NEWS OF THE WEEK affirmation that humans must protect Earth's environment. The Rio declaration instead is composed of 27 principles that cover much wider ground. Principle 5, for example, says all nations should cooperate in eradicating poverty in order to decrease disparities in standards of living. Principle 15 backs the "precautionary approach/' stating that 'lack of full scientific certainty should not be used as a reason for postponing cost-effective measures to prevent environmental degradation." The nonbinding Agenda 21 addresses issues varying from protection of the oceans to technology cooperation, and from toxic chemicals to biotechnology. Its current draft, however, is full of brackets containing alternative wordings, some of which contradict each other. And delegates were unable to agree on who will pay for the programs proposed in Agenda 21, or how much. The debate, which was to be finished by now, will continue in Rio. Meanwhile, the U.S. Senate last week passed a resolution, similar to one the House passed in March, urging President Bush to "play an active role" in preparing for UNCED and to personally attend. Bush still has not said if he will go. Pamela Zurer
New strategies devised for producing taxol Two research groups separately have devised new strategies for producing taxol, an anticancer drug currently in short supply because its sole source is extraction of bark from slow-growing Pacific yew trees. Researchers at Montana State University have developed a reactor that produces radiolabeled or native versions of taxol. And a group at Stanford University has developed a method of synthesizing the three-ring core of taxol from the inexpensive chemical pinene. The Montana State reactor could represent a low cost, continuous source of radiolabeled taxol for biosynthetic research, animal studies, or clinical studies. But several sources doubt the prospects of using the reactor to produce large quantities of taxol. The reactor concept emerged from development of an assay for carbon-148
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terest and need for labeled taxol. We would be interested in getting some for biochemical and pharmacological studies, and even for clinical pharmacology in patients, to give a better idea of what happens to the drug after it's administered." Schepartz says the reactor could be an easier way to make radiolabeled taxol, compared with conventional synthetic methods, but some key questions remain. For example, he says, "Have they shown that there's net production of taxol, or is the label coming from an exchange reaction?" Strobel replies that incorporation of carbon-13- or carbon-14-labeled Montana State researchers Stierle (left) and acetate throughout the taxol moleStrobel, who holds log from Pacific yew tree cule in his group's experiments "means there's de novo synthesis." labeled taxol by Montana State plant paCurrently, the reactor only makes labthologists Gary A. Strobel and Andrea Stierle, and chemist Frederik J. G. M. van scale quantities of taxol, but Strobel beKuijk, described in a paper soon to be lieves it may be possible to scale it up. published in Plant Science. Strobel and However, Richard A. Partyka, executive Stierle subsequently developed the taxol director of chemical process research at reactor, and have applied for patent pro- Bristol-Myers Squibb—which hopes to tection on it. Strobel was at the center of market taxol—says: "At this time we controversy a few years ago for release consider [the reactor] to be more of an of bacteria genetically engineered to con- academic achievement than anything trol Dutch elm disease. He was repri- that might be used in a commercial manded for not obtaining Environmen- sense.... It might be useful for preparatal Protection Agency clearance (C&EN, tion of isotopically labeled materials, [but] I don't see it displacing other techJan. 25,1988, page 15). The taxol reactor is a simple tube con- niques or approaches or options that we taining a buffered solution and a precur- have for making taxol in bulk." Moreover, Schepartz questions whethsor compound, such as acetate. The mixture is incubated with pieces of stem or er scaling up the reactor "should be as trunk from the Pacific yew—bark, sap- high a priority as pursuing needles and wood, or even sawdust. Fluid is contin- other renewable resources. To get the ually drained from the system, and fresh wood you still have to chop down the tree, and we want to stop doing that as solution added periodically. When radiolabeled acetate is the pre- soon as possible." Meanwhile, another path to taxol was cursor, says Strobel, "radiolabeled taxol comes out of the cell into the aqueous described at the American Chemical Somedium every day. Like a cow would ciety meeting last week by Paul Wender lactate, the cell produces taxol." Two and coworkers at Stanford's chemistry weeks' operation yields three to four department. They synthesized the threering core of taxol from pinene, a pinetimes the taxol from extraction alone. "Depending on what precursor you tree-derived product used in turpentine. use, you can cause certain parts of the Previously, syntheses have used starting molecule to be labeled," Strobel adds. materials from yew trees and bushes, For instance, labeled acetate gives en- such as 10-deacetyl baccatin III. Two of the three core rings have all richment throughout the molecule, whereas labeled phenylalanine precur- key functional groups in place, and sor appears in only two phenyl rings Wender's group is working to complete functionalization of the third. If on the taxol side chain. Saul A. Schepartz, deputy associate all goes well, it expects to achieve total director of the developmental therapeu- synthesis of taxol from pinene by tics program at the National Cancer In- year's end. Stu Borman stitute, notes, "There is considerable in-
