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Hyaluronic acid and Botox are arguably the two most popular products in the medical aesthetic industry today.
However, compared to hyaluronic acid, Botox can be described as both angel and devil. According to toxicological theory, just 1g of botulinum toxin could kill 1.5 million people. How was this potent biological toxin discovered? And how did it transform from a ‘devilish’ toxin into a ‘beauty-making’ agent? The answer lies in the formation of the Napoleonic Wars.
Part 01. Discovery process
In the late 18th and early 19th centuries, parts of Germany near the French border were impoverished due to the Napoleonic Wars. In Baden-Württemberg, which is located on the eastern bank of the Rhine, food was scarce and safety standards were declining. This led to a growing number of cases of food poisoning. Thirteen people in the village of Wildbart were poisoned in 1793, six of whom died. All of the victims had dilated pupils. Initially, doctors believed that the victims had ingested belladonna, but as more cases of poisoning with similar symptoms emerged, investigators discovered that they had all consumed a local delicacy: blood sausage. In light of these events, the Stuttgart Royal Government issued a warning in 1802 about the dangers of blood sausage. However, as the warning did not specify the toxic components, enthusiasm for blood sausage did not diminish.
In August 1811, faced with a steady stream of patients, the government resumed its investigation into blood poisoning of the intestines. While officials found the symptoms to be similar to those of hydrogen cyanide poisoning, Professor William Prukett of the University of Tübingen’s medical school questioned this, arguing that it was an organic poison derived from animals. John Ottenritt, one of the most influential medical professors at the university, supported the investigation and urged the government to collect as many cases of poisoning as possible. Justin Kenner, one of the medical officers who provided cases to Ottenritt, provided a complete description of symptoms, including diarrhoea, stomach cramps, vomiting, dilated pupils, respiratory muscle paralysis, dry mouth, general weakness and decreased sweating. He observed seventy-six patients and found that the primary causes of death were respiratory and cardiac failure.
To further understand why sausages were so poisonous, Kenner ingested a portion of the water-soluble extract in 1821. It tasted slightly sour, and just a few drops caused extreme dryness of the mouth and throat. Kenner believed that the toxin in the sausage was produced under anaerobic conditions due to spoilage, and that it was a biological substance acting on the nervous system — even small amounts could be fatal. Kenner also discovered that the toxin blocked the transmission of signals from the peripheral and autonomic nerves. Conversely, he thought it could perhaps be used to calm overexcited patients. Unfortunately, after several experiments, he was unable to successfully extract and isolate the toxin. In 1869, the German physician Johann Müller coined the term ‘botulism’ to describe the illness caused by sausage poisoning. However, the origin of the toxin remained unknown at this time.
It wasn’t until 1897 that the Belgian microbiologist Elmengen published his paper on the new bacteria, and it all began with a funeral. On 14 December 1895, a significant event took place in Ellezelles, a small Belgian village of just 4,000 people. At the funeral of an 87-year-old man, the local brass band, the Friends of Reunion, performed. Afterwards, as was their custom, the 34 musicians went to a tavern for a meal where they ate red meat and smoked ham. Afterwards, they all developed symptoms such as dilated pupils, difficulty swallowing and slurred speech. As their condition worsened, three of the musicians eventually died.
During autopsies, Ghent University microbiology professor Elmengen discovered traces of numerous anaerobic microorganisms and successfully isolated a new bacterium from ham. He named this bacterium Clostridium botulinum. However, in 1917, the American Bacteriological Society found that it matched the characteristics of the Clostridium genus more closely. Thus, the term Clostridium botulinum officially appeared, and aside from its professional academic application, it is generally abbreviated as botulinum.
Returning to Elmengen’s research, he conducted experiments on animals using isolated bacterial cultures, ham extracts and bacterial toxins. He discovered that the bacteria themselves did not cause poisoning, but rather released the world’s most potent toxin: botulinum toxin.
Initially, it was believed that Clostridium botulinum could only be found in meat. However, a poisoning incident involving canned white beans occurred in Germany in 1904. Of the 21 people affected, 11 exhibited classic symptoms of botulism and died. In 1910, German scientist Reichs discovered that the bacteria isolated from white beans and Elrdler ham were different strains, with different toxins, by comparing them. In 1919, Georg Nabke, a professor at Stanford University, named these two types of Clostridium botulinum A and B respectively, which furthered research into botulism.
Part 02. Medical Applications
In the 1970s, various anaesthetics and neurotoxins had failed to resolve the recurring problem of strabismus. Inspired by Daniel Drachman’s research on chicks at Johns Hopkins University, American ophthalmologist Alan Scott and his colleagues injected type A botulinum toxin into the extraocular muscles of monkeys in their strabismus research. They discovered that a very small amount of botulinum toxin could cause paralysis limited to the target muscle with no side effects and a long duration. This marked the first application of botulinum toxin in the medical field. In 1977, Scott began injecting the toxin into patients with strabismus, and by 1980 he had reported that type A botulinum toxin could be used to treat the condition in infants.
