Speaker 1: Hi, I'm Aaron Welsh, and this is this podcast will
Speaker 1: Kill You. You are listening to the latest and last, for
Speaker 1: now bonus episode in our mini series of bonus episodes
Speaker 1: that have been coming out over the last several months.
Speaker 1: I've had such a great time putting these episodes together,
Speaker 1: and I've learned so very much along the way. I'd
Speaker 1: love to pick up this series again in the future,
Speaker 1: so let's just consider this a break for now. If
Speaker 1: this is your first time tuning into one of these
Speaker 1: bonus episodes, I'll give a brief explanation of what they're
Speaker 1: all about. And if this is not your first time,
Speaker 1: then I'm sorry that you've had to hear this intro
Speaker 1: over and over again. In these bonus episodes, I'm taking
Speaker 1: some aspect of the topic we discussed in our previous
Speaker 1: week's regular season episode and bringing on an expert guest
Speaker 1: to help me investigate this subject in more depth. For instance,
Speaker 1: my guests and I have gone further down the rabbit
Speaker 1: hole of mixed andmatosis by following up with an episode
Speaker 1: on rabbit heemorrhagic disease virus. We've explored in more detail
Speaker 1: how electricity actually works, and we've re examined the origins
Speaker 1: of epidemiology. I'm also rounding out many of these discussions
Speaker 1: by asking my expert guest about their own journey into science,
Speaker 1: what they like about it and what they don't, and
Speaker 1: any advice they may have for people interested in pursuing
Speaker 1: a career in this field. And this week, I'm especially
Speaker 1: excited to learn more about the absolutely fascinating world of
Speaker 1: snake venoms. In our regular season episode last week, Aaron
Speaker 1: and I covered the different groups of venoms that some
Speaker 1: snakes produce and what happens to your body if you
Speaker 1: are unfortunate enough to be at the receiving end of
Speaker 1: a bite from a venomous snake. If you haven't listened
Speaker 1: to that episode yet, I recommend that you go back
Speaker 1: and listen to it before continuing on here, since that
Speaker 1: will provide some good background information on what's actually in
Speaker 1: these venoms and how they work, which turns out to
Speaker 1: be a pretty complicated subject, too complicated even for me
Speaker 1: to begin to scratch the surface of the different types
Speaker 1: of venoms in a recap here. But in addition to
Speaker 1: talking about the action of these different venoms, as well
Speaker 1: as the significance of snake bites as a neglected tropical disease.
Speaker 1: We also spent some time talking about how snakes may
Speaker 1: have played a role in primate evolution, specifically in the
Speaker 1: evolution of our visual systems. What we didn't discuss, however,
Speaker 1: was the big question of venom evolution. So many snakes
Speaker 1: and other animals have evolved the ability to use venom,
Speaker 1: and the resulting diversity of venoms is simply astounding, which
Speaker 1: is why for this bonus episode, I really wanted to
Speaker 1: take the time to dig into how these venoms evolved
Speaker 1: in the first place, why there is such diversity across
Speaker 1: venom type and function, and what happens when venoms evolve
Speaker 1: as a defense mechanism rather than as an aid and predation.
Speaker 1: And I'm absolutely thrilled to have one of the world's
Speaker 1: leading experts on venom evolution as my guide, Professor Nick Casewell.
Speaker 1: And with that, I think we'll just take a quick
Speaker 1: break here before diving in.
Speaker 2: My name is Nick Casewell. I'm a professor of Tropical
Speaker 2: disease biology at the Liverpool School of Tropical Medicine and
Speaker 2: I'm the director for the Center for Snake Bite Research
Speaker 2: and Interventions. This is a research group at LSTM, where
Speaker 2: we essentially study snake bite and try and develop new
Speaker 2: interventions to improve the lives and livelihoods of snake bite victims.
Speaker 1: Awesome, thank you so very much for joining me today.
Speaker 2: It's a real pleasure. Thanks for the invitation to talk
Speaker 2: snake venom and snake bite with you.
Speaker 1: Of course, I am so excited to learn more about
Speaker 1: these fascinating compounds. And so can you start us off
Speaker 1: by talking about exactly that, like, what do we know
Speaker 1: about the earliest emergence of venomous snakes and what is
Speaker 1: the about why this trait emerged when it did.
Speaker 2: So we start on a really tricky subject really in
Speaker 2: terms of we know lots about what's in the venom
Speaker 2: of snakes today, and actually we don't know all that
Speaker 2: much about the whys and the wares venom evolved in
Speaker 2: snakes and in fact, in many venomous animals. So what
Speaker 2: we do know is that venom evolved in snakes on
Speaker 2: one occasion. So all these venomous snakes we find today
Speaker 2: are all related to one another, and their venom systems
Speaker 2: are related to one another as well. And this probably happened, well,
Speaker 2: it certainly happened at least forty to fifty million years ago,
Speaker 2: so it's a relatively old trait and it may go
Speaker 2: back even further than that, But we don't know for sure,
Speaker 2: and we don't know why only this group of snakes
Speaker 2: have evolved a venom system compared to others. But what
Speaker 2: we do know today looking at snakes is that although
Speaker 2: those venom systems are effectively the same, or they evolve
Speaker 2: from the same common ancestor, they're actually rereadibly different. The
Speaker 2: toxins that you find in the venoms of these different
Speaker 2: snakes are very different. And the effects that these venoms
Speaker 2: have on a prey item they're trying to kill or immobilize,
Speaker 2: or on someone who's bitten by one of these snakes
Speaker 2: can be really really different depending on which snake you're
Speaker 2: bitten by.
Speaker 1: What are some of the drivers for this diversity? What
Speaker 1: is thought about that?
Speaker 2: So we think the primary reason that snakes ultimately evolve venom,
Speaker 2: and the primary driver that's kind of honing the competitions
Speaker 2: of venom we see today is for predation. So snakes
Speaker 2: are primarily using their venom systems to catch prey, to
Speaker 2: help them to catch prey, and if you think about
Speaker 2: a snake, it's pretty obvious why that might be right.
Speaker 2: These are limbless animals. They don't have claws or arms
Speaker 2: or legs to help them to catture their prey. All
Speaker 2: snakes are predators. They're all eating other animals. And what's
Speaker 2: interesting is that while some snakes use things like constrictions,
Speaker 2: so they wrap body coils around prey to immobilize them,
Speaker 2: many snakes have taken a different strategy, which is the
Speaker 2: use of a chemical weapon, which is injected into the
Speaker 2: prey and ultimately has the same effect. It immobilizes that animal,
Speaker 2: or it kills the animal, or in some way just
Speaker 2: enables the snake to actually feed on it relatively unharmed.
Speaker 2: So we know that the venom is really crucial for
Speaker 2: these snakes to catch their prey. Snakes can use their
Speaker 2: venom defensively too, but this is not the primary purpose.
Speaker 2: And the reason we think that is because there's been
Speaker 2: a number of scientific studies done over many years that
Speaker 2: show that there are associations between, for example, the potency
Speaker 2: of venom and the diet of that particular snake species.
Speaker 2: So you can start to see associations whereby certain snakes
Speaker 2: that feed predominantly on one type of animal, have venom
Speaker 2: toxins that are honed towards that particular prey type or
Speaker 2: even specific to that particular prey type. We also see
Speaker 2: evidence in some species where venom is no longer being
Speaker 2: used that venom system has started to degrade or disappear.
