Speaker 1: Hi.
Speaker 2: My name is Gwen, and this is my story. It
Speaker 2: was the last day of our ten day field trip.
Speaker 2: We were working and camping at our most remote field
Speaker 2: site in western Colorado, conducting botany surveys for a research project.
Speaker 2: My field assistant, Chloe, and I decided that we would
Speaker 2: spend the evening swimming and relaxing by the Dolores River.
Speaker 2: As the sun set, I started to get ready for bed.
Speaker 2: I was tired and ready to snuggle up in my
Speaker 2: sleeping bag. I walked over to the truck to refill
Speaker 2: my water bottle and grab my toothbrush. As I reached
Speaker 2: for the driver's side door handle, I heard a noise
Speaker 2: and looked down just in time to see a rattlesnake's
Speaker 2: fangs penetrate the skin on my right ankle. The snake
Speaker 2: coiled up and started rattling its tail, and I backed
Speaker 2: away quickly. Chloe and I decided to leave all of
Speaker 2: our camping gear and head straight to the hospital and
Speaker 2: Grand Junction, which was about a three hour drive. We
Speaker 2: left at about nine thirty at night, and the only
Speaker 2: road home was a two lane highway over the Uncompagra Plateau.
Speaker 2: Because we didn't have cell service, I used our satellite
Speaker 2: messenger to text my husband with the news and to
Speaker 2: call ahead to the hospital. I was in a lot
Speaker 2: of pain, really the most pain that I can remember.
Speaker 2: We were thirty minutes into the drive when I started
Speaker 2: throwing up. We didn't pull over because I didn't want
Speaker 2: to lose any time. I was heaving for about thirty minutes,
Speaker 2: but eventually I stopped. Sweaty and exhausted. At this point,
Speaker 2: I had to poop. I instructed Chloe to pull over now,
Speaker 2: and I pooped right there on the side of the road.
Speaker 2: Once I had nothing left in me, we continued on.
Speaker 2: Soon after, I began to experience muscle spasms. It began
Speaker 2: in the tips of my fingers and toes. All of
Speaker 2: my muscles tightened as the spasms worked their way up
Speaker 2: my extremities, so that my hands turned into fists and
Speaker 2: my arms and legs tightened. This was the only time
Speaker 2: during this experience that I thought I might not be okay.
Speaker 2: Chloe told me to focus on breathing, and I did.
Speaker 2: My body felt like a tight ball and was not
Speaker 2: in my control. Eventually, the spasms subsided. The emergency room
Speaker 2: staff was expecting me. I was admitted quickly and given
Speaker 2: a large dose of anti venin and a tetanus shot.
Speaker 2: While there, I believe I met every doctor and nurse
Speaker 2: in the emergency room. It turned out they didn't see
Speaker 2: snake bites very often and wanted to take this opportunity
Speaker 2: to look at my ten day unwashed foot. I happily
Speaker 2: told everyone my story. A lot of the pain had
Speaker 2: subsided and I was just so relieved to be safe.
Speaker 2: While there, I asked a lot of questions about the
Speaker 2: recovery and didn't get clear answers. It seemed like the
Speaker 2: recovery time could be quite variable. I was discharged from
Speaker 2: the hospital in twenty four hours. My husband picked me up,
Speaker 2: We picked up our gear from the campsite, and then
Speaker 2: headed home. My foot was a gray and blue, swollen
Speaker 2: lump for about a week, and people stared every that
Speaker 2: I went. Luckily, the recovery was quick for me, and
Speaker 2: I was just about back to normal in four weeks.
Speaker 2: Whenever I do field work now, I always have snakes
Speaker 2: on my mind. I don't really prefer doing field work
Speaker 2: in places where rattlesnakes are common or we might run
Speaker 2: into them. I always wear shoes, and sometimes I wear
Speaker 2: gators I prefer when I'm hiking for fun to go
Speaker 2: to higher elevation areas where there's really no chance we'll
Speaker 2: run into any kind of rattlesnake And I worry about
Speaker 2: my dogs a lot, but in the end, like I
Speaker 2: still do a lot of field work, it's just more
Speaker 2: present on my mind. And I tell everybody that I
Speaker 2: work with what happened to me and hope that they
Speaker 2: are more cautious as well.
Speaker 1: Wow.
Speaker 3: I mean that is absolutely terrifying, absolutely terrifying. I can't
Speaker 3: imagine what a long and just I don't know, awesome
Speaker 3: car ride.
Speaker 1: Wow.
Speaker 3: Yeah, thank you so so much, Gwen for taking the
Speaker 3: time to chat with me and for telling your story.
Speaker 3: I'm yeah, it's just we're really glad that you're better now.
Speaker 1: Yeah. Hi, I'm Aaron Welsh and I'm Erin almon Updyke.
Speaker 3: And this is this podcast Will Kill You, And today.
Speaker 1: We're taking a few steps outside of our comfort zone
Speaker 1: and we're talking about snake bites.
Speaker 3: We are specifically venomous snake bites. Yes, yeah, And there's
Speaker 3: a lot out there and there's a lot to this story.
Speaker 3: And just in advance, I want to say that you know,
Speaker 3: we're probably not going to cover everything that you would
Speaker 3: want us to cover about snakes and what's going on
Speaker 3: with snakes in the world and snake bites and stuff
Speaker 3: like that. But don't worry, because we are going to
Speaker 3: cover some very interesting things number one. Number two. I
Speaker 3: think this also leaves us open to revisiting snakes in
Speaker 3: the future, Like I really want to cover that snake
Speaker 3: fungus someday.
Speaker 1: Ooh, I don't even know about snake fungus Aaron. Yeah.
Speaker 3: Yeah, it's called snake fungal disease, and I don't, to
Speaker 3: be honest, know all that much more about it, but
Speaker 3: I've I remember seeing presentations about it.
Speaker 1: And like different conferences and I was entragued. So so
Speaker 1: we're not talking about that today. We'll just focusing on
Speaker 1: the venom that a lot of snakes produce and how
Speaker 1: it affects humans if we get bitten.
Speaker 3: That's correct. Yeah, And speaking of snake bites and what
Speaker 3: happens when you get bitten, should we talk about our
Speaker 3: quarantinie for this episode.
Speaker 1: What a great transition and I really loved it.
Speaker 3: It was not at all forced, it was super smooth.
Speaker 1: But our our quarantine for this week is the snake Bite.
Speaker 3: It's the snake Bite. It's a real it's a real drink,
Speaker 3: which makes our job, you know, easier in that regard.
Speaker 3: It's a very simple drink as well. It consists of
Speaker 3: two ingredients, cider and then either logger or stop up
Speaker 3: to you and we'll we'll post the full recipe for
Speaker 3: the snake Bite as well as the non alcoholic Placybrita.
Speaker 3: I'm very curious to see what I come up with
Speaker 3: same on our website this podcast will Kill You dot com,
Speaker 3: as well as on all of our social media channels.
Speaker 1: Our website This Podcast will Kill You dot com has
Speaker 1: some pretty incredible things that you can find on it
Speaker 1: if you haven't checked it out yet. We have our
Speaker 1: bookshop dot org, iphilia account, we have a good Reads list,
Speaker 1: We have all of the sources from all of our episodes.
Speaker 1: We have transcripts from them all. We have a link
Speaker 1: to Bloodmobile who provides the music. We have our Patreon,
Speaker 1: we have merch I might have missed a few things
Speaker 1: that that was all that one breath could handle.
Speaker 3: I think you did a great job. My post it
Speaker 3: is not currently with me, so I can't I can't
Speaker 3: verify and add what I forgot exactly, but that's okay.
Speaker 3: I don't think we have any more podcast business, so
Speaker 3: can we please get started. I am really really cureedious
Speaker 3: about snake venoms.
Speaker 1: I can't wait to talk about them right after this break.
Speaker 1: So here's the thing. We are not herpetologists, and like
Speaker 1: you said at the top, we're not going to pretend
Speaker 1: like we are for this episode. So I'm not going
Speaker 1: to be getting into a lot of detail about the
Speaker 1: snakes themselves, and I'm going to try to avoid getting
Speaker 1: anything wrong when it comes to the biology of snakes
Speaker 1: by mostly ignoring the snakes themselves. Yeah, I know herpetologists
Speaker 1: who follow us, I'm sorry. But what I am going
Speaker 1: to focus on instead is the venom and the effect
Speaker 1: that various types of venom have on our human body.
Speaker 1: And so what I hope that listeners will take away
Speaker 1: from this is the very broad strokes of the different
Speaker 1: varieties of venom and how they work, and why it
Speaker 1: is that some snake bites are so dangerous to humans.
Speaker 1: Shall we begin, Let's do it. Snakes are an incredibly
Speaker 1: diverse group of reptiles. I learned there are over thirty
Speaker 1: five hundred species of snakes, but today we're going to
Speaker 1: focus on just a few of the families of snakes
Speaker 1: in the claye Callubroides, oh that's how you say it,
Speaker 1: which contains the families and the subfamilies of snakes that
Speaker 1: are of quote human medical importance. And these snakes, there's
Speaker 1: three major groups of them, the Elapids and the fami Elapidae,
Speaker 1: which are the cobras, the mambas, the sea snakes, which
Speaker 1: I still to this day am terrified of the idea
Speaker 1: of sea snakes, even.
Speaker 3: Though they're the ones you're probably least likely to encounter.
Speaker 1: I know something about them. It is the most like,
Speaker 1: I'm not afraid of snakes. I think snakes are very cool,
Speaker 1: but sea snakes terrifying me. Something you learned about me today, Yeah, yeah.
Speaker 1: Also the group the Viperids in the family Viperidae, which
Speaker 1: include the vipers and pit vipers, which are like rattlesnakes
Speaker 1: and other things as well as adders. And then the
Speaker 1: subfamily and I might not pronounce this right, attract a spitina.
Speaker 1: This is mole vipers and stiletto snakes. It's a smaller group,
Speaker 1: not super common.
Speaker 3: Stiletto snakes. That's like a very cool.
Speaker 1: Band name I wonder if it is a band, I
Speaker 1: wonder it should be someone make it. And so these
Speaker 1: are the three major groups. The elapids, the viperia, and
Speaker 1: the attracta spinina snakes that are considered of medical importance
Speaker 1: because their bites are extra dangerous to humans. All of
Speaker 1: these types of snakes have venom glands on either side
Speaker 1: of their cute little faces, and these glands are connected
Speaker 1: to ducks that transfer the venom to the base of
Speaker 1: their fangs. And in many cases, these fangs are very cool.
Speaker 1: They have canals in their hollow fangs through which the
Speaker 1: venom travels and can then be rapidly injected into the
Speaker 1: victim with a bite.
Speaker 3: It's so cool, it is.
