Venom Tech

I've heard. But if you've been listening to this podcast for a while, you probably know Lauren and I sort of have a tradition that when Jonathan's away, the Scorpions will play, or or the creepy Crawley's of some kind. Whenever Jonathan is out, we tried to do a podcast about bugs, and it's surprisingly fruitful in terms of future technology. Yeah,

who knew. Um, So today we're going to talk about something that was an idea Lauren had and I think it actually turned out really cool, the potential for future technologies and current developing medical technologies based on positive uses of venom venom animal venom. Yes, Lauren, do you have a venom story? Have you ever been stung or bitten? By any kind of creature that put poison under your skin. Uh, No,

that's a boring answer. No good spiderbytes, scorpion stings, anything like. Um, I mean, I guess I've gotten like a tiny spider bite once or twice, but I mean, you know, or like an ant bite. Our ants venomous? Yes, yes, they are many creatures that inject some kind of poison into your body are venomous. Wait a minute, now, I think we're having a little vocabulary mix up because I think you just said poison, and that's not exactly the same thing as venom, is it. No, it's not, though in

sort of popular parlance it might be. But let's let's talk the science talk what does it actually mean? And when, like a biologist says venom versus poison? Well, I was curious about this, so I looked it up and there there's a paper called complex Cocktails, the Evolutionary Novelty of Venoms. That was it was report in Trends in Ecology and Evolution,

and this gave the following definition of venoms. Specifically, they said it's a secretion produced in a specialized gland in one animal and delivered to a target animal through the infliction of a wound, regardless of how tiny it could be, which contains molecules that disrupt normal physiological or biochemical processes so as to facilitate feeding or defense by the producing animal. That's kind of a mouthful, but it has a lot of detail there. That's kind of a good MEATIA definition.

So it it includes that it's not a passive distribution of the chemical. It's produced by the host animal. Uh. The animal delivers it to another animals somehow through like a bite. There's some kind of injection and it facilitates either defense or or predatory behavior. And this sort of goes in line with a popular definition just for the common speech level. I looked it up in Mariam Webster. They said venom was a poison that's produced by an animals such as a snake, used to kill or injure

another animal through biting or stinging. Uh So, basically, the difference between a venom and a poison is the delivery vector of the icky stuff, and venoms are injected by like specialized usually like hypodermic needle like teeth or stingers, and poisons are just secreted, uh like in lazy lazy frogs, oh, the poison dart frogs. Yeah. Yeah, they're the hippies of the animal kingdom. I'm telling you right right, because they just wait for you to come up and handle them. Yeah,

and that's how they get you. Yeah. So the easy rubric I guess is that if you seese up an die after an animal bites you or stings you, that animal was venomous. But if you die after you eat an animal or you catch it and rub it all over your naked flesh, that animal was probably poisonous. Probably, Although it's a good rule of thumb to not go around eating animals if you're not sure that they don't contain little sacks of really potent neurotoxins I, unless you're

really sure of what you're doing. Um, eating a venomous snake is really just as bad as eating a poisonous snake. And there are poisonous snakes. Some snakes are both venomous and poisonous. Really, like a snake that would be poisonous to eat or handle? Yeah, bad times, Stay away from that guy. I always thought that the use of poisonous snake was just kind of like people using the word wrong. So different different animals have all kinds of different stuff

going on. How true that is? And in fact, I came across a really interesting little fact on the side while I was researching for this episode. So, some poisonous animals, like the family of poison dart frogs, don't actually make their own poison, but they acquire it from the environment they live in. So it's thought that they eat some kind of poisonous prey and then they appropriate that poison

into the poison that they wear on their skins. So you rubbed the frog all over you and then you get sick or die, that's actually because of something that the frog itself acquired from nature. Okay, so let's do a few quick Venom facts before we get into the Venom tech. Joe and I might be really excited about this. If you cann't tell listeners, well, I just yeah, I

love venom wisdom Venom is that? Does that have something to do as Spider Man, because I don't feel like Venom had a lot of going on in the wisdom category. You are much more the comic book nerd around here. I think you know more about venom than I do. As we've established, I'm sort of a fake geek he's he's he's kind of a raging i'd sort of so, yeah, okay at any rate? Yeah, no, no no, no, just so