Speaker 2: So in c snakes, for example, that feed on fish eggs,
Speaker 2: they don't need venom to catch their fish egg prey anymore,
Speaker 2: and we actually see that the toxins in their venom
Speaker 2: have begun to degenerate, so they're not functionally intact anymore.
Speaker 2: They're not functionally active. And also the venom glands in
Speaker 2: the snakes themselves start to reduce in size too, so
Speaker 2: they did trophy. So there's this clear association between diet
Speaker 2: and venom itself. It may not be the only factor.
Speaker 2: There may be other things that come into play that
Speaker 2: may hone that final composition of venom, but without doubt,
Speaker 2: we think that the prey is the key thing that
Speaker 2: has driven venom evolution in snakes.
Speaker 1: In terms of the types of venoms that we see,
Speaker 1: you know, we have these neurotoxic or cytotoxic venoms. Is
Speaker 1: there any association between the type of prey you know,
Speaker 1: whether it's fast moving dents or something else, you know,
Speaker 1: and the actual type of composition of the venoms among
Speaker 1: different snakes or is that just sort of like an
Speaker 1: accident of evolution.
Speaker 2: Yeah, more the latter than the former. So there are
Speaker 2: lots of different kind of classes of venom, toxins and
Speaker 2: what they do. And there are different groups of venomous
Speaker 2: snakes as well. So the most famous ones we think
Speaker 2: of from a human context of vipers and a lapids.
Speaker 2: These are the two most medically important group of snakes
Speaker 2: to people. There are types of snakes that can put
Speaker 2: us in hospital and killers, and broadly speaking, they have
Speaker 2: quite different venoms with lapid snakes, so these are things
Speaker 2: like cobras or coral snakes or mambers. They typically have
Speaker 2: a neurotoxic venom that causes your nerves to be paralyzed
Speaker 2: and this causes particular issues when you're breathing, muscles ultimately
Speaker 2: stop working. Their venom is quite different to viper venoms.
Speaker 2: So with vipers, we're talking about things like rattle snakes,
Speaker 2: puff adders, Russell's vipers. These venoms broadly are hematoxic venoms.
Speaker 2: They have toxins in there that are causing damage to
Speaker 2: blood vessels. They're causing people to bleed internally or prey
Speaker 2: to bleed to cause strokes. And these two did very
Speaker 2: different groups of snakes ultimately are feeding on similar prey.
Speaker 2: So you know, some might be mammal specialists within a lapids,
Speaker 2: some might be mammal specialists within vipers. Some might have
Speaker 2: broad diets within lapids, some might have broad diets within
Speaker 2: the vipers. That kind of hemotoxicity versus neurotoxicity, Both those
Speaker 2: strategies are really great at killing prey quickly. Either you
Speaker 2: paralyze the prey or you cause it to have a stroke.
Speaker 2: Both strategies work equally well. And so although we do
Speaker 2: see some examples where certain snakes have very prey specific venom,
Speaker 2: it's not that this group of snakes only feed on mammals.
Speaker 2: They must have a neurotoxin. This group of snakes only
Speaker 2: feed on reptiles, they must have a blood acting venom.
Speaker 2: It's not quite as simple as that. So we see
Speaker 2: a lot of variation within those different groups. And I
Speaker 2: suppose there are a number of ways that a snake
Speaker 2: can rapidly kill its prey no matter what that prey is,
Speaker 2: and ultimately those snake families diversified many millions of years ago,
Speaker 2: when one snake family, the lapids, has evolved neurotoxins and
Speaker 2: really increased the abundance of neurotoxins in its venom, whereas
Speaker 2: the vipers have gone down a hemotoxin rout and they've
Speaker 2: really increased the abundance of those hemotoxins, and that's what's
Speaker 2: dictated those different kind of venom pathologies.
Speaker 1: So earlier you talked about sea snakes having slowly lost
Speaker 1: or losing their ability to produce venom or deliver venom
Speaker 1: because they don't use it as much, meaning that venom
Speaker 1: is probably a fairly costly thing to produce and maintain
Speaker 1: as a tree. And there's this thing I want to
Speaker 1: mention that's sort of in line with that, the economy
Speaker 1: of venom in the overkill hypothesis, where it seems like
Speaker 1: the deadliness or the toxicity of venom is much much
Speaker 1: greater than would actually be needed to kill a particular prey.
Speaker 1: Can you talk about why this may not fully capture
Speaker 1: the relationship between venom of snakes and their prey.
Speaker 2: Yeah, absolutely, so. This overkill hypothesis proposes that because snake
Speaker 2: venoms are so toxic, and because snakes, well, certain snakes,
Speaker 2: we are able to inject a lot of venom when
Speaker 2: they bite. When you kind of extrapolate that, you know,
Speaker 2: certain toxicity at a certain amount scale to how much
Speaker 2: they actually inject, it seems that for many snakes they're
Speaker 2: just they just have way more venom than they would
Speaker 2: actually need. And therefore, this idea that venoms are honed
Speaker 2: towards certain prey doesn't really hold, because no matter what
Speaker 2: the prey is, their venom is going to be sufficiently
Speaker 2: toxic to kill it. But this is quite a simplified view, really,
Speaker 2: because the toxicity of snake venoms is often modeled just
Speaker 2: basically in terms of their toxicity to laboratory animals. Usually
Speaker 2: this will have historically been lab mice, and these snakes
Speaker 2: aren't feeding on lab mice in the wild, and we
Speaker 2: know that from lots of different species. There's quite compelling
Speaker 2: evidence that prey items and on a predators have evolved
Speaker 2: at least some degree of resistance to many snake venoms.
Speaker 2: So to simply say that because a lot of venoms injected,
Speaker 2: you know, these snakes all kind of wasting their venom
Speaker 2: is simply not true. There's a lot of different prey
Speaker 2: out of there that have mechanisms that have enabled them
Speaker 2: to evolve resistance to snake venom, and we suspect probably
Speaker 2: that snake venoms are also responding and evolving further in
Speaker 2: response to that resistance. You have this kind of arms
Speaker 2: race between prey and predator in terms of the potency
Speaker 2: of the venom. And we also know that from a
Speaker 2: few studies at least, that there seems to be some
Speaker 2: evidence that snakes can meet to the amount of venom
Speaker 2: they might inject, and so certainly snakes will not use
Speaker 2: all of the venom they have in one bite. They
Speaker 2: may bite multiple times. But also lots of feeding attempts
Speaker 2: from snakes are unsuccessful, and so they need to retain
Speaker 2: enough venom to then go on and try and feed
Speaker 2: on the next prey item too. So we know snake
Speaker 2: venoms are toxic, but ultimately a lot of that extrapolation
Speaker 2: has been based on an artificial scenario. These snakes are
Speaker 2: not feeding on lab mice in the wild, and there
Speaker 2: are studies that have shown that certain snake venoms it
Speaker 2: may take, for example, half an hour to kill a
Speaker 2: scorpion which might be a natural prey. And clearly if
Speaker 2: these venoms were super toxic and overloading prey with a
Speaker 2: huge amount of venom, it would take much less time
Speaker 2: than that.
