So, like, there’s this super weird scientific duo that’s totally out of the ordinary. Jacob Glanville, he’s an immunologist who used to work for the big pharma company Pfizer, but then decided to do his own thing and start up some companies that focus on creating treatments for stuff like coronaviruses, malaria, HIV, and even snakebites. And then there’s Tim Friede, a dude from Wisconsin who’s a truck mechanic and also a total snake fanatic. Between 2001 and 2018, he let himself get bitten a whopping 856 times by some of the deadliest snakes in the world, like black mambas, water cobras, and kraits. And get this, he did it all on purpose.
Not really sure why this matters, but Friede basically let himself get bitten and even injected himself with snake venom to build up immunity. You know, so that if he ever got bitten accidentally by one of his many pet snakes, he’d be protected. (Just a heads up, don’t try this at home, folks. Friede came pretty close to kicking the bucket a few times.) Anyway, Friede had this crazy idea that maybe his blood, with all those anti-snake venom antibodies floating around, could be useful somehow. He was just waiting for a scientist to hit him up. And one day in 2017, Glanville did just that. He stumbled upon a YouTube video of Friede’s snake adventures and gave him a ring.
Glanville was like, “Dude, I’ve been waiting to talk to you forever.” And that’s how the collaboration between Glanville’s startup Centivax and Friede began. In 2017, Centivax snagged 40 milliliters of Friede’s blood, and fast forward eight years, they made a breakthrough that was just reported in Cell last Friday. They finally cracked the code on a universal antivenom that scientists have been chasing after for ages.
The need for better antivenoms is huge. Snakebites are considered a neglected tropical disease by the World Health Organization, with around 100,000 people dying from bites each year, mostly in developing countries. And up to 400,000 peeps end up losing limbs or getting permanently disabled. Right now, a lot of snakebite treatments involve using antivenom collected from horses that have been bitten by snakes. But that method can have some serious side effects, like anaphylaxis.
But here’s the kicker: big pharma companies have been kinda slacking off on developing new snakebite treatments or even selling the old ones. They’re not seeing the money in it, ya know? But a universal antivenom could be a game-changer. It might be more appealing to investors and big pharma peeps, and it could streamline the whole antivenom market, which is currently all over the place with different snakes needing different antivenoms.
The hunt for a universal antivenom has attracted some top-notch scientists who are using the latest tech. Just earlier this year, nobelist David Baker’s crew at the University of Washington dropped a paper in Nature showing how machine learning could help design venom-neutralizing proteins. And now, the collab between Glanville and Peter Kwong, a structural biologist who’s a big deal in AIDS research, has led to some major progress.
Glanville and Kwong joined forces to create a library of like 2 billion antibodies from Friede’s blood. These antibodies had a leg up on designed proteins because they had something called affinity matching. They just kept getting better at binding to and neutralizing toxins in snake venom every time Friede got bitten. But here’s the kicker: snake venoms are like these super complex mixtures of toxins that vary from snake to snake.
The team quickly zeroed in on an antibody that could protect against a whole bunch of long-chain neurotoxins found in loads of snake venoms. This shielded lab mice from croaking after being exposed to six different snake venoms. But when they shared this finding with Cell, the editor was all like, “Nah, you gotta do more. Make a bigger cocktail of antibodies that works even better.”
Kwong was like, “Let’s do this, Jake. Your company is all about getting results. Let’s tackle this challenge.” So they added a second antibody that could battle a bunch of smaller short-chain neurotoxins, and bam, the mice were protected from nine different snake species. And the clincher came when they tossed in a synthetic molecule called varespladib, a former heart disease treatment that can actually work as an antivenom by blocking one component of venom toxicity.
The three-part cocktail proved effective against the venoms of 19 snakes from the elapid family, which is basically the most dangerous snake fam in the world. Kwong was like, “This is huge, man. We found something that fights cobras, black mambas, and kraits. We’ve created a method for breaking down venom and building a killer cocktail.”
What they managed to whip up is a cocktail that shields against multiple venoms without needing antibodies for each and every one. The key was discovering, through X-ray crystallography, that many antibodies target the same receptor on various toxins. It’s like finding that sweet spot where the toxins latch onto cells, “like a docking port on a spaceship,” as Glanville put it.
Jose Maria Guitierrez, a top antivenom researcher, thought the work was pretty darn amazing. He dug how the team took a step-by-step approach to creating a powerful cocktail and how the X-ray crystallography results showed different antibodies locking onto the same region. He did raise a valid point about the potential cost of the new treatment once it’s ready. Will it be affordable in places where snakebites are common? If not, then what’s the point, right?
Most researchers didn’t see any ethical issues with the study since Friede had willingly put himself in harm’s way before the researchers approached him. Plus, he no longer needs to keep envenoming himself. And Glanville promised to split any profits from the antivenom with Friede. Another top antivenom researcher, Andreas Hougaard Laustsen-Kiel, thought the study was solid and a great proof of concept. But he warned that it’ll take time before a universal antivenom hits the market. Manufacturing these cocktails on the cheap and finding targets for other toxin families won’t be a walk in the park.
So, yeah, the road ahead is long, but hey, progress is progress. And who knows, maybe one day we’ll have a universal antivenom that can save lives around the world, one snakebite at a time.
