Science Vs - SNAKES!!!

Episode Date: March 25, 2021

Snake venom is a wily beast. It's packed with hundreds of toxins that can attack our blood vessels, muscles and nerves. That's why snake bites kill some 100,000 people each year. On today's show — dangerous snake bites and the bizarre way we make the only thing that can save you from them: antivenom. (Spoiler alert: it takes snake milkers and stables filled with horses.) We'll also look at the groundbreaking research that could eventually revolutionise all this. We speak to Captain Pete Bethune, snake venom researchers Dr. Christina Zdenek, Professor José María Gutiérrez, Dr. Laura Albulescu and snake milker Greivin Corales.  To read more about Pete Bethune's work: https://www.earthrace.net/  Our instagram is: science_vs Check out the transcript right here: https://bit.ly/3ffV8oE This episode was produced by Wendy Zukerman with help from Meryl Horn, Rose Rimler, Michelle Dang, Nick DelRose, and Taylor White. We’re edited by Blythe Terrell. Fact checking by Erica Akiko Howard. Mix and sound design by Bumi Hidaka. Music written by Peter Leonard, Marcus Bagala, Emma Munger, and Bobby Lord. A huge thanks to all the researchers we got in touch with for this episode, including Professor Abdul Razaq Habib, Dr. Gavin Smith, Professor Abina Crean, Professor Nick Casewell, Dr. Jessicah Kurere, and Dr. Tarek Mohamed. And special thanks to Pia Gadkari, the Zukerman family and Joseph Lavelle Wilson. Learn more about your ad choices. Visit podcastchoices.com/adchoices

Hi, I'm Wendy Zuckerman and you're listening to Science Versus from Gimlet. This is the show that pits facts against fangs. Wendy, how would you be? Yeah, I'm good. How are you? I'm alright, mate. I'm happy to be alive. This is Pete Bethune. Pete is a conservationist, G.I. Joe style. He stopped whalers out in the Pacific Ocean, rescued a dolphin held captive in a resort.

And recently, on one of his adventures, things went particularly sideways. It's just before Christmas. Pete is deep in the rainforests of Costa Rica with his team, a couple of guys. And they're looking for evidence of illegal logging and hunting. This is a lush forest, thick canopy, very hilly. It's up and down, up and down, up and down, really steep. Jungle is very spiky. You know, it's got the most ferocious ants on earth,

it's got poisonous spiders, it's got snakes. So it's a jungle you need to be really careful walking through. And Pete was about to work out that he wasn't being careful enough. He was walking through some leaf litter. Just a bunch of leaves on the ground. I just felt this bang in the back of my leg and my first thought was someone had hit me. Like it felt like someone had a big stick or a piece of wood in and whacked the back of my calf. And then I looked down and in horror I see this snake sort of recoiling away from me. And as soon as I saw it, like I knew it was a fertile ants.

Pete was bitten by this snake called a fertile ants, which means spearhead. It's a long snake with this brown diamond pattern down its body and it kills more people than any other snake in Central America. Pete's colleague grabs his cell phone, he's got one bar of reception, and calls up emergency services. And they did make it clear you need to get their guy to hospital as quickly as possible or he is going to die. And the clock is ticking. Because the longer that venom courses through Pete's body, the worse things are going to get. He has maybe six hours to get to a hospital.

And he's in the middle of this rainforest, so far away from help. Pete can already feel the venom moving up his leg. And it was so sore. It was such an intense pain. And in Pete's line of work, he's gotten into quite a few scrapes. He's even been stabbed twice. But he said the pain from this venom, it was worse. The worst pain he's ever felt. I remember thinking there's no way I'd make it out of there. I thought I was a dead man. I said to one of my guys, I said, you make sure you

tell Mick because I love them. Yeah, it was quite difficult, eh? Peter's thinking of his two daughters back in New Zealand. But his colleague says we've got to get moving. They scope out their options and figure that the fastest way out is sliding down these steep

and muddy creek beds. So I'm crawling on my ass, crawling down these little waterfalls, escarpments, banks, creek beds. I remember there was a waterfall that was really tricky for me to get down and I was looking at it and thinking, holy shit, how am I going to get down this? But as we're going down, I'm getting weaker and weaker. And the strobbing now has moved all the way up to my groin area and eventually gets to a stage where I just want to sleep. But I did think, I'm not going to make this. My number was up. He just keeps going, sneaking his way through waterfalls and mud and eventually gets to the edge of the rainforest and out onto a beach where he reaches the Coast Guard.

