The Taxol Story

[badger2]

Act I, 1962-1975

'The Pacific Yew, Taxus brevifolia, is a very slow-growing conifer found principally in the understory of old-growth forests in the Pacific Northwest, from northern California to Alaska. In 1962, as part of their sweep through California, Oregon, and Washington, collecting plant material at random for the NCI-USDA interagency plant screening programme, a USDA botanist, together with three graduate student helpers, sampled parts of Taxus brevifolia. They bagged, tagged and shipped the collection back to the East Coast for further analysis. Four years later, chemists at the Research Triangle Institute in North Carolina isolated a cytotoxic compound from the bark. The following year, 1967, they named the compound taxol. It had antitumor activity against L1210, a lymphoid leukemia.
....
By the time of Barclay's collection, there were only two published articles in recent times on Taxus brevifolia. Neither gave any indication that the tree was interesting from the point of view of cancer. Indeed, one of them dismissed the Taxus brevifolia as a likely candidate.
....
As old-growths were clear-cut and the land replanted to make way for even-age industrial forests, the stock of many unwanted species was being depleted without begin replaced. Neither the Forest Service nor the timber industry was concerned. One of the species unvalued and unwanted by the timber industry was Taxus brevifolia. By contrast, and unknown to everyone associated with the forest, Taxus brevifolia was becoming a very valuable species as a result of the events inside Monroe Wall's laboratory Wall's revelation that KB activity was concentrated in a chloroform fraction was turning the spotlight on the tree. By March 1966, an interesting juxtaposition had occurred. Perdue and Hartwell, responding to Wall, listed Taxus brevifolia as a high priority species; in the forest, it was nothing more than trash.'
(Goodman J, Walsh V, The Story of Taxol, Cambridge University Press, 2001)

 

[badger2]

'Smith: So when did the Federal agencies, as far as you know, know that the yew tree was going to be a valuable resource?

Chabner: None of us knew that the yew would be a valuable tree until late 1988 perhaps 1989....they became aware of the clinical activity at the same time we did. In was in the late 1980s.

Later in the hearing, it was the turn of Jim Jontz, Democrat Representative from Indiana and a member of the Committee on Agriculture to question Bruce Chabner.

Jontz: OK. Dr. Chabner, again, I want to follow up on my colleague from Oregon, Mr. Smith. As I understand what you told him, it was late 1988 or early 1989 when you made your substantive conversations with the Forest Service?

Chabner: No, I said that was the time at which we realized that the drug had activity in ovarian cancer. We had been dealing with people from Agriculture and the Forest Service about obtaining small amounts. Actually, we were doing this through a contractor.

Jontz: For how long?

Chabner: Well, it began in the early 1980s.

Jontz: So really the Forest Service should have had reason for 10 years to know that there was something important?

Chabner: No, I wouldn't say the knew something was important.

Jontz: Well, why would you be dealing with them if it weren't important?

Chabner: We didn't know it was important.

Jontz: When did you determine it was important?

Chander: In late 1988 or early 1989.

The exchange is important in that Chabner related taxol to Taxus brevifolia historically at the moment when the compound was reported as being active in patients with ovarian cancer. That is, the value of the one determined the value of the other at a particular point in time. There is, however, much at stake in this testimony. For one thing, Chabner was careful to say that taxol had 'no demonstrated activity' against cancer until 1988. As we have seen, taxol would not have been in the clinical stage to yield 1988 results (whatever they might have been) had the compound not shown significant activity in the experimental stages until that point; that is, against malignant cells, mouse tumors and human xenografts covering a period between 1966 and 1982. Taxol had, therefore, been showing activity for a much longer time.

