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Botulinum Toxin

Botulinum Toxin

Toxins are chemicals of protein nature of plant, animal, microbial, or another origin. They are highly toxic and have an extremely damaging effect on humans and animals. The essential difference of toxins from poisons of the non-protein nature lies in the fact that when they enter the human body, they exhibit antigenic properties and develop immunity. Until recently, toxins have been often considered to be a biological weapon based on the fact that producers of the most effective toxins from a military point of view are bacteria. However, unlike biological organisms, toxins are not viable. They have an incubation period. A possible latent period of the action in case of poisoning by toxins depends on the dose of the substance and the way it enters the body. These days, there are many different types of toxins, and botulinum toxin is one of them. It is one of the most powerful poisons known to the humankind. The purpose of the research paper is to study the action of botulinum toxin and its use as a biological weapon.

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History of Toxins

Toxin lesions are not contagious. They are not transmitted to other humans or animals. Toxins are formed long before they have penetrated the body. The tactical employment of toxins is possible on the basis of the same principles and the same methods that are characteristic of chemical weapons. Finally, toxins may be produced not only by microorganisms but also by animals and plants. They even may be prepared synthetically. There are numerous studies of the synthesis of fragments of modern toxins from 10-15 amino acids in the polypeptide chain in the laboratory scale. This fact gives reason to believe that toxins are one of the modern trends in the development of chemical weapons. French scientist Louis Pasteur started the study of toxins. He is considered to be the founder of modern immunology. His works were devoted to the establishment of the causes of rabies. Louis Pasteur postulated the existence of a specific rabies toxin and proposed the method of treatment of this disease through the use of anti-rabies serum successfully tested on humans in 1885 (Aktories & Just, 2000). In 1890, German bacteriologist Emil von Behring found that the serum of animals exposed to a small (sub-lethal) dose of toxins had preventive curative properties (Aktories & Just, 2000). The result of this research was the development of anti-diphtheria serum. This discovery marked the beginning of immunotherapy of common infectious diseases (Aktories & Just, 2000). However, toxins are extremely dangerous for humans in large doses.

General Notion on Botulinum Toxin

Roland Langford (2004) affirms that “Botulinum toxin is the toxic compound produced by the bacterium Clostridium botulinum” (p. 158). In 2011, the world used about 1 gram of pure toxin in medical and cosmetic purposes. Moreover, it is estimated that approximately two kilograms are enough to kill the entire population of the Earth. From soils, spores of clostridium botulinum can enter the food where they germinate in the shortage of oxygen. As a result, the toxin is accumulated in food. In such a way, it can cause poisoning. There may be reproduction of bacteria in the human body during infection of wounds and in the intestines of infants without a formed symbiotic microbial community. In all these cases, there is botulinum toxin poisoning. Thus, a pathological condition called botulism develops (Prasad, 2009). There are 7 different botulinum toxin types – A, B, C1, D, E, F, and G. They differ by structural features and mechanism of action. All types of toxins except for F and G have an effect on a person (Krenzelok, 2003).

