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Botulism the deadliest toxin

Thailand, 1998. Six people are admitted to the emergency room of a provincial hospital. Seven more are admitted the next day. All thirteen are determined to have eaten from the same batch of home-canned bamboo shoots.
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Thailand, 1998. Six people are admitted to the emergency room of a provincial hospital. Seven more are admitted the next day.

All thirteen are determined to have eaten from the same batch of home-canned bamboo shoots. They were all experiencing difficulty in speaking and swallowing, and were suffering from blurry vision. Two of the 13 patients died.

Arizona, 2012. Eight prison inmates are admitted to the infirmary in November with specific neurological symptoms. This was after four inmates had been hospitalized the previous August.

All of the inmates were reported to have been consuming pruno, an illicitly brewed alcoholic beverage.

Vancouver, 1985. Twenty-one patients were admitted to hospital experiencing various stages of paralysis. They each consumed a brand of liquid garlic used in a beef dip served at a local restaurant.

All of the restaurant patrons survived but four spent an extended period on respirators. The incident led to changes in regulations for garlic extracts by Health Canada.

All of these cases are outbreaks of botulism or "sausage poisoning" as it was originally termed. The disease is a result of a toxin produced by the bacterium Clostridium botulinum, a very common bacteria found around the world and in a wide variety of environments.

The name arises from the first incidence that was seriously studied. In 1793 Wildbad, Germany thirteen locals became sick and six died after eating a locally produced blood sausage. The disease had a long standing association with sausage dating back to Roman times.

By 1829, the regional health officer, Justinius Kerner, had described 230 more cases, most of which were associated with eating badly prepared versions of sausage. The name botulism stuck.

However, the bacterium can grow in any number of food items - from bamboo shoots to garlic-in-oil to illegal prison hooch to canned peas to rotting fish heads. The only requirements for botulism to develop are moderate temperatures and an anaerobic environment. The toxin is only produced when the bacterium is exposed to low oxygen levels.

There are actually seven distinct immunological toxins. They are denoted A to G, with humans being susceptible to A, B, E, F, and G. We are resistant to types C and D but these can affect other species such as squids, birds, and mammals.

The tetanus toxin is also produced by Clostridium bacteria - C. tetani in this case - and it resembles the botulism toxin in many of its structural properties along with its function.

Both botulism and tetanus toxins affect the neurotransmitters involved in muscle contraction. However, tetanus toxin blocks the transmitters in the central nervous system while the botulism toxins act on the peripheral nervous system.

The botulism toxins are proteins and would be susceptible to destruction by proteases in the stomach. However, when complexed with other proteins, they sneak through the stomach to the small intestine where the toxins are absorbed. Once in the blood, the toxins move to the peripheral nerves.

The toxins specifically catalyse the degradation of selective pre-synaptic proteins. The toxins enter motor neurons through the synaptic cleft and, once inside, block the actions of acetylcholine.

Motor neurons cause muscles to fire based on the release of acetylcholine from vesicles in the nerve ending. Each vesicle holds approximately 10,000 molecules of acetylcholine - think of a vesicle as a bag of molecules.

The strength of a muscle contraction is based on the number and frequency of vesicles that are emptied into the synapse. The more acetylcholine, the stronger the contraction.

The botulism toxins all block acetylcholine release but in different ways. For example, B,D, and F all result in a desynchronization of the acetylcholine release. The result is a potential insufficient to cause the muscle to contract. An analogy would be comparing a murmur to a shout.

There is evidence that all of the toxins act as proteolytic enzymes - compounds which break down proteins. It is their actions on various proteins which inhibit vesicle release and disconnect the nerve ending from the muscles.

These perfectly natural toxins are the most deadly compounds known. A dose as small as 10 ng can kill a 100 kg human being. The toxicity range is between 0.1 and 1.0 ng per kilogram of body weight. To put that in perspective, 1 nanogram is 0.000000001 g.

However, the toxins have found use in medicine. They are used to treat a variety of conditions resulting from sustained muscle contraction or spasm, collectively known as dystonias. Their use depends on being able to disconnect the muscle for the stimulating nerve ending.

Botulism toxin was first used therapeutically in 1973 to correct strabismus or squint in a patient by injecting into the muscles of the eye. Since then, injections have been used to treat ailments from cross eyes to protruding eyeballs to blurred vision.

Even a naturally occurring and deadly toxin can have a good side.