The Utility of Snake Venom Research
Table of Contents for this Hub Series on Snake Venom
Freeze-dried Snake Venom
Sheep are Injected with Snake Venom to Make Antivenom
Why study snake venom?
You are probably thinking one of two things right now: 1. "The only purpose for snake venom research is to produce better antivenom, right? So, as long as I never get bitten by a venomous snake, then venom research has no relevance to my life and I don't care to support it." or 2. "The only good snake is a dead snake!" Well, aside from antivenom production, which we will discuss only briefly, there is a potential for snake venom compounds to be used in research and pharmaceutical contexts. Since the majority of people reading this are not scientists, however, I'm going to strictly focus on the antivenom and pharmaceutical aspects of snake venom research.
As stated before, I will not dwell on this subject because it is explored in much greater detail elsewhere. For the sake of simplicity, I am going to focus this discussion on CroFab, the most used antivenom in the United States. Snake venom is injected into sheep in a manner that builds a high level of immunity to the venom toxins [often requiring multiple injections of increasingly higher doses over time (weeks/months)]. Blood is then taken from the immunized sheep and the IgG antibodies to the snake venom are isolated and purified. These IgG antibodies are then split to form one Fc fragment and two Fab fragments. The Fab fragments are collected and purified to form CroFab antivenom while the Fc fragments are discarded. This increases the specificity of the antivenom while decreasing the harmful side effects caused by intact IgG antibodies (which were used historically as the antivenom of choice in the U.S.).
Four different snake venoms are used in the production of CroFab, with each venom being injected into a different flock of sheep. These snakes are the Western Diamondback Rattlesnake (Crotalus atrox, responsible for the most venomous bites in the U.S.), Eastern Diamondback Rattlesnake (Crotalus adamanteus, the largest venomous snake in the U.S.), Mojave Rattlesnake (Crotalus scutulatus, frequently cited as one of the most toxic snakes in the U.S.), and the Cottonmouth (also known as the Water Moccasin, Agkistrodon piscivorus, known to frequent waterways in southeast U.S.). Including four different snakes in the CroFab antivenom mixture permits better cross-reactivity when attempting to neutralize envenomation symptoms from the other 50 or so species of pit-vipers in the United States. Snakes that like to feed upon front-fanged venomous snakes (including many of the nonvenomous rat/milk/king snakes) often possess high levels of resistance/immunity to those snake venoms. The innate resistance/immune mechanisms in these snakes could lead us to a better understanding of how to create more efficient antivenoms in humans.
Pharmaceutical Potential of Snake Venoms
Although most snake-derived drugs (see table below) currently in use are from snakes belonging to family Viperidae (vipers and rattlesnakes), there is at least one from family Elapidae (cobras: genus Naja). There are very few, if any, drugs designed from venom compounds in families Colubridae (rear-fanged "typical" snakes; if you don't know what "rear-fanged" means, please see parts 2-4 of this hub series on snake venom) or Atractaspididae (burrowing asps) at the present time. This is likely due to the fact that people have not been able to experiment on their venoms to a substantial degree, as opposed to the belief that those venoms are not "worthwhile." With over 1,200 species of venomous snakes in the world (spanning across the four snake families mentioned), it can be exceedingly difficult to collect every snake's venom (especially in a manner that captures all variation present within each species; please see part 5 in this hub series, which covers snake venom variation) and test it in all possible ways in order to determine what potential anthropogenic benefits can be derived from it. Since 2/3 of all new drugs designed (in the U.S.) from 1981 to 2006 were derived from natural sources in the environment, snake venom has great potential to be developed even further, leading us into our next section of discussion.
Commonly Used Drugs Made from Snake Venom
Snake Genus (species)
Bothrops (atrox, jararaca, jararacussu, moojeni)
Hemocoagulase, Reptilase, Captopril, Defibrase
hemorrhage, coagulation, high blood pressure, ischemia
heart attack, pro-coagulant
Assessing the Anti-Cancer Activity of Snake Venom
Taxon-specific Toxins Could be "Magic Bullets" for Cancer
In the image on the right ("Assessing the Anti-Cancer Activity of Snake Venom"), part of a microplate is shown, with each lane (column; labeled 1-7) representing a different treatment and each row (labeled A-D) just being a replicate (in order to average the results of each treatment among a sample size of 4). Although lane 1 just contained the control (cancer cells grown in liquid media without venom), lanes 2-7 contained both cancer cells and venom (in liquid media, incubated with the venom for a certain period of time before analysis), with each lane representing a different venom.
