117 | Snake Venom with Dr. Stephen Mackessy

Summary

In this engaging episode of Snake Talk, Dr. Chris Jenkins sits down with Dr. Stephen Mackessy from the University of Northern Colorado, an expert on snake venom biochemistry. They delve into the evolution, diversity, and medical potential of snake venom, revealing both the perils and possibilities it presents. Dr. Mackessy shares fascinating insights from his career, including tales of early encounters with venomous snakes and the evolutionary dance between venom and prey resistance. Listeners gain a deeper understanding of the biochemistry behind snake venom and its application in medical science as they explore how proteins and peptides in venom could lead to advancements in treating diseases like cancer.

Highlights

• The venom story: Dr. Mackessy recounts his teenage rattlesnake bite, turning a painful lesson into a lifelong passion. 🐍
• Deep dive into venom: Not just about killing prey, snake venom evolves due to an evolutionary chess game with resistant targets. ♟️
• Medical marvels: How snake venom analysis leads to drugs treating conditions like diabetes and cancer. 💉
• Unexpected applications: Dr. Mackessy's work showcases venom's potential beyond mythology, suggesting new medical uses. 🧪
• From fang to pharm: Charting the journey from venom extraction to viable therapeutics in modern medicine. 🏥

Key Takeaways

• Venoms are complex and diverse, with each snake species crafting its own unique biochemical concoction. 🐍
• Dr. Mackessy's journey into the world of snake venom began early, shaped by both curiosity and a rattlesnake bite as a teenager. 🏞️
• Snake venom is not just a deadly cocktail; it harbors potential cures for various human ailments, from blood pressure issues to cancer therapies. 💊
• Despite common misconceptions, baby rattlesnakes are not more dangerous than adults—Dr. Mackessy clarifies this age-old myth. 🐍
• The evolutionary arms race between snake venom and prey resistance is a captivating tale of adaptation and survival. 🌱

Overview

Dr. Stephen Mackessy, a leading expert in snake venom biochemistry, offers a riveting discussion on the evolution and impact of snake venom in the latest episode of Snake Talk. From a youthful encounter with a Southern Pacific rattlesnake to his illustrious career, Mackessy shares how venom's complexity continues to drive his research and fascination.

Exploring the intricacies of venom's biochemistry, the episode reveals how snakes have developed a myriad of proteins and peptides, leading to groundbreaking treatments in medicine. Dr. Mackessy uncovers how these biological compounds, through evolutionary processes, have potential applications ranging from managing diabetes to inhibiting cancer proliferation.

Listeners are taken on a scientific journey that dismantles common myths about snakes, especially the debated danger level of baby versus adult rattlesnakes. The exchange between Dr. Jenkins and Dr. Mackessy highlights their shared enthusiasm for understanding and conserving these oft-feared creatures, presenting venom as both a danger and a boon.

Chapters

• 00:00 - 01:00: Introduction and Guest Introduction The chapter titled 'Introduction and Guest Introduction' begins with the host, Dr. Chris Jenkins, who is the CEO of the Orian Society, introducing himself. He is also the host of the 'Snake Talk' podcast. The podcast focuses on educating listeners about snakes, which are often feared, misunderstood, and persecuted. Dr. Jenkins invites listeners to engage with the conversation to potentially reshape their perceptions from fear to understanding the deeper essence of these creatures.
• 01:00 - 04:00: Background and Early Interest in Snakes In this chapter titled 'Background and Early Interest in Snakes,' the focus is on introducing Dr. Steven Maxie, a professor from the University of Northern Colorado. The chapter sets the stage for discussing his background and early fascination with snakes.
• 04:00 - 09:00: Early Venomous Snake Handling Experience The chapter titled 'Early Venomous Snake Handling Experience' discusses a conversation with an expert in venom. The expert has done significant work in venom biochemistry and its potential uses in medicine and other areas. The discussion also touches on ecological and natural history aspects of venomous snakes. The conversation promises to be engaging, especially for those who regularly follow the series.
• 09:00 - 13:00: Education and Research Background The chapter 'Education and Research Background' discusses the background of a guest named Steve, who has previously appeared on the podcast. He was part of a panel episode at the Northwest partners and amphibian reptile conservation meeting. This chapter focuses on Steve's return to discuss his favorite subject, the venoms of snakes, indicating that his background and research are likely centered around herpetology and venom studies. The conversation suggests that Steve and the host, Chris, are already acquainted, pointing to an ongoing interest in these topics.
• 13:00 - 25:00: Venoms and Their Effects The chapter discusses the speaker's early interest in snakes and venom, beginning in childhood.
• 25:00 - 31:00: Venom Diversity and Evolution The chapter begins with the author's childhood experiences in Southern California, particularly in Monrovia, near the San Gabriel Mountains. The author recalls frequent hiking trips during which they occasionally encountered snakes, sparking an early interest in them. As a teenager, the author was introduced to a new business owner by a friend. The business was located in a place referred to as West Western, which played a role in the author's evolving interest in snakes and their venom.
• 31:00 - 58:00: Clinical and Practical Applications of Venom The chapter explores the clinical and practical applications of venom within zoological contexts. The narrative begins with the author's personal experience working at a zoological supply company during high school, where they took care of numerous venomous snakes from around the world. This job involved handling venomous animals that were imported from overseas and then distributed to zoos and schools, emphasizing the diverse range of venomous creatures managed by the company. The chapter highlights the significance of venom and its applications in various settings.
• 58:00 - 67:00: Future of Venom Research and Final Thoughts The chapter discusses the speaker's early interest and experience with snakes from around the world, including mambas, king cobras, spitting cobras, and various vipers. At the age of 15, the speaker had an accident with a Southern Pacific rattlesnake, highlighting the dangers and learning experiences associated with handling venomous snakes. This incident perhaps foreshadows the speaker's deeper engagement with venom research, hinting at the chapter’s exploration of the future of venom research and concluding thoughts on the subject.
• 67:00 - 69:00: Snake Story and Closing Remarks The chapter discusses an incident involving a rattlesnake bite from a Southern Pacific rattlesnake, which is considered fairly toxic. The speaker recounts how the bite led to a hospital stay of about six days due to severe swelling and injury. The story serves as a significant personal anecdote, illustrating the dangers posed by this type of snake in North America.

