Speaker 1: How does an animal end up with something like venom?
Speaker 1: I mean, I can see how it would be great
Speaker 1: to have something like venom to kill your prey, but
Speaker 1: could the evolutionary process through which venom is developed to
Speaker 1: be dangerous to you as well? Like, I'm notoriously clumsy,
Speaker 1: but I can't be the only one out there who's
Speaker 1: bitten their cheeks or their lips while they're eating. What
Speaker 1: if a snake accidentally bit itself? How do you keep
Speaker 1: from hurting yourself with your own venom? Or did something
Speaker 1: like personal anti venom to your own venom evolve at
Speaker 1: the same time? And what evolves first the venom or
Speaker 1: the fangs needed to deliver the venom. The evolution of
Speaker 1: snake venom is endlessly fascinating and is associated with all
Speaker 1: sorts of misconceptions. And we got super excited about this
Speaker 1: question after a listener asked us a prete particularly fun inquiry,
Speaker 1: which was this, if a rattlesnake bit an octopus, would
Speaker 1: its venom have any effect? So on today's show, we
Speaker 1: bring on venom expert doctor Matt Georgiani, who exhibits the
Speaker 1: patience of a saint as Daniel and I Pepperham with
Speaker 1: loads of weird questions about snake venom and his culinary
Speaker 1: work with hot dogs and marshmallows. Welcome to Daniel and
Speaker 1: Kelly's venomous universe.
Speaker 2: Hi.
Speaker 3: I'm Daniel. I'm a particle physicist and I've never been
Speaker 3: bitten by a snake.
Speaker 1: Hello. I'm Kelly Wainer Smith. I study parasites and space
Speaker 1: and for a whiler. Actually I thought it was going
Speaker 1: to be a herpetologist. I've been bitten by snakes a
Speaker 1: bunch of times, and I love them.
Speaker 3: You love being bitten by snakes or you love snakes
Speaker 3: despite being bitten.
Speaker 1: I love snakes despite being bit And I've never been
Speaker 1: bitten by anything dangerous that I worried about, but man,
Speaker 1: I love snakes.
Speaker 3: Tell us a story about how you got bitten by snakes.
Speaker 3: Were you going for a hike and one jumped down
Speaker 3: in front of you? Were you wrestling a python in
Speaker 3: the Amazon? What happened?
Speaker 1: I was working in a snake lab. Actually it was
Speaker 1: more of like a herpetology lab. We had all kinds
Speaker 1: of cool stuff in there, and I was feeding the
Speaker 1: animals over Christmas break and I it was my fault.
Speaker 1: I was not really paying attention. Because I was showing
Speaker 1: the snakes to some of my friends and I had
Speaker 1: put my hand in some rat water because I'm just
Speaker 1: really a disgusting human being.
Speaker 3: Wait, rat water is what exactly? That's rat flavored water.
Speaker 3: That's water for the rats. What is it?
Speaker 1: Well, you know you got to thaw out rats before
Speaker 1: you feed them to the giant boas. And so I
Speaker 1: had just finished thawing out a rat.
Speaker 3: It's rat juice.
Speaker 1: It's rat juice. And I had put my hand quickly
Speaker 1: into the container with the boa and I really should
Speaker 1: have very like, you know, slowly done it, but but
Speaker 1: I was talking to someone not really paying attention. The
Speaker 1: boa went for the rat and got my hand because
Speaker 1: all my fault, and it let it let go right away,
Speaker 1: and then it you know, backed off and was like,
Speaker 1: oh my gosh. You know, it was like apologizing in
Speaker 1: its own way. And anyway, I went to the doctor
Speaker 1: just to be like, oh, do you have to worry
Speaker 1: about like any bacteria or whatever. My mom insisted I
Speaker 1: go to the doctor and the doctor was like, no,
Speaker 1: you're You're probably fine. We'll give you some antibiot exist
Speaker 1: in case, but you are officially the weirdest case I've gotten.
Speaker 1: I think it was this year. It might have been today,
Speaker 1: but I think it was this year. And anyway, so
Speaker 1: I was, you know, proud of myself.
Speaker 3: How big a snake are we talking here? If it
Speaker 3: can eat a whole rat, then it could probably eat
Speaker 3: your hand, right, Like, this is a big snake.
Speaker 1: I mean, so boas can't like, you know, chew off
Speaker 1: your hand and separated from the rest of your body.
Speaker 1: That's not how they roll. They like swallow things whole.
Speaker 3: But they could like ingest your hand and then ingest
Speaker 3: your arm and just like gradually you could end up
Speaker 3: with like a boa arm. Right.
Speaker 1: It didn't have that kind of personality. We didn't have
Speaker 1: like hyper aggressive snakes. They were all very docile snakes
Speaker 1: in this lab.
Speaker 3: But this is a big snake we're talking.
Speaker 1: Anyway, Yes, yeah, it was a big w Wow.
Speaker 3: Wow, Kylie got bitten by a big snake. I did
Speaker 3: not know that. That's incredible.
Speaker 1: It was a very nice snake and it was one
Speaker 1: hundred percent my fault. I was not being careful. But anyway, yes,
Speaker 1: I've been bitten by snakes big and small, and I
Speaker 1: love them all. And when the rat snake gets into
Speaker 1: our coup, we very gently move it to another location.
Speaker 1: And yes, snake's the best.
Speaker 3: Yeah, I'm a fan of snakes the way i'm a
Speaker 3: fan of spiders, you know, like spiders eat mosquitoes, snakes
Speaker 3: eat rats. Like it's all part of the evolutionary war
Speaker 3: that's going on outside all the time.
Speaker 1: Yeah. When after we removed the rat snake from our coup,
Speaker 1: rats became a problem in the coop and that was
Speaker 1: way worse than the rat snake. I should have left
Speaker 1: the rat snake there, but I relocated it. And then
Speaker 1: I was like, I should have left the rat snake there,
Speaker 1: like it was the rent that it was. You know,
Speaker 1: it was eating like an egg every few days or something,
Speaker 1: and I should have let it do that in return
Speaker 1: for it rat control services.
Speaker 3: It's a pretty good deal.
Speaker 1: It was a pretty good deal, and I didn't realize it.
Speaker 3: Yeah, all right, Well today is a very sneaky episode
Speaker 3: of Daniel and Kelly's Extraordinary Universe, all inspired by a
Speaker 3: question we got from a listener.
Speaker 1: And this is an amazing question. This is a real
Speaker 1: head scratcher. We got lucky because Daniel has a friend
Speaker 1: who could answer it. But before we get to that,
Speaker 1: let's go ahead and listen to the question.
Speaker 2: Here it is for rattlesnake, but an octopus, But it's
Speaker 2: venom have any effect? Some toxins like fly spray are
Speaker 2: very specific as to what animals they harm, and rattlesnakes
Speaker 2: probably only care about what they can do to vertebrates.
Speaker 2: Are venom of snakes immune to their own venom? Does
Speaker 2: this give them resistance to the venom of other snake species?
Speaker 2: Do snakes if I try to envenom other snakes?
Speaker 3: So many great questions, and one of the things I
Speaker 3: love about science is knowing people who study so many
Speaker 3: different weird things. Say if you send me a super
Speaker 3: weird question and might just go, oh, I actually know
Speaker 3: a person who's dedicated their lives to understanding this particular
Speaker 3: question about the universe or snakes.
Speaker 1: I mean, I feel like that's one of the amazing
Speaker 1: things about grad school is you get thrown in with
Speaker 1: so many different kinds of people, and then twenty years
Speaker 1: later you could be like, I know someone who studies
Speaker 1: snake venom making as answer a question about whether a
Speaker 1: rattlesnake could kill an octopus if it'd beit it, I know.
Speaker 3: The guy exactly. But before we heard from the guy
Speaker 3: who might know the answer. We thought, what are the
Speaker 3: extraordinaries think about this extraordinary question? So Kelly sent this
Speaker 3: question to the list and here's what people had to say.
Speaker 4: I would say that there has to be some effect,
Speaker 4: but maybe not the one we are expecting. But wait,
Speaker 4: how would the two creatures find themselves in such a situation.
Speaker 5: I don't think the bite of a rattlesnake would have
Speaker 5: any effect on an octopus. Octopuses have their own incon venom,
Speaker 5: so I think a rattlesnake's bite might herd or stay octopus,
Speaker 5: but I don't think it would have any deliterious effect.
Speaker 6: Rattlesnake venom is not species specific.
Speaker 7: I would guess that octopus biology is not so diversently
Speaker 7: farm from typical prey that there is no effect.
Speaker 6: It seems plausible that rattlesnake venom can kill an octopus,
Speaker 6: because venoms can be effective across very different animal types.
Speaker 6: A blue ring octopus can kill a human, for example.
Speaker 4: I suspect it may depend on the species of rattlesnake
Speaker 4: and the species of octopus.
Speaker 7: I would think that the octopus don't they have some
Speaker 7: sort of neurological isolation between tentacles. Maybe that would allow
Speaker 7: it to kind of minimize or neutralize the neurolithic effects
Speaker 7: of a toxin.
Speaker 2: They are species that evolved in very different environments, and
Speaker 2: the octopus is not unusual prey to the rattlesnake.
Speaker 3: I don't know.