Botulinum toxin type A was approved for pharmaceutical use by the FDA in 1989. Its use in medical applications is subject to extremely rigorous principles of low dosage, high precision and strict control of the total amount. Treatment plans are adjusted according to individual patients and the diseases being treated. For instance, in the treatment of strabismus, botulinum toxin is typically diluted with a 0.9% sodium chloride solution to a concentration of between 2.5 and 5 units per millilitre. It is then injected precisely into the target muscles at multiple points to avoid affecting peripheral nerve function. Here, ‘u’ represents a botulinum toxin unit. One unit of botulinum toxin, when injected intraperitoneally into mice weighing 18–20g, is the generally accepted toxicological standard, resulting in a 50% mortality rate. The median lethal dose (LD₅₀) for a 70 kg adult male is approximately 5,000 units. Just one gram of the commonly used type A/B botulinum toxin can easily kill approximately one million people. For a 70-kilogram adult male, an intravenous injection of just 0.09–0.15 micrograms of pure crystalline type A/B botulinum toxin can be fatal, as can inhaling 0.8–0.9 micrograms or ingesting 70 micrograms.
These figures are inferred from primate studies. In other studies based on human cases and using mouse bioassays to quantify toxins, however, the figures are much lower.
Part 03. Cosmetic Injections
After discovering that botulinum toxin type A could be used to treat strabismus in infants, American plastic surgeon Dr Clark tried using it to treat complications arising from cosmetic surgery. In 1987, one of Dr Clark’s patients experienced left-sided forehead paralysis following a facelift, leaving only the muscles on the right side functioning normally. This resulted in drooping left eyebrows, raised right eyebrows and deep wrinkles on the right side of the forehead. Dr Clark successfully corrected the patient’s facial asymmetry using botulinum toxin, publishing the first specific treatment plan for wrinkle removal in the journal Plastic and Reconstructive Surgery in 1989. This marked the first application of botulinum toxin in the field of cosmetic surgery. In 2002, the FDA approved botulinum toxin type A for improving moderate to severe frown lines, and botulinum toxin type B was soon proven to be effective for cosmetic purposes too.
A wide variety of Botox brands are currently available on the market, making Botox injections a common cosmetic procedure. They are not only used for removing wrinkles, but also for slimming the face and shoulders. Different brands of Botox have different cosmetic applications. For example, the popular American brand – BOTOX is highly pure and has low diffusion, when used alongside meso needles for injection, it can effectively and precisely remove wrinkles around the eyes and on the forehead. The Chinese brand Hengli has a wider diffusion range, making it more suitable for leg slimming. Regardless of the type of Botox used, the dosage for cosmetic procedures is strictly controlled and multiple injections are required, with the amount varying depending on the area being treated.
Wrinkle removal usually requires only 5 to 25 units. To slim the masseter muscle on one side, 20–30 units are needed. For larger muscle areas, such as the shoulders or legs, some doctors opt for micro cannula injections rather than meso needles. 50 to 100 units are required per area. Different brands of botulinum toxin also have different dosage requirements, for example, a small vial of BOTOX typically contains 50 or 100 units of botulinum toxin. The recommended total treatment volume for frown lines is 0.5 ml (20 units). This involves diluting 50 units of vacuum-dried botulinum toxin with a sterile, preservative-free 0.9% sodium chloride solution to achieve a concentration of 4 units. This diluted solution is then injected into five different areas, at a rate of 0.1 ml per area: Two units are injected into the corrugator supercilii muscle on each side, and one unit is injected into the depressor supercilii muscle on each side, for a total of 20 units. This constitutes a complete treatment for frown lines.
According to data from the American Academy of Plastic Surgeons, around four million people in the United States received Botox injections in 2024. The global market size for Botox in cosmetic procedures exceeded ten billion US dollars in 2023. These high profits have led to numerous irregularities in the cosmetic industry. Those considering Botox injections should first choose a reputable institution, ensure that the procedure is performed by a licensed doctor and use brands that are certified by the relevant drug regulatory authority. Illegally smuggled injections cannot pass customs inspection and pose a high safety risk. Some products produced on the South Korean black market and smuggled into China, for example, are cheap, costing only tens of dollars per injection, but are then resold for thousands and can easily lead to poisoning. Most cases of poisoning from injections are iatrogenic, including those from cosmetic and medical aesthetic procedures, and this number is increasing. In March 2023, a report from the German International Health Regulations revealed that 71 cases of iatrogenic botulism had been reported in four European countries, 69 of cases were related to injection.
To date, seven types of Clostridium botulinum have been identified and classified by humans. While they differ in antigenicity and serology, they are structurally similar. Types C and D are toxic only to animals, while type G is rare. Types A, B, E and F primarily affect humans, with type AB being commonly used in commercial and medical applications.
Part 04. Others
Aside from treatments for related diseases and cosmetic purposes, the most common way we come into contact with botulism in everyday life is through what we eat. In an aerobic environment, Clostridium botulinum cannot reproduce or produce toxins. Therefore, fresh ingredients or properly sterilised foods are relatively safe. However, canned cured meats are considered high-risk foods, particularly in countries where a lot of canned food is consumed, such as those in Europe and America. Low-acid canned foods such as carrots, asparagus, green beans, beets and corn are often overlooked and can be even more dangerous than canned meat. Canned vegetables are generally not consumed in Asia. However, many people enjoy canned fruit, and some even make it themselves. When making fruit, canned goods, or pickled foods at home, it is important to pay attention to hygiene, temperature, and storage. Heat treatment may be necessary during the process. Furthermore, commercially available processed meats such as ham, bacon and sausages often contain nitrites or nitrates. These additives are not used to make food salty, but to reduce the growth of Clostridium botulinum and the production of toxins, and to preserve the food.
