Identifying a Killer, 1895

A contaminated ham put bacteriologist Émile Pierre-Marie van Ermengem on the path to discovering the microbe that produces botulinum toxin.

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Catherine Offord

After undergraduate research with spiders at the University of Oxford and graduate research with ants at Princeton University, Catherine left arthropods and academia to become a science writer. She has...

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Jul 1, 2021
Microscopic images showing spores in the Ellezelles ham (left) and rod-shaped bacteria that Émile Pierre-Marie van Ermengem cultured from the meat (right) 
VAN ERMENGEM, 1897

On December 14, 1895, more than 30 brass band musicians sat down to dinner at a pub in the Belgian village of Ellezelles. They’d just played at a funeral, and, as was tradition, had gone to Le Rustic for a meat-heavy meal, complete with a large quantity of smoked and pickled ham. Within 24 hours, almost all of them fell sick with stomach problems, blurred vision, speech difficulties, and even paralysis. A week later, three had died and ten more were critically ill. 

DEADLY OLIVES: The Philadelphia Inquirer in 1919 featured an article about multiple deaths caused by consuming botulinum-tainted olives. Canned and jarred foods contributed to several outbreaks of botulism in the US in the early 20th century: without proper sterilization, sealed containers of nonacidic foods provided the perfect environment for anaerobic bacteria such as Clostridium botulinum to grow. The deaths led to new food safety standards from the Bureau of Chemistry of the US Department of Agriculture (the predecessor of the Food and Drug Administration) that required cans of olives to be blasted with heat for 40 minutes to kill bacterial spores.
THE PHILADELPHIA INQUIRER

Suspicion quickly fell on the ham—musicians who hadn’t eaten it seemed unharmed—and local officials launched a full investigation, including interviews with survivors and background checks on the meat’s origins. Local medics would have suspected botulism, also known as “sausage poisoning,” says Frank Erbguth, a clinical neurologist at Paracelsus Medical University in Nuremberg who has studied the history of the condition. Associated with consumption of certain types of smoked meats and fish, botulism had been characterized earlier in the 19th century by German scientist Justinus Kerner, who identified the action of a toxin of unknown origin that could kill laboratory animals. The German government had also issued public warnings about the illness.

But what exactly caused botulism remained a mystery. Bacterial theories of illness were gaining in popularity at the time, explains Erbguth, so officials invited an expert on the topic from the University of Ghent, Émile Pierre-Marie van Ermengem, to take the case. “He was said to be the most experienced and competent bacteriologist,” Erbguth says. “He went there, took the dead bodies and the ham, and said, ‘Let’s compare [them], maybe there’s a bacterium inside.’”

Sure enough, when van Ermengem made microbial cultures from the two types of samples, he identified an anaerobic, rod-shaped bacterium that produced the potent botulinum toxin. The work “seems to us to demonstrate that the isolated anaerobic bacillus is the cause of the Ellezelles illness,” he wrote in an 1897 report (translated into English in 1979). He added that the toxin could be destroyed with heat. “If the Ellezelles ham had been roasted or boiled before being eaten,” he wrote, “no illness would have resulted.”

This can of soup was part of a batch linked to at least one botulism-related death in the early 1970s. The incident led to the recall of more than one million cans of soup, and an updating of regulations concerning the preparation of low-acid canned foods.

Discovery of the microbe, which van Ermengem called Bacillus botulinus (since renamed Clostridium botulinum), clearly demonstrated what Kerner and others had hypothesized: it wasn’t the food per se that was toxic, but poor storage and preparation that allowed dormant spores of this bacterium to grow and release a biological poison. The work was soon followed by more botulinum discoveries from other scientists. A 1904 outbreak caused by canned beans in Darmstadt, Germany, challenged the prevailing idea that the bacteria only grew on meat or fish. A subsequent comparison of bacteria from the Ellezelles ham and the Darmstadt beans identified two distinct strains of C. botulinum, each with its own toxin. Later research would reveal more toxins, designated by the letters A through H, as well as the mechanism by which the proteins paralyze their victims: by blocking acetylcholine signaling at neuromuscular junctions. 

There are still a handful of botulism cases every year in Germany (and around 100 annually in the US), typically from consuming home-preserved foods—although thanks to an antitoxin developed half a century ago, far fewer people die from it than in the past. Meanwhile, the toxin itself—especially types A and B—has found uses in many fields of research and medicine. The US has researched it as a bioweapon, and in the last couple of decades it’s become widely used in cosmetic procedures under the brand name Botox, among others. Since the 1970s, it’s also been successfully used to treat various muscular and neurological disorders, says Erbguth, who began using it clinically in the 1980s for dystonia and other conditions characterized by muscle spasms or nerve hyperactivity. “Every year, new indications appear” for which botulinum toxin shows therapeutic promise, he adds.

Earlier this year, botulinum researchers met to discuss future directions, such as modifying the toxin’s structure to deliver other drugs to neurons, Erbguth says. Recalling a talk he gave in the 1990s in which he told colleagues, “we have reached the climax of botulinum toxin research,” Erbguth says now: “This was not true. It’s still very interesting.”

Toxins produced by Clostridium botulinum have successfully been used to treat a number of conditions characterized by muscular overactivity. In the early 1970s, for example, clinicians began using injections of botulinum toxin A to treat strabismus; toxin A, and to a lesser extent toxin B, have also been successfully used in various types of focal dystonia, such as blepharospasm, in which a person involuntary scrunches up their face. Effects of the toxin are temporary: while some patients find that their dystonias subside over time or with treatment, people with continuing muscular problems require injections every few months.
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