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They couldn't get away from the lethal cone snails.
Even before J. Michael McIntosh finished his last classes at Midvale's Hillcrest High School, he was toiling in Baldomero Olivera's University of Utah biology laboratory to tease out the secrets of deadly cone snail venom. McIntosh's work in the lab focused on toxins extracted from an ivory and gray cone snail species known as the magician's cone.
Little did the incoming U. freshman know that his work with cone snail venom was the start of something big.
Extracted from the killer cocktail of compounds that the tropical cone snails unleash on fish - and the occasional human - comes the basis for a new pain drug. The Food and Drug Administration recently approved the drug Prialt, which is aimed at terminal cancer patients and others suffering from pain that traditional powerhouse drugs such as morphine fail to treat.
"Morphine is a great drug if you only have to use it once or twice," said Olivera. But eventually, patients develop a tolerance to the drug.
Research indicates that Prialt, from Irish drug company Elan Corp., avoids the tolerance problems, he said. The drug is injected into the fluid around the spinal cord.
When first isolating the cone snail compound, in 1979, neither McIntosh nor Olivera had any idea of where their discovery could lead. The basic research focused on testing dozens of active components found in cone snail venom. There was no end goal in mind.
McIntosh had not even taken his first U. science course when he got his start at Olivera's lab bench.
"We were allowed to work on cutting edge stuff," said McIntosh, now a psychiatry professor at the U. "We weren't just repeating experiments that someone else had done."
That excitement of being an undergrad immersed in science helped steer McIntosh into a research career.
Cone snails helped draw him back to the U., following medical school at the University of California, Los Angeles.
McIntosh continues research on the creatures with Olivera between his teaching and patient responsibilities. Olivera said he first assigned McIntosh to purify components of cone snail toxins and identify their chemical structure. In later work, one of McIntosh's compounds, known as omega-MVIIA, caused mice to shake.
"The therapeutic uses weren't so clear," Olivera said.
The U. decided not to pursue a patent. Later research mostly elsewhere revealed the toxin's potential as a pain killer.
Basically, omega-MVIIA blocks the pain signal that would travel from the spinal cord to the brain.
Olivera worked with a former University of Southern California colleague, George Miljanich, who moved to a company, Neurex Corp., to explore potential uses for the compound. Elan Corp. bought Neurex and finished developing the compound into a drug.
In the early research days, Olivera was more interested in how cone snail venoms killed fish. Studying the compounds revealed they were similar to poisonous substances found in cobras and pufferfish.
Though the omega-MVIIA compound from cone snails is identical to the new drug, Prialt is chemically manufactured, Olivera said.
Ongoing research at the U. lab involves finding more potentially useful compounds. The cone snails live in salt water aquariums.
To demonstrate how cone snails eat, Sean Christensen, a laboratory technician, rooted around the sandy bottom of the aquarium with salad tongs, kicking up a cloud of debris to find a Conus geographus snail.
Christensen grabbed a pair of metal forceps, clamped down on a 10-cent goldfish and waved the meal in front of the cone snail.
"We've had these guys for a while," he said of the nocturnal hunters. "They've gotten lazy."
Once the brown and white cone snail realized its prey was nearby, it extended a netlike structure to envelope the goldfish. With the fish ensnared, the snail delivered a paralyzing sting to its meal.
Other cone snails employ a harpoon strategy in paralyzing the fish first, then dragging it into the net.
Olivera's fascination with cone snails dates back to his youth in the Philippines. When he was about 9 years old, he would wait near tennis courts while his father played. Sitting near the clay courts were piles of cone snail shells dredged from Manila Bay.
The mostly broken shells were destined to be crushed and applied to the court's surfaces. Olivera rooted through these piles in search of whole shells.
"I was waiting for my dad and I had nothing else to do," he said.
As he grew up, his interest in cone snails grew. The ability of some snails to kill people helped fire his imagination.
Like McIntosh, Olivera has been unable to escape the clutches of the cone snail. For several years, he considered his work on the salt-water creatures to be a short-term side project. The work of Craig Clark, a former undergraduate, showed snail venom had many biologically active compounds and rekindled Oliver's interest.
Some of these unexplored compounds still lurking in the venom might join Prialt on the pharmacist's shelf. The U. researchers are not the last who will succumb to the lure of the cone snail.
Prialt facts
l Prialt, a new pain drug from Irish pharmaceutical company Elan Corp., is based on compounds found in the venom of a snail known as the magician's cone.
l A University of Utah lab helped discover the compound, though it was not until later that its therapeutic uses were discovered.
l The U.S. Food and Drug Administration approved the drug last month and it should be available later this month.
l Prialt is delivered to the fluids surrounding the spine. The drug is used on patients with cancer, AIDS, back surgery problems and others who suffer from severe pain.
l More information on the drug is available at http://www.elan.com.
- Sources: University of Utah, Elan Corp.