Turning Toxins Into Medicine: Q&A With Mandë Holford

Q&As

Dr. Mandë Holford © D. Finnin/AMNH

Dr. Mandë Holford

© D. Finnin/AMNH


When she first saw footage of a cone snail disabling a fish with a venomous harpoon and then forming a “pseudomouth” and engulfing its prey alive, biochemist Mandë Holford had a fairly common reaction. 

“I saw that video, and I said ‘Oh, no. That should never happen,’” says Dr. Holford. 

 

The snails’ unnerving hunting method, though, proved too fascinating for Holford to forget. Instead, the Hunter College professor and Museum research associate began studying these sea-dwelling stalkers and their close relatives, looking to repurpose their powerful venoms as medical treatments. 

In her SciCafe presentation on Wednesday, May 6, Holford will explain how marine snail venoms work and how some of these fatal cocktails could be used to treat pain. She sat down to answer a few questions and offer a preview of next week’s SciCafe.

How do you extract venom from a snail to study it? 

Slowly and carefully. Snail venom is produced in a venom gland, and we dissect that. Then, we either sequence the genes in the tissue of the gland or use a mass spectrometer to analyze the crude venom. We try to do it both ways, analyzing genetic sequences and chemicals simultaneously. 

The shell of the venomous cone snail Conus bullatus. © F. Moura

The shell of the venomous cone snail Conus bullatus.

© F. Moura


Are these snails dangerous to humans?

They can be. One species, Conus geographus, used to be known as the cigarette snail because the story was that once it stung a person, they had about enough time left to smoke a last cigarette. Several species are fatal to humans, but the snails are not aggressive, and they would only try to harpoon you if they feel threatened.

What are some of the ailments that snail venom could one day treat?

These venoms could one day provide therapies for ailments that can be manipulated by on/off switches, such as neuronal disorders, chronic pain, and cancer. These animals assemble different venom peptide cocktails from a myriad of different combinations of amino acids, and many of these venoms act as neurotoxins to turn neuronal signals on or off.

Cone snail venom is already seeing some medical uses, right?

Yes, the first drug based on cone snail venom, Prialt, came to market in 2004, and several others are being tested right now. One of the obstacles is that these peptides are large, complicated molecules, so delivery is a challenge. One thing that we’ll likely see work on in the future is the development of molecular Trojan horses that help deliver these peptides more effectively.

Terebrid snails, like the spotted auger shown here, are closely related to cone snails and produce similar toxins. © Y. Terryn

Terebrid snails, like the spotted auger shown here, are closely related to cone snails and produce similar toxins.

© Y. Terryn


 

You started your work on cone snails, but have moved on to their relatives, terebrid snails. Why?

Just like cone snails, terebrids also produce venoms, but they are distinct from those found in cone snails. That expands our toolbox of venom peptides that could have biomedical applications. They’re also completely understudied compared to other venomous animals. We’re creating a niche for ourselves where we can take a new look at these creatures and introduce the scientific community to what they’re capable of.

To learn more about Dr. Holford’s work, check out her SciCafe presentation on Wednesday, May 6, at 7 pm in the Wallach Orientation Center.