As the snake farmer carefully milks the highly toxic Malayan pit viper, gripping the reptile’s neck with his bare hands as it sinks its fangs into a latex film, Dr Lawan Chanhome leans over.
“I was once bitten by this species,” she says gently, nodding towards the reddish-brown viper and the venom oozing into a jar. “It happened many years ago… I received the antivenom within an hour, but I was hospitalised for four days. Fortunately in my case, I didn’t lose my finger.”
The bite – from a baby pit viper she was feeding – was an occupational hazard for Dr Chanhome, head of the world’s second largest snake farm, which is celebrating its centenary this year.
Tucked between skyscrapers at the Queen Saovabha Memorial Institute (QSMI) in downtown Bangkok, the unit is home to 1,500 snakes across 50 species, including some of southeast Asia’s deadliest.
“You can see this one has a slight injury,” says Mongkhon Phanloed as the cobra faces him, standing tall on the tiled floor and sporadically darting forward with a hiss. The snake handler is unfazed by the “warning” – he’s just 35, but has already worked here for 17 years. “It was donated yesterday, someone in Bangkok found it in their house.”
The ‘farm’ – where clinical corridors lead to small rooms stacked with boxes, each home to a single snake – includes around 600 cobras. Many are reared through the unit’s husbandry programme, others are provided by locals keen to get rid of unwanted houseguests.
The cobras – along with Malayan pit vipers and five other venomous snakes – are regularly ‘milked’ and their toxins extracted to produce antivenoms, which are used in Thailand and exported across southeast Asia. Roughly 242,600 people are bitten and 15,900 still die annually in the region.
Yet the process to produce these treatments has barely changed during the 100 years that QSMI has operated. Scientists still inject horses with tiny amounts of venom, before bleeding them to collect the antibodies produced in response to the poison.
Not only is this process laborious and expensive, it is also far from perfect. The resulting equine antivenoms are not well tolerated by humans and have to be given in a hospital setting due to the high potential for fatal allergic reactions.
A second problem stems from the diversity of snake venom. Every species has a different venom, meaning that dozens of different types of antivenoms need to be made.
All this means that the world also manufactures less than half of the antivenom it needs and even this covers just 60 per cent of venomous snakes. It explains why snakes still kill an estimated 138,000 people a year, and leave another 400,000 with life-altering disabilities.
Yet many believe updated antivenoms are, finally, on the horizon – and plants could be part of the answer.
Half an hour from QSMI, the founders of Chulalongkorn University’s first pharmaceutical start-up have a steady stream of visitors keen to inspect their plant-based antibody “factory”, on the 11th floor of an otherwise modest building.
They hope their approach could simplify and dramatically reduce the cost of producing antivenoms (a price that’s considered too high by many pharmaceutical companies), by cutting horses out of the process entirely and replacing them with tobacco plants.
“There’s been loads of progress on this over the last few years,” says Prof Suthira Taychakhoonavudh, who launched Baiya Phytopharm in 2019 alongside Prof Waranyoo Phoolcharoen.
The small tobacco plant shoots stacked on shelves in the shiny white lab will be infected with a genetically modified bacteria that prompts the plant to produce monoclonal antibodies to be used as antivenom. The genetic coding of the bacteria used will determine which species of snake toxin the antivenom will work against – or at least that’s the idea.
So far, the Baiya team has mainly focused on using the plant technology to make Covid-19 vaccines – their candidate is set to enter phase two trials by summer. But they’re confident that, much like mRNA, the “plant platform” can also be applied to other fields, including cancer treatments and antivenoms.
“We are in the process of fund raising for the snake antivenom’s production and testing. Hopefully, the trial can start some time next year,” says Prof Taychakhoonavudh. “Access is really important to us, so we really want to focus on unmet needs and neglected diseases – whether that’s cancers which have attracted less funding, or snakebite.”
She adds that recent research found that although access is strong in Thailand, partly due to QSMI, in Laos just four per cent of victims receive antivenom. In Indonesia that number is just 10 per cent, rising to 26 per cent in the Philippines and 37 per cent in Vietnam.
Improving availability – which relies on reducing production costs – across the region would prevent more than 9,00 fatalities and save $1.3 billion in lost economic potential, as most victims are young, the study found.
“These countries are emerging economies, so I see a huge market for antivenoms,” says Prof Taychakhoonavudh. “And using plants is much cheaper than bio-reactors – because plants are inexpensive to grow.”
Prof Nicholas Casewell, director of the Centre for Snakebite Research and Interventions at the Liverpool School of Tropical Medicine, says the plant based system could lower costs by creating big economies of scale. It’s a whole lot easier keeping plans than horses.
“I think the plant-based technology is interesting … because of the flexibility of the system and the ability to produce quite a large number of antibodies in a short turnaround,” says Prof Casewell.
“But the challenge that remains is: what are the antibodies that ultimately we would want to produce?” In other words, the plant technology does not get around the need for producing different antivenoms for all the different species and subspecies of potentially lethal snakes – about 200 in total.
Globally, several other research groups are working on this side of the equation and other problems thrown up by existing equine based antivenoms. Several of these projects are funded by the UK-based Wellcome Trust, which announced what it hopes will be a “game-changing” £80 million investment to transform snakebite research in 2019.
This includes Prof Andreas Laustsen’s team at the Technical University of Denmark, who are trying to identify existing human antibodies which can be used to target snake venom. They’ve already identified a cocktail of three human antibodies that neutralise black mamba venom in mice, and a promising combination for cobras.
It is hoped this approach would also reduce the risk of patients suffering an anaphylactic shock when given antivenom, because a “foreign” animal protein would not be needed.
Others are working on using camel antibodies instead of horses – they’re less susceptible to the heat, which means they could be used more widely as they wouldn’t need to be kept in a fridge.
Others still are focused on “small molecule” treatments, which aren’t antibodies at all. These have the advantage of working quickly in the body, are much cheaper to produce, and could be given in tablet form.
“These may not completely replace antivenoms, but could potentially be an early intervention – so patients get an oral drug first, which gives them time to access antivenom later,” says Prof Casewell. “In the long term, I envisage that people will get a combination of next-generation therapies.”
Then there’s work on a universal antivenom, considered by some as the ‘Holy Grail’ of snakebite research. The idea is that this would not only simplify treatment, but would make it more commercially viable for manufacturers because only one product would need to be produced to tackle all snake bites.
Yet both Prof Laustsen and Prof Casewell are sceptical about how feasible such a drug would be – partly because it would be incredibly complex, and likely expensive.
“From a technical point of view, the complexity of snake venom comes from the diversity of toxins found in different snakes. That is ultimately the key issue… it’s a real headache,” says Prof Casewell.
He added that drugs which could target “each major [snake] toxin family” were more likely. “In the next five years, we’ll have a much better sense of what’s achievable”, he said.
Back at the snake farm in downtown Bangkok, Mr Planloed scoops up the loose cobra without missing a beat and he returns the donated reptile to its box.
It’s set to spend the next three months in quarantine, to ensure it has no infections that could harm the rest of the snakes here, before being put to work – both within QSMI’s public education programme, and for venom extraction.
“These snakes are effectively helping to protect people from their own venom,” says Dr Chanhome in her office, where various reptile-themed memorabilia cover the walls and bookshelves. “I think the [production] process is unlikely to change for some time.”
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