Abstract
Physiological interpretations of Systems Biology have made many advances since the Principles of Systems Biology were first published in this journal in 2008. Those advances show that the main principle, Biological Relativity, is a logical necessity since no system can exist without the form of the system. That form creates the necessary boundary conditions for the integration of any equations for the mechanics by which the elements of the system interact. A further conclusion is that the Central Dogma of molecular biology is an incomplete representation of causation in biology. It neglects the multi-scale properties of living systems, and its assumption that DNA can self-replicate accurately enough is incorrect. The replicator cannot therefore be separate from its vehicle, the living cell. This failure has led to a gene-centric impasse: the failure of genomics to produce the expected cures for common fatal diseases. Physiology now needs to provide alternative ways in which this problem can be successfully addressed.