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The botulinum toxin enters the body with food or water and gets into the blood through the epithelial cells of the small intestine – enterocytes. The toxin can also be absorbed into the bloodstream through inhalation of its aerosol. From the blood, it gets into motor neurons. Once in the cell, the poison is not available for the action of the immune system. In such a way, the use of specific antibodies to the toxin for the treatment is effective only in the earliest stages of the disease. Botulinum toxin blocks the impulse transmission from the nerve endings to the muscle. It influences a process of the release of nerve endings of a neurotransmitter acetylcholine from vesicles. Vesicular transport is necessary for the life of all human cells. There is a mechanism for the targeted delivery of the vesicles to their destination in the cell – to the surface of cells or organelles of the vacuolar system – the system of internal membranes, which includes the Golgi apparatus, endoplasmic reticulum, and lysosomes. The directed transportation is possible due to the system of mutual recognition of vesicles and destination at the expense of protein binding embedded in their membranes (Ladant, Alouf, & Popoff, 2005). The mechanism of the directed transportation of intracellular vesicles plays a major role in the functioning of nerve cells as their numerous outgrowths form contacts with other cells and are functionally distinct. In particular, this system is required for neurotransmitter release and transmission of nerve impulses from neuron to the muscle. The neurotransmitter is transported to the nerve ending, which is stored near the presynaptic membrane and is released near the neuron excitation at the expense of the merger with transport vesicles and presynaptic membrane of the neuron. Botulinum toxin violates the normal process of release of the neurotransmitter acetylcholine by motor neurons splitting one of the molecules necessary to bind the vesicles with the presynaptic membrane. As a result, the neuromuscular transmission is blocked (Ladant, Alouf, & Popoff, 2005). As a consequence, muscle paralysis develops. If they affect respiratory muscles, it can lead to death. It is possible to help these patients by mechanical ventilation of lungs. It usually requires from four to six weeks. The action of the toxin lasts from several weeks to several months. After this, transmission of impulses becomes normal. There are two stages of the restoration of neurons after botulinum toxin poisoning. During the first stage, there is the growth of new nerve endings that provide the normal innervation of muscles. Then, the original function of the nerve ending restores (Ladant, Alouf, & Popoff, 2005).

From 1957 to 2011, the mainly pentavalent vaccine was used. However, it was active against toxins of A, B, C, D, and E types. Later, it was replaced by a new vaccine (Krenzelok, 2003). Immunization is also held among the staff working with botulinum toxin in medicine, industry, or research laboratories.

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Botulinum Toxin as a Military Weapon

Due to the high activity of the toxin, military agencies of different countries considered the possibility of its use as a biological weapon, as well as the terrorist threat. In the 20th century, new methods of the production of botulinum toxin for military and subversive purposes developed in the preparation for chemical and bacteriological warfare. In the United States, during World War II botulinum toxin was seen as a promising biological weapon. The military centers in the United States, Britain, and Canada considered using botulinum toxin of type A for these purposes (Croddy & Wirtz, 2005). This type is considered as the most dangerous to humans. There is a version that fighters of the Czechoslovak resistance applied botulinum toxin in the murder of Reinhard Heydrich (Croddy & Wirtz, 2005). In 1971, the UN General Assembly approved the Convention on the Prohibition of the Development, Production, and Stockpiling of Toxin Weapons and on Their Destruction. Author Dongyou Liu (2014) states that “Currently, 170 states parties are involved” (p. 1). In 1975, as a result of many years of researches, botulinum toxin of type A was adopted by the US Army under the code XR (Croddy & Wirtz, 2005). Its reserves are stored in Arkansas. The lethal outcome for a person may occur within three days. In the air, the spray is effective as a bioweapon within 12 hours (Croddy & Wirtz, 2005). It is possible to degas XR only with aqueous solutions of the active chlorine. XR formaldehyde solutions are especially easily deactivated. The biological weapon in the form of an aerosol is the most dangerous for the population (Croddy & Wirtz, 2005). It is associated with the fact that the toxin is readily absorbed by the mucous membranes of the eyes and upper respiratory tract. Nevertheless, respirators ensure reliable protection against aerosol XR. To protect against the possible poisoning of soldiers during World War II, the US Department of Defense developed the first vaccine against botulism (Croddy & Wirtz, 2005).

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Conclusion

These days, botulinum toxin is considered to be one of the most dangerous substances. Entering the body, the substance causes severe damage to the nervous system, progressive paralysis, and respiratory arrest. Botulinum toxin was used as a biological weapon on the fronts of World War II. Several decades later, the UN General Assembly approved the Convention on the Prohibition of the Development, Production, and Stockpiling of toxic weapons, including botulinum toxin. In my opinion, this convention has saved many lives as without it toxic weapons could be still used.

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