Speaker 1: Snake fangs are very cool. They vary a lot evolutionarily
Speaker 1: between groups, like some of them fold back, some of
Speaker 1: them fit into grooves. Some, like spitting vipers, can actually
Speaker 1: spit their venom out. It is very cool. Someone else
Speaker 1: can get into that. But let's talk about venoms. So
Speaker 1: Venoms are specialized types of toxins that have to be
Speaker 1: injected into their victim in order to have an effect,
Speaker 1: as opposed to a poison, which can exert its effect
Speaker 1: after ingestion or even just by diffusing across the skin. Right, So, venoms,
Speaker 1: including snake venoms, have a lot of large molecules as
Speaker 1: part of their composition that actually have to then be
Speaker 1: injected through the skin to enter the bloodstream and then
Speaker 1: exert an effect and venom. I know you know this erin,
Speaker 1: but a lot of listeners might not. Venom is inherently
Speaker 1: an ecological phenomenon. So the composition and the activity of
Speaker 1: any given animals, but especially any given snake's venom, inherently
Speaker 1: co evolved over time with the specific physiology and ecology
Speaker 1: of primarily the prey animals that this venom is being
Speaker 1: used to assist in eating, right, and probably to some
Speaker 1: extent as well, the predator that these snakes are in
Speaker 1: threat from. So some snakes their venom is primarily used
Speaker 1: to immobilize their prey. Other snakes, their venom is actually
Speaker 1: beginning the process of digestion for them, and other snakes
Speaker 1: they're using their venom primarily to ward off other predators.
Speaker 1: So there is an incredible amount of variation in snake venom.
Speaker 3: In it's unbelievable. It's so beautiful, Yeah, it really is.
Speaker 3: It's amazing. I just it's also, of course, a lot
Speaker 3: more diverse than I realized.
Speaker 1: As always. As always, so, humans, as it turns out,
Speaker 1: are probably not super important in the evolution of snakes
Speaker 1: or snake venom. And so I want to quote from
Speaker 1: a paper that I liked here, quote human in venomings
Speaker 1: are best viewed as collateral damage of the chemical arms
Speaker 1: race taking place between various snakes and their prey. I
Speaker 1: love that.
Speaker 3: It's definitely an arms race.
Speaker 1: Yeah, and we're just collateral damage. So that's how I
Speaker 1: want us to view all of these symptoms that you'll
Speaker 1: see when we talk about the different types of venoms, because,
Speaker 1: as it turns out, snake venoms are some of the most,
Speaker 1: if not the actual most complex venoms of the entire
Speaker 1: animal kingdom. Oh, lots of other animals, scorpions, bees, ants,
Speaker 1: lots of different animals make venom. Snake venom is incredibly complex.
Speaker 1: Each individual like venom that a specific snake is going
Speaker 1: to inject into you is composed of anywhere from fifty
Speaker 1: to two hundred different components, some of which are toxins
Speaker 1: are harmful, and some of which are not but serve
Speaker 1: some other purpose, right, like just helping facilitate the entry
Speaker 1: or something like that. So Venoms are comprised of proteins, carbohydrates, lipids,
Speaker 1: and the snake venoms that are of human medical importance.
Speaker 1: Despite their incredible complexity, can generally be broken down into
Speaker 1: three major categories based on how they exert their effects.
Speaker 1: These are the neurotoxic venoms which affect our nervous system,
Speaker 1: the hemotoxic venoms, which affect a lot of times our
Speaker 1: ability to coagulate blood and will get into it, and
Speaker 1: then cytotoxic venoms which cause tissue death and tissue damage.
Speaker 1: And the complexity of all these different toxins tends to
Speaker 1: fall into a few major like molecular biology or biochemistry
Speaker 1: groupings like there are certain proteins that are very common
Speaker 1: across snake venoms, but they don't necessarily neatly fall into
Speaker 1: these categories of neurotoxic, cytotoxic, hematoxic because there's a lot
Speaker 1: of variation in their potential sites of action, where specific
Speaker 1: toxins that might look similar actually have a very different
Speaker 1: clinical effect in different snake species, which is mind blowing,
Speaker 1: yeah complicated, and it's also often a generalization that's made
Speaker 1: that the venom from elapid snakes, so those cobras, mambas,
Speaker 1: coral snakes is primarily neurotoxic in nature, and venom from
Speaker 1: viperid snakes, vipers pit vipers rattlesnakes is primarily cytotoxic and hemotoxic,
Speaker 1: And these generalizations are true to some extent, but there
Speaker 1: is so much individual variation, and there are so many
Speaker 1: exceptions to those rules, like spitting cobras, which cobras are
Speaker 1: generally neurotoxic, but spitting cobras often have a lot of
Speaker 1: cytotoxicity hemotoxicity. Rattlesnakes generally have very hemotoxic venom, but some
Speaker 1: species also have neurotoxic properties, and a lot of Australian
Speaker 1: snakes just do the most wild and crazy things.
Speaker 3: Well, and isn't there also a lot of variation among
Speaker 3: populations or even individual to individual.
Speaker 1: Exactly exactly so even between for example, mojave rattlesnakes, some groups,
Speaker 1: some populations of that species of rattlesnake have more neurotoxic
Speaker 1: venom and others have more hemotoxic venom.
Speaker 3: So interesting.
Speaker 1: I can't even express how fascinating and mind blowing it is,
Speaker 1: but it's incredibly complicated and so to just be able
Speaker 1: to understand the basics of like the different ways that
Speaker 1: various snake venoms could affect our bodies. We're going to
Speaker 1: focus on those three broad categories of venoms cytotoxic, hemotoxic,
Speaker 1: and neurotoxic, and how each of those would present if
Speaker 1: you got bitten by snakes with these various venom properties.
Speaker 1: Shall we let's do it so the first big distinction
Speaker 1: between bite types if you get bitten by a snake, besides,
Speaker 1: I should mention is it a dry bite or is
Speaker 1: it an in envenomation because it's also important to note
Speaker 1: that while many snakes are venomous, not every venomous snake
Speaker 1: bite results in in venomation, because some bites are what
Speaker 1: we call dry, so they don't actually spit any of
Speaker 1: their venomount But other than that, we'll just focus on
Speaker 1: the venomous bites. The first big distinction is whether or
Speaker 1: not there are going to be any local effects of
Speaker 1: that bite. Cytotoxic venom causes a significant amount of local
Speaker 1: effects sido meaning sell toxic meaning toxic. So cytotoxic and
Speaker 1: venoming symptoms often look like incredibly painful and sometimes very
Speaker 1: severe sweat at the site of the bite, which can
Speaker 1: sometimes lead to very large like blood filled blisters or
Speaker 1: extensive deep tissue bruising. There can be tissue damage and
Speaker 1: necrosis or death of tissue of your arm or your
Speaker 1: leg or wherever the bite occurred, and it can be
Speaker 1: so severe that if it isn't surgically debrided or cared for,
Speaker 1: the limb can end up needing amputation. Because of how
Speaker 1: severe tissue death can be.
Speaker 3: I have in my research. I came across some pictures
Speaker 3: of it by accident, and.
Speaker 1: It's terrifying, terrifying. Yeah. Yeah, there's also in some snake
Speaker 1: venoms a type of tissue damage that occurs that ends
Speaker 1: up causing blood clots in small vessels that actually then
Speaker 1: contains the venom toxins to the site of the bite
Speaker 1: wound so that they don't travel more extensively, so that
Speaker 1: those toxins can ex their effect very locally, which I
Speaker 1: think is fascinating.
Speaker 3: Yeah.
Speaker 1: So if you have a snake bite that is very painful,
Speaker 1: very swollen, very obvious, then there's a component of cytotoxicity
Speaker 1: that's going on there. Okay, okay. Another place that cytotoxicity
Speaker 1: can come into play is actually in a more systemic way.
Speaker 1: So that was all kind of the local cytotoxic effects.
Speaker 1: But as snake venom travels through the lymphatics and reaches
Speaker 1: kind of the rest of the body, some snake venom
Speaker 1: toxins have specific effects on our muscle cells, which is
Speaker 1: known as myotoxicity. These end up actually damaging or killing
Speaker 1: primarily our skeletal muscle cells, so muscles in your arms,
Speaker 1: your legs, and this process of muscle cell breakdown leads
Speaker 1: to the release of a lot of enzymes from our
Speaker 1: muscle cells and proteins that actually are very damaging to
Speaker 1: our organs, especially our kidneys. So this process can actually
Speaker 1: lead to k kidney failure. This is called rhabdomyolysis. It's
Speaker 1: not specific to snake bites, but it's a really important
Speaker 1: complication of the skeletal muscle breakdown that snake venom toxins
Speaker 1: can induce that can then cause kidney failure and death.
Speaker 1: Your face has questions.
Speaker 3: I have a question.
Speaker 1: How is this so targeted?
Speaker 3: Like are we going to talk about the structure of
Speaker 3: these different venoms and like how they do the things
Speaker 3: that they do.
Speaker 1: Yeah, So that's a good questionnaire and I'm not. And
Speaker 1: it's not because it's not necessarily known, but it's because
Speaker 1: it is so incredibly complicated. So there are kind of
Speaker 1: a few dominant categories of proteins and enzymes that are
Speaker 1: involved in snake venom. Some are called phospholipases, some are
Speaker 1: called svmps snake venom metalloproteases or snake venom seerine proteases svsps,
Speaker 1: and then they're are three finger peptides. Those are the
Speaker 1: four kind of major groups of proteins that cause a
Speaker 1: lot of damage, and there's a lot of overlap. For example,
Speaker 1: the PLA two's the phospholie paces. They have a lot
Speaker 1: of the myotoxic and inflammatory cytotoxic effects, but they also
Speaker 1: are very neurotoxic as well different ones.
Speaker 3: So it's it's okay, so yeah, yeah, so.
Speaker 1: It gets really really complicated, but in general it are
Speaker 1: it is these phospholie paces that have a lot of
Speaker 1: that specific myotoxic activity. Okay, it's I just I know,
Speaker 1: I know, Aaron, And it's so like the there are
Speaker 1: so many different ways, even in under the grouping of
Speaker 1: say cytotoxic, there are so many different specific ways that
Speaker 1: these enzymes and these proteins and these toxins can end
Speaker 1: up killing cells. It's not just like one mechanism of
Speaker 1: act I see Okay, Yeah, but that's kind of the
Speaker 1: first category of big effects that you might see is
Speaker 1: tissue death either locally or more systemically with muscle breakdown. Okay,
Speaker 1: that's cider toxic venoms and cider toxic components. The next
Speaker 1: thing that you might notice or you might look for
Speaker 1: when it comes to a bite wound is is that
Speaker 1: bite wound oozing oozing? What oozing blood?
Speaker 3: Oozing?
Speaker 2: What?
Speaker 1: Oh? Blood? Okay?
Speaker 3: You pus or like clear liquid or something?
