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Taxol® Discovery Commemorated in Washington State; Plaque Honors Researchers Wall and Wani, and the First Pacific Yew Collection

On Aug. 21, 2002, in the state of Washington, a historical marker was unveiled to commemorate the collection of the original samples of Pacific yew (Taxus brevifolia Nutt., Taxaceae), which led to the eventual discovery of the anti-cancer compound Taxol¨ by Mansukh Wani, Ph.D., and the late Monroe Wall, Ph.D., at Research Triangle Institute (RTI).

The marker, consisting of a brass plaque affixed to a two-ton stone, is located in La Wis Wis Campground in the Gifford Pinchot National Forest near Packwood, approximately seven miles from the site where the first specimen was collected 40 years ago by a team of botanists led by Arthur Barclay, Ph.D., of the U.S. Department of Agriculture.

The marker is the result of efforts led by the Taxus Historical Marker Committee of the American Society of Pharmacognosy (ASP). John Beutler, Ph.D. (chair), Nicholas Oberlies of RTI, and other ASP members who all highly respect the work of Drs. Wall and Wani formed the ad hoc committee in July 2000. ASP funded the casting of the plaque.

"Wall and Wani's discovery of not one, but two natural product compounds that are now used to treat cancer is unprecedented. It is important for us to honor them for their accomplishments, as well as the other facets of research that, literally, helped turn a tree in the woods into one of the best recent advances in cancer treatment," said Oberlies.

"The marker also honors a tree," said Beutler, "and not just a tree, but the idea that preserving biodiversity can have important practical results. The collection of Pacific yew bark was just the first step in a long process that had a major impact on cancer therapy."

At the annual ASP meeting held in Seattle in 2000, five members of the committee scouted out the original collection site. When they found what they believed to be it, they discovered it was not ideal for the marker. Oberlies explained, "It was on the side of Highway 52 that is closed in the winter due to snow cover and has few specimens of Pacific yew nearby. We wanted the marker to be close to a specimen." With the assistance of the U.S. Forest Service (USFS), the committee identified a suitable spot at the campground site, 20 feet away from a 200-year-old Pacific yew.

Present at the unveiling of the marker on Aug. 21 were Drs. Wani, Beutler, Oberlies and other members of the Taxus Committee, as well as members of the USFS who had helped collect and harvest specimens when the supply of Taxol was scarce. A portrait of Dr. Wall was displayed in his memory during the ceremony. Both Dr. Wall, before his death in July 2002, and Dr. Wani expressed feelings of great honor in regard to the memorial.

Drs. Wall and Wani reported the structure of Taxol in 1971.1 The unique mode of action for the compound was found to be the stabilization of microtubule assembly, which inhibits cell division.2,3 Today, Taxol is used for the treatment of refractory ovarian cancer, metastatic breast and lung cancers, and Kaposi's sarcoma.4

RTI's Wall and Wani Fellowships

To further honor the work of Drs. Wall and Wani, RTI has started a prestigious program of post-graduate fellowships in natural products research. The ultimate goal is to fund the work of three fellows via an endowment that will pay for all of their compensation and benefits, ensuring that resources are going directly toward the effort needed at the research bench to find new generations of compounds to treat cancer. For more information or to make a donation to the endowment, visit <www.rti.org/wallwani>.

Nicholas H. Oberlies, Jennifer A. Greer and Mansukh C. Wani are all from the Natural Products Program at Research Triangle Institute, Research Triangle Park, N.C. John Beutler, from the National Cancer Institute, also contributed. A tribute to the late Dr. Wall is published in HerbalGram 56.

References:

1. Wani MC, Taylor HL, Wall ME, Coggin P, McPhail AT. Plant antitumor agents: VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. Journal of the American Chemical Society 1971;93:2325-2327.

2. Schiff PB, Fant J, Horwitz SB. Promotion of microtubule assembly in vitro by taxol. Nature 1979;277:665-667.

3. Schiff PB, Horwitz SB. Taxol stabilizes microtubules in mouse fibroblast cells. Proceedings of the National Academy of Sciences USA 1980;77(3):1561-1565.

4. Suffness M, Wall ME. Discovery and development of Taxol. In: Suffness M, ed. Taxol: Science and Applications. Boca Raton, FL: CRC Press, Inc.; 1995. p.3-25.