With Baldomero M. Olivera of the University of Utah, Howard Hughes Medical Institute.
The 700 species of predatory cone snails (Conus) use venom to capture prey, defend against predators, and deter competitors. One fish-hunting Conus species is the deadliest snail known, with a 70% human fatality rate without medical intervention. Each Conus venom contains ~100 peptide toxins; most of these act on a specific molecular target in the nervous system. The genes encoding the peptide toxins are among the most rapidly evolving animal genes known; in effect, every cone snail has its own distinct complement of venom peptides, with essentially no molecular overlap between species. One Conus venom peptide has become an approved drug for intractable pain, and several others have reached human clinical trials.
Cone snails evolved a pharmacological strategy millions of years ago that greatly pre-dates parallel recent developments in pharmacological science, such as using a combination drug strategy. While cone snails represent only a very minor fraction of the total biodiversity of venomous marine mollusks, future prospects are bright for systematically characterizing the vast number of novel peptides from other venomous molluscan lineages that will have potential biomedical applications.
