Interest in the concept of a virtual human model that can encompass human physiology and anatomy on a biophysical (mechanistic) basis, and can assist with the clinical diagnosis and treatment of disease, appears to be growing rapidly around the globe. When such models are personalised and coupled with continual diagnostic measurements, they are called 'digital twins'. We argue here that the most useful form of virtual human model will be one that is constrained by the laws of physics, contains a comprehensive knowledge graph of all human physiology and anatomy, is multiscale in the sense of linking systems physiology down to protein function, and can to some extent be personalized and linked directly with clinical records. We discuss current progress from the IUPS Physiome Project and the requirements for a framework to achieve such a model.