There is something peculiarly fascinating in the use of a deadly toxin as a life-saving medicine and the natural pharmacology that exists within animal venoms is a tremendous resource waiting to be tapped. This usefulness of venoms lies in their ability to affect the victim's systems by short-circuiting or getting around control mechanisms through action independent of co-factors or non-recognition by inhibitors. While venoms have long been used in homeopathic remedies, it was not until the late 1800s that venoms were scientifically investigated for use as medicinal compounds with the use of venom as therapeutic or diagnostic agents mostly falling into the two general categories of blood disorders and relief of severe and intractable pain. More recently venoms have been intensively investigated, not only for direct use as therapeutic agents or as diagnostic tools but also as scaffolds for drug design.

A large part of my research time is spent examining the molecular evolution of venoms. What I am studying is how venoms change with time, not just short time scales like variations between different populations of a particular species but also deep time changes occuring over millions of years and even going back to the original snake venom.

What we've discovered is that snake venom developed only one time in evolution, probably sometime during the Tertiary period over 60 million years ago.. This means it occurred right at the very base of the Colubroidea (Advanced snakes) evolutionary tree. The first venomous snake evolved from the heavy bodied swamp monsters similar to the anacondas of today. They needed a new tool to kill their prey since they were trading in the heavy muscle in order to become quicker and more athletic. Enter venom. They used this venom to feed on the cute little furry rodents that eventually became us.

 


Radiated rat snake (Coelognathus radiatus). These are not the friendliest snakes in the world but were certainly a fascinating research project!

 


That's my hand that has just been chomped on.

This origin of venom is so far back, that it occurred before the snakes we commonly think of as 'non-venomous' even showed up on the tree of life. We even isolated from a ratsnake the typical cobra-style neurotoxin, belonging to a toxin family called 3FTx (three-finger toxins) that is the signature of elapid venoms This toxin, which we named alpha-colubritoxin, is as potent as comparative elapid neurotoxins. Like the elapid toxins, it blocks the nicotinic acetylcholine receptor. What this does is stops the nerve signal from being able to cause the muscle fibre to twitch. No signal = no movement = couch potato. We've subsequently found these toxins in pretty much every 'colubrid' species we've looked at, showing that this toxin type is one of the oldest and that being venomous is the inherent condition of the advanced snakes.

Analysis of the venoms from as many different lineages as we could get our hands on showed that the 'colubrid' snake venoms are by and large just as complex as the elapid or viper venoms.

Some non-venomous snakes have been previously thought to have only mild 'toxic saliva' but these results shown that they actually possess true venoms. This makes perfect evolutionary sense, there cannot be a strong selection pressure for the development of advanced pieces of architecture like fangs unless there was already a potent venom worth delivering. Therefore, venom preceeded the fang just as the ability to make noise in the primates preceeded the voicebox . All pimates can make noises but we are the only lineage that can modify the sounds in an intricate way. The 'colubrids' still can deliver the venom (they have teeth after all). Fangs were an improvement that allowed for greatly improved delivery into prey. The developmnt enom was therefore a key prey-capture adaptation in snake evolution and the fangs came much later.

This research also shows that some of the snakes common in the overseas pet market actually produce highly potent venoms. However, this does not mean that all of them are going to be dangerous. What it does mean is that we need to reevaluate the relative danger. The relative danger can be assessed through four variables: 1. potency and complexity of venoms, 2. quantity of venom produced, 3. effectiveness of the delivery mechanism and 4. an effective antivenom being available.

 


Telescopus dhara (Egyptian catsnake) and Psammophis mossambicus (Olive sand snake). The venom glands in these 'colubrids' are as big as any elapid venom gland and bigger than some!

For most of the 'colubrids', most have very potent and complex venoms (variable 1). The venom yields range from small (e.g. the radiated ratsnake) to massive (Telescopus dhara) (viable 2). Indeed, as shown above Telescopus dhara have some of the biggest venom glands I've ever seen and Psammophis mossambicus was no slouch in this area either. No antivenom is produced against any of the 'colubrid' venoms except for the colubrine snake Dispholidus typus (boomslang) and the natricine snake Rhabdophis tigrinus (tiger keelback snake). This leaves variable three as the main one, how efficiently they are able to deliver the venom. The venom delivery for most of the 'colubrids' is vastly inferior to the highly efficient atractaspid, elapid, or viperid delivery systems. So at the end of the day, while the colubrids have potent, complex venoms that are in some cases produced in significant amounts, they are much less efficient at delivering it. However, the lack of antivenoms does complicate the situation. In a nutshell, while the various 'colubrids' are less likely to get you with a good solid envenomation, if they do then you are screwed.

The venom evolution project gave us all the excuse we needed to play with not only various 'colubrids', and vipers but also venomous primates and Komodo dragons! Too much fun!

 

 

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