Editing Paclitaxel (section)

===Plant screening program===
In 1955, the NCI in the United States set up the Cancer Chemotherapy National Service Center (CCNSC) to act as a public screening center for anticancer activity in compounds submitted by external institutions and companies.{{sfn|Goodman|Walsh|2001|p=17}} Although the majority of compounds screened were of synthetic origin, one chemist, Jonathan Hartwell, who was employed there from 1958 onwards, had experience with natural product derived compounds, and began a plant screening operation.{{sfn|Goodman|Walsh|2001|p=22}}

After some years of informal arrangements, in July 1960, the NCI commissioned the [[United States Department of Agriculture]] (USDA) botanists to collect samples from about 1,000 plant species per year.{{sfn|Goodman|Walsh|2001|pp=25,28}} On 21 August 1962, one of those botanists, Arthur S. Barclay, collected bark from a single Pacific yew tree in a forest north of the town of [[Packwood, Washington]], as part of a four-month trip to collect material from over 200 different species. The material was then processed by a number of specialist CCNSC subcontractors, and one of the tree's samples was found to be [[cytotoxic]] in a cellular assay on 22 May 1964.{{sfn|Goodman|Walsh|2001|p=51}}

Accordingly, in late 1964 or early 1965, the fractionation and isolation laboratory run by Monroe E. Wall in Research Triangle Park, North Carolina, began work on fresh ''Taxus'' samples,  isolating the active ingredient in September 1966 and announcing their findings at an April 1967 [[American Chemical Society]] meeting in [[Miami Beach]].<ref>{{cite journal | vauthors = Wall ME, Wani MC | title = Camptothecin and taxol: discovery to clinic—thirteenth Bruce F. Cain Memorial Award Lecture | journal = Cancer Research | volume = 55 | issue = 4 | pages = 753–760 | date = February 1995 | pmid = 7850785 }}</ref> They named the pure compound taxol in June 1967.{{sfn|Goodman|Walsh|2001|p=51}} Wall and his colleague Wani published their results, including the chemical structure, in 1971.<ref>{{cite journal | vauthors = Wani MC, Taylor HL, Wall ME, Coggon P, McPhail AT | title = Plant antitumor agents. VI. The isolation and structure of taxol, a novel antileukemic and antitumor agent from Taxus brevifolia | journal = Journal of the American Chemical Society | volume = 93 | issue = 9 | pages = 2325–2327 | date = May 1971 | pmid = 5553076 | doi = 10.1021/ja00738a045 | bibcode = 1971JAChS..93.2325W }}</ref>

The NCI continued to commission work to collect more ''Taxus'' bark and to isolate increasing quantities of taxol. By 1969, {{Cvt|28|kg|}} of crude extract had been isolated from almost {{Cvt|1200|kg|}} of bark, although this ultimately yielded only {{Cvt|10|g|}} of pure material,{{sfn|Goodman|Walsh|2001|p=81}} but for several years, no use was made of the compound by the NCI. In 1975, it was shown to be active in another ''[[in vitro]]'' system; two years later, a new department head reviewed the data and finally recommended taxol be moved on to the next stage in the discovery process.{{sfn|Goodman|Walsh|2001|pp=79,81}} This required increasing quantities of purified taxol, up to {{Cvt|600|g|}}, and in 1977 a further request for {{Cvt|7000|lb|}} of bark was made.

In 1978, two NCI researchers published a report showing that taxol was mildly effective in leukaemic mice.<ref>
{{cite journal | vauthors = Fuchs DA, Johnson RK | title = Cytologic evidence that taxol, an antineoplastic agent from Taxus brevifolia, acts as a mitotic spindle poison | journal = Cancer Treatment Reports | volume = 62 | issue = 8 | pages = 1219–1222 | date = August 1978 | pmid = 688258 }}</ref> In November 1978, taxol was shown to be effective in [[xenograft]] studies.{{sfn|Goodman|Walsh|2001|p=95}} Meanwhile, taxol began to be well known in the cell biology, as well as the cancer communities, with a publication in early 1979 by [[Susan Band Horwitz|Susan B. Horwitz]], a molecular pharmacologist at [[Albert Einstein College of Medicine]],  showing that taxol had a previously unknown mechanism of action involving the stabilization of microtubules. Together with formulation problems, this increased interest from researchers meant that, by 1980, the NCI envisaged needing to collect {{Cvt|20000|lb|}} of bark.<ref name="Goodman and Walsh p97">{{harvnb|Goodman|Walsh|2001|p=97}}</ref> Animal toxicology studies were completed by June 1982, and in November, the NCI applied for the [[Investigational New Drug|IND]] necessary to begin clinical trials in humans.<ref name="Goodman and Walsh p97"/>