The anomaly between Chabner's statement and the record turns on the word 'cancer.' In the NCI, the word 'cancer' was reserved exclusively for the disease state in humans, emerging as a word only with Phase II trials that did not begin until 1985. By referring to taxol's activity against cancer, Chabner was able to deflect attention away from all those years when the portfolio of taxol's activity was becoming increasingly rich in information. At the same time, speaking on behalf of the Forest Service and the Bureau of Land Management, Chabner dexterously deflected attention from their practices and, effectively, severely shortened the span of time over which Taxus brevifolia could have been viewed as an important species.'
(The Story of Taxol, pp. 197-8)

 

[badger2]

We here link Texas to Florida for taxol:

23 Mar 2019 Cancer-Causing Cloud Hovers Near 4th-Largest U.S. City
From Black Plume to Benzene Fumes, Houston's Plight Drags On

The irony is that the fungus that may be growing on Podocarpus in Florida is growing on an introduced tree. Is the fungus also from China, or is it a North American native that produces taxol?

Podocarpus / USDA Plants Database
Plants Profile for Podocarpus macrophyllus (yew plum pine)
'....introduced species....'

This well-known fungus actually produces taxol, though the Chinese article is unavailable for most every English speaker to read, and is another good reason for the development of a Japanese alphabet that aligns with the English alphabet.

Aspergillus fumigatus on Podocarpus in China Produces Taxol
[Isolation and identification of a taxol-producing endophytic fungus from Podocarpus]. - PubMed - NCBI

 

[badger2]

Chinese researchers in taxol-producing fungi, a strain called 'BT2' was published in 2006 in an African journal but the named genus of the fungus waited 7 years before finally emerging in the literature as Ozonium EFY21. The first 2006 article is not listed at Pubmed for the American reader:

Guo BH, Wang Y, Zhou X, Hu K, Tan F, Miao Z, et al, Shanghai Key Laboratory of Agrobiotechnology, Fudan-SJTU-Nottingham R&D Center, (2006) An Endophytic Taxol-producing Fungus BT2 Isolated from Taxus chinensis var. mairei, African Journal of Biotechnology 5: 875-877.

From the same Shanghai lab:

Aug 2013 Taxol-Producing Ozonium EFY21 from Taxus chinensis var. mairei
Agrobacterium tumefaciens-mediated genetic transformation of the Taxol-producing endophytic fungus Ozonium sp EFY21. - PubMed - NCBI

 

[badger2]

The Chinese fungus links to the Texas fungus:

Texas Root Rot (Ozonium Root Rot)
Texas root rot - Wikipedia

 

[The Sage of Main Street]

Act I, 1962-1975

'The Pacific Yew, Taxus brevifolia, is a very slow-growing conifer found principally in the understory of old-growth forests in the Pacific Northwest, from northern California to Alaska. In 1962, as part of their sweep through California, Oregon, and Washington, collecting plant material at random for the NCI-USDA interagency plant screening programme, a USDA botanist, together with three graduate student helpers, sampled parts of Taxus brevifolia. They bagged, tagged and shipped the collection back to the East Coast for further analysis. Four years later, chemists at the Research Triangle Institute in North Carolina isolated a cytotoxic compound from the bark. The following year, 1967, they named the compound taxol. It had antitumor activity against L1210, a lymphoid leukemia.
....
By the time of Barclay's collection, there were only two published articles in recent times on Taxus brevifolia. Neither gave any indication that the tree was interesting from the point of view of cancer. Indeed, one of them dismissed the Taxus brevifolia as a likely candidate.
....
As old-growths were clear-cut and the land replanted to make way for even-age industrial forests, the stock of many unwanted species was being depleted without begin replaced. Neither the Forest Service nor the timber industry was concerned. One of the species unvalued and unwanted by the timber industry was Taxus brevifolia. By contrast, and unknown to everyone associated with the forest, Taxus brevifolia was becoming a very valuable species as a result of the events inside Monroe Wall's laboratory Wall's revelation that KB activity was concentrated in a chloroform fraction was turning the spotlight on the tree. By March 1966, an interesting juxtaposition had occurred. Perdue and Hartwell, responding to Wall, listed Taxus brevifolia as a high priority species; in the forest, it was nothing more than trash.'
(Goodman J, Walsh V, The Story of Taxol, Cambridge University Press, 2001)

