New Antivenom, Thanks To 200 Intentional Snake Bites

What's it like to get bit by a venomous snake? "It's like a bee sting times a thousand," Tim Friede says. Tim would know. Over the past few decades, he's let himself be bitten over 200 times by all kinds of venomous snakes — black mambas, taipans, cobras, kraits and more. With time, he's gradually built immunity to multiple types of venom. Could scientists help him share that immunity with others? Science reporter Ari Daniel https://www.npr.org/people/297147967/ari-daniel joins Short Wave to explain how antivenom works, what scientists discovered and where the research may lead. Plus, what does Tim Friede have in common with Princess Bride? Want to hear about more medical discoveries? Email us at [email protected] mailto:[email protected] to tell us what areas of science you'd be interested in. Listen to every episode of Short Wave sponsor-free and support our work at NPR by signing up for Short Wave+ at plus.npr.org/shortwave http://plus.npr.org/shortwave. See pcm.adswizz.com https://pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences. NPR Privacy Policy https://www.npr.org/about-npr/179878450/privacy-policy

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• 0:00Speaker 00

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• 0:19Regina Barber?

  You're listening to Short Wave from NPR.

• 0:24Regina Barber?

  Hey, Short Wavers, Regina Barber here. And today I'm joined by reporter Ari Daniel, who's going to talk to us about snakes. Hey, Ari.

• 0:31Speaker 02

  Hi there, Regina. Yes, venomous snakes, to be exact. They're a big problem, especially in low and middle income countries and in the tropics. 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.

• 0:53Regina Barber?

  Oof, that is awful.

• 0:54Speaker 02

  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.

• 1:21Regina Barber?

  OK, this is not helping my fear of snakes.

• 1:23Speaker 02

  Well, would it help if I told you that I met a couple of researchers working on a potential solution?

• 1:29Regina Barber?

  Yes.

• 1:30Speaker 02

  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 antivenom.

• 1:40Regina Barber?

  Ooh, that's really, really cool. Yes, that does help quite a bit.

• 1:43Speaker 02

  Well, good, because this is happening. And it all started with this guy, Tim Friedy.

• 1:50Speaker 03

  My claim to fame is getting bit by snakes.

• 1:52Speaker 02

  For years, Regina, he's let snakes bite him.

• 1:56Regina Barber?

  Oh, gosh, OK. Tell me more, tell me more.

• 2:00Speaker 02

  Let me go back a little to 2001. Tim started with cobras because that's what he had on hand at the time.

• 2:06Speaker 03

  My first couple of bites are really crazy. It's like a beast in times of thousands. You can have levels of anxiety that goes through the roof.

• 2:13Speaker 02

  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.

• 2:32Regina Barber?

  Wow.

• 2:32Speaker 02

  By all kinds of snakes, black mambas, typhans, cobras, crates, and more.

• 2:38Regina Barber?

  Wow, wow, OK. But all of this biting, it's to help people, right?

• 2:43Speaker 02

  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.

• 2:51Regina Barber?

  Yes, I've memorized that movie.

• 2:53Speaker 02

  Perfect. So you already know that in the movie, there's this fictional poison called iocane powder.

• 2:59Regina Barber?

  Yes, this is what I thought of as soon as you told me about this story.

• 3:02Speaker 02

  Right.

• 3:03Speaker 04

  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.

• 3:12Speaker 02

  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.

• 3:27Speaker 04

  I spent the last few years building up an immunity to iocane powder.

• 3:32Speaker 02

  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.

• 3:42Speaker 03

  I was put in ICU after two cobra bites. I dropped in a coma for four days.

• 3:47Speaker 02

  He recovered, got more careful, and he kept on going.

• 3:51Regina Barber?

  Wow.

• 3:51Speaker 02

  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?

• 4:03Regina Barber?

  So today on the show, The Anti-Venom Man. We're talking about a different approach to developing a treatment to venomous snake bites and the researchers who used Tim Friede's antibodies to do it. Antibodies developed over a nearly quarter century of self-inflicted bites. You're listening to Short Wave, the science podcast from NPR.

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• 5:51Regina Barber?

  Okay, Ari, I think the first thing I want to understand is, like, what is antivenom? Like, what is it made out of exactly?

• 5:58Speaker 02

  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.

• 6:18Regina Barber?

  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?

• 6:25Speaker 02

  Yep, right.

• 6:25Regina Barber?

  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.

• 6:34Speaker 02

  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.

• 6:47Regina Barber?

  Gotcha.

• 6:47Speaker 02

  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.

• 7:03Regina Barber?

  Wow.

• 7:04Speaker 02

  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.