They lay me down on the ground and I remember just closing my eyes and thinking, you know, just hang on a little bit more, hang on a little bit more. They get Pete to the hospital and the doctor who sees him reckons that Pete is about an hour away from dying. His heart is racing and he passes out. When Pete comes to, he realizes that other stuff has gone wrong. The venom has attacked the blood vessels in his genitals, or as Pete put it, my balls and cock go all big and black. It is not an uncommon thing that happens with snake bite victims.

That doesn't mean it's not quite a shock. Oh, I remember asking one of the nurses, like, is this normal? And she'd come over and she'd just, yeah, yeah, kind of, maybe. By now, the doctors had quickly set up an IV drip for Pete and given him the one and only thing that could save his life. Antivenom. It races through his body, fighting back against the snake's venom. And if you didn't get antivenom, what would have happened? Oh, if I didn't get antivenom, I would have died. No question.

But instead, little by little, he feels better. And while in hospital, Pete starts making these videos of what's going on. Snake bite, day 11 update. So I started walking around for the first time. I walked for the first time. After around two weeks in hospital... Oh, mate, I'm feeling much better, eh? Much better. ..he finally walks out.

So happy to be out of hospital, eh? So happy to be out of hospital, eh? So happy to be out of there. Each time I'd wake up, they'd go, hey, I'm alive. I'm alive. And this little sense of euphoria. So, yeah, I was pretty lucky, eh? Pete was pretty lucky. Because if he'd done all that work of dragging himself to the hospital

and they didn't have the antivenom, he would have been a goner anyway. He needed that special little vial. But for loads of people around the world, they can't take it for granted that those little vials will be there when they need them. Each year, snakebites kill some hundred thousand people, and almost half a million end up with major injuries, with some needing to get their legs amputated. And part of the problem here is the way that we make antivenom today. It's bizarre and convoluted and involves a bucketload of snakes

and weirdly stables filled with horses. So that is what we're diving into today, the wild world of anti-venom. And then we'll look at the groundbreaking research that could eventually revolutionize all this. When it comes to snake bites, there's a lot of... My balls and cock. All right, so there's not a lot of that. But then there's science. Science versus anti-venom is coming up just after the break.

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and now host of the new podcast, Pioneers of AI. Think of it as your guide for all things AI, with the most human issues at the center. Join me every Wednesday for Pioneers of AI. And don't forget to subscribe wherever you tune in. Welcome back. On today's show, snake bites and the bizarre way we treat them. So when people get a nasty bite from a venomous snake. What they desperately need is anti-venom. And it turns out that this stuff is super tricky to make.

And a big reason why comes down to the venom itself. It's a wily beast, which can have a ton of treacherous toxins in it. It's an absolute biological chemical warfare going on. This is Christina Zdenek. She studies snake venom at the University of Queensland in Australia. And she told us how complicated snake venom is. Like, there could be up to 200 different toxins in it attacking your body in these different ways.

So, for example, in a fertile ant snake, some of the toxins go after your muscles. Yeah, it kills muscle cells. It's like you're almost getting digested alive. For other snakes, the toxins can attack your nerves, making it difficult to breathe. And if that wasn't bad enough, sometimes two different toxins can work together to kind of feed off each other and make everything worse. You've got one toxin that's pretty bad on its own and another one that's pretty bad on its own,

but when you put them together and they like tag team against you. Whoa. Yeah, it's like suck eggs. And when these toxins say suck eggs, here's what it looks like. So the venom of some vipers can go after your blood with a kind of one-two punch. Some of the toxins make it tricky for your blood to clot, while others make you bleed by kind of punching holes in your blood vessels. And so you've got a hole caused by the toxins that's now open

and you're spewing out red blood cells, but all of a sudden you can't stop the bleeding in that area. Then you're very susceptible to bleeding internally. Christina says sometimes people can bleed from all over their body. Yeah, yeah. So like your gums from your eyes, sometimes your ears or your sphincter, your butthole. Oh, Jesus. And even if it's really bad, there was a Taipan bite in Australia where a guy was,

it seemed like he was sweating blood from his back. Oh. And so to bring this back to the problem of making antivenom, what we're dealing with here is this nasty soup of toxins that's different for different snakes. And basically, we want something that can neutralize all those toxins, the perfect antivenom. So how on earth do we make the stuff that we have now? Well, the way that science has dealt with this incredibly complicated challenge is kind of absurd, and it all starts with a sort of snake whisperer. Hello, Wendy. So, my name is Graven Corrales. Graven's worked with snakes for more than a decade. He loves them.

