What's your poison?

Snake venom has long been used to cure as well as kill. Now, scientists have found that even harmless species provide toxins of vital medicinal use

A hundred years ago, Rudyard Kipling explained to the world how the elephant got its trunk. Now, scientists in Wales and Australia believe they have written an important addition to the
Just So Stories, "How the Serpent got its Venom".

A hundred years ago, Rudyard Kipling explained to the world how the elephant got its trunk. Now, scientists in Wales and Australia believe they have written an important addition to the Just So Stories, "How the Serpent got its Venom".

Research into the origins of venom production has revealed that there are 2,200 species of poisonous snake in the world - 2,000 more than previously believed. New evolution studies by Dr Bryan Grieg Fry at the University of Melbourne show that almost all snakes share a common, venomous, ancestor, and hundreds of harmless species - previously thought only to produce "toxic saliva" - have been shown to produce true venom. It seems that even the most harmless species, such as grass snakes and rat snakes, possess a venom of similar complexity to those of their most deadly cousins, such as vipers and cobras, albeit in small quantities and without the apparatus to deliver it efficiently.

It is estimated that about five million people each year are bitten by snakes, resulting in about 125,000 deaths. A better understanding of the composition of venoms - and the way that venoms of snakes of the same species can vary - can help doctors to develop more effective antivenoms. Furthermore, venoms contain substances such as neurotoxins that can have powerful pharmaceutical effects, and can be used to create new medicines. Several treatments, including the widely used anticoagulant Arvin, have already been derived from components of snake venom. According to these findings, therefore, there are thousands more types of snake venom that can be used in medical research than previously thought.

"Snake venoms are complex mixtures of proteins. There can be as many as several hundred individual components in one venom," says Dr Wolfgang Wüster of the University of Wales at Bangor, who carried out the research with Dr Fry. "Some of the components might interfere with blood coagulation, others make blood vessels leaky, while others block the transmission of nerve signals - causing paralysis."

Scientists can use some of the components in venom to have a beneficial effect on the body. For example, some poisons reduce blood pressure so quickly that a victim dies instantly. By isolating and reproducing the relevant component in this venom, scientists can make a drug that reduces blood pressure. Moreover, drugs that imitate snake poison are fast and effective, because venom has evolved over millions of years to be fast and effective.

"We see the first recognisable snakes in the Cretaceous Period, about 100 million years ago," says Dr Wüster. "If we examine the evolutionary tree we see a series of branches that lead to the living primitive snakes." Of the 2,700 species of snake known today, about 500 are classified as primitive. "In the late Cretaceous Period, and particularly the Tertiary," continues Dr Wüster, "we see a radiation of evolution of the modern snakes, with about 2,200 new species evolving. These include all the strongly venomous species, as well as many non-dangerous ones such as rat snakes and grass snakes. In this group, venom is widespread and present in most species, whether they are dangerous to people or not. Clearly, for most snakes venom is integral to their natural history. For us, the interesting question is: when did venom evolve? Did it arise again and again in different lineages, or did it evolve only once at the base of the tree, and was retained in some species and lost in others?"

To find out whether all 2,200 species shared a common venom-producing ancestor, researchers examined the anatomy of snakes from different branches of the evolutionary tree, together with the composition of venom. "Many snakes possess a venom gland, but do not produce a lot of venom and do not have the anatomical apparatus to deliver the venom effectively," says Dr Wüster. "Some snakes produce venom but have only simple, small teeth that make only a shallow wound in their prey into which some venom might seep. The next level of sophistication is for snakes to have longer, grooved teeth at the back of the upper jaw. The venom can flow down the channels in the teeth. The most sophisticated system, which is seen in the vipers, consists of two very long tubular fangs that are hinged and can swing forwards. Venom is squeezed out of the gland by muscles and squirted into the prey."

When the researchers analysed samples of venom across a large number of species, from the marginally venomous to the highly dangerous, they found that harmless snakes of the genus Coluber, such as the grass snake, had complex venoms similar to those of the more venomous snakes.

"All the snakes seemed to have similar classes of protein in their venom," says Dr Wüster. "This strongly suggests that venom was derived from a common origin. If it had been reinvented several times throughout the evolution of different species, you would expect different families of protein in each venom."

The scientists then analysed the sequence of the amino acid chains that make up the proteins. "This is a technique called molecular phylogeny," says Dr Wüster. "We can compare the sequences against those held in databases that show the evolutionary origin of proteins. What we found was that if you look at the evolution of the venom proteins and superimpose it on the evolution of the snakes, they arrive at a common focal point in the past - the beginning of the radiation of the modern snakes. In other words, we have found strong evidence that venom evolved in the common ancestor of the modern snakes."

