INTRODUCTION
The global medical botulinum toxin market is currently valued at 5.8 billion USD and is expected to rise to 15 billion USD by the year 2030.1 From its beginnings as a deadly food-borne toxin, botulinum toxin (BoNT) has had a revolutionary journey to its current powerful and versatile iteration, with indications for numerous cosmetic and medical applications.2-4 As future strides are made in novel uses and approvals for BoNT,5-7 it is worth remembering the historical foundation on which we stand, from the isolation of the toxin to the remarkable experiments that ultimately led to its pervasive medical use, summarized in Table 1.
1) Outbreaks of food poisoning led to the seminal discovery and isolation of the toxin (1793-1920s)
Commentary
The history of BoNT can be viewed as four distinct transformational stages:
1) Outbreaks of food poisoning led to the seminal discovery and isolation of the toxin (1793-1920s)
From the late 1700s to the early 1900s, multiple food-associated epidemics occurred across Europe and the United States of yet unknown cause, with numerous fatalities. Through experiments on animals and himself, Dr Justinius Kerner of Germany was the first to surmise the ultimate source of a sausage-poisoning epidemic was a biologic toxin acting on nerve signals to cause multi-organ and respiratory failure.8 Later on, Emile Pierre-Marie van Ermengem in Belgium identified Clostridium botulinum as the bacteria producing the exotoxin, and Dr Hermann Sommer of the US isolated the first crude form of botulinum toxin type A (BoNT-A).9
2) Threat of BoNT use in biological warfare (1940s-1970s)
After the bombing of Pearl Harbor by the Japanese in World War II, the US government placed increased attention on the covert study of wartime threats for offensive and defensive reasons, including the study of lethal toxins and biological agents, due to fears that the Germans were weaponizing such toxins and agents against Americans. A team of scientists including Carl Lamanna, Arthur Guyton, and Edward Schantz worked jointly at the US Biological Warfare Center to culture the first purified stores of BoNT-A and further study its physiologic effects in humans. When fears of the Germans using weaponized botulinum toxin were proven to be unfounded, the Americans abandoned the study of the use of the toxin for warfare.10,11 At the end of World War II in 1945 when the covert toxin experimentation concluded at Camp Detrick, Dr Schantz became the custodian for the remaining stores of purified BoNT-A. Starting in the 1950s and throughout his career after leaving Camp Detrick in 1972, he shared the toxin with qualified physicians and scientists for research purposes, sparking the next stage in the history of botulinum toxin.9 Dr Arnold Burgen in the UK, Dr Vernon Brooks in Canada, and Dr Daniel Drachman in the US performed separate experiments to collectively elucidate the effect of BoNT on neuronal synaptic terminals and its ultimate denervation of muscles through the neuromuscular junction.12-15
After the bombing of Pearl Harbor by the Japanese in World War II, the US government placed increased attention on the covert study of wartime threats for offensive and defensive reasons, including the study of lethal toxins and biological agents, due to fears that the Germans were weaponizing such toxins and agents against Americans. A team of scientists including Carl Lamanna, Arthur Guyton, and Edward Schantz worked jointly at the US Biological Warfare Center to culture the first purified stores of BoNT-A and further study its physiologic effects in humans. When fears of the Germans using weaponized botulinum toxin were proven to be unfounded, the Americans abandoned the study of the use of the toxin for warfare.10,11 At the end of World War II in 1945 when the covert toxin experimentation concluded at Camp Detrick, Dr Schantz became the custodian for the remaining stores of purified BoNT-A. Starting in the 1950s and throughout his career after leaving Camp Detrick in 1972, he shared the toxin with qualified physicians and scientists for research purposes, sparking the next stage in the history of botulinum toxin.9 Dr Arnold Burgen in the UK, Dr Vernon Brooks in Canada, and Dr Daniel Drachman in the US performed separate experiments to collectively elucidate the effect of BoNT on neuronal synaptic terminals and its ultimate denervation of muscles through the neuromuscular junction.12-15
3) Animal and human clinical trials spearheaded by ophthalmologist Dr Alan Scott (1972-1989)
Dr Alan Scott, an ophthalmologist and researcher at the Smith-Kettlewell Eye Research Institute in San Francisco who