Wipe This Over-Tolerated Unabomber Cult Off the Face of the Earth


Because the "other" side comprises the fathers of Trustfundie Treehuggers, leave it to me to expose the slippery logic of your anti-human scare story. First of all, there's no reason to block development by saving thousands of useless species because one of them might have a cure for cancer. That is the Van Gogh fallacy. Sure he was under-appreciated, but more than 99% of the other rejected artists deserved to have their junk art go unsold. The exception proves the rule. You bitter misfits know that; you are dishonestly grabbing at one extremely rare example to prove we should go back to the horrible eras before practical science was invented.

Second, there should be as many cures for cancer as there have been artificial sweeteners, etc. So we can afford to miss one and shouldn't be inhibited from developing the immense untapped and foolishly restricted resources that your pagan idol, Gaia, hoards for Herself.

But most of all, because you smug parasites have contempt for natural human ability and have successfully pushed the lie that society has a way of making sure that most creative geniuses are given full opportunities to develop themselves (as stated by your ilk's propaganda sheet, Time magazine). I know from personal experience that the real endangered species can only be human genius, not your precious vermin and vegetation. (Notice that your weak opponents never suggest repealing the Endangered (Unfit) Species Act). It would be consistent with the type of neglected people to whom we owe every invention that prevents us from living like wild animals that a laid-off lumberjack or forest-products employee is by your treasonous activity unable to buy his son a chemistry set that would start the kid on the way to cure cancer.

For that reason, geniuses should use their talent to destroy you vicious Unabombers. Calling you "silly idealists" is letting you off the hook; your ilk is the enemy of human prosperity and must have all power taken away from it. We must shame and silence you freaks and take you completely out of the national debate.

 

[badger2]

Nuts. SoMS has fallen behind in the required syllabus. No tree is needed when a fungus produces the same anticancer compound.

 

[mamooth]

Taxol is now produced semisynthetically. Yew trees aren't needed any more. It's been that way for many years. I'm not sure what the fuss is about here.

 

[The Sage of Main Street]

Nuts. SoMS has fallen behind in the required syllabus. No tree is needed when a fungus produces the same anticancer compound.

PhDs Don't Earn a Living Until They Are 30. That Produces Only Incompetents, Quacks, Crooks, and Crackpots

The fourth reason is that we can produce artificial chemical compounds without using molecules from exotic species.

Nature is the enemy of man and must be conquered, subdued, and changed radically. Without that Promethean attitude, mankind would have gone extinct long ago. Only primitive and pre-intelligent subhumans treat it with superstitious respect.

High IQs with self-respect, instead of the childish nerd weaklings we have today, could have cured cancer 50 years ago. But we saw no reason to sacrifice our youth so that an ungrateful public could live past middle age.
Those who don't believe students should be highly paid for their grades deserve to die.

 

[Crick]

I think you should drink less.

 

[badger2]

Nuts. At least one poster is clued up. The reaction here attempts to reify and reverse subjectivity. The point is: ecological insight into the physiology of cancer regardless of the source. How close does nature's anticancer chemistry come to the precise site of the benzene plume? We have already nailed Florida and the introduced Chinese tree.

'Bateson is sometimes hastily misread as suggesting that biology shows us a Mind guiding Nature, but this is a very poor reading since Bateson explicitly warns against such transcendence repeatedly. The mind/nature or nature/mind that he did try to describe is entirely immanent, and it is only coextensive with the material systemic process that has, Guattari would say, (produced [italics]) it, and Bateson would add, while simultaneously being produced by it. Already of interest here is that Bateson does not write of a Subject or intentionality, but rather of complex systems that treat as information only a "difference that makes a difference" for that system, a pragmatic process.

