Hi.
My name is Gwen, and this is my story. It was the last day of our ten day field trip. We were working and camping at our most remote field site in western Colorado, conducting botany surveys for a research project. My field assistant, Chloe, and I decided that we would spend the evening swimming and relaxing by the Dolores River. As the sun set, I started to get ready for bed. I was tired and ready to snuggle up in my sleeping bag. I walked over to the truck to refill
my water bottle and grab my toothbrush. As I reached for the driver's side door handle, I heard a noise and looked down just in time to see a rattlesnake's fangs penetrate the skin on my right ankle. The snake coiled up and started rattling its tail, and I backed away quickly. Chloe and I decided to leave all of our camping gear and head straight to the hospital and
Grand Junction, which was about a three hour drive. We left at about nine thirty at night, and the only road home was a two lane highway over the Uncompagra Plateau. Because we didn't have cell service, I used our satellite messenger to text my husband with the news and to call ahead to the hospital. I was in a lot of pain, really the most pain that I can remember. We were thirty minutes into the drive when I started throwing up. We didn't pull over because I didn't want
to lose any time. I was heaving for about thirty minutes, but eventually I stopped. Sweaty and exhausted. At this point, I had to poop. I instructed Chloe to pull over now, and I pooped right there on the side of the road. Once I had nothing left in me, we continued on. Soon after, I began to experience muscle spasms. It began in the tips of my fingers and toes. All of my muscles tightened as the spasms worked their way up my extremities, so that my hands turned into fists and
my arms and legs tightened. This was the only time during this experience that I thought I might not be okay. Chloe told me to focus on breathing, and I did. My body felt like a tight ball and was not in my control. Eventually, the spasms subsided. The emergency room staff was expecting me. I was admitted quickly and given a large dose of anti venin and a tetanus shot. While there, I believe I met every doctor and nurse
in the emergency room. It turned out they didn't see snake bites very often and wanted to take this opportunity to look at my ten day unwashed foot. I happily told everyone my story. A lot of the pain had subsided and I was just so relieved to be safe. While there, I asked a lot of questions about the recovery and didn't get clear answers. It seemed like the recovery time could be quite variable. I was discharged from
the hospital in twenty four hours. My husband picked me up, We picked up our gear from the campsite, and then headed home. My foot was a gray and blue, swollen lump for about a week, and people stared every that I went. Luckily, the recovery was quick for me, and I was just about back to normal in four weeks. Whenever I do field work now, I always have snakes on my mind. I don't really prefer doing field work in places where rattlesnakes are common or we might run
into them. I always wear shoes, and sometimes I wear gators I prefer when I'm hiking for fun to go to higher elevation areas where there's really no chance we'll run into any kind of rattlesnake And I worry about my dogs a lot, but in the end, like I still do a lot of field work, it's just more present on my mind. And I tell everybody that I work with what happened to me and hope that they are more cautious as well.
Wow.
I mean that is absolutely terrifying, absolutely terrifying. I can't imagine what a long and just I don't know, awesome car ride.
Wow.
Yeah, thank you so so much, Gwen for taking the time to chat with me and for telling your story. I'm yeah, it's just we're really glad that you're better now.
Yeah. Hi, I'm Aaron Welsh and I'm Erin almon Updyke.
And this is this podcast Will Kill You, And today.
We're taking a few steps outside of our comfort zone and we're talking about snake bites.
We are specifically venomous snake bites. Yes, yeah, And there's a lot out there and there's a lot to this story. And just in advance, I want to say that you know, we're probably not going to cover everything that you would want us to cover about snakes and what's going on with snakes in the world and snake bites and stuff like that. But don't worry, because we are going to
cover some very interesting things number one. Number two. I think this also leaves us open to revisiting snakes in the future, Like I really want to cover that snake fungus someday.
Ooh, I don't even know about snake fungus Aaron. Yeah.
Yeah, it's called snake fungal disease, and I don't, to be honest, know all that much more about it, but I've I remember seeing presentations about it.
And like different conferences and I was entragued. So so we're not talking about that today. We'll just focusing on the venom that a lot of snakes produce and how it affects humans if we get bitten.
That's correct. Yeah, And speaking of snake bites and what happens when you get bitten, should we talk about our quarantinie for this episode.
What a great transition and I really loved it.
It was not at all forced, it was super smooth.
But our our quarantine for this week is the snake Bite.
It's the snake Bite. It's a real it's a real drink, which makes our job, you know, easier in that regard. It's a very simple drink as well. It consists of two ingredients, cider and then either logger or stop up to you and we'll we'll post the full recipe for the snake Bite as well as the non alcoholic Placybrita. I'm very curious to see what I come up with same on our website this podcast will Kill You dot com, as well as on all of our social media channels.
Our website This Podcast will Kill You dot com has some pretty incredible things that you can find on it if you haven't checked it out yet. We have our bookshop dot org, iphilia account, we have a good Reads list, We have all of the sources from all of our episodes. We have transcripts from them all. We have a link to Bloodmobile who provides the music. We have our Patreon, we have merch I might have missed a few things that that was all that one breath could handle.
I think you did a great job. My post it is not currently with me, so I can't I can't verify and add what I forgot exactly, but that's okay. I don't think we have any more podcast business, so can we please get started. I am really really cureedious about snake venoms.
I can't wait to talk about them right after this break. So here's the thing. We are not herpetologists, and like you said at the top, we're not going to pretend like we are for this episode. So I'm not going to be getting into a lot of detail about the snakes themselves, and I'm going to try to avoid getting anything wrong when it comes to the biology of snakes by mostly ignoring the snakes themselves. Yeah, I know herpetologists
who follow us, I'm sorry. But what I am going to focus on instead is the venom and the effect that various types of venom have on our human body. And so what I hope that listeners will take away from this is the very broad strokes of the different varieties of venom and how they work, and why it is that some snake bites are so dangerous to humans. Shall we begin, Let's do it. Snakes are an incredibly
diverse group of reptiles. I learned there are over thirty five hundred species of snakes, but today we're going to focus on just a few of the families of snakes in the claye Callubroides, oh that's how you say it, which contains the families and the subfamilies of snakes that
are of quote human medical importance. And these snakes, there's three major groups of them, the Elapids and the fami Elapidae, which are the cobras, the mambas, the sea snakes, which I still to this day am terrified of the idea of sea snakes, even.
Though they're the ones you're probably least likely to encounter.
I know something about them. It is the most like, I'm not afraid of snakes. I think snakes are very cool, but sea snakes terrifying me. Something you learned about me today, Yeah, yeah. Also the group the Viperids in the family Viperidae, which include the vipers and pit vipers, which are like rattlesnakes and other things as well as adders. And then the subfamily and I might not pronounce this right, attract a spitina.
This is mole vipers and stiletto snakes. It's a smaller group, not super common.
Stiletto snakes. That's like a very cool.
Band name I wonder if it is a band, I wonder it should be someone make it. And so these are the three major groups. The elapids, the viperia, and the attracta spinina snakes that are considered of medical importance because their bites are extra dangerous to humans. All of these types of snakes have venom glands on either side of their cute little faces, and these glands are connected to ducks that transfer the venom to the base of their fangs. And in many cases, these fangs are very cool.
They have canals in their hollow fangs through which the venom travels and can then be rapidly injected into the victim with a bite.
It's so cool, it is.
