Abstract:The Nobel Prize in Physiology or Medicine 2020 was awarded jointly to Harvey J. Alter, Michael Houghton, and Charles M. Rice for their contributions in the discovery of hepatitis C virus (HCV). However, eight years lapsed between Houghton hunting down the virus in 1989 and Rice proving HCV alone could cause hepatitis in 1997. How did this seemingly low-hanging fruit turn out to take so long? We reviewed literature to piece together studies during those years, and determined contributions by different groups (Rice’s group included). Through a close look into its performance at two milestones (determining the 3′-terminal sequence of HCV genome RNA and constructing an infectious molecular clone), we analyzed, from dimensions of technology stack, path dependence and goal setting, why Rice’s group leapfrogged its competitive peers.