Speaker 1: So you mentioned arms races. So can we now kind
Speaker 1: of shift to talking about venom as a defense mechanism
Speaker 1: and sort of some of the ideas about spitting cobras.
Speaker 1: Why is venom spitting so unique and what are some
Speaker 1: of the drivers for its evolution.
Speaker 2: Yeah, venom spitting is a really interesting one because you know,
Speaker 2: we talked already about why venoms have evolved in snakes,
Speaker 2: and it's for predatory purposes, and there doesn't seem to
Speaker 2: be much evidence really that venom composition is evolving secondarily
Speaker 2: for defense, although snakes will use their venom defensively, right,
Speaker 2: every human snake bite that happens many millions every year,
Speaker 2: These are defensive snake bites. The snakes aren't trying to
Speaker 2: eat us. But there's actually very little evidence that the
Speaker 2: composition of venom is evolving in response to the use
Speaker 2: of that venom defensively, except with the spitting cobras. So,
Speaker 2: the spitting cobras are this one group of pretty closely
Speaker 2: related lapid snakes. So these are very highly venomous snakes.
Speaker 2: And within this group, on three independent occasions, we see
Speaker 2: the evolution of venom spitting. So this is the ability
Speaker 2: of these snakes to eject their venom in a stream
Speaker 2: of liquid from them mouth, directly targeting the eyes of
Speaker 2: a predator or aggressor over a couple of meters. So
Speaker 2: it's a really effective way. And what that venom does
Speaker 2: when it hits the eye or the area around the
Speaker 2: eyes is it causes extreme pain. And so this is
Speaker 2: a really nice strategy to deter a potential aggressor or
Speaker 2: a predator from eating you. It's by causing pain and
Speaker 2: to be left alone. But what's interesting here is that
Speaker 2: we find that there is some evidence that the venom
Speaker 2: composition has also changed in response to the evolution of
Speaker 2: this venom spitting trait. And so this goes against everything
Speaker 2: I've said. This is the exception. There's always in biology
Speaker 2: there are exceptions. This is a perfect example. And each
Speaker 2: of these three groups of spitting cobras, so the African
Speaker 2: spitting cores, the agent spitting cobras, and also in a
Speaker 2: closely related cobra species called the wrinkles, they've all evolved
Speaker 2: to increase the abundance of a particular toxin which works
Speaker 2: together with another toxin to cause this pain enhance pain
Speaker 2: causing effect. And so it's likely we think that only
Speaker 2: spitting cobras have evolved the ability to spit because of
Speaker 2: a variety of these what we would call preadaptations, if
Speaker 2: you like. There are a few things that these snakes
Speaker 2: had to have before spitting could evolve. So one of
Speaker 2: them is this toxin that can kind of cause a
Speaker 2: bit of pain and then could be enhanced upon later on.
Speaker 2: And the other thing is this defensive behavioral posture that
Speaker 2: cobras have in that they can kind of raise the
Speaker 2: first third of their body up in the air, which
Speaker 2: gives them a very nice kind of position from which
Speaker 2: they can spit. If you imagine most snakes lying flat
Speaker 2: on the ground, and if they open their mouth to
Speaker 2: spit their venom, it's just going to go straight into
Speaker 2: the ground. So they have to be able to raise
Speaker 2: their body up, and so this is kind of a
Speaker 2: defensive behavior that cobras would already have done prior to
Speaker 2: the evolution of spitting. So probably those two things have
Speaker 2: enabled this particular group of snakes to evolve this special
Speaker 2: defensive adaptation that we don't see in any other venomous snakes,
Speaker 2: and so we think, we think possibly that the driver
Speaker 2: for having a specialized defensive use of the venom in
Speaker 2: cobras it may have been stimulated by our ancestors, so
Speaker 2: ancestral hominins which in Africa came out onto the planes,
Speaker 2: they were bipedal. And we know that certainly many primate
Speaker 2: species will defend themselves from snakes. They will actively identify
Speaker 2: them and mob them, throw stones at them, try and
Speaker 2: kill them. And we suspect that for cobras it may
Speaker 2: well have been an advantage for them to have a
Speaker 2: long distance defensive weapon that could protect themselves from from
Speaker 2: our ancestors. And indeed, we know that the timing of
Speaker 2: the origin of venom spitting in Africa in African cobras
Speaker 2: about fifteen million years ago, correlates quite nicely from when
Speaker 2: our ancestors diverge from chimpanzees. So this remains a speculative hypothesis,
Speaker 2: but it may well be that human ancestors may have
Speaker 2: shaped snake ancestor as many million years ago.
Speaker 1: In terms of trade offs, are there tradeoffs that we've
Speaker 1: observed in terms of you know, where a more prey
Speaker 1: specific venom could mean a less effective defense venom.
Speaker 2: Yeah, I would really like to know the answer to
Speaker 2: that question. I think it's a great question. So if
Speaker 2: I go back to the example of the spitting cobras here,
Speaker 2: there's clearly potential for a tradeoff, right because you have
Speaker 2: a venom that's working to dual purpose that the snakes
Speaker 2: is still using that venom to catch their prey, but
Speaker 2: we know that they've also evolved certain venom components that
Speaker 2: are increased in their abundance to help them defend themselves.
Speaker 2: And so you know, in theory there should be a
Speaker 2: trade off there with a reduction in terms of the
Speaker 2: content of other toxins. And I think ultimately we don't
Speaker 2: understand this yet. We don't understand to what extent in
Speaker 2: a natural prey capturing scenario the evolution of a toxin
Speaker 2: that's helping that snake to defend itself might have upon
Speaker 2: capturing a prey item. And what's quite interesting with many
Speaker 2: of these venom toxins is that they can be multifunctional.
Speaker 2: There are toxins that have evolved to enhance the pain
Speaker 2: causing ability of the venom if it hits the eye
Speaker 2: of you or me. Actually, when that toxin is injected
Speaker 2: into the prey item, it's almost certainly still going to
Speaker 2: be helping the snake catch the prey. And whether that's
Speaker 2: just by destroying cell membranes and letting the snake permeate
Speaker 2: further into the prey, or whether it's by having a
Speaker 2: much more specific effect, it's likely not to have any
Speaker 2: detrimental effect on the ability of that snake to catch
Speaker 2: the prey item. Ultimately, there are still destructive venoms, but
Speaker 2: we do know there has been a change. Again using
Speaker 2: this example, if you look at all non spitting cobras
Speaker 2: and most of lapid snakes, we've talked about what their
Speaker 2: venoms usually do, and it's to cause neurotoxicity. So if
Speaker 2: you're bitten in Africa by a non spitting cobra, an
Speaker 2: Egyptian cobra, or a cape cobra, you will suffer from
Speaker 2: neurotoxic effects. If you're bit of my spitting cobra, chances
Speaker 2: are you won't suffer any neurotoxicity at all, And in
Speaker 2: fact what's likely to happen is you're likely to have
Speaker 2: a local tissue damage around the BikeE sites, you're likely
Speaker 2: to have swelling, pain, maybe some blistering, and maybe some
Speaker 2: destruction of your flesh. You're unlikely to die, whereas from
Speaker 2: a neurotoxic bite the risk is much higher. So the
Speaker 2: evolution of defense has had a knock on effect in
Speaker 2: terms of venom composition and in terms of venom functionality
Speaker 2: for humans. But to what extent that applies to natural
Speaker 2: prey is a far more difficult question to answer because
Speaker 2: there's very little research that's been performed upon how these
Speaker 2: venoms actually are incapacitating or killing prey items in the wild.