venom facts. Yeah. Yeah. So the obvious question that always comes up, it's like it's sort of the kids playground argument, right, what's the most venomous animal in the world. But actually that's a question that's kind of hard to answer because you can't measure it by which ones kill the most animals or humans, because this might be based more on like which ones were exposed to the most options, number of bytes, access to healthcare, and anti venom after you

get bittendis lots of these things. And it's not like a venom has a base level of toxicity that there's an easy litmus test for. It's it's really just how does it interact with cells? And and most venoms are made up of multiple proteins and peptides that have different effects on different cell structures, right, So one venom might have a bunch of different toxins in it, right. Um. The old method for measuring toxicity is called a substances l D fifty, which is the lethal dose l D

of a substance that will kill of test animals. It's measured by the weight of the substance needed per one or one m, depending on how big of a critter you're talking about of the test animals body weight, so low numbers are more deadly. For for example, a box jellyfish's venom has an l D fifty of zero point zero four. Uh, don't eat their stingers, that would be bad. Um. A coral snakes LD fifty is one point three um.

And now if this method sounds like a lot of animals were harmed in the making of this this research, you're correct, and that's why people don't use it so much anymore because it involves killing a whole lot of test animals. Really yeah, bad times. So a lot of times you'll see animals when when we're setting up these great venom competitions separated into different animal groups. So some people say, for example, that the most venomous snake might

be the inland type hand snake of Australia. A lot of these things hang out in Australia and they really do. Like these funnel web spiders like those those are just like these little eight like a Darth vaders that live on the ground in Australia. I feel bad for If we have any Australian listeners, please right in tell us about all the venomous creatures that you find in your bed at night. Uh but yeah, so the inland type hand. Supposedly, the amount of venom usually delivered in one bite by

this snake is enough to kill a hundred adult men. Fortunately, we have ways of treating this. We have an effective anti venom. By the way, do a quick Google image search if you're listening on a computer of the inland type hand. It does this thing where it raises a coiled section of its upper body up off the ground, and it looks so intimidating it's almost funny. It looks like it's some kind of like snake shaped airplane. In mid take off, it's like winding up into the sky.

In the next frame, it'll be off the ground, all right. Also another fact, taipan apparently means something like big shot or tycoon in Chinese. That's beautiful, that's that. And the spelling of that, if you're trying to look it up, is t A I P A N. So go go check that out. Um. But uh yeah, other other creatures, I mean, you know, a lot. Lots of things are venomous that you probably already know about, but some really interesting ones. We wanted to hit on a couple. Yeah. One,

I really like our cone snails. You know about these cone snails? Cone snails? Look them up? They live under the ocean. Uh. Some cone snails shoot prey with these bio harpoons they have containing neurotoxins. Snails have a lot of have a lot of harpoons going on, guys, anyway, go ahead. Yeah, there are also species of cone snail

that I just read about this today. They attack their prey with blasts of insulin, which cripples fish by drastically lowering their blood sugar, and then the snails can just kind of lurp them up. Yeah. Yeah, there's apparently a couple of different species of kinds down. Some of them have these little harpoons, and others have this kind of area effect. They they sort of let loose this this miasma of toxin stuff. And one of those toxins is insulin,

And that's crazy to me. They're they're looking into using, um,

the production of this insulin for like diabetes research. Yeah, and that highlights something we're going to talk about in the medical tech part of this episode, which is that a lot of these toxins can have a positive effect on the body in one way or another if you have a specific kind of thing you need to do, because these toxins are designed by evolution to be efficacious to create some kind of change in animal bodies, right, and if that's the kind of change you want to

create to help somebody's medical condition, it can be good news. Oh yeah, absolutely. Um. One more that is not useful as far as we know is platypus venom Did you guys, were you aware that platypuses are venomous? I did not know this before today. Is this common knowledge? I thank you for not using the word platypie. That's not a word. I don't I don't think it is correct. I think it's like octopuses, Like people have slowly started losing that bizarre poor latin um. I think I might have heard