Snake fangs are very cool. They vary a lot evolutionarily between groups, like some of them fold back, some of them fit into grooves. Some, like spitting vipers, can actually spit their venom out. It is very cool. Someone else can get into that. But let's talk about venoms. So Venoms are specialized types of toxins that have to be injected into their victim in order to have an effect, as opposed to a poison, which can exert its effect
after ingestion or even just by diffusing across the skin. Right, So, venoms, including snake venoms, have a lot of large molecules as part of their composition that actually have to then be injected through the skin to enter the bloodstream and then exert an effect and venom. I know you know this erin, but a lot of listeners might not. Venom is inherently
an ecological phenomenon. So the composition and the activity of any given animals, but especially any given snake's venom, inherently co evolved over time with the specific physiology and ecology of primarily the prey animals that this venom is being used to assist in eating, right, and probably to some extent as well, the predator that these snakes are in threat from. So some snakes their venom is primarily used
to immobilize their prey. Other snakes, their venom is actually beginning the process of digestion for them, and other snakes they're using their venom primarily to ward off other predators. So there is an incredible amount of variation in snake venom.
In it's unbelievable. It's so beautiful, Yeah, it really is. It's amazing. I just it's also, of course, a lot more diverse than I realized.
As always. As always, so, humans, as it turns out, are probably not super important in the evolution of snakes or snake venom. And so I want to quote from a paper that I liked here, quote human in venomings are best viewed as collateral damage of the chemical arms race taking place between various snakes and their prey. I love that.
It's definitely an arms race.
Yeah, and we're just collateral damage. So that's how I want us to view all of these symptoms that you'll see when we talk about the different types of venoms, because, as it turns out, snake venoms are some of the most, if not the actual most complex venoms of the entire animal kingdom. Oh, lots of other animals, scorpions, bees, ants, lots of different animals make venom. Snake venom is incredibly complex.
Each individual like venom that a specific snake is going to inject into you is composed of anywhere from fifty to two hundred different components, some of which are toxins are harmful, and some of which are not but serve some other purpose, right, like just helping facilitate the entry or something like that. So Venoms are comprised of proteins, carbohydrates, lipids, and the snake venoms that are of human medical importance.
Despite their incredible complexity, can generally be broken down into three major categories based on how they exert their effects. These are the neurotoxic venoms which affect our nervous system, the hemotoxic venoms, which affect a lot of times our ability to coagulate blood and will get into it, and then cytotoxic venoms which cause tissue death and tissue damage.
And the complexity of all these different toxins tends to fall into a few major like molecular biology or biochemistry groupings like there are certain proteins that are very common across snake venoms, but they don't necessarily neatly fall into these categories of neurotoxic, cytotoxic, hematoxic because there's a lot of variation in their potential sites of action, where specific toxins that might look similar actually have a very different
clinical effect in different snake species, which is mind blowing, yeah complicated, and it's also often a generalization that's made that the venom from elapid snakes, so those cobras, mambas, coral snakes is primarily neurotoxic in nature, and venom from viperid snakes, vipers pit vipers rattlesnakes is primarily cytotoxic and hemotoxic, And these generalizations are true to some extent, but there is so much individual variation, and there are so many
exceptions to those rules, like spitting cobras, which cobras are generally neurotoxic, but spitting cobras often have a lot of cytotoxicity hemotoxicity. Rattlesnakes generally have very hemotoxic venom, but some species also have neurotoxic properties, and a lot of Australian snakes just do the most wild and crazy things.
Well, and isn't there also a lot of variation among populations or even individual to individual.
Exactly exactly so even between for example, mojave rattlesnakes, some groups, some populations of that species of rattlesnake have more neurotoxic venom and others have more hemotoxic venom.
So interesting.
I can't even express how fascinating and mind blowing it is, but it's incredibly complicated and so to just be able to understand the basics of like the different ways that various snake venoms could affect our bodies. We're going to focus on those three broad categories of venoms cytotoxic, hemotoxic, and neurotoxic, and how each of those would present if you got bitten by snakes with these various venom properties.
Shall we let's do it so the first big distinction between bite types if you get bitten by a snake, besides, I should mention is it a dry bite or is it an in envenomation because it's also important to note that while many snakes are venomous, not every venomous snake bite results in in venomation, because some bites are what we call dry, so they don't actually spit any of their venomount But other than that, we'll just focus on
the venomous bites. The first big distinction is whether or not there are going to be any local effects of that bite. Cytotoxic venom causes a significant amount of local effects sido meaning sell toxic meaning toxic. So cytotoxic and venoming symptoms often look like incredibly painful and sometimes very severe sweat at the site of the bite, which can sometimes lead to very large like blood filled blisters or
extensive deep tissue bruising. There can be tissue damage and necrosis or death of tissue of your arm or your leg or wherever the bite occurred, and it can be so severe that if it isn't surgically debrided or cared for, the limb can end up needing amputation. Because of how severe tissue death can be.
I have in my research. I came across some pictures of it by accident, and.
It's terrifying, terrifying. Yeah. Yeah, there's also in some snake venoms a type of tissue damage that occurs that ends up causing blood clots in small vessels that actually then contains the venom toxins to the site of the bite wound so that they don't travel more extensively, so that those toxins can ex their effect very locally, which I think is fascinating.
Yeah.
So if you have a snake bite that is very painful, very swollen, very obvious, then there's a component of cytotoxicity that's going on there. Okay, okay. Another place that cytotoxicity can come into play is actually in a more systemic way. So that was all kind of the local cytotoxic effects. But as snake venom travels through the lymphatics and reaches kind of the rest of the body, some snake venom toxins have specific effects on our muscle cells, which is
known as myotoxicity. These end up actually damaging or killing primarily our skeletal muscle cells, so muscles in your arms, your legs, and this process of muscle cell breakdown leads to the release of a lot of enzymes from our muscle cells and proteins that actually are very damaging to our organs, especially our kidneys. So this process can actually
lead to k kidney failure. This is called rhabdomyolysis. It's not specific to snake bites, but it's a really important complication of the skeletal muscle breakdown that snake venom toxins can induce that can then cause kidney failure and death. Your face has questions.
I have a question.
How is this so targeted?
Like are we going to talk about the structure of these different venoms and like how they do the things that they do.
Yeah, So that's a good questionnaire and I'm not. And it's not because it's not necessarily known, but it's because it is so incredibly complicated. So there are kind of a few dominant categories of proteins and enzymes that are involved in snake venom. Some are called phospholipases, some are called svmps snake venom metalloproteases or snake venom seerine proteases svsps, and then they're are three finger peptides. Those are the four kind of major groups of proteins that cause a
lot of damage, and there's a lot of overlap. For example, the PLA two's the phospholie paces. They have a lot of the myotoxic and inflammatory cytotoxic effects, but they also are very neurotoxic as well different ones.
So it's it's okay, so yeah, yeah, so.
It gets really really complicated, but in general it are it is these phospholie paces that have a lot of that specific myotoxic activity. Okay, it's I just I know, I know, Aaron, And it's so like the there are so many different ways, even in under the grouping of say cytotoxic, there are so many different specific ways that these enzymes and these proteins and these toxins can end
up killing cells. It's not just like one mechanism of act I see Okay, Yeah, but that's kind of the first category of big effects that you might see is tissue death either locally or more systemically with muscle breakdown. Okay, that's cider toxic venoms and cider toxic components. The next thing that you might notice or you might look for when it comes to a bite wound is is that bite wound oozing oozing? What oozing blood?
Oozing?
What?
Oh? Blood? Okay?
You pus or like clear liquid or something?
