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Could Australia's Deadly Snakes Put Bite on Cancer?

Stephanie Peatling in Sydney
for National Geographic News
August 16, 2004
 
Bryan Grieg Fry spends his life getting up close and personal with creatures most people would do anything to avoid. But his work has also uncovered why so many of the world's most poisonous snakes ended up in Australia, how they are continuously adapting to remain highly effective killers—and how the chemistry they have mastered may be used to advance human health.

A childhood fascination with snakes developed into professional research for Fry. Now he is deputy director of the Australian Venom Research Unit, based at the University of Melbourne's medical school in the state of Victoria.

His specialty is researching the evolution of snake venom—work that allows him to spend large amounts of time on Australia's Great Barrier Reef investigating sea snakes or walking in the bush in search of their terrestrial cousins.



Snakes are believed to have colonized Australia between 15 and 20 million years ago, possibly from a single ancestral species. Over the millennia they diversified, adapting to Australia's multiplicity of habitats and abundant variety of food.

But it is the potency and diversity of Australia's poisonous snakes that make scientists the most excited. Seventeen of the world's most lethal snakes are found in Australia. Researchers are deciphering their chemical secrets, developed over millions of years—and in the process finding powerful new agents to fight disease.

Biological Lottery

Australia's snakes "hit a biological lottery and ended up incredibly different and toxic,'' Fry said. "Australian mammals aren't exactly a pushover.''

Presented with a huge variety of rodents, lizards, and small mammals to feed on, Australia's land snakes evolved different sorts of venoms to target different prey animals.

"The specialization that occurred has been fantastic,'' Fry said. "In sea snakes, the venom has become more streamlined because they're feeding on just one animal—fish.''

Venomous snakes have been slithering around Earth for more than 150 million years. Snakes were initially heavily muscled, swamp-based creatures much like today's anacondas of South America. But their bulk slowed them down. If they were going to catch new prey they needed to change.

Venom allowed snakes to "trade in" muscles and become leaner, faster, and more deadly.

Snakes develop toxins by deploying body proteins also commonly found in other animals, including humans. It's the way snakes modify the proteins that gives them entirely new functions.

For example, Australian snakes such as the taipan and the brown snake use two active enzymes in their venom that are also present in human blood: factor X and factor V. The enzymes play a role in the chemistry of blood, including clotting and bleeding.

The way the venomous snakes combine these two enzymes produces an almost perfect toxin that makes these snakes among the most lethal in the world.

Treasure Trove

Although Australia's high number of potentially lethal snake species may be intimidating for hikers and campers, the reptiles are a treasure trove for venom researchers.

The toxicity and potency of snake venom make it ideal as a building block for medicine.

Researchers at the University of South Australia are trying to isolate a compound in snake venom that can prevent cancer, for example.

Tony Woods, from the university's School of Pharmacy and Medical Sciences, says the compound speeds the destruction of blood vessels that that supply nutrients to tumors.

Tumors have rapidly multiplying cells that depend on nutrients and oxygen they receive from the host body's blood supply.

"U.S. researchers have found that if the blood supply to these tumors could be prevented from forming, or be damaged once formed, the tumors would not grow,'' Woods said.

"Our work has identified in some venoms a compound that can be used in very low concentrations. This means that the toxicity is much lower and it only affects the cells that we are interested in,'' Woods said.

Traditional cancer treatments such as chemotherapy and radiation kill both healthy and cancerous cells. But Woods's team has identified a compound in snake venom that targets only the growth of the endothelial cells in the blood vessels of tumors. Other cells are left apparently unaffected.

"These unique, special cells only occur in the lining of blood vessels. Endothelial cells must be in association with each other because they have a deeply engineered genetic function, which insists that they cohabitat,'' Woods said.

"A single cell on its own will die very quickly. By knowing how to destroy these cells, we can remove the lifeline of nutrients that keeps the tumors alive.''

Once the compound with the greatest effect is isolated, the team should be able to reproduce it artificially.

Snake venom is already being used in a variety of medications. Some of the most common are ACE inhibitors, which are prescribed for high blood pressure.
 

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