Venom is full of dualities. According to the UN’s World Health Organization, snakebite envenoming causes somewhere between 81,000 and 138,000 deaths per year, and even that is likely an undercount. Yet research into venom has yielded treatments for diabetes, cancer, erectile dysfunction, and even the celebrity favorite diabetes slash diet drug, Ozempic.

In this episode, we explore the world of venom, where fear and fascination go hand-in-hand, and the potential for healing comes with deadly stakes.

This is part II of our “Things That Can Kill You” miniseries, which also explores poison and allergies (coming April 10).

Featuring Sakthi Vaiyapuri. Thanks to Iva Tatić for her question.

ADDITIONAL MATERIALS

Here’s more on Sakthi Vaiyapuri’s community awareness programs in India and his team’s research on the socioeconomic impacts on rural populations in Tamil Nadu.

The UN’s World Health Organization’s fact sheet on snake envenoming as a high-priority neglected tropical disease

A great breakdown on why snakebite deaths are undercounted and the problem of missing data, written by global health researcher Saloni Dattani on Substack.

A Nature article on potential advances in antivenom

Check out this Science Friday film on the cool research on cone snails and the non-opoiod painkillers derived from their venom.

More on Ozempic and lots of other innovations with roots in venom research (New York Times)

SUPPORT

To share your questions and feedback with Outside/In, call the show’s hotline and leave us a voicemail. The number is 1-844-GO-OTTER. No question is too serious or too silly.

Outside/In is made possible with listener support. Click here to become a sustaining member of Outside/In.

Follow Outside/In on Instagram or join our private discussion group on Facebook.

CREDITS

Outside/In host: Nate Hegyi

Reported, produced, and mixed by Justine Paradis

Edited by Taylor Quimby

Executive Producer: Taylor Quimby

Our team also includes Felix Poon, Marina Henke, and Kate Dario.

NHPR’s Director of Podcasts is Rebecca Lavoie.

Music by Hatami Tsunami, OTE, Lofive, Marten Moses, and Blue Dot Sessions.

“The Indian Cobra in all her majesty; displaying the hood to scare away the threat.” Credit: Keshav Mukund Kandhadai on Flickr (CC BY 2.0).

download a transcript

Audio Transcript

Note: Episodes of Outside/In are made as pieces of audio, and some context and nuance may be lost on the page. Transcripts are generated using a combination of speech recognition software and human transcribers, and may contain errors.

Audio Transcript: Venom and the cure

Justine Paradis: Hello Nate.

Nate Hegyi: Hey Justine.

Justine Paradis: So, lately, on the show we’ve been exploring the theme of poison. We’ve asked listeners to submit their questions on the topic. Last week we answered a lot of them. But there was one I’d like to get to today which we have not discussed yet.

Iva Tatić: Hi, Outside/In. This is Iva Tatić, calling from a Mediterranean country, Croatia. My question is if you could please, once and for all, explain what the difference between poisonous and venomous is. Hopefully you can do it in a way where the explanation can be turned into a soundbite, one to be used forever and ever when this question appears. Thanks!

Nate Hegyi: Does Iva, do you think Iva gets this question a lot?

Justine Paradis: This must be, like, an issue in her life.

Nate Hegyi: Yeah, absolutely.

Justine Paradis: I think when she first wrote us, she asked the tone to be stern. Like, she wanted us to sternly explain. And I was like, I don’t know if I have that in me, we’ll see!

Nate Hegyi: There is someone in Iva’s life that needs a stern explanation.

Justine Paradis: Absolutely. So, to answer this one, I did get in touch with an expert in venom and snakebites. His name is Sakthi Vaiyapuri.

Sakthi Vaiyapuri: I'm Professor Sakthi Vaiyapuri. I'm a professor in cardiovascular and venom pharmacology at the University of Reading in England.

Justine Paradis: So I posed Iva’s question as accurately as I could. Could Sakthi supply us with a soundbite?

Nate Hegyi: [laughs]

Justine Paradis: And turns out, he had a pretty quick answer already prepared, almost as if he’s been asked it before.

