Going Nuts over Paclitaxel.

Extracting the lifesaving anticancer drug paclitaxel--better known by its brand name, Taxol--could cause less of an impact on the environment now that significant amounts of the drug have been found in the bark, leaves, limbs, shells, and fruit of the hazelnut tree. Even the fungi that are associated with the tree produce the drug. Although scientists caution that there is no proof that eating hazelnuts, or filberts, will provide anticancer effects, the finding offers great promise for providing an alternate source for this valuable drug.

Paclitaxel was first derived from the Pacific yew tree. Environmentalists have been concerned that cutting down enough trees to extract the drug, which is used to treat breast and ovarian cancer, might threaten the tree's existence.

Angela Hoffman, an associate professor of chemistry and physics at the University of Portland in Oregon--a state where hazelnut trees are grown in orchards--says certain varieties of the hazelnut tree produce as much as one-tenth of the paclitaxel found in the Pacific yew tree. Every gram of Pacific yew tree bark yields about 50-70 micrograms of paclitaxel; in branches and leaves of certain varieties of hazelnut, about 5 micrograms of paclitaxel can be extracted.

"It is relatively easy, chemically, to extract paclitaxel from the tree," Hoffman says. "It's quite difficult to synthesize the drug, which is why complete synthesis is not economically feasible." She says Bristol-Myers Squibb, the producer of Taxol, partially synthesizes the drug, using material from other yew varieties to produce the compound.

"We used exactly the same method for extracting paclitaxel from hazelnut as we used for extracting it from yew," Hoffman says. "Briefly, we grind the plant material with a coffee grinder, shake it for a while in methanol, centrifuge out the particles, evaporate the [methanol], extract the fat-soluble materials with hexane, and discard them. Then we remove the most water-soluble compounds. The remaining material contains paclitaxel and a lot of other compounds. These are separated ming a reverse phase method."

In reporting the discovery of paclitaxel in hazelnut trees at the 219th national meeting of the American Chemical Society in San Francisco last March, Hoffman said, "This is potentially good news for cancer patients. If you find another source for the drug, you can lower costs."

A typical course of Taxol can cost $10,000-12,000, says Gary Strobel, a professor of plant sciences at Montana State University in Bozeman. "New uses for Taxol in treating cancer are being found every day," he says. "It has become the first billion-dollar-a-year anticancer medication."

The presence of paclitaxel in the hazelnut tree was discovered serendipitously when Hoffman and other Oregon researchers were attempting to find answers to a fungal attack on hazelnuts known as eastern filbert blight.

In the process, says Laurence Daley, a professor of horticulture at Oregon State University in Corvallis who collaborated on that research, "we found something that looked like paclitaxel. We didn't believe it and we ran test after test to try and replicate the results." Their findings were published in the June 1998 issue of Spectroscopy.

Hoffman says she has found paclitaxel in more than 12 different varieties of hazelnut tree--although not in every variety--and in 8 species of fungus associated with hazelnuts. "We have been able to find paclitaxel in all parts of the tree that we have tested," she says. "The local farmers would very much like to [sell] their discarded tree parts, but so far there is no market for it. If and when such a market is created, I believe the currently discarded or burned tree limbs and shells could certainly become useful sources for paclitaxel." The researchers say that because paclitaxel may soon be produced by generic drug makers after Bristol-Myers Squibb's exclusive patent rights expire, hazelnut waste products may look even better, especially older growth, which tends to accumulate more paclitaxel. Daley also suggests that growing paclitaxel-producing fungi under laboratory conditions might allow for greater quantities of the drug to be produced at reduced costs.

Because the compound is found in two different species of trees that are very distant from each other, Daley suggests that other plants may also make paclitaxel. "Generally, these types of production pathways are not limited to one type of plant," he says. He adds that one important fact about the hazelnut trees is that they grow "like weeds" in contrast to the slow-growing Pacific yew.

"It's very humbling to know there is so much we don't know about the plant world," Daley says. "We certainly didn't expect to find another source for paclitaxel right under our noses in a field in Oregon."