Speaker 1: No oozing blood okay. Snake bites can cause both local
Speaker 1: and systemic hemorrhage, and the way that they do this
Speaker 1: can vary a lot, but there's two main mechanisms and
Speaker 1: they both fall under the umbrella of a hemotoxic venom.
Speaker 1: The hemotoxic venoms have two different presentations that, as we'll see,
Speaker 1: kind of go hand in hand and to create a
Speaker 1: very bad potential outcome. So some toxins, some hematoxic toxins
Speaker 1: in venom can cause vascular permeability, which we've talked about
Speaker 1: in other episodes in various ways. But Basically, these toxins
Speaker 1: attack and break down the basement membrane, the bottom layer
Speaker 1: of our blood vessels, especially in our small blood vessels,
Speaker 1: are capillaries, and this leads to leaky vessels, which leads
Speaker 1: to loss of fluid and what we call extravasation of
Speaker 1: the blood out of your blood vessels and just into
Speaker 1: your general spaces in your body. And that means that
Speaker 1: there's less fluid in our blood vessels, which can then
Speaker 1: lead to hypotension low blood pressure because you don't have
Speaker 1: enough fluid to have enough pressure in your blood vessels,
Speaker 1: and that can lead to shock, which is when you're
Speaker 1: not able to perfuse your tissues because of how low
Speaker 1: your blood pressure is.
Speaker 3: Okay, that can lead to death, and so that is
Speaker 3: indicated by an oozing a bloody oozing wound.
Speaker 1: Potentially that's one possible sign. Yeah, okay, okay. A number
Speaker 1: of other toxins might cause vasodilation, basically opening up our
Speaker 1: blood vessels in diameter, which has the same effect of
Speaker 1: reducing our blood pressure. Right. It's actually incidentally how a
Speaker 1: lot of our blood pressure lowering medications work. And I
Speaker 1: think you'll probably talk arin about how at least one
Speaker 1: anti hypertensive class of medicines was actually developed from snake venom.
Speaker 3: Yeah, I'll mention it very briefly, but it is one
Speaker 3: of the coolest things, and I yeah, I just I
Speaker 3: love it so much because it's such a beautiful little
Speaker 3: example of how we're like, let's take this thing that
Speaker 3: can be very harmful and wait a second, how is
Speaker 3: it useful?
Speaker 1: Exactly? Yeah, and it is. It's a very useful class
Speaker 1: of medicines. But basically in an venomation sense, where you're
Speaker 1: getting a large load of this all at once that
Speaker 1: can also lead to hypotension and shock. It's a different mechanism,
Speaker 1: it's the same end result. But the other part of
Speaker 1: hemotoxicity that I think is even more absolutely fascinating is
Speaker 1: that various different snake venom toxins have specific effects on
Speaker 1: our coagulation cascade.
Speaker 3: Which isn't it great that we did hemofemia? So if
Speaker 3: you've listened to it, you're familiar with the clotting cascade exactly.
Speaker 1: If you haven't, I'll refresh you. Basically, in short, the
Speaker 1: process of blood clot formation in our bodies, which begins
Speaker 1: when endothelial or our blood vessels are damaged in some
Speaker 1: way the process that we use to form a blood
Speaker 1: clot to fix and heal off that damage so that
Speaker 1: we don't just keep bleeding freely. It's a series of
Speaker 1: very complex steps where there are like thirteen or more
Speaker 1: different factors or proteins that have to be activated in
Speaker 1: series to then go on to activate other factors so
Speaker 1: that the end result is formation first of what we
Speaker 1: call a hemostatic plug, and that happens mostly with platelets,
Speaker 1: which are like our first line defense, and then eventually
Speaker 1: a fibrine enhanced really strong clot, and then eventually our
Speaker 1: body is able to repair that area. So this system,
Speaker 1: this coagulation cascade, is very tightly regulated in our body.
Speaker 1: It requires all thirteen plus of these factors to be
Speaker 1: activated in series to make that clot and then break
Speaker 1: that clot down to repair the area. Well. One of
Speaker 1: the hallmark effects of a lot of snake venom toxins
Speaker 1: is what's known as a consumption coagulopathy, which means that
Speaker 1: what they do is they activate factors in this coagulation cascade,
Speaker 1: and in so doing they use them all up, so
Speaker 1: then we have no factors left and we can't make
Speaker 1: a blood clot, so we bleed and bleed and bleed.
Speaker 3: Oh that's so interesting. So it causes both like clotting
Speaker 3: but also massive.
Speaker 1: Hemorrhage exactly, Aarin. Weird. Yeah, So what it tends to
Speaker 1: do is it causes clotting. That's because it's being activated
Speaker 1: by the snake venom toxins and not the normal coagulation cascade.
Speaker 1: It doesn't go through all of the steps, so the
Speaker 1: clots that tend to form get broken up very easily,
Speaker 1: and this process uses up all of our coagulation factors,
Speaker 1: so then we have none left to actually make a clot.
Speaker 1: That's amazing. And if you combine that with the fact
Speaker 1: that other toxins in this venom are also causing leaky
Speaker 1: blood vessels, now you have leak blood vessels and the
Speaker 1: inability to clot, you get massive hemorrhage, which, especially if
Speaker 1: it happens in somewhere like your brain, is life threatening. Right.
Speaker 1: It's fascinating, Aaron. And what's even more fascinating is how
Speaker 1: many different specific toxins, specific forms of those various proteins
Speaker 1: that I mentioned, affect different parts of this coagulation cascade.
Speaker 1: Almost every single step can be affected by different snake
Speaker 1: venom toxins.
Speaker 3: Evolution is an amazing thing. It really is.
Speaker 2: It is.
Speaker 1: It blows my mind if it wasn't so terrifying. Even
Speaker 1: though it is so terrifying, it is still kind of
Speaker 1: a beautiful, beautiful thing.
Speaker 3: It is. I mean, and I think that snakes are
Speaker 3: Fear of snakes is the most common or one of
Speaker 3: the most common phobias, and I get it. Yeah, And
Speaker 3: snakes have a really they hold really important meaning in
Speaker 3: human history. I read somewhere that up to fifty percent
Speaker 3: of people report dreaming about snakes at some point.
Speaker 1: And I dreamt about them, wasn't I.
Speaker 3: And it's it's amazing and so like I what I
Speaker 3: really don't want people to think after listening to this
Speaker 3: episode is that we don't like snakes or that snakes
Speaker 3: are bad or anything like that, because they're not. They're amazing,
Speaker 3: beautiful creatures and they just happen to sometimes bite people
Speaker 3: with these venoms that are very very bad.
Speaker 1: Yes, I know, I feel the same. I was really
Speaker 1: worried after all of this, where I'm like, this sounds
Speaker 1: so terrifying, and I know so many people are terrified
Speaker 1: of snakes, and it's not the snake's fault.
Speaker 3: Right, and it's I feel like it's definitely one of
Speaker 3: those cases where hopefully knowledge is power. Yeah, and the
Speaker 3: more you know about something, the less sort of mysterious
Speaker 3: and scary it might be, just if you have that understanding.
Speaker 3: But also it's it's reasonable to be afraid of snakes because.
Speaker 1: It's evolutionarily adaptive.
Speaker 3: Exactly exactly as I'll talk a lot more about.
Speaker 1: I can't wait. Okay, we have one more class of
Speaker 1: toxins to talk about, though, the neurotoxins. Neurotoxic envenoming symptoms
Speaker 1: often start with a descending paralysis, that is paralysis of
Speaker 1: the muscles, starting in our face, the small muscles of
Speaker 1: the face that are innervated by our cranial nerves, and
Speaker 1: it progresses downward through all the nerves and our body
Speaker 1: until it eventually affects our respiratory muscles and can cause
Speaker 1: death from respiratory failure. Does that sound familiar?
Speaker 3: It sounds like botulism.
Speaker 1: It sure does. I'm actually just going to do a
Speaker 1: lot of callbacks to old episodes in this episode. Okay,
Speaker 1: it's a lot like botulism, but the way in which
Speaker 1: snake venom toxins end up doing this paraly busness is
Speaker 1: amazingly variable. There are dozens of different specific targets that
Speaker 1: they have, and it almost all ends up in this
Speaker 1: same descending flaccid paralysis. So let's kind of go over
Speaker 1: it a little bit more detail in our botulism and
Speaker 1: our tetanus episodes, and I also think in a lot
Speaker 1: of our crossover episodes with mat from indefensive plants, because
Speaker 1: we end up talking about neurotransmitters a lot. But I've
Speaker 1: talked in detail about our nerves, our neuromuscular junction, which
Speaker 1: is the junction between where our nerves actually exert their
Speaker 1: effect on our muscles to cause them to contract, and
Speaker 1: I've talked about all of the various neurotransmitters that are
Speaker 1: involved in sending those signals and converting an electrical signal
Speaker 1: to a chemical signal to have the effect on the muscle.
Speaker 1: It turns out that snake venom toxins can affect almost
Speaker 1: any part of either the presynaptic that is, the nerve end,
Speaker 1: or the post synaptic that is the muscle receptor end
Speaker 1: of this neuromuscular junction. So some toxins that are presynaptic
Speaker 1: that act on the nerve itself like botulism does inhibit
Speaker 1: the release of certain neurotransmitters. Others cause the release of
Speaker 1: all of our neurotransmitters at once and use them all up.
Speaker 1: And both of those different mechanisms have the same effect
Speaker 1: of depleting the ability of our nerve to transmit a
Speaker 1: signal to our muscle. Some other toxins on the post
Speaker 1: synaptic or the muscle side block the breakdown of neurotransmitters
Speaker 1: after they've been sent, so that they can't unbind their
Speaker 1: receptor so that new or repeated signals can't go through.
Speaker 1: Some of them just block receptors directly or even interfere
Speaker 1: with the neurotransmitters while they're in that synapse, crossing the
Speaker 1: space between the nerve and the muscle. It is incredible
Speaker 1: and incredibly complex how many different specific mechanisms of this
Speaker 1: have evolved. And what is even more amazing is that
Speaker 1: the symptoms, regardless of those specific mechanisms, are an acute
Speaker 1: flacid so floppy paralysis that starts with the muscles of
Speaker 1: the face and travels downward regardless of where the bite
Speaker 1: wound was or what that specific receptor is involved.
Speaker 3: That is it is, it is, You're right, It is amazing,
Speaker 3: It is incredible, it is fascinating, and it just leaves
Speaker 3: me to wonder, are there any spots along that sequence
Speaker 3: that haven't been targeted by or like can't be targeted
Speaker 3: by venoms?
Speaker 1: You know what I mean? Because yes, it's a great question.
Speaker 3: There are so many different types of ways for this
Speaker 3: to happen, and they've all been check check, check done yep.
Speaker 1: And if not by snakes, then by scorpions or someone else.
Speaker 3: Right, Yeah, it's amazing, I know.
