Breakthrough: The Killer Snail Chemist

This video is part of “Breakthrough: Portraits of Women in Science,” a short film anthology from Science Friday and Howard Hughes Medical Institute (HHMI) that follows women working at the forefront of their fields. Hear Ira speak with Mandë Holford (and see some cone snails in action) here, and make sure to check out the rest of the Breakthrough series.

She roamed across the Sahara and the Serengeti, spotting elephants. She traveled south to the Amazon, where the brilliant colors of the birds and reptiles left her dazzled. She dove into the ocean and marveled at the great blue whales. And then, promptly at 5:45pm, she’d head to the elephant near the Hall of African Mammals, where she’d meet her mother.

“As a kid growing up in New York, you have a couple of places that are really special, and the American Museum of Natural History is one of those for me,” says Mandë Holford, a biochemist at Hunter College and the American Museum of Natural History. “My parents would sometimes use it as a way of babysitting.”

A self-professed nerd, she spent a lot of time reading as a child. But the museum offered more than any one book could cover. “It’s just a place of wonder…Going to the museum is like bringing that reading alive,” she says. “It was like a walking book for me.”

Those afternoons spent wandering through the museum set a tone for Holford’s life. She roamed through the halls finding new adventures and new sets of biological wonders. “What I didn’t understand as a child was that that was science,” she says.

Bridging The Gap

Holford went on to study science, but she didn’t find what she was looking for in a single field. As an undergrad, she studied under a physical chemist. But they weren’t just studying the bacteria they were working with—they were growing it themselves.

“So he was doing a little bit of recombinant biology, as well as physical chemistry, and so that was the first time I learned about science being collaborative and integrated,” Holford says.  “And I just got completely blown away that this was a career, and this was a job.” She thought to herself, “I want to do this. I absolutely want to do this.”

[This polar bear researcher begins her day with a thrilling helicopter ride.]

While she pursued her Ph.D. at Rockefeller University, a very “human-centric” biomedical institute, the natural world was never far from sight—both literally and figuratively. The university was located on the east side of Central Park, and the American Museum of Natural History on the west. A bridge stretched across the park from one institution to the other, and as she crossed it, Holford thought, “This is what I would like to do. I’d like to bridge the medical training that I received at Rockefeller with the natural history and the wonder and excitement of studying what’s here in biodiversity. And figure out how to make science—how to do the kind of work that is both beneficial to society, but also exploring the wonder that’s here on our planet.”

But she needed to find an organism that encompassed that—one that had a human, biomedical application, but was also strongly grounded in the natural world.

New Pathways, Old Problems

Then, she saw a video of a snail eating a fish.

Baldomero “Toto” Olivera, whose research focuses on venomous marine snails, visited Rockefeller to give a talk on cone snails. Encased within their delicate and stunning shells, the cone snail’s proboscis is tipped with venom, and it uses it to harpoon and paralyze its prey before engulfing it entirely in its mouth. In its natural form, the venom could be lethal even to humans. But the snails’ venom is made up of many peptides, molecules composed of amino acids. And some of the individual peptides have potential medical applications—they could offer promising treatments for cancer, as well as opioid-free solutions for chronic pain. Here was the link to Holford’s biomedical work.

“I was excited, because I saw an organism that had an evolutionary history that was exciting, that would have been of interest to someone working in a natural history museum,” she says. “And it had an application in that the venoms were a means to alleviate some of the issues and disorders that we have, the human disorders that are there.”

Holford went on to do a post-doc with the “Godfather of Snails,” as she christened Olivera, and continued her love affair with the killer cone snails.

“What’s wonderful is something that kills you can actually then potentially be something that cures you,” she says. “It’s like this strange twist of nature. You have this very, very [lethal] snail…And then, in a surprising twist, you can also extract some of the parts of this venom and use it to cure something, or to treat something that is causing pain.”

But Holford points out that looking to nature for answers is nothing new. For millions of years—from the Aztecs to ancient Asian cultures, to the Native Americans—we’ve been looking to our natural environment for cures to the things that ail us, she explains. Now, we’ve just gotten a bit more “strategic” about how we do it.

One of those strategic methods is venom research, which also lends itself to interdisciplinary studies. The venom itself is natural, but researchers extract it and learn about its components using analytical biochemical methods. And in the end, its applications are biological.

“What’s amazing about the peptides that we’re finding in the snail venom is not only are they giving us new drugs, but they’re also giving us new pathways for treating old problems,” says Holford.

The Deep End

Holford runs her own lab and is now at the forefront of biomedical research. But like anyone at the start of her career, she experienced a few growing pains.

For example, if you’ve never hunted for cone snails in the wild, you may need to learn on the fly. Holford’s first snail collection trip was in Panama, and she went in “completely green.

“I didn’t study evolutionary biology, or taxonomy, or anything that,” she says. “So this was like really just jumping into the deep end, literally, and trying to figure out, how do you find snails?”

In books, the cone snails’ shells are polished and shiny, and their patterns are strikingly visible. It’s a different story when the organisms are buried in the sand. Researchers must look for trails in the sand, and then dig up the snails.

“One of the first things they teach you when you’re learning to dive is, if it’s too beautiful, don’t touch it, and if it’s too ugly, don’t touch it. Because everything can potentially kill you, and it’s usually the beautiful or the ugly things that are lethal.”

And the consequences for a wrong choice are no small matter: “One of the first things they teach you when you’re learning to dive is, if it’s too beautiful, don’t touch it, and if it’s too ugly, don’t touch it,” says Holford. “Because everything can potentially kill you, and it’s usually the beautiful or the ugly things that are lethal.”

But the trials Holford encountered while snail hunting only provided practice for a career as a scientist.

“As a scientist, you’re always learning to deal with failure, because experiments fail all the time,” she says. “So you have to sort of have this tough skin to pick up and start again, and being in Panama was one of the first times.”

The “Cheapest” Career

Since that first expedition to Panama, Holford’s work has taken her all over the world. On a trip to Papua New Guinea, she noticed something about the local students with whom they were working.

“I would notice that they were staring at me,” she says. “And you know, in your subconscious, you’re like, ‘What is it? Is it my hair? Do I have something in my teeth? What’s going on?’”

It had nothing to do with her teeth.

Holford estimates that there were scientists from roughly 30 different countries on the collection trip. She also believes that she was the only black American woman on the trip who was coming as a chief scientist.

[Three scientists share stories about India’s first interplanetary mission, MOM.]

“I was the only New Yorker and the only New Yorker that looked like I did, and I looked very similar to the native Papua New Guinean people,” she says. A colleague pointed out that it was rare for the people of Papua New Guinea to see someone in her position look so similar to them.

“And it was something I wasn’t prepared for, because I didn’t view myself as a role model,” Holford says. “And I wasn’t trying to be anybody’s role model. You’re just trying to do your thing…And it’s a huge responsibility to be seen in that role. But it was also empowering.”

The reason it was empowering, Holford says, is because she wanted to convey to the students that they too could do the work that she was doing.

“I like to say that science is one of the cheapest careers. It’s like soccer—all you need is a ball. In science, all you need is a brain, and all of us are born that way. So if you’re interested in science, you can certainly become a scientist.”

“I like to say that science is one of the cheapest careers. It’s like soccer—all you need is a ball. In science, all you need is a brain, and all of us are born that way. So if you’re interested in science, you can certainly become a scientist.”

And that’s exactly what happened to Holford. Her path to becoming a scientist  began in the halls of the American Museum of Natural History, and her days at the museum may still end around 5:45pm. But now, she doesn’t need her mom to take her home.