No oozing blood okay. Snake bites can cause both local and systemic hemorrhage, and the way that they do this can vary a lot, but there's two main mechanisms and they both fall under the umbrella of a hemotoxic venom. The hemotoxic venoms have two different presentations that, as we'll see, kind of go hand in hand and to create a very bad potential outcome. So some toxins, some hematoxic toxins in venom can cause vascular permeability, which we've talked about
in other episodes in various ways. But Basically, these toxins attack and break down the basement membrane, the bottom layer of our blood vessels, especially in our small blood vessels, are capillaries, and this leads to leaky vessels, which leads to loss of fluid and what we call extravasation of the blood out of your blood vessels and just into
your general spaces in your body. And that means that there's less fluid in our blood vessels, which can then lead to hypotension low blood pressure because you don't have enough fluid to have enough pressure in your blood vessels, and that can lead to shock, which is when you're not able to perfuse your tissues because of how low your blood pressure is.
Okay, that can lead to death, and so that is indicated by an oozing a bloody oozing wound.
Potentially that's one possible sign. Yeah, okay, okay. A number of other toxins might cause vasodilation, basically opening up our blood vessels in diameter, which has the same effect of reducing our blood pressure. Right. It's actually incidentally how a lot of our blood pressure lowering medications work. And I think you'll probably talk arin about how at least one anti hypertensive class of medicines was actually developed from snake venom.
Yeah, I'll mention it very briefly, but it is one of the coolest things, and I yeah, I just I love it so much because it's such a beautiful little example of how we're like, let's take this thing that can be very harmful and wait a second, how is it useful?
Exactly? Yeah, and it is. It's a very useful class of medicines. But basically in an venomation sense, where you're getting a large load of this all at once that can also lead to hypotension and shock. It's a different mechanism, it's the same end result. But the other part of hemotoxicity that I think is even more absolutely fascinating is that various different snake venom toxins have specific effects on our coagulation cascade.
Which isn't it great that we did hemofemia? So if you've listened to it, you're familiar with the clotting cascade exactly.
If you haven't, I'll refresh you. Basically, in short, the process of blood clot formation in our bodies, which begins when endothelial or our blood vessels are damaged in some way the process that we use to form a blood clot to fix and heal off that damage so that
we don't just keep bleeding freely. It's a series of very complex steps where there are like thirteen or more different factors or proteins that have to be activated in series to then go on to activate other factors so that the end result is formation first of what we call a hemostatic plug, and that happens mostly with platelets, which are like our first line defense, and then eventually a fibrine enhanced really strong clot, and then eventually our
body is able to repair that area. So this system, this coagulation cascade, is very tightly regulated in our body. It requires all thirteen plus of these factors to be activated in series to make that clot and then break
that clot down to repair the area. Well. One of the hallmark effects of a lot of snake venom toxins is what's known as a consumption coagulopathy, which means that what they do is they activate factors in this coagulation cascade, and in so doing they use them all up, so then we have no factors left and we can't make a blood clot, so we bleed and bleed and bleed.
Oh that's so interesting. So it causes both like clotting but also massive.
Hemorrhage exactly, Aarin. Weird. Yeah, So what it tends to do is it causes clotting. That's because it's being activated by the snake venom toxins and not the normal coagulation cascade. It doesn't go through all of the steps, so the clots that tend to form get broken up very easily, and this process uses up all of our coagulation factors, so then we have none left to actually make a clot.
That's amazing. And if you combine that with the fact that other toxins in this venom are also causing leaky blood vessels, now you have leak blood vessels and the inability to clot, you get massive hemorrhage, which, especially if it happens in somewhere like your brain, is life threatening. Right.
It's fascinating, Aaron. And what's even more fascinating is how many different specific toxins, specific forms of those various proteins that I mentioned, affect different parts of this coagulation cascade. Almost every single step can be affected by different snake venom toxins.
Evolution is an amazing thing. It really is.
It is.
It blows my mind if it wasn't so terrifying. Even though it is so terrifying, it is still kind of a beautiful, beautiful thing.
It is. I mean, and I think that snakes are Fear of snakes is the most common or one of the most common phobias, and I get it. Yeah, And snakes have a really they hold really important meaning in human history. I read somewhere that up to fifty percent of people report dreaming about snakes at some point.
And I dreamt about them, wasn't I.
And it's it's amazing and so like I what I really don't want people to think after listening to this episode is that we don't like snakes or that snakes are bad or anything like that, because they're not. They're amazing, beautiful creatures and they just happen to sometimes bite people with these venoms that are very very bad.
Yes, I know, I feel the same. I was really worried after all of this, where I'm like, this sounds so terrifying, and I know so many people are terrified of snakes, and it's not the snake's fault.
Right, and it's I feel like it's definitely one of those cases where hopefully knowledge is power. Yeah, and the more you know about something, the less sort of mysterious and scary it might be, just if you have that understanding. But also it's it's reasonable to be afraid of snakes because.
It's evolutionarily adaptive.
Exactly exactly as I'll talk a lot more about.
I can't wait. Okay, we have one more class of toxins to talk about, though, the neurotoxins. Neurotoxic envenoming symptoms often start with a descending paralysis, that is paralysis of the muscles, starting in our face, the small muscles of the face that are innervated by our cranial nerves, and it progresses downward through all the nerves and our body until it eventually affects our respiratory muscles and can cause death from respiratory failure. Does that sound familiar?
It sounds like botulism.
It sure does. I'm actually just going to do a lot of callbacks to old episodes in this episode. Okay, it's a lot like botulism, but the way in which snake venom toxins end up doing this paraly busness is amazingly variable. There are dozens of different specific targets that they have, and it almost all ends up in this
same descending flaccid paralysis. So let's kind of go over it a little bit more detail in our botulism and our tetanus episodes, and I also think in a lot of our crossover episodes with mat from indefensive plants, because
we end up talking about neurotransmitters a lot. But I've talked in detail about our nerves, our neuromuscular junction, which is the junction between where our nerves actually exert their effect on our muscles to cause them to contract, and I've talked about all of the various neurotransmitters that are involved in sending those signals and converting an electrical signal to a chemical signal to have the effect on the muscle.
It turns out that snake venom toxins can affect almost any part of either the presynaptic that is, the nerve end, or the post synaptic that is the muscle receptor end of this neuromuscular junction. So some toxins that are presynaptic that act on the nerve itself like botulism does inhibit the release of certain neurotransmitters. Others cause the release of all of our neurotransmitters at once and use them all up.
And both of those different mechanisms have the same effect of depleting the ability of our nerve to transmit a signal to our muscle. Some other toxins on the post synaptic or the muscle side block the breakdown of neurotransmitters after they've been sent, so that they can't unbind their receptor so that new or repeated signals can't go through. Some of them just block receptors directly or even interfere with the neurotransmitters while they're in that synapse, crossing the
space between the nerve and the muscle. It is incredible and incredibly complex how many different specific mechanisms of this have evolved. And what is even more amazing is that the symptoms, regardless of those specific mechanisms, are an acute flacid so floppy paralysis that starts with the muscles of the face and travels downward regardless of where the bite wound was or what that specific receptor is involved.
That is it is, it is, You're right, It is amazing, It is incredible, it is fascinating, and it just leaves me to wonder, are there any spots along that sequence that haven't been targeted by or like can't be targeted by venoms?
You know what I mean? Because yes, it's a great question.
There are so many different types of ways for this to happen, and they've all been check check, check done yep.
And if not by snakes, then by scorpions or someone else.
Right, Yeah, it's amazing, I know.
