|Abstract||Industrial drug design methodology has undergone remarkable changes in the recent history. Up to the 1970s, the screening of large numbers of randomly selected substances in biological test system was often a crucial step in the development of novel drugs. From the early 1980s, such ‘blind’ screening was increasingly rejected by many pharmaceutical researchers and gave way to ‘rational drug design’, a method that grounds the design of new drugs on a detailed mechanistic understanding of the drug action. Surprisingly, however, the chance-based method of random screening returned to center stage of industrial drug development in the 1990s in the form of ‘high-throughput screening’ (HTS). I will argue in this paper that this to-and-fro in the prominence of random screening comes with fundamental changes in the epistemic signiﬁcance of chance experiments in pharmaceutical development. While up to the 1970s, random screening used to be chosen as an empirical search strategy primarily because suﬃ- cient knowledge of the mechanistic basis of drug action was lacking, it has turned with high-throughput screening into an experimental method that employs chance variation and testing to illuminate this mechanistic basis. As a consequence, research into the underlying mechanisms of drug action and the development of new drugs have become closely integrated. The rise of HTS therefore not only shows how chance experiments have assumed a new epistemic role in drug development. It also allows for a detailed study of the much debated emergence of a new relationship between scientiﬁc understanding and the development of technological artifacts.|
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