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Biting the hand that feeds: The evolution of snake venom

The views expressed are those of the author and are not necessarily those of Scientific American.


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"Snakes. Why did it have to be snakes?"—Indiana Jones in Raiders of the Lost Ark

Let’s face it. Snakes are not most people’s favorite animals. They slink and slither without making much noise, have a forked tongue with unblinking eyes, and fangs that bite or coils that wrap. Some snakes are so dangerous that people have died from the encounter. According to a 2010 report by the World Health Organization, at least 20,000 people are killed by poisonous snakebites every year. Not surprisingly, snakes are commonly feared, disliked, and even hated.

And yet, snakes are some of my favorite animals, and I have been bitten more than my fair share. When I tell the stories of how I’ve been bitten, I always acknowledge that it was my fault, and that the snakes were acting solely out of instinct and self-preservation.

In fact, being bitten allowed me to appreciate their uniqueness even more – the key is to look past the stereotypes and bad press they have received to reveal the amazing animal beneath. But many people still fear snakes, or even have a phobia against them.

Andrea Letamendi, a doctoral candidate in the Anxiety and Traumatic Stress Disorders Research Program at UCSD’s Department of Psychiatry, specializes in treating patients with phobias. She said that fear is an essential, natural and healthy part of the human experience and an important aspect of development.

"It is natural to feel somewhat fearful of particular objects and situations, such as heights, crowds, snakes, spiders, and the dark. These are environmental contexts that may pose an actual threat. Therefore, being vigilant and even avoidant of these "unsafe" contexts (fleeing, fighting, panicking) is a way that we keep ourselves alive."

A phobia, on the other hand, is an irrational fear that actually impairs an individual’s normal day-to-day life. According to Letamendi, the most successful treatments for phobias involve gradually exposing the patient to images, sounds or the actual object after learning various relaxation and coping techniques.

"Some fear is good!" she said. "But when it becomes so excessive that it interferes with the patient’s normal activities in their lives, it has moved beyond fear and become a phobia."

But, why is a fear or phobia of snakes so prevalent in society today?

A Perfect Chemical Cocktail

Snakes have been around for millions of years, and have used this time to become the incredibly effective hunters and predators that lurk in bushes and trees all over the world. But, like every good story, to fully understand snakes how they are today, you need to start from the beginning to understand how they got here.

Their story begins over 100 million years ago, when snakes diverged from lizards to evolve into smaller and faster predators to catch quick-moving prey. The options were either to outrace the prey, which requires a great deal of energy, or lie and wait for the prey to come to you and incapacitate it as quickly and quietly as possible.

The solution was venom – a complex chemical cocktail of proteins and enzymes evolved to kill or incapacitate the prey before the snake even begins digestion. But, as it turns out, snakes did not evolve venom like it is commonly believed. In fact, snake venom evolved from venom in a lizard ancestor over 200 million years ago.

Dr. Bryan Fry, an Associate Professor from the School of Biological Sciences at the University of Queensland in Australia, is an expert on snake venom and the scientist who discovered venom’s rather complex evolutionary history, which includes links to the Komodo dragon and Gila monster.

It’s Not the Bite That Kills You…

While the venom system evolved before snakes, it was they who took the rather simple product and gave it a sophisticated upgrade in its potency and variety.

"Venom is all about prey capture, so differences in prey result in different venoms being selected by evolutionary pressures," said Fry.

While it is difficult to classify the sheer variety of venom compounds into categories, a vast oversimplification is that there are three types of venom that snakes can possess, but most snakes utilize a mixture between the three: Cytotoxic, neurotoxic and haemotoxic.

Cytotoxins are basically digestive juices that begin to dissolve tissue and muscle from the bite site eventually causing hemorrhage and death. Neurotoxic venoms block the electrical signals from nerves cells reaching muscles, leading to paralysis and eventual suffocation and death. Haemotoxins affect the blood, either by rupturing red blood cells and causing massive internal bleeding, or ramping up clotting factors leading to blockages within vessels and arteries potentially leading to strokes and death.

