
Snakebites kill 130,000 people a year. This UK lab may have the answer
'This one is a big mean old girl,' said Edd Crittenden, a senior animal technician at Liverpool School of Tropical Medicine's Centre for Snakebite Research and Interventions, as he prepared to trap her to extract her venom. 'She has quite an attitude — she doesn't like us some days.'
A bite from this angry snake — 5ft long, with vivid yellow and black markings — has the potential to trigger internal bleeding and cause tissue to wither and die. If untreated, it can be fatal. More than two million people are bitten by venomous snakes around the world each year, and as many as 138,000 die as a result.
The 25 researchers working at the Liverpool snakebite centre, which holds one of the largest collections of tropical venomous snakes in Europe, is aiming to develop new treatments. And they are close to a breakthrough.
Next summer they will start trialling two pills for snakebite victims in Ghana and Brazil. The new approach could have a radical impact on snakebite mortality.
Currently the only treatment for a bite from a venomous snake is an antivenom — a medicine produced by extracting antibodies from the blood of sheep or horses that have been repeatedly dosed with snake venom. But that approach, which dates to the 19th century, is riddled with problems.
'Snake venoms vary from one species to the next,' said Nick Casewell, director of the centre. 'Each antivenom works only against certain snakes, and some of them are actually very poor. Even if they work, they have to be given in a major hospital, because they are given intravenously, via a drip, and people often have adverse reactions to them, so you want to be able to carefully monitor them. But in rural Africa or Asia or the Amazon rainforest, those kinds of facilities are often many hours or even days away.
'So what we're trying to do is develop an oral medication that can be given in the community soon after a bite. It doesn't need to be stored in a fridge like antivenom. And it can be given by anyone: you don't need any specialist training to give a pill.'
Eventually, tourists may be able to carry the pills if travelling in risky areas. Even in Britain, where snakes are often kept as pets, dangerous snakebites occur. Some 300 people, 72 of them children, were bitten by exotic snakes between 2009 and 2020, according to reports to the UK National Poisons Information Service. Antivenom was given in 17 cases, and one person died.
Deaths from native British snakes are far rarer — the last recorded death from an adder was in 1975.
Casewell's team has already carried out a phase 1 trial of one new snakebite treatment, a pill called unithiol, showing that it was safe on healthy patients in Kenya. Next year they will start a phase 2 trial on patients who have been bitten by snakes, alongside another treatment called marimastat. About 200 people will take part in the trial across Ghana and Brazil.
Both medicines were initially developed for other purposes — unithiol to treat poisoning from mercury, arsenic and lead, and marimastat to treat cancer.
They both work by reducing the impact of metalloproteinases — a type of enzyme which is active in metal poisoning, some forms of cancer and also, the team discovered, in snake venom.
'We realised these are a really important component,' said Casewell. 'Terciopelo, the Malayan pit viper, saw-scaled vipers, Russell's viper — they all have a lot of metalloproteinases in their venom. Our drugs are targeting that toxin family.'
He added: 'Our long-term vision is that we would have one pill to deal with some of the toxins and another to deal with some other toxins. And then it doesn't matter so much which snake you're being bitten by, you should be able to delay pathology. We're hoping those drugs will at the very least reduce the severity of envenoming, and buy that patient a lot more time to get secondary treatment.'
David Lalloo, vice-chancellor of the Liverpool School of Tropical Medicine and a world-leading snakebite expert, said: 'Oral treatments would be a game changer — there's no doubt at all.'
But he said a deeper problem is that snakebites have been ignored as a medical problem. 'The response globally has not been anywhere near as extensive or urgent as it needs to be.' As co-chair of a new Global Snakebite Taskforce, a group of doctors, scientists and world leaders formed at the World Health Assembly in Geneva in May, he is trying to raise political awareness and investment.
Until then, the researchers in Liverpool need more venom to test — which is why Crittenden was in the lab trying to trap the angry terciopelo. He had already extracted the venom from a pair of Malayan pit vipers and then a Mozambique spitting cobra — for which he wore a face shield, for fear of its 10ft spitting range.