I will say there are some exceptions, like there are some South American rattlesnake venoms that cause more of a spastic paralysis like tetanus does, but in general, almost across the board, it's a more flaccid paralysis. Interesting, I know. And so that's kind of all of the different types of venom. And I know that for a lot of people that probably wasn't enough detail, and you want to know a lot more. I have tons of good papers for you, and for some people that was probably like
way too much. But hopefully you know, we get at least the broad stroke pictures where different components of different types of venom can have a huge variety of effects on our human bodies, and when we look at it back evolutionarily, it's because of all the different ways that these specific snakes we're interacting with their prey or their predators to try and immobilize them or make sure that they die quickly or et cetera. There is treatment a lot of times.
Is it like I saw in Hey Dude growing up, sucking out the venom of the bite?
It absolutely is not. Please never suck the venom out of someone's bite or your own. That is a falsity. There's probably a lot of myths we can dispel right here. Don't suck out the venom, that's one. Please don't cut open the wound to try and let the venom drain.
Do that either that can make things so much worse.
So much worse and just invite more infection. Don't tournique off the limb because that can cause a lot more tissue damage, immobilizing the limb and potentially doing a pressure dressing, which is like think of like an ace wrap like you would put on sprained ankle, like that level of compression. But even that only if you're not having a lot of swelling, If you have a lot of cytotoxic local effects and your ankle, for example, gets really really swollen.
You wouldn't want a wrap to be so tight that you're cutting off blood supply, especially if you, like Gwen, have a three hour drive to wherever you're going. But immobilizing your limb can help reduce the spread of toxin through your lymphatics.
I also read something, and I want you to tell me if this is true or not, that you should that sometimes it is advised to not wash the wound very carefully because, especially if you don't know what kind of snake bit you, then it's important to be able to get the venom if there's any like around the wound.
So from what I read, it's only in Australia and New Guinea that they have the ability to swab a wound and be able to test for a specific type of venom okay, And so as far as I know, those are the only places where they have that type of detection available to be able to say what a specific venom is by swabbing a wound to try and find venom. Gotcha, So anywhere else if you have and especially if it's going to be a very long time until you can get medical care. Cleaning a wound is
always going to be a good idea. It just gently that makes sense. Yeah, good question though.
And then what about if you don't know what snake but you because like that's one of the biggest challenges, right is if you get bit by a snake, how do you get the proper treatment because that can vary a lot depending on the snake species you.
Are so correct erin. And it's also a problem because how do you identify a snake that you just got bitten by. That's very difficult to do. You might not have even seen it. It might have happened while you were sleeping, it might have happened in the dark. It might be that you don't know snakes very well. I don't know snakes. I would have I would know rattlesnake because of rattles otherwise generic snake, and that's literally all I've got. It's
a great question. It is very difficult to know exactly what snake bit someone. And one of the things they say sometimes is if you bring the snake with you to the hospital, then that can facilitate identification. But there's a huge butt to that. It's very dangerous to try and kill and then bring a snake in, So don't do it. I wouldn't recommend it. And even if you brought it to a hospital, there's no guarantee that there's going to be an expert herpetologist around who's going to
be able to say exactly what that snake was. The same holds true for trying to get a photograph of the snake to use that for identification. It can be very difficult. So to some extent, yes, being able to describe a snake might help in certain regions, to be able to identify is it an a lapid snake or is it a viperid snake? So is it more likely to be neurotoxic or is it more likely to be
hemotoxic or cytotoxic. But really what it comes down to is actually having to just evaluate it clinically, and you might never know exactly what snake it was. Oh, I see, okay, yeah, and you're right, it's important to know or to try and know what type of snake it was to be
able to give the right anti venom. Anti venom, by the way, is produced by hyper immunizing or exposing horses or sheep, usually to venoms from snakes and then purifying the antibodies that they make and using that as a therapeutic. So it's horse or sheep antibodies against snake venom that we use as therapy.
Do you know when anti venin and anti venom? Because I've seen it written both ways erin.
I never saw anti venin except for Pfizer's specific like trade name as anti venin. Okay, so I don't know. It might be an old timey name.
Yeah, maybe that's maybe that's the case, because I did see it in some older paper, but I did I didn't know if there was a difference.
I don't think there is. I think it's the same thing.
Okay, there is a difference between toxicology and toxicology. As I learned, I had.
To learn that too. I was like, are they doing typos right now? Yeah?
I oh, well, because even a word or Google or something was like, did you mean toxicology? And I was like, I don't think so.
No.
I googled it multiple times, more than twice to make sure I understood. But yeah, So knowing the snake can be very helpful in trying to get the right anti venom. It's not always possible. It's also the case that a lot of anti venoms are not specific to one snake anyway.
They're polyclonal. They're made from hyper immunizing horses against multiple different snakes that are present in a given region to try and provide immunity against a wider variety of snakes, which can be great, especially when you can't identify what type of snake you got bitten by. But the problem is that then it tends to be much lower tighters, so like a smaller amount of an anti venom that's going to help any one specific snake if that makes sense,
or one specific snake bite rather. But really, when somebody comes to a hospital with a snake bite, it's all about looking at what are the symptoms that they're having and doing a lot of blood work to see are you having problems with coagulation, are you having problems with tissue swelling, are you having evidence of that rhabdomyolysis, are you having any evidence of your eye lid is droopy, you're having paralysis, etc. And then you treat those based on And this is the other thing that I think
is so incredibly interesting and difficult about snake bites is how hyper local This knowledge all has to be right, because in Western Colorado, the profile of the types of venomous snakes you could possibly be bitten by is very different than in the Eastern United States or in Australia or in Sri Lanka. Right, It's incredibly different, And so it's all going to be specific to where you are and what your symptoms are to know what's the most likely type of anti venom to use to treat this.
Yeah, so I understand that the venoms are very variable and the composition and among the different types of venoms and so on. But are there certain types of venoms like hematoxic versus neurotoxic where you need to get the anti venom delivered sooner?
Very good question, Aaron. In general, there's a lot of studies that have shown that the sooner that anyone gets anti venom the better.
Right.
Of course, when it comes to especially neurotoxins, just like we saw with botulinum toxin and tetanus toxin. If we are talking about a presynaptic toxin, so something that affects the nerve end of a cell. Once those toxins bind, there is nothing that you can do anti venom doesn't do anything. So in those cases, especially the sooner that you can get an effective anti venom on board, the more likely it is you can prevent further toxins from binding.
In the case of postsynaptic and in the case of hematoxic, you have a lot more ability to reverse the damage with anti venoms. Okay.
And in terms of these neurotoxins, what we learned in tetnus is that basically how long those the tetanus toxins exist, how long they are functional. How long are these presynaptic neurotoxins functional.
It's a good question. I think it very much depends on the snake species. So I don't think there's an easy half life I can give you got it, okay, But people do tend to recover with supportive treatment. It's definitely treatable.
What is supportive treatment besides anti venom therapy.
Great question, of course, depends on the type of toxin. If it's something where it's cytotoxic and things need depreatment or they need cleaning, that sort of thing is going to be more supportive care. If it's a rhabdomyolysis, the most important thing is actually hydration, so it's a lot of ivy fluid administration to keep the kidneys from becoming
damaged from that muscle breakdown. And then in the case of neurotoxins, it's more about making sure that people have airway support, so mechanical ventilation and the same kinds of things we saw with tetanus toxin. Okay, yeah, and that's a lot.
It's a lot. I mean, it's fascinating, as we said a thousand times so far, but it's.