117 | Snake Venom with Dr. Stephen Mackessy Transcription

• 00:00 - 00:30 [Music] my name is Dr Chris Jenkins and I am the CEO of the orian society and the host of the snake Talk podcast the podcast where you learn about Nature's most feared maligned and persecuted animals I invite you to listen to this conversation and maybe you'll find that what you perceive as fear is is actually rooted in a deep
• 00:30 - 01:00 [Music] [Music] Fascination welcome to the snake Talk podcast I am sitting here with Dr Steven Maxie from the University of Northern Colorado where he is a professor and we
• 01:00 - 01:30 are going to have uh an interesting conversation today he is an expert on everything Venom um and in particular has done a lot of work around kind of the biochemistry of of Venom and um you know for example how it could be utilized in the medical field or or for for other things um he's done a lot of ecological and natural history related work I think we're going to have a a great conversation and for those of you that that listen to every episode you
• 01:30 - 02:00 will remember Steve has actually been on the podcast before he was part of the uh panel episode that we did at the uh Northwest partners and amphibian reptile conservation meeting so um welcome back to the podcast Steve how you doing today I'm doing pretty well Chris thank you for the invitation to talk about one of my favorite subjects venoms of snakes yeah great well you were um you've been on the podcast and we probably talked a little bit about your background but but
• 02:00 - 02:30 um I want to dive into it a little bit deeper so uh I want to start off at the very beginning and uh figure out how was it that you would get into something so strange as snakes and Venom and these types of things is this something that that uh bit you pun intended I guess as a child or um something that hit you later in life oh it it developed pretty early on
• 02:30 - 03:00 and it seemed kind of a natural move for me I grew up in Southern California born in San Francisco but moved to Southern California and town called Monrovia which is right against the S Gabriel mountains and so when we were kids we'd go hiking all the time and occasionally see snakes so I was interested in snakes then um as I started in my early teens a friend introduced me to another person who had just opened a business and this was a place called West Western
• 03:00 - 03:30 Zoological Supply in the same town that I grew up in and it turned out it developed that I worked there as a job all through high school and I was taking care of venomous snakes from all over the world so everything you can possibly imagine everything you've ever seen in zoos we had there because they were a supply company that brought things in from overseas and then supplied zoos and schools with all sorts of different venomous animals and that included like
• 03:30 - 04:00 mambas king cobras spitting cobras vipers of every flavor and type you can imagine from around the world so that got me quite interested in diversity of snakes um early on in that as a 15-year-old I had a little accident of sorts with a Southern Pacific rattlesnake where I picked it up with a snake hook like you're supposed to do and then I decided to hold it by the tail like you're not supposed to do and it very quickly turned around hit me in
• 04:00 - 04:30 the left hand long story short it put me in the hospital for about six days SW my up about double into the shoulder and uh gave me quite an incident to talk about if I remember right the so those were kind of early events Southern Pacific um is actually fairly toxic as far as North American rattlesnakes go is that true it's it's a reasonably dangerous kind of middle of the road rattlesnake tending towards the more toxic
• 04:30 - 05:00 um well as it turns out if you're going to be bitten by a rattlesnake it's much better to be bitten by a baby rattlesnake because contrary to um popular opinion they can actually control the Venom that they're injecting their venom is a little bit more toxic than the adults and what I found later as part of my Master's work it's about two times as toxic drop for drop but the amount that they can give you is so much smaller than an adult snake and like any
• 05:00 - 05:30 compound or drug dose determines effect and so a small snake can only produce about 10 microliters of Venom whereas an adult Southern Pacific rattlesnake can produce 500 microliters so the difference there is dose dependent yeah I'm glad you mentioned that the other thing about that bite I was just gonna say I'm glad you mentioned that because I give a lot of presentations in in all kinds of forums and you know that's always one of the questions I get I'm sure you get it every time you give a presentation to the public as well is it true that that baby rattlesnakes are
• 05:30 - 06:00 more dangerous than adults and you know I've changed my answer to that over the years and and now I I basically give the same answer that you gave um except I did not realize the component you talked about that the babies um actually you know drop for drop the Venom is more toxic and so I'm going to go back and find some of that work you were talking about you said it was from your Masters is that right yeah that was actually one of the early papers that that I did in 1988
• 06:00 - 06:30 looking at Venom monogyny so my Master's work was primarily looking at Southern Pacific and Northern Pacific rattlesnakes and how their venom is when they're first born and how it changes as they mature into a large adult and biochemically it changes quite a bit Yeah and we so one of those features is toxicity it becomes less toxic yeah and we've had Dr Young on the podcast talking about kind of the whole metering um you know question and all of that so I'm I'm glad mention that
• 06:30 - 07:00 I will go look that up but really really glad you mentioned that and we're going to talk about Venom and we're going to talk about things like that like does venom change as snakes you know turn into adults is that possible these types of things but um anyway so you're a high school student you're uh have this dream job for somebody who's interested in snakes and you're handling all kinds of venomous snakes and and you have this um potentially traumatic maybe exciting I don't know at least created a good story experience of um getting bit by a um uh
• 07:00 - 07:30 Southern Pacific or rattlesnake and so I want to ask you you're in high school doing this did you realize that as you went going into college that this was something you could potentially do as a career but before you hit that I want you were about to say something about that snake bite and I cut you off rudely so please uh talk a little more about that snake bite and then curious curious if you realized you could make a career out of this or not sure um one thing any kind of venomous
• 07:30 - 08:00 snake bite on a good day is a bad thing right and so no the whole experience was very unpleasant unless you enjoy the sensation of hammers being pounded on your arm and and throbbing pain and stuff like that which I don't what I was going to mention about the bite though is it was long enough ago that I did it back in the day when it was cheap I we didn't have insurance my dad was in between jobs at the time so I paid for it with my paper route
• 08:00 - 08:30 money and the whole thing that is six days in the hospital do Bill and antivenom the whole thing cost $1,000 wow now even normalized for inflation that was Dirt Cheap relative to what costs are these days and so you know people that are doing this free handling not only is it painful but you can incur a cost that can run a quarter to a half million dollars easily mhm and I've
• 08:30 - 09:00 heard that from several different sources over the last 5 or 10 years so it's an expensive accident so that that taught me to not do dumb things that I was doing as a a teenager strangely enough teenagers occasionally do things that are probably not the brightest in retrospect but as far as developing my career goals actually in high school I was very interested in language and took French German and Spanish and thought about becoming a un translator but when I
• 09:00 - 09:30 applied to school I declared a biology major because I was always interested in biology and when I started at University of California Santa Barbara as a freshman that was the track I was in and basically stayed in that track of biology zoology biochemistry for my entire academic career or student academic career gotcha and so where did you end up um you've already said your Masters um was looking at kind of
