Creager Angela N H
Department of History and Program in History of Science, Princeton University, Princeton, NJ 08544-1017, USA.
Stud Hist Philos Biol Biomed Sci. 2007 Mar;38(1):159-90. doi: 10.1016/j.shpsc.2006.06.016. Epub 2007 Feb 12.
The 1940s and 1950s were marked by intense debates over the origin of drug resistance in microbes. Bacteriologists had traditionally invoked the notions of 'training' and 'adaptation' to account for the ability of microbes to acquire new traits. As the field of bacterial genetics emerged, however, its participants rejected 'Lamarckian' views of microbial heredity, and offered statistical evidence that drug resistance resulted from the selection of random resistant mutants. Antibiotic resistance became a key issue among those disputing physiological (usually termed 'adaptationist') vs. genetic (mutation and selection) explanations of variation in bacteria. Postwar developments connected with the Lysenko affair gave this debate a new political valence. Proponents of the neo-Darwinian synthesis weighed in with support for the genetic theory. However, certain features of drug resistance seemed inexplicable by mutation and selection, particularly the phenomenon of 'multiple resistance'--the emergence of resistance in a single strain against several unrelated antibiotics. In the late 1950s, Tsutomu Watanabe and his collaborators solved this puzzle by determining that resistance could be conferred by cytoplasmic resistance factors rather than chromosomal mutation. These R factors could carry resistance to many antibiotics and seemed able to promote their own dissemination in bacterial populations. In the end, the vindication of the genetic view of drug resistance was accompanied by a recasting of the 'gene' to include extrachromosomal hereditary units carried on viruses and plasmids.
20世纪40年代和50年代，关于微生物耐药性起源的激烈争论此起彼伏。传统上，细菌学家援引“训练”和“适应”的概念来解释微生物获得新特性的能力。然而，随着细菌遗传学领域的兴起，该领域的参与者摒弃了关于微生物遗传的“拉马克式”观点，并提供了统计证据，证明耐药性是由随机耐药突变体的选择导致的。在那些对细菌变异的生理学（通常称为“适应论者”）与遗传学（突变和选择）解释存在争议的人当中，抗生素耐药性成为了一个关键问题。与李森科事件相关的战后发展给这场辩论赋予了新的政治色彩。新达尔文主义综合理论的支持者加入进来，支持遗传学理论。然而，耐药性的某些特征似乎无法用突变和选择来解释，尤其是“多重耐药性”现象——即单一菌株对几种不相关抗生素产生耐药性。20世纪50年代末，渡边力和他的合作者通过确定耐药性可由细胞质耐药因子而非染色体突变赋予，解开了这个谜团。这些R因子可以携带对多种抗生素的耐药性，并且似乎能够促进自身在细菌群体中的传播。最终，耐药性遗传学观点的证实伴随着对“基因”的重新定义，将病毒和质粒携带的染色体外遗传单位也纳入其中。