Speaker 1: I will say there are some exceptions, like there are
Speaker 1: some South American rattlesnake venoms that cause more of a
Speaker 1: spastic paralysis like tetanus does, but in general, almost across
Speaker 1: the board, it's a more flaccid paralysis. Interesting, I know.
Speaker 1: And so that's kind of all of the different types
Speaker 1: of venom. And I know that for a lot of
Speaker 1: people that probably wasn't enough detail, and you want to
Speaker 1: know a lot more. I have tons of good papers
Speaker 1: for you, and for some people that was probably like
Speaker 1: way too much. But hopefully you know, we get at
Speaker 1: least the broad stroke pictures where different components of different
Speaker 1: types of venom can have a huge variety of effects
Speaker 1: on our human bodies, and when we look at it
Speaker 1: back evolutionarily, it's because of all the different ways that
Speaker 1: these specific snakes we're interacting with their prey or their
Speaker 1: predators to try and immobilize them or make sure that
Speaker 1: they die quickly or et cetera. There is treatment a
Speaker 1: lot of times.
Speaker 3: Is it like I saw in Hey Dude growing up,
Speaker 3: sucking out the venom of the bite?
Speaker 1: It absolutely is not. Please never suck the venom out
Speaker 1: of someone's bite or your own. That is a falsity.
Speaker 1: There's probably a lot of myths we can dispel right here.
Speaker 1: Don't suck out the venom, that's one. Please don't cut
Speaker 1: open the wound to try and let the venom drain.
Speaker 3: Do that either that can make things so much worse.
Speaker 1: So much worse and just invite more infection. Don't tournique
Speaker 1: off the limb because that can cause a lot more
Speaker 1: tissue damage, immobilizing the limb and potentially doing a pressure dressing,
Speaker 1: which is like think of like an ace wrap like
Speaker 1: you would put on sprained ankle, like that level of compression.
Speaker 1: But even that only if you're not having a lot
Speaker 1: of swelling, If you have a lot of cytotoxic local
Speaker 1: effects and your ankle, for example, gets really really swollen.
Speaker 1: You wouldn't want a wrap to be so tight that
Speaker 1: you're cutting off blood supply, especially if you, like Gwen,
Speaker 1: have a three hour drive to wherever you're going. But
Speaker 1: immobilizing your limb can help reduce the spread of toxin
Speaker 1: through your lymphatics.
Speaker 3: I also read something, and I want you to tell
Speaker 3: me if this is true or not, that you should
Speaker 3: that sometimes it is advised to not wash the wound
Speaker 3: very carefully because, especially if you don't know what kind
Speaker 3: of snake bit you, then it's important to be able
Speaker 3: to get the venom if there's any like around the wound.
Speaker 1: So from what I read, it's only in Australia and
Speaker 1: New Guinea that they have the ability to swab a
Speaker 1: wound and be able to test for a specific type
Speaker 1: of venom okay, And so as far as I know,
Speaker 1: those are the only places where they have that type
Speaker 1: of detection available to be able to say what a
Speaker 1: specific venom is by swabbing a wound to try and
Speaker 1: find venom. Gotcha, So anywhere else if you have and
Speaker 1: especially if it's going to be a very long time
Speaker 1: until you can get medical care. Cleaning a wound is
Speaker 1: always going to be a good idea. It just gently
Speaker 1: that makes sense. Yeah, good question though.
Speaker 3: And then what about if you don't know what snake
Speaker 3: but you because like that's one of the biggest challenges,
Speaker 3: right is if you get bit by a snake, how
Speaker 3: do you get the proper treatment because that can vary
Speaker 3: a lot depending on the snake species you.
Speaker 1: Are so correct erin. And it's also a problem because
Speaker 1: how do you identify a snake that you just got
Speaker 1: bitten by. That's very difficult to do. You might not
Speaker 1: have even seen it. It might have happened while you were sleeping,
Speaker 1: it might have happened in the dark. It might be
Speaker 1: that you don't know snakes very well. I don't know snakes.
Speaker 1: I would have I would know rattlesnake because of rattles
Speaker 1: otherwise generic snake, and that's literally all I've got. It's
Speaker 1: a great question. It is very difficult to know exactly
Speaker 1: what snake bit someone. And one of the things they
Speaker 1: say sometimes is if you bring the snake with you
Speaker 1: to the hospital, then that can facilitate identification. But there's
Speaker 1: a huge butt to that. It's very dangerous to try
Speaker 1: and kill and then bring a snake in, So don't
Speaker 1: do it. I wouldn't recommend it. And even if you
Speaker 1: brought it to a hospital, there's no guarantee that there's
Speaker 1: going to be an expert herpetologist around who's going to
Speaker 1: be able to say exactly what that snake was. The
Speaker 1: same holds true for trying to get a photograph of
Speaker 1: the snake to use that for identification. It can be
Speaker 1: very difficult. So to some extent, yes, being able to
Speaker 1: describe a snake might help in certain regions, to be
Speaker 1: able to identify is it an a lapid snake or
Speaker 1: is it a viperid snake? So is it more likely
Speaker 1: to be neurotoxic or is it more likely to be
Speaker 1: hemotoxic or cytotoxic. But really what it comes down to
Speaker 1: is actually having to just evaluate it clinically, and you
Speaker 1: might never know exactly what snake it was. Oh, I see, okay, yeah,
Speaker 1: and you're right, it's important to know or to try
Speaker 1: and know what type of snake it was to be
Speaker 1: able to give the right anti venom. Anti venom, by
Speaker 1: the way, is produced by hyper immunizing or exposing horses
Speaker 1: or sheep, usually to venoms from snakes and then purifying
Speaker 1: the antibodies that they make and using that as a therapeutic.
Speaker 1: So it's horse or sheep antibodies against snake venom that
Speaker 1: we use as therapy.
Speaker 3: Do you know when anti venin and anti venom? Because
Speaker 3: I've seen it written both ways erin.
Speaker 1: I never saw anti venin except for Pfizer's specific like
Speaker 1: trade name as anti venin. Okay, so I don't know.
Speaker 1: It might be an old timey name.
Speaker 3: Yeah, maybe that's maybe that's the case, because I did
Speaker 3: see it in some older paper, but I did I
Speaker 3: didn't know if there was a difference.
Speaker 1: I don't think there is. I think it's the same thing.
Speaker 3: Okay, there is a difference between toxicology and toxicology. As
Speaker 3: I learned, I had.
Speaker 1: To learn that too. I was like, are they doing
Speaker 1: typos right now? Yeah?
Speaker 3: I oh, well, because even a word or Google or
Speaker 3: something was like, did you mean toxicology? And I was like,
Speaker 3: I don't think so.
Speaker 2: No.
Speaker 1: I googled it multiple times, more than twice to make
Speaker 1: sure I understood. But yeah, So knowing the snake can
Speaker 1: be very helpful in trying to get the right anti venom.
Speaker 1: It's not always possible. It's also the case that a
Speaker 1: lot of anti venoms are not specific to one snake anyway.
Speaker 1: They're polyclonal. They're made from hyper immunizing horses against multiple
Speaker 1: different snakes that are present in a given region to
Speaker 1: try and provide immunity against a wider variety of snakes,
Speaker 1: which can be great, especially when you can't identify what
Speaker 1: type of snake you got bitten by. But the problem
Speaker 1: is that then it tends to be much lower tighters,
Speaker 1: so like a smaller amount of an anti venom that's
Speaker 1: going to help any one specific snake if that makes sense,
Speaker 1: or one specific snake bite rather. But really, when somebody
Speaker 1: comes to a hospital with a snake bite, it's all
Speaker 1: about looking at what are the symptoms that they're having
Speaker 1: and doing a lot of blood work to see are
Speaker 1: you having problems with coagulation, are you having problems with
Speaker 1: tissue swelling, are you having evidence of that rhabdomyolysis, are
Speaker 1: you having any evidence of your eye lid is droopy,
Speaker 1: you're having paralysis, etc. And then you treat those based
Speaker 1: on And this is the other thing that I think
Speaker 1: is so incredibly interesting and difficult about snake bites is
Speaker 1: how hyper local This knowledge all has to be right,
Speaker 1: because in Western Colorado, the profile of the types of
Speaker 1: venomous snakes you could possibly be bitten by is very
Speaker 1: different than in the Eastern United States or in Australia
Speaker 1: or in Sri Lanka. Right, It's incredibly different, And so
Speaker 1: it's all going to be specific to where you are
Speaker 1: and what your symptoms are to know what's the most
Speaker 1: likely type of anti venom to use to treat this.
Speaker 3: Yeah, so I understand that the venoms are very variable
Speaker 3: and the composition and among the different types of venoms
Speaker 3: and so on. But are there certain types of venoms
Speaker 3: like hematoxic versus neurotoxic where you need to get the
Speaker 3: anti venom delivered sooner?
Speaker 1: Very good question, Aaron. In general, there's a lot of
Speaker 1: studies that have shown that the sooner that anyone gets
Speaker 1: anti venom the better.
Speaker 3: Right.
Speaker 1: Of course, when it comes to especially neurotoxins, just like
Speaker 1: we saw with botulinum toxin and tetanus toxin. If we
Speaker 1: are talking about a presynaptic toxin, so something that affects
Speaker 1: the nerve end of a cell. Once those toxins bind,
Speaker 1: there is nothing that you can do anti venom doesn't
Speaker 1: do anything. So in those cases, especially the sooner that
Speaker 1: you can get an effective anti venom on board, the
Speaker 1: more likely it is you can prevent further toxins from binding.
Speaker 1: In the case of postsynaptic and in the case of hematoxic,
Speaker 1: you have a lot more ability to reverse the damage
Speaker 1: with anti venoms. Okay.
Speaker 3: And in terms of these neurotoxins, what we learned in
Speaker 3: tetnus is that basically how long those the tetanus toxins exist,
Speaker 3: how long they are functional. How long are these presynaptic
Speaker 3: neurotoxins functional.
Speaker 1: It's a good question. I think it very much depends
Speaker 1: on the snake species. So I don't think there's an
Speaker 1: easy half life I can give you got it, okay,
Speaker 1: But people do tend to recover with supportive treatment. It's
Speaker 1: definitely treatable.
Speaker 3: What is supportive treatment besides anti venom therapy.
Speaker 1: Great question, of course, depends on the type of toxin.
Speaker 1: If it's something where it's cytotoxic and things need depreatment
Speaker 1: or they need cleaning, that sort of thing is going
Speaker 1: to be more supportive care. If it's a rhabdomyolysis, the
Speaker 1: most important thing is actually hydration, so it's a lot
Speaker 1: of ivy fluid administration to keep the kidneys from becoming
Speaker 1: damaged from that muscle breakdown. And then in the case
Speaker 1: of neurotoxins, it's more about making sure that people have
Speaker 1: airway support, so mechanical ventilation and the same kinds of
Speaker 1: things we saw with tetanus toxin. Okay, yeah, and that's
Speaker 1: a lot.
