Botulinum Toxins: The Good, The Bad, The Ugly
Clostridium botulinum is a gram-positive, anaerobic bacteria which can produce spores and a dangerous toxin that causes botulism. In food microbiology, it is one of the most dangerous microorganisms due to the botulism toxin that it produces. A lot of studies have been done to identify the presence of Clostridium botulinum within food products and how to effectively stop outbreaks that occur. The potency of the botulinum toxin has also made Clostridium botulinum one of the most tested microorganisms in the area of biological and chemical weapons. Its potential use in bioterrorism has been studied since World War I by some of the most powerful countries in the world. Despite the dangers related to this dangerous toxin, researchers have also investigated the uses of botulinum toxin as a form of medical treatment for various conditions, most famously in dermatology as Botox.
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Clostridium botulinum was discovered just before the turn of the 20th century by a microbiologist named Emile Pierre Van Ermengen who linked a case of what was known at the time as “sausage poisoning” to a spore forming, anaerobic, toxin-producing bacillus (Kopera, 2011). The medical condition of “sausage poisoning” was discovered in the first half of the 19th century by a German physician named Justinus Kerner who investigated numerous cases of food poisoning related to victims eating bad sausages (Kopera, 2011). In Kerner’s initial study and observation of victims, Kerner observed that a toxin in the sausage “interrupts chemical processes of nervous transmission in the same way that rust does not conduct electricity.” (Kopera, 2011). Over the next few years he was able to conclude that the toxin affected the nervous system which in fatal cases would lead to respiratory failure or cardiac failure (Kopera, 2011). Kerner also tried, but failed, to synthesize the toxin, which had he been successful would have been a blueprint into the use of botulinum toxin as a weapon.
Kerner also was able to identify techniques to prevent future outbreaks of the toxin by suggesting that sausages should be stored in dry places, heated through boiling, and that people should not eat sausage that doesn’t look right. Kerner also hypothesized that the toxin could be used in the future for medicinal purposes, but that it would need to be tested. Despite not knowing the microorganism that caused the botulinum toxin, Kerner was able to accurately identify the general mode of action caused by the toxin produced by Clostridium botulinum, the basis for prevention of foodborne intoxication, and correctly hypothesized the uses of the toxin in medicine and therapy. Kerner may have also, unintentionally, identified the potential use of botulinum toxin as a biological weapon in his attempts to synthesize the toxin, although it is likely that someone else would have discovered it later in history.
Botulinum Toxin: The Bad
One of the major concerns in foodborne illnesses is the botulinum toxin that is produced by Clostridium botulinum. Most commonly, the toxin is associated with improperly home canned foods. Poor heating techniques can leave behind spores produced by C. botulinum which, when put into an anaerobic environment, can revert to the vegetative state and produce the botulinum toxin. Clostridium botulinum is present in most environments but are mostly found in soil and the intestinal tracts of animals (Bintsis, 2017). Because of its abundance in soil C. botulinum outbreaks can occur frequently with fruits and vegetables that are canned and because of the abundance in animal intestinal tracts it has caused toxin production in meats like sausage (Bintsis, 2017).
Foodborne outbreaks of the botulinum toxin typically cause damaging effects on human health. Within two days of consumption, symptoms can begin to present as nausea and vomiting. Soon after, the neurological effects of the toxin can begin. These include facial and muscle paralysis that can extend down to the lungs, which can lead to respiratory failure and death (Bintsis, 2017). In cases that progress to respiratory failure, medical intubation is required to help patients breathe. Multiple case studies have been done on foodborne outbreaks that have occurred that required extended intubation and hospitalization.
One such case study that was done by Forss, et al, identified two women that were admitted to the hospital within three days of each other with stroke-like symptoms. The first patient was an elderly woman who presented neurological symptoms consistent with a stroke. Extensive imaging did not show any abnormal signs and within 12 hours of symptoms the patient could not speak or swallow. Further tests were done when the patient required intubation that led to the diagnosis of botulism and the antitoxin was administered three days past the beginning of symptoms. Despite the administration of the antitoxin and intubation the patient died. The second case involved a 29-year old female relative that was admitted three days after the first patient. The second patient also presented with stroke-like symptoms. The patient was administered the antitoxin and required assisted ventilation for three weeks. The main conclusion of the study was that the administration of the botulinum antitoxin is required as soon as possible to increase chances of patient survival.
Botulinum Toxin: The Good
Perhaps the most known use of botulinum toxin as a treatment is the dermatological use of Botox. The procedure involves injecting a small quantity of botulinum toxin into the skin to stop facial wrinkles. The injected toxin blocks signals to the muscles and causes them to relax, which allows for the smoothing of wrinkles (Sifferlin, 2017). The process is generally safe when administered by experts, although there are cases that cause infections. As of 2017, there had been 12.2 billion doses administer in 25 years (Sifferlin, 2017). Botulinum toxin has also been used in other dermatological aspects such as scar prevention, facial flushing, and to treat the chronic complications of herpes zoster (Yoon Seob Kim, et al. 2017). The field of dermatology is not the only one that is experimenting with the use of botulinum toxin.