Still so true. Listen, I don't even know where to begin to ask you, like, what's up with this this snake venom thing? Yeah, and how have humans interacted with snake venom and the idea of snake venom through time? Such good questions.
I'll do my best right after this break. This was definitely a tricky one to research because there is absolutely so very much that you could cover when it comes to the history of snakes or even how snakes have featured in human history. And before I started reading for this episode, I didn't really know where the research was going to take me or what story I wanted to tell, and it was kind of daunting. But I thought to myself, Okay, in this episode, we're talking about venomous snakes and what
happens when you get bitten by a venomous snake. So why don't I look into how humans have responded to these snakes and the bites from these snakes over time. And that led me down some very surprising but also very interesting roads, and I decided to structure the history
section in two parts. The first part deals with evolution, how the encounters that our primate ancestors had with snakes over millions of years may have shaped how we look at the world literally what, And the second part covers how more recently we have learned to deal with those encounters through the development of anti venom therapy. Ooh, I
am very excited, So let's dive in. Okay, first, the snake detection hypothesis oh okay, also sometimes called the snake detection theory, but I really don't like that it's called a theory since it isn't a theory strictly speaking, It's a hypothesis. Have you come across this before?
Nope? But I can't wait.
I am so excited. Okay, I'm so excited. At its core, the snake detection hypothesis proposes that humans and other primates have such excellent vision because of snakes, which were among the earliest and most important predators of early primates. Individuals that couldn't see the venomous snake in the grass or distinguish a snake from a vine were more likely to get eaten and less likely to pass along their genesh. This is a lot. Yeah, break it down, Okay, why vision?
First of all, primates are actually unique in that they have some of the best vision among mammals. Forward facing eyes gives them excellent depth perception. They have high visual acuity, and many species have trichromatic color vision, which allows us
to distinguish among like greens and reds and stuff. The parts of our brain that are devoted to visual processing, both the non conscious and conscious parts, are expanded, and these parts are the parts that provide like an automatic predator or threat detection and then allow us to process that information to decide what we want to do. It's our visual system and our reliance on vision as our primary sense in large part, that distinguishes us primates from
other mammals. Throughout the years, researchers have put forth different hypotheses to explain why primates have such good vision, for instance, resource acquisition, like grabbing insects or grabbing fruits, being able to do that visually directed movement with and grasping.
And like I've I've also read a lot of like recognizing, especially with color vision, being able to see red fruits in green trees, et cetera.
Yes, exactly, yeah. And then also there's the arboreal movement, so like moving through trees, being able to use that depth perception to reach and grasp branches so you can move better through trees. Those are some of the hypotheses. Most recently, there is the snake detection hypothesis, which was put forth by UC Davis professor lynn Isbel in two thousand and six. She proposes that primates evolved this excellent
vision to better detect snakes, specifically venomous snakes. To see how this might have happened, let's travel back to around sixty million years ago, a few million years after the massive extinction of that wiped out so many of the
non avian dinosaurs and other life on Earth. With the non avian dinosaurs gone, small mammals began to flourish, which opened up a new food source for snakes, which had been around for tens of millions of years already, but with the dinosaurs gone, they had even more opportunities to
expand and diversify, and so they did. After the huge Cretaceous Paleogene mass extinction event, venomous snakes began to appear, possibly in response to the emergence of faster moving mammals, so you could as a snake, you could hide, strike, and then wait for the venom to do its work, rather than having to get close enough to constrict, which is what most snakes used as their like prey kill
method before this. And it's thought that snakes also evolved large gapes, as in they can open their mouths really wide, so that they could take advantage of these diversifying mammals.
I'm loving this so much already, Aaron.
I'm glad. I'm glad.
I feel like I'm back at like a natural history museum and I'm walking through the like you know, evolution display at Field Museum, just like, Oh my goodness, that's how I feel right now.
I love it.
Oh, I love it so much. I love it. Yeah, I find this absolutely thought provoking. I'm I'm it's very interesting and so yeah, of course, venomous snakes and the earliest primates would have been well acquainted with each other. In fact, the earliest primates would have faced the continual threat of venomous snakes as predators well before the other important predators like wildcats or birds of prey emerged, which
was later on. If snakes are one of the biggest reasons why certain individuals aren't surviving long enough to reproduce, that's going to strongly select for traits that will help individuals avoid getting eaten, and in this case that's proposed to be vision. Being able to distinguish that well camouflaged, unmoving snake from a pile of leaves could save you.
And detecting snakes close up is more important than detecting them at a distance, unlike other predators, where you'd presumably want to have as much lead time as possible to run away or hide. So can we agree here that the logic seems to be there for the snake detection hypothesis?
Yeah? I like it.
It's logical, Okay, cool? What evidence is there to support it?
Is there? Is there? Tell me?
So?
Up to this point, I've basically been talking about primates as one large, homogeneous group which of course they are not. And it's actually some of these differences among groups of primates that provide some very compelling bits of support for the snake detection hypothesis. So when I say that primates have excellent vision, that's true in comparison with most other mammals, but within primates there's a good deal of variation within
visual ability. For instance, lemurs from Madagascar have some of the worst eye sight of all primates, and they only have dichromatic color vision, meaning they can see or distinguish among fewer colors. Okay, interesting thing about Madagascar no venomous snakes.
Okay, uh huh.
And if we look at the places where venomous snakes are the most numerous or have the most potent venom places like parts of Africa and Asia, the monkeys there have the most advanced vision, the best color vision, and some of the largest visual processing regions in their brains. And so this would suggest that lemurs, which did not evolve in the presence of venomous snakes, didn't experience as strong of drivers in terms of vision compared to these
other monkeys. It's cool, but it's also possible, of course that this pattern emerged for other reasons besides venomous snakes.
Yeah, something else.
Yeah, So let's get a little more specific by looking at some neuroscience, but without getting too much in the weeds, Okay, because I don't know anything about neuroscience. Earlier I mentioned that the visual processing areas of the brains of primates are expanded compared to most other mammals. One of these areas deals with non conscious automatic predator detection and then an immediate motor reaction. So imagine you're seeing a snake slither in front of you while you're out for a run.
You may react by freezing or leaping backwards, even without realizing you're doing it. You just do it completely unthinkingly. That region is called the pulvinar region, and in twenty thirteen a group of researchers set out to test whether
the snake detection hypothesis could be backed by neuroscience. They showed macaque monkeys who had never seen snakes before a series of images snakes, other macaque faces, macaque hands, and geometric shapes, and then they measured how strongly the neurons in the pulvinar region of these monkeys responded images with snakes led to the strongest and fastest responses compared to other categories. What and there's more. The position of the
snake also made a difference. Snakes that were in a threatening pose led to a stronger response.
And these are monkeys who were raised in a.
Labor and raised in captivity. Okay, yep, So this is a really nice piece of neuroscience support for the snake detection hypothesis. And I'll include this paper on our website. It's by Van Lee at All from twenty thirteen if
you're curious. What about humans though? Yeah, Another study from twenty seventeen measured responses to images of snake skin like close up images of snake skin versus bird feathers, so not images of like the complete animal, but just the patterns, and the images of snake skin got the earliest and
strongest response. Again, and yet another study compared fear responses in humans when presented with images of venomous snakes, non venomous snakes, and leaves, and found the strongest fear response with venomous snakes, which I think is interesting because I don't necessarily know if I know all the time whether snake is venomous or not. I know, it's like head shape matters, but it's not just head shape.