Speaker 1: So we're talking about some very complex things, right, complex behaviors,
Speaker 1: complex venoms themselves are incredibly complex. Can you walk us
Speaker 1: through how venom evolution happened in a genetic sense, or
Speaker 1: may have happened in a genetic sense. A non venomous
Speaker 1: snake didn't turn venomous overnight, So what might that process
Speaker 1: have looked like?
Speaker 2: Yeah? Absolutely right. So we're talking here about timescales of
Speaker 2: you know, forty to fifty million years from at least
Speaker 2: from the earliest inception of venom, if you like, in
Speaker 2: a snake ancestor to modern day snakes today. But in principle,
Speaker 2: we do understand at least some of the bases for
Speaker 2: how this may have happened. So venom glands are essentially
Speaker 2: modified salivary glands, the same as you or I have
Speaker 2: in our mouths, and these salivary glands produce proteins that
Speaker 2: are used for different purposes for us, that used to
Speaker 2: help digest our food, for example, And we believe that
Speaker 2: on many occasions snakes may have repurposed some of the
Speaker 2: protein that were being expressed in these salivary glands to
Speaker 2: turn them into kind of incipient or primitive venom toxins.
Speaker 2: And that doesn't mean that these proteins were only present
Speaker 2: in the slavary glands. There's quite good evidence that the
Speaker 2: kinds of toxins that evolt there are present today have
Speaker 2: evolved from proteins that are either expressed at low levels
Speaker 2: in lots of our different internal tissue, so whether that's
Speaker 2: the heart or the pancreas, lungs, wherever it might be.
Speaker 2: But there are certain examples. So there's a protein in
Speaker 2: our saliva called calikreine. This is a syriene protease, and
Speaker 2: this protein, amongst many of its rules, one of the
Speaker 2: things that it does is it drops your blood pressure,
Speaker 2: so it helps to reduce blood pressure. And we know
Speaker 2: that that calakrine protein is related to caliqreines that are
Speaker 2: found in snakes, that are toxins now found in snake
Speaker 2: vent And so what we think happened was that in
Speaker 2: early venomus snakes there were handful at least of these
Speaker 2: kind of incipient proteins that are probably doing a role
Speaker 2: that might be somewhat helpful to enable a snake to
Speaker 2: catch its prey. And then gradually, over a period of time,
Speaker 2: there's probably an increase in the abundance or the expression
Speaker 2: of these particular proteins to reinforce their use for capturing prey.
Speaker 2: And so in the case of caliquin, you can imagine
Speaker 2: a scenario whereby if you are using your saliva at
Speaker 2: that time soon to be venom to catch a prey item,
Speaker 2: having more of it might help because it might just
Speaker 2: reduce the blood pressure of an animal, which might just
Speaker 2: enable you to catch it slightly better than if it didn't.
Speaker 2: And so what we then see is that over those
Speaker 2: big time scales fifty million years, we see lots of
Speaker 2: changes to these kinds of toxins so as snakes diversified
Speaker 2: and split from one another, certain groups of snakes evolve
Speaker 2: new toxins or new protein types that became toxins of
Speaker 2: alve different types of toxins. So the example there is
Speaker 2: those lapid snakes having neurotoxins that we don't see in
Speaker 2: the vipers, and vipers having more hemotoxins that we don't
Speaker 2: see in the lapids. And one of the key things
Speaker 2: parts to this process that's ultimately generated the diversity we
Speaker 2: see in snake venoms today. So snake venoms can have
Speaker 2: anywhere from twenty to one hundred to two hundred different
Speaker 2: proteins in them. Now that's gone from a small number
Speaker 2: to a much larger number over those kind of forty
Speaker 2: to fifty million years. And one of the key processes
Speaker 2: that's underpinn that is gene duplication. So we know that
Speaker 2: the genes that are ultimately producing these proteins like this
Speaker 2: calikerine protein I mention, we know that in many venomous
Speaker 2: snakes those genes have been duplicated, and so instead of
Speaker 2: they're being just one of those calqarine genes in the genome,
Speaker 2: there might be two, or there might be three, or
Speaker 2: they might be four, or they might or they might
Speaker 2: be twenty or in actually some modern day snakes, we
Speaker 2: see more than twenty five isoforms related genes that produce
Speaker 2: related toxins within certain gene families, and that duplication process
Speaker 2: that certain toxins have been subjected to has seemingly been
Speaker 2: really important because it frees those genes up to evolve
Speaker 2: new functions. Ultimately, usually then snake venoms have evolved from
Speaker 2: these normal housekeeping proteins that are doing normal physiological roles,
Speaker 2: and they probably still are doing these normal physiological roles today,
Speaker 2: but following gene duplication, there are copies of those genes
Speaker 2: that are now free to do anything that enables that
Speaker 2: snake to better catch its pre and so we see,
Speaker 2: for example, with serium proteins as related to calaqrins, we
Speaker 2: know there are toxins that still cause hypotension. They're injected
Speaker 2: now they're venom toxins producing the venom gland. They cause
Speaker 2: hypotension much the same way as calqreins do. But there's
Speaker 2: other searing proteins that have evolved that chop up bits
Speaker 2: of your blood clotting proteins, for example, or that interact
Speaker 2: with platelets, or that do other functions that ultimately help
Speaker 2: those snake catch their prey. And so again, over those
Speaker 2: long evolutionary timescales, snakes have evolved a suite of toxins.
Speaker 2: They have multiple toxin families, and within those multiple toxin families,
Speaker 2: they have multiple toxins, lots of them doing different things
Speaker 2: and collectively having this really rapid and potent effect on
Speaker 2: their prey.
Speaker 1: It's easy to kind of group these things, group snakes
Speaker 1: into oh, well, these produce this type of toxin and
Speaker 1: this type of toxin, But there's so much diversity within that,
Speaker 1: even within a species, even within populations, where different populations
Speaker 1: of snakes can have different levels of certain toxins or
Speaker 1: different compositions of venoms, and we also see this, I think,
Speaker 1: in individuals within those populations. Why do these differences exist
Speaker 1: and what are some of the implications.
Speaker 2: You're absolutely right that the differences we see between venomus
Speaker 2: snakes can be really quite stark in terms of their
Speaker 2: toxin composition. And it's those processes, particularly that June duplication process,
Speaker 2: that give rise to that kind of substrate that then
Speaker 2: can be tinkered upon or varied between different snake species.
Speaker 2: But you make a really good point. This isn't just
Speaker 2: a variation from one species to the next. So although
Speaker 2: a cobra might have ten eurotoxins and two hemotoxins and
Speaker 2: a rattlesnake might have twelve heumotoxins and three cytotoxins and
Speaker 2: no neurotoxins, and that's the process that's generated that variation.