Speaker 3: It's a lot. I mean, it's fascinating, as we said
Speaker 3: a thousand times so far, but it's.
Speaker 1: Still so true. Listen, I don't even know where to
Speaker 1: begin to ask you, like, what's up with this this
Speaker 1: snake venom thing? Yeah, and how have humans interacted with
Speaker 1: snake venom and the idea of snake venom through time?
Speaker 1: Such good questions.
Speaker 3: I'll do my best right after this break. This was
Speaker 3: definitely a tricky one to research because there is absolutely
Speaker 3: so very much that you could cover when it comes
Speaker 3: to the history of snakes or even how snakes have
Speaker 3: featured in human history. And before I started reading for
Speaker 3: this episode, I didn't really know where the research was
Speaker 3: going to take me or what story I wanted to tell,
Speaker 3: and it was kind of daunting. But I thought to myself, Okay,
Speaker 3: in this episode, we're talking about venomous snakes and what
Speaker 3: happens when you get bitten by a venomous snake. So
Speaker 3: why don't I look into how humans have responded to
Speaker 3: these snakes and the bites from these snakes over time.
Speaker 3: And that led me down some very surprising but also
Speaker 3: very interesting roads, and I decided to structure the history
Speaker 3: section in two parts. The first part deals with evolution,
Speaker 3: how the encounters that our primate ancestors had with snakes
Speaker 3: over millions of years may have shaped how we look
Speaker 3: at the world literally what, And the second part covers
Speaker 3: how more recently we have learned to deal with those
Speaker 3: encounters through the development of anti venom therapy. Ooh, I
Speaker 3: am very excited, So let's dive in. Okay, first, the
Speaker 3: snake detection hypothesis oh okay, also sometimes called the snake
Speaker 3: detection theory, but I really don't like that it's called
Speaker 3: a theory since it isn't a theory strictly speaking, It's
Speaker 3: a hypothesis. Have you come across this before?
Speaker 1: Nope? But I can't wait.
Speaker 3: I am so excited. Okay, I'm so excited. At its core,
Speaker 3: the snake detection hypothesis proposes that humans and other primates
Speaker 3: have such excellent vision because of snakes, which were among
Speaker 3: the earliest and most important predators of early primates. Individuals
Speaker 3: that couldn't see the venomous snake in the grass or
Speaker 3: distinguish a snake from a vine were more likely to
Speaker 3: get eaten and less likely to pass along their genesh.
Speaker 3: This is a lot. Yeah, break it down, Okay, why vision?
Speaker 3: First of all, primates are actually unique in that they
Speaker 3: have some of the best vision among mammals. Forward facing
Speaker 3: eyes gives them excellent depth perception. They have high visual acuity,
Speaker 3: and many species have trichromatic color vision, which allows us
Speaker 3: to distinguish among like greens and reds and stuff. The
Speaker 3: parts of our brain that are devoted to visual processing,
Speaker 3: both the non conscious and conscious parts, are expanded, and
Speaker 3: these parts are the parts that provide like an automatic
Speaker 3: predator or threat detection and then allow us to process
Speaker 3: that information to decide what we want to do. It's
Speaker 3: our visual system and our reliance on vision as our
Speaker 3: primary sense in large part, that distinguishes us primates from
Speaker 3: other mammals. Throughout the years, researchers have put forth different
Speaker 3: hypotheses to explain why primates have such good vision, for instance,
Speaker 3: resource acquisition, like grabbing insects or grabbing fruits, being able
Speaker 3: to do that visually directed movement with and grasping.
Speaker 1: And like I've I've also read a lot of like recognizing,
Speaker 1: especially with color vision, being able to see red fruits
Speaker 1: in green trees, et cetera.
Speaker 3: Yes, exactly, yeah. And then also there's the arboreal movement,
Speaker 3: so like moving through trees, being able to use that
Speaker 3: depth perception to reach and grasp branches so you can
Speaker 3: move better through trees. Those are some of the hypotheses.
Speaker 3: Most recently, there is the snake detection hypothesis, which was
Speaker 3: put forth by UC Davis professor lynn Isbel in two
Speaker 3: thousand and six. She proposes that primates evolved this excellent
Speaker 3: vision to better detect snakes, specifically venomous snakes. To see
Speaker 3: how this might have happened, let's travel back to around
Speaker 3: sixty million years ago, a few million years after the
Speaker 3: massive extinction of that wiped out so many of the
Speaker 3: non avian dinosaurs and other life on Earth. With the
Speaker 3: non avian dinosaurs gone, small mammals began to flourish, which
Speaker 3: opened up a new food source for snakes, which had
Speaker 3: been around for tens of millions of years already, but
Speaker 3: with the dinosaurs gone, they had even more opportunities to
Speaker 3: expand and diversify, and so they did. After the huge
Speaker 3: Cretaceous Paleogene mass extinction event, venomous snakes began to appear,
Speaker 3: possibly in response to the emergence of faster moving mammals,
Speaker 3: so you could as a snake, you could hide, strike,
Speaker 3: and then wait for the venom to do its work,
Speaker 3: rather than having to get close enough to constrict, which
Speaker 3: is what most snakes used as their like prey kill
Speaker 3: method before this. And it's thought that snakes also evolved
Speaker 3: large gapes, as in they can open their mouths really wide,
Speaker 3: so that they could take advantage of these diversifying mammals.
Speaker 1: I'm loving this so much already, Aaron.
Speaker 3: I'm glad. I'm glad.
Speaker 1: I feel like I'm back at like a natural history
Speaker 1: museum and I'm walking through the like you know, evolution
Speaker 1: display at Field Museum, just like, Oh my goodness, that's
Speaker 1: how I feel right now.
Speaker 2: I love it.
Speaker 3: Oh, I love it so much. I love it. Yeah,
Speaker 3: I find this absolutely thought provoking. I'm I'm it's very
Speaker 3: interesting and so yeah, of course, venomous snakes and the
Speaker 3: earliest primates would have been well acquainted with each other.
Speaker 3: In fact, the earliest primates would have faced the continual
Speaker 3: threat of venomous snakes as predators well before the other
Speaker 3: important predators like wildcats or birds of prey emerged, which
Speaker 3: was later on. If snakes are one of the biggest
Speaker 3: reasons why certain individuals aren't surviving long enough to reproduce,
Speaker 3: that's going to strongly select for traits that will help
Speaker 3: individuals avoid getting eaten, and in this case that's proposed
Speaker 3: to be vision. Being able to distinguish that well camouflaged,
Speaker 3: unmoving snake from a pile of leaves could save you.
Speaker 3: And detecting snakes close up is more important than detecting
Speaker 3: them at a distance, unlike other predators, where you'd presumably
Speaker 3: want to have as much lead time as possible to
Speaker 3: run away or hide. So can we agree here that
Speaker 3: the logic seems to be there for the snake detection hypothesis?
Speaker 1: Yeah? I like it.
Speaker 3: It's logical, Okay, cool? What evidence is there to support it?
Speaker 1: Is there? Is there? Tell me?
Speaker 2: So?
Speaker 3: Up to this point, I've basically been talking about primates
Speaker 3: as one large, homogeneous group which of course they are not.
Speaker 3: And it's actually some of these differences among groups of
Speaker 3: primates that provide some very compelling bits of support for
Speaker 3: the snake detection hypothesis. So when I say that primates
Speaker 3: have excellent vision, that's true in comparison with most other mammals,
Speaker 3: but within primates there's a good deal of variation within
Speaker 3: visual ability. For instance, lemurs from Madagascar have some of
Speaker 3: the worst eye sight of all primates, and they only
Speaker 3: have dichromatic color vision, meaning they can see or distinguish
Speaker 3: among fewer colors. Okay, interesting thing about Madagascar no venomous snakes.
Speaker 1: Okay, uh huh.
Speaker 3: And if we look at the places where venomous snakes
Speaker 3: are the most numerous or have the most potent venom
Speaker 3: places like parts of Africa and Asia, the monkeys there
Speaker 3: have the most advanced vision, the best color vision, and
Speaker 3: some of the largest visual processing regions in their brains.
Speaker 3: And so this would suggest that lemurs, which did not
Speaker 3: evolve in the presence of venomous snakes, didn't experience as
Speaker 3: strong of drivers in terms of vision compared to these
Speaker 3: other monkeys. It's cool, but it's also possible, of course
Speaker 3: that this pattern emerged for other reasons besides venomous snakes.
Speaker 1: Yeah, something else.
Speaker 3: Yeah, So let's get a little more specific by looking
Speaker 3: at some neuroscience, but without getting too much in the weeds, Okay,
Speaker 3: because I don't know anything about neuroscience. Earlier I mentioned
Speaker 3: that the visual processing areas of the brains of primates
Speaker 3: are expanded compared to most other mammals. One of these
Speaker 3: areas deals with non conscious automatic predator detection and then
Speaker 3: an immediate motor reaction. So imagine you're seeing a snake
Speaker 3: slither in front of you while you're out for a run.
Speaker 3: You may react by freezing or leaping backwards, even without
Speaker 3: realizing you're doing it. You just do it completely unthinkingly.
Speaker 3: That region is called the pulvinar region, and in twenty
Speaker 3: thirteen a group of researchers set out to test whether
Speaker 3: the snake detection hypothesis could be backed by neuroscience. They
Speaker 3: showed macaque monkeys who had never seen snakes before a
Speaker 3: series of images snakes, other macaque faces, macaque hands, and
Speaker 3: geometric shapes, and then they measured how strongly the neurons
Speaker 3: in the pulvinar region of these monkeys responded images with
Speaker 3: snakes led to the strongest and fastest responses compared to
Speaker 3: other categories. What and there's more. The position of the
Speaker 3: snake also made a difference. Snakes that were in a
Speaker 3: threatening pose led to a stronger response.
Speaker 1: And these are monkeys who were raised in a.
Speaker 3: Labor and raised in captivity. Okay, yep, So this is
Speaker 3: a really nice piece of neuroscience support for the snake
Speaker 3: detection hypothesis. And I'll include this paper on our website.
Speaker 3: It's by Van Lee at All from twenty thirteen if
Speaker 3: you're curious. What about humans though? Yeah, Another study from
Speaker 3: twenty seventeen measured responses to images of snake skin like
Speaker 3: close up images of snake skin versus bird feathers, so
Speaker 3: not images of like the complete animal, but just the patterns,
Speaker 3: and the images of snake skin got the earliest and
Speaker 3: strongest response. Again, and yet another study compared fear responses
Speaker 3: in humans when presented with images of venomous snakes, non
Speaker 3: venomous snakes, and leaves, and found the strongest fear response
Speaker 3: with venomous snakes, which I think is interesting because I
Speaker 3: don't necessarily know if I know all the time whether
Speaker 3: snake is venomous or not. I know, it's like head
Speaker 3: shape matters, but it's not just head shape.
