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Science 1 March 2002:
Vol. 295. no. 5560, pp. 1664 - 1669
DOI: 10.1126/science.1069981
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Review

Reverse Engineering of Biological Complexity

Marie E. Csete,1 John C. Doyle2*

Advanced technologies and biology have extremely different physical implementations, but they are far more alike in systems-level organization than is widely appreciated. Convergent evolution in both domains produces modular architectures that are composed of elaborate hierarchies of protocols and layers of feedback regulation, are driven by demand for robustness to uncertain environments, and use often imprecise components. This complexity may be largely hidden in idealized laboratory settings and in normal operation, becoming conspicuous only when contributing to rare cascading failures. These puzzling and paradoxical features are neither accidental nor artificial, but derive from a deep and necessary interplay between complexity and robustness, modularity, feedback, and fragility. This review describes insights from engineering theory and practice that can shed some light on biological complexity.

1 Departments of Anesthesiology and Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
2 Control and Dynamical Systems, Electrical Engineering, and Bioengineering, California Institute of Technology, Pasadena, CA 91125, USA.
*   To whom correspondence should be addressed. E-mail: doyle{at}cds.caltech.edu

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