No, because even that, like the elapids have very different headshapes than the viperiods, and the elapids are incredibly venomous, so exactly that is really interesting.
Yeah.
Yeah, And these studies aren't alone. These are just like a couple that I'm mentioning. There have been quite a handful, a surprising handful of neuroscience or physiological studies that have tested this hypothesis and have generally found support for it, and I think that is so cool. But what I also find cool is the behavioral response that primates show towards snakes.
I have a question real quick before we get into the behavior in any of these like neurologic response studies, did they test other predators in addition to snakes.
It's a good question. I don't know. It's possible that there are There were a lot of studies out there, and I didn't read through them all in the ones that I mentioned, they did not, but there may they may have, And so I think that, Yeah, that is one criticism that this hypothesis often faces, as like, well, couldn't just be more generally be called the predator detection hypothesis, Like it seems a little bit much to pin all of our visual evolution, or not all, but most on one single predator.
Right.
That being said, I think that it's also interesting in that the predators of primates that we see today, like you think about lions or jaguars or birds of prey, a lot of those things would look very different sixty million years ago compared to how they look today, whereas snakes largely look kind of the same.
Yeah, that is interesting, is interesting, right that they they were our evolutionary pressures millions of years ago when this visual acuity was evolving.
Right, and so the general shape of them we may have evolved. Specific recognition of snakes as specific cues and the shapes of snakes, yeah, whereas like you know, larger cats we may not have. But I don't know. It's it's definitely a really good point, and I don't know.
I wonder if you compared it to other things like say alligator's, crocodiles, right that also existed millions of years ago, even sharks, right, although I guess we can't everceive sharks, so maybe not those.
Maybe not sharks, but also like, how how numerous in the landscape.
Were That's true, that's true. Good point.
There's there's like so much more that you could dig so much more deeply on this. Yeah, and I will definitely link to the book that lynn isbel wrote, this book about the snake detection hypothesis that has so much more information in it.
Cool. But yeah, so behavioral stuff.
Yeah, I just find behavior behavioral studies so interesting.
Oh yeah, we love it.
Oh yeah, So, while being afraid of snakes does seem to have a learned component to it among primates. So, for instance, a snake naive monkey as in it hasn't ever encountered snakes before, may show a fear response after watching a video of other monkeys responding fearfully to a snake. Okay, yeah, it also seems to be this fear of snakes seems to be innate to some degree. Macacs that were born and raised in captivity responded fearfully when seeing a snake
in a different study. And there are some studies showing that human infants startle in response to snakes and that their attention is grabbed by snakes. Yeah, although those infant studies do seem to have somewhat mixed results, like it's unclear whether it's just startle or fear. Is there actual fear to it? Yeah, and going back to our among primate group comparison, behavioral studies of lemurs from Madagascar show that they don't seem to react to snakes, at least
visually in like a fearful way. Smell might be a different thing, Okay, because there are constricting snakes on Madagascar. Yeah, some primate species have a completely distinct alert call that they only use in the presence of snakes, and often a group of primates will do something called mobbing. They'll approach, stare, and vocalize at the snake. Sometimes sometimes the mob turns violent, throwing sticks at the snake, or even beating the snake with a stick.
Oh my god, poor snake.
I feel so bad. So up to this point, I've talked a lot about evolution, but mostly in terms of primate vision evolving in response to venomous snakes. Yeah, but what about the snakes? Yeah, Aaron, did they ever feel pressure from primates, especially once we learn to mob the snakes or use tools to hurt.
Or kill them?
They may have research in the past few years suggests that spitting cobras may have evolved the ability to spit venom, which is a defensive behavior which I find so cool in response to threats from primates. Oh and even cooler is that this venom spitting has evolved three times independently. Amazing, It's very cool. Yeah, the venom spitting. There's so much more there, and I would love to dive deeper into why cobras spit right, and also the evolution of venom
in general. Why did snakes evolve venom? Why are there so many different types of venom? Where do we find the most venomous snakes? And why how do you milk a snake for venom? There is so much that I want to ask, but I'm going to have to wait for next week as well, all you listeners for when I interview Professor Nicholas Casewell, who is the director of the Center for Snake Bite Research and Interventions at the Liverpool School of Tropical Medicine.
I am so excited, Aaron, I can't wait for you to ask about how different snake species that feed on different types of prey have different venom and like, yes, oh my gosh, I'm so excited about it.
I am very excited too, and all of you out there mark your calendars. Yeah, it's going to be good. Okay. But back to the snake detection hypothesis. Yeah, okay, it's a very cool hypothesis and it does have some support from research. Yeah, but I do want to say that it is still just a hypothesis, a proposed explanation for
why things are the way they are. And while it's possible that snakes did play a role in the evolution of primates, most researchers include voting isbel don't claim that snakes have been the soul driver of vision evolution in primates. They may have like kickstarted a little bit of it, but enhanced vision was obviously useful for many other things, and there are some problems with this hypothesis, For instance, the suggestion that trichromatic color vision evolved to better recognize
camouflage snakes. Studies have actually shown that primates with di chromatic color vision, like those lemurs dramatic ascar detect camouflaged objects better than their trichromatic counterparts.
Oh interesting.
Yeah, and so, like you said, Aaron, the trichromatic color vision might be better explained by needing to distinguish ripe red fruits among green foliage. As with everything, more work needs to be done.
Oh but I love it. It's so fun to hypothesize, you know.
It is it is. I there's something about it that just I love. It's so fun to think about why, why things are the way they are.
I think that's why we ended up in academia for so long, Aaron, because that's how our brains just like to like ask those questions of why and think about possible explanations, and then also find a way to pick apart those explanations and find potential issues with them, and then ask more questions because of.
It, where are the limitations? And yeah, yeah, we're like we're perpetual toddlers. Why but why?
That's honestly so true.
Okay. Enhancement of vision may be one way that primates have dealt with the threat of venomous snakes throughout history, but what about other ways? A recent study from twenty twenty one showed that primates in Africa and Asia have increased levels of resistance to alpha neurotoxins, which are carried in the venom of some of the vipers In these regions,
what notably no resistance is seen in Madagascar lemurs. Yeah, but I I want to move past these discussions of evolutionary defenses to talk about the history of anti venom therapy. Snakes feature prominently throughout human history and culture. One of the oldest, if not the oldest, religious artifacts, is a stone python in a cave in Botswana. Archaeologists estimate that seventy thousand years ago people engaged in a ritual where
they sacrificed colorful spearheads to this python. Snakes hold a prominent position in many religions as creator or destroyer, as a symbol of fertility or one of evil, as a god or a demon, as representing wisdom or cunning, and this duality I think is really interesting when we think about how snake venoms can kill, but also how they
can be used as highly effective medications. It's beautiful and it's way beyond the scope of this episode to talk about the meaning that snake have held and continued to hold for different cultures throughout human history. But I think it goes almost without saying that snakes have held a great fascination for humans throughout all of time, likely because or at least in part because of the threat they
could pose. The famous physician Galen from ancient Rome wrote, quote, it seems that there is nothing more dangerous in life than poisons and the bites of noxious animals. Humans have always sought ways to protect from snake venom or find antidotes against it, drinking small amounts of venom, for instance, or using a venomous snake's flesh as an ingredient and an antidote recipe like theyac, which was a cure all
created in ancient Greece. And the variety of quote cures shows us just how feared snake bites were and how helpless physicians were entreating them. And part of their helplessness probably stemmed from the fact that no one really knew what was in the of some snakes that caused such horrible injury or death. For a long time, many people just believed it was bad spirits in the snakes. At one point, the Archbishop of Madrid reportedly exercised the venom from all snakes of Spain.
