Beyond reductionism: metabolic circularity as a guiding vision for a real biology of systems.

The definition of life has excited little interest among molecular biologists during the past half-century, and the enormous development in biology during that time has been largely based on an analytical approach in which all biological entities are studied in terms of their components, the process being extended to greater and greater detail without limit. The benefits of this reductionism are so obvious that they need no discussion, but there have been costs as well, and future advances, for example, for creating artificial life or for taking biotechnology beyond the level of tinkering, will need more serious attention to be given to the question of what makes a living organism living. According to Robert Rosen's theory of metabolism-replacement systems, the central idea missing from molecular biology is that of metabolic circularity, most evident from the obvious but commonly ignored fact that proteins are not given from outside but are products of metabolism, and thus metabolites. Among other consequences, this implies that the usual distinction between proteome and metabolome is conceptually artificial -- however useful it may be in practice -- as the proteome is part of the metabolome.