Accelerating drug discovery.

Drug development, from initial discovery of a promising target to the final medication, is an expensive, lengthy and incremental process. The ultimate goal is to identify a molecule with the desired effect in the human body and to establish its quality, safety and efficacy for treating patients. The latter requirements ensure that the approved medication improves patients’ quality of life, not only by curing their illness, but also by making sure that the cure does not become the cause of other problems, namely side effects (Snodin, 2002). It also means that this is a particularly costly and prolonged process. At present, bringing a single new drug to market costs around US$800 million, an amount that doubles every five years. According to the US Food and Drug Administration (FDA), it takes, on average, 12 years for an experimental drug to progress from bench to market. Annually, the North American and European pharmaceutical industries invest more than US$20 billion to identify and develop new drugs, about 22% of which is spent on screening assays and toxicity testing (Michelson & Joho, 2000). In addition to costs, administrative hurdles have become problematic, which contributes to the high failure rate of new drug candidates. Of 5,000 compounds that enter pre-clinical testing, only five, on average, are tested in human trials, and only one of these five receives approval for therapeutic use (Fig 1). It is not surprising that, while development costs have increased, the absolute number of newly approved drugs has constantly decreased for several years. These trends—increasing costs for drug development and testing and greater scrutiny of the approval process— create a growing problem both for the drug industry and for patients who are desperately waiting for new drugs to treat their illnesses. It is therefore timely to consider how new technologies, namely functional genomics, proteomics and the related field of toxicogenomics, can help to speed up drug development and make it more efficient. The current process of identifying a new drug and bringing it to market involves several lengthy steps (Fig 2). It starts with the synthesis of small molecules to target specific proteins or enzymatic activities in living cells. The next step is to identify those compounds that have the best chance of survival in clinical trials. These drug candidates are then subjected to a battery of in vitro tests to investigate potential classand compound-specific toxicity; it is in these early stages that most candidates fail. Compounds that make it through this stage are then subjected to acute and short-term in vivo toxicology studies. All information gathered in these preclinical stages is then used as a guide for subsequent clinical trials in human volunteers and patients. It is on these pre-clinical and clinical tests that new technologies could have the largest impact.