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by Janet Howard

Despite more than 25 years of diving around the world in search of unique marine creatures, William Fenical was baffled when he came across a strange, yellow coral growing on an underwater boulder in the Indian Ocean.

"Soft corals just don't look like that," said the Scripps professor of Marine Chemistry. "They looked like fingers sticking out all over the rock. I had no idea what they were when I collected them."

The coral named Eleutherobia turned out to be a rare species of softcoral that shows great promise as a potential drug to fight breast and ovarian cancer.

Fenical discovered Eleutherobia in 1993 while diving off the northwest coast of Australia. The research team had decided to explore a shallow area of water known as Bennett’s Shoal, which serves as home to a wide variety of marine life. Finding Bennett’s Shoal, however, was not easy.

"It was very murky and there were things swimming around all over the place. You couldn’t tell what was going on. Visibility was only a few feet.”

“We eventually found a guide—this very colorful, aging Aussie bloke,” Fenical said, staring out his office window overlooking the Scripps Pier and chuckling. “He was one of the only guys around there, sort of a folkloric character out of the middle of the Aussie outback. The guy was riddled with bullet hole scars and had survived some kind of boat fire.”

While regaling the team with shark stories, including how one had turned over his boat, the guide, who went by the name of Pancho, led the crew to Bennett’s Shoal.

“He knew how to get to it perfectly,” said Fenical. “I don’t know how, but he did. So we jumped over and it was a real spooky place. It was very murky and there were things swimming around all over the place. You couldn’t tell what was going on. Visibility was only a few feet.”

As Fenical approached a large boulder, he noticed some small organisms that resembled cheese puffs sticking out from the rock.

“I’ve been working on soft corals for 25 years and I never saw this species before,” he said. “I never saw anything like it.”

Recently patented and licensed to Bristol-Myers Squibb, a chemical called eleutherobin, extracted from the coral, appears to function similarly to taxol in preventing cancer cells from dividing. Heralded as a breakthrough treatment for breast and ovarian cancer, taxol is found in the bark of the Pacific yew tree. Because extracting the product resulted in the death of the slow-growing tree, Bristol-Myers Squibb began producing a semisynthetic verScrippsn of the drug from a precursor to taxol found in the trees’ needles. While it is a potent weapon against cancer, taxol is difficult to administer and has serious side effects, including immune system suppression, nausea, and hair loss.

One of Fenical’s students, Thomas Lindel, stumbled across eleutherobin’s taxol-like potential while studying the unusual coral in the lab. After extracting the chemical, Lindel tested it in a standard bioassay used to determine whether substances show activity against human colon cancer cells. He was stunned by what he saw. “The stuff was so extraordinarily potent that it was dangerous to handle,” said Fenical, director of the Scripps Center for Marine Biotechnology and Biomedicine. “You could dilute it a million-fold, and it still killed cells very powerfully.”

Further tests showed that eleutherobin mimics taxol’s very unusual method of blocking cell diviScrippsn. Like taxol, it binds to cellular structures called microtubules, which are part of the mitotic spindle and play a key role in cell division. Once eleutherobin has attached to the microtubules, they become extremely rigid and prevent the cancer cells from dividing.

“Taxol is important because it is the only drug discovered that acts by this very specific mechanism,” Fenical said. “People have looked for ten years and rarely found molecules anything like it, and we just stumbled across it in the middle
of this place off the coast of Australia.”