The Discovery, Developement and Controversy of the Anti-cancer Drug Taxol

Paclitaxel or Taxol is a mitotic inhibitor used as chemotherapy treatment for patients with lung, breast, ovarian, head, neck and other types of solid tumour cancer. In addition it can be used to treat advanced Kaposi’s sarcoma (a rare type of cancer) and to prevent restenosis (recurrence of stenosis, narrowing of the blood vessels). It is one of the most widely used anticancer agents in the world and according to the World Health Organisation (WHO) it is one of 350 essential medicines needed in any basic healthcare system.

Taxol was discovered in 1966 in a US National Cancer Institute (NCI) program at the Research Triangle Institute in North Carolina when Monroe Wall, Mansukh Wani and their colleagues isolated it from the bark of the Pacific Yew tree, Taxus brevifolia, naming it Taxol.Their findings were announced at an American Chemical Society meeting in Miami Beach in April of 1967.  The results and chemical structure were published in 1971.

The NCI found themselves under pressure to collect more Taxus bark so as to isolate larger quantities of Taxol for use in studies but in 1969 1,200kg of bark yielded only 10g of pure material. Harvesting the bark from the Pacific Yew Tree killed it in the process. Through the 1970s Taxol began to rise to fame in the scientific community as studies undergone by NCI researchers as well as cell biologists showed it to be an extremely effectiveanti-cancer agent. The increasing interest surrounding Taxol led to the NCI collecting pure material from 10,000kg of the Pacific Yew Tree bark. Animal toxicology studies of the drug were completed by 1982 and clinical trials began in 1984.

By May 1988 the drug had shown an effect in melanoma patient and had had a remarkable response rate of 30% in ovarian cancer patients, considering the drug was still be developed at the time this. At this point the NCI calculated to produce enough Taxol to treat every melanoma and ovarian cancer patient in the US would require the destruction of 360,000 Pacific Yew trees, the problems associated with supplying Taxol became suddenly all the more serious. From 1967 to 1993 all Taxol was produced from the bark of the Pacific Yew Tree but by 1992 there were now 30 teams working to synthesise Taxol using different methods. This was driven not only by the need for more practical commercial production of the drug but to produce more chemical understanding surrounding it. The Holton Taxol total synthesis method was discovered in 1994 and marked the end of the destruction of Pacific Yew Trees for the retrieval of this life changing drug.

-Izzie