Sense a theme?

"Venoms are extremely complex mixtures that can vary widely in content even within different populations of the same species," said Fry.

In fact, what venom type (or combination of types) the snake possesses largely depends on the habitat in which it lives and the prey in which it hunts. For example, fast-acting venom is needed for prey that can escape quickly like fish, while venom that acts slower works perfectly for prey that cannot get far, like mice.

But once a prey is caught, the venom must be injected using specialized teeth known as fangs.

With Fangs that Bite

Dr. Wolfgang Wüster, a lecturer at Bangor University in the UK and expert in venom and snake evolution, said that the understanding of the origin of the complete venom apparatus (venom glands, a duct to carry the venom and fangs) is incomplete, but appears to have evolved 80 million years ago. But, as mentioned above, recent research by Fry suggests that the venom glands themselves evolved long before that.

But what about fangs, the large curved teeth used to envenom the prey located at the business end of the snake?

In fact, like venom types, there is a large amount of variety present, but they can be roughly classified by the location of the fangs relative to the mouth: rear-fanged, forward fanged and hinged.

Rear-fanged snakes belong to the Colubridae family (such as the deadly boomslang snake, Dispholidus typus), which is a very large group that contains roughly two-thirds of all snake species. However, venomous snakes in this family posses fangs that are located at the rear of the mouth and do not inject the venom. Instead, says Wüster, pressure must be indirectly applied to the venom glands by chewing in order to envenomate the prey.

Front-fanged snakes belong to the Elapidae family that includes the rock stars of the venom world like King cobras, mambas and death adders. Their fangs are shorter and intensely curved towards the back to hold onto their prey once bitten. Their venom is known to be the most poisonous of all snakes.

"Vipers [from the family Viperidae] have fangs that are tubular and long, and lie along the roof of the mouth when the snake has its mouth closed," said Wüster. But, when it is time to bite, the large fangs swing into position to inject venom like a hypodermic needle, hence hinge-fanged. Snakes belonging to this family, like pit vipers, are considered to have the most advanced venom systems.

As sophisticated and amazing as snake fangs are, those are only one tool in the snake’s attack toolbox. The best weapon is one that can have multiple uses and constantly change, like a Swiss Army knife for predators.

"Venom evolves at a greatly accelerated rate relative to the organisms themselves," said Fry.

Evolution Revolution

In an analysis of 24 known snake venom proteins, Fry discovered that the proteins evolved in a very different way than expected. While it was commonly believed that venom evolved from modified saliva proteins, the researchers determined that 21 possessed similar amino acid sequences to proteins found throughout the body, such as in the heart, liver and brain.

According to Fry, through the process of natural selection, these proteins are recruited into service as new raw ingredients in the venom stew, and either disappear and are subsequently replaced, or mutated even further to become more lethal and permanent additions.

The main treatment for being poisoned is treatment with antivenom, which is created by obtaining venom from the snake and injecting it into an animal to obtain antibodies. It is important to know that antivenom neutralizes the target venom and prevents further effects, but does not reverse the damage already done. That is why it is important to obtain antivenom as soon as possible once bitten by a poisonous animal.

However, as venom continues to evolve, this creates areas Fry calls "hot spots," where venoms have evolved radically and could result in a decrease in the ability for antivenom to do its job. However, as dangerous as the situation can be, there is also opportunity.

These "hot spots" are where novel toxins will appear within venom, which can then be studied and analyzed for future use in drug design and development.

"Venoms have had a huge role in drug design and development such as Captropril, a high blood pressure medication developed from the study of the venom of Bothrops jararaca, [which] kill more people than any other in the region," said Fry.

Therefore, not only has antivenom saved countless people from pain, limb loss, and even death, but the study of venom has also helped develop various products that increase human health.