• 09:30 - 10:00 changes in venom in these two uh Pacific species uh and um over you know over basically young and old comparing younger and older snakes does does venom composition change so where was that was that in California were you at a California based University yeah it was kind of what's referred to as the Central Coast so primarily did include some sampling all the way down into LA County Los Angeles
• 10:00 - 10:30 County and then through Santa Barbara and San Lou biso counties so kind of that where California does the Big Bend and and change over from a influenced by Southern currents and Northern currents at Point conception there that kind of area you know in the greater Santa Barbara region and extending North and South so that was where most of my sampling was from and you know we did some other species kind of on the side side winders and red diamond rattlesnake and things like that during my
• 10:30 - 11:00 masters um but undergraduate and Masters at the University of California Santa Barbara and then I started a PhD in what was called the zoology department at that time at Washington State University and I had begun to look at the Venoms in much more detail and so the PHD was looking at the Venoms in a lot more detail taking them apart describing the biochemistry and such but also going very extensively into the
• 11:00 - 11:30 Venom gland structure and asking questions about how how do they store this Venom right next to their brain in this little sack of sorts for years without intoxicating themselves and having damage or having their venom fall apart so that led into a whole host of other studies as well gotcha and and where were you for the PhD
• 11:30 - 12:00 I was at Washington State un up in Pullman Washington that's right you said that um great and it was a very significant change from Santa Barbara I bet I bet I've been up to Pullman in every respect yeah climate and just yeah everything yeah so yeah it was a good school but it allowed me to focus and stay in the lab which I needed to do to finish yeah there you go so um you finished the PHD did you end up going directly to to Northern Colorado or were
• 12:00 - 12:30 there any kind of steps in between there no at the time um my wife and I moved to Southern Colorado I got a job at Colorado State University as a post-doctoral research associate in the biochemistry lab of Anthony 2 who was a world famous Venom researcher he started working in the 6s and continued publishing all through the early 2000s and he's retired now he's still alive I think he's either 93 or 94 living in
• 12:30 - 13:00 California but cor so I was working in his lab ostensively to pick up more techniques in Biochemistry so excellent and then on to Northern Colorado yeah at that point when I finished up there I started teaching part-time at UNC University of Northern Colorado in gy and in 1994 started a permanent tenure track position at I've been here ever since that time yeah
• 13:00 - 13:30 gotcha well let's let's transition a little bit and let's start talking about what has been the kind of the the center of your research program and I'm sure a component of your teaching and all of that over time and that that has to do with Venom and so let's just start right at the beginning and you know if I was to ask you the question what is venom how how would you describe it
• 13:30 - 14:00 well it's an interesting biologically synthesized material and we mentioned a little bit about how the snake has to store it safely we can get into that later but it's really a a mixture of different biochemicals primarily proteins and peptides and these are macro molecules larger molecules that are comprised of strings of amino acids and so when we talk about neurotoxins from Cobras for example I say they're as natural as
• 14:00 - 14:30 milk because milk has protein in it too and those proteins just are strings of amino acids in different sort of arrangements and of course they're non-toxic but we don't typically inject milk so we won't go there but it turns out that snakes haven't evolved this magical or denovo new stuff just out of thin air but instead you know if you kind of speak theologically snakes have looked around body of vertebrates and
• 14:30 - 15:00 said I'll take some of those regulatory compounds those Regulators those Regulators of all these different processes and then in the Venom glands they overexpress those so instead of inject instead of having a regulator that's present locally say in your bloodstream and causes blood vessels to dilate to expand or to contract instead of having a tiny tiny bit there that would be used as a regulator
• 15:00 - 15:30 they give tens of thousands of times more the the net effect of a rattlesnake and another venomous snake bite is system failure all sorts of different systems are affected almost simultaneously and when we have a human that intercepts that bite we get a very very complex and very evolving sort of dangerous scenario that can be lifethreatening and certainly is [Music] debilitating how about well so and
• 15:30 - 16:00 correct me if I'm wrong here and I probably I'm wrong but uh most or all of the venomous snakes are are more um recently evolved snakes and so I'm just curious um what you can tell us you know what we know about the evolution of of Venoms maybe you know across taxonomic groups but then more specifically with snakes is it indeed a more recent phenomenon or is it
• 16:00 - 16:30 something that we see going back you know 80 million 100 million years the answer to your question is yes and no which is always satisfying um if you look at the origins of venomous reptiles they certainly have a a history of at least a 100 million years um if you remember the Jurassic Park that documentary on reptiles and being
• 16:30 - 17:00 they had a venom spitting theasaurus that wasn't quite as far-fetched as it might seem it did have tooth structure and such that suggest that it may have actually been a venomous creature whether it's spat and the quantities that were in the film is debatable but in fact the basics are that Venoms evolved in reptiles fairly early on it turns out there's a couple of venomous mammals as well well so some weird things called selod some
• 17:00 - 17:30 of the shrews U platypus males have a Venom conducting spine on the hind leg and so we see Venoms in a lot of different verbic groups well in several different verbic groups I should say but really the reptiles and snakes in particular have Diversified that very extensively if you look at the fossil record and ask when do we see vipers and cobras and things like that there's good evidence from deposits that are around 25 million years old that you know these
• 17:30 - 18:00 groups we have good Cobra like animals and viper-like animals by that period of time and their their history is is probably much much more ancient than that so venomous snakes have been around in one form or another for 75 to 100 million years they have Diversified into representatives of the families that we see a little bit more recently but again they they have a fairly long history
• 18:00 - 18:30 evolutionary history and that has allowed for these Venoms then to have the geologic time frame necessary to diversify in all these different types of compounds okay so when we say proteins and peptides in the Venom we're not saying one protein and one peptide but if we really want to divide it out into the minutia a Venom can have as many as a hundred or more different protein peptide components ments some of them
• 18:30 - 19:00 are very similar to one another others are vastly different from one another but it's it's a complex mixture that again is produced biologically by the snake and in that complexity then those peptides and other peptides and proteins can be rearranged in different ways and and create diversity of Venoms across species and within species and on so that's um and that's the name of the game too y So speaking of diversity snakes when when the average person
• 19:00 - 19:30 thinks of Venom you know they a lot of people probably have heard and think of the terms hemotoxin and neurotoxin which would be broad categories of of of Venom types um that that various species Venoms may get put into so the first part of this question is um do you being somebody who knows these these Venoms as well as anybody on
• 19:30 - 20:00 the planet do do you subscribe to that do you categorize Venoms um and then you know or or do you just think everything's so diverse that it's just a spectrum or do you or you know and then if you indeed do what are some of the you know I mentioned those two that people probably think of most but what are you know I don't know whatever the top five six you know the top categories uh of Venoms that that you would um think
