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| How Venom Kills: {{youtube>Q87UkykCbvI?medium}} | How Venom Kills: {{youtube>Q87UkykCbvI?medium}} | ||
| - | ====== History ====== | + | ====== History of Snakes====== |
| Snakes are historically important creatures that have strong social and cultural significance (Boquet, 1979). They feature in many different religions and cultures across the globe and are considered omens of both good and evil (Boquet, 1979). It is this dichotomy of interpretations of the snake that make it a phenomenally interesting research topic. Although the focus of this wiki page is on snake venom in particular, it is important to consider the history of snakes in general. | Snakes are historically important creatures that have strong social and cultural significance (Boquet, 1979). They feature in many different religions and cultures across the globe and are considered omens of both good and evil (Boquet, 1979). It is this dichotomy of interpretations of the snake that make it a phenomenally interesting research topic. Although the focus of this wiki page is on snake venom in particular, it is important to consider the history of snakes in general. | ||
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| - | ====== Evolution of Venom ====== | + | ====== Evolution of Snake Venom ====== |
| There is an evolutionary relationship within the clade containing snakes, anguimorphs, iguanians, and amphisbaenians, lacertids and teiioids (Fry et al., 2012). In particular, within the clade of Toxicofera, which contains snakes, anguimorphs, and iguanians it has been demonstrated that the evolution of venom has diversified the species within this clade. In fact, 170 million years ago, there was an actual point at which venom within all these species diversified (Fry et al., 2012). | There is an evolutionary relationship within the clade containing snakes, anguimorphs, iguanians, and amphisbaenians, lacertids and teiioids (Fry et al., 2012). In particular, within the clade of Toxicofera, which contains snakes, anguimorphs, and iguanians it has been demonstrated that the evolution of venom has diversified the species within this clade. In fact, 170 million years ago, there was an actual point at which venom within all these species diversified (Fry et al., 2012). | ||
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| Snake venoms consist of a complex mixture of several biologically active proteins, peptides, enzymes, organic compounds and inorganic compounds (Vyas et al., 2013). One use of venom that has been studied to see for future use is in the area of cancer. It has been discovered that snake venom can inhibit cell proliferation and also promoting cell death in regards to cancer cells (Vyas et al., 2013). These processes occur due to increased calcium ion influx, decreasing or increasing the expression of proteins that control the cell cycle resulting in damage to the cell membrane, apoptosis induced cancer cells, promoting cytochrome C release, etc (Vyas et al., 2013). Certain proteins from snake venom have also been used to create drugs that help thrombin inhibition, blood thin, fibrinogen inhibition for strokes, help with high blood pressure, etc. (Koh et al., 2006). | Snake venoms consist of a complex mixture of several biologically active proteins, peptides, enzymes, organic compounds and inorganic compounds (Vyas et al., 2013). One use of venom that has been studied to see for future use is in the area of cancer. It has been discovered that snake venom can inhibit cell proliferation and also promoting cell death in regards to cancer cells (Vyas et al., 2013). These processes occur due to increased calcium ion influx, decreasing or increasing the expression of proteins that control the cell cycle resulting in damage to the cell membrane, apoptosis induced cancer cells, promoting cytochrome C release, etc (Vyas et al., 2013). Certain proteins from snake venom have also been used to create drugs that help thrombin inhibition, blood thin, fibrinogen inhibition for strokes, help with high blood pressure, etc. (Koh et al., 2006). | ||
| - | ====== Immunity ====== | + | ====== Modern Snake Bite Treatment, Antivenom, and Immunity ====== |
| + | |||
