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Systems Biology has two roots. It does not only derive from experimental molecular biology and genomics, but also from an even older tradition of physical chemistry and theoretical biology. As Systems Biology is about the emergence of function from the interactions of molecules, it is reminiscent of the early work on self-organization and non equilibrium thermodynamics. In this presentation we shall show how this early work was as interesting as incorrect. The culprit was the lack of detail. In Biology there should be little motive to make things as simple as possible. The complex nonlinearities may require one to be so close to reality that simplification should be carried out in ways that may be quite specific for the Biology being studied. Only with mosaic non equilibrium thermodynamics enough specificity was brought in to come to statements of a rather limited generality. The lin-log approach to kinetic modeling derives from this. Searches for more general principles of systems away from equilibrium have not led very far. As Systems Biology is about the emergence of function from interactions and as part of non-equilibrium thermodynamics is about the coupling of processes, one could hope for new progress in non-equilibrium thermodynamics developments as Systems Biology gains in momentum. The genomics root of Systems Biology is deaf to the principles of physics and chemistry. It determines correlations between concentrations and induces these observations to proposed networks. The induced networks, or at least the proposed flow through them, could well be inconsistent with physical chemical principles. However, the genomics paradigm does suggest a way to generalize the description of living cells as being determined by a complete set of gene-specified processes. This concept leads to two branches of bottom up Systems Biology called Hierarchical Control Analysis and Hierarchical Regulation Analysis. In this presentation I will show how these two approaches can be used in differential network-based drug design and in figuring out whether living organisms are determined exclusively by transcriptional regulation. I will also show how they lead to a number of general laws', which may well qualify to correspond to general principles non-equilibrium thermodynamics has been looking for. |
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