Thursday, 27 May 2010

The Curious Case of "The Total Synthesis of Taxol - K.C. Nicolaou"

This is an interesting case of scientific competition which is discussed in hushed tones amongst synthetic organic chemists. K.C. Nicolaou is one of the leading exponents of total synthesis of natural products. One of the early natural products to be produced synthetically was taxol which is the naturally occuring toxin in Yew trees. Taxol stops cell division and so it is a potential anti-cancer drug.

Nicolaou had been competing to be the first to produce a total synthesis against Robert Holton's group from the State University of Florida. Holton submitted his two papers on the synthesis to the Journal of the American Chemical Society on Dec 21st 1993. Nicolaou has submitted a paper on synthesis of related Taxoids three weeks earlier to the same journal on the 30th of November (this would appear in the February 1994 issue of JACs as the Holton papers).

Meanwhile Nicolaou submits a paper on the Total Synthesis of Taxol to Nature on the 24th of January which was accepted on the 31st of January and published in the 17th February edition of Nature. The paper before Nicolaou's in the journal was submitted 27th September 1993 and accepted 21st December 1993. So more usually it took 3 months to review a paper and not one week and even after acceptance Nature could take another six to seven weeks to publish not the two and a half weeks seen for Nicolaou's paper. Nicolaou would then go on to elaborate the synthesis in four papers published in JACS in 1995. Nicolaou included the synthesis of Taxol in his book Classics in Total Synthesis.

Now we cannot know whether Nicolaou was a reviewer for the Holton JACS paper but he would have been a logical choice unless Holton expressed that he should not be allowed to review because of a conflict of interest. Even if he did not review the paper, he was probably aware that it had been submitted but doesn't the rapid submission of the paper to Nature and its fast-track review and publication deserve some further investigation?

All in all this case raises questions about the publishing ethics of the journal Nature, the confidentiality of submissions to JACS and the integrity of scientists. Nicolaou has since gone on to be a highly acclaimed scientist with many significant international awards. Meanwhile Robert Holton's biography is rather more modest.

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