MUSIC: Caribbean Tobacco, Hatami Tsunami

Sakthi Vaiyapuri: If you bite something and eat it, and if you die, then it's poisonous. If something bites you and you die, it's venomous.

Nate Hegyi: I could see that in an instagram reel.

Justine Paradis: Right?

Nate Hegyi: It’s snappy. Memeable.

Justine Paradis: Did we do it?

Nate Hegyi: I think we did it. We could end this episode right now.

MUSIC SWELL AND FADE

Justine Paradis: But of course, I’m gonna add a little bit more to this snappy little soundbite.

So, venomous animals typically have some specialized gland which produces the venom and specialized parts, uh, which they use to deliver the venom. Like, the barb of a wasp or the fangs of a snake, for instance.

Nate Hegyi: Right.

Justine Paradis: If you do decide that it would be appropriate to eat that specialized gland, that venom is now potentially a poison.

Sakthi Vaiyapuri: That’s why the venomous animals can be considered as poisonous, but the poisonous animals can never become venomous because they don't have the glands and the delivery system. Yeah? So I wouldn't recommend anybody to eat venomous animals. Even if they eat, they have to chop off the venom gland completely and then eat.

Nate Hegyi: Lesson here: don’t go around biting the heads off rattlesnakes.

Justine Paradis: Definitely. I mean, there are people who eat snakes.

Nate Hegyi: Mhm.

Justine Paradis: They typically cut off their heads. But let me just say that the more I learned from Sakthi, the more I realized it would just be a travesty to simply touch on the wonders of venom and then just leave it at that.

MUSIC: Fainting Goats, OTE

Justine Paradis: Because, first of all, venomous animals are wonderful and diverse. It’s a vast world of venom.

Second, venom is a huge public health issue. Like in 2021, in India, more deaths were caused by snakebites than AIDS-related deaths.

Nate Hegyi: Wow. That’s amazing. You don’t hear about that in the news.

Justine Paradis: You don’t! But also, venom is the secret sauce behind many of humanity’s most powerful medicines.

Sakthi Vaiyapuri: Absolutely. I normally call venom as “bio treasure.” Okay. because the more you hunt, the more you are going to find out in venoms.

Nate Hegyi: Venom as bio treasure!

Justine Paradis: The more you hunt, the more you find.

MUSIC SWELL

Nate Hegyi: This is part II of what I suppose we’re calling “Things That Can Kill You”, a special miniseries from Outside/In. I’m Nate Hegyi. Today, producer Justine Paradis is looking a gift snake in the mouth – and peering into the world of venom, where fear and fascination, life and death, walk hand in hand.

Justine Paradis: Gift snake in the mouth. Is that a workable metaphor? Do we think that that makes any sense?

Nate Hegyi: We’re keeping it, Justine.

Justine Paradis: We’re keeping it.

Nate Hegyi: We’re keepin’ it.

Justine Paradis: It’s in the show.

MUSIC FADE

Justine Paradis: When I say “venom,” what might come to mind first are images of your cliche scary animals. Like snakes, spiders, and scorpions. But the world of venom is infinitely big, weird, and beautiful.

MUSIC: Ringing the Shard, Blue Dot Sessions

Justine Paradis: It includes platypuses, which have a venomous spur on their ankles, like a backwards thumb poking out from their webbed feet.

In sun-dappled coral reefs, lurk mesmerizing cone snails that can shoot a little harpoon laced with venom deadly enough to kill a grown man.

There’s the slow loris, a deceivingly adorable primate that can coat its teeth with a venomous oil secreted from its upper arm.

Again and again, venom has evolved, separately, in totally different species, all over the planet, in an example of what’s known as convergent evolution.

Sakthi Vaiyapuri: And that's why each venom could be different.

MUSIC FADE

Even though there are several families of animals, even within the family, the venom could be different.

Justine Paradis: This again is Sakthi Vaiyapuri. He explained that venom can be used to catch prey or to defend against predators. Individual venomous animals can also adapt their venom to different environments, and they can do it fast.

