CHAPTER 5: The Structural Biology and Biochemistry of the Ricin Toxin and the Military Use and Inhalation Toxicology of Ricin Aerosols¹ Check Access

The US Government has classified the biological agents most commonly associated with military and terrorist use as biological select agents and toxins (BSATs) because of the severe threat that they pose to public health and safety. The agents have become particularly attractive to foreign states and terrorist groups because they are relatively inexpensive to produce and require minimal technical infrastructures. The most widely recognized BSAT is the ricin protein toxin found in the seeds of the castor bean plant Ricinus communis. This chapter reviews the structural biology and biochemistry of the ricin protein, especially in terms of its internalization into eukaryotic host cells and the details of its N-glycosidase activity responsible for inactivating ribosome function in protein synthesis. The chapter also reviews some of the more applied aspects of using the toxin as an offensive weapon, including an account the brief history of ricin weaponization programs during World Wars I and II. Also, because aerosol delivery of appropriately formulated ricin powders is the most effective means for its use as an offensive weapon, there is a sharp focus on the particle dynamics of aerosolized ricin, its aerodynamics within the respiratory tract and the signs, symptoms and inhalation toxicology associated with ricin exposure. Much of the respiratory dynamics and inhalation toxicology information derives from testing laboratory animals, especially nonhuman primates, because human exposures to BSAT aerosols are exceedingly rare. Finally, the expected difficulties and caveats of using aerosolized ricin as an agent of bioterrorism are addressed in the Conclusion section.