Speaker 8: May not work poison, would not work an octopus because
Speaker 8: snake poison is formulated by nature to only work on
Speaker 8: land mammals. Possibly would kill an octopus, but heathery getting
Speaker 8: together or I'm not sure the hell of a blonde
Speaker 8: dit what? I didn't know octopus has had any venom
Speaker 8: at all, so that's spectacular. Now as to anza and honesty,
Speaker 8: I actually.
Speaker 3: Have no clue.
Speaker 9: If a rattlesnake then an octopus, its venom would be
Speaker 9: devastating to the octopus. Also, I don't know how the
Speaker 9: rattlesnake would get its scuba regulator back in its mouth
Speaker 9: with no hands.
Speaker 4: It probably would not enjoy it at all, but I
Speaker 4: don't know if it would kill it.
Speaker 8: Can a rattlesnake transfer is vendom to the octopus, I
Speaker 8: don't think so, but who knows. The octopus could then
Speaker 8: transfer his or her back into him. But octopus like
Speaker 8: a blue ring octopus for example.
Speaker 10: Uh so, for example, a venomous snake might be more
Speaker 10: venomous to one type of mammal than another. But what
Speaker 10: I have no idea about an octopus.
Speaker 6: Yes, but we need a bigger collider. Oh wait the
Speaker 6: other one.
Speaker 4: Uh it depends now.
Speaker 1: I don't want to be too negative, but there were
Speaker 1: a lot of people who were like, well, this premise
Speaker 1: is unrealistic, and I have to wonder, are you all
Speaker 1: not fun to watch science fiction movies with because we
Speaker 1: asked you to suspend your disbelief for this one.
Speaker 3: That's true, and we probably are not making our audience
Speaker 3: better at watching science fiction movies by teaching them all
Speaker 3: this science, right, we're probably making them into the well
Speaker 3: actually people watching those movies.
Speaker 1: On the other hand, I did laugh out loud at
Speaker 1: a lot of these answers.
Speaker 3: These are great. These are great, So thank you everybody
Speaker 3: for speculating. If you would like to be part of
Speaker 3: this segment for a future episode, don't be shy. We
Speaker 3: would love to add your voice to the chorus. Questions
Speaker 3: at Danielankelly dot org will get you on.
Speaker 1: The list, all right, So, without further ado let's bring
Speaker 1: the guy on the show to answer this amazing question.
Speaker 3: So then it's my great pleasure to introduce to the
Speaker 3: podcast my friend, my colleague, Matt Georgiani. He is an
Speaker 3: evolutionary biologist and a research scientist at the University of Maryland.
Speaker 3: He's also a long standing adjunct faculty member at the
Speaker 3: Whites And Research Institute, where he's best known for his
Speaker 3: pioneering work regarding hot dogs and marshmallows. True story, what.
Speaker 1: What is that?
Speaker 10: What?
Speaker 1: You all are colleagues on his work at the whites
Speaker 1: And Research Institute.
Speaker 8: Yeah, that's the work I'm most proud of by far.
Speaker 3: It's your enduring legacy. Whenever we mention you, Hazel goes, wait,
Speaker 3: is that the marshmallow hot dog guy? And we go Yes,
Speaker 3: that's exactly that guy, because they have burned into their memory.
Speaker 3: One time when we were all on vacation together, I
Speaker 3: think was it in North Carolina and we had hot
Speaker 3: dogs and Matt was like, hmmm, I'm gonna put marshmallows
Speaker 3: a hot dog, and it blew their little minds.
Speaker 8: Well, the key was the giant marshmallow and then tunneling
Speaker 8: a hole for the hot dog. So it was a
Speaker 8: marshmallow bun to a hot dog.
Speaker 1: Right, amazing?
Speaker 3: Yes, incredible?
Speaker 1: Was this a bonfire?
Speaker 3: No bonfire is required for this amount.
Speaker 1: Of creedy A normal So wow, WHOA.
Speaker 3: Now you see the kind of out of the box
Speaker 3: thinking that Matt is capable of, which is why we
Speaker 3: thought it would be great for him to come to
Speaker 3: the podcast and answer all of our out of the
Speaker 3: box questions.
Speaker 1: Well, I'm kind of amazed that a teenager would focus
Speaker 1: on the hot dogs and marshmallows thing when you had
Speaker 1: someone at the house who studies snake venom, which seems
Speaker 1: way more epic than marshmallows and weenies. But let's dig
Speaker 1: into a little bit more. We've got a bit of
Speaker 1: a picture now of what kind of a person Matt is.
Speaker 1: He's innovative in the kitchen, but Matt as someone who
Speaker 1: studies snake venom? Are you like? Also the kind of
Speaker 1: person who owns a snake hook and is like regularly
Speaker 1: picking up venomous snakes? Like, what kind of a snake
Speaker 1: person are you?
Speaker 8: So this is where I get to disappoint all your
Speaker 8: audience members right away. Oh amazing, I am not a
Speaker 8: snake person by nature. I did not grow up handling
Speaker 8: lots of snakes. I don't necessarily like I didn't have
Speaker 8: like some love for them, but I came to them
Speaker 8: through sort of as an evolutionary question, and I've since
Speaker 8: then become quite enamored by them.
Speaker 3: Have you ever eaten a snake inside of marshmallow?
Speaker 10: No?
Speaker 8: But essentially a snake and a hot dog are the
Speaker 8: same thing. Neither one has legs. They're both just tubes
Speaker 8: of meat.
Speaker 1: So I see why you two get along, now, how
Speaker 1: you How where did your two meet?
Speaker 8: In graduate school?
Speaker 3: So?
Speaker 8: He was in Chicago and I was. I was a
Speaker 8: graduate school in the University of Chicago, and uh, and
Speaker 8: Daniel and his physics crew would like come and hang
Speaker 8: out like the cool kids with their leather jackets.
Speaker 1: And I don't believe any of this.
Speaker 3: Now, let's fact check that story. So that was in
Speaker 3: grad school with Katrina. They're both the University of Chicago
Speaker 3: and biology, and I was a physics interlooper. It was
Speaker 3: not at University of Chicago, but since continuing I were
Speaker 3: living near campus, the physics department gave me an office,
Speaker 3: so I got to hang out. And I mostly hung
Speaker 3: out with the biologists, to be honest, because there were
Speaker 3: more fun. But I would also bring a bunch of
Speaker 3: physicists to the biology parties.
Speaker 1: Oh okay, great.
Speaker 3: Which always improves the party, right, I.
Speaker 1: Mean until we start talking about poop. But you know,
Speaker 1: I mean I think that's fun too. Okay, So you
Speaker 1: weren't snake wrangling when you were younger. Are you someone
Speaker 1: who handles the venomous snakes now or am I? Am
Speaker 1: I pushing this still?
Speaker 8: No, I'm still quite a coward. I've only so we've
Speaker 8: gone down to extract venom and to extract tissues and
Speaker 8: things like that. So the only snakes I've handled, well,
Speaker 8: I have handled some dangerous snakes. That's only really after
Speaker 8: they're dead. And so I've dissected out venom glands and
Speaker 8: I've done these sort of things, and it's they're great
Speaker 8: and they're exciting. But I went into a room that
Speaker 8: was full of rattlesnakes and I walk in the room
Speaker 8: and they instantly all pop up and start rattling, and
Speaker 8: I bath had a heart attack right there. So some
Speaker 8: people go forward into that room and other people are like, yeah,
Speaker 8: this is not safe.
Speaker 3: So you came to this question. You were saying from
Speaker 3: an evolution airpoint of you got excited by the scientific
Speaker 3: question of them. So let's dig into that, and let's
Speaker 3: ask some first basic questions like how common is it
Speaker 3: for snakes to produce venom?
Speaker 8: Right?
Speaker 3: How many different species produce venom? Do you know how
Speaker 3: many times this evolved in the history of snakes? And
Speaker 3: why don't hot dogs make venom?
Speaker 8: Well that you know of.
Speaker 1: If you let them sit out too long, they kind
Speaker 1: of do.
Speaker 8: So there is something like you know we have, there's
Speaker 8: something like four thousand species of snakes, and and within
Speaker 8: venom is primarily in two groups of these snakes. And
Speaker 8: so I'll say three names now just to get like
Speaker 8: these are of names, I'll probably keep saying a lot.
Speaker 8: So within the sort of advanced snakes, which is is
Speaker 8: going to be most of the snakes that you're aware of,
Speaker 8: but does not include a few little guys and some
Speaker 8: big fat like pythons and boas. But all the rest
Speaker 8: of them fall into three groups, which are the elapids,
Speaker 8: which are like your cobras and crates. There's vipers, which
Speaker 8: include rattlesnakes, and then clubrids, which is most of your
Speaker 8: garden snakes and rat snakes, king snakes, all your little
Speaker 8: friendly guys, and so those three groups are many of
Speaker 8: the species, probably more than half of the species of snakes,
Speaker 8: and kalubrids being the biggest group of them. But elapids
Speaker 8: and vipers are your two big branches that are venomous,
Speaker 8: and those are each about three to four hundred snakes
Speaker 8: each or species.
Speaker 3: So there's hundreds of kinds of venomous snakes.
Speaker 8: There are, yes, wow, yeah, quite a few.
Speaker 1: And did venom evolve once and then branch into both
Speaker 1: groups or did it evolve multiple times?
