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  • How does a sea snail catch a fish?

  • I mean, it's a snail, so it's slow,

  • and the fish is not.

  • But yet, this happens.

  • Hidden under the sand is a cone snail.

  • And that orange thing you see is kind of like a tongue.

  • We call it a proboscis.

  • It uses that to track and subdue this unsuspecting fish.

  • In this predator-prey interaction,

  • these are clearly not your garden variety escargots.

  • These are assassins of the sea.

  • And their weapon of choice is venom.

  • Venom, like the venom you find in venomous snakes and scorpions,

  • these sea snails, they use their venom to subdue fish, worms

  • and other snails.

  • And the venom of these snails,

  • it's not just one thing,

  • it's actually a cocktail of toxic molecules

  • that are packaged and delivered through a false tooth called a radula.

  • You can think of the radulas as hypodermic needles.

  • Now, no need to worry,

  • these snails are practicing good needle habits,

  • because each radula is only used once.

  • Now from your own knowledge about venomous organisms,

  • and the keep-you-up-at-night fish-killing video that I just showed you,

  • you might think that venom is dangerous and all bad.

  • Well, yes and no.

  • A more accurate way of thinking of venom

  • is to think of it as both a supervillain and a superhero.

  • In my lab, we study the evolution of venom in these sea snails

  • as a force for good.

  • Sounds like a stretch,

  • or maybe even snake oil,

  • but actually,

  • while there are snakes involved, the product is legit.

  • One reason the venom product is so successful

  • is that it transforms a physical warfare into a biochemical one.

  • Where usually the predator-prey interaction is one of brute force,

  • venom takes it to a molecular scale.

  • And it's not size that matters,

  • but the mixture of your venom arsenal.

  • The chemistry of the toxins in your arsenal

  • is what's going to enable David to conquer Goliath.

  • And in our scenario, David is clearly the snail.

  • Another feature of venom that makes it so successful

  • is that the toxins work with the precision of a Swiss Army knife.

  • And so these toxins,

  • they come for strongholds that help an organism to function.

  • So they target blood, brain and membranes.

  • Whether it's snail venom or snake venom,

  • they each have components that can do things

  • like cause your blood to clot,

  • what we call "hemotoxic."

  • Or they cause neurons in your brains to not function normally,

  • what we call "neurotoxic."

  • Or they have toxins that will poke holes into the membranes of your cells,

  • causing them to rupture and, basically, explode,

  • what we call "cytotoxic."

  • Cellular explosion, people.

  • Now, if that is not all powerful and all present,

  • nothing is.

  • Now a little about me,

  • and why I'm so obsessed with venom.

  • I grew up in New York City

  • with forced access to the Natural History Museum.

  • I say "forced access,"

  • because I'm one of five kids,

  • and my parents used museums as a form of childcare.

  • There were two rules:

  • Don't lose anybody

  • and meet Mom and Dad at the African elephants

  • at 5:30, when the museum closes.

  • Those totally unsupervised days running through the halls of the museum

  • were full of adventure and exploration.

  • And that's how I feel when I'm studying venom.

  • It's a scientific adventure.

  • We're boldly exploring this entity that connects nature and humanity.

  • Another reason that I'm obsessed with venom

  • is because of its duality.

  • When you inject the components of a venom arsenal into an organism,

  • it can kill or it can cure.

  • At a molecular level, several things can happen.

  • You saw one thing, paralysis in the fish.

  • Now that was happening because the toxins in the venom

  • were attacking how the fish's cells communicate with each other,

  • preventing it from swimming away.

  • Are there other things that I would like to use venom to attack?

  • For sure.

  • And one of those is cancer.

  • Cancer tumors are cells.

  • And like all cells,

  • they communicate with themselves and their environment around them.

  • So we would like to find venom components

  • that are very good at disrupting how the tumor cells communicate.

  • Similar to how the venom disrupted how the fish cells communicated

  • and the fish couldn't swim away.

  • In my lab, we study cancer as a channelopathy.

  • What this means is, basically, we're looking for venom components

  • that will target channels that are overexpressed in tumor cells

  • versus normal cells.

  • The cancer that we're most focused on right now

  • is liver cancer.

