Towards a theory of biological robustness

Robustness is one of the fundamental characteristics of biological systems. Numerous reports have been published on how robustness is involved in various biological processes and on mechanisms that give rise to robustness in living systems (Savageau, 1985a, b, 1998; Barkai and Leibler, 1997; Alon et al, 1999; von Dassow et al, 2000; Bhalla and Iyengar, 2001; Csete and Doyle, 2002, 2004; Kitano et al, 2004, 2004a, b; Stelling et al, 2004; Kitano and Oda, 2006; Kitano, 2007a). With increasing interest in systems biology, properties at the system level such as robustness have attracted serious scientific research. Nevertheless, a mathematical foundation that provides a unified perspective on robustness is yet to be established. For systems biology to mature into a solid scientific discipline, there must be a solid theoretical and methodological foundation. Often, systems biology is equated with computer simulation of cells and organs. Although computer simulation is a powerful technique for clarifying the complex dynamics of biological systems, it is also a useful tool for exploring the foundation of biological systems. While investigation on the dynamic properties of specific aspects of organisms is scientifically significant and can be widely applied, it is a study on specific instances of design within a design space that is shaped by fundamental principles, structural, environmental, and evolutionary constraints. The scientific goal of systems biology is not merely to create precision models of cells and organs, but also to discover fundamental and structural principles behind biological systems that define the possible design space of life (Figure 1). The value of understanding fundamental and structural theories is that they provide deeper insights into the governing principles that complex evolvable systems including biological systems follow. Building a solid theoretical foundation of biological robustness, and in particular defining a mathematical formulation of robustness, represents a key challenge in Systems Biology. Such a framework would be enormously useful, as it would provide general constraints on possible architectural features of living organisms.