• 20:00 - 20:30 about reptiles face many challenges from habitat loss to climate change as an example Turtles are the most threatened group of animals on the planet with over 60% of species classified as endangered the orian society is working hard to secure a thriving future for these incredible animals to engage in the critical work we're doing explore our website at
• 20:30 - 21:00 [Music] www.an.com Toxin and neurotoxin and they say something like a rattlesnake is a hemotoxin or a cobra is a neurotoxin that's really a misnomer because any
• 21:00 - 21:30 rattlesnake species has all these different components some of them may affect tissu some of them may affect the blood directly some of them like in Mojave rattlesnakes mif faded rattlesnakes tiger rattlesnakes some of them actually are preoptic neurotoxins so they actually bind two channels and receptors on nerves and incapacitate the ability of a nerve to tell a muscle to contract so when you say it's this or
• 21:30 - 22:00 that that really oversimplifies and and is actually inappropriate for describing the Venom now if you talk about the clinical signs of inv venim if a cobra bites you one of the well depends on the Cobra but let's just say an Indian cobra bites you one of the major things you need to be concerned about right away are the neurotoxins that are in those Venoms and these are molecules called three-finger toxins because they look
• 22:00 - 22:30 like three fingers pointing down and they're very very potent Inhibitors of the receptor that's on our muscles that receives the signal from nerves that says contract and so if you block those then we have the situation of flaccid paralysis where the person can't move and those molecules in the Venom are small so they move fairly quickly through the system and they can be life-threatening because the frenic nerve diaphragm that controls your breathing muscles can be compromised and
• 22:30 - 23:00 so you get paralysis of the breathing and without treatment or without artificial respiration iron lung kind of therapy a person could in fact die fairly quickly from that if we go to the other end the hemotoxin there are a few things that are actually toxic to the blood which is how that term translates but what I prefer to use is something like tissue damaging Venoms because what we see in rattlesnake bites in particular particular in the United States is that most species produce very
• 23:00 - 23:30 very severe damage local damage to muscle and you may have seen pictures online and I'm sure people have where it almost looks like if you were bitten in the hand you put your hand over a fire and toasted it and it's all blbs and blisters and necrotic lesions developing and things like that and those are due to some of the digestive enzymes the specialized proteins that are in fact causing local tissue damage that then spreads in without treatment could take
• 23:30 - 24:00 your entire limb or kill you for that matter so although we can talk about Venoms as hemotoxic and neurotoxic from a clinical perspective that's what we need to deal with quickly neurotoxic or tissue damaging effects Venoms are much more complex than that and we also get into a situation where as we get into different clades of venomous animals in particular the so-called rear Fang snakes that are largely harmless to humans but occasionally have produced
• 24:00 - 24:30 some some weird effects those and some of the front fangs as well produce Venom components that are very very specific to certain types of organisms so for example the brown tree snake many people have been bitten by the brown tree snake in the control efforts on Guam to try to keep it from spreading to other islands and they don't show severe effects they may show local reactions well it turns out they have three-finger toxins that Str Al look almost identical to what we
• 24:30 - 25:00 find in cobras and coral snakes and some of the mambas and things like that but it's a different molecule and it doesn't really affect mammals to any significant effect but it's a lethal toxin to birds and lizards and so that got us very interested in that whole line of research into what we refer to as taxon specific effects of Venom proteins because on on the one hand if you look at the crystal structure where we have the whole molecule in threedimensional space modeled of a
• 25:00 - 25:30 cobra Toxin and a brown tree snake Toxin and you overlay them they're almost a perfect match but if you look at the individual amino acids go back to that this natural as milk sort of thing if you look at the amino acids those are different in those two um different snakes Venoms and that has the effect of being specific for this or that type of prey so wow that's interesting so same at least superficial structure um but
• 25:30 - 26:00 you have the the brown tree snake that really wouldn't impact mammals much but does impact the birds due to the details if you will of the amino acids and then the opposite for the cobra that's that's um that's really fascinating so how about these other classifications people might hear I was going to say like um give an example of like cytotoxins or there's you know uh
• 26:00 - 26:30 how would you do you have other major categories of Venoms and even if even if that's not how scientists would typically think about it but um maybe it's more um like you were talking about kind of in the the treatment of and the symptoms of a particular bite or do you classify those all under you know tissue damaging or it's interesting that you bring up the cytotoxins in particular because
• 26:30 - 27:00 some of the spitting cobras have some very nasty effects locally that are not neurotoxic and some of those effects are actually by these same kind of three-finger toxins but in this case they're not binding to components of the neuromuscular system but instead they're causing damage to local tissu cytotoxic effects cytotoxin simply means cell toxic or cell damaging and we've done a lot of work with cancer cells in the lab
• 27:00 - 27:30 we can grow them in the lab up to Millions to tens of millions very readily in a couple of days then you can ask the question what effect does this Venom or that Venom have on the viability of the cells does it killed them or not and a lot of the different snake Venoms whether we're talking about the elapids like cobras and their allies or we're talking about the Vipers rattlesnakes and such kill cells very nicely um so they have cytotoxic effects
• 27:30 - 28:00 but the cytotoxic effects on those cells are different in some of the different Venoms it also turns out that some of the most dangerously toxic rattlesnake Venoms such as the South American rattlesnake cerisis that is not particularly toxic to cancer cells at all in the lab and you put a fair amount of that material on them and it doesn't have much of an killing effect on the cells if you put that into a human or into another mammal
• 28:00 - 28:30 like a mouse it's very rapidly lethal so there's some differential effects that we can have in the lab in vitro or in X Vivo compared to what we see in a whole animal in venom so I'm we have come up with a a dichotomy in Rattlesnake Venoms that early on held very nicely type one versus type two Venoms type one being more digestive function type two being less in the way of the
• 28:30 - 29:00 metalloproteinases it causes structural damage and a lot of hemorrhaging and things like that but has instead neurotoxins in the Venom and these pre synaptic neurotoxins it turns out that there's a lot of gry Zone in there things in biology never fall out as this or that and there you can set up those ends of a Continuum but there are a lot of things in the middle there and as we've gone into more and more research in different species of rattlesnakes patterns that we
• 29:00 - 29:30 thought were generally applicable like the Venom monogyny effects that we saw in the pafic rattlesnakes don't necessarily apply to other species of rattlesnakes even even fairly closely related species yep well you've talked about how first of all there's a diversity of Venoms and that in talking about how they impact whatever type of say blood cell or or tissue cell that um you've talked a lot about receptors
• 29:30 - 30:00 and so I'm curious if you in a very uh you know imagine I'm a um you know a sixth grader um tell me how biochemically this is a generalization and it may it may be so different across Venoms that you can't describe it but you know get to that level the level of like you've got a Venom molecule you then you've got a receptor on a cell like how does Venom biochemic Ally um
• 30:00 - 30:30 destroy a human cell or or or maybe destroy is the wrong word um how does it impact a human cell well again what we have are a whole bunch of different molecules in the Venom and these are really modified Regulators of all sorts of different processes in the body and so these various molecules affect very different sort of parts of the systems