The furious terciopelo posed a different challenge. Using a long-handled tool, a band of rubber stretched across two prongs, Crittenden pinned the snake against the floor and reached down, grasping it just behind its jaws. It bared its fangs, trying to whip its head around to bite his wrist, but his grip stopped the movement.
Together with his colleague Paul Rowley, who secured the tail, they carried the snake to a beaker with a silicone lid. The viper — which was donated to the centre by a pet shop in Bristol — bit down through the silicone, yellowish venom dripping into the glass.
Crittenden and Paul Rowley trap the angry terciopelo
SUNDAY TIMES PHOTOGRAPHER JAMES GLOSSOP
'What I find really interesting is venom's biological variability,' said Casewell, as Crittenden labelled the beaker to store away. 'You're bitten by one snake and you might bleed. You're bitten by another snake, you might have a breathing paralysis. You're bitten by another snake, you might have none of those and just some really severe local tissue damage.
'Now we're able to apply the knowledge gained to hopefully make a real impact on people who are bitten by snakes.'
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In Singapore, for instance, only male Wolbachia-infected mosquitoes are released. When they mate with wild, Wolbachia-free females, their eggs become infertile and do not hatch, causing the overall insect population to gradually get smaller over time. However, to be effective a constant stream of Wolbachia-carrying males have to be released. Brazil uses a different technique, reliant on both male and female Wolbachia-infected mosquitoes. When these bacteria-carrying insects mate, they pass the Wolbachia onto their offspring. The aim is that, after several generations, the majority of insects in any given area carry the bacteria, which then helps to suppress the spread of disease. 'In our case we want to have the replacement of the [mosquito] population, so that this becomes sustainable over time,' said Dr Moreira. 'We did a set of releases in 2014 and 2015. In those areas, Wolbachia is still in the mosquitoes. We don't need to do new releases again and again.' Since scientists at Monash University in Australia first identified the dengue-blocking capacity of Wolbachia some 15 years ago, multiple real-world studies have confirmed that this concept works – and it's safe. In 2020, a major randomised control trial in Indonesia found dengue cases dropped by 77 per cent in areas of Yogyakarta city where Wolbachia mosquitoes were released, while results in 2023 showed incidence fell by at least 94 per cent in three Colombian cities. But Dr Moreira warned the intervention is not an overnight fix. 'Wolbachia is a very powerful tool, especially when it is integrated with other measures,' he said. 'But it takes time for Wolbachia mosquitoes to establish. 'Politicians call in the middle of an epidemic and say they want us to come next month. We are clear and transparent that this won't help next month, it might take a year or two.' 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'The way we reared mosquitoes in the facilities for instance at Fiocrux, was a simple way: in trays and with lots of labour and hand processes,' said Dr Moreira. 'With the creation of our big factory now, we are bringing new equipment. We have machines to hatch the eggs… and we feed mosquitoes with automated devices.' He added that the facility also has a highly-controlled environment, to optimise conditions for the eggs, larvae and mosquitoes. Temperatures range from 27C to 29C depending on the stage of the life cycle, with humidity at 70 to 80 per cent, while insects are fed sugar, fish food and horse blood (a replacement for biting live animals, including humans). But only a small proportion of the eggs actually hatch in the factory. The vast majority will be shipped by car, plane and boat across the vast country as eggs, before local health officials add water and rear the larvae. 'We dry the eggs, and they don't hatch until they [come] into contact with the water,' said Dr Moreira. 'We put the eggs in capsules, or we can ship in filter paper. They can be [stored] for two or three months, they will still survive.' He added that the government has earmarked 40 cities, each home to more than 100,000 people, where they would like these eggs to be sent. Six cities have already been selected, where the first Curitiba-bred mosquitoes will be released as early as August. 'It will be exciting to get to that moment,' said Dr Moreira, who was working in the lab in Australia in 2009, when scientists first identified Wolbachia's disease-blocking potential. 'It's been a long time coming, slowly going through the scientific evidence and expanding into a robust programme in Brazil,' he added. 'Wolbachia is only one element of the solution for dengue, but I think it will be a very significant one for the country.'