But these snakes don't always love him back. A few years ago, a Sri Lankan green pit viper bit his pinky finger. So I actually lose a little part of my finger. Oh, wow. It's like one centimetre less than it used to be. When you look at your finger now, what does it look like? Beautiful. I like it.

It's really nice for scratching. You kind of got to have his attitude if you do what Graven does. He works at a lab in Costa Rica called the Clodomiro Picado Institute. They make antivenoms for Central America, including the antivenom that ended up saving Pete's life. And inside that building where Graven works, it's a little bit like a giant storage locker with boxes filled with snakes. So we have about 500 snakes. What? Yeah, yeah. And to make anti-venom, first up, we need venom. So to make the stuff that was injected into Pete, Graven walks past the hundreds of snakes to get to the very species that got Pete,

the Fertilance. We know before we open the box, it's going to fight. Because they are very explosive. They strike many times and it's one of the most difficult snakes to handle. Graven and his colleague carefully take the snake out of the box using wooden poles. And then they sedate the snake by popping it in a basket with carbon dioxide gas. This is safer for Graven and also less stressful for the snake. So with the snake all good and sleepy, Graven then picks up the snake's head

while his teammate holds the snake's body steady. When it goes under, when it's sedated, how long do you have before it wakes up generally? Around five minutes. Five minutes. So what's going through your mind as you're doing this? Yeah, I know it sounds kind of crazy, but nothing. Like in this moment, I have to be very focused. You're holding not just the snake, but your partner's life. In that moment, you cannot feel no fear.

You have to be fearless. And so, with the snake's head in his hands, Graven uses large tweezers to guide the fangs of the snake into a jar. And then, the moment of truth. Graven starts pressing down on the snake's venom gland, which sits behind the snake's eye. Now, normally in the wild, to release its own venom, the snakey will squish muscles around the gland,

squeezing the venom out. But with the snake sedated, it's up to Graven to coax the venom out by gently pushing on the right spot. This is sometimes called milking the snake. But Graven likes to say, So we have to do a little massage. Massage?

A massage, yeah. You have to do it gently. What does it feel like when you massage its gland? Actually, you can feel when it's full of venom. So it's, I don't see something similar to give you an example. Is it like when you have a really big pimple and you're like squishing out the oil in the pimple? No, not at all.

What about like a chicken when you make like cooking chicken? Does it? No, nah. No. At 2am, at 2am tonight, you'll wake up and you'll be like, it's like my grandmother's hair. Yeah, I got it. Yeah. Eventually, Graven was like, think about it like a slice of orange sitting under snake skin. And you're juicing it little by little until you see drops of yellow liquid coming from the fangs. Once Graven has collected that snake juice, he passes it off and we go to our next step. For that, we're going to leave Graven. So say goodbye to the snakes.

Bye. And it's time to call in the cavalry. Yeah, to make the antivenom that saved Pete's life, we're going to now need another group of animals, horses. At the centre where Pete's antivenom was made, there's about 120 horses, and I know what you're thinking about them. Do they have names?

Yes, they have names. In fact, there was one horse one time with my name, so I was very proud of that. This is Jose Maria Gutierrez. He used to head up this institute and now he works there as a professor. And Jose Maria, he loves the horses and doesn't play favorites. I like all of them. They're really fantastic animals. And these fantastic animals are literally the workhorses that pump out most of the antivenom that we use today, which must be hard to do, right? Working the microscopes with their big hooves. Luckily, they're making the anti-venom inside their body. Here's how. The first time Chris and Maria's team start working with a horse,

they'll take that venom that Graven got from the snakes and then... You inject little amounts of venom into horses. And when a horse is first injected with, say, a tiny amount of venom into horses. And when a horse is first injected with, say, a tiny amount of venom, how do they react? Are they like, nay? Do you think it would be like a mosquito bite? I think it would be a little more than that because we are injecting a toxic substance,

but you don't see any evidence of tissue damage. And they don't seem pissed off or anything. Exactly. The horse might have a bit of swelling, but nothing too serious. These horses then get injected again and again every two weeks or so. But here is why we're doing all of this. Because all the while, the horse's immune system is creating antibodies against this venom. You're kind of vaccinating the horse against it. And then after several of these

injections, usually a couple of months, for instance, at that point, the horses are bled. Bled. About two months into all of this, they'll take around six liters of blood from the horse, which Jose Maria says is the horsey equivalent of donating a bag of blood at a blood bank. And that's why they use horses, by the way, because they're big animals with lots of blood to give. Some labs use sheep instead. And so, after all of this, we get the very thing we've been waiting for, the miraculous drug that can fend off that super complicated cocktail of venom. The horse antibodies.