Sakthi Vaiyapuri: So based on the situation, they can rapidly change the venom. For example, if you keep the same snake – for example, cobra – in captivity for one year, and then if you compare that venom with the cobra caught in the wild, there could be some differences, because they can change based on the prey.

Justine Paradis: So, every venom is unique, sometimes even down to individual animals. But, what exactly is venom?

MUSIC: Dasta Bala, Hatami Tsunami

Sakthi Vaiyapuri: So, venom is a complex mixture of different proteins, peptides, and some other organic molecules… sort of like a cocktail mixture of different components. Some venoms might have, like, 20, 25 proteins. Some venoms are known to have more than 1000 components.

Justine Paradis: This cocktail is energetically expensive for an animal to produce. This is why sometimes, even when you’re bitten by a venomous snake, it can be a dry bite – all fang, no venom. This ability is called “venom optimization” or “venom metering.”

Snakes don’t like to waste their venom – it’s precious. Actually, in one review I read, the authors described the level of complexity in venom as “lavish” – delightful language for a scientific paper, in my experience.

MUSIC FADE

Justine Paradis: But I would use very different language to describe the effects of venom on the human body. Like, vipers can produce enzyme-based venoms that literally digest your tissues.

Sakthi Vaiyapuri: For example, an enzyme called metalloprotease in viper venom, they can digest the collagen around our vasculature and muscle. So, collagen is the most important component to hold our blood vessels and muscle. When they keep digesting this collagen, okay, the vasculature will start to leak. And similarly the muscle will get destroyed and they cannot regenerate.

Justine Paradis: You start to leak. Eventually, this can lead to tissue death, aka gangrene.

Sakthi Vaiyapuri: So if you don't seek the treatment on time, you have to go and amputate that arm or leg.

Justine Paradis: Sometimes, a venom will mess with your blood’s ability to clot. depending on the species, either preventing blood clotting or causing too much clotting. Both with pretty catastrophic results.

Sakthi Vaiyapuri: For example, we are working with some scorpion venoms… So if they block the blood clotting so you will bleed slowly in internal organs. And if they induce blood clotting, they will try to consume our clotting factors in our body and make random blood clots everywhere. And then later on that will lead to bleeding complications.

Justine Paradis: Each venom can have such specific, unique, and targeted effects on the body. That’s why they can be so very dangerous… and, thrillingly, so very useful.

MUSIC: Rasteplass, Blue Dot Sessions

Justine Paradis: There’s an ancient symbol of medicine which is still used today by the American Medical Association and others. It’s a staff, with a snake curled around it.

It comes from the Rod of Asclepius, the Greek deity of healing and medicinal arts.

And one way to interpret that symbol is: the poison and the cure are intertwined. Or rather, the venom and the cure.

Sakthi Vaiyapuri: Okay, so I normally say in my lectures, like you can find a cure for any disease in a human using venom.

MUSIC FADE

Justine Paradis: Okay, maybe that’s an exaggeration – but, maybe not. Like, the list of medications with roots in venom is not short.

MUSIC: Bitcrush Tornado, Lofive

Justine Paradis: Take Ozempic.

E! News: Ozempic. The medication that has previously only been prescribed to people with diabetes has taken Hollywood by storm.

Justine Paradis: Originally a drug for diabetes, it’s now also a stylish weight loss pill. And it was originally derived from research into the venom of the Gila monster.

Venom collected from cone snails has led to the FDA-approval of a powerful non-opioid painkiller.

Peptides found in scorpion venom can be used to identify and treat malignant tumors.

A bite from a banana spider can cause prolonged and painful erections, so scientists in Brazil are now studying how its venom might be used to treat erectile dysfunction.

Sakthi Vaiyapuri: People tested venoms for Covid… Hypertension, the first medication came from venom. Yeah, captopril came from venom. Blood clotting, stroke, heart attack, cancer... the more we hunt, the more we can find out.

MUSIC SWELL AND FADE

Justine Paradis: But when it comes to obtaining venoms – it’s not always very simple. For example, those cone snails? They tend to live in coral reefs, so their habitat is extremely threatened because of the impacts of climate change.

And even when researchers have easier access to the venomous animal, it’s dangerous territory.

