Botulinum Toxin: A Bioterrorism Weapon

Botulinum toxin, one of the most toxic poisons known, is derived from the spore-forming bacteria Clostridium botulinum. This bacteria occurs naturally in forest soils, lake and stream sediments and the intestinal tracts of some fish and animals. Botulinum toxin gained public attention after a vial of the bacteria was found by investigators in Iraq after the ouster of Saddam Hussein. At the end of the 1991 Gulf War, Iraq claimed it had produced 19,000 liters of the toxin; if true, it was an amount capable of killing the entire population of the earth.1 Botulinum toxin is also in the news because it is the ingredient in Botox, the much-publicized injection used to remove wrinkles and reduce aging effects.

What Is Botulinum Toxin?

Clostridium botulinum belongs to a family of Gram-positive bacteria that are capable of existing both as rod-shaped bacterial cells and as spores. Spores are heat-resistant and can survive in food that is improperly or minimally processed. The toxin produced by the bacteria is an enzymatic zinc-containing protein that breaks up one of the proteins involved in the release of acetylcholine into the neuromuscular junction. It is thus a potent and fast-acting neurotoxin. It is listed as "the most toxic substance known."2 It is estimated that a single gram of pure crystalline toxin, evenly dispersed and inhaled, could kill as many as one million people.3 However, such a dissemination would be technically unfeasible, since an effective mechanism for producing a large aerosol of botulinum has not been successfully developed.3

Botulinum toxin can be absorbed through the gastrointestinal or respiratory tracts; however, it is not absorbed by intact skin. The estimated lethal dose for a 91-kg (200-pound) person is 0.9–1.2 micrograms per kilogram by inhalation, and approximately 90 micrograms per kilogram by oral ingestion.4 Symptoms of botulinum toxin poisoning can occur within as little as two hours of exposure, or as late as eight days after.4

The toxin is a white crystalline solid; in liquid form, it is odorless, colorless and (as far as known) tasteless.3 The toxin is a protein and is sensitive to heat; it is destroyed when exposed to temperatures above 176ºF (80ºC) for a

10-minute period.5 Thus the toxin does not survive in foods that are properly cooked during preparation. The spores are more heat-resistant and can survive higher temperatures and longer periods of heating. Most naturally occurring outbreaks have resulted from eating improperly cooked foods like home-preserved foods, canned meats and cream cheese, or raw vegetables and fruits. Natural outbreaks are rare, but occur in the U.S. an average of 20 times per year and are distributed throughout all 50 states.6

Based on antigenic specificity, seven subtypes of botulinum toxin are recognized. Types A, B, E and F cause disease in humans. Types C and D cause cases mostly in animals and poultry. Type G, isolated from soil samples in Argentina, is not known to have caused any outbreaks to date.5

Botulinum Toxin as a Weapon

Since the 9/11 and anthrax letter events in 2001, the possibility of a biological attack on this country by terrorists has become an unfortunate reality. Botulinum toxin has always been on the list of top bioweapon candidate agents, because of its extremely high toxicity: 50–100 times more toxic orally than sodium cyanide. The bacteria are easy to grow, and the toxin is relatively easy to produce in large quantities. This makes it a prime candidate for the bioterrorist's arsenal. The U.S. and Russia gave up trying to utilize botulinum because it could not be effectively "weaponized" like anthrax and smallpox. Weaponizing a bio-agent is a complex, multi-stage process. The final stage of weaponizing entails binding the bacteria to ultra-finely powdered materials like bentonite or silica gel. This allows the material to stay suspended, forming a stable aerosol vehicle for dissemination.7 However, studies done by the U.S. military indicate that a point-source aerosol release of weaponized botulinum toxin could incapacitate or even kill 10% of the people downwind for a distance of one-third of a mile (1.760 feet).7 Such a release in a subway, shopping mall or a large enclosed event like a basketball game would have a major impact on a city, especially if multiple releases occurred at different locations simultaneously.