The following text is an edited version of a recent interview with Sydney Brenner who has been at the forefront of many developments in molecular biology since the 1950s. It provides a participant's view on current issues in the history and epistemology of molecular biology. The main issue raised by Brenner regards the relation of molecular biology to the new field of systems biology. Brenner defends the original programme of molecular biology-the molecular explanation of living processes-that in his view has yet to be completed. The programme of systems biology in contrast he views as either trivial or as not achievable since it purports to deal with inverse problems that are impossible to solve in complex living systems. Other issues covered in the conversation concern the impact of the human genome sequencing project, the commercial turn in molecular biology and the contested disciplinary status of the science.