You won't find Taxomyces andreanae in even the latestdirectory of taxonomy. But you will find it in newspaperheadlines and TV news programs.
You will also find it as the fungal focus of a paper in Thursday'sissue of Science, titled "Taxol and Taxane Production byTaxomyces andreanae, an Endophytic Fungus of Pacific Yew."
Its lead author, chemistry research assistant professor AndreaStierle at Montana State University, Bozeman, gave her givenname to designate the species of the Taxomyces genus, whichshe found in the woods. That genus is new, too, said its co-discoverer, plant pathologist Gary Strobel. The taxonomicdesignation will be formalized when his article on the fungusappears in a forthcoming issue of Mycotaxon, the journal offungal taxonomy.
But it wasn't mycology 101 that brought the media, andpharmaceutical companies large and small, beating a path tothe Montana scientists' door. It was the vision of a large newsource of taxol, a compound that has been hailed as the "cancerdrug of the decade."
If a fungus can make it in commercial quantities, then the rarePacific yew tree, Taxus brevifolia, can be released from deathrow, where it has faced early extinction ever since the taxol inits bark started shrinking advanced ovarian cancers in 30percent of woman who received the drug.
The catch has been that a single yew tree's inner bark yieldsonly trace amounts of taxol. It takes four trees to completelytreat one patient. Last year, Bristol-Myers Squibb, taxol's solecommercial supplier, harvested 1.6 million pounds of bark. Thisis nominally enough to treat 26,666 patients with 10 cycleseach of taxol The company's wholesale price is $986 per cycle.
In late January, Bristol-Myers announced it would not harvestany more yew trees because its semisynthetic tissue-cultureproduction had reached a point of meeting existing demand.
That demand could escalate if and when the FDA approvestaxol for breast cancer chemotherapy -- and when and if theprice comes down.
Bristol-Myers is one of two large pharmaceutical companies toaccept the Montana university patent office's invitation todiscuss licensing its pending patent on fungal taxol. "Itexpressed interest," Strobel told BioWorld. So did LederleLaboratories and a number of smaller companies, includingPharmagenesis, Escagenetics and Phyton Catalytic, a juniortaxol partner of Bristol-Myers.
In initial culture, T. andreanae yielded 50 nanograms per literof broth, Stierle told BioWorld.
She believes that Bristol-Myers achieves 1 to 4 milligrams perliter, with its extraction and tissue culture of yew needles. "Butall fungal cultures start out with low yields," she added, "andnow we are applying standard growth-promoting procedures toincrease output -- and doing better." Also, a mutation specialistis joining their team.
"Basically it's not ready to be commercialized, because it'smaking such low amounts of compound," Strobel told BioWorld."But we have some promising indications we can quickly jackup production. There's a method we're using that I can't tellyou about that allows us some rather substantial increases."
Escagenetics Corp. of San Carlos, Calif., is challenging Bristol-Myers' hold on taxol tissue culture. Peter Hylands, Escagenetics'vice-president and chief scientist, told BioWorld that since theMontana discovery "is a fungus, about which a lot is known infermentation optimization, they have very good chances ofincreasing its productivity."
Escagenetics is increasing its own taxol productivity byenlisting Genencor of Rochester, N.Y., which Hylands describedas "specialists on scale-up of plant cells," to take Escagenetics'taxol output from the research stage to the market phase.
For two years, Stierle and her husband, Don, a chemist, walkedthe wild woods of northern Montana, intrigued by the old-growth Pacific yew trees, and sampling their inner bark fortraces of a possible taxol-producing symbiant microorganism.Two years ago, "by serendipity," she said, she found the fungusin a single tree, mimicking its host's taxol synthesis. Itreminded her of a similar experience some 60 years ago whena Japanese scientist discovered a different fungus, cohabitingwith rice plants, and churning out its own copy of that plant'sgrowth hormone, gibberellin.
Taxol, by contrast, is a growth inhibitor. Its mode of action inshrinking cancer cells "is unique among anti-cancer agents,"Stierle declared. It works by stimulating a cell's synthesis ofmicrotubulin, a key structural component. Taxol creates"supertubulin," which essentially stiffens the cell to a standstill.
Strobel sees "three important messages" in the fungal taxolstory, besides those laid out in the Science paper:
-- "About 90 to 95 percent of the world's fungi are in ataxonomic no-man's-land. We don't know anything aboutthem."
-- "There's an entire 'inner space,' the interstitial tissues ofplants in which microorganisms live. If this phenomenon ofgenetic interchange works with the taxus yew, we may belooking at a totally novel way of finding microorganisms thatmake drugs with important human medicinal uses.
-- "This fungus has been found in only one tree in one location.We can't find the same fungus from other T. brevifolia in anyother location in the Pacific Northwest. So, if we cut a path, ordid an under-burning or allowed Nature to take her coursehere, this would never have been found. What does that sayabout tropical or temperate rain-forests? Savannah?Wilderness areas every place from the desert to the sea floor?The eventual biological union between these two organisms,fungus and tree, in which they get familiar with one another,exchange occurs, and they're adapting or mimicking the higherplant they're living with is a long, slow process."
The Science paper ends with these words: "... the application ofgenetic engineering may improve taxol production by T.andreanae." Such as taking out the fungal gene for taxol andinserting it in a high-yield host organism. "That's my ultimatedream," Stierle told BioWorld.
-- David N. Leff Science Editor
(c) 1997 American Health Consultants. All rights reserved.