Philip Cohen: Driving drug development
Today the MRC is honouring two of our most eminent scientists with the MRC Millennium Medal, which recognises research that has led to significant health and economic benefits. In the first of our profiles of the recipients, we meet Sir Philip Cohen, who has devoted his 40-year career to studying a type of cell regulation called protein phosphorylation. His collaborations with the pharmaceutical industry have helped to accelerate the development of new drugs for a variety of diseases. He spoke to Katherine Nightingale about ‘blue skies’ research, working with industry and birdwatching.
If you need reminding of just how long researchers need to toil away in the lab before their findings might impact on the ‘real world’, look no further than Philip Cohen. Now credited as partly responsible for one of the largest and fastest growing areas of drug discovery, it was 25 years before he first got a call from a pharmaceutical company.
“People used to say ‘Oh, what you’re doing is interesting but it will never be the slightest bit of use for improving health or for wealth creation’,” Philip recalls.
That ‘interesting’ area is phosphorylation, a type of cell regulation that involves the attachment to, or removal of, phosphate groups from proteins, thereby switching their biological functions on or off, or making them more or less stable. Once thought to be a highly specialised process, Philip’s research helped to show that it was, in fact, a universal control mechanism.
“The deregulation of the process is the cause of many diseases, such as arthritis, cancer and diabetes,” says Philip. “There are now many cancer drugs that target phosphorylation processes, and excitingly, the first two drugs for immune disorders such as rheumatoid arthritis have recently been approved.”
There are now 24 approved drugs and a further 150 in clinical trials. The sales of these drugs were £18 billion globally in 2011.
“That shows how important it is to fund ‘blue skies’ research. It can take an awfully long time for research to reach the stage where it becomes obvious how it can be exploited for the benefit of mankind.”
Collaboration is key
That first industry phone call came in 1994, when Philip was asked to join an advisory board of SmithKline Beecham (now GlaxoSmithKline). He accepted and found it was mutually beneficial. “We were able to get hold of a compound that was relevant to our research, and they got hold of our reagents. That was when I first realised the potential benefit to patients of our work.”
It also became the model for how Philip has collaborated with industry ever since.
In 1998 he established the Division of Signal Transduction Therapy (DSTT), a unique collaboration between researchers from the MRC Protein Phosphorylation Unit (PPU) — of which Philip was the first Director when it was established in 1990 — the College of Life Sciences at the University of Dundee and six pharmaceutical companies. The collaboration involves 200 research and support staff in Dundee and has brought in more than £50m in funding in its 14-year history.
For Philip, this unusual longevity is down to a few simple things. The critical mass of leading researchers in one place means it’s easy for companies to access all the knowledge they need about phosphorylation, as well as key technologies and reagents. The academic labs work to industrial standards, deliver first class reagents on time and maintain confidentiality — of all which have led to trust developing between the academic and industrial partners.
Instead of spinning out companies, Philip is happy in this kind of collaboration. “My academic salary is perfectly adequate — I’m not interested in making money for myself and I’m too busy to set up my own companies! I try to put in place the systems that interest companies in coming to Dundee and which help these companies to thrive — we help them develop drugs or to market reagents and technologies, and these are also useful in our own research.”
He’s recently replicated this model as founding Director of the Scottish Institute for Cell Signalling, a unit set up in 2008 with £10m funding from the Scottish Government. Its first division, the Protein Ubiquitylation Unit, aims to create a similar critical mass of researchers and expertise, this time in the discipline of ubiquitylation, a cell regulation process that could prove just as fertile ground for drug discovery as phosphorylation.
And just because Philip doesn’t set up spin outs himself, it doesn’t mean that they haven’t resulted from research in the MRC unit and the DSTT. For example, Dundee-based Upstate, a spin out that commercialised a DSTT technology called kinase profiling, grew from nothing in 1999 to 125 employees in 2004, paying considerable royalties to the MRC PPU.
No end in sight
Philip has been funded by the MRC since 1978, when he was awarded his first programme grant for research on how insulin and adrenalin regulate carbohydrate metabolism. Later, as the general significance of phosphorylation came to be realised, he used the technologies and approaches he had developed during this research to tackle other projects.
Seven years ago he switched research fields to study the regulation of the immune system, a move he puts down to the security of his MRC funding. Bedding into the new field was a steep learning curve, he says, but one that’s beginning to pay off.
Philip might not have got into biochemistry at all if he hadn’t imagined it to be a kind of combination of his beloved bird watching and chemistry — a subject he was good at in school.
“My father was a chemist — he invented the ink used to print the first ever colour supplement of a Sunday newspaper, the Sunday Times, around 1963 — and it was somehow expected that I would go into science rather than the arts. I stayed on to do a PhD at University College London after graduating and got hooked on research.”
And he’s not thinking of leaving research anytime soon. “I have funding until about April 2018, by which time I’ll be 73. But as long as I’m having fun and still making significant contributions, I’m not planning to stop.”