Speaker 2: But ultimately we see huge examples where there can be
Speaker 2: really extensive variation within species at the population level ontogenetically,
Speaker 2: so as an animal develops from being a juvenile to
Speaker 2: being an adult, we can see major shifts in venom
Speaker 2: composition in certain species, and also sexual differences between males
Speaker 2: and females have been reported too. So this variation in
Speaker 2: venom composition is ubiquitous across every level between snake families
Speaker 2: you know a lappas vipers, between species within those families,
Speaker 2: but also within a particular species, and the implications to
Speaker 2: that can be quite substantial. There are examples in the
Speaker 2: Southwest US, for example, where there is a rattlesnake species
Speaker 2: where you know from one place, if you're bitten by
Speaker 2: that snake, you'll have swelling and bleeding disturbances two hundred
Speaker 2: miles or two hundred kilometers, whichever you prefer, up the road,
Speaker 2: you know, you would have a neurotoxic syndrome. You wouldn't
Speaker 2: have that local swelling or hemotoxicity at all. So there's
Speaker 2: clear medical implications to this venom variation and how we
Speaker 2: go about actually preventing the pathology that those different snake
Speaker 2: venoms cause too. So I mean understanding venom variation, I
Speaker 2: think is one of the critical roles that the scientific
Speaker 2: community has to serve relating to snake bite because without
Speaker 2: that understanding, we can't make effective treatments for the populations
Speaker 2: you need it.
Speaker 1: Ultimately, of course, all snakes should be respected. But what
Speaker 1: factors determine which venomus snakes pose more of a risk
Speaker 1: than others? You know, are there things like urban versus
Speaker 1: rural propensity to strike, how much venom is typically delivered,
Speaker 1: potency of the venom, et cetera.
Speaker 2: Yeah, it's a really good question. This. I like teaching
Speaker 2: students about this as well, because you know, one of
Speaker 2: the things that we focus on around snakes or you know,
Speaker 2: if you watch any kind of nature documentary is which
Speaker 2: snake is the most deadly, Which has got the most
Speaker 2: toxic venom. And there's always this list list where I
Speaker 2: think like nine out of the top ten or maybe
Speaker 2: eight out of the top ten snakes are based in
Speaker 2: Australia that have the most toxic venom. But the reality
Speaker 2: is very very rarely do people die of snake bite
Speaker 2: in Australia, of course, and so are lots of factors
Speaker 2: that come into play here in the context of snake
Speaker 2: bite that makes a snake dangerous to a person or not.
Speaker 2: One of the key things that you alluded to, the
Speaker 2: potential for an interaction. So the inland taipan in Australia,
Speaker 2: in theory, has the most toxic venom to a lab
Speaker 2: mouse in the world based on previous studies. It lives
Speaker 2: in the middle of the outback. Almost no one interacts
Speaker 2: with that snake because there's no one in the outback
Speaker 2: and so bites thankfully are extremely rare. And compare that
Speaker 2: to a small snake called the sauce scale viper in
Speaker 2: West Africa. There's a snake about well up to a
Speaker 2: meter long. It's living in an environment where lots of
Speaker 2: people are working, so agricultural farmers, they're kind of working
Speaker 2: the earth with their hands or herdsmen. They're walking around
Speaker 2: better footed. These environments in savannah areas of West Africa
Speaker 2: are heavily populated by saurce scale vipers, so the potential
Speaker 2: for bites are really really high. Snake behaviors another factor.
Speaker 2: These surce scale vipers are sitting weight predators. They use
Speaker 2: camouflage to kind of protect themselves if you like, and
Speaker 2: so they won't move if they hear you coming, They'll
Speaker 2: just sit there. The inland tipan in Australia is a
Speaker 2: really active snake. It's using its senses to hunt its prey.
Speaker 2: It will detect you coming long before you will detect it,
Speaker 2: and so it will chances that are disappear before it
Speaker 2: you have the opportunity to see it. And then we've
Speaker 2: got the kind of the venom toxicity if you like.
Speaker 2: Venom toxicity is another factor that comes into this. Of
Speaker 2: course it does, but by and large, most venomous snakes
Speaker 2: have the most medically important venom. Snakes have the potential
Speaker 2: to cause you harm. Some may do it more rapidly
Speaker 2: than others, but I think the key thing here is
Speaker 2: the ability for the health infrastructure to protect you from
Speaker 2: the consequence of that bite. So in Australia, even if
Speaker 2: you're bitten in the outback, there is the flying doctor
Speaker 2: service that can get you to a health center that
Speaker 2: maybe thousands of miles away, and there is very specific
Speaker 2: anti venom that is very effective available in those hospitals
Speaker 2: to treat that bite. The same is not true in Africa.
Speaker 2: So you can be bittered by a source cal of
Speaker 2: that venom is much less toxic, and you might have
Speaker 2: much longer to live if you like, if the venom's
Speaker 2: acting less quickly than that of a type. But if
Speaker 2: it takes you a day to get to a health
Speaker 2: center and there's no antivenom then at that health center
Speaker 2: and you have to go on to the next place
Speaker 2: or the next place after that, then there is clearly
Speaker 2: going to be more possibility for a poor outcome for
Speaker 2: that patient. So the socioeconomics of the situation, most snake
Speaker 2: bite deaths are occurring in lower middle income countries. The
Speaker 2: health infrastructure and the availability of effective treatment is at least,
Speaker 2: if not much more important than the biology surrounding the snake.
Speaker 1: We are going to take a quick break here and
Speaker 1: when we get back, I want to hear all about
Speaker 1: you and your journey into snake venom research. Welcome back everyone.
Speaker 1: We have been having such a fascinating conversation about the
Speaker 1: world of snake venoms and snake venom evolution. But now
Speaker 1: I want to turn towards what it's like to actually
Speaker 1: study these snakes and how you got started in the
Speaker 1: first place. So what did you think about snakes growing up?
Speaker 1: How did you become involved with snake venom research?
Speaker 2: Yeah, so, I mean I always had a fascination with animals,
Speaker 2: I would say when I was growing up, and I yeah,
Speaker 2: I was always interested in animals. I didn't I necessarily
Speaker 2: have a specific fascination with snakes, I would say, but
Speaker 2: you know, I can remember, you know, being on holiday
Speaker 2: in France and seeing snakes in the wild, you know,
Speaker 2: just walking around, and you know, being really intrigued by them.
Speaker 2: I mean, it doesn't take much to look at a
Speaker 2: snake and to realize it's quite an unusual animal when
Speaker 2: you think of other vertebrates, right, they have these long,
Speaker 2: elongated bodies and no limbs, and I think there's something
Speaker 2: certainly about them that can can fascinate. Of course, often
Speaker 2: snakes can do the opposite, and people can be very
Speaker 2: fearful of them, but I think usually they provoke a
Speaker 2: response in a person. They certainly did with me. But
Speaker 2: really I kind of, in a way, I fell into
Speaker 2: snake bite. I studied zoology at the University of Liverpool
Speaker 2: and at that time I became quite interested in the
Speaker 2: interplay between animals and humans, but mostly from studying parasite
Speaker 2: interactions at that time, and that's what really then took
Speaker 2: me to the Liverpool School of Tropical Medicine, which is
Speaker 2: where I work now, because they were teaching courses relating
Speaker 2: to tropical diseases and particularly how parasites caused tropical diseases.
