Doctor administering a vaccine

Ricin Intoxication

Ricin is a Biothreat

Ricin toxin is one of the most potent poisons known. It is easily manufactured from mash from local castor bean production or as a byproduct from castor oil production, making it a Category B Biothreat agent. Ricin acts by shutting down protein synthesis within any mammalian cell it comes in contact with, causing cell death. Because ricin can penetrate cells within 4 hours of exposure, its effects are rapidly irreversible. There are no prophylactic or therapeutic treatments for ricin intoxication. Current research has identified that a vaccination approach can be effective at preventing serious side effects and death due to ricin exposure, while therapeutic treatments must be administered within 4 hours of exposure to have significant efficacy. In the context of a bioattack the 4 hour window is considered too short a time in which to both identify the causative agent and obtain and deliver an effective treatment. Vaccination, aimed at warfighters and emergency first responders in particular, may be effective at preventing serious injury and death after ricin exposure.

What is Ricin Poisoning?

Ricin is an easily produced, stable white powder. It can be delivered by injection, by ingestion or by inhalation. Inhalation is considered the most lethal route of administration, capable of targeting the largest potential population at one time.

Ricin is one of the most potent poisons known.

How does ricin kill cells?

Ricin toxin is made up of two covalently linked protein subunits, each of which has a different role:

  1. The Ricin Toxin A chain (RTA) is a ribosome inhibiting protein which blocks protein synthesis within the cell. Even one molecule of ricin within a cell can shut down all protein synthesis. Without protein synthesis, the affected cell dies. Once RTA is inside the cell, there is no known way to remove and/or block its effects.
  2. The Ricin Toxin B chain (RTB) is known as a lectin protein. Its primary role is to cause the toxin to be taken into a mammalian cell.

The combined effects of the A and B chains give ricin its extreme potency – rapid cell penetration is governed by the B chain while subsequent toxicity is driven by the A chain.

Symptoms of Ricin Intoxication

Ricin kills any mammalian cells it comes in contact with and, therefore, initial symptoms of ricin poisoning are dependent on the route of exposure. In all cases, individuals may be symptom free for the first few hours or days depending on exposure level. Ultimately though, sufficient exposure to ricin results in death through organ failure.

Inhalation of ricin toxin may cause any of the following symptoms:

  • Difficulty breathing
  • Fever
  • Cough
  • Nausea
  • Sweating
  • Ultimately, low blood pressure, fluid in the lungs and respiratory failure may occur, leading to death

Injection with ricin toxin may cause any of the following symptoms:

  • Local tissue injury in the tissue and muscle
  • Swollen lymph nodes
  • Dehydration
  • Liver, kidney or spleen failure
  • Ultimately, multi-organ failure can lead to death

Ingestion of ricin toxin requires exposure to larger amounts of ricin. Initial symptoms might include:

  • Vomiting
  • Diarrhea (including bloody diarrhea)
  • Dehydration
  • Hallucinations
  • Seizures
  • Blood in urine
  • Ultimately, multi-organ failure can lead to death

What is the Risk of Ricin Poisoning?

Ricin has a long history of use in espionage and warfare. Economic surveys have shown that there are over 1 million tons of castor beans produced in the world annually. Ricin toxin can constitute up to 5 percent of the total protein of the bean. The global commercial production has the potential to yield approximately 50,000 tons of pure ricin. The fate of much of this ricin in countries outside of the US is unknown.

Ricin is highly stable at room temperature and difficult to inactivate by conventional methods. Because of the high content of ricin in castor beans, ricin toxin can be extracted from the mash produced as a by-product of castor oil production by several simple enrichment steps, and is therefore easy to stockpile.

While ricin is second in toxicity only to botulinum toxin, it is far easier to obtain, prepare, and use. Before the 1990 war, the Iraqi military had attempted to devise ways to disseminate ricin as an explosive bomb. These attempts were forestalled by the war and ensuing events.

Ricin has also been detected in a powder form sent in a letter addressed to Senator Bill Frist in 2004, and several other similar but less publicized incidents. More recently, there have been sporadic reports of ricin stockpiles and attempted use of ricin in the US and Europe.

Once exposed to lethal doses of ricin, the effects are essentially irreversible. The current expectation that drives vaccine development is that ricin is most likely to be distributed as an aerosol form, since it is highly lethal by this route.

Treatment Options

There are NO FDA-approved prophylactic or post-exposure therapies for ricin toxin exposure. If ricin exposure is suspected, immediate medical attention should be sought, as early supportive care to mitigate the symptoms from organ damage may be needed, including respiratory support, intravenous fluids and medications to treat seizures and low blood pressure.

Where Soligenix Comes in

Recognizing that treatment options are limited due to the rapid onset of irreversible symptoms, Soligenix is developing a ricin toxin vaccine, RiVax®, which can be administered to warfighters, emergency first responders and other individuals considered to be at risk for ricin exposure.

Soligenix is the world leader in ricin toxin vaccine development.

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