• 30:30 - 31:00 and one of the reasons I don't like to say well a Venom is cytotoxic is it can have that effect but there can be many of those molecules in there that don't bind to cells at all instead they bind to things like there are proteins that make up our blood vessels right and that holds the whole thing together our blood vessels are comprised of cells but they have specialized molecules proteins that act to hold it together and so some of
• 31:00 - 31:30 these Venom components and these are referred to as metalloproteinases are enzymes and enzymes are proteins that catalyze reactions that otherwise wouldn't happen and they can keep doing that over and over and over again and so those Venom Metallo proteinases are attracted to that surrounding layer of protein that holds blood vessels together and they begin to break it apart they have particular parts of the molecule that act as you
• 31:30 - 32:00 can think of them as molecular scissors and so they're cutting apart the structure well the blood vessel itself is under pressure as well you start chopping apart the the things that hold that tube together and it begins to rupture and when it ruptures that produces what we call a hemorrhage and that can affect all sorts of different systems because now blood is not staying pressurized and staying in the system but it's leaking out blood pressure can fall are other components in the Venom same Venom of rattlesnakes that actually
• 32:00 - 32:30 cut a little Protein that's circulating in the blood you cut a big protein they cut a little peptide out of it and that has the effect of causing our blood vessels to relax or dilate become bigger and if that happens suddenly it can lead to a cataclysmic crash in blood pressure ah and you may have heard about the hel monster bite that occurred in the Denver area that killed a guy just this last spring and in part helila monster venom has a
• 32:30 - 33:00 large amount of that particular type of enzyme in there he apparently got a very large dose of Venom and one of the first things that happened is that he just almost passed out fell to the floor because his blood pressure crashed and it just things went downhill from there he had a you know ended up dying from the bite it was terrifically horrible yeah so these Venoms again we're just speaking about a general snake the Venoms are very diverse very complex
• 33:00 - 33:30 hard to categorize as we've already talked about and so then talking about kind of the mechanics of some of this then this venom goes into a human body or whatever a prey animals body and that there's different components of the Venom that act on different parts of the body you might have some attaching to a blood cell you might you know you might have some as you said attacking proteins around a vessel you might have others that are going off and attaching to you
• 33:30 - 34:00 know some type of nerve or whatever it might be um that's interesting so there must be a all of these all of that biochemistry must happen at kind of different rates if you will and and so there must be kind of a a natural progression of symptoms to a snake bite depending on say the species and maybe a lot of other factors but is that something you see and snake bites where maybe you get some initial light
• 34:00 - 34:30 paralysis and this is completely hypothetical right and then you start to see tissue break down around the area of the bite and then later on they'll start losing their sight or whatever it might be but um do you get this kind of natural progression with certain species where where these you have all these molecules in the body they're affecting different things and and those happen at different times or am I completely off you know my rocker here no no I think that's a good
• 34:30 - 35:00 generalization I have to state that I'm not a physician and I haven't I've experienced snake by but I haven't treated it personally um but from discussions with a lot of clinicians that do emergency medicine and actually work with these things yeah this is a progressive issue and Dr Sean Bush a number of years ago came up with a little adage time is tissue and that's meant to be that indicate
• 35:00 - 35:30 that what you should do is get to clinical help get to a hospital as quickly as possible and the longer you have in a delay of that time the more of an effect is going to be unchecked we you don't have your own antivenom typically that you would inject and so when a snake bites most of the snakes will strike and venomade and release and rattlesnakes can do that in about a quarter to a half of a second so they're very very fast what they do is release a large
• 35:30 - 36:00 Bolis of Venom that can you can think of as is now deposit as a Depot typically Under the Skin if for some reason it happens to get into a blood vessel that can be very problematic very quickly and we've had some incidences that seem like that's what's happened um and had fatal out outcome from something like a prairie rattlesnake a couple of years ago here um so if it's deposited Under the Skin not in
• 36:00 - 36:30 a vessel though it's going to diffuse out from that site and so the effects you're going to see locally are going to be most extreme and then what we see are various aspects depending on the type of Venom it is and so if it has neurotoxic um components in its venom then we'll start seeing neuromuscular functioning compromis and that can in fact be manifested in problems with
• 36:30 - 37:00 blinking with swallowing and of course if it goes systemic and gets into the body proper then we start having breathing problems as well and that that's where we can have you know when when if a cobra gives a good bite delivers a lot of Venom to a person then those molecules diffuse through and they can get to the site of the franic nerve diaphragm and compromise breathing muscles fairly quickly and if that again if that happens that can kill a person
• 37:00 - 37:30 fairly fairly quickly half an hour to an hour so um so yeah the the whole aspect though is that things tend to get worse before they get better and when you go to a hospital and seek treatment for something like a rattlesnake bite you have an expectation that okay now you're at the hospital things are going to get better but that venom has been in place for some period of time ideally a very short period of time perhaps hours or or even longer and
• 37:30 - 38:00 so as that happens not only does it have effects on the tissue that's closest but it also liberates things from your own body and your own cells that can be promoting damage as well so again that's why there is this adage of getting to a hospital as quickly as possible and the idea of the best first aid are your car keys I get in your car and get to the hospital quickly as possible yeah um because
• 38:00 - 38:30 that's that's really antivenom therapy is still the major therapy that we have [Music] available couple more questions about Venom and then I want to talk a little more specifically about some of the research you've been working on with Venom but um we talked about diversity of Venoms and I think we have kind of been talking about it in in a sense kind of like say among taxonomic groups among species or or families even but um talk
• 38:30 - 39:00 a little bit about Venom diversity um even within a species both maybe space and time and and what I mean by that I'll take animal I work with quite a bit timber rattlesnake so um you know I know there's been a fair amount of work looking at Venom in different parts of the rattlesnakes range so that's what I mean in space is their diversity does it vary and then in time maybe talking a little bit about you know some of the types of things you've worked on say during your Master's
• 39:00 - 39:30 research sure um well one of the things I've always kept in mind is you should always have something in your backyard to work on right something that's convenient and proximal to where you are and so we have three species of rattlesnakes in Colorado and we've worked with all of them and all and Venoms and aspects of their biology with all all three species but primarily been focused on masaga rattlesnakes which are
• 39:30 - 40:00 a species of special concern in the Southeastern part of the state and fated rattlesnakes that we have a field project going on right now that's funded by BLM looking at distribution excuse me and relative abundance in the western part of the state and primarily in the west Northwestern part of Colorado and then into Utah in the canyon country but it turns out Ratt Prairie rattlesnakes which we kind of were ignoring because they're very widespread
