Botox

Historical aspects of botulinum toxin

Introduction
In recent years, the molecular mode of action of the neurotoxins produced by different strains of Clostridium botulinum has been successfully elucidated. [1] [2] Simultaneously, botulinum toxin type A has proved to be effective and safe in the treatment of conditions caused by focal contractions of skeletal muscles, such as strabismus,hemifacial spasm, focal dystonias, spasticity, and some autonomic disorders. [3] [4] [5] [6] [7] [8] [9] [10] [11] Therapeutic chemodenervation with botulinum toxin was pioneered by Alan B. Scott in 1973 with monkey experiments [10] and in 1980 with human applications. [11]
The first accurate and complete description of the clinical symptoms of food-borne botulism was published between 1817 and 1822by the German physician and poet Justinus Kerner (1786-1862) (), who also developed the idea of a possible therapeutic use of botulinum toxin, which he called "sausage poison." Kerner's approach to the problems of food poisoning during the period of enlightenment was a scientific one: after describing and categorizing empirical phenomena, he started animal experiments and clinical experiments onhimself, developed hypotheses on the pathophysiology of the toxin, suggested measures for prevention and treatment of botulism, and, finally, developed visions and ideas about future perspectives regarding the toxin, including the idea of its therapeutic use. It is fascinating to see his ideas being validated over the last 20 years.

Figure 1. Justinus Kerner, age 48. (Crayon painting by O.Muller, 1834.)

The increase in food poisoning in Wurttemberg during the Napoleonic wars between 1795 and 1813.
At the beginning of the 19th century, the medical administration of the Dukedom and later Kingdom of Wurttemberg in Stuttgart noticed an increase in cases of fatal food poisoning throughout the country. The reason was a decline in hygienic measures for rural food production due to thegeneral economic poverty caused by the devastating Napoleonic warfare. In July 1802, the government in Stuttgart issued a public notice and warning about the "harmful consumption of smoked blood-sausages." In August 1811, the medical section of the Department of Internal Affairs of the Kingdom of Wurttemberg again discussed the problem of "sausage poisoning" and regarded it as caused by prussic acid.In the end, the Medical Faculty of the University of Tubingen was asked for advice. The first answer came from the senior of the faculty, Wilhelm Gottfried von Ploucqet (1744-1814), in which he disputed that prussic acid could be the toxic agent in sausages, suspecting a "zoonic, possibly organic poison." [12] [13] In a second statement, one of the important medical professors of the Universityof Tubingen, Johann Heinrich Ferdinand Autenrieth (1772-1835), asked the government to collect the reports of general practitioners and health officers on cases of food poisoning. After Autenrieth had studied these reports, he issued a list of symptoms of the so-called "sausage poisoning" such as gastrointestinal problems, double vision, and mydriasis, and added a comment in which he blamed thehousewives for the poisoning because they did not dunk the sausages long enough in boiling water, trying to prevent the sausages from bursting. [12]
In 1815, a health officer in Herrenberg, J.G. Steinbuch (1770-1818), sent the case reports of seven intoxicated patients who had eaten the same meal (liver sausage and peas) to Professor Autenrieth. Three of the patients had died and the autopsies hadbeen carried out by Steinbuch himself. [14]

Kerner's experiences and publications on botulism--1817, 1820, 1822.
Simultaneously with Steinbuch, the 29-year-old Kerner, then medical officer in a small town, also reported a lethal food poisoning. Autenrieth considered the two reports from Steinbuch and Kerner as accurate and important observations and decided to publish them in 1817 in the...