12 Medical Defense Against Protein Toxin Weapons

The term "toxin weapon" has been used to describe poisons, classically of natural origin but increasingly accessible by modern synthetic methods, which are suitable for delivery on a battlefield in a form that causes death or severe incapacitation at relatively low concentrations (reviewed in ref. I). Several of the most important toxin weapons are proteins, and these molecules are the focus of this chapter. Recent technological changes have increased the importance of protein toxins for biological warfare (BW): (a) progress in biotechnology has made large-scale production and purification feasible for a larger number of protein toxins; (b) molecular biology techniques, especially the polymerase chain reaction, have enabled the identification, isolation and comparison of extended families of previously obscure natural toxins; and (c) gene manipulation and microbiology have greatly expanded the accessible delivery vehicles for protein toxins to include, for example, natural or genetically modified bacteria and engineered viruses. Advances in biotechnology notwithstanding, if we consider only those protein toxins with characteristics suitable for direct use as mass-casualty weapons in the absence of replicating, biological delivery systems, then only a small subset of known proteins are of immediate concern (1). The list of practicable toxin weapons is small because: (a) proteins are not volatile and generally do not persist long in the environment; (b) simple, physical protection offers an effective natural defense against foreign proteins; and (c) relatively sophisticated research, development, testing, and evaluation is required to establish conclusively that each specific protein toxin is a viable open-air, aerosol weapon. Although small in number, toxin weapons should not be neglected. Similarly to chemical weapons or noninfectious biological agents such as anthrax spores, toxins offer the aggressor a tactical weapon to strike at the enemy in a controlled manner that is difficult or impossible with infectious agents, for example by the selective contamination of key terrain or high-value targets. Aerosolized protein toxins can be used both as lethal agents and as severe incapacitating agents, thereby greatly burdening medical