Not too bad for an animal long thought to symbolize evil.

References:

WHO Guidelines for the Production Control and Regulation of Snake Antivenom Immunoglobulins. 2010 World Health Organization. Accessed January 22, 2011.

Fry, B. G., et al. 2006. Early evolution of the venom system in lizards and snakes. Nature Letters 49 (2): 584-588.

Fry, B. G., et al. 2008. Evolution of an Arsenal. Molecular & Cellular Proteomics 7.2: 215-246.

Fry, B. G., et al. 2009. Evolution and diversification of the Toxicofera reptile venom system. Journal of Proteomics. 72: 127-136.

Image Credits:

1) Photo of Green Mamba (Dendroaspis viridis) posted to Wikimedia Commons by Patrick Coin (Creative Commons license).

2) Photo by Bryan G. Fry, via his Web site www.venomdoc.com

3) Photo of Gaboon viper (Bitis gabonica) posted to Wikimedia Commons by Brian McKay (Creative Commons license).

 

About the Author: David Manly is a Canadian freelance science journalist, who holds degrees in Biology and Zoology, as well as a Masters of Journalism. He has worked with dozens of animals in his career as a scientist, and now spends a lot of time writing about the wondrous world of animals for Lab Spaces, as well as for his own blog The Definitive Host, and you can always find him on Twitter (his handle is @davidmanly). When he’s not writing, you can usually find him reading a good book or watching one of the countless animal documentaries that he owns. He has been bitten by a total of three non-venomous snakes, twice on his left hand and once on his right arm, but bears them no ill will. His favorite snakes are the Green Mamba and Green Tree Python.

The views expressed are those of the author and are not necessarily those of Scientific American.






Comments 7 Comments

Add Comment
  1. 1. lilolme 2:42 pm 01/26/2011

    That’s a fascinating article. It amazes me that snake venom is changing so quickly that we will need to modify our anti-venoms.

    They are spectacular creatures that have many highly refined characteristics and I feel are really under-appreciated for their unique abilities. Some snakes can sense a temperature change of 100th of a degree where a prey animal had been sitting!

    Thanks for the article! An animal specialization series would be great, Scientific American.

    Link to this
  2. 2. JamesDavis 3:02 pm 01/26/2011

    I don’t hate snakes, but I’m crazy about them neither. There are copperheads where I live and those dog-gone things are always chasing me around in the yard and out in the woods…they are really aggressive. Thank God, I haven’t been bit by one yet.

    Link to this
  3. 3. ejwillingham 4:07 pm 01/26/2011

    Gaboon viper, Bitis gabonica (natch). Most beautiful snake in the world.

    Can someone explain why snake venom has nerve growth factor? That’s a question that’s been on my mind for awhile.

    Link to this
  4. 4. DavidManly 4:37 pm 01/26/2011

    Thanks lilolme.
    Snake venom is a fascinating hodge-podge of chemicals, proteins and enzymes that can change much faster than anyone anticipated.

    I agree that an animal specialization series would be a great idea for Scientific American, and I’d love to write it! What do you think, Scientific American?

    Link to this
  5. 5. johnhei 9:50 pm 01/31/2011

    The evolution of snakes! After reading the article one can only wonder where the story part ends, and the real science begins. And where natural selection would acquire the necessary perspective to put a ‘hodge-podge’of chemicals, proteins and enzymes together in such an effective way.

    Link to this
  6. 6. Michael_01 5:25 pm 01/21/2012

    Thanks for sharing this very informative post. I am sure that this will help people know more about the evolution of snake venom. Here I would also like to share a link (venomoussnakes.net/prehistoricsnakes.htm) where you can find great information about some of the most Prehistoric and gigantic snakes.

    Link to this
  7. 7. janvones 12:33 am 06/8/2012

    To answer the question above, growth factors in large amounts act as poisons. One of the active agents in Agent Orange was a plant growth factor.

    Link to this

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