Medical researchers have turned snake wranglers to harness an unusual source of new drugs
The small mottled brown snake coiled up in a box doesn’t look especially scary, compared with some of the bigger specimens that are eyeing me through their glass enclosures. But such saw-scaled vipers are responsible for more deaths than any other snake in the world.
It’s partly because they are so abundant in certain parts of Africa and Asia, but also because they are aggressively defensive and quick to strike, says Professor Nick Casewell, who is showing me around Liverpool School of Tropical Medicine’s Centre for Snakebite Research & Interventions.
The centre is home to about 150 of the world’s deadliest snakes, whose venom is regularly extracted through “milking”. Surprising as it may seem, the lethal compounds in snake venom are being used to develop a range of new, potentially life-saving medicines.
The Liverpool scientists are developing treatments not only for snakebites – which take a huge toll in low-income countries – but also for completely unrelated conditions including strokes, blood clots and haemophilia.
The reason is that snake venom contains an array of unusual biochemicals, honed by millions of years of evolution to manipulate our biology. And manipulating our biology is exactly what medical researchers seek to do.
This approach has a proven track record. The new weight-loss injections, Wegovy and Mounjaro, were developed thanks to research into the saliva of Gila monsters, a venomous lizard. “You’re leveraging evolution, in a way,” says Professor Casewell.
Safety precautions
For visitors such as myself, the precautions for visiting the snake room are not too onerous. I wear safety goggles – because there’s a spitting cobra, which likes to aim for the eyes – and have a brief safety talk, where I learn there’s a tiny chance I could have an allergic reaction to venom molecules floating in the air.
For the scientists collecting the snake venom, though, safety hinges on following a well rehearsed set of procedures, always working in a pair.
Professor Casewell holds the snake’s body, while his partner, herpetologist Paul Rowley, holds the head, right behind the jaws, and encourages the creature to bite into a membrane-covered pot. The yellow venom drips down the walls and pools at the bottom.
They work slowly and methodically, to ensure that at least one has control of the snake at all times.
“If you go too quickly, then there’s a risk for a bite,” says Professor Casewell. “There are lots of small verbal cues between you to ensure that at each step, your understanding of what the other person has done is correct.”
A saw-scaled viper lies coiled on the ground
The saw-scaled viper is quick to strike (Photo: Nandakumar M/Getty Images)
How the milking process goes can depend on the snake’s mood on the day. A fearsome brown cobra is fairly placid while it is handled, only rearing up and inflating his hood when it’s all over, as if to show he’s not really a pushover.
A large puff adder, however, seems to writhe around angrily while being handled, and it takes a few tries to get him in the right position.
When the pair aren’t holding the snake firmly with their hands, they use a variety of home-made tools to keep it at a distance. They look like long sticks terminating in a hook or other implement.
Snake on the loose
Occasionally, a snake will break free.
But this is no cause for panic, says Professor Casewell. The pair just step back, before gently pinning down the snake on the room’s soft mat with their tools.
“The most challenging thing is with the large snakes, like the mambas and cobras, because they’re very, very quick,” he says. Black mambas are one of the world’s deadliest snakes, because their venom is so potent. “You can find that they’re climbing up your hook – you have to throw the hook down.”
And should the worst happen, there is always antivenom, stored at a nearby hospital. This is made by injecting a small harmless dose of venom into sheep or horses. The animals make antibodies against the toxic compounds, which can be collected from their blood.
Antivenom is a lifesaver, and is given to hundreds of thousands of people a year. But it has some drawbacks, including that it is specific to each snake – so you have a problem if you don’t know which kind of snake bit you – and it has to be injected, so people in poor and rural areas may die before reaching a hospital where it can be administered.
Better snakebite treatments are desperately needed. And this is where the Liverpool team come in. They are developing a range of new medicines, including more sophisticated forms of antivenom that are effective against multiple kinds of snake.
A variable bush viper hangs from a thin branch
Variable bush vipers hang around in trees
Another strategy is to create an oral medicine that could be stored and administered away from hospitals.
This is possible because many of the toxins in different snake venoms are reactive molecules that have an atom of zinc at their core. The Liverpool team are developing treatments that bind to zinc, stopping the toxin from working.
The lead candidate is a medicine called unithiol that is already used in lower doses as a treatment for metal poisoning.
In higher doses, the drug blocked the effects of snakebite in animal tests and earlier this month passed an initial safety trial in people. The first tests in snakebite victims will start next year.
New medicines
It may seem more unlikely that a snakebite lab could produce treatments for unrelated medical conditions, like stroke. But there’s a long history in medical research of turning deadly venoms into new drugs.
For instance, a group of blood pressure drugs called ACE inhibitors, were developed from a chemical in the venom of the Brazilian Viper – which kills by causing a catastrophic drop in blood pressure.
Different snake venoms have different effects on the body – some affect nerves, while others directly break down tissues. The Liverpool team are interested in a third major group of venoms, which affect blood clotting.
Blood clotting is a highly complex process. Blood should normally flow freely through our veins, but it must be able to quickly solidify at sites of injury – our lives may depend on it. The clotting process depends on dozens of different cells and biochemicals reacting to turn liquid into a jelly-like plug.
Like many snakes, the saw-scaled viper’s venom works by blocking that clotting process, causing victims to bleed to death. Professor Casewell’s team is investigating exactly which parts of the blood-clotting cascade it targets. It could lead to treatments for diseases that involve blood clots, which includes strokes, heart attacks and deep-vein thrombosis.
Other universities around the world are investigating different venoms that, conversely, boost blood clotting. These could form the basis of treatments for when someone is bleeding too freely, after surgery or childbirth.
Professor Casewell says more scientists and drug companies are getting interested in the potential of venom research as it has led to a small but growing number of successful medicines.
As well as the recent explosion in the world’s use of weight-loss injections, a potent painkiller called ziconotide was discovered in the venom of cone snails. These sea-living snails use the chemical’s nerve-blocking effect to paralyse fish so they can be eaten alive.
“The natural libraries of compounds that are out there in animal venoms are really interesting for potential therapeutics,” says Professor Casewell. “For drug discovery, that’s a really exciting starting point.”