Chemical advances in evolution by and changes in use of space during time.

The general features of theoretical biology are outlined, starting from the beginnings of modern bioenergetics, energy transduction, in 1961. The major characteristics of the bioenergetic systems are then described and it is pointed out that especially the treatment of energized, directed chemical flow in divided space in cells is central to this activity. It is also the major theoretical problem of many other cellular activities. The development of bioenergetics until today, based on the theories of flows of electrons, protons and other chemical materials in structures, is then outlined. Great benefit has accrued from the knowledge of the structures which allow controlled flow, diffusion. In a speculative forward look at the theoretical biology of cells based on this outline the usefulness of further reductive analysis of extracted molecular units is considered as descriptions of mobility within structures of large molecules and membranes as well as in free space. Such structures are central to catalysed control and flow. The possibility of a more holistic approach is then examined. This will require markers of flow states and spatial structures. It is shown that as the flow system is one of a combined environment and organisms the study of metal ions in both has particular advantages. Consideration is given as to how this study can assist a broad understanding of the chemistry of the evolution of organisms. The changes of the metallome, strongly linked to the proteome, the genome and the environment, is a ready source of information concerning the manner in which changes in catalysts and controls of flow of organic chemicals have evolved in the divided space of cells and of cellular systems. The connection of the code changes to the environment via the metallome changes is then mooted.