New medicines rise from ocean

Powerful pain-killer, Prialt, is derived from snail venom

Health & Fitness

July 29, 2005|By Knight Ridder / Tribune

PHILADELPHIA -- Suffering from colorectal cancer, Tom McAuliffe was in such pain that he had to sleep standing up, propped against a couch.

Now he can rest easier, thanks to a new pain medicine derived from an unlikely source: the venom of a snail from a coral reef off the Philippines.

When the drug received clearance from the Food and Drug Administration in December, it was believed to be the first time the agency has approved a medicine that is an exact copy of a chemical found in the ocean. Called Prialt, it is used for patients with severe, chronic pain not alleviated by other treatment.

The compound was first isolated by a University of Utah scientist who, as a boy in the Philippines, had been warned to be careful of swimming near the venomous snail.

"I was blown away" to learn the drug's origin, said McAuliffe, 57, a former executive in the arcade-game industry.

Ancient source of help

Scientists say the ocean is a largely untapped reservoir of possible medicines, with at least as much potential as the rain forests that have been popular pharmaceutical hunting grounds. And environmentalists are encouraged, hoping that drug companies will be allies in the quest to prevent the destruction of corals and sponges by fishing trawlers.

Oceana, a nonprofit group based in Washington, expects word this month on its federal petition to stop trawling in unexplored waters. The group's primary goal is to preserve fish habitat, but officials say the promise of the ocean as a medicine cabinet is an added bonus.

George Miljanich, a research fellow at Elan Corp., the Irish firm that makes Prialt, agreed. "We need to preserve these habitats so that we have the time to find the next great drug," he said.

Although the deep reaches of the ocean are largely unexplored, making medicines from so-called natural products is not new. Plants and their extracts have been used to treat ailments for many thousands of years, almost as long as people have been getting sick, said Frank Koehn, director of natural-products discovery for Wyeth Pharmaceuticals.

In the modern era, perhaps the most famous "natural" medicine is Alexander Fleming's accidental discovery, in 1928, of the bacteria-fighting mold that he named penicillin. And in the 1950s, drug makers modified compounds found in sea sponges to create antiviral medicines. Almost half of the drugs on the market today trace their origin to a compound found in nature, Koehn said.

"Mother Nature was there first and has structures and molecules that we've never seen," said David J. Newman, acting chief of the natural-products branch at the National Cancer Institute in Frederick.

Wyeth, along with Bayer and Novartis, is among the few large drug companies with big natural-products programs, focusing its efforts on microbes from the soil and the sea. Wyeth said it had more than 20 scientists working in the field but declined to disclose its spending.

Most natural-product discovery and testing is handled by smaller firms and by academic institutions, such as the Scripps Institution of Oceanography in California, which then license their discoveries to companies.

About 15 drug candidates derived from marine organisms are in various stages of clinical trials for cancer, Newman said. Another half-dozen trials are under way for other diseases. One compound, derived from a creature called the sea squirt, is being tested on cancer at Fox Chase Cancer Center.

Supporters caution against the idea that every plant or animal is brimming with potential medicines. Wyeth's Koehn estimated that of the thousands of microbial strains in the company's library, fewer than 1 percent score a "hit" -- some type of biological response that is worth pursuing -- when tested in the lab on a particular enzyme or cell.

But the odds are good enough, said Newman -- especially in the ocean. We share common ancestors with marine life, and so it is not surprising that marine-based compounds could provoke various impacts in humans, he said.

"The odds are better for natural products" than for the man-made variety, Newman said. "Mother Nature has designed them to do things."

And because sea creatures live in the water, any compounds that they secrete are likely to be potent because they must overcome dilution, he said.

The snail toxin now being injected into Tom McAuliffe's spine, for example, is 1,000 times as potent as morphine.

Cone snail used

Prialt's road from ocean to doctor's office was a long one.

Although scientists have since learned how to make the drug in the lab, the compound initially was extracted from a cone snail -- one of several hundred such species that possess a startling method of catching their prey. The animal injects venom into passing fish through its tubular tongue and then swallows its catch with a stomach-like appendage.

Baldomero Olivera, the scientist who learned of the snail as a boy in the Philippines, published a paper in 1985 about toxins in the animal's venom after one of his students isolated them.

One toxin was discovered to block calcium channels that are the key to transmitting impulses from pain nerves to the spinal cord. Morphine has a similar effect, albeit indirectly, and Miljanich, then at the University of California, decided to test it as a medication.

Though more powerful than morphine, Prialt is not addictive, and users do not build up tolerance to it, Miljanich said. But there can be serious side effects, including dizziness, nausea and confusion, and it is reserved for those with severe, chronic pain.

McAuliffe, for one, said he could live with some mental "fogginess" in exchange for being able to sleep at night.

Two days after starting the drug, he said, the excruciating waves of nerve pain were mostly gone.

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