that platypuses are venomous. But tell me about it, Okay. So, male platypuses specifically have spurs on their hind legs, like one on each hind leg that can provide a sting um. Females are born with these spurs, but they fall off before they reach adulthood. Um. And these spurs are used in defense against predators because I mean, I would not attack a platypus because it's really cute. But I understand that not everything in the wild has those reluctances. But um,

they can also be used. The spurs can also be used used offensively during mating season against against platypuses competitors for a specific mate. I'm yeah, yeah. Um. They deliver enough of a punch to to kill something the size of a of a platypus or say a dog, but not a human, although their venom does cause a great deal of pain in humans, and it does so by

some neurotoxin mechanism that is not regulated by morphine. So so if you get stung by a platypus and you go ow lots of ow, and a normal doctor response would be to be like, well, oh, here's some morphine that will help you feel not ow anymore. Doesn't work?

Oh wow, Yeah, that's crazy. It's like they thought of everything, you know, though, I do have to imagine in the wild, most platypus deaths are the result of over zealous nineteenth century naturalists from like the Great London Society that that sounds likely. It's a very sad there should really be a conservancy group, Pip Pip. Yeah. But despite all this, I want to highlight that it's really important not to demonize venomous animals, especially platypus. Is right, we don't need

to wipe platypuses off the face of the earth. We don't need to get rid of the inland type. And generally these animals are not very threatening to humans. They just want to be left alone. Venom is a strength trait that these creatures possessed to survive, just like your dogs teeth and jaw muscles, or your meaty hands which I point out are perfect for punching and strangling, or your big mutant brain. I mean, all kinds of creatures

have defense and predation mechanisms. Just because it's scary to you doesn't mean that these creatures are worth being looked at a scance, right right, And as we mentioned briefly earlier and are about to go into in detail, a lot of the venoms that these things produce have these awesome medical uses, another reason not to demonize them. Yes,

a lot of time venoms are neurotoxins. These see, they affect the nervous system and can cause on on the negative end, anything from like dizziness to difficulty breathing, to blurred vision to muscle seizure. And and that idea in nature is generally to either paralyzed prey so that you can eat it yea um, or to hurt predators enough

so that you can escape from them. And uh. Other toxins might like affect other types of cells like blood or skin cells, which um you know, usually by killing them by like rupturing the cell walls or something like that. One really common one, um you might have heard of it before, is using a proteins from snake venoms to help dissolve blood clots in patients experiencing a heart attack or a stroke. I think that's kind of the the commonly heard of venom technology. Um, but lots of toxins

can be very useful. Yeah, And in fact, we already use all kinds of toxins from venom in medical research today. And we wanted to highlight a few of the strangest and cool idea as we came across, and especially the kind of upcoming ones things that are still being sort of ironed out. Yeah, so I want to talk about attacking brain tumors with scorpion venom. Okay, let's pretty weird idea.

Uh yeah, I would not. I mean if I had a brain tumor and my first thought would not be let's get some scorpions, Well, it might be soon, and I want to paint a picture for you and help explain why this would be. So. So let's say you have a tumor in your brain. Obviously you want to get that tumor out of there. Yes, So you need to have a surgical procedure where they go in, they open up your skull and they remove all the tumor tissue so that it doesn't spread to other parts of

your body or keep growing and eventually kill you. So you want to cut out all of the cancer cells while we're moving as little healthy tissue as possible. But especially in the brain, that's really tricky. Yeah yeah, yeah, Well it's not always as easy to tell the difference as you might think. So you can take a pre op m r I. You can put somebody in an m r I machine and get a picture of the inside of their head to try to get some idea

of what the edges of the tumor look like. But this isn't perfect and you can miss sections and that's really bad. This often happens. You hear about this, people going to have a brain tumor removed, and it only turns out later like, oh no, right, we didn't get all of it, and then they might have to have another surgery, and uh, it's a very bad thing. On the other hand, if you cut too much, we're talking about the brain here, it's pretty obvious why that is

not a good option. You don't want to remove healthy tissue. You can have debilitating effects. So there's a guy named Jim Olson who's a pediatric oncologist, mean he treats cancer and children and a clinical researcher at the Fred Hutchinson Cancer Research Center in Seattle, And for a while now he's been leading research on a medical technology to help with this problem. And it's called tumor paint. Tumor paint, weird name, but hold on for a second here and