| + | Snake bites in the present day are managed using a series of steps (Ahmed et al., 2008). The first step in this management protocol is first-aid. Usually this entails ensuring the snake bite victim knows that he or she may not have been bitten by a venomous snake. This is because only 30% of snake bites are venomous. First aid treatment also includes restricting movement of the bitten limb and then moving the victim to a hospital. The second step involves treatment at a hospital. In the emergency department this will include assessing, “airway, breathing, circulatory status, and consciousness” (Ahmed et al., 2008) and performing resuscitation, if needed, or providing supplementary oxygen to victims. Also the victim’s medical history will be checked, the severity of the bite assessed, and a physical examination will be performed. The next step is to perform several laboratory tests. One such test is the 20-minute whole blood clotting test. In this test, blood is drawn from the victim and left alone in a test tube for 20 minutes to see if the blood has coagulated. If it has not then this is evidence the victim was bitten by a viper. Finally the last clinical step involves specific treatment such as administering anti-snake venom (Ahmed et al., 2008). | ||
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| + | Anti-snake venom is a specific immunoglobulin treatment to manage venomous snakebites and is the only known antidote for snake venom (Ahmed et al., 2008). It is created by injecting a vertebrate organism, like a horse or a sheep, an immunization and then booster shots (“How do you make antivenom?”, n.d.). The idea is to allow the organism’s immune system to create antibodies to fight off whatever was injected into their bloodstream. The blood can then be extracted from this organism and be used to create antivenom (“How do you make antivenom?”, n.d.). | ||
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| + | Although antivenom is a treatment for venomous snake bites (Ahmed et al., 2008), it raises the question: can the human body itself develop immunity to snake venom? One man that could provide interesting answers to this question is Steve Ludwin. Ludwin is a British man that has been injecting himself with a cocktail of venom from different snakes over several years (Froissart, 2017). He believes that by doing so he can self-immunize himself (Froissart, 2017). The scientific community is interested in testing the veracity of his claims (Froissart, 2017). | ||
| ====== Traditional Venom Treatments ====== | ====== Traditional Venom Treatments ====== | ||
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| Colonial remedies were quite different from the current treatment for venomous snake bites. A case in 1868 revealed some of these methods when a man was bitten by a venomous snake (Hobbins, 2017). The surgeon was tied a ligature around the patient’s arm to cut the site of bite. He then poured ammonia on the wound site in an attempt to neutralize the venom and then made the patient drink six ounces of brandy to rouse his circulation. The surgeon next proceeded by waving a powerful smelling salt under the patient’s nose and subsequently applied a mustard poultice to his abdomen, hands and feet to ease internal congestion. Another medical professor then injected ammonia into one of his veins in the bitten arm and surprisingly, saved the patient’s life. In addition to this scenario, traditional venom treatments commonly included suction or ligature to expel the venom and limit further circulation in the bloodstream (Hobbins, 2017). Furthermore, medicinal plants are also commonly used to treat venomous snake bites, as they are safe, effective, inexpensive and attainable from neighbouring forests (Gupta & Peshin, 2012). For example, Vitis vinifera L. seeds are extracted and used due to their neutralization effects of edema, from viperine snake bites (Gupta & Peshin, 2012). | Colonial remedies were quite different from the current treatment for venomous snake bites. A case in 1868 revealed some of these methods when a man was bitten by a venomous snake (Hobbins, 2017). The surgeon was tied a ligature around the patient’s arm to cut the site of bite. He then poured ammonia on the wound site in an attempt to neutralize the venom and then made the patient drink six ounces of brandy to rouse his circulation. The surgeon next proceeded by waving a powerful smelling salt under the patient’s nose and subsequently