ROANOKE TIMES
Copyright (c) 1997, Roanoke Times
DATE: Monday, February 10, 1997 TAG: 9702100137
SECTION: NATIONAL/INTERNATIONAL PAGE: A-1 EDITION: METRO
DATELINE: SAN FRANCISCO
SOURCE: Associated Press
In a dark cave 100 feet below the surface of the Pacific, hidden in the tissue of a rare sea creature, scientists found one of the most powerful cancer-fighting compounds they'd ever seen.
They have not been able to find it again.
The discoverer, William Fenical of the Scripps Institution of Oceanography, has returned repeatedly to the Philippine island of Siquijor in a vain search for more of the chemical.
``We've been looking for years, and still have never found it again,'' he says. ``We find some creatures that look a lot like it, but none of the animals there had the right compound.''
Researchers don't even know if the creature itself produced the compound, or if it was a by-product of some symbiotic fungus or bacterium.
But the story, reminiscent of the 1992 fictional movie ``Medicine Man'' in which Sean Connery finds - and then loses - a cure for cancer in the Amazon, may have a happy ending.
Researchers at the University of California, Santa Cruz saved some of the sample, and say within a few years they expect to synthesize the compound, called diazonomide A.
Fenical's team, working on a National Cancer Institute grant, made their discovery in 1991.
They collected samples of a rare creature called Diazona chinensis, a jellylike animal related to the sea squirt, which attaches itself to rocks and filters its food from the ocean.
The creature had been studied two or three decades earlier, but showed no promise.
This time, laboratory tests turned up something new.
``Much to our surprise and shock, there were enormous amounts of this new molecule, and the molecule had the ability to kill human colon cancer cells with very high proficiency,'' Fenical says. ``It was very potent at very small doses.''
He emphasizes that such test tube success doesn't mean the compound works in human beings. That can only be determined by clinical trials, and many times such compounds prove too toxic for medical use. But the lab tests were exciting.
Diazonomide A was also exotic structurally, with an unusually rigid, compact form that interested chemists. Fenical sent some to chemistry professor Joseph Konopelski at UC Santa Cruz.
``My own interest was in the fascinating structure of the molecule itself,'' Konopelski says.
But when he tried to build a model of the molecule using plastic balls to represent its 99 atoms, it wouldn't work.
``The pieces don't fit - you have to jam them in,'' Konopelski said. ``Nature seems to have gone to a lot of trouble to put this thing together.''
No one is certain what role it plays in the sea creatures. It may help the soft-bodied animals repel predators, Konopelski said.
Fenical wanted more of the compound to run more elaborate cancer tests. Konopelski wanted to explore its chemical properties.
But despite repeated efforts by Fenical, including more than two months of actual search time over four years, none of the creatures they found contained diazonomide A.
So Konopelski stepped in with a $500,000 American Cancer Society grant and began trying to synthesize the compound.
``This is the most challenging project I've ever been associated with,'' he says.
Slowly he has assembled pieces of the molecule, and believes the end is in sight.
``Our goal is to make enough of this stuff to test, and I believe we will succeed,'' Konopelski says. ``I have two graduate students who are betting their Ph.D.s on it.''
In the long run, both Fenical and Konopelski say, the failure to find a natural source of diazonomide A again may be for the best.
``It's one thing to have taxol that comes from a yew tree,'' Konopelski says, referring to another cancer fighter. ``But if you have to go down 60 meters to get something, you're always going to have a supply problem.''
In addition, pharmaceutical companies cannot patent natural compounds; so to develop and market a drug, they need to change its chemical nature.
Fenical says synthesizing the drug also opens up more possibilities.
``If I had found the original molecule, I would only have a single chemical substance, and it might have been abandoned as a potential drug and nobody would have looked at anything else,'' he says.
By assembling the molecule, Konopelski and others can try variations that may prove more successful.
Ultimately, Konopelski will succeed in synthesizing the compound and perhaps even more effective compounds, Fenical asserts.
``So I don't feel like the medicine man in the movie.''
LENGTH: Medium: 91 linesby CNB