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ARKIB : 01/11/2004

Farming killer cone snails for research is a risky affair

GOLD fish is used as bait to lure salt-water snail into using its harpoon, orange extension shown here at the Clarkson University lab in Potsdam, New York, Aug 4. - APpix.

POTSDAM (New York) - Jon-Paul Bingham puts his life on the line every week for the sake of science. One wrong move, and he could become the hapless victim of a snail attack that could kill him.

Bingham, a biochemist at Clarkson University, is a self-described ``conehead'' whose livelihood depends on scuba diving for tropical marine cone snails and coaxing them to discharge their venom in his laboratory.

``It's like snake-charming,'' he said with a grin.

Cone snails churn out a cocktail of toxins, each with its own unique chemical properties. Scientists are studying these poisons with the hope of turning them into potential drugs that could one day treat chronic pain, epilepsy and neurological disorders such as Alzheimer's.

For centuries, shell collectors have bagged cone shells for their intricately patterned armour. Cone snails are among the sea's most abundant creatures with more than 500 species, and are mostly found in coral reef environments in the IndoPacific region.

But cone snails are potentially dangerous, especially the fish-eating types. There is no antidote if a person gets stung. Usually, the victim is paralyzed and can't breathe, and is immediately placed on respiratory support in the emergency room. Recovery can take several hours to a few weeks.

In unfortunate cases, a person can die within an hour of being stung. Some 30 people have been reported killed by cone snails during sea expeditions dating back to the 1930s.

Several companies worldwide are testing different cone snail toxins in animals and humans. The most advanced work is being done by Elan Corp., a biotechnology company based in Dublin, Ireland, which is trying to get Food and Drug Administration approval for its pain-killer Prialt.

Prialt is synthetically made from a naturally occurring toxin from the marine snail Conus magus, and works by blocking nerve channels in the body responsible for transmitting pain signals.

The drug, which is injected into the fluid surrounding the spinal cord, reduced severe chronic pain in human patients in three experiments carried out by the company.

Scientists believe cone snail venom may someday be used in pain management as an alternative to or in tandem with morphine, but without morphine's addicting side effects. Yet its use may be limited because of the way it's administered, said David Goldstein, a pain researcher at Indiana University and a board member of the American Society for Clinical Pharmacology and Therapeutics.

To get venom from snails, most scientists either dissect dead cone snails found in nature or create it chemically in the lab.

Bingham thinks he can reap a more diverse mixture of toxins by milking cone snails in captivity. He is one of the few scientists in the world who farms cone snails in his lab nestled in the northern foothills of New York's rustic Adirondack Mountains near the Canadian border.

Bingham, a 33-year-old Australian who has milked snails for over a decade, has never been stung and he never wants to be. But just in case there's an accident, his medical file at the Canton-Potsdam Hospital down the road from the university contains instructions on how to treat a sting.

Baldomero Olivera, a biologist at the University of Utah and a pioneer in the field, used to milk cone snails in his lab, but hardly does it anymore because the task became too monotonous.

``The problem with milking is that it's quite tedious,'' Baldomero said. Not only do researchers need to perform several milkings to get a good sample, but how much venom they collect is also dependent on the cone snails' behavior on a particular day, he said.

Olivera, who has been studying cone snails since the 1960s, discovered early on that certain snail venom - made up of protein-like molecules called peptides - can work as an anesthetic.

In the 1980s, students in his lab injected different snail toxins into the nervous systems of mice. Depending on the type of toxin, the mice acted differently. Some would shake and others would sleep, leading scientists to isolate the chemical properties of the venom for potential medicinal use.

In 1996, Olivera and a colleague founded Cognetix Inc., a privately held biopharmaceutical company based in Salt Lake City that studies cone snail venom.

One day recently, Bingham demonstrated the milking process.

Inside Bingham's lab is an average-sized fish tank carrying an ominous warning on the lid: ``Danger! Venomous Snails.'' Nine fish-eating snails collected from Panama four years ago live in the tank filled with salt water and beach sand for them to bury themselves. Only the largest one - at 2 1/2 inches (6.4 centimetres) - is named: Big Bertha.

With his bare hands, Bingham took a pair of long metal forceps, stirred the water and waited. The ripple effect caused the elephant trunk-like noses of the cone snails to slowly poke out of the sand.

Like a surgeon getting ready for an operation, Bingham got everything in order. He gingerly picked up the snails with the forceps, lined them all up on one side of the tank and counted them to make sure none was hiding in the sand - a potential recipe for a surprise sting.

Now the milking can begin.

Hunching over the tank, Bingham dangled the bait - an unsuspecting goldfish - in his left hand using a pair of forceps. Behind the fish, Bingham held a small plastic container shaped like an inverted triangle with a piece of non-lubricated condom slipped over the opening.

The trick, Bingham explained, is to entice the snails to sting the fish and release their venom into the container.

Big Bertha, smelling the fish, inched forward and whipped out her harpoon-like proboscis. She stung the fish, but her proboscis failed to penetrate the condom. No venom was released into the container.

Looking disappointed, Bingham tried again.

Lying in wait like a hunter, he got into position and eyed his gloveless hands holding the trap. The room is silent. Bingham wrinkled his nose and licked his lips.

Another snail came forward toward the twitching, paralyzed fish. This time, its proboscis penetrated the fish's tail straight through the condom, pumping poison into the container. The milking was over in the wink of an eye.

Out of four tries that day, only one milking was successful. Bingham got a droplet of the venom no larger than a poppy seed. On good days, he gets much more. The next step is to put the poison in the freezer where its chemical content will be studied later.

Scientists studying cone snail poison have found that a single snail can produce up to 100 different kinds of toxins. Now they're trying to find out why and how it happens.

``These animals are like craps players,'' Bingham explained. ``Every time they roll the dice, they make a new compound.''

On the Net:

Clarkson University:

Elan Corp:

American Society for Clinical Pharmacology and Therapeutics: - AP

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