Toxic tools: frogs down under pack their own poison.

For years, researchers demonstrated repeatedly that poisonous frogs don't make their own toxic chemicals. Instead, the scientists found, a frog obtains these skin compounds by ingesting arthropods that contain them.

Now, researchers of the same group say they've found a type of frog that seems to synthesize its own poisons.

Scientists suspect that frogs use skin poisons as a defense against predators and microbes. Pharmaceutical makers are using variations of these chemicals to develop drugs for people.

In their skin, Australian frogs of the genus Pseudophryne contain two classes of the poisonous chemicals called alkaloids. One class, pumiliotoxins, is found in frogs of many genera worldwide. The other, pseudophrynamines, has turned up only in Australian Pseudophryne species.

Researchers were studying how Pseudophryne frogs take up alkaloids. Thomas Spande of the National Institutes of Health in Bethesda, Md., says that he and his colleagues were surprised to find that skin extracts from frogs raised in captivity--away from any alkaloid sources--had high concentrations of pseudophrynamines, although no pumiliotoxins were present. In contrast, wild frogs contain primarily pumiliotoxins and only small amounts of pseudophrynamines. Those results suggest that the frogs obtain pumiliotoxins but not pseudophrynamines from their environment, says Spande.

Spande, John Daly, also of NIH, and their colleagues at NIH and Adelaide University in Australia suggest in an upcoming issue of the Journal of Natural Products that the accumulation of large amounts of pumiliotoxins from the animals' natural diets turns off the synthesis of pseudophrynamines. The results are also scheduled to be discussed by Daly this week in Orlando at a meeting of the American Chemical Society.

"When it comes to alkaloids, given what Daly has been showing over the years, I would not have bet on a frog that makes its own [alkaloid]," says Thomas Eisner of Cornell University.

One of the next steps for the researchers is to determine how the frog makes pseudophrynamines, says Spande. He also says that Pseudophryne frogs could take up pumiliotoxins by an unusual mechanism. The frogs might provide researchers with clues to new ways to administer drugs to people, he speculates.

"I'm happy for the Australian frogs," Eisner adds. "They're well-armed even when they're hungry."