One of his most philosophically passionate summings up is an essay entitled "Form, Substance, and Difference" where a further step is made from the way mind is dependent upon the larger contexts, the interconnecting patterns, and that this complex unit (or assemblage) of the "organism-and-its environment" is actually what survives in natural selection. Ultimately, Bateson argues that mind is not something located inside and isolated entity, but rather "immanent in the large biological system -- the ecosystem." But because this interdependent system has co-evolved, because mind in this sens has been selected, this implies an obligation on our part to attend to the survival of the whole context, not the isolated individual or species. A vital consequence of this is summed up in Bateson's paramount conclusion that has not yet been fully taken on board: "The identity between the unit of mind and the unit of evolutionary survival is of very great importance, not only theoretical, but also ethical....Mind co-evolves into brain, and does not suddenly appear after that organ magically appears on the scene."
(Heroux E, Guattari's Triplex Discourses of Ecology in An (Un)Likely Alliance, pp. 181-2)

This evolved taxol anticancer chemistry is still in major use today for cancer treatment, for the survival of Homo sapiens. It is an evolved system that "learned" a pragmatic chemistry by way of differences.

 

[The Sage of Main Street]

Nuts. At least one poster is clued up. The reaction here attempts to reify and reverse subjectivity. The point is: ecological insight into the physiology of cancer regardless of the source. How close does nature's anticancer chemistry come to the precise site of the benzene plume? We have already nailed Florida and the introduced Chinese tree.

'Bateson is sometimes hastily misread as suggesting that biology shows us a Mind guiding Nature, but this is a very poor reading since Bateson explicitly warns against such transcendence repeatedly. The mind/nature or nature/mind that he did try to describe is entirely immanent, and it is only coextensive with the material systemic process that has, Guattari would say, (produced [italics]) it, and Bateson would add, while simultaneously being produced by it. Already of interest here is that Bateson does not write of a Subject or intentionality, but rather of complex systems that treat as information only a "difference that makes a difference" for that system, a pragmatic process.

One of his most philosophically passionate summings up is an essay entitled "Form, Substance, and Difference" where a further step is made from the way mind is dependent upon the larger contexts, the interconnecting patterns, and that this complex unit (or assemblage) of the "organism-and-its environment" is actually what survives in natural selection. Ultimately, Bateson argues that mind is not something located inside and isolated entity, but rather "immanent in the large biological system -- the ecosystem." But because this interdependent system has co-evolved, because mind in this sens has been selected, this implies an obligation on our part to attend to the survival of the whole context, not the isolated individual or species. A vital consequence of this is summed up in Bateson's paramount conclusion that has not yet been fully taken on board: "The identity between the unit of mind and the unit of evolutionary survival is of very great importance, not only theoretical, but also ethical....Mind co-evolves into brain, and does not suddenly appear after that organ magically appears on the scene."
(Heroux E, Guattari's Triplex Discourses of Ecology in An (Un)Likely Alliance, pp. 181-2)

This evolved taxol anticancer chemistry is still in major use today for cancer treatment, for the survival of Homo sapiens. It is an evolved system that "learned" a pragmatic chemistry by way of differences.

Only the Gutless Believe in a GUT

A deep loneliness and alienation from reality, caused by hiding from it in books, make nerds desperately seek a sense of connectedness with some greater structure. The attraction of this fantasy is that it is extended to invite their personal participation; that way they can feel they belong to the selected elite, By the same process of imitating an anti-intelligence escapist goal set by teleological wanderings, the superstitious fill their emptiness with a connection to some imaginary Higher Power.

 

[The Sage of Main Street]

I think you should drink less.

Up Crick's Shit

Your mind is the fossilized form of some extinct bacterium that never evolved because it was so alienated from the rational world that it ate itself rather than have any contact with intelligent life-forms.