Speaker 2: And it was there that I was really exposed to
Speaker 2: kind of the detail of snake bite as a global,
Speaker 2: kind of neglected tropical disease. And there again I really
Speaker 2: just got sucked into the interesting biology. In particular, I
Speaker 2: was really fascinated by this idea that we've talked about
Speaker 2: that there are different venoms in different snakes, and this
Speaker 2: variation between the different toxins you find in different species
Speaker 2: can have such implications for people who were bitten by them,
Speaker 2: and that was really interesting to me because I guess
Speaker 2: it lent on two things. I was passionate about one
Speaker 2: was the kind of zoological side of understanding animals and
Speaker 2: the biology of animals, and the other hand the global
Speaker 2: health aspect in terms of ultimately wanting to try and
Speaker 2: do research that can have an impact on people and
Speaker 2: people's lives. So snake bite really really pulled both on
Speaker 2: both of those strings for me, and you know it
Speaker 2: can continues to fascinate me today.
Speaker 1: To be honest, one of the ways that people study
Speaker 1: snake venoms is of course by milking snakes. So first
Speaker 1: of all, how on earth do you milk a snake?
Speaker 1: And second, what was your first time milking a snake? Like,
Speaker 1: were you terrified? Were you completely confident? Yeah?
Speaker 2: Good questions, So get you're right. So LSTM we have
Speaker 2: a collection of about two hundred venomu snakes and the
Speaker 2: facility and we have now thankfully a team of people
Speaker 2: who look after these snakes and do the really dangerous
Speaker 2: stuff of venom extractions. And I suppose in many ways
Speaker 2: it's relatively straightforward, and I hope they won't you judge
Speaker 2: me for saying that it takes a certain degree of nerves.
Speaker 2: For sure, it takes a lot of skill and kind
Speaker 2: of calmness. And one of the key things is obviously
Speaker 2: safely restraining the animal, and so we use specialized tools
Speaker 2: and we use soft matting to make sure we don't
Speaker 2: hurt the animals when we do this, and we're able
Speaker 2: to then restrain the animals so that ultimately we can
Speaker 2: pick it up behind the head so kind of on
Speaker 2: the neck area, so that it can't turn around and
Speaker 2: bite us. We always do this in a pair and
Speaker 2: in our facility, so there's always two people working together.
Speaker 2: And then what we will simply do is we'll just
Speaker 2: gently move that head towards a glass dish, often covered
Speaker 2: in a material to kind of simulate the fangs biting
Speaker 2: through a prey item. Not always if the snake is
Speaker 2: small and has delicate fangs, we won't do that. And
Speaker 2: then as the snake's head goes towards that dish, it
Speaker 2: will instinctively bite, so it will put its mouth around
Speaker 2: the glass dish, and then it will expel venom into
Speaker 2: into the container. And then we kind of reverse the process,
Speaker 2: so we have to then safely restrain the animal again,
Speaker 2: let it go, put it back in its enclosure, and
Speaker 2: we're left with this venom. The substance obviously that we
Speaker 2: want to use for our research, and we freeze that
Speaker 2: overnight and then the next day we'll use a special
Speaker 2: instrument called a liophaalizer, which extracts the water out of
Speaker 2: this sample. It turns the venom into a powder, and
Speaker 2: we do this because it keeps the venom extremely stable
Speaker 2: for a long period of time, so we can use
Speaker 2: it for lots of different purposes over a period of
Speaker 2: many different years. So that's kind of the analytical side
Speaker 2: of it, if you like it's The difficulty is that
Speaker 2: every venom extraction is different because the snakes are wow
Speaker 2: that you know, they're animals and they have behaviors, and
Speaker 2: you know, irrespective of how well you know a snake
Speaker 2: or how many years you've worked with it, they can
Speaker 2: be unpredictable, and so you really do have to have
Speaker 2: high levels of concentration at all times and make sure
Speaker 2: that you know what you're doing, and when you're working
Speaker 2: in a pair, it's really important that you kind of
Speaker 2: build up that relationship so that you know what the
Speaker 2: other person is doing as well, and that that's really
Speaker 2: been one of the keys to working safely. So we
Speaker 2: have two people at LSTM who do our venom extractions now,
Speaker 2: and they're both excellent. One of whom trained me when
Speaker 2: I started working on on venom many years ago now,
Speaker 2: And yes I was nervous, for sure, but he was
Speaker 2: doing the hard work, he was doing the really dangerous work,
Speaker 2: and I was helping and that that definitely made a
Speaker 2: big difference. He was also someone with a lot of experience,
Speaker 2: So I think kind of the key to this is
Speaker 2: being trained by someone who kind of instills that calm
Speaker 2: and confidence in you. And yeah, that certainly helped me
Speaker 2: kind of get over those jitters around what we were
Speaker 2: going to do.
Speaker 1: Yeah, I bet have you ever had any close calls
Speaker 1: with venomous snakes, either you know, in the field or
Speaker 1: ones you're working on, or just throughout the research that
Speaker 1: you've been doing with other animals while doing snake research.
Speaker 2: Yes, but yeah, I mean it does happen. Of course
Speaker 2: it does. You know, it is a risk of the job,
Speaker 2: I can. Yeah, that's so. There's a few times working
Speaker 2: in our facility where you know, there are things that
Speaker 2: you reflect back on and think, well, Okay, you know
Speaker 2: that we could have done that better, or you know,
Speaker 2: we could have given ourselves more space and more time
Speaker 2: to do something but I think not really any near
Speaker 2: misses as such. I think field work is tougher for
Speaker 2: obvious reasons. You're far more isolated, you're out of your
Speaker 2: comfort zone, you're more at risk of something, if something
Speaker 2: does go wrong, the consequences of it being serious, I guess.
Speaker 2: For me, I can remember we were we filmed a
Speaker 2: documentary with the BBC around snake bite a few years
Speaker 2: ago when at the time we were there, I was
Speaker 2: working with a colleague, sorry, this was in Kenya. I
Speaker 2: was working with a colleague there and he received a
Speaker 2: call that one of the local villagers had a red
Speaker 2: spitting cobra that was upper tree and in the middle
Speaker 2: of this village and could he come and come and
Speaker 2: rescue it because there was you know, there's a risk
Speaker 2: obviously to the villagers there. And so we went to
Speaker 2: to find this snake and the snake was quite high
Speaker 2: up this tree, and so between the two of us
Speaker 2: we had to try and catch the snake, obviously safely,
Speaker 2: with a big crowd of villagers watching us. And when
Speaker 2: you're balancing halfway up a tree using snake tongues with
Speaker 2: a hand and clinging on with another hand, and it's
Speaker 2: obviously not an ideal situation, and it's not perfect when
Speaker 2: you have a crowd kind of judging your capability at
Speaker 2: the same time. So that was an interesting experience and
Speaker 2: it's it's yeah, it's not an experience I would like
Speaker 2: to have every day, soul, we say, but always well
Speaker 2: in the end, So yeah, the snake, we safely caught it.
Speaker 2: It was quite tired by that time because I think
Speaker 2: it had been spitting at the villagers for so long,
Speaker 2: and so in the end we were able to get
Speaker 2: it and bag it up safely, and we took that
Speaker 2: and then released it into the wild well away from
Speaker 2: the villagers next day. And so I mean, it's satisfying
Speaker 2: doing something like that, even though it's quite challenging at
Speaker 2: the time, you do feel that you know that you
Speaker 2: are helping in your own small way to try and
Speaker 2: avert something from happening.
Speaker 1: Do you have a favorite venom, particular venom, or a
Speaker 1: favorite snake or a favorite story in Venom Evolution.