applied a mustard poultice to his abdomen, hands and feet to ease internal congestion. Another medical professor then injected ammonia into one of his veins in the bitten arm and surprisingly, saved the patient’s life. In addition to this scenario, traditional venom treatments commonly included suction or ligature to expel the venom and limit further circulation in the bloodstream (Hobbins, 2017). Furthermore, medicinal plants are also commonly used to treat venomous snake bites, as they are safe, effective, inexpensive and attainable from neighbouring forests (Gupta & Peshin, 2012). For example, Vitis vinifera L. seeds are extracted and used due to their neutralization effects of edema, from viperine snake bites (Gupta & Peshin, 2012). | ||
| - | ====== Current and Future Studies ====== | + | ====== Past, Current, and Future Research ====== |
| + | |||
| + | In the late twentieth century there has been significant research on understanding the biochemical and physiological mechanisms associated with the toxins found in the venom of a variety of organisms, and snakes in particular (Fox and Serrano, 2007). Even more recently, there has also been increasing interest in harvesting the toxins found in venom to try to create therapeutic agents that can be used in pharmaceutical interventions (Fox and Serrano, 2007) against disease and other conditions that adversely affects one’s health. Of the many toxins found in snake venom, snake venom metalloproteinases (SVMPs) are the most commonly found in the class viperidae (Takeda, Takeya, and Iwanaga, 2012). This toxin can cause hemorrhage and can affect the hemostatic system (Takeda, Takeya, and Iwanaga, 2012). | ||
| Figure 11 Source: https://www.ncbi.nlm.nih.gov/pubmed/19344655 | Figure 11 Source: https://www.ncbi.nlm.nih.gov/pubmed/19344655 | ||
| - | {{:0000000000.png?500|}} | + | {{:0000000000.png?800|}} |
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| + | **Figure 11: Timeline of Snake Venom Metalloproteinases (SVMPs) Research** | ||
| - | **Figure 11: Venom used in pharmaceutical research.** | + | In particular, there has been, “significant progress…regarding the function, structure and role of the snake venom metalloproteinases (SVMPs) in viperid venom pathogenesis” (Fox and Serrano, 2009). As seen in Figure 11, since 1881 to the time of Fox and Serrano’s review paper in 2007, there have been several notable discoveries (Fox and Serrano, 2009). To begin with, in 1881 it was proposed that venoms could be proteolytic and in 1990 when it was seen that venom could coagulate blood, the proteolytic enzyme activity of venom was hinted at. Then around 1960, toxins extracted from snake venom were discovered to be proteinases and were shown to have a high metal content. Thus researchers came to know of snake venom metalloproteinases. Then over the next half century numerous SVMPs have been identified and their various roles and functions have been speculated upon. One of the key discoveries made was the connection between SVMPs and the ADAMs group of proteins. This led to the creation of the protein group: reprolysins. Current research, around 2007, focused on the evolutionary basis for SVMPs and future studies may focus on elucidating a better understanding of the structure and function of different SVMP types (Fox and Serrano, 2009). |
| ====== Conclusion ====== | ====== Conclusion ====== | ||
| In conclusion, snakes inject venom to either inflict harm on a prey or predator for offensive and defensive purposes, respectively (Kang et al., 2011). India is the most affected by venomous snake bites and has 35000-50000 deaths every year from snake bites (Nielson, n.d). Through jaw-walking, they are able to prey on animals larger than them but they also prey on small animals such as fish, frogs, and mice (Kang et al., 2011). Although venomous snakes come in a variety of colors based on their geographical location, colorful snakes are most likely venomous and can cause the most harm (Underwood, 1979; Savage & Slowinski, 1992 and Reed, 2003). The three families of venomous snakes are atractaspidids, elapids, and viperids with atractaspidids snakes having a less toxic venom, elapids producing neurotoxins and viperids producing hemotoxic venom (Underwood, 1979; Savage & Slowinski, 1992 and Reed, 2003). All the venomous snakes have one of three fang