Take snakes. Collectors will take something like a small glass beaker, and cover the top in parafilm – basically, plastic wrap.

Sakthi Vaiyapuri: And then you hold the snake near the head, and then try to squeeze the venom gland area, around the neck area, and the snake will get angry, open the mouth and bite that parafilm. When they bite the parafilm, they’ve got the massive fangs… so the fangs are like hypodermic needles, so they will inject the venom so the venom will drip into the beaker…

Justine Paradis: That's, um, that's very hands on.

Sakthi Vaiyapuri: Yeah.

Justine Paradis: Yeah.

Sakthi Vaiyapuri: That's why we need skilled experts to handle the snake. Because even if you handle a snake, you can hold the snake one inch below the neck. It can turn around and bite. And it's a deadly job. It’s a seriously deadly job.

Justine Paradis: But while there might be lots of exciting research into how venom might be used in other areas of healthcare, there’s another aspect of the science of venom which is under-researched.

The impact on people when they actually get bitten by venomous snakes.

MUSIC: Zuberi, Hatami Tsunami

Justine Paradis: Sakthi explained that there are significant gaps in both diagnosis and treatment of venomous snakebites, and it’s a public health issue in certain parts of the world. The UN’s World Health Organization actually called snake envenoming a “high priority neglected tropical disease.”

And part of the reason why probably has to do with who’s getting bitten.

Sakthi Vaiyapuri: The most important problem here is the snakebites are predominantly affecting poor people who are living in remote rural areas. They are marginalized people and their issues never come to light, put it in that way.

Justine Paradis: That’s after the break.

BREAK

Justine Paradis: This is Outside/In. I’m Justine Paradis. I’ve been sharing my conversation with Sakthi Vaiyapuri, an expert on venom toxicology and snakebites.

Sakthi Vaiyapuri: So, I come from India. I come from a small village in south India. So, from my childhood, I've seen a lot of snake bite victims, some people even dying due to snake bites. So when I decided to do my PhD and to divert my entire career to science, I wanted to do research that's going to directly benefit poor people, particularly living in rural areas. And that's why I chose this area in contrast to any other areas.

Justine Paradis: Perhaps you might think that decades of studying snakebites and venom, might mean that someone like Sakthi is pretty used to snakes. Not so.

Sakthi Vaiyapuri: To be honest, I've been working on venoms for 20 years. I'm exceptionally scared of snakes.

MUSIC: Cross Purposes, Blue Dot Sessions

Still now I have to be at least ten feet away from snakes [laughs]. Even if it is a non-venomous snake, I will not go near to it.

Justine Paradis: India is often called the “world capital of snake bites.” More people die there from snake envenoming than anywhere else in the world. There are four major species of note in India, but one species stands out above the rest. They call it “the ruler of India.” The Russell’s viper.

Sakthi Vaiyapuri: This one seems to be somehow unique… and it can induce a plethora of effects which I don’t think any other snakes can induce to this level.

Justine Paradis: The Russell’s viper is large and, honestly, beautiful: with chains of dark, leopard-like spots running down its spine. Its preferred food is rodents. Which means they're often attracted to human settlements.

When the Russell’s viper bites, it tends to inject a huge amount of venom. That venom digests tissue around the bite, both causes and prevents blood clots, and down the road, it can lead to kidney failure, and death.

According to one scientific review I read, “recovery is rarely complete.”

Sakthi Vaiyapuri: It can easily camouflage as well. So it's really hard to find whether it's there or not. It's the nastiest snake you can find.

MUSIC FADE

Justine Paradis: In Hindi, one of the names for the Russell’s viper translates to “the lurker.” It really likes to hang out and hide in rice paddies. When it’s hot, they come out at night. Which means farmers are particularly at risk.

Sakthi Vaiyapuri: So in countries like India, people, the farmers usually go out in the farms in the night times to irrigate the fields. Okay. That is when they will get the full electricity, three-phase electricity… And many people walk in bare feet. And these snakes will come to the pavement or footpath… And as soon as you step on, they can bite.

Justine Paradis: Snake-human encounters are also increasing with habitat loss and with extreme heat caused by climate change. Just like people, snakes get grumpy when it’s hot.