• 40:00 - 40:30 and common you know these other things are sexier SES to work with turns out that the patterns that we see in prairie rattlesnake Venoms are really quite interesting and one of my PhD students that finished up a couple years ago Cara Smith who now poststocking at a lab down in nons medical center in Denver was the one that spearheaded this work looking at prairie rattlesnake venom and its composition all the way from right at the edge of Southern Canada down to the edge of Mexico and it occurs
• 40:30 - 41:00 very broadly across the Great Plains long story short what she found is that right in the vicinity of Interstate 70 we just use that as a marker because most people know where that interstate is the Venom shows a very disjunct change and so north of that the Venom is dominated by low amounts of these tissue damaging components the metalloproteinases but high amounts of a small peptide toxin called myotoxin a south of that we see the opposite
• 41:00 - 41:30 situation that these digestive enzymes metalloproteases are much much higher and the amount of that myotoxin a is very very low relative to what we see north of that so right in the middle of Colorado we see this disjunction in the Venom composition and that Northern phenotype or Northern type of Venom that we see is like that all the way up through Montana right into the border with Canada and Southern phenotype that we see on the south side is like that
• 41:30 - 42:00 all the way down to the Mexican border so that begs the question of why this big difference in venom composition and Cara was very good at trying to get at that looked at differential pre use and things like that long story short again we're not completely sure what the driving force is for that kind of difference except perhaps during glaci iation events a lot of the ranges of rattlesnakes were
• 42:00 - 42:30 shifted far south and then after the glaciers retreated snakes move north and we see that in a lot of the snakes as well so it's possible that associated with that response to changing climate there was also a change in the Venom composition but that's that's pretty hypothetical there's some kind of loose correlations with difference in prey use so in the northern groups we see almost exclusive use of mammals in southern
• 42:30 - 43:00 groups we see mammals but also lizards are eaten lizards are much more abundant As you move farther south as well different species are found in those areas so there is also an possibility of one of the factors being this U more diverse prey leading to a different type of Venom in the southern snakes so there are a number of examples like that as we go across around the world and look at species that show this north south
• 43:00 - 43:30 latitudinal difference in distribution India has cobras in the North and the South their Venoms are different enough that sometimes the antivenom that's produced mostly against the southern is less effective against the northern and some of the East West differences as well so it has practical consideration so the prairie rattlesnake turns out you know we're kind of looking down our nose at it initially but it actually is a very interesting species to look at in more detail you mentioned
• 43:30 - 44:00 as as part of that uh description of prayer rattlesnake venom mentioned myotoxin what is a myotoxin well again there's debate on where exactly that molecule hits but it's not an enzyme it doesn't catalyze reactions doesn't chop up proteins and things like that instead what it seems to do is bind to a particular type of protein on a particular part of the muscle that produces the effects and this is
• 44:00 - 44:30 based on work when I was a postto with Anthony 2 at Colorado State University he had a PhD student ponac uton from Thailand who did some really good work looking for where does that molecule actually affect skeletal muscle because what we see is mice that are either injected with that or bitten by Prairie rattlesnakes in the northern area one of the first things that happens is they hyperextend their limbs
• 44:30 - 45:00 and they're they show what's called a tetanic paralysis so their muscles are contracted but they can't move at all and it happens it immobilizes mice just like that so prair rattlesnake from our area of Weld County Colorado if it hits a mouse that Mouse isn't killed immediately but is stopped almost instantaneously so it's a very potent toxin from that perspective as far as stomping prey which is what snakes want to do right stopping mammals or stopping all all
• 45:00 - 45:30 prey well that's another interesting aspect of the molecule we've done comparative toxicity studies both in animals but also in tissue baths and have shown that it has almost no effect against lizards so you can give a very high dose to a lizard like a fence lizard or earless lizard has no effect on it lizards are primarily eaten by smaller snakes it's just a size based thing adults will will
• 45:30 - 46:00 take things opportunistically but they typically want to feed on mammals bigger package better protein load and all that kind of thing well it turns out that in the baby rattlesnakes in the same area where the high myotoxin levels are in the adults they have half or a third as much of that myotoxin as the adults and they actually show more in the way of those digestive enzymes in their venom than the adult do so that pattern is kind of backwards
• 46:00 - 46:30 from what we saw in the Pacific rattles snaks when I did my masters so many years ago so yeah fascinating rather interesting thing there is this association with dominant pre type Venom composition in some cases but yeah if you enjoy listening to the snake Talk podcast stay in the loop with the orian society's latest con conservation updates from the field read about new
• 46:30 - 47:00 published research as well as fascinating insights on the species we work with by following us on social media follow like share let's spread the word together we can make a difference find the orian society on Instagram Facebook X or LinkedIn and be part of the conversation well uh let's let's move on and talk a little
• 47:00 - 47:30 bit about um talk about kind of some of the work you've done in your lab relative to you know you talked about practicality like the uses of Venom whether that be for you know say the medical field human health um or or other kind of uses and um so maybe I'll just kind of leave it at that but um maybe could start off by talking about Venom we've talked about how complex it
• 47:30 - 48:00 is but why um maybe why has venom been uh a a fruitful place to examine for for all kinds of practical uses um and and then maybe kind of get into some of the things that that you've been working on over the years in in that Arena well Venom interest in Venoms and Venom actions and composition and what's in all these Venoms has been of interest
• 48:00 - 48:30 to people for a very long period of time primarily because when they get bitten by venomous snakes you know Terrible Things tend to happen and before we had modern medicine interventions there wasn't a whole lot that people could do you know chop off a limb hope for the best those kind of things come up with some kind of magic incantations or something but as we move more into the modern world of analytical chemistry biochemistry molecular biology
• 48:30 - 49:00 and then into the genomics proteomics era our ability to go in and ask what is that Venom made up of has increased tremendously and as that has happened it turns out that Venoms that have a 100 different components for example those are not a 100 different proteins they're only about 15 or 20 different proteins but the genes that code for them have been duplicated some cases many many times and so we have all of these
• 49:00 - 49:30 different genetic copies that are slightly different from one another well this is exactly what a combinatorial chemist does if they're looking for drugs for treating whatever mality we might think of they're looking for things that are closely related they typically have some idea of a compound that might go in and interact with a cancer cell let's say on a Surface based protein in a certain fashion but it doesn't really do what they want and so changing
• 49:30 - 50:00 the chemistry of that molecule slightly trying the experiment again again and again well snakes have done that over the last 50 to 100 million years they've tinkered around evolutionarily with these molecules that hit all these different systems and so again we have one class of proteins say those Metallo protases and one of the things that interested me very early on was okay if you want to use something like that to digest blood vessels and tissues
