The case for open‐access chemical biology

Abstract

Policy‐makers and scientists are increasingly worried about the declining productivity of the pharmaceutical industry. Despite growing levels of investment from governments and industry, the number of new medicines that are approved each year has declined slowly during the past three decades (Betz, 2005; Booth & Zemmel, 2004; Cuatrecasas, 2006). The increased costs of drug discovery and development can no longer be supported by healthcare systems, and regulators are implementing control mechanisms such as price control schemes and increased regulatory demands, which could ultimately affect the drug discovery process by altering the financial and regulatory landscapes for new research programmes (Ess et al , 2003; Miller & Henderson, 2007). > The increased costs of drug discovery and development can no longer be supported by healthcare systems… Over the years, the industry has relied on various technologies to improve drug discovery. However, despite the use of structure‐based drug design, high‐throughput screening, combinatorial chemistry and the various ‘‐omics’ technologies, productivity continues to decline. The various explanations for this lack of success include increasing regulatory requirements, the depletion of therapeutic opportunities and ‘druggable’ targets, competition and organizational inefficiencies (Booth & Zemmel, 2004; Cuatrecasas, 2006; Dickson & Gagnon, 2004; Garnier, 2008). Although each of these explanations rings true, at the heart of the problem is a lack of proper scientific understanding of human biology and disease mechanisms. This is ultimately manifested in the high fraction of clinical programmes that fail owing to a lack of efficacy or safety, often in spite of excellent pre‐clinical data (Fingleton, 2008; Kola & Landis, 2004). Without a doubt, improved drug‐target validation would improve the success rate of drug discovery programmes, but this necessitates a better understanding of fundamental biological processes and the biological role of the drug target—usually a protein—under investigation. Paradoxically, …