FEATURE: Beautiful But Deadly Creatures Both Kill And Cure

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Written By Maggie Fox, Health and Science Correspondent

NEW YORK (Reuters) – The tiny red-and-yellow striped frog looked harmless enough but just a single touch to the skin of the jewel-like creature could mean instant death.

For weeks it had been kept carefully imprisoned and denied the insects it normally ate. What Edson Albuquerque and his colleagues hoped was that their theory would prove right — the frog got its alkaloid poisons from eating ants or some other insect and the toxins would disappear after the special diet.

“To prove whether this was true we held the frog in our hands to see whether it would kill us or not,” Albuquerque told a recent seminar. That he was alive to tell the tale showed the value of his theory.

But the poison-dart frog is more than a curiosity. People living in the Amazon for centuries used the toxins produced by the frogs on arrows and darts to hunt with — thus the name.

Aimed at a monkey high in a tree, they were mercilessly deadly.

”One shot and goodbye,” Albuquerque said. Now it seems these poisons could benefit more than just hunters. Chemical analysis has shown they are targeted at some of the most basic cell processes, and just a little tweaking can turn something deadly into a valuable human drug.

For instance, fugu pufferfish are a thrilling delicacy in Japan because they must be prepared by an expert chef or the gourmet who eats them may die. The reason is tetrodoxin, a poison that is “exquisitely” targeted against sodium channels, according to Dr. Bruce Bean of Harvard Medical School.

Sodium channels are molecular doorways on the surface of the cell that control how much sodium goes in and out. Tetrodoxin acts to prop open the sodium channels, letting too much sodium into the cells and destroying them.

‘NATURE PROVIDED IT’

“This is a molecule that you would never think of making from scratch but nature provided it,” Bean told a seminar in New York on the value of animals, plants and microbes to human health sponsored by the American Museum of Natural History.

Scientists have begun to appreciate this and are combing nature for new compounds. For example, one of the poisons made by the tiny Amazon frogs, known as batrachotoxin, also works against sodium channels.

Since the frog does not make the poison, as Albuquerque’s experiment proved, why does it not die when it eats the ants or whatever it is that does make the poison? “Over millions of years the frog has made subtle modifications of the receptor molecule and it has become insensitive to the effects of batrachotoxin,” Albuquerque said.

If scientists could figure out just what the modifications are, they could possibly use the same mechanism to treat human diseases in which sodium can destroy cells such as Alzheimer’s and Parkinson’s, both fatal and incurable brain diseases.

Another of the little Amazon frogs, the epipedobates, produces epibatadine. This chemical works on the nicotinic receptor, another important cellular doorway best known because one of the chemicals whose effects it mediates is nicotine.

Abbott Laboratories says the effects of epibatidine can help scientists understand diseases ranging from Alzheimer’s to epilepsy. Michael Williams, head of neurological and urological diseases at Abbott, said the company was developing a synthetic version it calls ABT-594.

PAINKILLER WITH 200 TIMES POWER OF MORPHINE

Epibatidine can also act as a painkiller — one that is 200 times more powerful than morphine — but it does not work though the opioid mechanism that morphine uses.

“Unlike morphine it lacks the major side-effects that make morphine undesirable,” Williams said. These include constipation, addiction and the need to keep using use more of the drug to get the same effect.

Other poisonous animals kill in other ways and can offer intriguing new treatments for a range of diseases. Robert Gould, executive director of pharmacology at Merck Research Laboratories, tells how snakes can help prevent heart attacks.

Researchers at Merck knew the Indian tree viper’s bite caused victims to bleed to death. Thinking the venom might carry an agent useful for fighting blood clots, which cause heart attacks and stroke, they started milking snakes for their venom and analyzing it.

They isolated a protein they named echistatin from a viper found in North Africa. It had some components that were similar to fibrinogen, which helps “glue” blood platelets together to make clots, so they knew they were on the right track.

A little fiddling in the lab and they came up with a small molecule that could stop platelets from aggregating. They developed it into Aggrastat, known generically as tirofiban, and doctors who advise the Food and Drug Administration have urged the FDA to approve it for preventing heart attacks in people with unstable angina or who have had an attack already.

It could be on the market within a few months as the FDA usually follows the advice of its advisory committees. Some of the deadly creatures that can provide useful medicines live in the sea. William Fenical, director of the Center for Marine Biotechnology and Biomedicine at the Scripps Institution of Oceanography in San Diego, says a soft coral known as pseudopterogorgia, the Caribbean sea whip, produces a compound that can control inflammation and pain.

“This is the future for breast and ovarian cancer,” he said.

REUTERS