  • And that's because since the 1980s,

  • the death rate of liver cancer has doubled,

  • and it's an emerging threat in the US.

  • In a screen in which we had cervical,

  • neuroblastoma, prostate and liver cancer cells,

  • we found a compound from a terebrid snail

  • that seems to attack liver cancer cells,

  • and only liver cancer cells, and none of the others that were tested.

  • And then, when we took this compound and we injected it into mouse models

  • that were expressing liver cancer cells,

  • it significantly inhibited the growth of the tumors.

  • We're not quite sure how this works yet,

  • we're still investigating the mechanism

  • and how we can make this compound more effective,

  • so you can't rush out to the pharmacy

  • and order up a killer snail liver-cancer therapy treatment.

  • Not yet.

  • Basically, what we think is happening

  • is that the compound is blocking a specific channel,

  • prohibiting the transmission of a specific chemical

  • that leads to downstream signaling

  • that enables the tumor to multiply and draw blood to itself.

  • What we're doing in studying the components of venom

  • to find treatments for human diseases and disorders,

  • is not new,

  • it's what we call natural products drug discovery,

  • and it's been happening for centuries,

  • and in cultures all over the world.

  • Venoms are not only giving us cool new compounds,

  • but they're also giving us new ways of thinking

  • about how we treat human diseases and disorders.

  • And I'll give you three examples.

  • The first is from killer snails, of course.

  • And so the first drug from these snails that is on the market

  • is called ziconotide, or Prialt,

  • and it's used to treat chronic pain in HIV and cancer patients.

  • Prialt is a nonaddictive pain therapy.

  • Three magic words when you think about how we're treating pain currently.

  • We're using things that have a huge cost of addiction.

  • So think of morphine

  • or think of any of your favorite opioid out there.

  • What the snails have done

  • is they've shown us a way to treat pain without the addiction,

  • which is huge.

  • The next example comes from the Brazilian pit viper.

  • From these snakes, we've derived a compound called captopril.

  • Captopril is used to treat high blood pressure,

  • and captopril is a breakthrough drug.

  • But not only in and of itself,

  • but because it advanced a whole class of drugs,

  • what we know as ACE inhibitors,

  • which are the most commonly [prescribed] for treating hypertension

  • and heart failure.

  • The last example is from the Gila monster.

  • And this is a really exciting example of understanding the ecology

  • of these organisms,

  • and pairing it with efficient drug discovery.

  • And Gila monsters are binge eaters.

  • So when they bite into a large meal,

  • they release things in their venom that lower blood sugar.

  • So what's the drug that you think we found from the Gila monster?

  • A compound that is used to lower the blood sugar in diabetic patients.

  • Now these are three marvelous examples,

  • but we've just scratched the surface.

  • There's so much more venom out there for us to study.

  • In fact, we think that 15 percent of all the animals on the planet

  • are venomous.

  • And I think this is a low estimate,

  • given the fact that we haven't surveyed all the animals on the planet.

  • But nature seems to have found something that she likes,

  • and she's repeated it over and over and over again,

  • leading to the vast array of animals that we see around us

  • and all throughout the tree of life.

  • So whether we're talking about my fave, killer snails,

  • or jellyfish,

  • or the larvae of butterflies and moths,

  • or platypus or slow lorises,

  • whether by sea, land or air,

  • you're sure to encounter a venomous creature.

  • Remember when I told you

  • that venom can be both a superhero and a supervillain,

  • and you doubted me?

  • Mhm.

  • We're in a race to harness all of this venom goodness

  • before we lose the vast majority of animals on our planet.

  • It's a holistic process.

  • You can't have the therapeutic treatments without having the animals.

  • And you can't have the animals

  • without having their ecosystems.

  • So for me and the snails,

  • what it means is we have to save the oceans.

  • And because venomous animals are found everywhere,

  • we basically have to save the planet.

  • So do it for the venomous animals,

  • if you don't want to do it for yourself.

  • And who knows,

  • some day, snail venom might just save your life.

  • Thank you.

How does a sea snail catch a fish?

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B2 venom snail cancer venomous liver fish

The power of venom -- and how it could one day save your life | Mandë Holford

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    林宜悉 posted on 2020/11/18
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