Systems and integrative biology as alternative guises for pharmacology:: Prime time for an iPharm concept?

Understanding the molecular basis of human disease pathophysiology is critical to accurate disease diagnosis, defining disease progression and to identifying new drugs that more specifically address target diseases. Advances in the understanding of tissue function (including draft maps of the human genome) coupled with industrial-scale, 'enabling' technologies like high throughput screening, combinatorial chemistry, proteomics, etc., have generated data on a scale never before possible. Despite this, there continues to be a dearth of new drug approvals ascribed to: (i) the challenges of working with novel, often non-validated disease targets; (ii) targeting diseases (stroke, Alzheimer's) with limited (if any) treatment and ill-defined clinical trial endpoints; (iii) enhanced regulatory hurdles for drug approval; (iv) insufficient time for the new knowledge and enabling technologies to have reached a productive level. An alternate viewpoint is that unfettered access to such technologies, where exclusion rather than integration has been the hallmark, has markedly reduced the intellectual competent of the biomedical research endeavor, with perceived technological 'quick fixes' displacing the integrative, hierarchical approach of pharmacology, that with medicinal chemistry, represents the core of the drug discovery process. After two decades of profound neglect, pharmacology has re-emerged as the key discipline in providing context to the drug discovery process, facilitating more timely, context-relevant and data-driven outcomes in the search for new drugs. Rather than viewing the future of drug discovery in terms of the 'new' biologies, systems and integrative, a rubric along the lines of iPharm, integrating both established and new technologies, is required. (c) 2005 Elsevier Inc. All rights reserved.