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To understand biology at the system level, we must examine the structure and dynamics of cellular and organismal function, rather than the characteristics of isolated parts of a cell or organism. Properties of systems, such as robustness, emerge as central issues, and understanding these properties may have an impact on the future of medicine. However, many breakthroughs in experimental devices, advanced software, and analytical methods are required before the achievements of systems biology can live up to their much-touted potentiaL
Since the days of Norbert Weiner, system-level understanding has been a recurrent theme in biological science (1). The major reason it is gaining renewed interest today is that progress in molecular biology, particularly in genome sequencing and high-throughput measurements, enables us to collect comprehensive data sets on system performance and gain information on the underlying molecules. This was not possible in the days of Weiner, when molecular biology was still an emerging discipline. There is now a golden opportunity for system-level analysis to be grounded in molecular-level understanding, resulting in a continuous spectrum of knowledge.
System-level understanding, the approach advocated in systems biology (2), requires a shift in our notion of "what to look for" in biology. While an understanding of genes and proteins continues to be important, the focus is on understanding a system's structure and dynamics. Because a system is not just an assembly of genes and proteins, its properties cannot be fully understood merely by drawing diagrams of their interconnections. Although such a diagram represents an important first step, it is analogous to a static roadmap, whereas what we really seek to know are the traffic patterns, why such traffic patterns emerge, and how we can control them.
Identifying all the genes and proteins in an organism is like listing all the parts of an airplane. While such a list provides a catalog of the individual components, by itself it is not sufficient to understand the complexity underlying the engineered object. We need to know how these parts are assembled to form the structure of the airplane. This is analogous to drawing an exhaustive diagram of gene-regulatory networks and their biochemical interactions. Such diagrams provide limited knowledge of how changes to one part of a system may affect other parts, but...