In 1894, French immunologist Albert Calmette produced the first successful antivenom by injecting horses with small doses of Indian cobra venom, then harvesting their antibodies.
For 130 years afterwards, these life-saving concoctions — along with their considerable defects — have remained fundamentally the same. Each one works only against a single species, making treatment tricky if you can’t identify the snake that bit you. Plus, because they originate in animals, the foreign antibodies can prompt a severe immune response.
Over the past decade, however, antivenom experts have begun to envision a new future. Hoping to release the field from its 19th-century roots, they’ve adopted next-generation therapies to address a public-health scourge that kills upward of 100,000 people every year in tropical countries, and leaves many more permanently disabled. Their work is starting to pay off.
A New Antivenom Emerges
Earlier this year, in what they framed as a major step toward a “universal antivenom,” an international consortium of researchers unveiled 95Mat5: an antibody that counteracts a deadly toxin found in various snake species around the world.
Read More: How Is Antivenom Made?
What’s more, the antibody is what scientists call “recombinant” — that is, derived from human cell lines cultured in the lab. No need for horses, and thus no danger of allergic reactions.
The study, published in Science Translational Medicine, validates an approach that critics have long dismissed as far-fetched, according to Andreas Hougaard Laustsen-Kiel, a professor at the Technical University of Denmark who was not involved with the study.
“This shows that you can actually neutralize more or less an entire subfamily of toxins with just one antibody,” he says. “It’s difficult, but it’s not impossible.”
Combating Venom’s Dizzying Diversity
We sometimes talk about cancer like it’s a single disease, when really the term encompasses hundreds of distinct maladies. In the same way, snake venom is not one thing but a constellation of toxins, thousands of them, enough to make your head spin. Every species has a unique mix, and even among members of the same species, the exact proportions can vary.
For anyone trying to tackle the problem of snake bites, this wild variation is daunting. “I wouldn’t have imagined that it’s possible to design something that would work across such scale,” says Kartik Sunagar, a venomics researcher at the Indian Institute of Science and co-author of the study.
Fortunately, venom evolved mainly for use against prey animals, not us, so many of its components aren’t lethal to humans. And the few that do cause widespread harm to humans conveniently cluster into groups, which serve as targets for broadly neutralizing antibodies.
How the New Antivenom Works
In the case of 95Mat5, the target is a class of venom proteins called three-finger toxins, which disrupt the nervous system. They’re present in all snakes from the elapid family, which includes cobras, mambas, and taipans, among others. When Kartik and his colleagues tested the antibody’s effect on mice injected with three-finger toxins from several species, it not only kept them alive but also prevented paralysis.
Read More: Is the 50-Foot Congo Snake Fact or Fiction?
Though their success was surprising, Sunagar says that when they saw what was happening on the microscopic level, it made sense: 95Mat5 mimicked the cellular receptor three-finger toxins normally bind to, so they latched on to the decoy instead. “It was acting like a sponge,” he says, “pulling out these toxins from the system, away from the receptors.”
In Laustsen’s opinion, the team’s key insight was that the antibody’s effectiveness came from its physical shape, a clue that could help researchers reproduce the feat with other toxins.
“The important thing, seen from a drug development point of view, is to look at the structures,” he says. “Which things have the same geometry, which things have the same 3D structure?” In other words, when you want to blow up a fortress, it helps to have the blueprints first.
Universal vs. Regional Solutions
Having devised a treatment for one class of toxins, Sunagar and his colleagues are already at work on another for vipers. In the long term, they hope to combine 95Mat5 with other ingredients to form a single “cocktail” that would protect against all the world’s medically significant snakes.
For the so-called “Big Four” of his home country (the Indian cobra, common krait, Russell’s viper and saw-scaled viper), Sunagar thinks just two or three antibodies might suffice. Add a couple more and you’d have a global solution that could be administered to victims throughout Asia, Australia, Africa, and South America.
Laustsen — who helped discover a similar, though less effective, antibody in 2023 — is more conservative. “Three to four to cover the world, forget about it,” he says. “The main takeaway is the ballpark number: We’re not talking about hundreds of antibodies. It is handfuls.” Lausten also argues it’s best to keep them separate, or perhaps combine a few into regional cocktails. In a paper that isn’t yet published, he and his colleagues are attempting to do just that for American coral snakes.
Still, there’s a practical reason to limit the number of antibodies in a single antivenom. With each addition the mixture becomes more diluted, requiring a larger dose for any given snake bite and thus raising production prices. Maybe a blend of 15 would thwart a wider range of toxins, but the cost to make it would be prohibitive.
Read More: Yes, Snakes Can Hear Sound
Sunagar acknowledges this challenge. If the universal recipe winds up exceeding his antibody estimate, he agrees it would be better to pivot to regional treatments. “Whatever solutions we are looking at,” he says, “we always ensure that these are not going to be very expensive, because then it defeats the purpose.” The people who need them most, typically farm laborers, wouldn’t be able to afford them.
Whatever geographic scale they’re ultimately engineered for, 95Mat5 and the strategy it represents are a big step for recombinant, broadly neutralizing antivenoms. “It validates that generally there are multiple approaches you can use to make these types of molecules,” Laustsen says. “It’s not just a one-hit wonder.”
The Problems Facing Antivenom Research
Even as the antivenom field seems to be entering a renaissance, it faces serious hurdles, many a function of the target demographic. “The thing is, this is a poor man’s problem,” Sunagar says. “Snake bite victims are in rural areas, and that’s why nobody bothers too much about this.”
Then there’s the regulatory approval process, which is ill-defined for next-generation antivenoms. Researchers may be honing their tactics for discovering useful products, Sunagar says, “but it’s a completely different thing to take something into the market. You need a lot of scientific and financial investment.”
Nevertheless, Sunagar believes investors will get on board as manufacturing costs drop and public health agencies clarify the path to clinical trials. And he argues there’s a clear financial incentive for governments to throw greater weight behind antivenom programs: For every death by envenomation, another four people are permanently disabled, resulting in a huge loss of productivity.
Read More: Slither Aside, Titanoboa, This Ancient Snake Was Also a 50-Footer
It may take many years for these new antivenoms to come to fruition, but Laustsen optimistically notes that “we are beyond speculating what might work.” Now, as the technical obstacles begin to fall, it’s mainly a socio-political matter of directing resources to pharmaceutical development.
“More and more weird diseases are being solved,” Lautsen says. “Snakes — it’s going to be their time at some point.”
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Cody Cottier is a contributing writer at Discover who loves exploring big questions about the universe and our home planet, the nature of consciousness, the ethical implications of science and more. He holds a bachelor’s degree in journalism and media production from Washington State University.
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