Collaboration in Action: Noel Buckley

Let’s say it like it was. When I first set out on my scientific journey, I regarded pharma as risk-averse, unadventurous and myopic. Real research had to be high risk, stepping into virgin snow and unpolluted by commercial gain. We’ve come a long way in the last forty-odd years. Partly a change in my thinking and partly a shift in the way that a lot of pharma operates. My focus for this narrative is our team’s partnership with GSK under the Oxford-GSK Functional Genomics Initiative. Our proposal was to use machine learning (ML) to identify Alzheimer’s disease cellular phenotype and to develop a proof of concept that success could be translated into a screen that could identify therapeutics that could flip the disease to a normal phenotype. Simple? Not!  

Please could you give us an insight into what it has been like working in this collaboration?

We developed the work plan(s) collaboratively – truly collaboratively. Maybe the biggest difference between drawing up a work plan with pharma partners compared with the equivalent exercise for a Research Council grant is the “hardness” of the milestones, deliverables and the scary GO/NO-GO. I am a firm believer in the mantra “there is nothing like a deadline to focus the mind”, but when achieving milestones has consequences then that focus can be stressful. If you are using and developing novel approaches to problem-solving you have to expect that things do not always to work out in the manner that was so beautifully conceived prior to lifting a pipette (aka “the best laid schemes o' mice an' men”), so even the hardest deadline needs flexibility.  

An example. We soon discovered that we needed cells derived from more than one donor to ensure our ML was not overfitting its discriminatory power to distinguish disease from normal driven simply by the underlying genotype – after all, the difference between the risk and neutral allele that we focus on is a singular base, yet any two individuals differ by over 3 million bases. So, mid-project, we meet, we agree and the outcome is to provide the resources to quadruple the number of donors and carry out the editing to produce an isogenic suite. Hard to imagine doing this with Research Council funding. 

What are your takeaways from this experience and advice to others for nurturing successful collaborations?  

I have found this current collaboration immensely rewarding. Not without pressure, but what venture comes without that? Be it industry or academia, I think the key to a successful collaboration is not just the plan but the personal connection – the click factor. It doesn’t have to be there immediately but it does need to be nurtured. That way, when you hit a roadblock, and you will, you have people working with you to troubleshoot the problem and resource the solution. 

So, full circle; let’s say it like it is. These days, I find pharma less risk-averse than traditional academic funding routes such as Research Councils. Pharma will take a punt on a novel and/or high-risk project if the value of success is high. Pharma has the flexibility to adapt, change and provide resources as a project unfolds – as long as it looks like value will still be achieved. Value is usefulness not papers; that is not to say both cannot be achieved but the former is the priority.