This is a scientific and philosophical autobiography written around a collection of Denis Noble's most significant papers. It traces a remarkable journey from naïve reductionism to a rigorous systems approach to living systems. It is rigorous because Denis Noble was one of the first biologists to construct computer models of cells and organs of the body. His theoretical work is entirely mathematically based, with no room for ambiguity. Far from the denigration of the systems approach as holistic ‘hand-waving’, his work is now regarded by pharmaceutical companies and regulators as the gold standard of modelling in the development of new medication.Systems Biology is an idea in search of a definition. This book explains why this is true: it is an approach rather than a subject. Denis Noble's work is one of the clearest examples of the systems approach in practice since it reveals the nature of some of the forms of downward causation in multilevel analysis. The story will delight readers who like to see how scientific controversy is resolved, since many of the developments described in each chapter were highly controversial when they occurred.