Systems biology versus molecular biology

Systems biology and molecular biology can answer the same question in quite different ways, and frequently the answers given by one sub-discipline seem no answer at all to the other. For many molecular biologists, a systemslevel explanation leaves them feeling that, until the underlying molecular mechanisms are known, the approach is hopelessly superficial. For systems biologists, on the other hand, an account of the genes and gene interactions responsible for a phenomenon is just a list, and they hunger for the underlying principles that make sense out of the list. I believe that these two styles of answering questions are complementary; at best, a more complete understanding is reached when the two approaches are unified. I shall illustrate how these two approaches differ by considering the different answers they give to two questions. Why do separate neocortical areas exist? And why are the cortical areas arranged in the way they are? The example I give is flawed, however, and the nature of the flaw is revealing about the challenges facing systems and molecular biology. Since Brodmann [1], we have recognized the existence of many anatomically and molecularly distinct neocortical areas, each with a different function. About 100 areas have now been identified in the human cortex, ranging from the primary visual cortex (V1) through temporal and frontal lobe language areas. The first question, then, is: why are the neurons responsible for a particular calculation grouped together in one region of cortex? A given area, V1 for example, varies considerably in size and in its precise location from one individual to the next (and from one species to the next), but its relations to other areas never change. For example, V1 is always next to V2 and never next to V3 (V2 and V3 are other areas devoted to vision). The second question is: why are these neighbor relations the same from one individual to the next?