Snakes - Venom, Antivenom and Medicinal Uses

Chris -   Snake venom, we're lucky in this country in that we've only got one poisonous snake, Ireland and New Zealand don't have any!  But why do snakes produce this venom and how does it work?

Gavin -   Snakes, over millions and millions of years have evolved a very complex array, like an arsenal, in order to defend themselves or immobilise their prey before eating it.  We're only just discovering the complexity of a lot of the venoms present in certain snakes because they seem to have a very specific role; either they can immobilise by inhibiting the action of the nerves or they can immobilise by causing a complete thrombosis of the haemostatic system.

Chris -   But snakes don't need to bite us do they?  If you look at cobras they spit venom in people's eyes.  Is that effective or do they do that to blind you and then come in to bite?

Gavin -   Spitting cobras have this wonderful adaptation where they have holes in the front of their fangs, so you can get a plume, like an aerosol plume of snake venom, and if you get it in your eyes you can get a chemical conjunctivitis.  It's very painful but it won't envenom you in that way, the reaction is purely local.  These spitting cobras can also bit with these fangs and can immobilise because the venom is neurotoxic, can paralyse a patient in the worst case scenario.

Chris -   You don't seem to need much venom to see a pretty bug effect on a person who gets bitten.

Gavin -   That is true, the most toxic of the venoms is probably the inland Taipan of Australia.  It's got a very low LD 50, which is the standardised unit of lethality.  You 're right, you only need a very small amount of circulating snake venom in order to cause a huge disturbance in you, and if you survive you can become a cripple for the rest of your life if it's left untreated.

Chris -   I've got an email here from Arjan Hoek, who's listening from Delft in the Netherlands and he says:  "I think your show is one of the best podcasts in the world" (That's his opinion, of course.)  "When I heard that you were going to talk about venoms and toxins on this week's show I was wondering how you produce antivenom?"

Gavin -   Okay, antivenom has been around for at least 100 years, but the techniques of producing antivenom have not really altered a lot in that time.  What normally happens is a very large animal is immunised over a long time with very small amounts of snake venom, so it won't harm the animal; traditionally they have used horses.

Chris -   So what you would do is milk the snake, get some of its venom and then inject that into the horse.

Gavin -   Yes, in very small quantities, so the horse will not be affected at all, it's only a tiny amount.  The horse will then raise antibodies against this antigen that's been injected in the same way that humans immunised with smallpox would be raising antibodies against that.

Chris -   So the horse gets antibodies in the bloodstream.

Gavin -   That's correct, and over a long period of time, say eight months or so, the horse will then become hyper-immune.  Every so often, some serum is then drawn from the horse and immunoglobulins are purified from that, and from that you can split the immunoglobulins into smaller components such as the FAB or the FAB prime-2.  And these would then be infused intravenously to a person who presents themselves in hospital who has been envenomed.

Chris -   And so the antibodies would, in that victim, lock on to the venom and neutralise it?

Gavin -   They would.  They would seek out the circulating venom in the patient and immobilise it.  They would form an immune complex and would be completely harmless and would then be flushed away normally.

Chris -   Just to finish off then Gavin, you are also using the way in which these venoms work in people for clues about the way in which our own bodies work.  What have you flushed out from doing that and how does that process work?

Gavin -   Well there's a lot of proteins that have been isolated from snake venoms that have been seen as very useful over the years.  Particularly in our kind of work, we've isolated proteins that have inhibited or activated platelets.  Now these are very important in clotting and we've seen various signalling events that happen in the course of activation and inhibition of platelets.  These could be perhaps exploited as a therapeutic targets which could be explored in the future, if only we had far more research income or pharmaceutical companies could pick up on this.

Chris -   So better ways to make the blood not clot in people who have clotting illnesses such as heart attacks, strokes, or other hypercoagulable disorders.