• 50:00 - 50:30 of prey that's great why not produce a huge amount of one why are there three different classes of them and perhaps 15 different versions of all those in a single Venom from a single individual in part it's because there's this Dynamic play between predator and prey so if the snake's on top the Venom works really well kills the prey quickly it gets a meal every and the snake's happy the mouse is not but that sets up
• 50:30 - 51:00 a selection scenario where if there is something in the physiology of the prey that gives it Greater resistance to that Venom those mice are going to be survivors so we get this Dynamic back and forth complex interaction between predator and prey that some people have referred to as this co-evolutionary adjustment back and forth and that has in fact largely been responsible We Believe to
• 51:00 - 51:30 why there are so many different Venom components going back to using those as Therapeutics or possible drugs again those V various variants have already been provided for us now back in the 60s I came across a paper where Cobra Venom crude Cobra Venom was being used to treat schizophrenia at that time they knew that there were neurotoxins in the Venom schizophrenia had to do with the nervous system so maybe put those together and
• 51:30 - 52:00 something happens well it's a very simplistic sort of um mindset and the analogy that I use is you can remove a tumor from someone with a shotgun but that's going to cause a lot of collateral damage and that's how these Venoms are on the other hand if you purify those Venom components characterize them carefully and have some idea of what you're looking for in all those different variants that have
• 52:00 - 52:30 evolved in a prairie rattlesnake or a Timber rattles snake or your favorite venomous snake from around the world those may actually have some use in doing something very different from what the purpose was that evolved and I can give you an example of that that involves molecules that are referred to as disintegrants so a number of years ago in collaboration with David chazar who was a a professor of psychology down at the
• 52:30 - 53:00 University of Colorado Boulder he's since passed he and one of his students Anthony saviola and I worked on this project together asking the question okay David showed that snakes once they've inven a mouse can actually follow the inven trail preferentially and go after Mouse and if you do why mazes and all these other types of Behavioral tests you can show that very nicely the basic question was how do they do that and so what we did we began taking
• 53:00 - 53:30 the Venom apart and we hypothesize that some of these proteins that are toxic and cause all sorts of horrible tissue damage and changes to prey would be the ones responsible for that turns out that's not the case there's a little molecule in a small amount called a desron it's not even very toxic if you put it in with cells it doesn't really kill them that molecule by itself self when injected into a mouse allows a snake to
• 53:30 - 54:00 be able to relocate a prey that was inv venomed even though it was just a fraction of the Venom not the entire Venom so the snake has this relocator protein in its venom which is makes sense and we only find it in vipers we don't find it in snakes that are strike and hold feeders like most of the elapids people have looked at disintegrin and Anthony decided to look at disintegrin in more Det detail as well it turns out that they have some
• 54:00 - 54:30 very interesting properties for for treating Cancers and in some of the cancers what happens is when the cells begin to migrate away from the S side of an initial tumor formation they become metastatic they actually have little legs called integrant that they use to move out and they digest their way through tissues and such to move about the body and that's when cancer has become very critically hazardous well these disintegrant actually bind to those integrants and they inhibit the
• 54:30 - 55:00 ability of those cells to move around and Anthony showed that with a molecule from a tropical rattlesnake that we got on a on a confiscation years ago and did some very interesting work in the lab in working with cancer cells and showed that that molecule by itself inhibited metastatic activity or movement activity of cancer cells so here we've got something that has potential as a therapeutic
• 55:00 - 55:30 development and there's a lab in USC and Southern California Frank Markland he did a lot of work with one from Copperhead Venom and in fact here it has anti-cancer properties perhaps but the snake didn't evolve this this didn't evolve in the snake for our use for treating cancers right it uses it for something very very different so it's kind of an interesting example of where
• 55:30 - 56:00 basic biology basic chemistry can inform applied chemistry so we've got these two things that are seemingly different but involve the same molecule yeah that's fascinating um and uh so any other examples that that you've been involved with of of say snake venom being developed whether it's in the medical field or or something else I mean I know there's a lot of examples of never heard like Mamba Venom being used to develop medicines for ALS or heal a
• 56:00 - 56:30 monster Venom or or or or whatever it might be um blood thinners but are there any other examples that you've been involved with that that you think would be worth kind of mentioning well we're really in the business on that end of things of evaluating Mo molecules for uh drug Discovery rather than clinical applications and this is where when when we some of our work has gotten into the lay press newspapers in particular we
• 56:30 - 57:00 get calls from people asking if you know they can enroll in a therapeutic trial or something and we don't we don't do that at all I mean that's that's a whole different ball game um so we have worked with a number of different Venom protic enzymes these ones that clip proteins cut up proteins amongst them that we talked about the Metallo protases those kind of wreck havoc with blood vessels and tissue and things like that but there's another group of them called the Serene
• 57:00 - 57:30 proteinases a different type of protein that tends to be much more specific in its action and again we've characterized a number of these from things like U fad rattlesnakes and from uh Russell's Viper from India and I had a had a visiting scientist here for a year that did a lot of work with with one from the Russell Viper in particular um and that has the possibility being developed as a anticlotting agent if you will and
• 57:30 - 58:00 that has certain applications for times during surgery Etc you might want to drop one's ability to form clots but you don't want to keep it depressed but just for a short period of time so we've had a little bit of that more tangential not really direct therapeutic development but some ideas here along that line correct you mentioned the heila monster and there are two Blockbuster drugs that have been developed from helila Monster Venom one of these is beteta that's been
• 58:00 - 58:30 used to treat type 2 diabetes and then more recently a very similar molecule OIC that also was developed for type 2 diabetes but is used for um obesity control and in that role that thing has gone off the charts as far as sales and such um so there are some compounds that are out there that have been developed from Venoms and are very very successful drugs there's a ace inhibitor captopril
• 58:30 - 59:00 that was developed based on some peptides found in South American vipers Venoms and that probably is the single most important drug from Venoms as far as how many people globally are are helped with high blood pressure from either that drug captive P or some of the spin-off secondary drugs that have been developed based on that and then again that comes back to the whole
• 59:00 - 59:30 Venom the whole Venom is very very damaging because it's kind of like that shotgun blast but here if we look at particular molecules and we know a little bit about what to look for we can actually find some things that have very good therapeutic value so well we've been going almost an hour so I don't think we're going to be able to get into the topic of kind of genetics ecology natural history but um just want to recognize that that you do
• 59:30 - 60:00 also work in those Arenas um but one last Venom question then we're going to begin to wrap this up um so we've talked a lot about Venom we've talked about different research projects um both you know whether it's more towards Evolution and uh or towards very practical applied uses um what do you see as uh you know you've you know assuming you'll be doing research for a good number of years now but you're you know you're on the uh the other side of the curve in your career
