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Pick Your Poison
MAY 2005
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Take Two Starfish and Call Me in the Morning

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Photograph by Cary Wolinsky

Marine animals with no armor and limited mobility, such as starfish, rely on poison for defense. It's called "animal chemical warfare," says National Cancer Institute scientist David Newman, who evaluates marine animal toxins for potential cancer drugs.

By Cathy Newman

Picture this. You're an innocent little sponge sitting on a coral reef. You're cemented onto a rock. You can't swim, float, or scuttle away from a predator that might want a small snack. You have no armor. What's left?
"Chemical warfare," says David Newman, a chemist who heads the marine collection program at the Natural Products branch of the National Cancer Institute's drug development program. "The animal with the best chemistry set wins." Their chemical weapons are diluted by huge amounts of saltwater, so poisons produced by marine organisms are extremely concentrated and potent because they have to be, which helps make them potentially useful to humans as well. The sea is a rich hunting ground for toxins with potential as cancer-fighting drugs. "All anti-tumor drugs are toxins," Newman points out. So each year he and his colleagues evaluate 500 to 600 marine organisms—sponges, worms, coral, algae, and starfish, among others—that have been collected, frozen, and air-shipped from 20 different countries.
Once the specimens have been processed (step one involves pulverizing the frozen organism in a meat grinder) and rendered into an extract, the compounds are tested on nine different cancer-tumor types, including breast, prostate, colon, lung, and liver. Those that make the initial cut go on to further trials.
Currently there are about four dozen or so compounds derived from marine organisms in different stages of the research process, but don't look for these pharmaceuticals in your local drugstore just yet. The time lag from drug candidate to Federal Drug Administration (FDA) approval is ten years plus. Taxol, a breast cancer drug derived from the yew plant, took 20 years to develop. "You have a better chance of winning the lottery than developing a new drug," Newman says.
Still, when the numbers line up, everyone wins. The first marine compound to make it to the drugstore, Newman continues, will be Ziconotide, a painkiller derived from a cone shell snail found in the South Pacific. Ziconotide, approved by the FDA on December 30, 2004, is about 50 times more potent than morphine, but without being addictive. The cone shell hunts fish with a venom-tipped harpoon, or extendable tooth. The venom, a mix of more than 20 different toxins, anesthetizes and paralyzes its prey. Conotoxins act on a particular pain receptor in the brain, giving them a potentially low side-effect profile. The downside is that they can only be delivered by injection. There are other possible payoffs in the marine toxin lottery. Bryostatin, a toxin derived from a marine bryozoan, or moss animal, is being paired with arsenic compounds as treatment for an acute form of leukemia. Soblidotin, a chemical modification of a nudibranch toxin, is being evaluated as a treatment for lung cancer. And DMBX, a subtle chemical modification of a worm toxin, is a possible treatment for Alzheimer's disease.
That marine toxins have pharmacological potential is no surprise. When you look at them from a molecular point of view, Newman says, you see lots of similarities. Saframycin, an antibiotic derived from bacteria, has basically the same molecule that can be found in a sponge. "Nature uses the same thing again and again. What works, works."
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