Taxus baccata L. (Taxaceae)


English yew

A familiar, if somewhat gloomy sight in most churchyards, the English yew tree can live for thousands of years. Still a youngster, the largest yew tree growing in the Oxford Botanic Garden is also the garden's oldest tree, planted in 1645 by the first Curator, Jacob Bobart. Despite herbalists at the time saying yew 'had no place among medicinal plants', Bobart planted an avenue of these trees in what was Britain's very first physic (medicinal) garden. More likely to be used in the seventeenth century for making longbows or knife handles, almost four centuries later, we know now that yew does indeed have a place among medicinal plants.

In 1962 a sample of Taxus brevifolia (Pacific yew) bark was collected, from which a potent anti-cancer substance was subsequently isolated. This substance was found in such small amounts that six fully mature trees were required to provide enough drug substance to treat a single patient. Bark removal necessitated killing the trees - clearly not a sustainable source of supply. However, the mode of action of paclitaxel was unravelled and found to be novel. Paclitaxel binds to a protein called tubulin which plays a key role in cell division (mitosis). The microtubules it binds to are prevented from disassembling, thereby stopping cell division. New modes of action are appealing to the pharmaceutical industry as the drug should have a different (and hopefully improved) profile to existing drugs. So the hunt began for an alternative supply.

The chemical structure of paclitaxel is complex and whilst several academic groups have achieved chemical synthesis in the laboratory it is not feasible to produce commercial quantities in this manner. Different species in the same genus often contain similar molecules and so other species of yew from across the globe were tested to see if they contained paclitaxel. Eventually it was found that a similar molecule could be isolated from Taxus baccata leaves. With a small amount of modification in the laboratory this molecule could be converted to paclitaxel. Today paclitaxel (Taxol) has been joined on the market by docetaxel (Taxotere), a slightly more water-soluble analogue. Paclitaxel is used to treat ovarian cancer and both drugs are used to treat breast cancer and non-small cell lung cancer. Commercial supplies of paclitaxel now come from a plant cell culture technique initially developed by scientists in the United States Department of Agriculture and then licensed to a commercial company.

Further reading
Goodman J, Walsh V 2006. The story of taxol: nature and politics in the pursuit of an anti-cancer drug. Cambridge University Press.

Alison Foster