Speaker 8: Right, So this is the great question that we get
Speaker 8: at and one of the reasons that like that we
Speaker 8: were so excited to study it. So venom is cool
Speaker 8: because it's secreted, you know, it's secreted from these venom glands,
Speaker 8: and it's in this hyper pouch and they have like
Speaker 8: syringe like teeth and they can excrete it. But because
Speaker 8: it's in this kind of specialized pouch, it seems like
Speaker 8: evolution can run a little wild in there. So one
Speaker 8: of the things about most evolutionary novelties and things that
Speaker 8: happen in evolution is that you're trying to modify proteins
Speaker 8: or processes that exist elsewhere in the body. So if
Speaker 8: you mutate those things, you can have problems everywhere. You
Speaker 8: can have problems in your development or in other processes
Speaker 8: or other physiological things. But if you can just sort
Speaker 8: of sequester these venom genes to just the venom gland,
Speaker 8: you can sec laboratory and you can start to just
Speaker 8: mess with these things. And it seems that that's what
Speaker 8: snakes have done well.
Speaker 3: And let's back up and unpack that because not all
Speaker 3: of us are evolutionologists. Yeah, sure, you're saying that evolution
Speaker 3: works best when it's adapting existing genes. That's because it
Speaker 3: takes like fewer mutations to like turn my spit into
Speaker 3: acid then to like develop an entirely new fluid inside
Speaker 3: the body, right.
Speaker 8: Right, And I mean new genes, like whole scale new
Speaker 8: proteins are very very rare. I truly, new things are
Speaker 8: very hard to develop or to evolve because you have
Speaker 8: to come from something usually, and so most things that
Speaker 8: evolution are sort of piecing together bits from other you know,
Speaker 8: maybe merging things together or mutating things that exist already.
Speaker 8: But it could be difficult if the thing you're trying
Speaker 8: to mutate already has a really important function, and so
Speaker 8: if you want it for a new role. It's difficult.
Speaker 3: I see. So you're mutating one thing, but you also
Speaker 3: have to not mess up the system that already works.
Speaker 8: Yes, that's really critical.
Speaker 1: But if you were to be evolving a fluid into
Speaker 1: an acid, you wouldn't want that acid all over your body.
Speaker 1: So if you could just get acid in a little spot,
Speaker 1: that would be helpful. But then how do you evolve
Speaker 1: that little sac? Where does the sac come from?
Speaker 8: Right? So this is where and this gets into that
Speaker 8: question of where does venom come from? When did it
Speaker 8: first evolve? And then so we'll start with just with
Speaker 8: those two groups of elapids and vipers, so they are
Speaker 8: sort of separated by this middle group that calubrids. So
Speaker 8: we have like this, there's an original ancestor of all
Speaker 8: three of those groups, and then there's the vipers branch
Speaker 8: off into their group, and then the next a little
Speaker 8: after that, some several million years later, calubrids and a
Speaker 8: lapids branch apart from each other. So because calubrids are
Speaker 8: largely not venomous, we kind of have this all right,
Speaker 8: So where did did venom come from? In each one separately?
Speaker 8: But when we start to look, when scientists have looked
Speaker 8: back at ancestors of these snakes. They can see commonalities
Speaker 8: of like common proteins that are expressed in both of
Speaker 8: those venoms, and sometimes they see it in some of
Speaker 8: the oral glands or tissues of those middle group that calubrids.
Speaker 8: So that tells us that the ancestor of all three
Speaker 8: of them had some stuff that we know is in
Speaker 8: venom today, and so it's very likely that some kind
Speaker 8: of venom capacity or some quite dangerous spit, let's say,
Speaker 8: was probably present in that ancestor.
Speaker 3: Hold On, you're saying that because there's commonalities in their venom,
Speaker 3: that it's likely that it evolved before the split, Right,
Speaker 3: But isn't there another hypothesis there that, like maybe they
Speaker 3: discovered the same combination was useful independently, Like maybe you're
Speaker 3: not the only person to put marshmallows and hot dogs together, right,
Speaker 3: Other people can discover these delicious combinations.
Speaker 8: I'll definitely argue that point. But so this there is, Yeah,
Speaker 8: that's a really good point that we can get these
Speaker 8: things what we call convergently when two different groups evolve
Speaker 8: the same thing. However, in this situation, what we're talking
Speaker 8: about often is a particular gene, a venom gene that
Speaker 8: gets recruited. We say recruited because we mean that it's
Speaker 8: expression while maybe normally that's expression was in the liver
Speaker 8: to help digest zimes, and now suddenly it's gained a
Speaker 8: new expression in this oral gland or in this what
Speaker 8: will be the venom gland. And we consider that event
Speaker 8: to be a somewhat rare, exceedingly rare process because developing
Speaker 8: the new like, you know, because you're just changing nucleotides
Speaker 8: at the DNA level in the genome and you're saying,
Speaker 8: here's a new instruction set, I'd like you to now
Speaker 8: be expressed, let's say in the venom gland, and that
Speaker 8: thing we think, we think that step is rare enough
Speaker 8: that when we see it in two animals, we don't
Speaker 8: generally think that that's a conversion event, but rather than
Speaker 8: it might, it might indicate a shared ancestry. And when
Speaker 8: we see it out multiple genes, then that sort of
Speaker 8: reinforces that idea. And sometimes, and although people haven't done
Speaker 8: this part yet, if we could know what that instruction
Speaker 8: kit was, you could say, here's the specific instruction set,
Speaker 8: and we can see that it's the shared between the
Speaker 8: two groups, and that would tell us really that, like,
Speaker 8: this event is so rare that it must have happened
Speaker 8: further back. So that that is often the deal when
Speaker 8: we're talking about because many times when we talk about
Speaker 8: conversion events, it is conversion strategies to approach something. But
Speaker 8: rarely do we think it's the same mutations that have
Speaker 8: fled to that.
Speaker 3: I see the way that like, for example, bats and
Speaker 3: insects both evolved flight independently, but the mechanisms underneath are
Speaker 3: quite different, and that's how we know that they're independent.
Speaker 8: That's right.
Speaker 3: If they had exactly the same internal structures, you would
Speaker 3: suspect that it really had a common origin.
Speaker 8: That's right.
Speaker 3: But it's not a definitive argument, right, it's just more likely.
Speaker 3: I mean, these things are always statistical, and you're that's right,
Speaker 3: making arguments, but it's not a smoking gun.
Speaker 8: That's right. No, absolutely true. So you could imagine if
Speaker 8: there were something very special about these particular proteins that
Speaker 8: we would see that you know, that maybe there's enough
Speaker 8: pressure that we could see a multiple conversion events happening
Speaker 8: at once.
Speaker 1: Would it also be fair to say that, like, so
Speaker 1: you know, if you're looking at individuals who are very
Speaker 1: closely related to each other and are you know, splitting
Speaker 1: off from one another over time. In order for them
Speaker 1: to have independently evolved very similar ways of doing things,
Speaker 1: wouldn't they have had to have like lost traits and
Speaker 1: then gained them again since they were like so you know,
Speaker 1: if you split from a common ancestor, you probably have
Speaker 1: the same set of instructions for doing something. And so
Speaker 1: I feel like what Daniel is implying is that they
Speaker 1: would have had to have lost the ability to do
Speaker 1: something and then independently gained it at another point, because
Speaker 1: given that they were common ancestors, they probably both had
Speaker 1: the ability to do it. Or Is that not the
Speaker 1: right way to think about it?
Speaker 10: No?
Speaker 8: I mean it's so lost. We think it's really important
Speaker 8: in evolution as well. So we think of oftentimes that
Speaker 8: evolution can be like gaining things, but like snakes will
Speaker 8: right away, you should just remember, like they lost their legs, yeah, right,
Speaker 8: and so that's a really important step for them. It
Speaker 8: wasn't just like they fell off, they just it was
Speaker 8: a really important We.
Speaker 3: All lost our gills, right, I can't breathe them the
Speaker 3: water to my grade frustration.
Speaker 8: Right, And so these things are really important men. And
Speaker 8: so it could have been that there was the ancestor
Speaker 8: to all these snakes was venomous, and that in the
Speaker 8: Colubrid line they lost that the instruction to say this
Speaker 8: is venomous.
Speaker 3: Oh, I see.
Speaker 8: But really what I think what ends up happening is
Speaker 8: we look at this complement of venom genes, so venom.
Speaker 8: I maybe I didn't really establish this, but venom is
Speaker 8: a cocktail of proteins, so it is it is somewhere
Speaker 8: in the you know, seven to ten proteins or and
Speaker 8: these are you know, proteins that are parts of large
Speaker 8: protein families, proteins that are conserved across all animals that
Speaker 8: are used in various physiological purposes. So they're important genes.
Speaker 8: We don't know what they all do natively in different
Speaker 8: animals necessarily, but they are large. They are largely conserved
Speaker 8: proteins that are that are important in all kinds of things.
Speaker 8: And a lot of these proteins have multiple There are
Speaker 8: families of proteins because there are many versions of these proteins,
Speaker 8: and this might be like a protease. So proteases are
Speaker 8: digesting proteins, and there are many types of proteases, but
Speaker 8: they are all related evolutionarily, and that relatedness goes all
Speaker 8: the way back into history to the base of animals
Speaker 8: in many cases, if not further back, and so in
Speaker 8: the same way that like species are radiating across the planet,
Speaker 8: like you can imagine that these protein families are radiating,
Speaker 8: because once you have a protease, it's really useful. If
Speaker 8: you can make it and change it and slightly modify it,
Speaker 8: maybe it does something really important for you.