Lane 1 and 7 were virtually the same color (gold), indicating that the venom added to lane 7 was ineffective at killing cancer cells. Lanes 2, 3, 4, and 6 were also the same color (purple), indicating that they were all highly effective at killing cancer cells, with lane 5 being only moderately effective (since it had a lighter purple color; its lane number is circled). Although it may be tempting to conclude that you should focus most of your research efforts on studying the venom in lanes 2, 3, 4, and 6, those venoms may be overly "powerful/destructive" to be used in a clinical setting (causing too much collateral damage). It is possible that the venom in lane 5, with its moderate anti-cancer activity, might be a more practical chemotherapeutic compound. Even the venom in lane 7 could have therapeutic potential, as you don't necessarily have to outright destroy cancer cells, just inhibit their growth or their ability to metastasize (migrate to other sites in the body).
The process of finding a "miracle venom" possessing high anti-neoplastic activity is not that simple, however, as each venom can have 10-100 different individual compounds within it. Each venom compound must be isolated and tested individually in order to truly gauge its effectiveness against cancer cells (and that's ignoring the possibility that some venom compounds can synergize with one another) and determine its mechanism of action (how it physically acts on the cancer cells). If you believe there are an average of 50 distinct compounds in each snake's venom, and consider that there are over 1,200 different species of snakes alive today, you arrive at a number of 60,000 potentially distinct snake venom compounds. Each of these compounds could have unique structures/functions, making snake venoms a huge source for novel drug design. When prey-specificity is taken into account, there is the potential that we could discover a venom compound that is harmless against healthy human cells, but exhibits anti-cancer activity (thus becoming a "magic bullet," see the Brown Treesnake image above-right).
Conclusion - Why Conserve Snakes?
So, the next time you are posed with the question, "Why study snake venom?," you can answer with, "Drugs developed from it could save your life one day." Also keep in mind that even nonvenomous snakes can contribute to Science by offering insights into how to construct better antivenoms for humans. Snakes are also play a vital role in their natural environment, often feasting upon many creatures humans consider as pests (animals that cost humans billions of dollars every year): slugs, spiders, centipedes, rodents, squirrels, rabbits, and sparrows. Whenever you are faced with a snake encounter, please consider leaving the animal be or having it safely relocated by an expert, as opposed to killing it.
You may take the quiz below to test whether you now understand why we should engage in snake venom research before moving onto the next hub, which presents a guide for snakebite. You can also check out the video below, which shows an example of a snake that is a rear-fanged venomous constrictor. If you would like to learn more about the usefulness of snake venom research, please see the Amazon links below for some useful book resources. If you have further questions about snakes that are not addressed by this article on the usefulness of snake venom research (or any other articles in this Snake Venom hub series), please see my hub on FAQs About Snakes.
Do you understand why snake venom research is worthwhile?view quiz statistics
Constricting Snakes Can Be Venomous, Too!
This hub is intended to educate people ranging from snake experts to laymen on why we should perform research on snake venom. This information contains generalizations and by no means encompasses all exceptions to the most common "rules" presented here. This information comes from my personal experience/knowledge as well as various primary (journal articles) and secondary (books) literature sources (and can be made available upon request). All pictures and videos, unless specifically noted otherwise, are my property and may not be used in any form, to any degree, without my express permission (please send email inquiries to email@example.com).
I wholly believe feedback can be a useful tool for helping make the world a better place, so I welcome any (positive or negative) that you might feel compelled to offer. But, before actually leaving feedback, please consider the following two points: 1. Please mention in your positive comments what you thought was done well, and mention in your negative comments how the article can be altered to better suit your needs/expectations; 2. If you intend on criticizing "missing" information that you feel would be relevant to this hub, please be sure you read through all of the other hubs in this Snake Venom series first in order to see if your concerns are addressed elsewhere.
If you enjoyed this article and would like to find out how you can help support snake venom research examining the pharmaceutical potential of various snake venom compounds, please check out my profile. Thank you for reading!
© 2012 Christopher Rex