Speaker 1: No, because even that, like the elapids have very different
Speaker 1: headshapes than the viperiods, and the elapids are incredibly venomous,
Speaker 1: so exactly that is really interesting.
Speaker 2: Yeah.
Speaker 3: Yeah, And these studies aren't alone. These are just like
Speaker 3: a couple that I'm mentioning. There have been quite a handful,
Speaker 3: a surprising handful of neuroscience or physiological studies that have
Speaker 3: tested this hypothesis and have generally found support for it,
Speaker 3: and I think that is so cool. But what I
Speaker 3: also find cool is the behavioral response that primates show
Speaker 3: towards snakes.
Speaker 1: I have a question real quick before we get into
Speaker 1: the behavior in any of these like neurologic response studies,
Speaker 1: did they test other predators in addition to snakes.
Speaker 3: It's a good question. I don't know. It's possible that
Speaker 3: there are There were a lot of studies out there,
Speaker 3: and I didn't read through them all in the ones
Speaker 3: that I mentioned, they did not, but there may they
Speaker 3: may have, And so I think that, Yeah, that is
Speaker 3: one criticism that this hypothesis often faces, as like, well,
Speaker 3: couldn't just be more generally be called the predator detection hypothesis,
Speaker 3: Like it seems a little bit much to pin all
Speaker 3: of our visual evolution, or not all, but most on
Speaker 3: one single predator.
Speaker 2: Right.
Speaker 3: That being said, I think that it's also interesting in
Speaker 3: that the predators of primates that we see today, like
Speaker 3: you think about lions or jaguars or birds of prey,
Speaker 3: a lot of those things would look very different sixty
Speaker 3: million years ago compared to how they look today, whereas
Speaker 3: snakes largely look kind of the same.
Speaker 1: Yeah, that is interesting, is interesting, right that they they
Speaker 1: were our evolutionary pressures millions of years ago when this
Speaker 1: visual acuity was evolving.
Speaker 3: Right, and so the general shape of them we may
Speaker 3: have evolved. Specific recognition of snakes as specific cues and
Speaker 3: the shapes of snakes, yeah, whereas like you know, larger
Speaker 3: cats we may not have. But I don't know. It's
Speaker 3: it's definitely a really good point, and I don't know.
Speaker 1: I wonder if you compared it to other things like
Speaker 1: say alligator's, crocodiles, right that also existed millions of years ago,
Speaker 1: even sharks, right, although I guess we can't everceive sharks,
Speaker 1: so maybe not those.
Speaker 3: Maybe not sharks, but also like, how how numerous in
Speaker 3: the landscape.
Speaker 1: Were That's true, that's true. Good point.
Speaker 3: There's there's like so much more that you could dig
Speaker 3: so much more deeply on this. Yeah, and I will
Speaker 3: definitely link to the book that lynn isbel wrote, this
Speaker 3: book about the snake detection hypothesis that has so much
Speaker 3: more information in it.
Speaker 1: Cool. But yeah, so behavioral stuff.
Speaker 3: Yeah, I just find behavior behavioral studies so interesting.
Speaker 1: Oh yeah, we love it.
Speaker 3: Oh yeah, So, while being afraid of snakes does seem
Speaker 3: to have a learned component to it among primates. So,
Speaker 3: for instance, a snake naive monkey as in it hasn't
Speaker 3: ever encountered snakes before, may show a fear response after
Speaker 3: watching a video of other monkeys responding fearfully to a snake. Okay, yeah,
Speaker 3: it also seems to be this fear of snakes seems
Speaker 3: to be innate to some degree. Macacs that were born
Speaker 3: and raised in captivity responded fearfully when seeing a snake
Speaker 3: in a different study. And there are some studies showing
Speaker 3: that human infants startle in response to snakes and that
Speaker 3: their attention is grabbed by snakes. Yeah, although those infant
Speaker 3: studies do seem to have somewhat mixed results, like it's
Speaker 3: unclear whether it's just startle or fear. Is there actual
Speaker 3: fear to it? Yeah, and going back to our among
Speaker 3: primate group comparison, behavioral studies of lemurs from Madagascar show
Speaker 3: that they don't seem to react to snakes, at least
Speaker 3: visually in like a fearful way. Smell might be a
Speaker 3: different thing, Okay, because there are constricting snakes on Madagascar. Yeah,
Speaker 3: some primate species have a completely distinct alert call that
Speaker 3: they only use in the presence of snakes, and often
Speaker 3: a group of primates will do something called mobbing. They'll approach, stare,
Speaker 3: and vocalize at the snake. Sometimes sometimes the mob turns violent,
Speaker 3: throwing sticks at the snake, or even beating the snake
Speaker 3: with a stick.
Speaker 1: Oh my god, poor snake.
Speaker 3: I feel so bad. So up to this point, I've
Speaker 3: talked a lot about evolution, but mostly in terms of
Speaker 3: primate vision evolving in response to venomous snakes. Yeah, but
Speaker 3: what about the snakes? Yeah, Aaron, did they ever feel
Speaker 3: pressure from primates, especially once we learn to mob the
Speaker 3: snakes or use tools to hurt.
Speaker 1: Or kill them?
Speaker 3: They may have research in the past few years suggests
Speaker 3: that spitting cobras may have evolved the ability to spit venom,
Speaker 3: which is a defensive behavior which I find so cool
Speaker 3: in response to threats from primates. Oh and even cooler
Speaker 3: is that this venom spitting has evolved three times independently. Amazing,
Speaker 3: It's very cool. Yeah, the venom spitting. There's so much
Speaker 3: more there, and I would love to dive deeper into
Speaker 3: why cobras spit right, and also the evolution of venom
Speaker 3: in general. Why did snakes evolve venom? Why are there
Speaker 3: so many different types of venom? Where do we find
Speaker 3: the most venomous snakes? And why how do you milk
Speaker 3: a snake for venom? There is so much that I
Speaker 3: want to ask, but I'm going to have to wait
Speaker 3: for next week as well, all you listeners for when
Speaker 3: I interview Professor Nicholas Casewell, who is the director of
Speaker 3: the Center for Snake Bite Research and Interventions at the
Speaker 3: Liverpool School of Tropical Medicine.
Speaker 1: I am so excited, Aaron, I can't wait for you
Speaker 1: to ask about how different snake species that feed on
Speaker 1: different types of prey have different venom and like, yes,
Speaker 1: oh my gosh, I'm so excited about it.
Speaker 3: I am very excited too, and all of you out
Speaker 3: there mark your calendars. Yeah, it's going to be good. Okay.
Speaker 3: But back to the snake detection hypothesis. Yeah, okay, it's
Speaker 3: a very cool hypothesis and it does have some support
Speaker 3: from research. Yeah, but I do want to say that
Speaker 3: it is still just a hypothesis, a proposed explanation for
Speaker 3: why things are the way they are. And while it's
Speaker 3: possible that snakes did play a role in the evolution
Speaker 3: of primates, most researchers include voting isbel don't claim that
Speaker 3: snakes have been the soul driver of vision evolution in primates.
Speaker 3: They may have like kickstarted a little bit of it,
Speaker 3: but enhanced vision was obviously useful for many other things,
Speaker 3: and there are some problems with this hypothesis, For instance,
Speaker 3: the suggestion that trichromatic color vision evolved to better recognize
Speaker 3: camouflage snakes. Studies have actually shown that primates with di
Speaker 3: chromatic color vision, like those lemurs dramatic ascar detect camouflaged
Speaker 3: objects better than their trichromatic counterparts.
Speaker 1: Oh interesting.
Speaker 3: Yeah, and so, like you said, Aaron, the trichromatic color
Speaker 3: vision might be better explained by needing to distinguish ripe
Speaker 3: red fruits among green foliage. As with everything, more work
Speaker 3: needs to be done.
Speaker 1: Oh but I love it. It's so fun to hypothesize,
Speaker 1: you know.
Speaker 3: It is it is. I there's something about it that
Speaker 3: just I love. It's so fun to think about why,
Speaker 3: why things are the way they are.
Speaker 1: I think that's why we ended up in academia for
Speaker 1: so long, Aaron, because that's how our brains just like
Speaker 1: to like ask those questions of why and think about
Speaker 1: possible explanations, and then also find a way to pick
Speaker 1: apart those explanations and find potential issues with them, and
Speaker 1: then ask more questions because of.
Speaker 3: It, where are the limitations? And yeah, yeah, we're like
Speaker 3: we're perpetual toddlers. Why but why?
Speaker 1: That's honestly so true.
Speaker 3: Okay. Enhancement of vision may be one way that primates
Speaker 3: have dealt with the threat of venomous snakes throughout history,
Speaker 3: but what about other ways? A recent study from twenty
Speaker 3: twenty one showed that primates in Africa and Asia have
Speaker 3: increased levels of resistance to alpha neurotoxins, which are carried
Speaker 3: in the venom of some of the vipers In these regions,
Speaker 3: what notably no resistance is seen in Madagascar lemurs. Yeah,
Speaker 3: but I I want to move past these discussions of
Speaker 3: evolutionary defenses to talk about the history of anti venom therapy.
Speaker 3: Snakes feature prominently throughout human history and culture. One of
Speaker 3: the oldest, if not the oldest, religious artifacts, is a
Speaker 3: stone python in a cave in Botswana. Archaeologists estimate that
Speaker 3: seventy thousand years ago people engaged in a ritual where
Speaker 3: they sacrificed colorful spearheads to this python. Snakes hold a
Speaker 3: prominent position in many religions as creator or destroyer, as
Speaker 3: a symbol of fertility or one of evil, as a
Speaker 3: god or a demon, as representing wisdom or cunning, and
Speaker 3: this duality I think is really interesting when we think
Speaker 3: about how snake venoms can kill, but also how they
Speaker 3: can be used as highly effective medications. It's beautiful and
Speaker 3: it's way beyond the scope of this episode to talk
Speaker 3: about the meaning that snake have held and continued to
Speaker 3: hold for different cultures throughout human history. But I think
Speaker 3: it goes almost without saying that snakes have held a
Speaker 3: great fascination for humans throughout all of time, likely because
Speaker 3: or at least in part because of the threat they
Speaker 3: could pose. The famous physician Galen from ancient Rome wrote, quote,
Speaker 3: it seems that there is nothing more dangerous in life
Speaker 3: than poisons and the bites of noxious animals. Humans have
Speaker 3: always sought ways to protect from snake venom or find
Speaker 3: antidotes against it, drinking small amounts of venom, for instance,
Speaker 3: or using a venomous snake's flesh as an ingredient and
Speaker 3: an antidote recipe like theyac, which was a cure all
Speaker 3: created in ancient Greece. And the variety of quote cures
Speaker 3: shows us just how feared snake bites were and how
Speaker 3: helpless physicians were entreating them. And part of their helplessness
Speaker 3: probably stemmed from the fact that no one really knew
Speaker 3: what was in the of some snakes that caused such
Speaker 3: horrible injury or death. For a long time, many people
Speaker 3: just believed it was bad spirits in the snakes. At
Speaker 3: one point, the Archbishop of Madrid reportedly exercised the venom
Speaker 3: from all snakes of Spain.