Speaker 3: So then we think that venom evolved once in an
Speaker 3: early ancestor to snakes or for the split into different categories.
Speaker 8: So one of the theories out there is that that's
Speaker 8: the case, and there are other theories that even say
Speaker 8: that it goes further back into their ancestors in the
Speaker 8: lizard world, which would be something like the iguanats or
Speaker 8: the komodo dragon. Now this gets a little more suspect,
Speaker 8: but there is some idea that there's a whole clade
Speaker 8: of animals called toxic Coofra as a name that's often
Speaker 8: used for this oo and the way to think of
Speaker 8: it might just be that they have a spit that's
Speaker 8: kind of cool, that has a lot of cool endzigne.
Speaker 8: But if we just want to focus on the advanced
Speaker 8: snakes and where our big powerful venom guys come from,
Speaker 8: it seems reasonable that they had some kind of spit
Speaker 8: oral gland cocktail that was doing something and maybe it
Speaker 8: just helped digestion. Maybe it's like you know, you bite
Speaker 8: a you eat a mouse, and you just need help
Speaker 8: digesting it, so you have a lot of enzymes and proteases.
Speaker 3: Wait, I have two questions before you get you further. Yes,
Speaker 3: are there lizards that have venom like spit? Is that
Speaker 3: a thing?
Speaker 8: This is a little bit unclear, and this gets a
Speaker 8: little bit out of where I know. But like for
Speaker 8: the most part, they don't have the ability to inject
Speaker 8: a venom. Kimodo dragons are associated with certain bad outcomes
Speaker 8: for their prey, but that might be more to do
Speaker 8: with other parts of their spit and so it's not
Speaker 8: clear that it's a venom in this case. But it
Speaker 8: could be that these families, these genes that I'm talking
Speaker 8: about have started to be used in that oral structure.
Speaker 3: I see.
Speaker 1: I thought HeLa monsters had the grooves in their teeth
Speaker 1: and like a venom thing that drip down the grooves.
Speaker 8: Right, right, Yeah, So it's exactly that sort of thing.
Speaker 8: And how these things are, you know, whether we call
Speaker 8: them venom or not, becomes a little tricky at times, okay.
Speaker 3: And does this give us any insight into the question
Speaker 3: of like venom and fangs, Like does venom precede fangs,
Speaker 3: because like, why would you have these like syringe like
Speaker 3: teeth if you didn't have something to ingestate rights?
Speaker 8: It's a really good point, right, and so you could
Speaker 8: think about like what step would probably come first? Having
Speaker 8: really sharp fangs does seem reasonable as a thing to
Speaker 8: catch animals with alone, But really, it does seem that
Speaker 8: the evolution of fangs, so between those lapids and those vipers,
Speaker 8: the evolution of the fang seems to be a convergent situation.
Speaker 8: So morphologically they're different enough that it seems that fangs
Speaker 8: evolved twice. And so Klubras, those guys in the middle,
Speaker 8: your garter snakes, they don't have big fangs either, right,
Speaker 8: but it seems like a lapids did. And then they
Speaker 8: associated with that that vn and that oral gland became
Speaker 8: this really powerful venom gland, and the same thing along
Speaker 8: the lines of vipers, so they develop a slightly different
Speaker 8: tube like tooth that can inject, you know, using all
Speaker 8: the muscles around a big and large venom gland, and
Speaker 8: from that they can you know, subdue their prey. And
Speaker 8: so it does seem that maybe while venom might have evolved,
Speaker 8: the sort of the capacity for some kind of venom
Speaker 8: of alls first, we then see the fangs develop.
Speaker 3: So wait before you have the like syringe to inject
Speaker 3: the venom. And to animal, venom is still beneficial because
Speaker 3: you're like biting something and your whole mouth is coded
Speaker 3: in venom and you're smearing it on the surface, and
Speaker 3: it's not as effective.
Speaker 8: But well, we don't know if it was used to
Speaker 8: kill prey at the time I see, or if it's
Speaker 8: just really a digestive thing, or if it was some
Speaker 8: other purpose.
Speaker 3: Could you just been like a season ex right? Ooh,
Speaker 3: I like spicy food.
Speaker 8: Even because I've read this report of you know, so
Speaker 8: we all we have enzymes in our saliva as well, right,
Speaker 8: and we don't think of ourselves as toxic. However, I
Speaker 8: guess there's these reports of people that used to take
Speaker 8: human saliva and inject it in their in this was
Speaker 8: the reporter read. It was like to get out of prison,
Speaker 8: but it would it were to get like to the
Speaker 8: hospital in the prison, because it would create on a reaction.
Speaker 8: So if you inject enough of something, right, and you
Speaker 8: inject enough enzymes into you, oh, I see, it's going
Speaker 8: to have some kind of effect. And so what we've
Speaker 8: always questioned early on was, well, you know the key
Speaker 8: thing about a lapids and vipers, So they have massive
Speaker 8: amounts of this vendom that they can inject. And are
Speaker 8: these venom proteins actually super dangerous? Are they that much
Speaker 8: different than the proteins they evolved from or is it
Speaker 8: just the amount that you're injecting in interesting?
Speaker 3: And why hasn't anybody made a snake venom based hot
Speaker 3: sauce yet?
Speaker 8: This is a great question because I mean, I'm sure
Speaker 8: you'll get tingly mouth. It'll be.
Speaker 3: I mean it sounds like wow, delicious, right, I mean,
Speaker 3: capsation evolved, as you know, an animal plant warfare toxin,
Speaker 3: and so like, why not double down on that. I
Speaker 3: think this is a billion dollar idea.
Speaker 1: Let's give the extraordinaries a moment to ponder this amazing
Speaker 1: question that Daniel has shared with us, and when we
Speaker 1: get back, we will return to chatting about venom with Matt.
Speaker 3: Okay, we're back and we're talking to Matt Georgiani about
Speaker 3: snake venom and whether it would be tasty on a
Speaker 3: hot dog. Matt, give us some insight into the chemistry
Speaker 3: of venom. You've talked about it as proteins. We've talked
Speaker 3: about how enzymes in your mouth do stuff. What is
Speaker 3: venom doing? Why is it so bad to get injected
Speaker 3: with venom? What does it do to you?
Speaker 8: Right? So, there are two major flavors of venom.
Speaker 3: And spicy and extra I see.
Speaker 8: So one of those one of those main types is
Speaker 8: a neuotoxin. And so these are there's a few selecting
Speaker 8: proteins and peptides that are targeting nerve receptors and so anyway,
Speaker 8: they're disrupting the nervous system and this can result in
Speaker 8: paralysis and you know, shock or various like organ failure
Speaker 8: that happens.
Speaker 3: To me after I eat a big burrito.
Speaker 8: Anyway, or this might help reinject the system, I don't know,
Speaker 8: might start you right back up.
Speaker 3: No, we're joking, but this is this is quite serious, right.
Speaker 8: Yeah, yeah, so it certainly is. I mean, it is
Speaker 8: fun to joke about this other than there's a real
Speaker 8: obviously there's a real human component to what venoms can do.
Speaker 8: But the other major flavor are what we call, let's
Speaker 8: say broadly, we'll call them heemorrhagic. And so these are
Speaker 8: these are proteins that target the blood and the hemostatics system.
Speaker 8: So you know, it's a very important for us to
Speaker 8: have our blood like flowing nicely, and then if you
Speaker 8: get cut, you know, you have to be able to
Speaker 8: clot that blood and prevent it from from having hemorrhage
Speaker 8: for example. And a lot of these proteins are targeting
Speaker 8: elements of that system. Some of them are causing massive clotting,
Speaker 8: which can then disrupt all your other blood systems as
Speaker 8: well as throwing clots throughout your system, which is never good.
Speaker 8: But some of them are kind of doing the reverse
Speaker 8: where they are essentially disrupting the clotting system completely such
Speaker 8: that there is you just bleed, I mean, you just
Speaker 8: have massive hemorrhage because and so this creates obviously a
Speaker 8: lot of problems if you can't clot after a wound,
Speaker 8: or especially if the damage starts to spread, and then
Speaker 8: there are many other components that are then targeting that
Speaker 8: sort of the vascular system or the muscle system and
Speaker 8: degrading cells and chopping up parts of that, you know,
Speaker 8: the cell membranes that are essentially really important for the
Speaker 8: integrity of your body.
Speaker 3: So these are two very different mechanisms, right, Yeah, targeting
Speaker 3: the nervous system or targeting your plotting. I thought earlier
Speaker 3: we were saying that we thought there was a common
Speaker 3: origin of venom because the fundamental mechanisms of them were
Speaker 3: so similar. But now there's two different ones. Are the
Speaker 3: isolated in the two different groups of snakes or how
Speaker 3: does that all fit together?
Speaker 8: I mean, this is why it gets It's where it
Speaker 8: gets so exciting. So that what I talked about the
Speaker 8: commonality is that, like at the base, there are some
Speaker 8: components of this system that are shared. But when the
Speaker 8: vipers in a lapid split, they each start to recruit
Speaker 8: new genes into their venom, and those are the ones
Speaker 8: that are the real are the ones we really talk about,
Speaker 8: the real dangerous guys. And I see along the elapid
Speaker 8: lineage they developed some really powerful neurotoxins, and largely speaking,
Speaker 8: but not exclusively, they are neurotoxic venoms, and they have
Speaker 8: components of that heemorrhagic venom, and they have elements that
Speaker 8: are disrupting cell integrity. But they also have really powerful neurotoxins,
Speaker 8: and that's why those snakes can be really, really deadly
Speaker 8: and act quite quickly.