we'll we'll explain how it works. So, tumor paint is a protein linked fluorescent dye and it's derived from a toxin that you find in the venom of a death stalker scorpion. Death stalker scorpion. Best name for an animal ever come up with by anyone, the death stalker scorpion. So the relevant toxin is called chloro toxin, and this is a toxin that works by blocking chloride ion channels

and cells. And the death stalker scorpion uses the toxin to paralyze its prey, which would be you know, tasty insects like cockroaches or something, to paralyze them, not not monom eatum up. The thing about chlorotoxin is that it's not toxic to humans. Side note, this does not mean that death stalker venom is harmless to humans. There is other stuff in there that will get you. Don't go playing with those things in general, do not go play

with scarpions. No. But when applied to humans, chlorotoxin actually tends to bind or it's sort of like prefers to bind to glioma cells. And that's one type of it's a particular type of brain cancer cell. So you make the tumor paint by joining two ingredients, you've got a chlorotoxin based substance that does what it does. It binds to these tumor cells in the body. It seeks out the cancer cells and it penetrates them and then linked

to that, you've got to die. That lights up when viewed under a special camera and lit up with a near infrared laser. So in the surgical context, what you do is you have someone with a brain tumor and you're about to go in for surgery, and you inject

some tumor paint into the patient. It binds to the cancer cells in the brain tumor, and then the surgeon can shine that near infrared laser at the brain section to make a hidden tumor into a glow in the dark tumor, and it's easy to disting ship from the surrounding tissue, and viewed through that special camera that they have right next to the operating table, it glows this

blue green. Therefore, it's easier for the surgeon to manage the margins with precision, you know, getting all of the cancer with without removing too much healthy tissue around the sides. According to s September press release from the Fred Hutchinson Center, version of tumor paint called b l Z one hundred

was approved for clinical trials in the United States. And that's really exciting news, but it's also a reminder that you know, the safety and efficacy of this method is not fully proven yet and the treatment has a lot of testing left to undergo, so we don't know everything about it yet. But it's really interesting and exciting that this could be a big breakthrough and how to help people with brain tumors. But as great as it sounds, it might not be the only application of tumor paint.

In addition to these brain cancer cells the glioma, it might be useful in pinpointing other can't your cells like lung cancer, breast cancer, prostate cancer, colorectal and sarcoma's. They've even talked about using it to pinpoint non pigmented skin cancer cells that are hard to see. Wow. Yeah, yeah, Oh that's terrific. None, none of the things that I have been researching for for this podcast are quite at the clinical trial stage yet. They're all still being done

in in animal testing, but are nonetheless pretty exciting. Um there there's some indication that a particular type of spider venom could be the viagra of the future. Really now, see, okay, I have to reveal here. Oh this that sounds weird No, I was just going to say that, I am. I don't like spiders, okay, I mean, I really appreciate them as animals. Actually, I love looking like at pictures of spiders on the computer and stuff. I don't like it

when they're in my house. They kind of freaked me out. I think that's that's completely understandable. There's a whole science behind why we find spiders super creepy. Um. They they set off all of these evolutionary things that are like, why is that thing moving that way? And why is it scuttling towards me? Um, scuttling. The scuttling has a lot to do with it. They do seem like, even though they're quite common on Earth, they seem like aliens. Yeah. No,

I'm with you. They're super creepy. I think they're very beautiful. But um, okay. So one side effect of some arthur pod venoms is priapism, which is after the gods, right, is it is that? How that gets there? That's cool? I believe I believe he was a an amorous deity of Greek origin. Okay, yes, so, so priapism is a painfully extensive erection, all right, um of the penile tissue and uh specifically two or three Arthur pods, all of

them from Brazil. We've got the extremely toxic Brazilian wandering spider and the Brazilian yellow scorpion um have been the two that I've seen most commonly researched for this. Um that they have venoms containing chemicals that can cause priapism in their victims. Now, obviously that's not a condition you want to seek out actually occurs, No, I would not. I mean they're also pretty deadly and that is awful. Yes, uh so, okay, it was a good while before anyone