structures, including proteroglyphous, solenoglyphous, or opisthoglyphous (Vonk et al, 2008 and Warrell, 2010) through which they inject the five different types of venom including hemotoxic, myotoxic, neurotoxic, cytotoxic and haemorrhagic (Chang, 1979; Karlssoni, 1979; Ohsaka, 1979 and Russell, 1980). Fang contact plays an important role on envenomation during defensive bites with viperids striking and releasing the target and elapid snakes holding onto the target for more venom delivery (Malasit et al., 1986). Different toxins target different body components and process including action potentials and red blood cells and have various physiological effects including difficulty breathing, vomiting, interference with platelet aggregation (Kini and Evans, 1990). The toxins found in snake venoms consist of a complex mixture of several biologically active proteins, peptides, enzymes, organic compounds and inorganic compounds and one use of venom that has been studied to see for future use is in the area of cancer where venom can inhibit cell proliferation and also promote cell death (Vyas et al., 2013). | In conclusion, snakes inject venom to either inflict harm on a prey or predator for offensive and defensive purposes, respectively (Kang et al., 2011). India is the most affected by venomous snake bites and has 35000-50000 deaths every year from snake bites (Nielson, n.d). Through jaw-walking, they are able to prey on animals larger than them but they also prey on small animals such as fish, frogs, and mice (Kang et al., 2011). Although venomous snakes come in a variety of colors based on their geographical location, colorful snakes are most likely venomous and can cause the most harm (Underwood, 1979; Savage & Slowinski, 1992 and Reed, 2003). The three families of venomous snakes are atractaspidids, elapids, and viperids with atractaspidids snakes having a less toxic venom, elapids producing neurotoxins and viperids producing hemotoxic venom (Underwood, 1979; Savage & Slowinski, 1992 and Reed, 2003). All the venomous snakes have one of three fang structures, including proteroglyphous, solenoglyphous, or opisthoglyphous (Vonk et al, 2008 and Warrell, 2010) through which they inject the five different types of venom including hemotoxic, myotoxic, neurotoxic, cytotoxic and haemorrhagic (Chang, 1979; Karlssoni, 1979; Ohsaka, 1979 and Russell, 1980). Fang contact plays an important role on envenomation during defensive bites with viperids striking and releasing the target and elapid snakes holding onto the target for more venom delivery (Malasit et al., 1986). Different toxins target different body components and process including action potentials and red blood cells and have various physiological effects including difficulty breathing, vomiting, interference with platelet aggregation (Kini and Evans, 1990). The toxins found in snake venoms consist of a complex mixture of several biologically active proteins, peptides, enzymes, organic compounds and inorganic compounds and one use of venom that has been studied to see for future use is in the area of cancer where venom can inhibit cell proliferation and also promote cell death (Vyas et al., 2013). | ||
| ====== References ====== | ====== References ====== | ||
| + | Ahmed, S. M., Ahmed, M., Nadeem, A., Mahajan, J., Choudhary, A., & Pal, J. (2008). Emergency treatment of a snake bite: Pearls from literature. Journal of Emergencies, Trauma and Shock, 1(2), 97. | ||
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| Basic facts about snakes. (2017). Defenders of wildlife. Retrieved 1 December 2017, from https://defenders.org/snakes/basic-facts | Basic facts about snakes. (2017). Defenders of wildlife. Retrieved 1 December 2017, from https://defenders.org/snakes/basic-facts | ||
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| + | Boquet, P. (1979). History of snake venom research. In Snake venoms (pp. 3-14). Springer, Berlin, Heidelberg. | ||
| Casewell, N. R., Wagstaff, S. C., Wüster, W., Cook, D. A. N., Bolton, F. M. S., King, S. I., … Harrison, R. A. (2014). Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. //Proceedings of the National Academy of Sciences, 111(25)//, 9205–9210. https://doi.org/10.1073/pnas.1405484111 | Casewell, N. R., Wagstaff, S. C., Wüster, W., Cook, D. A. N., Bolton, F. M. S., King, S. I., … Harrison, R. A. (2014). Medically important differences in snake venom composition are dictated by distinct postgenomic mechanisms. //Proceedings of the National Academy of Sciences, 111(25)//, 9205–9210. https://doi.org/10.1073/pnas.1405484111 | ||