Speaker 1: Just like it's gone, it leaves you, it's gone. Nice job.
Speaker 3: It seems that the Italian physician Francesco Ready was the
Speaker 3: first to suggest that rather than bad spirits, it was
Speaker 3: actually this substance coming from a snake's fangs, the venom
Speaker 3: that was responsible for all of the symptoms experienced after
Speaker 3: a bite. And side note, the word venom is derived
Speaker 3: from the Latin word veninum, meaning a magical charm, as
Speaker 3: well as poison.
Speaker 1: Oh, that's kind of fun. I didn't know that.
Speaker 3: Yeah, and his conclusions were not widely accepted. Several physicians
Speaker 3: insisted that it was bad spirits, but Reddy refused to budge,
Speaker 3: and about one hundred years after his work, his ideas
Speaker 3: found support in research done by Felice Fontana on the
Speaker 3: mechanism of in venomation and some characteristics of venoms in
Speaker 3: the European viper. Fontana, who is often referred to as
Speaker 3: the founder of modern toxinology, also determined that the European
Speaker 3: viper was immune to its own venom, which raised the
Speaker 3: question if snakes are immune to their own venom, does
Speaker 3: this mean that other animals can become immune as well.
Speaker 1: I don't know why my mind is so blown by that,
Speaker 1: because it's amazing.
Speaker 3: Yeah, it's amazing. Yeah. And so Fontana published his book
Speaker 3: in seventeen eighty one, so that was a little bit,
Speaker 3: I think, a little bit ahead of its time, right,
Speaker 3: And about one hundred years after this publication, let's see,
Speaker 3: let's take stock of things, right, germ theory was well
Speaker 3: underway and immuneology had also gotten its start. So the
Speaker 3: study of how immune systems respond to foreign substances, toxins, whatever,
Speaker 3: and if humans and other animals could become immune to pathogens,
Speaker 3: did that mean that they could also become immune to toxins.
Speaker 3: Henry Sewell, who was a researcher at the University of Michigan,
Speaker 3: decided to test this question in the context of snake venoms.
Speaker 3: Using the venom from the eastern Massasauga, which is a
Speaker 3: type of rattlesnake found in the US, Sewell injected small
Speaker 3: amounts of diluted venom into pigeons, and he repeated these
Speaker 3: injections over the course of weeks and found that after
Speaker 3: about a month, the tolerance of the pigeons had increased.
Speaker 3: Whereas previously less than a single drop of venom could
Speaker 3: kill the bird, at the end of the experiment, it
Speaker 3: took closer to four whole drops. Wow, which to me,
Speaker 3: I was like four whole drops that's still not a
Speaker 3: ton of venom. But what's really cool I think about
Speaker 3: this is that it demonstrated that animals could gain some
Speaker 3: immunity to toxins and suggests did also that the serum
Speaker 3: from those animals could be used to counteract the effects
Speaker 3: of the toxins in others.
Speaker 1: That is the part that I really truly love that
Speaker 1: it was so early that people came up with this.
Speaker 3: Yes, I do too, And this is what's really what's
Speaker 3: really amazing is that this was before the work of
Speaker 3: Qui Desado, Shabbasaburo and Emo von Bering in eighteen ninety
Speaker 3: on tetanus, which, as I said in our Tetanus episode,
Speaker 3: you know, people consider these two scientists the fathers of
Speaker 3: modern serum therapy, and which of course they had huge
Speaker 3: significance in the history of dipitheria anti toxin and tetnos
Speaker 3: anti toxin. But Suwell may have gotten there first, right
Speaker 3: with these snake venoms. Yeah, and so he's generally overlooked
Speaker 3: and not just overlooked in the history of serum therapy,
Speaker 3: but also overlooked in the history of anti venom therapy,
Speaker 3: which generally starts with the French physician Albert Chalmee, who
Speaker 3: the sea in the BCG tuberculosis vaccine.
Speaker 1: That's why that name is familiar.
Speaker 3: Uh huh. In eighteen ninety one, cal May started as
Speaker 3: director of the Vaccine Institute in what was then known
Speaker 3: as Saigon now ho Chi Min City. He had been
Speaker 3: picked for the job by none other than Louis Pasture.
Speaker 3: While at the institute, very exciting. While at the institute,
Speaker 3: Calmay became interested in the venom of the Indian cobra
Speaker 3: scientific name Naya Naya. For several years he tried to
Speaker 3: induce immunity to this venom in animals, but it wasn't
Speaker 3: until he used the methods described by Sewell that he
Speaker 3: got anti coobra serum, which he could use as an
Speaker 3: actual therapy for cobra byte. I mean this was monumental
Speaker 3: to be able to actually counteract the effects of a
Speaker 3: cobra byte, which previously would have been at least severe injury,
Speaker 3: if not death.
Speaker 1: Yeah.
Speaker 3: Other researchers had been doing similar work around the same
Speaker 3: time as cal May, but their work focused more on
Speaker 3: how the venom worked and how snakes were immune to
Speaker 3: their own venom, rather than focusing on applications for their research,
Speaker 3: whereas Calme's Anticobra serum, which he began production on in
Speaker 3: eighteen ninety five, was revolutionary because it laid the groundwork
Speaker 3: for other people to create their own anti venom for
Speaker 3: venomous snakes in their particular region. Right, although Calme wasn't
Speaker 3: convinced that snake specific venoms were needed, Oh ok, yeah,
Speaker 3: he thought that his Anticobra serum would save you from
Speaker 3: any snake bite.
Speaker 1: Ah, I see, yeah.
Speaker 3: But this misconception was eventually set straight by Brazilian physician
Speaker 3: vital Brazil. He noticed that in sal Paolo, where snake
Speaker 3: bites were a huge problem and estimated five thousand people
Speaker 3: died each year from venomous snake bites in the state
Speaker 3: Whoa at that time. Yeah, So he noticed that snake
Speaker 3: venoms seemed to produce different reactions in people, right, Sometimes
Speaker 3: there was this paralysis, sometimes there was this like blood,
Speaker 3: sometimes there was a cytotoxic effect. And this suggested to
Speaker 3: him that there were different venoms causing these different reactions.
Speaker 3: And this idea made sense, especially in light of the
Speaker 3: fact that when he had used Calmet's Anticobra serum it
Speaker 3: was not very effective. Yeah, So Vitel Brazil set to
Speaker 3: making his own anti venoms, and also made mixtures for
Speaker 3: when the identity of the snake was not known. I love,
Speaker 3: it's amazing, And so by the early nineteen hundreds, the
Speaker 3: building blocks for making anti venom for most any venomous
Speaker 3: snake or even any other creature were pretty well established.
Speaker 3: The rest was really just tweaking things such as the
Speaker 3: quality of serum. One person who received anti venom for
Speaker 3: a tiger snake bite in nineteen thirty said quote, the
Speaker 3: discomfort of the serum sickness which followed a large intravenous
Speaker 3: injection of crude venom was worse than anything the snake
Speaker 3: venom could have done.
Speaker 1: Oh dear, Yeah, that's a problem.
Speaker 3: Yeah yeah. And also, of course people developed more specific
Speaker 3: anti venoms as well as general ones that would be
Speaker 3: effective against a wide range of toxins, and improvements were
Speaker 3: made not just in the quality and availability of anti venom.
Speaker 3: There have also been some amazing strides made in terms
Speaker 3: of vaccines against venom. For instance, the rattlesnake vaccine that
Speaker 3: is available for some pets. I believe because anti venom
Speaker 3: is great, but you need to get it to the
Speaker 3: person or the animal very quickly, and so preventing the
Speaker 3: reaction in the first place is really the golden ticket.
Speaker 3: And finally, what I feel like is one of the
Speaker 3: most beautiful developments in the history of how humans have
Speaker 3: dealt with snake venoms came in nineteen eighty one with
Speaker 3: the approval of the first animal toxin based drug, captipril,
Speaker 3: which is a hypertension and congestive heart failure medication derived
Speaker 3: from a compound in both rops javraraka snake venom specifically,
Speaker 3: if you're interested, it's the Brady kind of potentiating factor.
Speaker 1: It's thrilling, it is amazing. It's a Now it's an
Speaker 1: entire class of anti hypertensive medications that are like, literally
Speaker 1: our first line anti hypertensive anti high blood pressure medicines
Speaker 1: are the ACE inhibitors, of which capta pril was like
Speaker 1: the first one.
Speaker 3: It is so cool.
Speaker 1: Yeah, there is sore too. Now there's so many relas
Speaker 1: and inhibitors. Yeah, oh my goodness.
Speaker 3: I counted. So there was a paper that I read,
Speaker 3: I think it was from twenty twenty maybe, and I
Speaker 3: counted at least eight other medications based on snake venom
Speaker 3: alone that have been approved, and there are many, many
Speaker 3: more in clinical trials.
Speaker 1: Yep.
Speaker 3: Yeah, but even with all of this amazing work and
Speaker 3: the huge strides that have been made in anti venom therapies,
Speaker 3: we still have a long way to go, especially in
Speaker 3: terms of making those therapies available to those who need
Speaker 3: them when they need them. So I'll stop here and
Speaker 3: let you tell me erin more about where we currently
Speaker 3: stand with a neglected tropical disease of snake bites today.
Speaker 1: I can't wait. Those a beautiful segue.
Speaker 3: Thank you.
Speaker 1: We'll take a quick break and then get into it.
Speaker 1: So I'm glad that you said it already. Erin the
Speaker 1: World Health Organization has listed snake bite envenoming as a
Speaker 1: neglected tropical disease and in fact, a neglected tropical disease
Speaker 1: of like incredible importance.
Speaker 3: Yeah.
Speaker 1: The World Health Organization estimates that between four and a
Speaker 1: half and about five and a half million people human
Speaker 1: people get bitten by snakes every year and that this
Speaker 1: results in between one point eight and two point seven
Speaker 1: million in venomations, wow, one point eight and two point
Speaker 1: seven million in venomations and clinical illnesses every year worldwide
Speaker 1: and an estimated anywhere from eighty one thousand to one
Speaker 1: hundred and thirty eight thousand deaths and potentially three to
Speaker 1: five times that number of like long term morbidity from
Speaker 1: these invenomations.
Speaker 3: It's a lot, and it's a lot more than I thought,
Speaker 3: so much.
Speaker 1: More than I had any idea. I can't overstate how
Speaker 1: much I would have underestimated that number. Yeah, yeah, And
Speaker 1: like in I think probably every TPWUKY episode, those numbers
Speaker 1: are definitely estimates because of how much under reporting there
Speaker 1: is that happens, right if we wanted to break things
Speaker 1: down by region, which I think is important because those
Speaker 1: snakes are found worldwide, and venomous snakes are found on
Speaker 1: every continent except I think Antarctica. There's nuts there. These
Speaker 1: snake bite in venomations are not evenly distributed across the globe.
