Over the last forty years biological sciences have undergone a revolution, as new techniques of analysis and information handling have produced masses of data on the key molecules in living cells. And although the concept of ‘systems biology’ has a longer history, the Human Genome Project and subsequent reductionist –omics projects, have given rise to ‘systems biology’ as a new trend in the life sciences where the focus shifts towards the integration of data on different levels, from (part of) cells to virtual organs and potentially whole organisms. After the establishment of the Institute for Systems Biology in Seattle and the Systems Biology Institute in Tokyo at the turn of the millennium, systems biology spread into national science policy programmes and became institutionalized in countries such as the United States, the United Kingdom, the Netherlands and Germany. This paper explicitly studies the entanglement of epistemic and social transformations in the emergence of systems biology, analysing new ways of doing research as well as the political and institutional structures in which the research is performed. Special attention will be given to different local and national patterns of emergence – from modeling yeast in Manchester to the creation of the German virtual liver. This research into the intellectual and social history of systems biology aims to help drafting the history of new biology and its relation to research policies, funding structures, university transformation, etc. in a way which can inform both academic and policy discussions.