really tracked down what these chemicals are. But because erectile dysfunction is a shall we say, fertile business is a multibillion dollar industry, UM researchers have been working on it, and to be serious, it really is a very important quality of life issue, especially in men who have lost function as a side effect of, you know, receiving really

important treatment for serious diseases like prostate cancer. UM So, it's it's not all goofy ha ha, penis times um so so around though, a group out of the Medical College of Georgia, which is here in Georgia. It's down in augusta UM started isolating a peptide called p n t X two dash six. Okay, so this is a specific peptide found in the venom of these Brazilian Yes, and I do not understand how this process works. UM. According to studies that these researchers released, the peptide effects

excitable ion channels, mainly sodium channels. So I'm pretty sure it has to do with the chemical activation of electromuscular responses. UM. And furthermore, it happens to target or or I guess more precisely preferentially localize in penile tissues, sort of the same way that your your your brain cancer tumor paint stuff UM preferentially selects brain cancers else. So Uh, nature

is great, UM and terrifying. But wait a minute, does this mean we're going to have people like people in the pharmaceutical industry like mass milking spiders to create pills for rectile dysfunction. Uh No, which is good, because that is the worst thing I've thought of all day. Um. No, No,

no one is planning huge farms filled with deadly spiders. Um. Some peptides, as it turns out, are really easy to recreate artificially in labs, generally by by scooping out bits of DNA from bacteria and replacing them with the genetic code for the production of whatever peptide you want to create. UM. So, so you're just turning bacteria into little peptide cows um and and and this is one of those peptides that it's pretty easy to do that with. UM. The next

one that we are going to talk about is as well. Well, you know, every time you get the chance, you bring it back to bees. Are you going to talk about bees? So going to talk about bees? Why do you love bees so much? Because they're the best? Because I love bees. If I didn't love bees as much as you did, I'd say, not the bees. But I'm not going to say that, So instead, Lauren, please the bees, please? All right. So, supposedly be venom has been used in medicine for thousands

of years already. Hippocrates is said to have used it in the treatment of arthritis. So I don't want to be a downer about that, but I get the feeling looking at some of this bee venom literature that I think there are a lot of kind of hokey claims out there about Oh be venom, it'll do this, it'll do that, Get yourself stung by a bee, it'll be terrific. Yeah.

It sounds like one of those old world kind of remedies where it's like, oh, no, you've got the rheumatism, Go rub your face on the bark of a tree that was used to hang a man who stole the duck. Well, there there are some alternative medicine claims that I am not sure of the veracity of about be venom out there, and I certainly do not recommend that anyone go out and get themselves stung by bees in order to cure

whatever it is that you want to cure. But b venom is being her being year no uh, or it's being investigated rather for for cancer therapies scientists, by legit scientists, not by all farmer Jim down by the watering hole. Well,

let's hear all about it, all right. So there was a study done at Washington University in stan Louis that was published in two thousand nine took one of the operative toxins in b venom, which is a peptide called malitten or molten or meltinin or something to that extent, but at any rate that they can insert malitten into nanoparticles called flora carbons, which you may remember us talking

about in our episode on artificial blood back in August. Okay, so these were kind of like they wanted to create artificial oxygen carrying cells. Right. As it turns out, these things were really crap at delivering oxygen, but they're pretty good at delivering venom peptides. Just what I needed, and I'm out of blood. To give me some venom, right,

that's what runs through mob blood UM and AH. In a ridiculous or possibly ridiculously brilliant like research marketing move, the team chose to call these um mulighten bonded per flora carbons nanobees. Nanobees. Nanobes. They know how to get some media attention. Nanobees, y'all. Nanobees. That's a good word. It feels good to say. They sting cancer tumors to death was an actual headline that appeared on the Telegraph. The Telegraph also knows how to do headlines. They do nanobees.

