On the vital role of fluid movement in organisms and cells: a brief historical account from Harvey to Coulson, extending the hypothesis of circulation.

The importance of the orchestrated movement of substrates over multicatalytic enzymes, topographically arranged for maximum efficacy for metabolic function, means that the organization of the body right down to the subcellular level is based upon the principle of perfusion for most normal living processes. The history of the development of this idea, which is contrary to the received wisdom arising and still persisting since the early days of biochemistry, will be followed from the time when the overall need for a circulation at the gross level was fully appreciated, extending the argument through a historical perspective to include the control of flow within the individual cell. Life, seen from this new perspective, seems to be inherently dependent upon this principle to such an extent that it leads to a clearer distinction between the living and the dead, and provides a framework for more critical experiments concerning control mechanisms in the cell.