Sakthi Vaiyapuri: So the increasing heat can also increase the anger of the animal. Okay. Because they are cold-blooded animals. So they can inject more venom than the normal ones. And we don't know at the moment, but the temperature could be altering the venom composition as well… And the other problem is the deforestation. So people are keep cutting down all the trees, trying to make more and more homes. And the snakes, where will they go? They’ll try to come into the dwelling areas and cause more and more bites. So the increasing human-snake conflicts will ultimately increase snakebite numbers.

MUSIC: Brevik Strand, Blue Dot Sessions

Justine Paradis: According to the Indian government, snakebite death rates aren’t too bad – around 1,000 deaths a year. But that’s WAY under the number from UN’s World Health Organization – the WHO – which estimates 58,000 annual deaths in India.

Sakthi told me the Indian government’s data is inadequate for a bunch of reasons: for one, it only includes government hospitals, and 75% of snakebite victims in India don’t ever make it to ANY hospital at all.

So, when you look at commonly available charts comparing leading causes of death across the world, snakebites aren’t even on there as their own category.

But, the WHO’s count of people who die from snakebites every year is in the range of 80,000 to 138,000.

If you were to place those numbers on that chart, snakebites are comparable to deaths caused by fire or alcohol use disorder. That’s not to mention the nearly half a million people permanently disabled from snakebites every year.

And Sakthi thinks even the WHO’s estimate is probably a dramatic undercount.

Sakthi Vaiyapuri: But this is the number, approximate number, we have based on the available literature. But in reality, this could be much higher. For example, in India we are suggesting… the deaths could be even up to 200,000. But we don't have the actual data. Many people don't make it to the hospital. Many people die on the way to hospital. And in some hospitals they don't collect accurate statistics. So that's why it's a huge underestimation.

MUSIC FADE

Justine Paradis: A lot of snakebite stories tend to have a lot of misinformation. Like the idea that you should cut a snakebite wound, or even suck and spit out the venom?

Sakthi Vaiyapuri: It's a myth. Completely myth. Because that's what we’ve seen in movies all the time. If you look at the Bollywood movies …

The Velvet Vampire (1971): Jesus, a snake! … If I don’t suck out the blood, the poison’ll spread…

Justine Paradis: By sucking on the wound, all you’re really doing is introducing your oral bacteria into the wound – which adds infection, on top of everything else.

But Sakthi says the worst thing someone can do is use a tourniquet. Tying a rope tightly around an arm or a leg above the snakebite. The idea behind it is to cut off blood flow to try to prevent the venom from spreading — but cutting off your blood flow is really bad for you. It will eventually cause tissue death – aka, gangrene.

Sakthi Vaiyapuri: So by the time you go to the hospital, you may have to amputate the entire arm or leg and remove it. That's worse than the actual snake bite.

Justine Paradis: There’s only one surefire way to treat a venomous snake bite. And that’s with anti-venom. But that brings up a whole bunch of other issues.

MUSIC: Orcas, Marten Moses

Justine Paradis: Antivenom is produced by injecting a very small amount of venom into a large animal, typically a horse.

Sakthi Vaiyapuri: So, the horse’s immune system will recognize these venom as foreign molecule and then produce these antibodies – that’s immune molecules – against them. Then after certain time, we can collect the blood and isolate those antibodies and then use them as antivenom to treat snake bites.

Justine Paradis: Once that happens, antivenom needs to be kept cold. In remote, rural areas, where a lot of snakebites tend to happen, that can be a major challenge.

And, remember, different animals produce wildly different kinds of venom. So there’s no universal antivenom, at least not right now. This process essentially has to be repeated for all the different kinds of venoms out there.

These might be challenges that could be overcome, if there was a huge demand for anti-venom coming from wealthy countries.

But as it is, the market is relatively small and unprofitable – and hard to predict, due to the challenges in accurately tracking snakebites. That’s led some drug manufacturers to stop producing it, which then causes low supply, and higher prices.

