Pacific yew (Taxus brevifolia)
TAXACEAE, Yew Family
Species of yew (Taxus) have been used by humans for thousands of years. Wood from these trees and shrubs made excellent bows for English archers and lutes for musicians, and in cold climates yew wood was used for snowshoe frames. Several chemicals from yew were also known, especially the alkaloid taxine, which is toxic to humans, cows, and horses. Native tribes in western North America long used Pacific yew (T. brevifolia) for its healing powers. Only recently, though, pharmacologists have conducted conclusive studies to show that taxol, a complex molecule in Pacific yew, found in all parts of the plant, is effective for chemotherapy of ovarian and possibly other cancers.
Pacific yew is a very common tree or shrub in the coniferous forest understory of western North America, along the coastal ranges from southeastern Alaska to northern California and in the southern Canadian Rockies to central Idaho and neighboring Montana. The plant grows slowly but reproduces easily from seed or vegetatively from old stumps and roots. The wood is very decay resistant, and it therefore makes superb fence posts.
In 1963 researchers at the National Cancer Institute demonstrated that a bark extract of Pacific yew showed activity against certain cancer-cell tissue cultures, and in 1966 Dr. Monroe Wall isolated the active principle, taxol. Molecular structure of taxol was published in 1971; it is a complex diterpene with an ester side chain and a unique oxetane ring. Researchers determined that taxol inhibits replication of human tumor cells by arresting the division of microtubules, minute cellular organelles vital to cell division (1977). Ten years later the NCI contracted for the harvest of 60,000 pounds of yew bark, from which approximately two kilograms of taxol were isolated. Taxol was used in 1988 in chemotherapy of unresponsive cases of ovarian cancer, and 30% improvement was obtained. In 1990 a 48% tumor shrinkage was obtained with metastatic breast cancer after the patients had already experienced one prior chemotherapy regime. By this time, taxol became regarded as the most promising cancer fighting compound discovered in recent years, best since vincaleukoblastine (VLB) from Catharanthus roseus, Madagascar periwinkle.
Taxol occurs especially in bark, needles, and heartwood of T. brevifolia, and its isolation is difficult, low yield, and expensive. A harvester earns about $2 per pound of bark and $100-150 per day in wages working in the forest. Bark is harvested with a knife, ground to uniform size, dried, and then chemically extracted. Synthesis of taxol was finally achieved in the lab a couple years ago. Similar compounds have also been made using leaves of T. baccata.
In 1993, the United States government, in collaboration with Bristol-Myers Squibb, encouraged the production of 25 kilograms of taxol from 750,000 pounds of bark, enough to treat 12,000 patients. For a larger operation two million pounds could yield 130 kg of taxol and treat 65,000 cancer patients, and there are even options of harvesting up to 30 million pounds of bark during a five-year period (185,000 patients). These numbers need to be viewed in light of other U.S. statistics. Each year 1,130,000 Americans are diagnosed with cancer and 520,000 die. Of those, 21,000 are diagnosed with ovarian cancer and 13,000 others die. To date ovarian cancer has been mostly undetectable until almost too late, and a five-year survival rate is only 19%.
Nearly everyone is convinced that taxol can be obtained in an environmentally sound manner, while work in the laboratory finds the most effective uses of taxol, ways to synthesize the compound at a reasonable cost, and investigates similar molecules that may be made that are as or more effective in cancer treatments. These issues will continually be raised each time a new cancer-controlling substance is isolated from a plant, e.g., in a tropical rain forest. The beauty of this test case is that both United States and Canadian governments have the resources and methods to insure that overexploitation will not destroy the forest, but in poverty-torn tropical countries, such controls are lacking. Hopefully, our colleges are breeding new policymakers, who can permit these ventures to be profitable for business, environmentally correct, and priced within means for the desperate users.