26 May, 2020
Many scientists are faced with a key decision at some point in their career; to either persist with an academic career, with its high attrition rate and treadmill of grant writing, or look to move into industry. Back when I was a PhD student (1987-1991) there was a certain snobbery about industrial bioscience - some told me it was ‘boring’, ‘turning-the-handle’, and ‘not very creative’. My own experience has been somewhat different.
I was fortunate to develop my research career in some excellent labs; first as a PhD student with Michael Wakelam at the University of Glasgow and then as a post-doc with Frank McCormick, initially at the Cetus Corporation and then ONYX Pharmaceuticals, both in the San Francisco Bay Area. In both of these labs I was exposed to some great emerging bioscience. But I was also exposed to something else; what now might be called ‘target validation’.
My PhD was actually a CASE studentship, supported by the SERC (a precursor of the BBSRC) with Wellcome (then a pharmaceutical giant) as the industrial partner. I was able to spend time at the Wellcome labs in Beckenham, which was a great experience. In the McCormick lab (1991-97) we were trying to understand how the then emerging RAS effector pathways were regulated and their role in RAS biology; the big picture of course was to validate which of these pathways were required for RAS transformation and might therefore be good drug targets (i.e. target validation). At first the portents were not good; as a new post-doc I (in)famously sat in a meeting with the investors who launched ONYX Pharmaceuticals and said “I didn’t come here to do drug discovery”. Frank laughed nervously, managed not to fire me on the spot and things got better.
I was lucky to work alongside brilliant and generous colleagues (I hope just a little of this rubbed off) and together we started to unpick a few details of the RAS-RAF-MEK-ERK pathway. Assays were established and used by ONYX and Bayer (our partners) to find the first RAF inhibitor, SorafenibTM. We also established assays in the Inflammation Project (in collaboration with Len Stephens and Phill Hawkins in the case of PI3K), which were progressed with Parke-Davis (now Pfizer). In both cases we were simply studying signalling pathways, seeking to understand their role and regulation. It was interesting and exciting research. It was also target validation that underpinned drug discovery; by stealth I had ended up doing what I said I wouldn’t!
After 6 years I left ONYX. It was a wrench to do so as I had made many good friends and the Bay Area was a great place to live (and run!). My reasons were partly personal but I also recognised that I wanted to return to academia. I guess my main driver was academic freedom; I wanted to work on the things I found interesting and not be told “this project stops today; tomorrow we will work on this”. So I started my own research group in 1997 here at the Babraham Institute, attracted by the world leading signalling researchers (Len, Phill and the late Mike Berridge). So far it seems to be going OK.
I learnt a fair amount about drug discovery at ONYX; one lesson being that I didn’t want to do it for the rest of my life. However, the knowledge certainly helps me now when I interact with researchers from biotech and pharma organisations, as I find I can speak the same language and understand something of their needs and expectations. I understand what they mean by ‘target validation’, ‘druggable target’, ‘redundancy’ ‘target engagement’ and ‘mechanism-based efficacy’. And these same issues are relevant to basic biology; working with industry has allowed us to get access to emerging drugs as research tools to probe the normal functions of signalling pathways. As a result, my lab has worked closely with biotech and pharma companies over the last 20 years, to the benefit of all parties.
In that time industrial bioscience has changed. Small start-up companies have always been keen to embrace new and emerging technologies, being hungry but cash-limited and needing unique, innovative technologies to give them an edge over competitors (many such companies are on our doorstep here at the Babraham Research Campus). Now, large pharma companies have, to varying degrees, recognised the need to embrace change. In many disease areas the ‘obvious targets’ (low-hanging fruit) have already been drugged, and so new innovative approaches are needed for target discovery, validation and patient stratification including genomics, proteomics, RNAi, CRISPRi, CRISPRa, protein interference, etc. This in turn has led to close relationships being formed between pharma and academics to develop these new tools. Today one is just as likely to be exposed to exciting and cutting-edge, innovative technologies in the industrial sector as in academia.
Such developments have meant that key skill sets are now increasingly interchangeable. Put simply, there has never been an easier time to cross between academia and industry (and back again). Many of the PhD students or post-docs I have trained have gone on to work in biotech and pharma organisations. And while historically an early-stage researcher’s move into industry was often viewed as a ‘one-way street’, the common research skill sets now required mean that it is easier than ever to move between industry and academia. Indeed, some research councils run funding schemes (for instance the secondment schemes offered by the Royal Society and UKRI), to support movement in both directions. So perhaps as scientists we need to get away from binary notions like academia or industry and be more ‘sector fluid’? Great science flourishes at these interfaces.
Header image credit: 'San Francisco Oakland Bay Bridge at night'; by Caroline Culler is licensed under CC BY-SA 3.0.
26 May 2020
By Simon Cook