Speaker 1: They are primarily affecting rural and impoverished areas that lack
Speaker 1: a lot of public health and medical infrastructure. If we
Speaker 1: break some of those numbers down by region, at least
Speaker 1: one paper had estimates of different regions of the world,
Speaker 1: So in Sub Saharan Africa, it's estimated there are ninety
Speaker 1: to four hundred twenty thousand envenomings, resulting in three thousand
Speaker 1: to thirty two thousand deaths, huge range of estimate there.
Speaker 1: In North Africa and the Middle East, it's estimated there
Speaker 1: are between three thousand to eight thousand bytes that lead
Speaker 1: to four thousand to eight thousand deaths. I feel like
Speaker 1: that's a pretty important distinction there where the death rate
Speaker 1: is essentially the bite rate. Right in Latin America and
Speaker 1: the Caribbean Islands, it's estimated there are between eighty and
Speaker 1: one hundred and twenty nine thousand envenomings leading to five
Speaker 1: hundred forty to twenty three hundred deaths. So like smaller numbers,
Speaker 1: but again huge range. In the US and Canada, check
Speaker 1: these numbers, sixty five hundred bytes a year, that's a law. Yeah,
Speaker 1: five to six deaths, oh wow. Yeah. And then in
Speaker 1: Southeast and South Asia, I couldn't find exact numbers, but
Speaker 1: the overall mortality rate of snake bites is between one
Speaker 1: point zero five and five point four to two deaths
Speaker 1: per one hundred thousand people, so like significant mortality.
Speaker 2: Yeah.
Speaker 1: And then a lot of the rest of Asia, including China, Japan, Korea,
Speaker 1: and then Central and North Asia like Russia. There's just
Speaker 1: not a lot of data on snake bites. One study
Speaker 1: estimated a significantly lower mortality rate in a lot of China,
Speaker 1: that's like much less than one per one hundred thousand,
Speaker 1: less than point five per one hundred thousand. Australia likely
Speaker 1: between five hundred and three thousand bytes, but only two
Speaker 1: point two deaths annually. Oh wow. And in Europe there
Speaker 1: is an estimated byte rate of one point zero six
Speaker 1: bytes per one hundred thousand people and four deaths annually. Okay,
Speaker 1: you can see that the vast majority of deaths are
Speaker 1: happening in Sub Saharan and North Africa, the Middle East,
Speaker 1: some in Latin America as well, and then Southeast Asia.
Speaker 1: And this also follows the distribution of venomous snakes as well,
Speaker 1: where you're having a lot of high contact but also
Speaker 1: a large proportion of the populations that are living in
Speaker 1: areas and in conditions that put them in close contact
Speaker 1: with these snakes and without access to the infrastructure to
Speaker 1: provide them with antivenom.
Speaker 3: Right, I feel like you could do some sort of
Speaker 3: risk of death per bite calculation based on these different
Speaker 3: regions or something.
Speaker 1: Totally, and it's not all to do with of course,
Speaker 1: these are different snakes and so different toxicities of different venoms,
Speaker 1: but that's not what's driving this. It's access. And one
Speaker 1: of the problems with the fact that and we've talked
Speaker 1: about this before, but I think it's especially poignant in
Speaker 1: talking about snake bites is that underestimation of the cases
Speaker 1: of snake and snake and venomation leads to difficulty in
Speaker 1: estimating the need for anti venom and what types of
Speaker 1: anti venom are needed and how much of it you need,
Speaker 1: because while anti venom can be very effective, if there
Speaker 1: isn't a quote perceived demand for it, then producers who
Speaker 1: are in it to make money stop making it, and
Speaker 1: then there isn't enough of it, so then the price increases,
Speaker 1: then it becomes unaffordable for the people and the populations
Speaker 1: who actually need it. And that is exactly what has
Speaker 1: happened with a lot of snake anti venom manufacturers because capitalism.
Speaker 3: I mean, unsurprising, but I know, yeah, frustrating.
Speaker 1: It's incredibly frustrating. Yeah, And I think that process over
Speaker 1: the last few decades has been part of why the
Speaker 1: World Health Organization has such a push to reduce snake
Speaker 1: bite mortality. Right now, they have a big series of
Speaker 1: innsie that were started in twenty nineteen twenty twenty, but
Speaker 1: I haven't actually been able to figure out exactly where
Speaker 1: they stand in that progression, and I would guess that,
Speaker 1: like everything else, it's been massively disrupted by COVID. Uh huh, yep, yeah,
Speaker 1: there has been because of this recognition of how important
Speaker 1: snake bite, snake and venoming is in terms of a
Speaker 1: public health issue, and the difficulties in anti venom not
Speaker 1: just because of capitalism and manufacturers not wanting to produce
Speaker 1: specific types of venom if they don't perceive a need,
Speaker 1: but also in that, like we talked about in the
Speaker 1: biology section, it's often very difficult to know what snake
Speaker 1: you got bitten by and what the best anti venom
Speaker 1: might be or how much of it you might need,
Speaker 1: especially when we're talking about a polyclonal antibody that comes
Speaker 1: from a lot of different snakes, right right. So there
Speaker 1: has been so much incredible research being done, all in
Speaker 1: pretty early stages, but on things like recombinant anti venoms,
Speaker 1: so being able to make in the lab anti venoms
Speaker 1: that don't have to rely on horses and that whole process,
Speaker 1: or even using small molecule inhibitors to affect entire classes
Speaker 1: of toxins so that anti venom treatments wouldn't have to
Speaker 1: be so specific, and also looking at mixtures of modalities
Speaker 1: that might have multiple effects on the various toxins present
Speaker 1: in a wide variety of snake venoms. So it's I
Speaker 1: think really interesting, especially because while snake bites are a
Speaker 1: global issue, they are also an incredibly local one, right
Speaker 1: where every region is going to have different specific issues
Speaker 1: of different types of snakes that they're coming into contact with,
Speaker 1: and that can make anti venom manufacturing and administration really difficult.
Speaker 1: And so I think that this type of research is
Speaker 1: so compelling and interesting because it can help really even
Speaker 1: the playing field in a lot of ways.
Speaker 3: Yeah, that's very cool.
Speaker 1: Yeah, and then, like you said and kind of mentioned,
Speaker 1: there's also a ton of really interesting research on the
Speaker 1: utilization of the properties of these toxins in these venoms
Speaker 1: to actually use them as therapeutics. So there's a lot
Speaker 1: of really cool, interesting research being done both in terms
Speaker 1: of the treatment of snake bites and also in the
Speaker 1: utilization of snake venom, which I really love.
Speaker 3: It's amazing.
Speaker 1: Yeah, it's amazing, and.
Speaker 3: There's still so much to be learned. There's still so
Speaker 3: much out there in terms of questions like snake ecology,
Speaker 3: for instance, exactly how much does land use change and
Speaker 3: climate change? How are those things impacting our encounter rate
Speaker 3: with snakes?
Speaker 2: Right?
Speaker 3: It's very interesting.
Speaker 1: I also really do want to emphasize for all of
Speaker 1: our listeners, especially those of you who might be a
Speaker 1: afraid of snakes or terrified of snakes, even and now
Speaker 1: even more so because of this episode. There historically has
Speaker 1: been a lot of like push of like kill all
Speaker 1: the snakes, right, and blah blah blah. Snakes are an
Speaker 1: incredibly important part of ecosystems, and killing them is not
Speaker 1: the answer. I don't know. I just don't want people
Speaker 1: to leave this only terrified of snakes with nothing else.
Speaker 1: I think that they are an incredibly fascinating group of
Speaker 1: creatures and while the venoms can be very scary, it's
Speaker 1: just collateral damage.
Speaker 3: It is, and for me, what always helps is learning
Speaker 3: more about them, learning.
Speaker 1: The local snakes in your area, and being able to
Speaker 1: identify which are the venomous ones which are not, and
Speaker 1: how you can avoid them so that you don't have
Speaker 1: an encounter with a snake.
Speaker 3: Snakes are very cool and beautiful, don't hate them?
Speaker 1: Yeah, anyways, should we do sources, Let's do sources.
Speaker 3: I have a ridiculous amount of sources actually for this episode,
Speaker 3: and so I am going to shout out two alone
Speaker 3: that were very helpful for the two different sections of
Speaker 3: the history section. The first one, of course, is the
Speaker 3: book by Lynn Isabel titled The Fruit, the Tree and
Speaker 3: the Serpent Why We See So Well ooh. And the
Speaker 3: other one is a paper by Squiella Baptisto at All
Speaker 3: from twenty eighteen called the History of Anti Venoms Development
Speaker 3: Beyond Calmet and Vitel Brazil. Those were both great.
Speaker 1: I had a few papers for this episode, a couple
Speaker 1: that I want to shout out, especially if you're interested
Speaker 1: in more detail on the biochemistry of these toxins. There
Speaker 1: was a paper called Multifunctional Toxins and Snake Venoms and
Speaker 1: Therapeutic Implications from Pain to hemorrhage and Necrosis. I think
Speaker 1: that was my favorite, just like broad picture one and
Speaker 1: another one that had a lot of diagnostic algorithms on
Speaker 1: like how you can in different regions of the world
Speaker 1: know what types of snake you're bitten by, et cetera.
Speaker 1: It was called snake bite Envenoming Diagnosis and diagnostics. I
Speaker 1: liked that one too, but we will post all of
Speaker 1: our sources from this episode and all of our episodes
Speaker 1: on our website, This podcast will kill You dot Com.
Speaker 3: We will Thanks again so much to Gwen for taking
Speaker 3: the time to chat. It was really terrifying and awesome
Speaker 3: to hear your story and we're really glad that you
Speaker 3: were willing to share it.
Speaker 1: Yeah, thank you for sharing it with us and all
Speaker 1: of our listeners. Thank you also to Bloodmobile for providing
Speaker 1: the music for this episode and all of our episodes.
Speaker 3: Listen, subscribe, leave us a review on Amazon Music, Apple Podcasts,
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Speaker 1: And thank you also to Exactly Right Network, of whom
Speaker 1: we are proud.
Speaker 3: To be a part, And thank you to you listeners.
Speaker 3: We hope you liked this one, yeah, and hope it
Speaker 3: made you want to read more about snakes and learn
Speaker 3: more about snakes if you aren't already a herpetologist.
Speaker 1: And if you are, I hope we didn't get things
Speaker 1: too incorrect. Yeah, and a special shout out to our patrons.
Speaker 1: Thank you so much for supporting us. We love you.
Speaker 3: Yes, thank you well. Until next time, wash your hands
Speaker 1: You filthy animals.