this fashion. Although injection can produce severe morbidity and mortality, obvious technical barriers make the use of ricin by this route as a weapon of mass destruction unlikely.
This does not mean it cannot be used by this route as an agent of terror or murder, however. Georgi Markov was an exiled Bulgarian dissident living in London during the height of the Cold War, who was broadcasting scathing anti-Soviet views on the BBC. He was almost assuredly assassinated by a ricin-containing pellet, delivered by means of a modified umbrella (5).
SIGNS AND SYMPTOMS
The signs and symptoms of ricin poisoning depend on the mode of exposure. Scenarios involving oral, injected, and inhaled poisoning are all possible.
Oral. The symptoms encountered in epidemic oral ricin toxicity would likely resemble cases of castor bean ingestion reported in the medical literature (6, 7, 8, 9). As such, health care providers should expect to see abdominal pain, nausea, vomiting, and diarrhea occurring within several hours of ingestion; the vomiting and diarrhea may be bloody. This initial gastrointestinal phase may be followed by hypovolemia and circulatory collapse. Hepatotoxicity may occur several days later in moderate to severe cases.
Inhalation. Ricin might be aerosolized for use as a bioweapon. In humans, fulminant inhalational ricin toxicity
has not been reported. Inhalational ricin toxicity has been studied in animals, however (10, 11), and human inhalational ricin poisoning would likely resemble the symptoms seen in these experimental models. Health care providers should expect to see toxicity developing several hours after exposure. This dose-related toxicity may range from a simple cough in cases of trivial exposure to pulmonary edema and acute respiratory failure in more severe cases.
has not been reported. Inhalational ricin toxicity has been studied in animals, however (10, 11), and human inhalational ricin poisoning would likely resemble the symptoms seen in these experimental models. Health care providers should expect to see toxicity developing several hours after exposure. This dose-related toxicity may range from a simple cough in cases of trivial exposure to pulmonary edema and acute respiratory failure in more severe cases.
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