Part 4 of TED Radio Hour Episode A Love Letter To The Ocean
Cone snails are deadly sea predators; their venom can kill fish and even humans. But chemical biologist Mandë Holford says that powerful venom can actually be used for good — to treat human diseases.
About Mandë Holford
Mandë Holford is a chemical biologist and venom scientist, and an associate professor in chemistry and biochemistry at Hunter College and CUNY-Graduate Center.
She also has scientific appointments at The American Museum of Natural History and Weill Cornell Medicine. Her interdisciplinary research focuses on venomous marine snails, and how their venom can be used to treat human diseases and disorders.
She is also the co-founder of Killer Snails, an edtech game company that has created award-winning games like Assassins of the Sea and Killer Snails All Around.
Holford received her B.S. in mathematics and chemistry from York College, City University of New York, and her Ph.D. in synthetic protein chemistry from The Rockefeller University.
MANOUSH ZOMORODI, HOST:
On the show today, a love letter to the ocean, even to its less lovable inhabitants. We started the hour with a story about sea urchins. We'll end with another terrifying but unassuming creature.
MANDE HOLFORD: I call them killer snails. I love to call them killer snails, I mean, because that's what they do, right? They kill things.
ZOMORODI: This is venom scientist Mande Holford. She studies cone snails, a group of venomous predatory snails found all over the world and at all depths of the ocean.
HOLFORD: They are net hunters, so they open their rostrums, which their mouths, really wide, like you're going to, you know, swallow something. And they are. They're going to swallow fish. So they usually eat a school of fish. So they open their mouths really wide, engulf the fish, and then they start to individually harpoon the fish with venom once they're in their mouth.
ZOMORODI: So they sting the fish. Or if you disturb them, they'll sting you, right? And then what happens? How does the venom work?
HOLFORD: So inside of venom, you have peptides that are very specific to what they do. And I like to say that they target blood, brains and membranes. They come at you all at once, and they are trying to shut down or disrupt the normal physiology of the prey so that you're in sort of this excited shock state. Or they're ripping membranes apart, so they're tearing apart the different membranes on the cells. And so...
ZOMORODI: It's violent.
HOLFORD: It's very violent (laughter). It's very violent in your body. Your body doesn't know what's hit it...
HOLFORD: ...Right? But it's designed so to be this all-powerful shock-and-awe kind of campaign that happens when it's injected into the prey, where it's fanning out to hit these, you know, molecular targets, hit these ion channels on membranes of cells to disrupt how they would normally function. And so you should be cautious of them, you know, when you encounter them on the beach because from the source of where they're injected, it starts to get sort of paralyzed. And that paralysis creeps up to your diaphragm eventually and prevents you from being able to breathe normally.
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HOLFORD: And so you die from that and some also from the heart attack of just realizing that you can't breathe as well.
ZOMORODI: (Laughter) OK, at this point, I do not feel like writing these things a love letter. But, Mande, you are really deeply in love with these snails and with what they can do, right?
HOLFORD: (Laughter) You know, we think of snails as supervillains because they feed on fish, snails and worms, and their venom can be lethal to humans, too, right? So a snail can kill a human. But we also think of them as superheroes because if we tease out the components in their venom, we can identify therapeutics that are very effective against pain and cancer. And that's how we're able to use venom from snails as a superpower for good.
ZOMORODI: Here's more from Mande Holford on the therapeutic properties of venom in her TED talk.
(SOUNDBITE OF TED TALK)
HOLFORD: Sounds like a stretch, or maybe even snake oil, but actually, while there are snakes involved, the product is legit. The toxins work with the precision of a Swiss Army knife. 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. The cancer that we're most focused on right now is liver cancer. We found a compound from a terebrid snail that seems to attack liver cancer cells. 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.
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HOLFORD: 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.
ZOMORODI: So just to sum up - the components in venom that kill prey are exactly what makes it possible to target specific illnesses and potentially treat them.
HOLFORD: Yes, exactly.
ZOMORODI: Wild. And I know that your lab is working on using sea snails for cancer treatments. But there are some other medications made from venom already that are on the market, right? Where are we in terms of what is out there, what's gotten approved and what's hopefully still on the way?
HOLFORD: So for our peptide, we're still a ways away from getting it into clinical trials 'cause we have to prove the mechanism of how it works and all of that. But currently, there are at least six different drugs that have been approved by the FDA that are on the market that are either the venom peptide itself or derived from venom peptides that you can go and get a prescription for from a doctor.