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Some of the conditions that botulinum toxin has been experimented on in recent years include; chronic migraines, plantar fasciitis, overactive bladder, forefoot equinus in cerebral palsy, essential tremors, tennis elbow, excessive sweating, muscle spasms, and spastic equinovarus deformity in stroke patients (Harvey, 2014). With these conditions, the botulinum toxin works to block efferent neurons which signals muscular contractions (Harvey, 2014). Medical professionals are continuously using small amounts of botulism toxin to treat an ever-growing list of conditions. Botox is now starting to be used off-label to treat an even wider array of medical conditions such as teeth grinding, premature ejaculation, back pain, Parkinson’s disease, anal fissures/ulcers, and even depression (Sifferlin, 2017).
Botulinum Toxin: The Ugly
Besides the dangers of botulinum toxin in food, the potential use of the toxin in bioterrorism is a major concern. The potency of the dangerous neurotoxin means that if it were to be weaponized it could potentially kill millions of people. To better understand the danger of botulinum toxin as a bioweapon, it is important to note that after the Persian Gulf War, Iraq admitted to producing 19,000 liters of concentrated botulinum toxin (Arnon, 2001). That amount of botulinum toxin was estimated to be three times the amount needed to kill the entire world’s population (Arnon, 2001). The toxin produced by Clostridium botulinum is about 100,000 times more toxin than sarin, which has been used in terrorist acts (Pita, 2014).
There have already been unsuccessful terrorist attacks that have attempted to aerosolize the botulinum toxin, which took place in the 1990s in Japan using extracted Clostridium botulinum from soil (Pita, 2014). The biggest reason why we haven’t seen a successful large-scale terrorist attack using this toxin is likely because of its difficulty to be effectively aerosolized, which would potentially be the most lethal way of distributing the toxin to the mass public. Some research has been done to identify other potential ways that the toxin could be administered to the public in a terror attack.
One such study was the capability of botulinum toxin to be administered to different stages of milk pasteurization. Despite the pasteurization high heat process, enough of the toxin is capable of surviving and reaching the bottling stage in commercially sold milk to cause a mass casualty event. In a study done by Wein and Liu in 2005, using just one 50,000-gallon milk silo tank over a 72-hour period, enough toxin could be present in the milk to affect roughly 568,000 consumers. With 1g of undetected toxin the number of causalities with 3-6 days could be up to 100,000 people, and with 10g of undetected surviving toxin, up to the entire 568,000 affected population could be casualties. The model used to predict the number of potential casualties presented different outcomes based on the amount of neurotoxin that goes undetected in the milk production, which can be seen in Figure 1 below. This figure shows how drastically the casualty numbers increase with each tenfold increase in surviving botulinum toxin in just one 50,000-gallon milk silo over a 72-hour period (Wein and Liu, 2005). The dangers of botulinum toxin as a biological weapon are a real concern for the future, and one that could present itself in a successful terrorist attack or in warfare as more is learned about how to best use the toxin as a weapon.
Figure 1, Mean poisoned population over time at different levels of undetected botulinum toxin from one 50,000-gallon milk silo producing milk over a 72-hour period. (Wein and Liu, 2005)
- Arnon SS, Schechter R, Inglesby TV, et al. Botulinum Toxin as a Biological WeaponMedical and Public Health Management. JAMA. 2001;285(8):1059–1070. doi:10.1001/jama.285.8.1059
- Bintsis, T. (2017, June 29). Foodborne Pathogens. AIMS Press, 529-563.
- Forss, N., Ramstad, R., Backlund, T., Lindstrom, M., & Kolho, E. (2012, June 21). Difficulties in Diagnosing Food-Borne Botulism. Case Reports in Neurology, 113-115.
- Harvey, M. (2014). A different wrinkle – on Botulinum Toxin. Podiatry Review, 71(5), 6–7. Retrieved from https://ezproxy.mtsu.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=107818681&site=eds-live&scope=site
- Harvey, M. (2014). A different wrinkle – on Botulinum Toxin – Part 2 Development of medical uses and method of action. Podiatry Review, 71(6), 8–11. Retrieved from https://ezproxy.mtsu.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=ccm&AN=107837144&site=eds-live&scope=site
- Kopera, D. (2011), Botulinum toxin historical aspects: from food poisoning to pharmaceutical. International Journal of Dermatology, 50: 976-980. doi:10.1111/j.1365-4632.2010.04821.x
- Pita, R., & Romero, A. (2014). Toxins as Weapons: A Historical Review. Forensic Science Review, 26(2), 85. Retrieved from https://ezproxy.mtsu.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=edb&AN=96808717&site=eds-live&scope=site
- Sifferlin, A. (2017). The Drug That’s Treating Everything. (cover story). Time, 189(3), 38–44. Retrieved from https://ezproxy.mtsu.edu/login?url=http://search.ebscohost.com/login.aspx?direct=true&db=bth&AN=120565249&site=eds-live&scope=site
- Wein, L. M., & Liu, L. (2005, July 12). Analyzing a bioterror attack on the food supply: The case of botulinum toxin in milk. PNAS, 102(28), pp. 9984-9989.
- Yoon Seob Kim, Eun Sun Hong, & Hei Sung Kim. (2017). Botulinum Toxin in the Field of Dermatology: Novel Indications. Toxins, Vol 9, Iss 12, p 403 (2017), (12), 403. https://doi-org.ezproxy.mtsu.edu/10.3390/toxins9120403