Scientists explore how the powerful peptides found in marine cone snail venom can be used for medicinal and therapeutic purposes.
How Killer Snail Venom Plays a Key Role in Drug Development
Published: February 11, 2021
David Pogue: Time to meet my first Professor of Venoms, Mandë Holford, of Hunter College.
Now, I couldn’t help noticing, there’s a huge, terrifying tarantula on me. Is she poisonous?
Mandë Holford: No, no, she’s not poisonous.
Pogue: Oh, whew!
Holford: She is, however, venomous and could still be lethal.
Pogue: Thanks for bringing that up. Poisonous and venomous don’t mean the same thing?
Holford: No, no, no, not at all.
Pogue: Poisonous versus venomous: it all comes down to the delivery system. If you bite it and get sick, it’s poisonous, but if it bites you and you get sick, it’s venomous. In general, the source of their toxins is different, as well.
This poison dart frog becomes poisonous from its diet. If raised in captivity, on different foods, it can become non-toxic, whereas this rattlesnake generates its own venom. It’s built into its D.N.A. So, snakes, scorpions, spiders: which fearsome creature is the focus of Mandë’s work?
Killer snails? Is it accurate to say that you study killer snails?
Holford: Killer snails are actually my affectionate term for venomous marine snails. And so, these are snails that live in the sea, and they have a venom, like snakes or scorpions or spiders, and the venom can be very lethal to humans.
Pogue: It’s true that the snail can kill you, but usually it’s just looking for dinner, a worm or a fish.
So, I’m a fish. What happens to me?
Holford: Well, what happens is this guy will smell that you’re in the water, right? He puts out something called a siphon, and it’s a chemosensory organ, smells that, “Hmm, tasty meal in the water,” then it sticks out something like a tongue. It’s called a “false” tongue, “proboscis.” And, on the tip of the tongue, it has a little tooth, filled with venom that then will get injected into the fish. The fish instantly will become paralyzed, depending on what cocktail of venom gets injected into it. The snail will then open its mouth really wide, swallow the fish whole and have a really nice, tasty meal.
Pogue: The whole thing sounds so improbable.
Holford: I love it. Just when you think you’ve heard of everything, nature will surprise you with something new.
Pogue: So, what’s in that paralyzing venom? To find out, Mandë and her team collect specimens from around the world. Back at the lab, they analyze tissue samples from the snail’s muscular foot and its venom gland.
Juliette Gorson: So, we’re eventually going to look at the D.N.A., so we can make a species identification. That, we can use the foot tissue for. And then the venom gland tissue we can use to look for the individual venom toxins within the venom duct.
Pogue: Turns out, the cone snail’s venom isn’t one thing but a cocktail of as many as 250 short “mini” proteins, also called peptides.
Holford: So, if you think of venom, think of it not as like a single bullet, right? It’s more like, I like to describe it as a cluster bomb. It’s a series of bullets coming at you, and each individual bullet has a target in the physiological system.
Pogue: Each venom peptide has evolved to mount a very specific attack, often acting as keys that fit a cell’s lock-like receptors. In the case of the nervous system, that can prevent a specific neuron from transmitting an impulse or, conversely, jam the neuron open, generating a flood of signals.
In the wild, all those targeted attacks paralyze the snail’s prey, but the precision with which the venom peptides act also means that they may have another role as medicines.
Holford: And so, we study these venoms to try to figure out novel medicines for treating things in pain and cancer. Actually, they make great drugs because they’re highly specific, very fast-acting and very potent.
Pogue: A venom curing instead of killing? Wouldn’t be the first time.
There are currently at least seven drugs on the market developed out of the study of venoms. They include an anticoagulant derived from medicinal leeches and a diabetes medicine from Gila monsters. There’s even one already from cone snails, an analgesic to treat severe chronic pain.
Holford: And it’s the exact peptide that you would find in the venom. It’s not a derivative of it, it’s not a small molecule, it’s exactly as nature expressed it in the animal.
Gorson: And I’ll just run a simple D.N.A. extraction.
Pogue: Mandë’s team has already made some major breakthroughs.
Tanya Napolitano: So, I could do a nano-LC-MS and see what’s inside of here.
Pogue: In 2014, they identified a peptide from another venomous snail that attacks liver tumor cells, inhibiting their growth. It’s cutting-edge work that’s reaping the rewards to be found at the intersection of chemistry and biology.
Holford: Learning how the venom is used more in ecological settings helps to further us in terms of how we understand how it can be applied for medicinal or therapeutic applications. And so, right now, it’s a fun time to be a venom scientist, because those worlds are colliding.
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