HOLFORD: You can find venom in lots of creatures. Venom is found all throughout the tree of life, so, you know, snakes, spiders, scorpions. So the six that are currently on the market - one is from cone snail. It's a pain therapy called Prialt that they use for chronic pain in HIV and cancer patients. One from the Brazilian pit viper is Captopril. And they use it for hypertension. From the Gila monster, there's Exenatide, which is used to lower blood sugar in diabetes. From the medicinal leech, we find something called Angiomax, and they use it for blood thinning. And then we have something from another viper, Aggrastat, which is also a blood thinner. And then the pygmy rattlesnake gives you another blood thinner. So those six. So we've got three snakes, a leech, a snail and a Gila monster.
ZOMORODI: That is quite a group of pharmacists you've got there. So what is your hope for them in the next, say, five to 10 years?
HOLFORD: Oh, my God. In the next five, 10 years, I think the venom field is going to really explode. I really think we're at a point in which the technology has advanced so much that it's enabled us to be able to study these fields, study these organisms in ways that are less invasive, so we don't need as many, right?
And also, we can get so much depth in terms of what their genes are doing and how the genes are made. And for that - that I think is the most exciting part, is we are interested in looking for things that would give us pain therapies that are nonaddictive or looking for ways in which we can talk about treating cancer that would be easier for the patient - so looking for selective treatments for cancer that did not have the side effect that all the current treatments have, which is that they're really horrible. They're just as bad as the disease.
HOLFORD: So those were our two sort of marching orders when we wanted to use venom for good. Can we find a pain therapeutic that is not addictive - so an alternative to the opioids to address the opioid crisis? And can we identify a cancer treatment that was selected for tumors versus healthy cells so that patients don't have to go through this agony when they're going on their cancer treatment?
(SOUNDBITE OF TED TALK)
HOLFORD: There's so much more venom out there for us to study. In fact, we think that 15% 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.
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.
ZOMORODI: I want to tie this back to what our episode is all about, which is this idea of our love of the ocean, our need to remind ourselves there are lots of reasons to invest in saving the ocean. And the reasons that you're describing are - kind of appeal to our self-interest in many ways. You know, whether we will suffer from cancer or diabetes or high blood pressure, these are all things that humans desperately could use treatment for. And so we need - is this - is that an OK reason to want to preserve the oceans?
HOLFORD: Oh, yes. No, altruism is a good thing. But self-interest is even better. And so when...
HOLFORD: ...People think that this can help me, I want it, then they seem to, you know, behave accordingly. And so, yes, whatever the motivation for saving the oceans, we've got to do it, right? And in this case, these snails are helping to make our lives possible by allowing us to find novel treatments for ailments that are not going away, right?
HOLFORD: And if that isn't enough, if it isn't enough to say that, hey, my dad or my mom, who - or myself, who is this cancer patient suffering, and I know a snail that can help that, and in order for me to get that snail what it needs, I've got to not pollute my ocean, I'm going to say yes to that 'cause I want my mom around, or I want to be around myself. And so I think bringing in the story of how we tie nature in humanity is a powerful one for how we're going to be able to maybe change behaviors and protect our oceans.
ZOMORODI: That's venom scientist Mande Holford. You can see her full talk at ted.com. And there is more of our love for the oceans coming soon. Join us in two weeks for part two on the ocean, ideas on how to protect the seas and all the amazing marine life that lives in them. Thank you so much for joining us today. To learn more about the people who were on this episode, go to ted.npr.org. And to see hundreds more TED Talks, check out ted.com or the TED app. And by the way, if you have been enjoying the show, we would be so grateful if you left a review on Apple Podcasts. It's the best way for us to reach new listeners.
This episode was produced by Rachel Faulkner, James Delahoussaye, Katie Monteleone and Fiona Geiran. It was edited by Sanaz Meshkinpour. Our production staff at NPR also includes Jeff Rogers, Diba Mohtasham, J.C. Howard, Christina Cala, Matthew Cloutier and Janet Woojeong Lee. Our audio engineer is Daniel Shukin. Our intern is Harrison Vijay Tsui. Our theme music was written by Ramtin Arablouei. Our partners at TED are Chris Anderson, Colin Helms, Anna Phelan, Michelle Quint and Micah Eams. I'm Manoush Zomorodi, and you've been listening to the TED Radio Hour from NPR.
(SOUNDBITE OF MUSIC) Transcript provided by NPR, Copyright NPR.