Speaker 2: Well, we talked through my favorite story at the moment
Speaker 2: on Venom Evolution, and that's the spitting Cobra story, which
Speaker 2: I just it was such a fascinating project to be
Speaker 2: involved in, to try and understand how, you know, a
Speaker 2: defensive trait within the context of venomous snakes had evolved
Speaker 2: and also perhaps why it had evolved and what the
Speaker 2: consequences of that were. And it was really it was
Speaker 2: really satisfying because it was it was a large project.
Speaker 2: There's many many years, and also involved a lot of
Speaker 2: people from a lot of different places all over the
Speaker 2: world with lots of different expertise coming together and bridging
Speaker 2: that kind of laboratory research and ecological natural history research divide.
Speaker 2: That was really satisfying as a scientist to be part of.
Speaker 2: In terms of my favorite venoms, my favorite venoms I
Speaker 2: think will always be the source scale viper venoms. This
Speaker 2: is a group of snakes found throughout kind of Northern Africa,
Speaker 2: Middle East and into India and Sri Lanka, and they're
Speaker 2: probably the most medically important group of snakes in the world.
Speaker 2: Most people haven't heard of them. They're quite small and innocuous,
Speaker 2: but you know they killed tens of thousands of people
Speaker 2: every single year. And they're my favorite because they're what
Speaker 2: I uh dedicated for years of my life studying as
Speaker 2: part of my PhD, and so I was keen to
Speaker 2: understand what was in the venoms of these snakes, what
Speaker 2: do they do, how are they different from one species
Speaker 2: to the next, and what does that mean for treatment
Speaker 2: of snake bites? So if species X is different from
Speaker 2: species Y, does it matter if you're bitten by those
Speaker 2: snakes and there's one anti venom available or actually, is
Speaker 2: that a real problem because we haven't got an effective treatment.
Speaker 2: And so that was my training as a scientist. So
Speaker 2: that was really an exciting period of my kind of
Speaker 2: scientific life. And I got to do some fieldwork and
Speaker 2: collect source scale vipers and work with them and still
Speaker 2: work with them today. You know, they are a really
Speaker 2: important group of snakes. We've been developing new treatments against
Speaker 2: them in recent years, and yeah, I think it's pretty
Speaker 2: hard for me to think that anything will replace them
Speaker 2: in the future.
Speaker 1: Many, many people are afraid of snakes. Fear of snakes
Speaker 1: is one of the most common, if not the most
Speaker 1: common phobia. But knowledge is power, as we kept saying
Speaker 1: in our previous episode, can you talk about why you
Speaker 1: feel outreach and science communication about venomous snakes is so important.
Speaker 2: Yeah? Absolutely, I mean I think one of the key
Speaker 2: things here is what you've said already, snakes you know,
Speaker 2: they provoke a reaction, They proke fear in many people.
Speaker 2: And it's interesting, you know, when we tour people around
Speaker 2: our facility talk to them about what we do would
Speaker 2: show them the snakes, lots of people do have an
Speaker 2: inherent reaction to them. Lots of people already are frightened
Speaker 2: of them, but lots of people are also just fascinated
Speaker 2: by them. I think it's important that we don't demonize snakes. Ultimately, yes,
Speaker 2: they are a problem. I mean that they you know,
Speaker 2: they kill one hundred and thirty eight thousand people a year,
Speaker 2: so snake bite is a real public health challenge, particularly
Speaker 2: in the parts of the tropics. But in these same
Speaker 2: areas of the world, the snakes are really doing an
Speaker 2: important ecological role. They are killing the pests that would
Speaker 2: otherwise destroy the agricultural crops that these people are growing
Speaker 2: to survive, and so simply culling snakes, even if it
Speaker 2: was feasible, is not a very sensible strategy in that
Speaker 2: economically these people would suffer too. I think the other
Speaker 2: argument as well, that these venomus snakes are of intrinsic
Speaker 2: value to study. Their venoms are interesting. Their venoms are
Speaker 2: a source of potential new drugs and treatments for lots
Speaker 2: of different diseases. We already have medications that have been
Speaker 2: developed from snake venoms that treat high blood pressure or
Speaker 2: bleeding disturbances, and lots of people are looking at toxins
Speaker 2: in venoms potential cancer treatments as well, and so there
Speaker 2: is a pharmaceutical value to these animals too. But ultimately,
Speaker 2: I think every group of animals in the world has
Speaker 2: an intrinsic value and intrinsic right to be protected. So
Speaker 2: snakes are fascinating to many, interesting from a pharmaceutical point
Speaker 2: of view, and fundamentally crucial for the economic livelihoods of
Speaker 2: many people living in lower middle income countries. And I
Speaker 2: think those arguments are really important to convey the other
Speaker 2: side of the coin to snake bite.
Speaker 1: So we've spent most of this interview so far, at
Speaker 1: least a significant part of it, talking about the research
Speaker 1: that you do on snake venoms and snake venom evolution.
Speaker 1: But I want to round out our conversation by hearing
Speaker 1: more about the work that is being done at the
Speaker 1: Center for Snake Bite Research and Interventions. So what are
Speaker 1: some of the missions of the center and what are
Speaker 1: some of the work being done there.
Speaker 2: So the mission of the center is really to it's
Speaker 2: scientific research that's focuses on developing, testing, and implementing strategies
Speaker 2: to try and mitigate the burden of tropical snake bites.
Speaker 2: So ultimately we're performing a variety of different research from
Speaker 2: laboratory research all the way through to hospital research and
Speaker 2: public health research to try and improve outcomes for snake
Speaker 2: bite victims, with a predominant focus on the tropics and
Speaker 2: the subtropics. So the kind of research that we do
Speaker 2: is quite diverse. On a very fundamental level, things that
Speaker 2: we've touched on already. We want to understand whats are
Speaker 2: in the venom of snake X and what do those
Speaker 2: toxins do, How do those toxins cause damage in a
Speaker 2: person who's bitten by them. We want to understand how
Speaker 2: well or not existing treatments might work at preventing that
Speaker 2: damage if someone is bitten. We're also doing quite a
Speaker 2: lot of research to try and just make much better treatments,
Speaker 2: much broader treatments than those that exist today. So current
Speaker 2: anti venoms are quite limited in many ways. You need
Speaker 2: different anti venoms for different parts of the world. That's
Speaker 2: because again we have venom variation between different snake species,
Speaker 2: but also lots of people have adverse reactions to treatment.
Speaker 2: They're quite expensive in the context of low middle income countries,
Speaker 2: and also they have to be given to a snakelike
Speaker 2: victim in a hospital environment. You have to manage the
Speaker 2: adverse reactions that might happen to the drug, and you
Speaker 2: also have to give the anti venoms intravenously need a
Speaker 2: certain amount of kind of clinical capability to do that.