 

[badger2]

Applying Book Learning to the Cancer Trajectory, by badger2

Because there are about 35 other situations whereby fungal associations with plants are producing taxol, this evolutionary history of the chemistry should be conserved across the planet. An example for those interested in photodynamic therapy for benzene-induced Texas cancers, would be the light connection:

Darkness: A Crucial Factor in Fungal Taxol Production
(United Arab Emirates, Canada, Egypt)
Darkness: A Crucial Factor in Fungal Taxol Production. - PubMed - NCBI

 

[badger2]

Ironically, fungi on the nearest fruit trees to the benzene leak may actually be producing taxol:

Interactions Between Co-Habiting Fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants
Interactions between Co-Habitating fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants
'....Paraconiothyrium....'

Novel Paraconiothyrium Species on Stone Fruit Trees and Other Woody Hosts
https://www.ncbi.nlm.nih.gov/pubmed/pmc/2865355

 

[badger2]

Novel Paraconiothyrium species on stone fruit trees and other woody hosts. - PubMed - NCBI

 

[badger2]

Aspergillus fumigatus is a fungus that produces taxol. It also produces cancer-causing aflatoxin B1 and can metabolize benzene. Therefore, there are likely strains of A. fumigatus growing precisely at the site of the Texas benzene plume. These fungal strains growing around the manufacturing plant should be documented, because humans getting cancer from benzene will have comparable genomic and epigenetic chemistry between them.

Wild Turkey Resistance to Aflatoxin B1 / Dinitrobenzene
Alpha-class glutathione S-transferases in wild turkeys (Meleagris gallopavo): characterization and role in resistance to the carcinogenic mycotoxin... - PubMed - NCBI
'....wild turkeys (Eastern and Rio Grande subspecies)....'

Certain current approaches to the synthesis of anti-cancer compounds use the anthracenyl moiety, and coal is an old substrate for Aspergillus.

Biodegradation of Anthracene by Aspergillus
Biodegradation of anthracene by Aspergillus fumigatus. - PubMed - NCBI
' Meanwhile, the strain could utilize some aromatic hydrocarbons such as benzene, toluene, phenol, etc. as sole source of carbon and energy.'

 

[The Sage of Main Street]

Ironically, fungi on the nearest fruit trees to the benzene leak may actually be producing taxol:

Interactions Between Co-Habiting Fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants
Interactions between Co-Habitating fungi Elicit Synthesis of Taxol from an Endophytic Fungus in Host Taxus Plants
'....Paraconiothyrium....'

Novel Paraconiothyrium Species on Stone Fruit Trees and Other Woody Hosts
https://www.ncbi.nlm.nih.gov/pubmed/pmc/2865355

Nothing in Nature Is Where It Belongs Unless Man Put It There

That brings up another objection that your fake opponents miss. They are actually trying to convince you, whereas I despise Enviros too much to bother with that.

What if we save an endangered species that turns out to be the only carrier of an incurably fatal viruses? Low-IQ partisans are incapable of seeing that as an equally possible outcome of your superstitious pre-intelligence worship of nature.

 

[badger2]

27 Mar 2019 New York Times Interior Nominee Helped to Quash Pesticide Report

 

[badger2]

Homo sapiens still does not know if the fungus produces the taxol for certain.

Taxomyces andreanae: A Presumed Paclitaxel Producer Demystified?
Thieme - Login
'....All in all, our results suggest that specific plant environment may be required for the induction of of paclitaxel biosynthetic genes in the fungal symbiont. Identifying the regulatory mechanisms will be of considerable future interest and will provide further insight into the true nature of the fine-tuned equilibrium of plant-microbe interactions.

As the highly desirable search for sustainable and economically feasible paclitaxel has tempted various authors to draw premature conclusions proclaiming endophytes to be true taxane biofactories, and reviewers still seem to dwell on the potential of the microbial taxane synthesizers to revolutionize the pharmaceutical arena, we contend that such reports should be viewed as extraordinary claims that demand ultimate justification, namely: unambiguous evidence for the molecular blueprint underlying the postulated microbial paclitaxel biosynthesis, suggesting a means for its activation and manipulation.'

Ecologically then, what are the ultimate sources of taxol?