I dare you, I dare you listener to look at the word nanobees like a head write it down on a piece of paper on your computer right now and look at it and try not to laugh. Na, it's physically impossible. It's the best word, Okay, But seriously, um so they so they added to these nanoparticles, um the the b venom peptide maliten, and also a targeting agent that binds to a particular molecule that's found on the surface of newly developing blood vessels, which tumors are super

rife with. Yeah, um so uh. As as a bonus to all of these tumors are also hoarders, they keep particles in so once these nanoparticles uh you know, attached to the surface of the blood vessels and then get

into the tumor, they don't get pushed out. And I'm a little bit shady on the exact science of of the next part, because again I'm not a scientist, but it sounds like these nanoparticles take advantage of a really specific like cell membrane protein transfer process to get the m lighten into the cancer cells and then destroy them from the inside out. So that's pretty super uh. And the same process basically might be able to kill the human immuno deficiency virus wo HIV. Yeah, let's heart that

all right. So another study done at Washington University in St. Louis published in applied m lighten to to this other task. The researchers noted that m lighten can destroy the skin

or the coding that protects an HIV virus. And I know he's just said virus twice, but yes, so I mean m lighten destroys lots of cells and to keep the other cells around these virus is safe, the researchers load the m lighten into those little nanoparticle structures, which also happened in a into the stuff that I said earlier with the cancer. They also happened to create little

like bumpers around uh the mu lightened particle. So your blood cells are huge and they bounce off the bumpers, but anything as small as a virus will slip right through the bumpers and come into contact with the MU lighten and totally die. Wow. So they sound like big claims about bevinom so I'm sure we would have heard more about them if the if the research was really far along, right. Uh yeah, okay, So so they're they're really hoping and when they put out press releases about

this research being published. Um, they said that, you know, with further testing, they might be able to do fabulous things like develop a gel that can be applied vaginally that will reduce HIV transmission, or that uh into into something that could even be injected into the blood stream of infected patients to reduce that infection in the body. And and those are big hopes. But there you know,

they haven't been tested out yet. This is all ill uh in in vitro I believe being done in laboratories, in glass dishes, uh, not in live animals, and so there's still a lot of testing to be done. I if you've seen headlines about this and someone was going like, yes, it is the cure for HIV, uh, that's just the media doing what the media does with medical news and overstating things dramatically. It's easy to get excited about promising

preliminary research. Yeah, we do it here sometimes of course, it's when somebody says, hey, we could cure something, especially if we could cure it in a really bizarre and interesting way that includes b venom Yeah, and nanobees. Yeah, We're like, yeah, we're on nanobe's lead us into the future. Well, I hope the nanobees and all these other things do turn out. But this isn't even be half of it.

There are all kinds of claims out there, some more well substantiated than others, that various venoms cure or at least provide partial relief from a wide range of ailment. So it's one of those things where I think there there's a ton left that we could find out. Venoms are are an interesting source of medicine because we already know that their potent at doing things. You know, it's not like, hey, let's try a capsule made from the bark of some random tree and see does it do anything?

Uh No, I mean yeah, it's not like you have to boil a venom down to I mean I mean usually just very tiny particles within them, very small proteins and peptides and stuff. Are so efficient. Yeah, yeah, that they do a job within bodies already. Usually it's a job that you don't want done to your body, but it might be something that actually saves your life. So I think this has been a lot of fun to

talk about. So maybe in the future we will revisit the topic of venom and bring even more research into developing venom tech and venom medicine. Yeah, yeah, there's there's a bunch of stuff that we didn't quite get a chance to cover today. So if there's anything that you can think of that we have not discussed about venom, then you should get in touch with us. The ways that you can do that are via email at FW

Thinking at how Stuff Works dot com. You can go to our website FW thinking dot com to yea to check stuff out look around, I mean, if you're into websites. If you're not into websites, if you're into social media, then you can find us on Twitter, Facebook, and Google Plus, where in our screen names are variations of f W thinking. You guys, are you're you're smart, You'll you'll find us

um and yeah, let's let us know. Let us know what you thought about this episode, what you think about venom, what other topics you would like us to discuss, because we really love getting all of your incredible ideas and turning them into really good podcasts. So do that, uh, And whether or not we hear from you, you will hear from us again very soon. For more on this topic and the future of technology, visit Forward Thinking dot Com brought to you by Toyota Let's Go Places,