In the inky darkness of a lush Brazilian rainforest, a hungry predator is on the hunt. A Brazilian pit viper (Bothrops jararaca) is coiled, ready to ambush any prey that crosses its path. A patient hunter, it waits for the perfect moment to strike. An unsuspecting rodent scurries past. In a flash, the viper strikes. Two hypodermic needle-like fangs sink into the rodent, injecting it with lethal venom. The viper’s venom wreaks havoc on the rodent’s circulatory system. Within seconds, the cocktail of toxins present in the venom causes a severe drop in the rodent’s blood pressure, rendering it unconscious. Soon, the rodent stops moving. The snake can now feast on its prey. The venom has done its job.
Thousands of miles away, an adult human male is on the prowl. He scans through the colourful racks of the pharmacy, looking for his prescription medication. Like millions of humans, he suffers from hypertension, a contributor to humanity’s biggest killer—heart disease. He finally finds his medication: Captopril, a tablet that keeps his blood pressure in check. Its origin? Elements from the lethal pit viper venom which just killed the rodent. Behold snake venom: an unlikely elixir for humans.
It isn’t easy being a snake in the wild. Food is scarce and hunting prey is a task. Having no limbs and being dependent on external factors to regulate body temperature don’t help either. What weapon could snakes possibly deploy to counter these disadvantages?
A weapon which rapidly debilitates prey would be ideal. Over millions of years, snakes have evolved proteins, peptides, and enzymes in highly specialised glands to produce just that kind of weapon: venom.
These proteins, peptides, and enzymes act as toxins and attack specific biological pathways. Toxins are generally classified into three types: neurotoxic (impacting the central and peripheral nervous system), cytotoxic (impacting cells), and haemotoxic (impacting the cardiovascular system). Evidently, snake venom has evolved to attack some of the most sensitive systems in any animal. With its circulatory or nervous system in jeopardy, an envenomated animal’s chances of escaping from a snake are greatly reduced. However, it’s not just snakes that evolved to produce venom. Through random genetic mutations, distinct taxa such as sea anemones, bees, scorpions, and even some primates independently evolved to produce venom in ‘repurposed’ salivary glands—a phenomenon called convergent evolution. When these mutations proved advantageous, those species thrived due to natural selection favouring them.
The toxins started out as proteins involved in everyday physiological processes. Through genetic mutations, these seemingly harmless proteins evolved to be highly effective toxins that could target specific biological pathways. Take, for example, phospholipase type A2 (PLA2), a protein that is present in the venom of virtually all snake species. An ancestral, non-toxic PLA2 probably helped cells maintain a steady state. But a series of random genetic mutations eventually led to the evolution of PLA2 with an arsenal of neurotoxic, myotoxic, and haemotoxic functions.
Venom is fast-acting, effective, and debilitating. But is that all there is to it?
Beyond a deadly cocktail
Angiotensin-converting enzyme (ACE) is an enzyme that promotes the constriction of blood vessels, resulting in an increase in blood pressure. In the late 1960s, researchers discovered that Brazilian pit viper venom contained a peptide called Bradykinin potentiating factor (BPF) that could selectively inhibit ACE. This discovery aligned well with the fact that snake venom functioned by inducing a drastic drop in blood pressure, and was leveraged to develop a synthetic analogue of BPF, which could be used to treat hypertension by lowering blood pressure. Thus, Captopril (sold under the brand name Capoten) was the first ACE-inhibitor hypertension drug to be approved for human use.
Snake venom has proved to be a hit among drugs for cardiovascular ailments: Tirofiban (sold under the brand name Aggrastat) is used to treat unstable angina, a condition where insufficient blood flow to the heart—usually due to the formation of blood clots in the coronary artery—results in chest pain. Tirofiban is a synthetic version of a protein found in the venom of the saw-scaled viper (Echis carinatus), a snake responsible for a significant number of envenomations in India. Saw-scaled viper bites usually result in internal haemorrhaging. This is due to a protein in their venom known as echistatin, which binds to certain receptors on platelets, thereby preventing the timely formation of blood clots and leading to internal bleeding and shock.. While the viper uses this protein to ensure its prey is immobilised, humans benefit from a synthetic version of echistatin by using its clot-preventing property to treat unstable angina.
Another example is Integrilin, a drug used to prevent clot formation in heart attack patients, which uses a similar synthetic protein derived from the venom of the Southeastern pygmy rattlesnake (Sistrurus miliarius barbouri).
What does the future hold?
While these are but a few of the snake venom-derived drugs currently used to treat human ailments, there are several others undergoing testing. From the possibility of black mamba venom being used as a formidable painkiller to the prospect of desert black snake venom being used to treat infertility, snake venom is proving to be a treasure trove of potential treatments for various human conditions.
Snakes are generally looked upon with fear and disgust. The general attitude toward snakes, especially venomous snakes, is that they are repulsive and scary creatures. Evidently, there is a whole lot more to venomous snakes. Perhaps it’s time to stop looking at snakes as vermin, and instead, look at them as animals who, although dangerous at times, have the potential to do humanity much good.
- Jenner, R. and E. Undheim. 2017. Venom: The secrets of nature’s deadliest weapon (Illustrated ed.). Smithsonian Books.
- Mohamed Abd El-Aziz, T., A. Garcia Soares and J. D. Stockand. 2019. Snake venoms in drug discovery: Valuable therapeutic tools for life saving. Toxins 11(10): 564.
- Shaw, A. (n.d.). How venoms are shaping medical advances. BBC Earth. https://www.bbcearth.com/news/how-venoms-are-shaping-medical-advances