The sequencing of the first complete bacterial genome in 1995 heralded a new era of hope for antibacterial drug discoverers, who now had the tools to search entire genomes for new antibacterial targets. Several companies, including GlaxoSmithKline, moved back into the antibacterials area and embraced a genomics-derived, target-based approach to screen for new classes of drugs with novel modes of action. Here, we share our experience of evaluating more than 300 genes and 70 high-throughput screening campaigns over a period of 7 years, and look at what we learned and how that has influenced GlaxoSmithKline's antibacterials strategy going forward.

Experimental medicine is the use of innovative measurements, models and designs in studying human subjects for establishing proof of mechanism and concept of new drugs, for exploring the potential for market differentiation for successful drug candidates, and for efficiently terminating the development of unsuccessful ones. Humans are the ultimate 'model' because of the uncertain validity and efficacy of novel targets and drug candidates that emerge from genomics, combinatorial chemistry and high-throughput screening and the use of poorly predictive preclinical models. The in-depth investigation of the effects of drugs and the nature of disease progression is becoming ever more feasible because of advances in clinical biomarkers.