Old-Growth Yew Spared as Cancer Drug Source : Health: Drug firm decides it can’t risk millions producing medication that comes only from slow-growing wild trees. Instead, it uses ornamental varieties grown in nurseries.

Just two years ago, bark from the Pacific yew was in such high demand to produce the new anti-cancer drug Taxol that poachers were stealing it from the Northwest’s national forests.

Now the Pacific yew that falls in the course of logging on federal land is left to rot, unless someone wants the strong wood for fence posts or traditional English longbows.

And the special law passed in 1992 that made it illegal to waste yew bark on national forests is headed for the sunset, said Jim Simonson, yew coordinator for the Willamette National Forest.

Everything changed a year ago when Bristol-Myers Squibb Co. decided it couldn’t risk millions of dollars on producing a drug that came only from slow-growing trees in the wild that could be snatched away by forest fires, drought or environmentalists saving old-growth forests for the northern spotted owl.

Commercially available for the last year, Taxol is approved by the Food and Drug Administration as a second stage of treatment for ovarian cancer and is recommended for approval as a treatment for breast cancer.

Once its contract with supplier Hauser Northwest runs out at the end of July, Bristol-Myers Squibb will produce all the Taxol anybody wants from ornamental varieties of yew grown in nurseries.

“There was a lot of concern that we would use up all the trees, we would get into the old-growth forest, we were destroying unknown sources of new drugs as we cut the forest,” Jonathan Adams, head of the clinical research pharmacy section of the National Cancer Institute, recalled of the early Taxol years.

“We found out there are plenty of these trees and they grow everywhere. The scientists found out a way to make it from clippings so we didn’t have to kill the trees,” he said. “This was a very good learning experience that maybe we should use as a guide for the future.”

Taxol was first isolated nearly 30 years ago, but it was 1971 before scientists mapped out the complex molecular structure.

Susan Horwitz, professor of molecular pharmacology at Albert Einstein College of Medicine in New York City, discovered in 1979 that Taxol had a unique way of stopping the uncontrolled cell growth in cancerous tumors.

The National Cancer Institute soon began testing the drug. By 1991 it signed a five-year cooperative research and development agreement with Bristol-Myers Squibb that gave the drug company exclusive access to the yew bark harvested on national forests.

In exchange, Bristol-Myers Squibb spent more than $5 million for the Forest Service for research, law enforcement and an environmental impact statement, and provided the National Cancer Institute with free Taxol for clinical testing on 7,000 people.

That led to passage of the Pacific Yew Act in 1992 and a special environmental impact statement in 1993 to assure that yew bark wouldn’t be wasted and demand wouldn’t wipe out the tree.

But logging on national forests was being cut back drastically to preserve habitat for the northern spotted owl, a threatened species, and Bristol-Myers Squibb went looking for a steady supply.

It found it in a process that takes a precursor of Taxol, called 10-deacetylbaccatin III, that is found in ornamental shrub varieties of yew, and partially synthesizes the drug.

“In the pharmaceutical industry, we always felt that nature provided the best lead,” said M. Dianne DiFuria, senior director of business development for Bristol-Myers Squibb. “But it is up to the industry to either improve that lead or come up with alternative sources.”

That sent stock tumbling for Hauser Northwest, which was the sole supplier of Taxol to Bristol-Myers Squibb. The company is still collecting a little Pacific yew bark from private lands, but gave up collecting on national forests because of all the restrictions, said Phil Hassrick, executive vice president of the Boulder, Colo., company.

Bristol-Myers Squibb buys the Taxol precursor from a company based in Milan, Italy, that makes it from the European and Himalayan varieties of yew.

Scientists at Florida State University recently announced that they can now wholly synthesize Taxol, but the process has little chance of ever being cheap enough to compete with partial synthesis, DiFuria said.

Nonetheless, Bristol-Myers Squibb continues to pursue research into new ways to produce Taxol, such as tissue culture, as well as related compounds that may also be potent cancer fighters, DiFuria said.

And it expects to soon face competition from other drug makers, notably Rhone-Poulenc Rorer, a French company developing a related drug called “taxotere.”

Weyerhaeuser, the nation’s biggest timber producer, hopes to take over as the top source of the Taxol precursor.

Weyerhaeuser has planted more than 12 million ornamental yews, testing them for Taxol as well as the precursor and related compounds, said Dick Piesch, manager of the company’s Taxol program in Centralia, Wash.

Last September, Weyerhaeuser harvested 40,000 4-year-old seedlings of a hybrid of Japanese and European yews and gave them to Bristol-Myers Squibb for testing, Piesch said.

“There is no question that the bark of older trees as a commercial resource would disappear long before the demand would,” said Piesch. “I think we can all say . . . that Taxol is not limiting any more. There is plenty of it to go around.”

The only Taxol approved by the Food and Drug Administration is made from Pacific yew bark, but Taxol partially synthesized from ornamental yews is likely to be approved before the end of the year, said Saul Schepartz, deputy associate director of the developmental therapeutics program at the National Cancer Institute.

The new process will have to be approved to meet the growing demand. Breast cancer kills 46,000 women a year and ovarian cancer 13,600.

Scientists are testing Taxol against a variety of other cancers, particularly lung cancer and cancers of the head and neck, said Adams.