Nature Biotechnology22, 1253 - 1259 (2004)
Published online: 6 October 2004; | doi:10.1038/nbt1017
Systems biology in drug discovery
Eugene C Butcher1, 2, Ellen L Berg3
& Eric J Kunkel3
1
Laboratory of Immunology and Vascular Biology, Department of Pathology (5324), Stanford University School of Medicine, Stanford, California 94305-5324, USA.
2
The Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA.
3
BioSeek Inc., 863-C Mitten Rd., Burlingame, California 94010, USA.
The hope of the rapid translation of 'genes to drugs' has foundered on the reality that disease biology is complex, and that drug development must be driven by insights into biological responses. Systems biology aims to describe and to understand the operation of complex biological systems and ultimately to develop predictive models of human disease. Although meaningful molecular level models of human cell and tissue function are a distant goal, systems biology efforts are already influencing drug discovery. Large-scale gene, protein and metabolite measurements ('omics') dramatically accelerate hypothesis generation and testing in disease models. Computer simulations integrating knowledge of organ and system-level responses help prioritize targets and design clinical trials. Automation of complex primary human cell−based assay systems designed to capture emergent properties can now integrate a broad range of disease-relevant human biology into the drug discovery process, informing target and compound validation, lead optimization, and clinical indication selection. These systems biology approaches promise to improve decision making in pharmaceutical development.
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