New Antivenom, Thanks To 200 Intentional Snake Bites
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Hey, Shore Wavers, Regina Barber here. And today I'm joined by reporter Ari Daniel, who's going to talk to us about snakes. Hey, Ari. Hi there, Regina. Yes, venomous snakes, to be exact. They're a big problem, especially in low and middle income countries and in the tropic.

The World Health Organization estimates that every year tens of thousands of people die as a result of venomous snake bites and that they permanently disable several hundred thousand more. That is awful. Absolutely. The specific health risks vary.

And that's partly because venoms are a brew of different chemicals. There are neurotoxic venoms that can lead to paralysis, including of the airway. So people suffocate. Other venoms can affect the blood, causing it either to fail to clot or to form clots too readily. Some venoms cause intense pain and others cause no pain at all. Okay.

This is not helping my fear of snakes. Well, would it help if I told you that I met a couple of researchers working on a potential solution? Yes. It's a cocktail that works against a diverse collection of venomous snakes using a process they hope could one day lead to a universal anti-venom. Ooh, that's really, really cool. Yes, that does help quite a bit. Well, good, because this is happening.

And it all started with this guy, Tim Friede. My claim to fame is getting bit by snakes. For years, Regina, he's let snakes bite him. Oh, gosh. Okay. Tell me more. Tell me more. Let me go back a little to 2001. Tim started with cobras because that's what he had on hand at the time. Right.

Tim's been fascinated with snakes for as long as he can remember. He used to hunt garter snakes growing up in Wisconsin. They're harmless. But over the years, to raise awareness of the actual danger that venomous snake bites pose, he's allowed himself to be bit some 200 times. Wow.

By all kinds of snakes, black mambas, taipans, cobras, crates, and more. Wow. Wow. Okay. But-

All of this biting, it's to help people, right? Yes, that's right. So this may be kind of a deep cut, Gina, but you've probably seen the 80s fantasy movie, The Princess Bride. Yes, I've memorized that movie. Perfect. So you already know that in the movie, there's this fictional poison called Iocane powder. Yes, this is what I thought of as soon as you told me about this story. Right. I smell nothing.

What you do not smell is called iocane powder. It is odorless, tasteless, dissolves instantly in liquid, and is among the more deadly poisons known to man. Wesley, he's one of the main characters who was just speaking, he ultimately reveals that he's built up an immunity to this poison by starting with a small dose that wasn't enough to kill him and gradually increasing that dosage over time. I spent the last few years building up an immunity to iocane powder.

This is more or less what Tim did, Regina, except with snake venom. He admits it's been something of a rocky road, though, right out of the gate, he says this happened. He recovered, got more careful.

And he kept on going. Wow. Then at some point, he was like, hey, could my immunity to this swirl of toxins provide some kind of roadmap to making a broad kind of antivenom? So today on the show, the antivenom man. We're talking about a different approach to developing a treatment to venomous snake bites. And the researchers who use Tim Friede's antibodies to do it. Antibodies developed over a nearly quarter century of self-inflicted bites.

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Okay, Ari, I think the first thing I want to understand is, like, what is antivenom? Like, what is it made out of exactly? Right. So usually when the human body encounters a foreign substance, whether it's a poison or a parasite or virus, it'll trigger some kind of immune response, which involves the production of antibodies.

specialized proteins that specifically recognize that substance, bind to it and neutralize or destroy it. Right, right. I kind of know about this. Like even after the toxin has left your body, you retain like immune memory of it, right? Yeah, right. So that if you like encounter this like foreign substance again, your body will recognize it and ideally mobilize against it more quickly. Like some vaccines work like this.

Exactly. So, pit viper antivenom, for example, is made from antibodies that already recognize pit viper venom and know how to handle it. And those antibodies can be used as a treatment.

Gotcha. But here's the thing about existing antivenoms that might be administered. The antibodies that they contain aren't produced by human immune systems. For decades, they've come from animals like horses that have been injected repeatedly with small amounts of venom. Wow. But this guy named Jacob Glanville, he's the CEO of a biotech company called Centivax. He wondered about a different approach.

making antivenoms from antibodies produced by humans. So he started calling around. I was calling, hoping for a clumsy snake researcher, and I was coming up empty. Wait, clumsy like somebody who's been bitten a lot? Yes.

And then Jacob read about Tim. If anybody has broken through the problem of getting the immune system to focus, it's this guy by this repeated stimulation with all these snakes. So he found his way to Tim and called him up. Tim remembers Jacob saying to him, You're the guy I'm looking for. We need your blood. We need your antibodies. I'm like, wow, cool, great.

