Cone Snail

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Cone snail venom is incredibly toxic — it might also be a surprising treatment for human pain

One snail’s toxin is another human’s antidote.

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If you think all snails are cute, harmless creatures, you haven’t met the cone snail. The sea dweller lives underwater and preys on fish, worms, and other gastropod mollusks. Snails don’t have claws, razor fangs, or enormous stature to attack their prey. Instead, the creatures have evolved some rather unique — and painful — skills to hunt. And one newly discovered technique might actually help treat human pain.

Among roughly a thousand living cone snail species, researchers have identified two known hunting tactics:

  • Taser-and-tether: The cone snail tasers its prey with rapid chemical electrocution, paralyzing and tethering it in seconds. This is the most widespread and best-studied strategy.
  • Net hunting: The cone snail releases venomous components into the water to make the prey groggy, and then captures the prey with a mouth-net. This method has been observed in only two species, Conus geographus and Conus tulipa from the Gastridium clade.

Researchers at the University of Copenhagen have observed a third way that cone snails hunt, one that also uses cone snail venom (conotoxins). Like net hunting, this new method has only been observed in one clade.

However, one snail’s toxin is another human’s antidote. The venom used in this newly discovered method shows promise as a treatment for pain, cancer, and endocrine disorders in humans. The researchers detail this new method and its possible applications in a paper published this week in the journal Science Advances.

What’s new — Researchers describe the new hunting method as “Ambush-and-assess.” The newly observed process differs from the other two in that it’s slow acting. The snail stings its prey, and then it takes one to three hours for the prey to become lethargic. The snail ambushes its lunch with a surprise sting, and then patiently waits for its venom to do the trick. So far, this hunting method is unique to cone snails of the Asprella clade. The researchers hypothesize this method is to slay potentially dangerous prey so that the cone snail won’t get ambushed itself after an attempted taser-and-tether.

Three Asprella snails off the coast of Cebu Island in the Philippines served as the test subjects. In addition to preferred eating methods, this clade of cone snail stands out from its cousins because it dwells in deeper waters, and also has a different venom composition.

But that’s not the only discovery. It turns out that this conotoxin used in ambush-and-assess contains a peptide called somatostatin, which can be used to treat pain, inflammation, cancer, and endocrine disorders in humans.

Ramiro and her team found that a clade of cone snails use a third hunting strategy that involves stinging prey with slow-acting venom that paralyzes the fish about an hour later.Ramiro et al., Science Advances, March 23, 2022

Why it matters — Somatostatin is a neuropeptide and hormone that humans produce. It inhibits growth hormone secretion and cell reproduction. Cone snails venom, this team found, contains a compound called Consomatin Ro1 that closely resembles somatostatin.

Somatostatin is of great interest as a possible treatment for things like cancer, diabetes, and pain. However, the human-made peptide has a half-life of only one to three minutes, so it dissipates rapidly. Other researchers have been trying to create a pharmaceutical version of somatostatin that lasts longer so it can function as an effective treatment. These artificially produced somatostatins are called analogs because they’re copycats. One existing treatment is octreotide, a.k.a. Sandostatin, which has a half-life of 90 minutes after intravenous infusion.

The cone snail’s compound clocks in with a half-life of more than 158 hours (more than six and a half days) after in vitro treatment. That means compared to natural human somatostatin, this peptide will stick around for much longer.

The cone snail’s version of the peptide looks like ours in terms of how it’s sequenced. But they also function in the human body. We have five somatostatin receptors that this peptide binds to in order to activate this inhibition. Conosomatin Ro1 binds to receptors one and four, making it an effective compound.

“It has the potential to become a lead for treatment for pain, because two of those human receptors that the Conosomatin targets are involved in pain,” first author Iris Bea Ramiro tells Inverse. Ramiro is a Ph.D. student at the University of Copenhagen. “So that's what we pursued and found out that it actually works.”

Digging into the details — Ramiro and her team looked at Conosomatin Ro1 in mice. While it may be a while before snail juice ever gets to humans, this discovery is still a noteworthy step.

To study this peptide’s effects in mice, the team used the tail-flick test. Researchers injected the mice with varying dosages of either Conosomatin Ro1, morphine, or saline, and lowered them into a chamber of hot water. Ramiro’s team tested how long it took for the mice to curl their tails away from the hot water, indicating their pain reception. The higher the dosage of Conosomatin Ro1, the longer it took for the mice to flick their tails, indicating their sensitivity to pain had decreased.

There are now three known hunting methods cone snails employ: taser-and-tether, net hunting, and the newest one, ambush-and-assess.Ramiro et al., Science Advances, March 23, 2022

What’s next — With hundreds of cone snail species, possibilities for other somatostatin analogs abound. Perhaps Ramiro and her team will find enough types of venom that bind to all five human receptors.

“We're looking at the other species of cone snails which also have some other somatostatin-like analogs,” Ramiro says.

And to be clear, don’t go looking for an Asprella sting for pain treatment. The Conus geographus so far is the only cone snail to have reportedly killed humans, but it may not be the only one. “You don’t want to sting yourself with a cone snail,” Ramiro says. “I think the cocktail is probably too strong.”

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