Speaker 2: So because antithems have to be given in a hospital,
Speaker 2: there's often this big time lag between someone being bitten
Speaker 2: and treatment starting, and that's a real problem because it
Speaker 2: leads to poor patient outcomes. So a lot of our
Speaker 2: researchers trying to circumvent those limitations. We want to make
Speaker 2: more effective, more broadly effective antivenoms that are more affordable,
Speaker 2: that are safer, and that might be able to be
Speaker 2: given to a patient much sooner after a bite, so
Speaker 2: for example, as an oral tablet in the community rather
Speaker 2: than in a health clinic. But we also do work
Speaker 2: in snake bite affected countries too, So we're active at
Speaker 2: the moment in Kenya, in in Nigeria, and in Swatini
Speaker 2: and in India India, working with partners in those countries
Speaker 2: to better understand the burden of snake bite, the cost
Speaker 2: of illness to the hospitals and to the governments, and
Speaker 2: also trialing how different interventions might work or might be
Speaker 2: effective to reduce the kind of the burden of snake
Speaker 2: bite on those populations. So this could be community education,
Speaker 2: or it could be for example, using a motorcycle to
Speaker 2: try and more rapidly transport someone to hospital as an ambulance.
Speaker 2: And ultimately, the kind of the last key pillar of
Speaker 2: the work that we do is to strengthen the capacity
Speaker 2: of people in those countries to undertake snake bite research.
Speaker 2: So we've been fortunate enough to receive funding to help
Speaker 2: develop snake BikeE research centers in Kenya where they've established
Speaker 2: their own herbetarium to collect snakes and venoms, develop capacity
Speaker 2: for them to perform medical research on snake bite victims
Speaker 2: so they can understand what to expect when someone is
Speaker 2: bitten by a species of snake or a different species
Speaker 2: of snake. And ultimately, we believe that's really important that
Speaker 2: those can trees where snake bite is a real problem,
Speaker 2: that individuals in those countries have the capacity to perform
Speaker 2: the research to enable policy changes and to have a
Speaker 2: real impact in terms of mitigating this disease in the
Speaker 2: long run.
Speaker 1: Are there any projects that are currently being done? I
Speaker 1: know you discussed a broad variety of all the different
Speaker 1: work that's being done at the center. Are there any
Speaker 1: particular projects, maybe in anti venom therapy or access to
Speaker 1: anti venoms that you are most excited about that is
Speaker 1: being worked done at the Center.
Speaker 2: Yeah, I think there's a couple, if I'm honest with you. So,
Speaker 2: in terms of therapy, we have three main strategies at
Speaker 2: the moment. One is to try and improve existing treatments,
Speaker 2: and so we're looking at ways that we can quite
Speaker 2: quickly improve the potency of existing products, kind of as
Speaker 2: a short term solution to tackling snake bite. And then
Speaker 2: there's the more longer term approach where we're completely changing
Speaker 2: the strategy, if you like, from how current treatments are
Speaker 2: made to a new format, almost like a next generation approach.
Speaker 2: And one of these is is looking at drugs that
Speaker 2: have been used for other diseases and seeing whether they
Speaker 2: can be repurposed for snake bite. So, for example, there
Speaker 2: are toxins in the venom of snakes that are also
Speaker 2: related to proteins found in URI. So I mentioned the
Speaker 2: syrium proteases earlier on with the caligrines, and there's other
Speaker 2: proteins called metalloproteinases and phospholipases. These are proteins that are
Speaker 2: in URI, and they're actually the targets for medications related
Speaker 2: to other diseases. So metallur proteases were an important target
Speaker 2: for cancer, and phospholipases for coronary heart diseases. So drug
Speaker 2: companies develop molecules that would block these proteins, trying to
Speaker 2: develop new treatments for those conditions. And what we're doing
Speaker 2: at the moment is we're trying to understand whether any
Speaker 2: of these drugs that ultimately didn't make it or got
Speaker 2: close to making it as medications for those diseases might
Speaker 2: be useful for snake bite. And so one of those
Speaker 2: drugs is actually a medication that was used for treating
Speaker 2: heavy metal poisoning. And this is a metal key LATA
Speaker 2: that's a licensed medication. It's used in Europe already, and
Speaker 2: we've been able to show that it has some ability
Speaker 2: to block source scale viper venom and so we're now
Speaker 2: moving into clinical trials with that medication for snake bite
Speaker 2: to see whether it's able to actually prevent some of
Speaker 2: the toxicity or the life threatening effects of source scale
Speaker 2: viper venom as an oral drug, so as a drug
Speaker 2: that could be taken quite quickly after a snake bite,
Speaker 2: still with a patient going to hospital and still potentially
Speaker 2: getting antivenom too, but whether that early oral medication ultimately
Speaker 2: might be able to have a lasting benefit and give
Speaker 2: that patient a much better chance of surviving or reducing
Speaker 2: the severity of a bite. I think it's a real
Speaker 2: exciting time for snake white treatment. So collectively, as kind
Speaker 2: of a snake bite research community, we've been very fortunate
Speaker 2: that the Welcome Trust about four years ago invested eighty
Speaker 2: million pounds into research for snake bite and predominantly around
Speaker 2: that translational biomedical therapy diagnostic space, and they've funded a
Speaker 2: number of projects to ourselves but also to lots of
Speaker 2: other groups all over the world looking at innovative strategies
Speaker 2: to combat snake bites, so to try and bring treatments
Speaker 2: into the modern day. We don't know which are going
Speaker 2: to be the best strategies ultimately, as treatments, and there
Speaker 2: are lots of different ways of doing this, and we
Speaker 2: might need certain strategies for certain toxins and different ones
Speaker 2: for other toxins. So I think it's really exciting at
Speaker 2: the moment. There are different groups with different ideas and
Speaker 2: that collectively as a community, I hope in the next
Speaker 2: five years we're going to be much clearer as to
Speaker 2: which strategies are going to give us those broad, effective
Speaker 2: and safe therapies. In the long run, it does take
Speaker 2: many years, of course, to develop new medications, so this
Speaker 2: is not a short term thing. But I am very
Speaker 2: hopeful that in the next five to ten years we
Speaker 2: will have at least a couple new treatments for snake
Speaker 2: bite that hopefully will deliver real impact over above current
Speaker 2: strategies we have for mitigating the seas. But it's not
Speaker 2: all about treatment. Sadly, it would be lovely if we
Speaker 2: could just have these magic bullets that solve everything, but
Speaker 2: the World Health Organization stresses as well the importance of
Speaker 2: getting those treatments to the right places and getting the
Speaker 2: people to the right places too, So there really is
Speaker 2: still a lot of work that needs to be done
Speaker 2: around the kind of the health seeking behavior and the
Speaker 2: health infrastructure relating to snake bite and of course many
Speaker 2: other tropical conditions too. It's only with that kind of
Speaker 2: collective push that I think will have a real impact
Speaker 2: on reducing the burden of snake bite across the world.
Speaker 1: Thank you so so much, Professor Casewell. What an absolutely
Speaker 1: fun and fascinating conversation. I feel like I could have
Speaker 1: just asked endless questions about snakes and snake venoms and
Speaker 1: anti venoms. It's is so cool. And if you would
Speaker 1: also like to learn more about venom evolution or the
Speaker 1: incredible work that the Center for Snakebite Research and Interventions
Speaker 1: is doing, check out the post for this episode on
Speaker 1: our website, This Podcast will Kill You dot com, where
Speaker 1: I'll link to a few papers and videos, as well
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Speaker 1: in the Wondery app. I want to give a big
Speaker 1: thank you to all of my guests for these bonus
Speaker 1: episodes over the past few months. I have absolutely loved
Speaker 1: chatting with you, and I appreciate so much the time
Speaker 1: that you've taken to share some of your knowledge. It's
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