That's what we're going to harness. The antibodies get purified from the horse's blood, put into a vial and freeze dried. And remarkably, even though the antibodies come from horses, they work in us. So once that stuff gets injected into people like Pete. So these antibodies, these horse antibodies would get into the bloodstream. They find the toxins and then they block the action of the toxins.

And so even though we say antibodies as if it's like one thing, within that vial of antivenom, there could be 50 different antibodies that go after 50 different toxins in the blood. Exactly. Actually, it's a mixture of antibodies. And there are antibodies against each of the toxins. And Jose Maria says that after all this work, each bag of horse blood will eventually get you enough antivenom

to treat roughly 15 people. That's it. And even then, you've only made a treatment against whatever venom you injected into that horse. So, for example, if you just made Fertilance antivenom, that's not going to work on someone who got bit by a coral snake. It wouldn't work at all. No, it wouldn't work at all because the antibodies are specific. And get this, this way of making antivenom with all the horses and the snakes,

the basic steps haven't changed since this process was first invented in the late 1800s. There's been some improvements along the way, like sometimes horses will get injected with more than one kind of snake venom. So the horses pump out antibodies for, say, three different kinds of snakes. But still, what all of this means is that to make antivenom for all the scary snakes across the globe, you have to repeat all this stuff over and over again. And that's what we do. Around the world, in Indonesia, India, Egypt, South Africa, Australia, there are labs like Jose Maria's piled high with horses, injected with venom and pumping out

anti-venom for all kinds of snakes. And bottom line, to make enough of this stuff for everyone who needs it, you need thousands of horses. Yes, you do need a huge amount of horses. You need huge facilities. It has been said that just in sub-Saharan Africa, there is a need for one million vials of antivenom per year. Wow. This is a big problem.

So the whole thing is really complicated. Because this process is so bespoke. According to a report from The Lancet, there are more than 100 dangerous snakes out there that we just don't make antivenom for. So if you get bit by one of those snakes, good luck. And even if a vial is waiting for you at a hospital, you might run into another problem. Because we're injecting bits of a horse into a human,

people can have severe allergic reactions, like anaphylaxis. So that is how we make antivenom today. And the bones of it have been the same for more than 100 years. But after the break, things are finally about to change. Welcome back. Today, we're talking about nasty snake bites and the kind of antiquated way that we make the one and only treatment that can save you from them, antivenom. But it's time for this life-saving medicine to enter the digital age, so to speak.

And recently, something happened that breathed new life into the world of snake bites. In 2017, the World Health Organization got all hot and bothered about this and dubbed snake bites the most important kind of neglected tropical disease. And for snake bites, which kill some 100,000 people each year worldwide, this is like winning an Oscar. You get extra attention and more money for research. Here's Professor José María Gutiérrez again. Things have really changed. The world in general is paying much more attention to this disease. And it's really exciting.

And one of the exciting things that scientists are cooking up? Well, think about it a bit like a universal antivenom. One drug to battle lots of different kinds of snakes. So remember, a big problem with creating a drug like this is that scary snakes have a bunch of toxins in their venom, attacking your body in slightly different ways. And then on top of that, different kinds of snakes have different stuff in their venom. So that's why we need the horses to make all those antibodies against all those different

toxins. Because if we tried to cook up a drug like that without the horses around? Well, Dr. Christina Zdenek says, forget about it. Oh, well, you're talking about thousands upon thousands of toxins, like a ridiculous variety. So you really wouldn't have so much of a chance. You really need to find a way to group them together. Group them. And this is the new way forward, how scientists are tackling this problem now.

By scouring through the dangerous stuff in venom, they've found that there are these big families of toxins that do similar stuff. Like there's this one family that goes after our blood vessels. It's the ones that are punching holes in them. These are enzymes, and they're actually found in the venom of heaps of snakes all around the world.

So scientists figure, hey, if we can stop those enzymes from causing all that damage, then maybe we could have one treatment that works against all those different kinds of snakes. And one nerd who's testing this out is... Yeah, so I'm Laura Oblescu. Laura is at the Liverpool School of Tropical Medicine in the UK. And she told us about something that might help them tackle that bloody family of toxins.

