Clostridium botulinum is a bacterium found in soils. When it encounters an environment that lacks oxygen (anaerobic), such as the human gut, it grows and releases botulinum toxin. The botulinum neurotoxin (BoNT) produces its effects by inhibiting the release of acetylcholine at the nerve endings causing profound paralysis and eventually death through respiratory failure. However, this same action when used in appropriate doses and in localized muscle groups produces relaxation of muscles.
The history of BoNT began in 1735 when an outbreak of botulinum poisoning was recorded in southwest Germany from the consumption of sausages. In 1820, a German medical officer, Justinus Kerner, gave the first clinical description of “sausage poisoning.” He is credited with observing that the toxin was produced under anaerobic conditions and that only a minute amount is needed to produce the paralyzing effects. Dr. Kerner was the first to suggest that the toxin could have therapeutic uses. However, it was not until 1895 that the bacteria Clostridium botulinum was identified as the causative organism. The word botulinum is derived from the Latin word for sausage, “botulus.”
Botulinum toxin poisoning was a danger in the early days of the canned food industry. Even though canned food was available after the Civil War, it did not become a national industry until the early 1900’s. An outbreak of botulism from California canned olives in late 1919 and early 1920 led to the development of stricter production methods and inspections. During World War II the weaponization of botulinum toxin was developed but never used and the Chemical Corps was disbanded.
The modern medical use of BoNT began in 1980 when Dr. Alan B. Scott injected the toxin in eye muscles to treat a condition called strabismus, where the eyes do not align properly when looking at an object. In December of 1989, the toxin was approved by the FDA for strabismus and blepharospasm (abnormal
twitching of the eyelid). The use of botulinum toxin was popularized in 2002 when the drug Botox was approved to treat skin wrinkles and frown lines. The clinical use of BoNT is mainly for the treatment of abnormal, excessive, or inappropriate muscle contractions, however, the uses continue to expand and include treatment of a variety of ophthalmologic, gastrointestinal, urologic, orthopedic, dermatologic, dental, secretory, and cosmetic conditions. Only a few of the uses are approved by the FDA; most clinical uses are what is called off-label use, though these are supported by research. Off-label uses are those conditions that are not expressly indicated in a medication package insert. More recently there have been other approved uses of BoNT such as in the treatment of migraine headaches, underarm sweating, and muscle pain. Additionally, research is being conducted using the toxin to treat depression.
Other notable instances when toxic substances are used as remedies are Salvarsan (arsphenamine) an arsenic compound used to treat syphilis in the early 1900’s. More recently the venom from the Brazilian pit viper was used to develop the class of drugs known as ACE inhibitors used for hypertension. In fact, lisinopril, an ACE inhibitor, is the most prescribed medication in the USA.
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