Just like it's gone, it leaves you, it's gone. Nice job.
It seems that the Italian physician Francesco Ready was the first to suggest that rather than bad spirits, it was actually this substance coming from a snake's fangs, the venom that was responsible for all of the symptoms experienced after a bite. And side note, the word venom is derived from the Latin word veninum, meaning a magical charm, as well as poison.
Oh, that's kind of fun. I didn't know that.
Yeah, and his conclusions were not widely accepted. Several physicians insisted that it was bad spirits, but Reddy refused to budge, and about one hundred years after his work, his ideas found support in research done by Felice Fontana on the mechanism of in venomation and some characteristics of venoms in
the European viper. Fontana, who is often referred to as the founder of modern toxinology, also determined that the European viper was immune to its own venom, which raised the question if snakes are immune to their own venom, does this mean that other animals can become immune as well.
I don't know why my mind is so blown by that, because it's amazing.
Yeah, it's amazing. Yeah. And so Fontana published his book in seventeen eighty one, so that was a little bit, I think, a little bit ahead of its time, right, And about one hundred years after this publication, let's see, let's take stock of things, right, germ theory was well
underway and immuneology had also gotten its start. So the study of how immune systems respond to foreign substances, toxins, whatever, and if humans and other animals could become immune to pathogens, did that mean that they could also become immune to toxins. Henry Sewell, who was a researcher at the University of Michigan, decided to test this question in the context of snake venoms.
Using the venom from the eastern Massasauga, which is a type of rattlesnake found in the US, Sewell injected small amounts of diluted venom into pigeons, and he repeated these injections over the course of weeks and found that after about a month, the tolerance of the pigeons had increased. Whereas previously less than a single drop of venom could kill the bird, at the end of the experiment, it took closer to four whole drops. Wow, which to me, I was like four whole drops that's still not a
ton of venom. But what's really cool I think about this is that it demonstrated that animals could gain some immunity to toxins and suggests did also that the serum from those animals could be used to counteract the effects of the toxins in others.
That is the part that I really truly love that it was so early that people came up with this.
Yes, I do too, And this is what's really what's really amazing is that this was before the work of Qui Desado, Shabbasaburo and Emo von Bering in eighteen ninety on tetanus, which, as I said in our Tetanus episode, you know, people consider these two scientists the fathers of modern serum therapy, and which of course they had huge significance in the history of dipitheria anti toxin and tetnos anti toxin. But Suwell may have gotten there first, right
with these snake venoms. Yeah, and so he's generally overlooked and not just overlooked in the history of serum therapy, but also overlooked in the history of anti venom therapy, which generally starts with the French physician Albert Chalmee, who the sea in the BCG tuberculosis vaccine.
That's why that name is familiar.
Uh huh. In eighteen ninety one, cal May started as director of the Vaccine Institute in what was then known as Saigon now ho Chi Min City. He had been picked for the job by none other than Louis Pasture. While at the institute, very exciting. While at the institute, Calmay became interested in the venom of the Indian cobra
scientific name Naya Naya. For several years he tried to induce immunity to this venom in animals, but it wasn't until he used the methods described by Sewell that he got anti coobra serum, which he could use as an actual therapy for cobra byte. I mean this was monumental to be able to actually counteract the effects of a cobra byte, which previously would have been at least severe injury, if not death.
Yeah.
Other researchers had been doing similar work around the same time as cal May, but their work focused more on how the venom worked and how snakes were immune to their own venom, rather than focusing on applications for their research, whereas Calme's Anticobra serum, which he began production on in eighteen ninety five, was revolutionary because it laid the groundwork for other people to create their own anti venom for
venomous snakes in their particular region. Right, although Calme wasn't convinced that snake specific venoms were needed, Oh ok, yeah, he thought that his Anticobra serum would save you from any snake bite.
Ah, I see, yeah.
But this misconception was eventually set straight by Brazilian physician vital Brazil. He noticed that in sal Paolo, where snake bites were a huge problem and estimated five thousand people died each year from venomous snake bites in the state Whoa at that time. Yeah, So he noticed that snake venoms seemed to produce different reactions in people, right, Sometimes there was this paralysis, sometimes there was this like blood,
sometimes there was a cytotoxic effect. And this suggested to him that there were different venoms causing these different reactions. And this idea made sense, especially in light of the fact that when he had used Calmet's Anticobra serum it was not very effective. Yeah, So Vitel Brazil set to making his own anti venoms, and also made mixtures for
when the identity of the snake was not known. I love, it's amazing, And so by the early nineteen hundreds, the building blocks for making anti venom for most any venomous snake or even any other creature were pretty well established. The rest was really just tweaking things such as the
quality of serum. One person who received anti venom for a tiger snake bite in nineteen thirty said quote, the discomfort of the serum sickness which followed a large intravenous injection of crude venom was worse than anything the snake venom could have done.
Oh dear, Yeah, that's a problem.
Yeah yeah. And also, of course people developed more specific anti venoms as well as general ones that would be effective against a wide range of toxins, and improvements were made not just in the quality and availability of anti venom. There have also been some amazing strides made in terms of vaccines against venom. For instance, the rattlesnake vaccine that
is available for some pets. I believe because anti venom is great, but you need to get it to the person or the animal very quickly, and so preventing the reaction in the first place is really the golden ticket.
And finally, what I feel like is one of the most beautiful developments in the history of how humans have dealt with snake venoms came in nineteen eighty one with the approval of the first animal toxin based drug, captipril, which is a hypertension and congestive heart failure medication derived from a compound in both rops javraraka snake venom specifically, if you're interested, it's the Brady kind of potentiating factor.
It's thrilling, it is amazing. It's a Now it's an entire class of anti hypertensive medications that are like, literally our first line anti hypertensive anti high blood pressure medicines are the ACE inhibitors, of which capta pril was like the first one.
It is so cool.
Yeah, there is sore too. Now there's so many relas and inhibitors. Yeah, oh my goodness.
I counted. So there was a paper that I read, I think it was from twenty twenty maybe, and I counted at least eight other medications based on snake venom alone that have been approved, and there are many, many more in clinical trials.
Yep.
Yeah, but even with all of this amazing work and the huge strides that have been made in anti venom therapies, we still have a long way to go, especially in terms of making those therapies available to those who need them when they need them. So I'll stop here and let you tell me erin more about where we currently stand with a neglected tropical disease of snake bites today.
I can't wait. Those a beautiful segue.
Thank you.
We'll take a quick break and then get into it. So I'm glad that you said it already. Erin the World Health Organization has listed snake bite envenoming as a neglected tropical disease and in fact, a neglected tropical disease of like incredible importance.
Yeah.
The World Health Organization estimates that between four and a half and about five and a half million people human people get bitten by snakes every year and that this results in between one point eight and two point seven million in venomations, wow, one point eight and two point seven million in venomations and clinical illnesses every year worldwide and an estimated anywhere from eighty one thousand to one hundred and thirty eight thousand deaths and potentially three to
five times that number of like long term morbidity from these invenomations.
It's a lot, and it's a lot more than I thought, so much.