MUSIC SWELL AND FADE

Justine Paradis: Here's another problem. In most of the world, there is no diagnostic test to tell what kind of snake bit you, and if the snake was venomous, if it actually injected venom when it bit you. Because sometimes again it can be a dry bite.

Sakthi Vaiyapuri: So, so far we don't have any diagnostic kit for snakebites anywhere in the world except one kit in Australia. In Australia, that kit will identify specific snakes, but it doesn't work anywhere else.

Justine Paradis: So there’s no way to quickly assess if you’re at risk of death, or if you’re going to be totally fine. Sakthi and his colleagues are trying to fix this. Like, they’re developing a kind of a rapid test for snake bites, which allows people can test their urine or a drop of blood to see if their body contains venom.

He’s also working on other tests that can identify the family of snake which bit you. And he’s also piloted community awareness campaigns to help dispel some of the myths – like sucking on snakebite wounds or using tourniquets.

But the gaps here don’t stop at diagnostic kits and antivenom. They also extend to treatment.

Sakthi Vaiyapuri: So currently there is no treatment at all for snake bite induced muscle damage. So the clinicians are only using surgical procedures, for example debridement to remove all the affected tissues… and in worst case, they had to go for amputation. So in our lab we are developing some combinational therapies that can be injected locally around the bite site so that we can prevent this extensive muscle damage. And even if the damage happened already, we can try to recover the muscle… so it’s still in laboratory stage, but we are making really good progress.

Justine Paradis: Why – why haven't we invested to create a diagnostic or treatment tool, uh, yet in the world?

Sakthi Vaiyapuri: Um. If you look worldwide, there are only around 20, 25 research groups working in this area. Working with venoms is not really easy task. Maintaining snakes, collecting venoms, working with venom. It's quite tedious job. So most people just neglected this area seriously in the past. But in the last 10, 15 years, it's getting visibility. So people are getting funding here and there… and people are trying to make better diagnostics and therapeutics. But still, I would say this is not enough…

MUSIC: Badeng, Hatami Tsunami

Justine Paradis: This topic of venom requires holding a lot of truths at once, as represented in the symbol of medicine, the Rod of Asclepius – that snake wrapped around the staff.

But when it comes to why snake envenoming is so neglected, I don’t know that there’s a lot of conflicting truths that need to be held. Because again, a major reason why snakebites are neglected is probably who’s getting bitten.

Justine Paradis: Venomous animals and humans have lived together for a very long time. Snakes, spiders, scorpions – these animals are part of some of our oldest and most famous stories. And we’re constantly learning new ways to benefit from their chemical wonders.

But when it comes to snakes, increasing snake-human conflict is exacerbated by habitat loss, climate change, poverty, and inequity. These are human inventions.

Which means they’re in our power to address. Which, of course, is good news and bad news.

There’s that metaphor again: the potential for deadly consequences, and the possibility of wondrous healing.

Thanks, Asclepius.

CREDITS

Nate Hegyi: Our “Things that Can Kill You” miniseries continues next week with one final installment: allergies.

Mara Hoplamazian: I feel like I have so many questions about allergies. Like where do they come from?

Dan Tuohy: As you get older do allergies get worse?

Jackie Harris: So, I’m really curious if people grow out of allergies.

Mara Hoplamazian: Also does taking bee pollen actually work?

And a reminder that we are seeking your questions for our next Outside/Inbox listener mailbag round-up. The theme is sound. So, think: animal communication. How sound moves underwater, in space. Sound as therapy, as a weapon, or crowd control. White noise, brown noise, rainbow noise… you name it.

You can send us your questions by recording yourself on a voice memo, and emailing that to us – outsidein@nhpr.org. Or you can call our hotline. We’re at 1-844-GO-OTTER.

This episode of Outside/In was produced, reported, and mixed by Justine Paradis. It was edited by our executive producer, Taylor Quimby. I’m your host, Nate Hegyi. Our team also includes Marina Henke, Felix Poon, and Kate Dario.

Our director of podcasts is Rebecca Lavoie.

Music came from Hatami Tsunami, OTE, Lofive, Marten Moses, and Blue Dot Sessions.

Outside/In is a production of NHPR.