Taxol: The Blessing of the Yew Tree

Screening the plant kingdom

In 1960 the US National Cancer Institute (NCI) began testing extracts from thousands of plants for anticancer activity. In August 1962 the botanist Arthur Barclay collected bark from a Pacific yew tree in a forest in Washington State. Two years later its extract killed cancer cells in the laboratory. At the Research Triangle Institute in North Carolina, Monroe Wall and Mansukh Wani spent years separating the active compound from the bark’s many components, and in 1966 they isolated it and named it taxol.

A molecule of extraordinary complexity

Paclitaxel, $\ce{C47H51NO14}$, has a core of fused six- and eight-membered rings, 11 stereocentres, a rare four-membered oxetane ring, and many functional groups: esters, alcohols, a ketone, an amide and three benzene rings. Its structure, published in 1971, was a triumph of chemical analysis and X-ray crystallography. Making it in the laboratory took more than twenty more years: the first total syntheses, by Robert Holton and K. C. Nicolaou, were both completed in 1994, each needing dozens of steps.

A new way to stop cancer cells

When a cell divides, protein fibres called microtubules form a spindle that pulls the copies of the chromosomes apart, then dismantle. In 1979 Susan Horwitz discovered that paclitaxel works in an unexpected way: instead of breaking microtubules down, it binds to them and stabilizes them, so the spindle cannot be dismantled and the cell cannot finish dividing. Rapidly dividing cancer cells are hit hardest.

Saving the yew

The bark contains very little paclitaxel, and stripping it kills the slow-growing Pacific yew. Treating every patient would have needed bark from several mature trees, threatening the species. Chemistry provided the solution: in 1988 a semi-synthesis was developed from a related compound, 10-deacetylbaccatin III, which is plentiful in the needles of the common European yew and can be harvested without killing the tree. Since the 2000s much of the world’s supply has been made by growing yew cells in fermentation tanks.