In the Beginning, There Was Serendipity

Abstract

“A lucky accident dropped the medicine into our hands”; this is how a publication on August 14, 1886, from Arnold Cahn and Paul Hepp in the Centralblatt für Klinische Medizin began. The history of drug research is punctuated by lucky accidents. As a general rule, detailed knowledge of biological systems was absent. So it is not surprising that the working hypotheses were often wrong, and the obtained results differed from the expectations. The case of accidental success fell into the background over time. Today happenstance as a strategy has been replaced by the arduous and ambitious goal of preparing drugs by using a straightforward approach. The only exception to this is the kind of shotgun-style testing of large and diverse chemical compound libraries, including microbial and plant extracts that is done with the goal of finding new lead structures. In this case, serendipity is desired to find as large and diverse a palette of lead structures (Chaps. 6, “The Classical Search for Lead Structures” and 7, “Screening Technologies for Lead Structure Discovery”) with potential for further optimization (Chaps. 8, “Optimization of Lead Structures” and 9, “Designing Prodrugs”).