Toxic assets

Abstract

By a lucky twist of fate, molecular biologist Baldomero “Toto” Olivera has found himself surveying a compellingly new ecological frontier, inhabited by a class of tiny, intricately designed marine gastropods with the unfortunate name of turrids (Turridae). Early last year, a film crew had accompanied the researcher to the Philippine island of Mactan, the site of Olivera's long-running research on venomous cone snails (Conidae). On a whim, Olivera suggested that the crew shoot scenes of fishermen retrieving their nets to gather seashells they planned to sell to Asian collectors. “I'd actually never been present before when the fishers hauled in their nets”, Olivera recalled in a recent telephone interview. “But as they were shaking them out, I realized that a lot of the things they had captured were alive! And then I thought, ‘we should analyze what's in the net’.” Olivera and his colleagues found that a single haul from depths of up to 50 meters contained several thousand different gastropod specimens. There were not only cone snails, which were roughly the size of a baby's hand, but also as many as 50 different species of turrids, some no larger than a small beetle. As he gazed at his find, back on the beach at Mactan, Olivera said he immediately understood why the tiny shells – some brilliantly pink, others boldly striped – have become a favorite among Japanese hobbyists. “They're beautiful, and there's always something new [to admire]”, he said. Even more exciting, however, is the turrids' potential to contribute to biomedical progress. Cone snail research has already sparked a pharmaceutical treasure hunt, inspired by scientists' revelations about the mollusks' chemical arsenal. The toxins they produce are surprisingly precise in their action, working only on specific cell receptors. In recent years, the peptides have shown promise as potential ingredients for novel drugs and also as a tool we can use to learn about the human brain and possibly to detect some cancers. In a major coup during the early 1980s, Michael McIntosh, then an undergraduate student in Olivera's lab, isolated a toxin from Conus magus (magician's cone) – the synthetic form of which, under the brand name of Prialt, has since been used to treat intractable pain in more than 7000 patients who have grown tolerant to opiates. (Prialt stands for “primary alternative” to morphine.) In an illustration of the toxin's specificity, it blocks communication between nerves that carry pain signals without affecting a patient's sense of temperature or touch, or interfering with mobility. Another half-dozen cone-snail-derived drugs are currently in clinical trials for the treatment of pain and epileptic seizures, and to minimize damage from heart attacks. Writing in the journal Science in 2003, Eric Chivian – founder and director of the Center for Health and the Global Environment at Harvard University – called cone snails possibly the largest and most clinically important pharmacopoeia of any genus in nature. But that was before Chivian learned about turrids. “We know almost nothing about cone snails, but what we know is so incredibly exciting”, he told me. “And we know nothing at all about turrids, which is a whole parallel universe that may be incredibly important.” Olivera is continuing to study conotoxins, in the Philippines and at his lab at the University of Utah, but in recent months he has expanded his research into turrids. He says that each time he visits his fishermen friends in the Philippines, their nets bring up what are likely several entirely new species. His research colleagues in Manila have yet to identify about 50 specimens that may turn out to be unknown to science. Olivera's original interest in cone snails was another, mostly serendipitous event. After completing his education in the US, he returned to his native country, only to discover that his new lab at the University of the Philippines had no equipment. In an effort to figure out low-tech avenues of research, Olivera remembered his childhood afternoons spent collecting snail shells. “I knew one species that was potentially deadly to people, so I decided to try to figure out what made them lethal”, he said. “That ended up being a more sophisticated question than anyone had expected.”