Tim Friede has a superpower – he is immune to snake bite.
A self-taught herpetologist (reptile nerd) and venomous snake collector, he began injecting himself with diluted venom from his collection in case he ever got bitten accidentally. Over the last twenty years he has taken on more than 700 doses of snake venom, each slightly stronger than the last, to boost his immunity. He is still alive despite 856 injections and more than 200 bites!
Amongst the snakes in his collection are eastern brown snakes, inland taipans and tiger snakes. All potentially lethal.
Now researchers from the Columbia University’s spinout Centivax, say Friede’s blood and its antibodies could potentially save lives.
“The donor, for a period of nearly 18 years, had undertaken hundreds of bites and self-immunizations with escalating doses from 16 species of very lethal snakes that would normally a kill a horse,” says first author biotechnologist Dr Jacob Glanville of Centivax.
“What was exciting about the donor was his once-in-a-lifetime unique immune history,” says Glanville. “Not only did he potentially create these broadly neutralizing antibodies, in this case, it could give rise to a broad-spectrum or universal antivenom.”
Building the antivenom included creating a testing panel with 19 of the World Health organisation’s (WHOs) category 1 and 2 deadliest elapid snakes, including coral snakes, cobras, taipans, mambas and kraits. Elapids are a family of mostly-venomous snakes with permanently erect fangs at the front of the mouth.
The team then isolated antibodies from Friede’s blood which were then reacted with the neurotoxins found in the snakes’ venom. Testing the antibodies one by one, they were able to build a cocktail with enough components to “render all the venoms ineffective” says Glanville.
The cocktail contained three major components, including a donor antibody, which protected mice from a lethal dose of whole venom from six of the panel’s snake species, says Glanville. Further strengthening with ‘varespladib’, a known toxin inhibitor, protected against three more species. Adding a second Friede antibody gave protection across the full panel, he adds.
“By the time we reached 3 components, we had a dramatically unparalleled breadth of full protection for 13 of the 19 species and then partial protection for the remaining that we looked at,” says Glanville.
“We were looking down at our list and thought, ‘what’s that fourth agent’? And if we could neutralize that, do we get further protection?” Even without a fourth agent, their results suggest that the three-part cocktail could be effective against many other, if not most, elapid snakes not tested in this study.
“We’re turning the crank now, setting up reagents to go through this iterative process of saying what’s the minimum sufficient cocktail to provide broad protection against venom from the viperids,” says co author Professor Peter Kwong, of Columbia University.
“The final contemplated product would be a single, pan-antivenom cocktail or we potentially would make two: one that is for the elapids and another that is for the viperids because some areas of the world only have one or the other.”
“This is a really cool study,” Dr Timothy Jackson of the Australian Venom Research Unit at the University of Melbourne told Cosmos. “It looks really comprehensive, what they’ve done scientifically, and I applaud them, but we shouldn’t then report it as if it is going to be ‘game-over’ for solving snake-bite.”
“There are going to be things that elude these sorts of broad-spectrum products.” Which means you add more, he says.
“These designed cocktails are the way of the future” he adds, not relying on a horse or some other large animal to produce all the right antibodies, but isolating them, amplifying them, growing our own from those we know are effective at making cocktails. So, this is the right approach.”
But there is much more to solving snakebite than drugs, Jackson says. Making an antivenom is the easiest part of the story, not the end of it, he adds.
“We know how to make an antivenom. Australia has had great antivenoms for decades, and we can make better and better ones with sexier methods”
“But a drug is only as good as your capacity to get it into a patient in a timely manner when they need it. “
Jackson and his team have been working in Papua New Guinea. “The problem in PNG has not been the non-existence of a good taipan anti venom. Australia has been making this for several decades, and it works perfectly well against PNG taipans.”
The problem has been the cost. “The PNG government couldn’t afford enough of it. But even more profoundly, the problem has been distribution, because most of PNG’s population lives outside the major urban centres.”
What if somebody gets bitten but is 10 hours away from the nearest hospital because they don’t have a car and there are no roads? Jackson asks. “How are we going to get that drug to them in time to ensure that the venom’s damage is not irreversible? They may end up on a mechanical ventilator, always assuming there is one available.
“As the World Health Organisation describes it, snakebite envenomation is a multifactorial problem,” says Jackson
The researchers plan to approach philanthropic foundations, governments, and pharmaceutical companies about supporting manufacturing and clinical development of the broad-spectrum antivenom. “This is critical, because although there are millions of snake envenomations per year, the majority of those are in the developing world, disproportionately affecting rural communities,” Glanville says.
The paper was published in Cell
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