|Justinus Kerner in old age, taken a few years before his death. circa 1860. Taken by Friedrich Brandseph. Scanned from Klaus Günzel: Die deutschen Romantiker. Via Wikimedia.|
Of the various kinds of food poisoning that afflict mankind, botulism is the most dangerous. It has likely occurred for many centuries, as shown by sundry dietary laws such as the prohibition of making blood sausages in the tenth century in the Byzantine Empire. At the end of the eighteenth century several outbreaks of so-called “sausage disease” occurred in southern Germany. In 1815-1817 Justinus Kerner, a medical officer and romantic poet, described the clinical features. In 1870 another German physician, John Muller, called the disease botulism, from botulus, Latin for sausage. Kerner had been prescient in predicting that someday the substance causing this disease will have medicinal applications but was much ahead of his time. For many years the cause of the disease remained a mystery.
The answer came in 1895 from the laboratory of Professor Pierre Emile van Ermengem (1851-1932). Graduating in 1875 from the faculty of medicine in Leuven, Belgium, he later studied in Paris, London, Edinburgh, and Vienna, then also spent time in the laboratory of Robert Koch in Berlin. In 1888 he was appointed Professor in Hygiene and Bacteriology at the State University of Ghent and subsequently became Dean of the Faculty of Medicine.
A fatal dinner
In December 1895 thirty-four members of a music club attended a funeral service in the small village of Ellezelles in Belgium and in the evening were served cured ham at a local pub. Most of them became ill the following day, and eventually three young musicians died and ten others were described as having been in “mortal danger.”
After the meal, they all noted nausea, vomiting, and colicky pains. Disturbances of vision followed 36 to 48 hours later, with objects appearing indistinctly, like through a mist. Ptosis and complete immobility of the eyeball was noted in some, also double vision, with pupils markedly dilated and unreactive to light. Some had no secretion of saliva, mucous membranes were dry and shiny, and the voice muffled, sounding as if “the tongue was half paralyzed.” Those worst afflicted could not speak at all. Some had croup-like symptoms and trouble urinating. Consciousness was not impaired, but all were so weak that they were confined to bed for several weeks.
After some three weeks the eye symptoms began to improve. The dilatation of the pupils subsided; near vision became more distinct, and it became possible to read with glasses. Normal vision returned after six to eight months and swallowing problems, abnormal salivation, and the other symptoms also subsided.
From the outset cured ham figured as the prime suspect. Those who had not eaten it were not affected, but some not present at the dinner and ate it later also fell ill. A judicial inquiry was set up. The innkeeper who had sold the hams and cut them up testified he had observed no changes in the meat and no abnormal smell. The meat had been salted twenty-four hours after slaughter, and the salting had taken place in the usual manner. Autopsies of the victims provided no useful clues.
The hams were carefully examined in the laboratory of Professor Van Ermengem at the State University of Ghent. Histological sections were studied, and different parts of the specimens were cultured. Cultures for aerobic organisms were negative, but those for anaerobic culture revealed a large number of microorganisms. On microscopy, groups of small, elongated, ellipsoidal, refringent bodies were seen between the muscle bundles and were interpreted as being the free spores of the bacteria. Experiments with extracts obtained from the hams produced paralysis in several species of animals, therefore fulfilling Koch’s postulates.
It was thus established that the disease was caused by a Gram-positive bacillus anaerobic organism, first named Bacillus botulinum, later changed to Clostridium botulinum. Found in water, soil, the intestines of animals, and certain foods, it has eight serological types named A to H, all producing spores that may secrete a toxin. Heat destroys the bacteria and their spores but not the toxin. Foodborne disease is caused by ingesting the toxin present in improperly prepared food, notably canned produce. Wound botulism occurs when infected wounds become contaminated with Clostridium spores that germinate under anaerobic conditions and release their toxin. Rare forms occur in infants when toxins are absorbed from their immature intestines (floppy baby syndrome) and also in some adults with intestinal abnormalities.
Botulism has been described not only in man but also in horses, donkeys, and other animals. The toxin acts by irreversibly blocking the release of acetylcholine at the cholinergic neuromuscular junctions. Cranial nerves are especially affected, hence the predominance of visual symptoms, but the poison may also affect the innervation of skeletal muscles and cause respiratory paralysis. Once the nerves have been depleted of acetylcholine, new material has to be synthesized, hence the slow recovery from the disease. Each year episodes of botulism are reported, both in developed and developing countries. In man, mortality is about 5%, from respiratory failure, more so in the absence of appropriate treatment. An antidote destroys the toxin and may be used to prevent the worsening of symptoms but will not reverse existing nerve damage.
Botulinum is the most poisonous biological substance known to man. Efforts to purify it began in the 1920s but were not successful until Dr. Edward J. Schantz, working at Camp Detrick in Maryland, purified type A toxin in crystalline form in 1946. It was first used in clinical medicine in the early 1970s by Alan B. Scott of San Francisco, who began experimenting with chemodenervation of the extraocular muscles as an alternative to surgery. He established, first in animal experiments and then in clinical trials, that injecting botulinum toxin (Botox, Allergan) was the most effective method to paralyze a muscle temporarily. He also showed that this powerful neurotoxin could be used safely in a highly diluted solution. In 1989 Botox was approved by the FDA for treating strabismus and blepharospasm. Over the years it became known as the “miracle poison” and now is used to treat muscular spasms after strokes; spinal cord injury; cerebral palsy; spasms of the head, neck, eyelids, vocal cords, esophagus, vagina, anus, and bladder; urinary incontinence; excessive sweating; and prevention of migraines.
In 1987, in the course of using Botox to treat strabismus, Drs. Jean and Alastair Carruthers discovered accidentally that when they used Botox the crow’s feet lines around the eyes and wrinkles in the face smoothed out or disappeared. This was the beginning of the use of Botox in plastic surgery, which so exploded that in 2018 more than seven million people received botulinum injections.
The history of botulism exemplifies the slow process by which medical knowledge advances. Clinical descriptions of a disease come first, followed later by the discovery of how it is caused. Therapeutic advances require a better understanding of physiology and pathology but are often made serendipitously. They thus confirm Pasteur’s adages that genius is one percent inspiration and ninety-nine percent perspiration; but also that although many great advances are made by accident, “chance favors the prepared mind.”
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GEORGE DUNEA, MD, Editor-in-Chief