More than I had any idea. I can't overstate how much I would have underestimated that number. Yeah, yeah, And like in I think probably every TPWUKY episode, those numbers are definitely estimates because of how much under reporting there is that happens, right if we wanted to break things down by region, which I think is important because those snakes are found worldwide, and venomous snakes are found on
every continent except I think Antarctica. There's nuts there. These snake bite in venomations are not evenly distributed across the globe. They are primarily affecting rural and impoverished areas that lack
a lot of public health and medical infrastructure. If we break some of those numbers down by region, at least one paper had estimates of different regions of the world, So in Sub Saharan Africa, it's estimated there are ninety to four hundred twenty thousand envenomings, resulting in three thousand to thirty two thousand deaths, huge range of estimate there. In North Africa and the Middle East, it's estimated there are between three thousand to eight thousand bytes that lead
to four thousand to eight thousand deaths. I feel like that's a pretty important distinction there where the death rate is essentially the bite rate. Right in Latin America and the Caribbean Islands, it's estimated there are between eighty and one hundred and twenty nine thousand envenomings leading to five hundred forty to twenty three hundred deaths. So like smaller numbers, but again huge range. In the US and Canada, check these numbers, sixty five hundred bytes a year, that's a law. Yeah,
five to six deaths, oh wow. Yeah. And then in Southeast and South Asia, I couldn't find exact numbers, but the overall mortality rate of snake bites is between one point zero five and five point four to two deaths per one hundred thousand people, so like significant mortality.
Yeah.
And then a lot of the rest of Asia, including China, Japan, Korea, and then Central and North Asia like Russia. There's just not a lot of data on snake bites. One study estimated a significantly lower mortality rate in a lot of China, that's like much less than one per one hundred thousand, less than point five per one hundred thousand. Australia likely between five hundred and three thousand bytes, but only two
point two deaths annually. Oh wow. And in Europe there is an estimated byte rate of one point zero six bytes per one hundred thousand people and four deaths annually. Okay, you can see that the vast majority of deaths are happening in Sub Saharan and North Africa, the Middle East, some in Latin America as well, and then Southeast Asia.
And this also follows the distribution of venomous snakes as well, where you're having a lot of high contact but also a large proportion of the populations that are living in areas and in conditions that put them in close contact with these snakes and without access to the infrastructure to provide them with antivenom.
Right, I feel like you could do some sort of risk of death per bite calculation based on these different regions or something.
Totally, and it's not all to do with of course, these are different snakes and so different toxicities of different venoms,
but that's not what's driving this. It's access. And one of the problems with the fact that and we've talked about this before, but I think it's especially poignant in talking about snake bites is that underestimation of the cases of snake and snake and venomation leads to difficulty in estimating the need for anti venom and what types of anti venom are needed and how much of it you need, because while anti venom can be very effective, if there
isn't a quote perceived demand for it, then producers who are in it to make money stop making it, and then there isn't enough of it, so then the price increases, then it becomes unaffordable for the people and the populations who actually need it. And that is exactly what has happened with a lot of snake anti venom manufacturers because capitalism.
I mean, unsurprising, but I know, yeah, frustrating.
It's incredibly frustrating. Yeah, And I think that process over the last few decades has been part of why the World Health Organization has such a push to reduce snake bite mortality. Right now, they have a big series of innsie that were started in twenty nineteen twenty twenty, but I haven't actually been able to figure out exactly where they stand in that progression, and I would guess that,
like everything else, it's been massively disrupted by COVID. Uh huh, yep, yeah, there has been because of this recognition of how important snake bite, snake and venoming is in terms of a public health issue, and the difficulties in anti venom not just because of capitalism and manufacturers not wanting to produce specific types of venom if they don't perceive a need, but also in that, like we talked about in the biology section, it's often very difficult to know what snake
you got bitten by and what the best anti venom might be or how much of it you might need, especially when we're talking about a polyclonal antibody that comes
from a lot of different snakes, right right. So there has been so much incredible research being done, all in pretty early stages, but on things like recombinant anti venoms, so being able to make in the lab anti venoms that don't have to rely on horses and that whole process, or even using small molecule inhibitors to affect entire classes of toxins so that anti venom treatments wouldn't have to be so specific, and also looking at mixtures of modalities
that might have multiple effects on the various toxins present in a wide variety of snake venoms. So it's I think really interesting, especially because while snake bites are a global issue, they are also an incredibly local one, right where every region is going to have different specific issues of different types of snakes that they're coming into contact with, and that can make anti venom manufacturing and administration really difficult.
And so I think that this type of research is so compelling and interesting because it can help really even the playing field in a lot of ways.
Yeah, that's very cool.
Yeah, and then, like you said and kind of mentioned, there's also a ton of really interesting research on the utilization of the properties of these toxins in these venoms to actually use them as therapeutics. So there's a lot of really cool, interesting research being done both in terms of the treatment of snake bites and also in the utilization of snake venom, which I really love.
It's amazing.
Yeah, it's amazing, and.
There's still so much to be learned. There's still so much out there in terms of questions like snake ecology, for instance, exactly how much does land use change and climate change? How are those things impacting our encounter rate with snakes?
Right?
It's very interesting.
I also really do want to emphasize for all of our listeners, especially those of you who might be a afraid of snakes or terrified of snakes, even and now even more so because of this episode. There historically has been a lot of like push of like kill all the snakes, right, and blah blah blah. Snakes are an incredibly important part of ecosystems, and killing them is not the answer. I don't know. I just don't want people to leave this only terrified of snakes with nothing else.
I think that they are an incredibly fascinating group of creatures and while the venoms can be very scary, it's just collateral damage.
It is, and for me, what always helps is learning more about them, learning.
The local snakes in your area, and being able to identify which are the venomous ones which are not, and how you can avoid them so that you don't have an encounter with a snake.
Snakes are very cool and beautiful, don't hate them?
Yeah, anyways, should we do sources, Let's do sources.
I have a ridiculous amount of sources actually for this episode, and so I am going to shout out two alone that were very helpful for the two different sections of the history section. The first one, of course, is the book by Lynn Isabel titled The Fruit, the Tree and the Serpent Why We See So Well ooh. And the other one is a paper by Squiella Baptisto at All from twenty eighteen called the History of Anti Venoms Development Beyond Calmet and Vitel Brazil. Those were both great.
I had a few papers for this episode, a couple that I want to shout out, especially if you're interested in more detail on the biochemistry of these toxins. There was a paper called Multifunctional Toxins and Snake Venoms and
Therapeutic Implications from Pain to hemorrhage and Necrosis. I think that was my favorite, just like broad picture one and another one that had a lot of diagnostic algorithms on like how you can in different regions of the world know what types of snake you're bitten by, et cetera. It was called snake bite Envenoming Diagnosis and diagnostics. I liked that one too, but we will post all of our sources from this episode and all of our episodes on our website, This podcast will kill You dot Com.
We will Thanks again so much to Gwen for taking the time to chat. It was really terrifying and awesome to hear your story and we're really glad that you were willing to share it.
Yeah, thank you for sharing it with us and all of our listeners. Thank you also to Bloodmobile for providing the music for this episode and all of our episodes.
Listen, subscribe, leave us a review on Amazon Music, Apple Podcasts, or wherever you get your podcasts, and don't forget. You can hear every episode one week early and ad free by subscribing to Wondery Plus in the Wondery app.
And thank you also to Exactly Right Network, of whom we are proud.
To be a part, And thank you to you listeners. We hope you liked this one, yeah, and hope it made you want to read more about snakes and learn more about snakes if you aren't already a herpetologist.
And if you are, I hope we didn't get things too incorrect. Yeah, and a special shout out to our patrons. Thank you so much for supporting us. We love you.
Yes, thank you well. Until next time, wash your hands
You filthy animals.