"This makes perfect evolutionary sense," adds Dr Fry. "There could not have been 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 preceded the fang just as the ability to make noise in the primates preceded the voicebox.

"The colubrids can still deliver the venom - they have teeth, after all," he continues. "Fangs were an improvement that allowed for greatly improved delivery into prey. The development of venom was therefore a key prey-capture adaptation in snake evolution and the fangs came much later."

The findings, however, have raised new questions. "What is in this venom in the colubrid snakes?" asks Dr Wüster. "There is a huge diversity of these snakes and, until now, they have been almost completely ignored from the point of view of their venom. We would like to know what is in these venoms - have they generated new families of toxins that might have potential medical applications?"

Meanwhile, the evolution of venoms continues within individual populations. "Often you find that closely related species of snake, and even snakes of the same species but in different locations, can have substantially different venoms," says Dr Wüster. In a pioneering piece of research, one of Dr Wüster's colleagues, Jennifer Daltry, collected venom from a large number of Malaysian pit vipers in the wild, together with records of the snakes' diet. Snakes in some localities fed mainly on reptiles, while those in others fed mainly on mammals; others ate both. Populations that had a similar diet had similar venom. "So the composition of the venom was being tailored genetically to the type of prey eaten," says Dr Wüster. "This strongly suggests that natural selection is at work, and would account for populations of the same species having radically different venoms."

Intriguingly, it seems that it is not only snakes that evolve to deal with their prey: there is evidence that prey evolves a resistance to venom, too. "For example, one species of amphibious snake called the sea krait feeds on moray eels," says Dr Wüster. "In areas where morays are preyed upon by kraits, the eels have developed resistance to the venom. An eel from a population that is not routinely preyed upon by the snake can be killed by a tiny amount of venom, whereas one from a population that is routinely preyed upon requires a thousand times more. In the same way that snakes must adjust the composition of their venom to best suit their prey, the prey itself can evolve resistance. What seems to be going on is an evolutionary arms race, whereby beasts of prey are evolving resistance and the snakes in turn adjust the composition of their venom to make it more effective."

Dr Fry has also made advances in analysing the genetic structure of venom. While studying the development of venom, he found that, rather that being derived from saliva, 21 of the 24 known snake-venom toxins were found to have derived originally from proteins normally expressed in other body tissues, including the brain, eye, lung, heart, liver, muscle, mammary gland, ovary and testis. He says: "By recruiting and tweaking proteins from other body tissues, snakes developed a clever mechanism for creating more specific and highly potent toxins, ones that would cause their victims' bodies to turn against themselves upon injection." This discovery, too, has implications for the medical scientists. Armed with the information that particular proteins in snake venom come from different areas of the body, they can look at that area when working out how the protein was originally produced. They have a starting point in the long process of deciding how to reproduce the beneficial component of the poisonous venom.

"There is something peculiarly fascinating in the use of a deadly toxin as a life-saving medicine," says Dr Fry. "The natural pharmacology that exists within animal venoms is a tremendous resource waiting to be tapped."

A VENOMOUS HISTORY

The use of snake venom in medicine was pioneered by Dr Alistair Reid in the 1960s and 1970s. While he was investigating the effects of snake bite in groups of people bitten by the Malayan pit viper, he found that it was extremely difficult to stop bleeding in affected patients. Dr Reid demonstrated that this was due to the effect of venom on clotting agents, fibrins, in the blood. Scientists were able to isolate the anticoagulant components in the venom, and the resulting drug, Arvin, has been used clinically since 1968.

"The benefits of snake venoms for heart patients are well-known," says Professor Sir Charles George, medical director of the British Heart Foundation. "They led to the introduction of ACE inhibitors that lower blood pressure."

New research is taking place in Oxford, Birmingham and at the Alistair Reid Venom Research Unit at the Liverpool School of Tropical Medicine intoisolating substances in snake venom that inhibit the action of platelets in the blood and prevent clotting.

Alice Fordham

Start your day with The Independent, sign up for daily news emails
News
Ben Little, right, is a Labour supporter while Jonathan Rogers supports the Green Party
general election 2015
News
The 91st Hakone Ekiden Qualifier at Showa Kinen Park, Tokyo, 2014
news
Life and Style
Former helicopter pilot Major Tim Peake will become the first UK astronaut in space for over 20 years
food + drinkNothing but the best for British astronaut as chef Heston Blumenthal cooks up his rations
News
Kim Wilde began gardening in the 1990s when she moved to the countryside
peopleThe singer is leading an appeal for the charity Thrive, which uses the therapy of horticulture
Sport
Alexis Sanchez celebrates scoring a second for Arsenal against Reading
football
Life and Style
health
Voices
An easy-peel potato; Dave Hax has come up with an ingenious method in food preparation
voicesDave Hax's domestic tips are reminiscent of George Orwell's tea routine. The world might need revolution, but we like to sweat the small stuff, says DJ Taylor
News
i100
News
Japan's population is projected to fall dramatically in the next 50 years (Wikimedia)
news
Life and Style
Buyers of secondhand cars are searching out shades last seen in cop show ‘The Sweeney’
motoringFlares and flounce are back on catwalks but a revival in ’70s car paintjobs was a stack-heeled step too far – until now
ebooks
ebooksA special investigation by Andy McSmith
  • Get to the point
Latest stories from i100
Have you tried new the Independent Digital Edition apps?
Independent Dating
and  