Speaker 1: Can you remind me elapids are vipers? Is that right?
Speaker 8: So elapids are going to be your cobras and crates
Speaker 8: and some sex so anything in Australia. I don't know
Speaker 8: why people would ever go there, some of the deadliest things.
Speaker 3: Because everybody who lives there is smart and good looking.
Speaker 3: That's why people.
Speaker 5: Would go there.
Speaker 3: No, that's true pandering to our listeners.
Speaker 8: Because they are surviving snakes all the time.
Speaker 1: They even have like venomous trees in Australia, like poisonous trees,
Speaker 1: not anyway crazy.
Speaker 3: They probably already put venom on their hot dogs down
Speaker 3: in Australia. They just don't even talk.
Speaker 8: It's so boring.
Speaker 1: That's great. So cobras and Australia stuff.
Speaker 8: So there's a lot of these things, and they have
Speaker 8: the super potent neurotoxin, so they're very dangerous in that respect.
Speaker 8: So vipers along that lineas they developed a lot of
Speaker 8: like theycruited in a lot of proteass and other genes
Speaker 8: that help really disrupt that hemostatic system, but they also
Speaker 8: have taken some of those and turned those into neurotoxins
Speaker 8: as well. So they've they've mutated some of these proteins
Speaker 8: that were initially we think used for disrupting the hemostatic
Speaker 8: system or disrupting the cells, and change them and modified
Speaker 8: them and turn them into neurotoxins as well. So we
Speaker 8: see neurotoxicity within vipers additions, So vipers again are rattlesnakes,
Speaker 8: but then there's a ton of those snakes over in
Speaker 8: Europe and in Africa, Asia, so all of these snakes
Speaker 8: are kind of all over the world for the most part,
Speaker 8: but there are no vipers. There are no vipers in Australia.
Speaker 3: I see. So the answer because its biology is it
Speaker 3: depends or it's complicated, and so it seems like, if
Speaker 3: I'm understanding, there is some common origin to the venom.
Speaker 3: But then after the split, they continue to evolve and
Speaker 3: the vipers become neurotoxins, and the cobras become neurotoxins, and
Speaker 3: the rattlesnakes become hemorrhagic. And so now they've also separated, right,
Speaker 3: and so there's some elements of both to the story
Speaker 3: that is fascinating.
Speaker 8: Yeah, each lineage, you know, and this is only they
Speaker 8: maybe thirty maybe it's forty million years ago, and each
Speaker 8: lineage starts to develop just really starts to experiment and
Speaker 8: play with the things they can do with this venom.
Speaker 8: And so this is the part that we came in
Speaker 8: as being very interested and my focus initially was in
Speaker 8: mostly in vipers. But they took one gene, for example,
Speaker 8: one metalloprotease, and it seems to be recruited into the
Speaker 8: venom gland, something they would excrete and if you look
Speaker 8: at it, if you look in a cuman, we have
Speaker 8: this metaloprotiase and in the same genomic location. So we
Speaker 8: have a few flanking genes that are conserved across all vertebrates,
Speaker 8: and we could say, oh, yeah, there's gene X and
Speaker 8: gene Y, and then there's this metaloprotiase, and then there's
Speaker 8: some other genes. But in a rattlesnake in the western diamondback,
Speaker 8: for example, there might be up to thirty copies of
Speaker 8: that metallic proteus and they're all different. They have fairly
Speaker 8: conserved areas, but they have the proteins have been modified
Speaker 8: and changed, and we don't know why. We have no
Speaker 8: idea why they have so many copies of this gene
Speaker 8: and why they're also different from each other.
Speaker 1: And some more copies doesn't mean you necessarily mean you
Speaker 1: make more, but it means what you make, you make
Speaker 1: different versions of it or.
Speaker 8: So right, they're slight. There are like different variations in
Speaker 8: the same way that there are thousands of variations of
Speaker 8: hot sauces. These are different variations of these proteins, and
Speaker 8: we assume and we don't know really how they function differently,
Speaker 8: but we assume it has to do with the prey
Speaker 8: that they're eating, yeah, or the predators are avoiding, and
Speaker 8: that they are constantly tweaking these genes to be more
Speaker 8: effective against different types of prey, potentially in the same
Speaker 8: way that the prey is kind of going like, I
Speaker 8: really should figure out how to stop this.
Speaker 3: So that's the other part I wanted to ask about,
Speaker 3: because the missing part of the story is the evolutionary
Speaker 3: context in which they're evolving, right, the things that they're
Speaker 3: injecting the venom into. So do we understand, for example,
Speaker 3: why these two lineages split and develop different kinds of toxins.
Speaker 3: Are they effective on different kinds of prey? Are they
Speaker 3: in different parts of the world. Why do we understand
Speaker 3: the motivation for that split at all?
Speaker 8: Well, they split in the way then every species split
Speaker 8: all the time. Who knows exactly We have no idea
Speaker 8: exactly what context led this, you know, the split, but
Speaker 8: you know, and initially it was one little snake hanging
Speaker 8: out and occasionally, you know, if you look soon after
Speaker 8: the split, it would seem like the exact same you know,
Speaker 8: a couple of sister species or something like that. What
Speaker 8: led you know, when maybe once the lineage for vipers
Speaker 8: starts to evolve one type of venom, it maybe they
Speaker 8: focused on one kind of prey that was different than
Speaker 8: what a lapet's did and a lapid behavior and it's
Speaker 8: very different than viper behavior in any ways.
Speaker 3: So the venom evolution could either just be like, look,
Speaker 3: we're in a random different direction because we were separate species.
Speaker 3: Or it could be that it worked better on the
Speaker 3: kind of prey that they were tending to snap.
Speaker 8: I mean, you know, these mutations and these recruitment events
Speaker 8: are random, we think, right, and so that they are
Speaker 8: that they just happened in one linians versus another might
Speaker 8: just be all that I needed to thoroughly start to
Speaker 8: delineate these two groups. And there might have been other elements,
Speaker 8: like give the snakes, do you have some other physiological
Speaker 8: differences with between each other? But you know they largely Yeah,
Speaker 8: exactly what led to the split between the two, It's
Speaker 8: hard to say.
Speaker 1: Do we see any patterns where like, uh, if you are,
Speaker 1: for example, a snake that goes after rodents versus a
Speaker 1: snake that goes after I don't know, birds, is there
Speaker 1: certain kinds of venom that are more helpful depending on
Speaker 1: what kind of prey you're going after or what kind
Speaker 1: of predators you're trying to avoid.
Speaker 8: Yeah, there certainly seems to be some correlations, but it's
Speaker 8: not great. It's not I think people have done some
Speaker 8: nice studies, but they've tried to look at the prey that's,
Speaker 8: you know, that what they're eating, and then see if
Speaker 8: the different venom types are correlating. But it's not. It's
Speaker 8: not great. It's like there's some correlations there, but it
Speaker 8: doesn't seem like some smoking gun like this is clearly
Speaker 8: what's driving the differences.
Speaker 3: And what about non snake venoms. I know, we talked
Speaker 3: about lizards, and you mentioned trees or whatever in others
Speaker 3: shees that develop venoms. Is there any similarity to snake
Speaker 3: venom in terms of the chemistry or.
Speaker 8: The history the chemistry is so, there's so. One of
Speaker 8: the genes, one of the interesting genes that we study
Speaker 8: is called phospholipace A two, and so fosplit A two
Speaker 8: is a part of this large family of proteins, and
Speaker 8: that's in the viper venom. They use one of these,
Speaker 8: the elap It's also recruited a phospholipase A two, but
Speaker 8: a different family member, a deeply diverged version of it.
Speaker 8: So we call that a group A group one pel
Speaker 8: A two and and the vipers use group two and
Speaker 8: bees use group three in there in the venom that
Speaker 8: they have. So there, in that case you have a
Speaker 8: conversient use of a similar enzyme that can be used
Speaker 8: when injected to cause pain or to disrupt the prey
Speaker 8: or whatever you're trying to sting. But other molecules, especially
Speaker 8: like in cone snails and stuff, they use very different
Speaker 8: kinds of molecules that work effectively at you know, they
Speaker 8: can often work as neurotoxins or some other effect, but
Speaker 8: we suspect that. So I don't know a lot of
Speaker 8: the chemistry about all the different kinds of venoms, but
Speaker 8: that I suspect that the evolutionary sort of effects of
Speaker 8: these or the result of gaining toxin or gaining venom,
Speaker 8: and then what we see following that in terms of
Speaker 8: the diversity of toxins or the evolution of those toxins
Speaker 8: once acquired, we might have some similarities in there.
Speaker 1: I probably shouldn't have used the word venom for the trees.
Speaker 1: It's probably some other word was the right word. But
Speaker 1: so you mentioned that the prey are probably wanting quote unquote,
Speaker 1: you know, to evolve a way around being susceptible to
Speaker 1: the venom. Do we see prey evolving ways around the venom?
Speaker 1: Like can you get bit by a rattle snake and
Speaker 1: just kind of shake that off if you're a mouse,
Speaker 1: for example.
