Creativity in large pharmaceutical research organizations: unleash the hungry drug hunter

Productivity remains a critical issue for the pharmaceutical industry and biomedical research, as illustrated by the low number of new molecular and biological entities that were approved in 2016 (Mullard, 2017). The failure rate in drug discovery programmes is high, and the returns on smallmolecule R&D remain below their capital costs (David et al., 2009). The quest for a new paradigm that would radically change the pharmaceutical industry and create a highperformance R&D organization remains a major goal. Many solutions have been proposed to tackle the problem of productivity in pharmaceutical R&D, but it is striking that little attention has been paid to perhaps what can be considered as the primary culprit of the pharma R&D crisis: the lack of scientific creativity. This is particularly annoying in an era of highly innovative medicines, which progressed from the less demanding era of ‘me-too’ or ‘slightly-mebetter’ drugs (Swinney and Anthony, 2011). Research in the drug discovery industry is performed by scientists whose creativity and passion for science are the impetus for innovation. In an attempt to understand what drives major differences in productivity, Edwards et al. (2011) and Ringel et al. (2013) identified a core set of behaviours as critical success factors, among which talent, as measured by publication productivity (e.g. h-index; Hirsch, 2005), is strongly correlated with laboratory performance. Talented scientists act as boundary spanners, coupling seemingly disparate fields and extracting new sources of information, and they are proficient at gathering external knowledge. A recent study that explored the pharmaceutical R&D dynamics by examining the publication activities of all R&D laboratories revealed a marked decline in the total number of publications by large firms (Rafols et al., 2014). While this observation confirms the increasing reliance of pharma on external research, it also emphasizes that less (quality?) science is performed in R&D laboratories, perhaps due to a shortage of talent, a phenomenon that further illustrates the decline in big pharma’s R&D. Talent is necessary, although it is not sufficient to assure success. Drug discovery research thrives in a creative, flexible, non-autocratic corporate environment (Cuatrecasas, 2006), in which proper managerial strategies, along with fully empowered key research leaders, are employed to guide and inspire scientists. Such an environment includes biotechor academic-style research projects that ‘put scientists in the driving seat’ (Zhong and Moseley, 2007), while keeping the requirement of experimental rigour, which is more prominent in big pharma (Ehlers, 2016). The (success) stories of the pioneering biotech companies, Genentech and Vertex Pharmaceutical, are probably the best illustration of how great innovation thrives with a mixture of outstanding research leaders (Herbert Boyer and Joshua Boger, respectively), highly focused groups of committed talented young scientists and visionary neck-exposed risk takers (Bob Swanson for Genentech), these latter creating an environment that supports disruptive science. These biotech companies grew spectacularly quickly because they pushed the boundaries of what is possible in medicine and delivered genuine clinical breakthroughs by translating highly innovative scientific research (e.g. recombinant DNA technology, crystal structure for the protease of the hepatitis C virus and rational drug design) into drugs that have brought substantial benefits to patients (human insulin and growth hormone, protease inhibitors). While today these companies are much larger (Genentech is a Roche company), they have kept their unique culture of relentless commitment to science. A recent analysis of R&D productivity in pharma BJP British Journal of Pharmacology British Journal of Pharmacology (2017) 174 2152–2153 2152