It's an Achilles heel. You see, the enzymes in that family need this very particular thing to work. Zinc. That's what makes the enzyme tick, I would say. So what makes it active. And therefore, if you block it, then the enzyme can no longer function. And it turns out there are drugs out there that block zinc. So Laura and her team took one of those, combined it with another drug that deals with other stuff in snake venom, and put it to the ultimate test. They enlisted some heroic little white mice and injected them with snake venom from some of the most dangerous snakes in the world. We are looking at vipers from Africa, from India, from Central America.

They waited a bit to let the venom set in, then gave them her concoction, the two drugs. Now, if this didn't work, chances are... These mice would all die within a four-hour window. But instead, the team saw something different. The mice started moving around, sniffing. They seemed to be recovering. And hours later... Oh, these animals are still alive and look healthy.

And how are you feeling? Yeah, I was feeling great. I didn't expect it to work so well uh venoms that are so different from each other yeah to work for a fertile ants from Central America and then an Asian you had source scaled viper yeah how big is that in the world of anti-venom. This is amazing. It's really great. Now, science being science, we've still got work to do. The venom did kill one of the mice after 18 hours. Laura's cocktail of drugs won't help for all snakes out there. And of course, we need to show that this works in people. But ultimately, if this new way of tackling snake venom does work in humans, then that would mean that after more than a hundred years of injecting all those horses

with all that venom, then things could start to change. And maybe in the future, we could cook up these drugs in labs, just like regular medicine. You wouldn't need, you know, farms to inoculate all of these animals. It's massively different. And this is just one exciting thing that's in the pipeline that could change the way we treat snake bites. There are other drugs that mess with zinc that are being tested, and one is actually going through a clinical trial in people right now. Other researchers are looking at genetically modifying human antibodies

so that they can battle against some types of venom. So perhaps one day, all those horses will finally be able to hang up their lab coats and retire. Okay, so just before we shed our skin and say goodbye, you gotta know that even though snake bites can be scary and snakes can be deadly, researchers like Christina aren't ready to throw snakes in the bin once and for all. Goodness, no, that would be horrible. She says that some of the toxins in venom are actually helping us. They've been put into medicines. Like there are drugs on the market right now based on snake venom, treating stuff like high blood pressure and blood clots. And away from

all that, as Christina and I were talking about snakes, she basically went Steve Irwin on me. I've loved snakes ever since I can remember. You know, I sort of skipped the fear phase and went straight into fascination. What were you fascinated by in particular? Oh, gosh, their forked tongue. I was fascinated with how they eat, you know, consuming prey whole. You know, they don't chew it. They don't have legs like us.

Just the way that they move, that sort of caterpillar motion. Oh, some of the patterns on snakes, it's just amazing. It's hard to deny they are beautiful. They really are. And even Pete Bethune, whose leg is getting better and better by the day, holds a little place in his heart for the snake that bit him. I'm happy that guy's still alive and up there, chilling out, mate. So you don't hold a grudge against the snakey?

No, I don't hold a grudge against the snake. He was just doing snake things. That's Science Versus. This week we have 117 citations. 117. So if you want to read more about snakes or you have any questions about this episode, then just look at the show notes and you can click on our link to the transcript. You'll see them all there.

And if you want to see beautiful photos of snakes, then you got to head to our Instagram account. It's science underscore VS. While you're there, you can also see a photo of Pete's puffed up leg. Looks pretty gnarly. Not only all of that, but we've actually collaborated with the podcast 99% Invisible to make a version of this very episode with them. It's so much fun. So you should definitely keep an eye on the 99% Invisible feed and you should see an episode about snakes and anti-venom popping up very soon. All right, time for the credits. This episode was produced by me, Wendy Zuckerman, with help from Meryl Horne, Rose Rimler, Michelle Dang, Nick Delrose and Taylor White.

We're edited by Blythe Terrell. Backchecking by Erica Akiko Howard. Mix and sound design by Bumi Hidaka. Music written by Peter Leonard, Marcus Begala, Emma Munger and Bobby Lord. A huge thanks to all the researchers we got in touch with for this episode, including Professor Abdul Razak Habib, Dr Gavin Smith, Professor Abina Kreen, Professor Nick Casewell, Dr Jessica Karari, and Dr Tariq

Mohamed. And a special thanks to Pia Gedkari, the Zuckerman family, and Joseph Lavelle-Wilson. I'm Wendy Zuckerman. Back to you next time.