Speaker 8: So it seems that at least in the one good
Speaker 8: example is the California ground squirrel, which has evolved the
Speaker 8: resistance to the Pacific rattlesnake. So this is in Oregon
Speaker 8: and northern California, and in some of those locations, what
Speaker 8: we have are a ground squirrel that can take a
Speaker 8: bite and survive. Wow. So it's invented by like sort
Speaker 8: of recruiting in some little proteins, some small proteins that
Speaker 8: act as inhibitors to those hemorrhagic toxins. So that's a
Speaker 8: pretty cool invention and very really good for the squirrel.
Speaker 3: Yeah, and why isn't that more widespread?
Speaker 8: So that's a great question. And it seems that it's
Speaker 8: unclear because let's say that we have a lot of
Speaker 8: snakes are hunting small mice, and it seems, at least
Speaker 8: to me naively that a big bite from a big
Speaker 8: rattlesnake is going to be quite damaging to you, regardless
Speaker 8: of it whether or not it has venom. Now, a
Speaker 8: viper generally speaking, will strike hid an animal and then
Speaker 8: kind of pull back, and the animal will walk off
Speaker 8: and die somewhere, and it will follow and find the
Speaker 8: prey that it killed and then eat it. And this
Speaker 8: is largely because they don't really want to tussle that much,
Speaker 8: you know, because you have potential for injury. If all
Speaker 8: you are is a hot dog with teeth, it's really
Speaker 8: easy for something to.
Speaker 1: Get you with no marshmallow armor.
Speaker 3: You try to belittle it. You try to belittle it,
Speaker 3: but that's still that's the inspiration for a horror movie
Speaker 3: right there. Yeah, that's a hot dog with teeth that
Speaker 3: follows you.
Speaker 8: So you know, vipers are also often ambush predators. So
Speaker 8: rattlesanks don't go seeking out their prey, but they kind
Speaker 8: of hang tight. They wait for animals to go by
Speaker 8: and they nip at them, whereas the lapids tend to
Speaker 8: hunt stock things out. So the things that rattlestanks are eating,
Speaker 8: why is there not more? There may be more resistance,
Speaker 8: and it might be that the history that the reason
Speaker 8: that that venom is so complex might reveal an evolutionary
Speaker 8: history of prey resistance and then trying to overcome it
Speaker 8: with by either recruit again new toxins or duplicating and
Speaker 8: multiplying the toxins you do have and changing them.
Speaker 3: Give an arms race going on.
Speaker 8: Right, We think this might really truly be a really
Speaker 8: good example of an arms race, but we don't know.
Speaker 8: It's hard to look at the history because all the
Speaker 8: animals that kind of came along the way are all
Speaker 8: dead now. But where we also see a lot of
Speaker 8: resistance is actually in predators of snakes, and so these
Speaker 8: are ones that are like in Africa, there's like the
Speaker 8: honey badger or the mongoose, or even meerkats have evolved,
Speaker 8: i think, in some cases convergently ways to prevent the
Speaker 8: neurotoxin from affecting them. And these are all animals that eat,
Speaker 8: you know, cobras and other snakes, because essentially they're really juicy,
Speaker 8: tasty hot dogs. And so if you want to eat
Speaker 8: a hot dog that can bite you back when you're
Speaker 8: trying to eat it, like you that's a then if
Speaker 8: you're depending on that for your diet, there might, it might,
Speaker 8: it's possible. There's even stronger sort of pressure to sort
Speaker 8: of evolve a resistance.
Speaker 3: All right, we're going to take a break, and when
Speaker 3: we come back, we're going to ask Matt all the
Speaker 3: really weird snake venom questions we've been holding back on.
Speaker 1: We're back. We have been hitting Matt with all the
Speaker 1: hot dog related questions we could think of, but now
Speaker 1: we are going to hit him with the weird venom
Speaker 1: related questions that we've got, including venom related questions from
Speaker 1: the listeners. So first, all right, Matt, if a snake
Speaker 1: accidentally bit itself, would it be immune to its own venom.
Speaker 8: Perfect. It seems valuable.
Speaker 10: Right.
Speaker 8: And if I told you especially that rattlesnakes are living
Speaker 8: in these big dens often, right, you know, there's tons
Speaker 8: of them around. If you ever see videos, you can
Speaker 8: see videos of these guys swarming all over each other
Speaker 8: and the young ones, you might are nip it at
Speaker 8: each other. You don't want a ton of death. So
Speaker 8: it does turn out that rattlesnakes have resistance to their
Speaker 8: own venom.
Speaker 3: Wow, And this.
Speaker 8: Seems like that's probably important. It might be because the
Speaker 8: big fangs and they're trying to chomp at something. Maybe
Speaker 8: they bite themselves occasionally. Maybe it's happening. We don't really
Speaker 8: know exactly where and when they might be nipping each
Speaker 8: other or getting their own venom. But it does seem
Speaker 8: like they really do have a few layers potentially of resistance,
Speaker 8: which makes perfect sense.
Speaker 3: Which makes perfect sense. And now a question that requires
Speaker 3: a qualifier that you're not a medical doctor and not
Speaker 3: giving medical advice. But what should you do if you
Speaker 3: are bitten by a venomous snake? Should you cut it
Speaker 3: with an X and suck it out?
Speaker 8: I think you should just cry a little bit first,
Speaker 8: but don't take too long. So the most abortant they gets. Course,
Speaker 8: it's just to stay calm. And if you're in the
Speaker 8: United States, and if it's a rattlesnake, you're gonna live. Oh,
Speaker 8: I mean, if you can get to a hospital. There's
Speaker 8: anti venoms, and there's generally speaking, you know, there are
Speaker 8: I think I looked it up for this. So there's
Speaker 8: you know, some seven to eight thousand bites a year
Speaker 8: within the US, and there's five or six deaths, which
Speaker 8: is tragic, but is a good survival rate for sure. Yeah,
Speaker 8: and as long as there's access to some medical care,
Speaker 8: you're going to be just fine.
Speaker 3: That's fewer people than are killed by sharks, I think,
Speaker 3: otherwise known as ocean based hot dogs.
Speaker 1: Daniel, I've been listening to some of our past episodes
Speaker 1: and you often compare things to shark deaths. Do you
Speaker 1: actually know how many people are killed by sharks every year?
Speaker 1: This isn't the first time you've used that as a baseline.
Speaker 3: I use that as a baseline because it's something people
Speaker 3: think of as very rare, and it is quite rare,
Speaker 3: but they're still terrified of and you know, I think
Speaker 3: people don't have a great sense of the frequency at
Speaker 3: which you can be killed by various things. And so
Speaker 3: it's just a fun example. And no, thank you for
Speaker 3: putting me on the spot. I do not have that
Speaker 3: number off the top of my head.
Speaker 8: I'll have to I'll send you. I have this diagram
Speaker 8: that has like human deaths caused by animals and it's
Speaker 8: really great because well, not great, great in that it
Speaker 8: does put all of it into a framework. And so
Speaker 8: obviously the number one, of course is misciitis. Are killing
Speaker 8: these and then it's like humans depressive, other dangerous. But
Speaker 8: then snakes is third. Right, So as much as snake
Speaker 8: bites in the US are not really they're not not
Speaker 8: you should be like it's nothing, but it's it is
Speaker 8: like not the problem it is in Africa or in
Speaker 8: out in Asia where it's a significant problem, of course.
Speaker 3: And do we know how anti venoms work, Like is
Speaker 3: it just some chemistry where this chemical attacks that chemical
Speaker 3: and breaks it apart, or is it like go into
Speaker 3: your system and the way it does in this squirrel
Speaker 3: and like block it somehow.
Speaker 8: No, So by and large, what we've done is created
Speaker 8: antibody based antiveatoms. And so what this is essentially as
Speaker 8: they'll take venom, they'll inject it in a horse initially,
Speaker 8: initially people do these horses or cheap and then you're
Speaker 8: essentially just creating asking the animals immune system to create
Speaker 8: a series of antibodies that'll that'll block the toxins, and
Speaker 8: so they'll take you know, they'll take a few of
Speaker 8: the snakes that are here. So the one, the main
Speaker 8: one in the United States, takes venom from four different animals,
Speaker 8: four different snakes, puts it together, puts it in sheep
Speaker 8: or ant or horse, and then it does some it
Speaker 8: will try to do some purification. But then you take
Speaker 8: that that that polyclonal antibody, and then you essentially just
Speaker 8: put that in vials and then you you have to
Speaker 8: take it if you get bit. And this system is
Speaker 8: sort of this working around the world where they take
Speaker 8: the venom from the snakes in the area and then
Speaker 8: they try to try to put it, try to create
Speaker 8: antibodies against it. Unfortunately, is that not like while it's
Speaker 8: very good in that it saves or save lives and
Speaker 8: prevents damage like to some degree, it is also it's
Speaker 8: not like the most perfect system because people can develop
Speaker 8: allergies to these kinds of antibodies, and they're extraordinarily expensive.
