During the 50s, Edouard Kellenberger, director of the new laboratory of "Biophysics", formed a group of researchers to work on the genetics of bacteriophages. This group included Werner Arber, who became his first assistant in 1953, and Grete Kellenberger-Gujer, Richard Epstein and Lucien Caro, who all worked on the genetics of the bacteriophage T4.
In the beginning of the 60s, the group of biologists expanded by the recruitement of Alfred Tissières (from Cambridge, UK) and Pierre-François Spahr (from Harvard), who formed together the Department of Biochemical Genetics in Sciences I. They worked on the biosynthesis of proteins and transcription. In 1964, this Department and the Biophysics Department, directed by Edouard Kellenberger, fused together and became the first Institute of Molecular Biology in Switzerland. The certificate of specialisation in molecular biology was created at that time. Ulrich Laemmli, Bernard Hirt and Dimitri Karamata formed the first class.
In 1960, Werner Arber became a faculty member in the Department of Biophysics and, starting from 1964, of the new Institute of Molecular Biology, where he stayed until 1970. During these six years, he worked on the mechanism by which the bacteria resist infection by bacteriophages. His research led to the discovery of restriction enzymes, which proved essential for the development of molecular biology. For this discovery he was awarded together with Hamilton Smith and Daniel Nathans the Nobel Prize in Physiology and Medicine in 1978 .
In 1969, the Department of Molecular Biology was formed from the Institute of Molecular Biology and in 1970 it moved from Sciences I to Sciences II. In 1971, Lucien Caro (from the Rockerfeller Institute), Harvey Eisen (from UCSF), Jeffrey Miller (from CSH) and Roger Weil (from UNIL) joined Alfred Tissières, Pierre-François Spahr and Richard Epstein. In the same decade Edouard Kellenberger and Werner Arber went to Basle to create the Biozentrum, a new center of research.
Throughout the following years, new professors joined the Department: Bernard Allet (currently, retired), Erich Nigg (currently, director of the Biozentrum), Susan Gasser (currently, director of the Friedrich Miescher Institute), Ulrich Laemmli (currently, honorary professor), Jean-David Rochaix, Ueli Schibler, David Shore, Robbie Loewith, Thanos Halazonetis, Stéphane Thore and Thomas Schalch.
In 2003, the Department moved to Sciences III, where it joined the other Departments of the section of Biology.