• 60:00 - 60:30 um what's the future of Venom research um what are the big things that that we need to know or people are starting to to look at um you know just and that could be just in the basic biology of Venoms all the way down to some of these practical um uses well it's interesting as we develop more sophis icated analytical tools we can ask the same questions and probe
• 60:30 - 61:00 that much deeper right and so as proteomics and genomics have become much more commonplace we can ask questions like what's the Venom made of what are the genes that code for it how are those regulated Etc and they can also you snakes and snake venom glands can be used as models for all sorts of other types of processes secretion of materials Etc things like that that would occur in in non Venom systems as well as far as evolutionary questions
• 61:00 - 61:30 wide open you know what are the driving forces for first evolution of Venom we have some ideas on that you know being able to stop something chemically by injecting it and getting out of the way while it's going through fits until it's mobilized direct Advantage there why do we see all these different types of Venoms if you look at a cobra Venom versus rattlesnake venom the components are are really quite different there's some shared things but there are a lot of things that are unique to each one you know why do we see diversification
• 61:30 - 62:00 along that line in that lineage and along this line in a very different lineage of snake so all sorts of different evolutionary questions can um we can start addressing those in a lot more detail now um more recently there's been a lot of interest in small molecule therapies for treating snake bite or alternative therapies to antivenoms and we've had an opportunity to interact with a number of different groups and this is where collaboration between
• 62:00 - 62:30 people that have different skill sets has led to some really cool and really rapid advances in our understanding and so we're seeing molecules that were used in clinical trials for treating cancers or treating some other disease they failed in clinical trials but they actually are targeting molecules in cancers that are very similar to what we find in Venoms and so can we repurpose those drugs that have already gone through some clinical
• 62:30 - 63:00 trials in humans as far as safety and apply them to a different situation and system and that's what's happening right now even more interesting is the use of what are called mini binder proteins so there's a group in Seattle at the University of Washington that are essentially Wizards at doing ins silico design so instead of having wet bench chemistry trying this and trying that of all these different variants of molecules they're able to model those
• 63:00 - 63:30 the toxic molecule and then something that might neutralize that and we've collaborated with that group we have a paper that's under review in nature right now that hopefully will be published shortly that shows these mini binders are incredibly potent Inhibitors of some of the most hazardous three-finger toxins these neurotoxins that par paralyze and kill animals and including humans very very quickly and they are useful up to a half an hour
• 63:30 - 64:00 after we've only gone to a half an hour but they're useful as a therapeutic a half an hour after a toxin has been administered and so that's really encouraging as far as here's something that may not replace antivenoms but in fact can be used as a first aid therapy can be given as a im shot in your arm just like you get with a vaccine or something like that it's fairly stable molecule it doesn't require refrigerators so we can that
• 64:00 - 64:30 problem of having a long period of time between when the bite occurred and when you reach treatment we might be able to shorten that in rural areas around the globe where snake bite is most problematic to a much better chance of surviving the bite and also decreasing morbidity because you can survive something like a s scale Viper or Puff out or bite but you may may lose your limb and if you are an agrarian individual that greatly compromises your
• 64:30 - 65:00 livelihood so so there are a lot of different areas like that in snake venom biology a lot of people have gotten interested in in the field in general because there's a nice correlation between the phenotype the genotype and the fitness component I if a Venom doesn't work it's not going to be too useful for a snake so well I like as as you know um I like all of my guests to tell me a good snake
• 65:00 - 65:30 story so uh what's your uh you have a good snake story for us today Steve a good snake story well I guess there could be a couple of them um but one of the most profound ones came from my earlier childhood that is my teen years working at this company that's zoos and schools and as I mentioned took care of all sorts of venomous snakes one set of these were
• 65:30 - 66:00 three king cobras that we had in one cage the small ones were 11 and 12 feet the big one was 14 feet and it was my job to clean the cage and so I moved these from a the cage to a trash can one of the snakes the biggest one 14er would have nothing of it and so for the next 20 minutes or so we did this pirouette dance of sorts where the snake would Hood about 4T off the ground chase after me I would get
• 66:00 - 66:30 outside the door close the door snake would turn around would go through the same thing trying to get it back under control so that went on for like I say 10 or 20 minutes one time I didn't get the door closed quick enough got out of the door got out of the secondary door into the main room where we have the harmless snakes and uh we were able to Corral it into another room that was for amphibians that was colder that's when I decided Well let's see $3 an
• 66:30 - 67:00 hour this is probably above my pay grade at right now called the boss in he ended up pinning it down and we contained the snake so no no one was damaged no snakes were injured in this whole Adventure but it was a fairly profound demonstration that uh you know some of these snakes have a lot more going for them than we might give them credit great story and hearing that story and also you know a lot of what we talked about just thinking you must be like in a Cook's nightmare in terms of
• 67:00 - 67:30 you know your your sub subjecting certain animals you're injecting them with Venom and then you know the human safety component for those listeners that don't know an iook is like a um university entity that looks at Animal Welfare issues and human safety and all of these things so um I'm sure you deal with that quite a bit maybe you probably chair the committee just so anyways I've been on the committee and I'm an advisor to it um I've been here for about 30 years and in
• 67:30 - 68:00 that time we've handled thousands of snakes and we had no accidents and so you know having a an unblemished record of working with venomous snakes um does help considerably yep so yeah that's that's great and you've only had the one bite it sounds like or you didn't tell any others so yourself you've and I've only I've never had a a venomous snake bite and um mostly have handled vipers but you know I've had Bush Masters and
• 68:00 - 68:30 some other more serious vipers over the years and um but I've probably had trying to calculate it you know probably over 10,000 handling events some of those are same snakes over and over and I've never had a bite and to me that's a badge of honor people often you know it's always a question did you get a snake bite or you know people want to talk about that but the idea of of not getting a snake bite that that's what I'm proud of not want to show off the rattles B I got you know so they make for good stories but I'm glad I've never
• 68:30 - 69:00 had yeah yeah when Anthony gave his defense seminar a question at the end was have you ever been bitten and he said no and I intend to keep it that way and the person's like well you know doesn't that give you some Street Credit if you've been bitten and he's like no it does not it means you were careless yeah there you go and so we try to keep that in mind and and again again there's snake bite is something you should experience vicariant go online and see the pictures
• 69:00 - 69:30 and let it go at that um it's really on a good day it's a miserable experience on a bad day it can leave you permanently damaged or dead so um free handlers no no reason for doing that well Steve thank you so much for uh joining us today on snake talk it's my pleasure and I just wanted to thank the audience and tell everybody to remember
• 69:30 - 70:00 snakes are animals too and it's a privilege to see one in the while [Music]