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| Ellis, M. (2017b). Snake Bites. Healthline. Retrieved 17 November 2017, from https://www.healthline.com/health/snake-bites#overview1 | Ellis, M. (2017b). Snake Bites. Healthline. Retrieved 17 November 2017, from https://www.healthline.com/health/snake-bites#overview1 | ||
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| + | Fox, J. W., & Serrano, S. M. (2007). Approaching the golden age of natural product pharmaceuticals from venom libraries: an overview of toxins and toxin-derivatives currently involved in therapeutic or diagnostic applications. Current pharmaceutical design, 13(28), 2927-2934. | ||
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| + | Fox, J. W., & Serrano, S. M. (2009). Timeline of key events in snake venom metalloproteinase research. Journal of PROTEOMICS, 72(2), 200-209. | ||
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| + | Froissart, P. (2017). Snake man's venom habit holds hope for new antidote. Phys.org. Retrieved 29 November 2017, from https://phys.org/news/2017-11-snake-venom-habit-antidote.html | ||
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| + | Fry, B. G., Casewell, N. R., Wüster, W., Vidal, N., Young, B., & Jackson, T. N. (2012). The structural and functional diversification of the Toxicofera reptile venom system. Toxicon, 60(4), 434-448. | ||
| Gong, B., Liu, M., & Qi, Z. (2008). Membrane potential dependent duration of action potentials in cultured rat hippocampal neurons. //Cellular and Molecular Neurobiology, 28(1)//, 49-56. https://doi.org/10.1007/s10571-007-9230-5 | Gong, B., Liu, M., & Qi, Z. (2008). Membrane potential dependent duration of action potentials in cultured rat hippocampal neurons. //Cellular and Molecular Neurobiology, 28(1)//, 49-56. https://doi.org/10.1007/s10571-007-9230-5 | ||
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| Hobbins, P. (n.d.). Hissstory: how the science of snake bite treatments has changed. Retrieved November 25, 2017, from http://theconversation.com/hissstory-how-the-science-of-snake-bite-treatments-has-changed-71408 | Hobbins, P. (n.d.). Hissstory: how the science of snake bite treatments has changed. Retrieved November 25, 2017, from http://theconversation.com/hissstory-how-the-science-of-snake-bite-treatments-has-changed-71408 | ||
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| + | How do you make antivenom? | VIPER. Viper.arizona.edu. Retrieved 2 December 2017, from http://viper.arizona.edu/faq/how-do-you-make-antivenom | ||
| Johnson, s. (2012). Venomous Snake FAQs. Ufwildlife.ifas.ufl.edu. Retrieved 25 November 2017, from http://ufwildlife.ifas.ufl.edu/venomous_snake_faqs.shtml | Johnson, s. (2012). Venomous Snake FAQs. Ufwildlife.ifas.ufl.edu. Retrieved 25 November 2017, from http://ufwildlife.ifas.ufl.edu/venomous_snake_faqs.shtml | ||
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| Savage, J. M.,& Slowinski, J. B. (1992). The colouration of the venomous coral snakes (family Elapidae) and their mimics (families Aniliidae and Colubridae). Biological Journal of the Linnean Society, 45(3), 235-254. | Savage, J. M.,& Slowinski, J. B. (1992). The colouration of the venomous coral snakes (family Elapidae) and their mimics (families Aniliidae and Colubridae). Biological Journal of the Linnean Society, 45(3), 235-254. | ||
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| + | Takeda, S., Takeya, H., & Iwanaga, S. (2012). Snake venom metalloproteinases: structure, function and relevance to the mammalian ADAM/ADAMTS family proteins. Biochimica et Biophysica Acta (BBA)-Proteins and Proteomics, 1824(1), 164-176. | ||
| Tang, E. L. H., Tan, C. H., Fung, S. Y., & Tan, N. H. (2016). Venomics of calloselasma rhodostoma, the malayan pit viper: A complex toxin arsenal unraveled. //Journal of Proteomics, 148//, 44-56. https://doi.org/10.1016/j.jprot.2016.07.006 | Tang, E. L. H., Tan, C. H., Fung, S. Y., & Tan, N. H. (2016). Venomics of calloselasma rhodostoma, the malayan pit viper: A complex toxin arsenal unraveled. //Journal of Proteomics, 148//, 44-56. https://doi.org/10.1016/j.jprot.2016.07.006 | ||
