Encaustic painting ÒPacific YewÓ by Raquel Edwards

 

The evergreen Yew is a slow growing, long-lived and highly poisonous tree. Unlike most other plants in the De Materia Medica, Dioscorides warns against using this plant, or even enjoying its shade:

“Chickens that eat the fruit of [the Yew] which grows in Italy turn black, and men that eat it fall into unconsciousness. [The Yew] growing in Narbonie has such great strength that those who sit underneath (or fall asleep) are hurt by the shade, and that frequently they die.”

In 1962, Arthur Barclay collected a sample of the Pacific Yew from the Gifford Pinchot National Forest in Washington State as part of a screening program funded by the U.S. National Cancer Institute. It was the first step in what would be one of the most important and influential cancer drugs ever discovered.

Because only small quantities exist in the bark, the isolation of the Yew’s alkaloids presented a challenge. In 1966, researchers Monroe Wall and Mansukh C. Want finally isolated the active compound, taxol, but further work on elucidating the alkaloid’s structure was put on hold as the scientists worked on their other exciting lead, camptothecin (see the post on camptothecin here).

Because of taxol’s shortcomings as a drug candidate, the response to its discovery was underwhelming. This is because it required a lot of plant material for a low yield, it was difficult to formulate, it worked by an unknown mechanism of action, and its only known activity was against leukemia, for which other drugs existed.

It wasn’t until the alkaloid showed extremely promising results against ovarian and breast cancers – coupled with Susan Horowitz’s discover that the alkaloid promoted the assembly of tubular into microtubules – that interest in taxol increased.

Taxol’s promise soon ran into ecological concerns and political protests, however, as demand for the Pacific Yew skyrocketed. It was estimated that in order to keep pace with the projected need, 360,000 trees would have to be killed each year. It was clear that an alternative supply route was desperately needed, and researchers raced to find a solution. Finally, in 1991, a semisynthetic process was developed that utilized the needles of the much more common English Yew. Recently, a plant tissue culture method was discovered that eliminates the need for hazardous chemicals, and it requires less energy to produce.

Today, taxol based drugs are some of the best cancer treatments available. Taxol is included on the World Health Organziation’s list of essential medicines – a list of the necessary and most important medications needed to support a basic health care system. It is used to treat breast cancer, ovarian cancer, non-small cell lung cancer, pancreatic cancer, and AIDS related Kaposi sarcoma.

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