Wow. So, like, what happens next? Like, were the researchers able to, like, synthesize something from Tim that, like, maybe could work as an antivitam? Well, once Tim agreed to participate, Jacob got a blood sample from him, and he scanned it for its immune memory. He searched the troves of antibodies for those that neutralized the neurotoxins of multiple snakes. And then that's how we found the ultra-broad antibody

antibody that had this very remarkable ability to go bind right on the conserved site that the neurotoxin uses to cause paralysis. The antibody, which has a name that's just a string of letters and numbers like a license plate, gave mice full protection against five snakes, the black mamba, and a mix of cobras.

So Jacob and his colleagues wrote the journal Cell to gauge their interest in publishing the research. One of those colleagues was Peter Kwong, a structural biologist at Columbia University. A really smart editor said, look, antibodies are wonderful, but I think we could actually go further. And she proposed something like a working cocktail. A working cocktail of more than just one antibody? Yes, one that would take on even more snakes. This is so cool.

The team agreed it was worth a try. First, they added a small synthetic molecule, one that had already been shown to work against some venoms. Here's Jacob again. And some additional species were suddenly covered, some completely and some partially. The team also went back to Tim's blood and found a second broad-acting antibody.

And so we added that in, and that's when we suddenly saw this coherent protection that was happening across this large panel. This cocktail of three components offered mice complete protection against 13 species and partial protection against six more, representing a set of genetically diverse venomous snakes from Asia, Africa, Australia, North America, and more. Wow, that is really, really cool. Is this the biggest number of snakes targeted by an antivenom, like, until now? Yeah.

There are other antivenoms that can neutralize a broad set of snakes, but this is the first one to do it using this approach. Wow. Okay, so what's the next step here? Well, eventually human trials, which Jacob hopes are a couple years out. But before that, the team's planning to test their new cocktail in dogs that have been bit by venomous snakes in Australia. Okay. So this is a first step, but others in the field say it's an important one.

because it's answering some of the questions we have about how to properly design universal antibodies. This is David Williams. He evaluates antivenoms for the World Health Organization. He cautions that further developing this cocktail into a truly universal antivenom will inevitably have its challenges. Like right now, the recipe doesn't work on any vipers, which are a large portion of the venomous snakes that are out there. Wow.

And another researcher I talked to, Stuart Ainsworth, he's a molecular biologist at the University of Liverpool who studies snake bites, antivenoms, and antibodies. He told me that now we know this cocktail works in mice, he's eager to see how it'll work in people, given that venoms are complex chemical mixes. There are lots of other different components in venoms. And we don't know, going forward, if we just neutralize the key components in the venom, what will the other toxins do? And this is why it's very important to do clinical trials. Okay.

Okay, that makes sense. But let me ask you, Ari, like what happened to that like snake bite dude, like Tim Friede? He became director of herpetology at Centivax, that biotech company. Wow. When he heard that his antibodies had helped create this new anti-venom cocktail, he says he was happy. I couldn't believe it. I really couldn't believe it. I'm doing something for humanity and getting back to science. Aww. Aww.

So is he still like letting snakes bite him? He's retired from the snake bite life for multiple reasons. But Tim told me he sometimes still misses it. Really? Yeah. Mostly in terms of just knowing where it could take his mind.

It's a no-brainer. You can beat that and keep her calm and keep her cool. It's a wonderful thing. Wow. Okay. Well, I'm glad he sees it this way. I could not do this. Nor should you, Regina. No one suggests you take the Princess Bride approach to snake venoms. Message received. Don't learn from TV. It's fantasy for a reason. Ari, thank you so much for bringing us this story. I had a great time. For sure, Gina. Thanks for having me. Thank you.

This episode was produced by Hannah Chin and edited by our showrunner, Rebecca Ramirez. Tyler Jones checked the facts. Jimmy Keeley was the audio engineer. Special thanks to Johannes Dergi. Beth Donovan is our senior director and Colin Campbell is our senior vice president of podcasting strategy. I'm Regina Barber. Thanks for listening to Shortwave from NPR.

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At Thrive Market, they go beyond the standards, curating the highest quality products for you and your family while focusing on organic first and restricting more than 1,000 harmful ingredients. All shipped to your door. Shop at a grocery store that actually cares for your health at thrivemarket.com slash podcast for 30% off your first order plus a $60 free gift.