In silico medicine is still forging a road for itself in the current biomedical landscape. Discursively and rhetorically, it is using a three-way positioning, first, deploying discourses of personalised medicine, second, extending the 3Rs from animal to clinical research, and third, aligning its methods with experimental methods. The discursive and rhetorical positioning in promotions and statements of the programme gives us insight into the sociability of the scientific labour of advancing the programme. Its progress depends on complex social, institutional and (...) technological conditions which are not external to its epistemology, but intricately interwoven with it. This article sets out to show that this is the case through an analysis of the process of computational modelling that is at the core of its epistemology. In this paper I show that the very notion of ‘model’ needs to be re-thought for in silico medicine, and propose a replacement, in the form of the ‘Model-Simulation-Experiment-System’ or MSE-system, which is simultaneously an epistemological, social and technological system. I argue that the MSE-system is radically mediated by social relations, technologies and symbolic systems. We need now to understand how such mediations operate effectively in the construction of robust MSE-systems. (shrink)