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Cone snail species Conus hirasei
Cone snail species Conus hirasei. Cone snails are marine snails found in reef environments throughout the world. They belong to the family Conidae, genus Conus, and there are more than 1,000 species known. Cone snails prey on other marine organisms, immobilizing them with unique venoms. [See related images of other cone snail species including Conus hirasei, Conus eburneus, Conus aurisiacus, Conus magus and Conus textile.] (Year of image: 1998)
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Baldomero "Toto" Olivera, a biochemist at the University of Utah, may have discovered relief for thousands who suffer from intractable pain, epilepsy or neurodegenerative disorders.
For the past 30 years, Olivera has studied the cone snail species Conus geographus, an animal so lethal that one sting kills an adult within hours.
When Olivera began his cone snail research in the 1960s, while living in the Philippines, his initial goal was to purify whatever caused human fatalities from C. geographus. His early research involved injecting C. geographus venom into the abdomens of mice, causing them to immediately became paralyzed. In order to find the secret paralyzing ingredient in snail venom, Olivera and his research team chemically divided the venom into a series of different fractions and injected them one by one into mice. They discovered that the venom contained not one, but many different nerve toxins, which turned out to be peptides--small, protein-like molecules.
Several years later, Craig Clark, an undergraduate student on Olivera's team at the University of Utah, came up with the idea to inject components of the venom directly into the central nervous system, instead of into the abdomen of mice. Depending on which peptide the researchers injected, the mice would shake, sleep, scratch, convulse or become sluggish. One of the peptides even caused different reactions, depending on the age of the mouse--it put newborn mice to sleep but whipped adult mice into a hyperactive frenzy. This raised a number of questions: What were the peptides doing? How did they work? Could he find which ingredient caused the odd behaviors? Could it be harnessed as a medicine?
To really understand how the venom works, Olivera's group isolated and characterized individual toxins in the deadly potions. His team discovered that each toxin hones in on just one type of molecule. In many cases, these molecules are "channel" proteins that control the flow of electrically charged particles such as calcium, sodium and potassium, into and out of cells. By blocking these channels, the toxins shut down messages between the brain and muscles, causing paralysis or electrical shock in a snail's prey.
Olivera discovered that the peptide that puts newborn mice to sleep locks onto a corner of one type of brain protein. In fact, these peptides are so accurate in pinpointing their targets that they are now used by neuroscientists to identify and study specific brain proteins.
Pharmaceutical companies realize that peptides with such specificity may hold promise in the development of highly effective medications with very few side effects. Some have already begun to tap the potential of dozens of cone snail peptides to treat disorders including pain, epilepsy, cardiovascular disease and various neurological disorders.
The clinical applications of Conus toxins are inspired by the snails own biology. Paralyzing peptides might be used as anesthetics. "Sleepy" or "sluggish" peptides could be used as anti-epilepsy medications to tame nerve cells that fire out of control during seizures. Olivera's long-term goal is to use the peptides to treat even more elusive conditions such as Alzheimer's and Parkinson's disease, schizophrenia and depression. [This text was adapted from an article by Alisa Zapp Machalek, "Secrets of the Killer Snails."]
Credit: K.S. Matz
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