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紫杉醇——真菌次生代谢产物还是人工制品?

Paclitaxel - a Product of Fungal Secondary Metabolism or an Artefact?

作者信息

Gärditz Klaus Ferdinand, Czesnick Hjördis

机构信息

Institute of Public Law, University of Bonn, Bonn, Germany.

Ombudsman for suspected cases of scientific misconduct, University of Bonn, Bonn, Germany.

出版信息

Planta Med. 2024 Aug;90(9):726-735. doi: 10.1055/a-2309-6298. Epub 2024 May 16.

Abstract

Taxol (common name: paclitaxel) is an extremely important component of drugs for the treatment of various cancers. Thirty years after the discovery of its effectiveness, a metabolic precursor of Taxol (10-deacetylbaccatin III) is still primarily extracted from needles of European yew trees. In order to meet the considerable demand, hopes were pinned on the possibilities of biotechnological production from the very beginning. In 1993, as if by chance, Taxol was supposedly discovered in fungi that grow endobiotically in yew trees. This finding aroused hopes of biotechnological use to produce fungal Taxol in large quantities in fermenters. It never came to that. Instead, a confusing flood of publications emerged that claimed to have detected Taxol in more and more eukaryotic and even prokaryotic species. However, researchers never reproduced these rather puzzling results, and they could certainly not be applied on an industrial scale. This paper will show that some of the misguided approaches were apparently based on a seemingly careless handling of sparse evidence and on at least questionable publications. Apparently, the desired gold rush of commercial exploitation was seductive. Scientific skepticism as an indispensable core of good scientific practice was often neglected, and the peer review process has not exerted its corrective effect. Self-critical reflection and more healthy skepticism could help to reduce the risk of such aberrations in drug development. This article uses this case study as a striking example to show what can be learned from the Taxol case in terms of research ethics and the avoidance of questionable research practices.

摘要

紫杉醇(通用名:paclitaxel)是治疗多种癌症药物的极其重要的成分。在其有效性被发现30年后,紫杉醇的一种代谢前体(10 - 去乙酰巴卡亭III)仍主要从欧洲红豆杉的针叶中提取。为了满足巨大的需求,从一开始人们就寄希望于生物技术生产的可能性。1993年,仿佛是偶然间,据说在红豆杉内生生长的真菌中发现了紫杉醇。这一发现燃起了通过生物技术在发酵罐中大量生产真菌紫杉醇的希望。但事情并未如此发展。相反,涌现出大量令人困惑的出版物,声称在越来越多的真核甚至原核物种中检测到了紫杉醇。然而,研究人员从未重现这些相当令人费解的结果,而且它们肯定无法应用于工业规模。本文将表明,一些误导性的方法显然是基于对稀少证据的看似粗心的处理以及至少是有问题的出版物。显然,商业开发所期望的淘金热极具吸引力。作为良好科学实践不可或缺核心的科学怀疑论常常被忽视,同行评审过程也未发挥其纠正作用。自我批评性反思和更健康的怀疑态度有助于降低药物研发中此类偏差的风险。本文以这个案例研究作为一个突出的例子,展示了从紫杉醇案例中在研究伦理和避免有问题的研究实践方面可以学到什么。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3cd0/11254485/7ac0e41dbdf1/10-1055-a-2309-6298-ii0057pm01.jpg

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