Speaker 8: I mean, even if in the US, like you're getting,
Speaker 8: I think you might have to get like ten vials
Speaker 8: of an anti venom and if there are a few
Speaker 8: thousand a pop, that's gonna Yeah it's significant, and yeah,
Speaker 8: they require refrigeration. So this is like why steak bite
Speaker 8: is such a problem in the developing world where they
Speaker 8: don't have access to this sort of these sort of
Speaker 8: anti venoms. For they're costly, they have to be handled correctly,
Speaker 8: and the bigger problem in many cases is that the
Speaker 8: diversity of snakes, even regionally, the venoms are different enough
Speaker 8: that your anti venom might not be sufficient to cover
Speaker 8: you if you're bitten in a slightly different area by
Speaker 8: a slightly different sister species.
Speaker 1: So for horses, I had imagine maybe you go with
Speaker 1: horses because they're gigantic and so you can hit them
Speaker 1: a little bit of venom and they, you know, their
Speaker 1: bodies are big enough that they can handle it and survive.
Speaker 1: Why why sheep?
Speaker 8: I think you can just have a lot more sheep. Okay,
Speaker 8: all right, I think it's just easier. Honestly, I don't know, Okay,
Speaker 8: but because.
Speaker 1: They survive this, right, They need you to mount an
Speaker 1: immune response.
Speaker 8: They do. They do. After that, though, we need to
Speaker 8: get the blood out to get the antibodies. I'm not
Speaker 8: sure how much. I don't want to. I shouldn't speak
Speaker 8: for their industry, but I don't know that it's great?
Speaker 1: Got it? Okay?
Speaker 3: And do antibodies developed by sheep always work for humans?
Speaker 3: Is it transfer that way? I was reading about this
Speaker 3: crazy guy who like injects himself with venoms to develop antibodies.
Speaker 8: Right, So this guy's he's great. I mean, I don't
Speaker 8: know that great, but he's insane. Right, So a human
Speaker 8: antibody is way better for humans because we don't have
Speaker 8: the same allergic reaction to having a foreign body foreign
Speaker 8: antibody being used. So if we can develop human based
Speaker 8: antibodies as the best, and there are people doing that,
Speaker 8: and there's someone that's they've been doing that recently for
Speaker 8: our neurotoxin that cobras have, and they've done it against
Speaker 8: a synthetic library of human antibodies.
Speaker 3: But that means injecting a human with steak venom intentionally, right.
Speaker 8: In this case, it's actually just taking a library, like
Speaker 8: a library of antibodies. So that's not in a human
Speaker 8: but it's rather you know, in a tube essentially, and
Speaker 8: then testing to see which ones are reactive or which
Speaker 8: ones can bind, and then using those specifically as therapeutics
Speaker 8: or treatments. And so those might be much that are
Speaker 8: you know. The other issue is here that we're I
Speaker 8: talked about a cocktail of proteins, right, and we actually
Speaker 8: as much as we know that the different kinds of
Speaker 8: actions that the different kinds of toxins can do, we
Speaker 8: don't really know what contributes the most to like a fatality.
Speaker 8: We don't really know like specifically, is it all of
Speaker 8: them are needed or are some of them? So some
Speaker 8: of these like and when you throw a bunch of
Speaker 8: snake venoms in there and you put a bunch of
Speaker 8: antibodies against all of them, or you hope that you're
Speaker 8: gathering all of them, you don't know exactly what you're
Speaker 8: stopping or blocking. And so I think some people are
Speaker 8: now trying to like specifically target a few proteins alone
Speaker 8: and say like maybe this is the worst one and
Speaker 8: this is the one we should stop.
Speaker 3: But the best antivenom comes from humans, which is why
Speaker 3: we're so ingratiated to Tim Freed who's injected himself more
Speaker 3: than seven hundred times voluntarily with venom to develop an
Speaker 3: unparalleled snake anti venom. That's amazing, thank you too.
Speaker 1: But that's not going to be sustainable for an industry.
Speaker 8: It's not very sustainable. I mean, I don't know all
Speaker 8: what's planned with it. But while that might be good,
Speaker 8: it's I think there will be other methods too, and
Speaker 8: I think there are some. There's some work now with
Speaker 8: what are called nanobodies, and so this is if you
Speaker 8: inject lamas and alpacas or they have a slightly different
Speaker 8: immune system, like the antibodies that they generators are different
Speaker 8: enough that they can be essentially broken up so that
Speaker 8: they take away the animal, like the law of specific part,
Speaker 8: and so they might be able to function without these
Speaker 8: same kind of allergic reactions as side effects that are possible.
Speaker 8: So there's some of that, And then I think there's
Speaker 8: also some people trying to develop like just small molecule inhibitors,
Speaker 8: things that are just like you can generate as a
Speaker 8: chemical and then and maybe give that to people. And
Speaker 8: so those are the kind of things that might be
Speaker 8: even better because especially when we're talking about like snakebite
Speaker 8: as a health issue. It is the biggest issue and
Speaker 8: the main reason why so many people are dying injured
Speaker 8: is they just have no access to medical care or
Speaker 8: it's so delayed that by the time they're given it
Speaker 8: it's too late. And part of that is like those
Speaker 8: there's rural hospitals don't have the DNIM stocked and all
Speaker 8: this other stuff. And if we can come up with
Speaker 8: things that are that you might take into the field
Speaker 8: with you, or things that you don't have to be refrigerated,
Speaker 8: that's like the real goal, the real then you can
Speaker 8: really save you know, a million lives a year or whatever,
Speaker 8: or one hundred thousand lives a year.
Speaker 3: Well, if you think that an anti venom industry based
Speaker 3: on one guy named him is impractical, here's an idea
Speaker 3: for you. What if you made snakes out of anti matter,
Speaker 3: so you have anti snakes and their venom is anti venom.
Speaker 3: Can't you just use that as anti venom?
Speaker 8: Amazing? Wow, because I suspect you could keep an anti
Speaker 8: snake with you.
Speaker 6: At all times.
Speaker 8: And then you have like a little pan anti snake
Speaker 8: and you ever get bit, you can just have the
Speaker 8: anti snake bite you.
Speaker 3: If your anti snake in some sort of magnetic bottle.
Speaker 3: I mean, I just come up with the ideas. The
Speaker 3: engineers need to figure.
Speaker 8: It out, right, I think it's that's that Part's the
Speaker 8: easy part.
Speaker 1: This is why we need integrative research projects.
Speaker 3: Yes, exactly, cross disciplinary ideas. You can see how useful
Speaker 3: they are.
Speaker 1: Every biology project needs a physicist and vice versa.
Speaker 3: So then let's get to the actual question of the episode.
Speaker 3: Now that we have some understanding of snakes and venoms,
Speaker 3: if a rattlesnake bid an octopus, would its venom have
Speaker 3: any effect?
Speaker 8: First of all, this is like one of the greatest
Speaker 8: questions you could ever ask.
Speaker 3: And imagine a scenario where this happens.
Speaker 8: Yeah, I'm already it's just amazing.
Speaker 3: Snake's on a plane and crashes in the ocean. I
Speaker 3: don't know, dot.
Speaker 8: Dot dot, man, I really got to figure this out.
Speaker 8: This is important.
Speaker 3: Are you saying this is not currently the top question
Speaker 3: in snake venom science?
Speaker 8: But that's a failure of top venom science and not
Speaker 8: a failure anymore. So, uh, to try to get at
Speaker 8: this question, I can't really know. But if we think
Speaker 8: about those viper venoms that are designed around sort of
Speaker 8: mammalian blood systems, and disrupting clotting or causing it those
Speaker 8: hemorrhagic type venoms. You know, you might, you might. Octopus
Speaker 8: doesn't really have the same kind of clotting systems, but
Speaker 8: they do have cells that are still made of like
Speaker 8: thame kind of membranes that these venoms do target. So
Speaker 8: I suspect it could still do quite a bit of
Speaker 8: damage and probably just really disrupt those tissues. Octopuses, of course,
Speaker 8: can kind of some of them can grow their limbs back,
Speaker 8: so they may not actually care too much.
Speaker 3: Amazing.
Speaker 8: That might be one thing that as far as the
Speaker 8: neurotoxic snakes, you know, these are still they still have
Speaker 8: muscles and that still have you know, neurotoxin. You know,
Speaker 8: they have receptors on them that these neurotoxins could target.
Speaker 8: Now they certainly haven't evolved to do that or you know,
Speaker 8: and this is definitely outside of the sort of outside
Speaker 8: of mammals, let's say, mammals and reptiles that most snakes
Speaker 8: are eating. Let's say, so all bets are sort of
Speaker 8: off on how effective it would actually be, But there's
Speaker 8: reasons I think that even these venoms would still be
Speaker 8: pretty damaging to an octopus amazing.
Speaker 3: So you wouldn't recommend to an octopus to get bitten
Speaker 3: by reddle snake.
Speaker 8: I wouldn't, But I mean, honestly, an octopus with all
Speaker 8: those eight tentacles and the snake, I don't know how
Speaker 8: that's hot dog. It's a picture I to have is
Speaker 8: a is a marshmallow surrounding an octopus hot dog, And
Speaker 8: I don't know. I don't know what the snake could.
Speaker 3: Do Australian OCTOPI probably shrugged off.
Speaker 1: Yeah, there are some venomous sea snakes right.
Speaker 8: There are yes, So there are a lapids that are
Speaker 8: especially come off the coast of Australia, and those things
Speaker 8: are super deadly, primarily because they're in the ocean and
Speaker 8: they're just they mostly hunt fish. But this is the
Speaker 8: closest we're gonna get to, like if this thing is
Speaker 8: happening in real life.
Speaker 1: Okay, So I.
