Toxic Snail Venoms Yielding New Painkillers, Drugs

John Roach
for National Geographic News
June 14, 2005
In chronic pain? Don't be surprised if you find yourself at a corner pharmacy filling a prescription for synthetic snail venom sometime soon.

Last December the U.S. Food and Drug Administration approved the first painkiller derived from a cocktail of potent chemicals produced by cone snails.

The creatures, which are also known as cone shells, inhabit the world's dwindling coral reefs. There are more than 500 known cone snail species.

Studying cone snail venom, researchers have derived other new treatments for pain, epilepsy, and incontinence. The drugs are in clinical and preclinical trials. Scientists say more experimental drugs are in development at research labs around the world.

"They could have a cure to prostate cancer, a cure to AIDS. I have no idea," said Jon-Paul Bingham, a biochemist at Clarkson University in Potsdam, New York.

Bingham is a leading researcher on cone snails. He said there are more than 500 cone snail species, each able to produce more than a hundred unique toxins.

Each toxin is a potential new drug. Scientists have studied less than one percent of them.

Bingham worries that "it's getting harder and harder to [collect] these snails."

Cone snails are found primarily in coral reefs in warm, tropical waters. But as Eric Chivian, the founder and director of the Center for Health and the Global Environment at the Harvard Medical School in Cambridge, Massachusetts, noted, "We are destroying coral reefs."

According to Chivian, some 26 percent of the world's reefs are damaged beyond repair, and another 30 to 50 percent are severely degraded.

The proven potential of drugs derived from cone snail venom is the best example of the cost associated with the loss of the world's coral reefs, Chivian said.

"I'm totally convinced cone snails as a group may have more potential for new medicines than any other genus in nature," Chivian said. (A genus is a group of closely related species.) "The number of different toxins they have developed over some 30 to 50 million years of evolution is unparalleled in nature."

Toxin Factories

In nature, cone snails use their venom to immobilize prey, such as fish, mollusks, and worms. Cone snails harpoon their prey with pointed tongues that are shaped like hypodermic needles. The snails then pump their prey's flesh full of toxins.

"The poor animal, even if it gets away, [it] breaks off the harpoon. The likelihood of it being fatal is 100 percent, basically," Bingham said. "For any [human] who has been stung by a cone shell, the chance of mortality is 90 percent."

The potency and complexity of the venom fascinates scientists. Over millions of years cone snails have evolved toxins that target specific species in specific environments. No one toxin is exactly like another.

In addition, any cone snail can alter the compounds in its venom at will.

Scientists are studying how each cone snail toxin affects its victim. The results are improving our understanding of how cells, such as those that make up the nervous system, interact and communicate. The research is also leading to the development of new drugs.

"We are learning what nature has put in these animals and applying the strategy to other organisms," Bingham said.

Consider, for example, the painkiller ziconotide, the cone-snail-venom-derived drug that was approved by the FDA in December.

The painkiller (brand name: Prialt) is injected through a special pump into the fluid surrounding a patient's spinal cord. The drug blocks nerve channels that ordinarily transmit pain.

Unlike opium-derived painkillers, such as morphine, ziconotide is said to pose a low risk of addiction or increased tolerance and has few side effects. "If you stop using the drug, the pain comes back. And no matter how long you've used [the drug], you don't have to increase the dosage to kill the pain," Bingham said.

Given the potential of snail venom in the development of new drugs, Bingham said he is concerned that the rush to discover more promising toxins may contribute to the decline the world's cone snail species.

Cone Snail Conservation

Chivian, of Harvard Medical School, said the main threat to cone snails is the loss of coral reefs, which he attributes to bleaching (a type of slow death evident when multihued coral reefs turn a ghostly white) and disease outbreaks induced by global warming. Coastal development, pollution, and destructive fishing practices also negatively affect coral reefs.

As for cone snails, their shells are collected and sold by the thousands at curio shops to tourists. Chivian said that additional collecting for biomedical research, if done irresponsibly, could further imperil the snails.

But by far the greatest impact on the snails has been caused by the loss of coral reefs, Chivian said.

Bingham, the Clarkson University researcher, is taking no chances. He advocates responsible use of cone snails, including minimal collection for research. To that end, Bingham and his colleagues are among the few scientists in the world who "milk" cone snails for venom.

Milking involves a tricky—and potentially deadly—process: enticing a captive cone snail to harpoon a condom-covered test tube opening. (Other scientists typically retrieve venom by dissecting the venom glands of dead snails.)

Bingham notes that milking reduces the number of cone snails he needs to take from the wild for research. The process also allows him to study how and why the snails change the compounds in their venom over time.

Each change in venom compounds yields a new toxin with unknown potential.

Once scientists identify the compounds in any given cone snail toxin, researchers can readily make it in synthetic form, Bingham added, noting that this eliminates the need to extract more venom from the snails.

Chivian, meanwhile, said any measure to protect cone snails is appreciated. "We are losing species at a great rate without identifying them and without any knowledge of what value they may have for our health and our lives," he said.

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