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Venom as a Prelude to New Drug Treatments

Apparently snakes have "learned" to make these proteins in their salivary or venom glands. And not just the normal versions of those proteins but mutated versions that in many cases make them lethally more potent than the parent proteins.

Some snakes, for example, make modified versions of chemicals that normally help nerve cells communicate with muscle cells -- and they do it so well they lock up the system, causing paralysis. Other snakes have "recruited" a protein that normally deactivates enzymes and altered it to deactivate an enzyme that mammals use defensively to break down one of the snake's toxins. Still other snakes produce mutated versions of blood-clotting factors that trigger countless small clots in the victims' blood. That uses up victims' own clotting factors and leads to deadly hemorrhaging.

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"They're throwing our natural clotting factors right back at us," Fry said.

By comparing different versions of snake toxins that arose at various points in evolution, Fry was also able to get good estimates of which toxins appeared first. He has identified 10 that date to the earliest days of poisonous snakes. Contrary to previous wisdom, none of those are related to pancreatic enzymes, although at least one major toxin type eventually appeared from that source.

Evolutionary studies also indicate that the first snake toxins appeared well before specialized delivery systems such as fangs, Fry said. At first venomous snakes developed grooves in their teeth to direct venom into a bite, and later they developed sophisticated venom pumps and fangs, including some that fold elegantly inside the mouth and others that remain rigid.

Elazar Kochva, a zoologist who studies snake venoms at Tel Aviv University in Israel, praised the new analysis as "the first to show in such detail how many of these toxins are recruited from these other tissues." Kochva studies sarafotoxin from the burrowing asp. It is a potent mimic of the normal body hormone endothelin, which constricts blood vessels and can raise blood pressure to deadly heights.

"It powerfully affects contraction of the heart. I can attest to that," Kochva said, adding, as an afterthought, "fortunately."

For snake-venom researchers, every first-person story of a snakebite is a happy one.


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