Speaker 8: Mean, you know, when I was a kid, it was
Speaker 8: the giant squid and the and the sperm whale and
Speaker 8: like no one had ever seen the battle. So I
Speaker 8: think this is really on par with that. Whales also
Speaker 8: lost their legs, So I feel like we're really kind
Speaker 8: of into this, likeliss animals versus squids and octopies.
Speaker 1: I think we got to try to sell the movie
Speaker 1: rates pretty good.
Speaker 3: And also we should add a qualifier. Matt is not
Speaker 3: an octopus doctor, So if you're an octopus and you're listening,
Speaker 3: don't take his advice as medical advice.
Speaker 8: Just chop off one of your legs and craw it back.
Speaker 3: Not medical advice. People don't listen to him seriously.
Speaker 1: The listener also sent us an extended question and wanted
Speaker 1: to know. So we already established that like if a
Speaker 1: diamondback rattlesnake bit another diamondback rattlesnake or bit itself, it
Speaker 1: would probably be fine. But what if like a diamondback
Speaker 1: rattlesnake bit a cobra or a cobra bit a diamondback rattlesnake,
Speaker 1: what would happen?
Speaker 10: Then?
Speaker 8: This is a great question. I suspect that if we
Speaker 8: go between a lappas and vipers, we might see that
Speaker 8: they don't have the same kind of resistance to that patom.
Speaker 3: Yeah.
Speaker 8: The one that I'm not sure about is that so
Speaker 8: the king cobra, it's called a king because it eats
Speaker 8: other snakes and it probably so I actould really know
Speaker 8: this but it probably has. It probably could have some
Speaker 8: resistance to other vipers that it could be eating.
Speaker 3: You're totally going to do this experiment this afternoon, aren't you.
Speaker 8: Yeah. I do have a few in the back, so
Speaker 8: I will just make sure I throw them together and
Speaker 8: see what happens.
Speaker 1: You need an eye of cook for that.
Speaker 8: But even within rattlesnakes, we don't know, you know, within
Speaker 8: within rattlesnakes biting each other, I think the further they
Speaker 8: are apart from each other evolutionarily, it's possible that they
Speaker 8: won't have that same resistance. And there are some rattlesnakes
Speaker 8: that are have neurotoxic venoms, and so how those two
Speaker 8: would react with each other, I don't know.
Speaker 1: I'd like to say that I think it's probably good
Speaker 1: we don't have the answers to some of these, because
Speaker 1: it suggests perhaps a lack of ethics that we've like,
Speaker 1: you know, thrown snakes together and been like what happens? Now, Like,
Speaker 1: I'm kind of glad we don't know.
Speaker 8: It's probably the best now.
Speaker 3: Yeah, So within ethical guidelines, what kind of questions are
Speaker 3: being investigated at the cutting edge of snake venom science?
Speaker 3: What are the big arguments at the Snake Venom conferences
Speaker 3: all about.
Speaker 8: I think that, well, there's let's see.
Speaker 3: And is this a nice community or is it toxic?
Speaker 8: I don't even think I can respond to that. I
Speaker 8: think the stake community is quite nice. It can be. Uh,
Speaker 8: there's a lot of collaboration that I see out there.
Speaker 8: These many snakes scientists and snake scidists. Many of these
Speaker 8: guys are true herpetologists. So these are the guys that
Speaker 8: do really love to get the snake hook out and
Speaker 8: pick them up and show pictures of themselves holding sakes,
Speaker 8: which I cannot do I will not do. But there
Speaker 8: is a lot that's into So there's a lot of
Speaker 8: the snake world that is into the populations of snakes
Speaker 8: and how they move and react and tracing the evolutionary
Speaker 8: history of those snakes. So there's a lot of I
Speaker 8: think in today's world, there's a lot of genomics has
Speaker 8: become a lot easier to use to study variation and
Speaker 8: distribution of animals, and in the sake world that's so different,
Speaker 8: and so there's a lot of work that's breaking down
Speaker 8: these genomes and then trying to compare them across different
Speaker 8: snake lineages and and try to learn the history of
Speaker 8: those snakes and where they've come from. And then with
Speaker 8: respect to venom, then there's always like cases of you know,
Speaker 8: trying to understand where venoms are coming from, and it
Speaker 8: just there's so many ones you could study. So there's
Speaker 8: a number of different lineages or lines of you know,
Speaker 8: studying different venoms.
Speaker 1: And so I want to know. My last questions are,
Speaker 1: as a like rattlesnake venom person, what question do you
Speaker 1: get asked most often? And what is the most common
Speaker 1: misconception you encounter?
Speaker 8: Yes, so I most often am asked if I ever
Speaker 8: get to hold the snakes or carter touch.
Speaker 1: But that's where I started.
Speaker 8: Yeah, it's what everybody wants to it's but it's the
Speaker 8: right question because you if you talk to like my
Speaker 8: I have a coworker who is very much the guy like,
Speaker 8: oh yeah, oh absolutely, And we have a big debate
Speaker 8: because I like to I like to toeut vipers as
Speaker 8: the better venom bet a snake, and he is a
Speaker 8: big a lapet friend. And part of that has to
Speaker 8: do with the joy of holding in the lap which
Speaker 8: I'm like, fine, he could do that.
Speaker 1: OK.
Speaker 8: So that's that's one of those things that that's always asked,
Speaker 8: of course, and then and then a lot of like
Speaker 8: you know, what is what is venom? Or what does
Speaker 8: it do to you? Those kind of questions are great
Speaker 8: in terms of misconceptions. I think generally speaking, they're the
Speaker 8: idea that I mean, if you watch any kind of
Speaker 8: movie about with snakes in it is often somehow incorrect.
Speaker 8: And they're hunting. They're usually like looking for humans and
Speaker 8: trying to bite them. And of course snakes are really
Speaker 8: gentle and they're really fearful. They just are trying to hide.
Speaker 8: They just want to be basking in the sun. But
Speaker 8: they react to pray that the predators that are things
Speaker 8: that they perceived as predators, and so oftentimes they get
Speaker 8: perceived as a danger when there they may not be,
Speaker 8: and they just need to be moved away or sort
Speaker 8: of gently encouraged to not do not to sit where
Speaker 8: they are sitting.
Speaker 3: The poor misunderstood venomous snake.
Speaker 8: Yep, yes, I like snakes.
Speaker 3: Well, then let me ask you my favorite question, which is,
Speaker 3: you are landing on an alien planet on which you
Speaker 3: think there's probably life, do you expect there to be snakes?
Speaker 3: Do you expect there to be venom? How universal do
Speaker 3: you think this is across the universe?
Speaker 8: Well, snakes like as a you know, as a tube,
Speaker 8: like worms. I think a tube is a really great
Speaker 8: simple body system. So the stakes obviously came from a
Speaker 8: more complex evolutionary history of having atlantic legs and having
Speaker 8: used to swim in the sea, and now they're walking
Speaker 8: on land, and now they lost the legs, and now
Speaker 8: they're crawling on the dirt into the sea again. So
Speaker 8: they've done all kinds of stuff. And so tubes I
Speaker 8: think are really probably pretty cool systems we'll see in
Speaker 8: any on any alien planet.
Speaker 3: But you're not giving up your legs, right, you know,
Speaker 3: becoming tubular.
Speaker 8: I prefer my legs, you know, so I'll keep them
Speaker 8: for now. But you know, whales did great things without them,
Speaker 8: and so have snakes.
Speaker 3: A big fan of whales work.
Speaker 8: Yeah, yeah, neat everyone should be.
Speaker 3: So you think there probably are tubular animals on alien planets.
Speaker 8: It just seems like a very easy body system, right,
Speaker 8: So essentially all we are tubes with just ornamentation, right,
Speaker 8: you know, all animals essentially are just a tube from
Speaker 8: mouth to butt or whatever you say here and then
Speaker 8: and and we just do we just decorate it with
Speaker 8: different kinds of legs and pinchers or other teeth or
Speaker 8: whatever you want. But like it's all just basically a
Speaker 8: tube to get food through and uh and reproduced.
Speaker 3: So if you meet a biologist in your life, folks,
Speaker 3: they are thinking about you as an ornamented mouth to
Speaker 3: butt tube.
Speaker 8: Yep, that's exactly what you are.
Speaker 3: That tells me glory about how biologists see the world.
Speaker 1: I think of you as a parasite host, So it
Speaker 1: depends on the biology.
Speaker 8: Yeah, and so many parasites are just a little worms,
Speaker 8: So they're a little tubes.
Speaker 1: That's a good point. That's a good point. But do
Speaker 1: you think that those tubes are going to be venomous?
Speaker 8: I mean, look, venom, it seems to be a system
Speaker 8: that works in a lot of different animal systems. If
Speaker 8: you can use chemicals as a defense system, great, And
Speaker 8: if you need to bite into something or if you're
Speaker 8: tussling with something and you need to poke it and
Speaker 8: make it stop, then venom's a really great system. So
Speaker 8: I would expect that you would see, you know, venom
Speaker 8: kind of anywhere you see conflict between animals.
Speaker 1: Well, I have learned a lot about snake venom and
Speaker 1: a lot about ways to cook hot dogs and I
Speaker 1: will never see a human the same way again.
Speaker 8: Good So thank you.
Speaker 1: So much MATD for being on the show. This was fantastic.
Speaker 8: It's my absolute pleasure. Thank you guys.
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