Tuesday, January 1st 2013
I was completely taken by surprise when receiving the news that I was being recommended for an OBE for contributions to science. It made me reflect on how I got where I am today.
The answer was simple – thanks to the huge support of family and of many valued colleagues with whom I had worked over many years. I realised too that I have been working on CF for the best part of 30 years – from before the gene was identified, to the present day as we test to see whether gene therapy may be clinically useful.
In 198I, I interviewed for an MRC Recombinant DNA Research Fellowship to work with Ed Southern and was asked the question 'how would you clone the CF gene?' I must have said something at least half plausible because I got the Fellowship, perhaps in part because I put the question back to the panel to which they answered 'we haven't a clue, that is why we asked you'. Of course we all now know what happened next – in 1985 the gene for CF was linked to chromosome 7 and the CFTR gene itself was cloned in 1989, kick-starting the whole Human Genome Project. The CF Trust awarded me my first grant in 1985, which proposed a novel approach to clone the gene through somatic gene targeting. It was a long shot that we would succeed ahead do the other established grouped, but it prepared us to engineer a mouse model through the newly established capacity gene targeting in ES cells as soon as the gene was cloned.
That was what Julia Dorin achieved in 1992, work that start of our long-standing collaboration with Eric Alton. It coincided too with a friendly rivalry with Steve Hyde and Deborah Gill, who were collaborating with the Cambridge group, under gene targeting pioneer (and later Nobel prize winner) Martin Evans.
The Edinburgh, London and Oxford groups were all motivated to use these models to establish proof-of-principle for gene therapy, which we all did successfully. Within a remarkably short space of time, London, Oxford and Edinburgh had independently taken non-viral gene therapy to the clinic, each with some evidence for success, but we only saw partial gene correction and it was short-lived.Rosie Barnes, then Chairman of the CF Trust and recently awarded an OBE for her charitable work, recognised the added value that would accrue if we could all work together rather than in competition.
And so the UK Cystic Fibrosis Gene Therapy Consortium was established in 2001. This has been enormously challenging, but also hugely rewarding and a true testament to the collective achievements of a very large group of talented scientists and clinicians.Working as part of that Consortium has given me as much satisfaction as any in my research career. There is still a way to go, but I am deeply impressed by the sterling efforts of Eric Alton, Uta Griesenbach, Jane Davies and Tracy Higgins and their team in London, together with Steve Hyde and Deborah Gill and their team in Oxford and with Chris Boyd and Alastair Innes and their team in Edinburgh.
The Consortium has a successful Phase 1 single dose study under its belt and is now in the throes of a Phase 2 multi-dose study that will really test the Consortium's approach. Importantly, the Consortium also has exciting new ideas for next-generation gene therapies undergoing evaluation in the laboratory. Funds permitting, a further phase of clinical trials could start in the next 3-4 years.
"There is cause for cautious optimism that they are on track to make gene therapy a viable option in the long term for treating CF."
Prof David Porteous OBE