Journal of Bioterrorism & Biodefense
Open Access

Ricin; Castor bean; Ribosome-inactivating protein; Bioterrorism; Toxin; Cell death; Protein synthesis Inhibition; Immunotoxin

Introduction

Ricin is one of the most toxic naturally occurring substances and is classified as a ribosome-inactivating protein (RIP) [1]. Isolated from Ricinus communis, it remains widely available due to the industrial use of castor oil. Ricin’s ease of extraction and lethality has prompted its classification as a Category B bioterrorism agent by the CDC [2]. Although its molecular properties are well understood, clinical diagnosis, treatment, and preparedness strategies remain challenging.

Description

Structure and chemistry

Ricin is a type 2 RIP composed of two polypeptide chains, the A chain (RTA) and the B chain (RTB), joined by a disulfide bond. The RTA inactivates ribosomes by enzymatic depurination, while the RTB facilitates cellular entry by binding galactose residues on the cell surface [3].

Mechanism of action

After cellular binding via RTB, ricin undergoes endocytosis. The A chain translocates into the cytosol where it cleaves an adenine base from the 28S rRNA of the 60S ribosomal subunit, effectively halting protein synthesis and leading to apoptosis [4].

Routes of exposure

Ricin may enter the body through inhalation, ingestion, injection, or dermal exposure. Inhalation is particularly lethal due to rapid systemic absorption, whereas dermal exposure is less effective unless the skin is compromised [5].

Results

Toxicity data

Ricin's LD₅₀ via inhalation in humans is estimated at 3–5 µg/kg, with oral LD₅₀ in animals ranging from 1–20 mg/kg [6]. The assassination of Bulgarian dissident Georgi Markov in 1978 via ricin-tipped umbrella demonstrated the high lethality of small parenteral doses [7]. Animal studies confirm multi-organ failure and severe pulmonary effects depending on the exposure route [8].

Discussion

Clinical presentation and diagnosis

Symptoms depend on the route of exposure:

• Inhalation: cough, dyspnea, and pulmonary edema
• Ingestion: vomiting, abdominal pain, hemorrhagic diarrhea, hepatic and renal failure
• Injection: localized pain, systemic toxicity

Diagnosis is difficult due to non-specific symptoms. Confirmatory tests include ELISA, mass spectrometry, RT-PCR, and immunohistochemistry [9].

Treatment and management

No approved antidote exists. Management is supportive and includes IV fluids, oxygen supplementation, and symptomatic treatment. Activated charcoal may help if ingestion is recent. Experimental interventions include:

• Monoclonal antibodies targeting ricin A or B chains
• Vaccine candidates like RiVax
• Small molecules disrupting intracellular trafficking of ricin [10]

Ricin as a bioweapon

Ricin has attracted interest for bioweapon development due to its simplicity in production, environmental stability, and high lethality. The U.S. and several other nations have studied ricin in military contexts. Notably, ricin has appeared in domestic terror plots and mail attacks targeting political figures, underscoring the continuing threat [2,6].

Conclusion

Ricin remains a critical focus for biosecurity due to its high toxicity, accessibility, and ease of weaponization. While its molecular mechanism is well characterized, clinical management remains largely supportive. Efforts to develop vaccines and therapeutics must be accelerated. Vigilance in public health preparedness, rapid diagnostic capabilities, and global regulatory oversight are essential to mitigate the threat posed by ricin.