紫杉醇--真菌二次代谢的产物还是假象?

IF 2.1 4区 医学 Q3 CHEMISTRY, MEDICINAL
Planta medica Pub Date : 2024-08-01 Epub Date: 2024-05-16 DOI:10.1055/a-2309-6298
Klaus Ferdinand Gärditz, Hjördis Czesnick
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引用次数: 0

摘要

紫杉醇(通用名称:紫杉醇)是治疗各种癌症的药物中极为重要的成分。在发现紫杉醇的有效性 30 年后,其代谢前体(10-脱乙酰基巴卡丁 III)仍主要从欧洲紫杉树的针叶中提取。为了满足巨大的需求,人们从一开始就寄希望于生物技术生产的可能性。1993 年,一个偶然的机会,人们在紫杉树内生真菌中发现了紫杉醇。这一发现唤起了人们利用生物技术在发酵罐中大量生产真菌 Taxol 的希望。但这从未实现。相反,出现了大量令人困惑的出版物,声称在越来越多的真核生物甚至原核生物物种中检测到了紫杉醇。然而,研究人员从未再现过这些令人费解的结果,当然也无法将其应用于工业规模。本文将说明,一些错误的方法显然是基于对稀少证据看似粗心的处理,以及至少是基于有疑问的出版物。显然,所期望的商业开发淘金热具有诱惑力。科学怀疑主义作为良好科学实践不可或缺的核心往往被忽视,同行评审程序也没有发挥其纠正作用。自我批判性的反思和更健康的怀疑精神有助于降低药物研发中出现此类偏差的风险。本文以这一案例研究为例,说明从 Taxol 案例中可以汲取哪些研究伦理方面的教训,避免有问题的研究实践。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Paclitaxel - a Product of Fungal Secondary Metabolism or an Artefact?

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.

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来源期刊
Planta medica
Planta medica 医学-药学
CiteScore
5.10
自引率
3.70%
发文量
101
审稿时长
1.8 months
期刊介绍: Planta Medica is one of the leading international journals in the field of natural products – including marine organisms, fungi as well as micro-organisms – and medicinal plants. Planta Medica accepts original research papers, reviews, minireviews and perspectives from researchers worldwide. The journal publishes 18 issues per year. The following areas of medicinal plants and natural product research are covered: -Biological and Pharmacological Activities -Natural Product Chemistry & Analytical Studies -Pharmacokinetic Investigations -Formulation and Delivery Systems of Natural Products. The journal explicitly encourages the submission of chemically characterized extracts.
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