Toxicogenomics, Drug Discovery, and the Pathologist

The e eld of toxicogenomics, which currently focuses on the application of large-scale differential gene expression (DGE) data to toxicology, is startingtoineuencedrugdiscoveryanddevelopmentinthepharmaceuticalindustry.Toxicologicalpathologists, whoplaykeyrolesinthedevelopment oftherapeuticagents,havemuchtocontributetoDGEstudies,especiallyintheexperimentaldesignandinterpretationphases.Theintelligentapplication of DGE to drug discovery can reveal the potential for both desired (therapeutic) and undesired (toxic) responses. The pathologist’s understanding of anatomic, physiologic, biochemical, immune, and other underlying factors that drive mechanisms of tissue responses to noxious agents turns a bewildering array of gene expression data into focused research programs. The latter process is critical for the successful application of DGE to toxicology. Pattern recognition is a useful e rst step, but mechanistically based DGE interpretation is where the long-term future of these new technologies lies. Pathologists trained to carry out such interpretations will become important members of the research teams needed to successfully apply these technologies to drug discovery and safety assessment. As a pathologist using DGE, you will need to learn to read DGE data in the same way you learned to read glass slides, patiently and with a desire to learn and, later, to teach. In return, you will gain a greater depth of understanding of cell and tissue function, both in health and disease.