• 7:18Speaker 06

  I was calling, hoping for a clumsy snake researcher, and I was coming up empty.

• 7:23Regina Barber?

  Wait, clumsy like somebody who's been bitten a lot?

• 7:26Speaker 02

  Yes. And then Jacob read about Tim.

• 7:29Speaker 06

  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.

• 7:36Speaker 02

  So he found his way to Tim and called him up. Tim remembers Jacob saying to him.

• 7:42Speaker 03

  This is the guy I'm looking for. We need your blood. We need your antibodies. I'm like, wow, cool, great.

• 7:49Regina Barber?

  Wow. So like, what happens next? Like, were the researchers able to like synthesize something from Tim that like maybe could work as an antivenom?

• 7:58Speaker 02

  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.

• 8:12Speaker 06

  And then that's how we found the ultra broad antibody that had this very remarkable ability to go bind right on the conserve site that the neurotoxin uses to cause paralysis.

• 8:22Speaker 02

  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.

• 8:31Regina Barber?

  Wow.

• 8:32Speaker 02

  The black mamba and a mix of cobras.

• 8:34Regina Barber?

  Wow.

• 8:35Speaker 02

  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.

• 8:46Speaker 07

  Said, look, antibodies are wonderful, but I think we could actually go further. And she proposed something like a working cocktail.

• 8:54Regina Barber?

  A working cocktail of more than just one antibody?

• 8:57Speaker 02

  Yes, one that would take on even more snakes.

• 9:01Regina Barber?

  This is so cool.

• 9:02Speaker 02

  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.

• 9:12Speaker 06

  And some additional species were suddenly covered, some completely and some partially.

• 9:15Speaker 02

  The team also went back to Tim's blood and found a second broad-acting antibody.

• 9:20Speaker 06

  And so we added that in, and that's when we suddenly saw this coherent protection that was happening across this large panel.

• 9:26Speaker 02

  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.

• 9:42Regina Barber?

  Wow, that is really, really cool. Is this the biggest number of snakes targeted by an antivenom, like, until now?

• 9:48Speaker 02

  There are other antivenoms that can neutralize a broad set of snakes, but this is the first one to do it using this approach.

• 9:55Regina Barber?

  Wow, okay, so what's the next step here?

• 9:58Speaker 02

  Well, eventually, human trials, which Jacob hopes are a couple of years out. But before that, the team's planning to test their new cocktail in dogs.

• 10:07Regina Barber?

  Oh.

• 10:07Speaker 02

  That have been bit by venomous snakes in Australia.

• 10:10Regina Barber?

  Okay.

• 10:10Speaker 02

  So this is a first step, but others in the field say it's an important one.

• 10:14Speaker 07

  Because it's answering some of the questions we have about how to properly design universal antibodies.

• 10:21Speaker 02

  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.

• 10:41Regina Barber?

  Wow.

• 10:41Speaker 02

  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.

• 11:04Regina Barber?

  The key components in the venom, what will the other toxins do? And this is why it's very important to do clinical trials. OK, that that makes sense. But let me ask you, Ari, like, what happened to that, like, snakebite dude, like, Tim Friedy?

• 11:16Speaker 02

  He became director of herpetology at Centivax, that biotech company.

• 11:20Regina Barber?

  Wow.

• 11:21Speaker 02

  When he heard that his antibodies had helped create this new antivenom cocktail, he says he was happy.

• 11:27Speaker 03

  I couldn't believe it. I really couldn't believe it. I'm doing something for humanity and came back to science.

• 11:33Regina Barber?

  Oh, so is he still, like, letting snakes bite him?

• 11:36Speaker 02

  He's retired from the snakebite life for multiple reasons.

• 11:40Regina Barber?

  OK.

• 11:40Speaker 02

  But Tim told me he sometimes still misses it.

• 11:44Regina Barber?

  Really?

• 11:44Speaker 02

  Yeah, mostly in terms of just knowing where it could take his mind.

• 11:50Speaker 03

  So knowing you can beat that and keep your calm and keep your cool, it's a wonderful thing.

• 11:55Regina Barber?

  Wow, OK. Well, I'm glad he sees it this way. I could not do this.

• 12:00Speaker 02

  Nor should you, Regina. No one suggests you take the princess bride approach to snake venoms.

• 12:06Regina Barber?

  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.

• 12:14Speaker 02

  For sure, Gina. Thanks for having me.

• 12:19Regina Barber?

  This episode was produced by Hannah Chin and edited by our showrunner, Rebecca Ramirez. Tyler Jones checked the facts. Jimmy Keely was the audio engineer. Special thanks to Johannes Sturgie. 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 Short Wave from NPR.

• 12:44Speaker 00

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