Book Review

The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug

N Engl J Med 2001; 344:1335-1336April 26, 2001

Article

The Story of Taxol: Nature and Politics in the Pursuit of an Anti-Cancer Drug
By Jordan Goodman and Vivien Walsh. 282 pp. New York, Cambridge University Press, 2001. $27.95. ISBN: 0-521-56123-X

For anyone wanting all the details of the development of paclitaxel (Taxol) from its very beginning until it was marketed as a new, natural-product anticancer drug, this book is an excellent source of information. It is carefully researched and detailed, and as someone who was at the National Cancer Institute (NCI) during part of the development of Taxol, I found it factually accurate.

In the book, Taxol and the source of Taxol, the bark of the tree Taxus brevifolia, are treated as unique characters in a historical novel. The authors weave the story of the discovery of this drug and the intricacies of developing it from its natural source with the politics and effects of harvesting the tree from the forests of the Northwest. The book ends with a discussion of the impact of harvesting T. brevifolia on the local economy and the negative repercussions of the successful development by Bristol-Myers Squibb of a semisynthetic process for producing the drug.

Here, however, perception departs from reality. For example, cancer chemotherapy and the drug-development program of the NCI are wrongly portrayed as Goliaths in cancer treatment at the time, as compared with surgery and radiotherapy. The drug-development process is portrayed as having gone awry with Taxol, and Bristol-Myers Squibb is depicted as a robber baron who ran off with the credit for its discovery and with the rights for a drug developed with the public's money. Worst of all, after two decades during which methods for refining the harvesting process without continued damage to the forests were sought, the synthesis of Taxol by Bristol-Myers Squibb is said to have deprived a depressed economy in the Northwest of a source of income.

The actual story is quite different. First of all, although Taxol is a very effective natural product, it is not unique. There were other drugs before Taxol and some after it with equal effects and equally compelling stories. Some of them, like the vinca alkaloids and the epipodophyllotoxins, have been associated with bona fide cures of major cancers. Then there is the fascinating story, spanning three decades, of the development of the camptothecins, three of which are in clinical use. This is a far more intriguing story than that of Taxol and matches it in terms of integrating issues of forestry and drug development.

The NCI drug-development program, including the natural-products program, was established and maintained by pioneers such as Ken Endicott, Murray Shear, Jonathan Hartwell, Gordon Zubrod, and others for the purpose of finding new and effective treatments for cancer at a time when screening for anticancer drugs was largely derided by the academic community. All of them are mentioned in the book, but out of context, and in history context is all important.

The development of Taxol did not go awry at all. It worked according to plan, despite long odds and near misses. For example, had not the NCI drug-screening program been changed in the early 1970s to include human tumor xenografts in nude mice, the drug might have been abandoned for lack of activity in the old screening programs. It was also a small miracle that the crude extraction techniques used at the time could actually isolate activity from natural products. It was also remarkable that the people responsible for sending out teams to isolate bark for annual collections had the foresight to continue the collections while clinicians pondered whether the drug was worth it. A misstep could have cost additional years, at a minimum, or could have stopped the development process altogether.

From the beginning, the NCI drug-development program for both natural products and synthetic agents was intended to take the risks that pharmaceutical companies could not take to establish whether drugs could actually cure cancer (until recently, this was a hotly disputed issue) and whether there were drugs in nature that could be useful anticancer agents. It also was intended to determine whether there was a market for these drugs (also a disputed issue). It was never the intent of the NCI to stay involved in the development of any of the drugs it discovered or developed in collaboration with industry, nor was it possible for it to do so. It meant to offer such drugs at the earliest possible moment to established companies for development and marketing. Always included were plans to find ways to develop reliable methods for synthesizing very complex molecules to ensure a steady supply.

All this worked. When the program was established, there was no anticancer-drug market. Now, this market is profitable enough to attract major companies, and accordingly the amount of taxpayer money used by the NCI for this purpose over the years has declined substantially, as its need to be the risk taker has diminished. Most important, drugs can cure cancer, and thousands of lives have been saved or extended. Bristol-Myers Squibb has profited from its association with the NCI, but so have Americans who have cancer, and Bristol-Myers Squibb was one of the first companies to make a substantial investment in the development of anticancer drugs. The company is more a trailblazer than it is a robber baron.

With regard to credit: the chemists who initially extracted Taxol from the bark of T. brevifolia are fine and dedicated scientists. In truth, however, they were not the discoverers of Taxol in the usual scientific sense. The bark was given to them for extraction. The real “discoverers” were, once again, the people who supported the process of drug development, according to what appeared to be a utopian concept. They developed a relationship with the Department of Agriculture for collections, and they established contracts with natural-product chemists to extract active materials from collected plants. They defended the program annually before the Office of Management and Budget and the Congress, despite the fact that for many years, because of the long delay between discovery and application, the program was mostly regarded as a failure. It is really they who discovered Taxol and many other drugs.

Although this is an excellent and well-written book, its focus on the environmental and economic issues surrounding the extraction of drugs from forests clouds the history of a unique government program established by a handful of visionaries in the 1950s and 1960s.

Vincent T. DeVita, Jr., M.D.
Yale University School of Medicine, New Haven, CT 06520