CHPC Supports Web Site to Explore Cone Snail Biology Interactively
Cone snails (Conus) are very successful predators. These abundant small marine animals use their venom to defend themselves and to capture prey by delivering fast-acting toxins that paralyze the victim. Even though the nearly 500 living species of the cone snail cannot swim, many survive by eating live fish. Dead fish just won't do. The snails have developed sophisticated venom production apparatus and delivery systems. Some of the fish-eating snails have teeth which act as both harpoon and needle for delivering the venom to fish. Others engulf their prey with large distensible mouths, like a fisherman with a net, before delivering the fatal sting. The venom varies widely from one species to the next, each having evolved to work most effectively on the specific targets. The venom of Conus geographus, the geography cone, is extremely toxic to humans. The sting has been fatal in 70 percent of the untreated cases.
Baldomero M. "Toto" Olivera, a distinguished professor of biology at the University of Utah, grew up in the Philippines, where cone snails were a common staple in the fish markets. Olivera learned of the cone snail's poisonous venom in occasional stories of fishermen dying after being stung. For the past three decades, Olivera has been studying these venoms, composed mostly of peptides, to identify the specific peptide structures of the thousands of toxins that have evolved. Cone snails manufacture a variety of toxins each having a particular role to play in the capturing of prey, working effectively as a combination drug therapy. For example, a group of toxins at the injection site will immediately stun the prey while a second group will travel into the neuromuscular system causing paralysis so the prey remains immobilized while it is devoured. In addition, the snails produce precisely targeted toxins that work on particular receptors. The evolution of the targeting capabilities of cone snail venom has been a primary focus of Olivera's work. Drugs that have precise targeting abilities are less likely to have severe side effects, a great benefit to patients who take medicines for chronic conditions.
CHPC is working with Olivera's research group to create and maintain a web site that presents their research findings. Go to http://www.neogastropodtol.org to see videos of predatory cone snails in action as they immobilize and consume their prey.
Cone snail research has already led to the development of medicines for nervous system and cardiovascular disorders. Prialt, a drug which can be injected into fluid surrounding the spinal cord as a treatment for severe pain due to cancer, AIDS, injury and failed back surgery, was developed from cone snail research. The venomous cone snail Conus geographus produces a substance named conantokin-G. Cognetix Inc., a Salt Lake City company cofounded by Olivera in 1996, now is developing CGX-1007, a compound derived from conantokin-G, as a possible treatment to control seizures in patients with intractable epilepsy.
Understanding precisely how specific toxins work on their targets could also lead to additional methods of pain control. J. Michael McIntosh, one of Olivera's colleagues at the University of Utah Center for Neuropeptide Pharmacology, published findings in 2002 about two cone snail toxins RgIA and Vc1.1 that treat nerve hypersensitivity and pain in rats by blocking a cell molecule known as the "alpha9alpha10 nicotinic acetylcholine receptor." The toxins were particularly effective in alleviating pain in rats with severe sciatic nerve damage. McIntosh plans to use these findings to develop a treatment for severe pain in humans that would similarly target the alpha9alpha10 nicotinic receptors found in nerve cells.
Cone snail research has also provided provocative insights into human evolution. Olivera and his colleagues, biologists Pradip Bandyopadhyay and James E. Garrett, published the results of their research on a gene found in humans, fruit flies and cone snails that makes gamma-glutamyl carboxylase or GGC. Composed of "junk DNA" -- portions of the genetic code that are within genes but have no apparent function -- this gene is not only present in all three, it is also located in the same place in the genetic sequence, indicating that the gene and the enzyme it produces originated very early in the evolutionary chain. This discovery provides an interesting possibility that "junk DNA" is not a relatively recent addition to the human gene pool as many scientists argue.
Nor is it "junk." Olivera speculates that it may have played a developmental role in the growth of embryos, giving chemical signals that prompted embryonic cells to differentiate into the types of cells needed within a living organism.