By clicking 'Search' you
are agreeing to our
Terms of Use.

iJobs Job Widget
iJobs General

Recruitment Genius: Project Implementation Executive

£18000 - £23000 per annum: Recruitment Genius: They work with major vehicle ma...

Recruitment Genius: Chiropractic Assistant

£16500 per annum: Recruitment Genius: A Chiropractic Assistant is needed in a ...

Recruitment Genius: Digital Account Executive - Midlands

£18000 - £26000 per annum: Recruitment Genius: They work with major vehicle ma...

Recruitment Genius: Web Developer

£28000 - £30000 per annum: Recruitment Genius: This company provides coaching ...

Day In a Page

NHS struggling to monitor the safety and efficacy of its services outsourced to private providers

Who's monitoring the outsourced NHS services?

A report finds that private firms are not being properly assessed for their quality of care
Zac Goldsmith: 'I'll trigger a by-election over Heathrow'

Zac Goldsmith: 'I'll trigger a by-election over Heathrow'

The Tory MP said he did not want to stand again unless his party's manifesto ruled out a third runway. But he's doing so. Watch this space
How do Greek voters feel about Syriza's backtracking on its anti-austerity pledge?

How do Greeks feel about Syriza?

Five voters from different backgrounds tell us what they expect from Syriza's charismatic leader Alexis Tsipras
From Iraq to Libya and Syria: The wars that come back to haunt us

The wars that come back to haunt us

David Cameron should not escape blame for his role in conflicts that are still raging, argues Patrick Cockburn
Sam Baker and Lauren Laverne: Too busy to surf? Head to The Pool

Too busy to surf? Head to The Pool

A new website is trying to declutter the internet to help busy women. Holly Williams meets the founders
Heston Blumenthal to cook up a spice odyssey for British astronaut manning the International Space Station

UK's Major Tum to blast off on a spice odyssey

Nothing but the best for British astronaut as chef Heston Blumenthal cooks up his rations
John Harrison's 'longitude' clock sets new record - 300 years on

‘Longitude’ clock sets new record - 300 years on

Greenwich horologists celebrate as it keeps to within a second of real time over a 100-day test
Fears in the US of being outgunned in the vital propaganda wars by Russia, China - and even Isis - have prompted a rethink on overseas broadcasters

Let the propaganda wars begin - again

'Accurate, objective, comprehensive': that was Voice of America's creed, but now its masters want it to promote US policy, reports Rupert Cornwell
Why Japan's incredible long-distance runners will never win the London Marathon

Japan's incredible long-distance runners

Every year, Japanese long-distance runners post some of the world's fastest times – yet, come next weekend, not a single elite competitor from the country will be at the London Marathon
Why does Tom Drury remain the greatest writer you've never heard of?

Tom Drury: The quiet American

His debut was considered one of the finest novels of the past 50 years, and he is every bit the equal of his contemporaries, Jonathan Franzen, Dave Eggers and David Foster Wallace
You should judge a person by how they peel a potato

You should judge a person by how they peel a potato

Dave Hax's domestic tips are reminiscent of George Orwell's tea routine. The world might need revolution, but we like to sweat the small stuff, says DJ Taylor
Beige is back: The drab car colours of the 1970s are proving popular again

Beige to the future

Flares and flounce are back on catwalks but a revival in ’70s car paintjobs was a stack-heeled step too far – until now
Bill Granger recipes: Our chef's dishes highlight the delicate essence of fresh cheeses

Bill Granger cooks with fresh cheeses

More delicate on the palate, milder, fresh cheeses can also be kinder to the waistline
Aston Villa vs Liverpool: 'This FA Cup run has been wonderful,' says veteran Shay Given

Shay Given: 'This FA Cup run has been wonderful'

The Villa keeper has been overlooked for a long time and has unhappy memories of the national stadium – but he is savouring his chance to play at Wembley
Timeless drama of Championship race in league of its own - Michael Calvin

Michael Calvin's Last Word

Timeless drama of Championship race in league of its own