Nobel Laureate Sir Martin Evans gives seminar in Clore Laboratory

6 March 2009

Sir Martin Evans & Professor Mike CawthornePrior to receiving an Honorary Degree from the University of Buckingham on 27 February 2009, Sir Martin Evans gave a seminar in the Clore Laboratory entitled ‘The origin of embryonic stem cells’.

In introducing Sir Martin, Mike Cawthorne, Director of Metabolic Research, noted that Sir Martin received his Novel Prize in conjunction with Mario Capecchi and Oliver Smithies for their discoveries of principles for introducing specific gene modification in mice by the use of embryonic stem cells. Whilst today we routinely use knock-out and transgenic mice in research studies, the background studies that led to the isolation of embryonic stem cells and their potential uses in medicine were less widely known.

Sir Martin’s research started in the 1960s working on early Xenopus (frog) embryos but he realised that molecular developmental studies require an organism with a better genetic potential than Xenopus. At that time mammalian embryos were extremely inaccessible but in vitro culture of the early pre-implantation stages had been developed.

After completing his PhD in 1969, he started on his own research programme. A colleague drew his attention to studies on mouse teratocarcinomas. These tumours were transplantable and originated from primordial germ cells in the foetal testis. From mice carrying the tumours Evans established clonal tissue culture, which retained their ability to differentiate as tumours in vivo. In 1975 he postulated that embryonic stem cells should be able to be cultured directly from normal embryos but it was another 6 years before this was achieved. Later it was shown that embryonic stem cells could be introduced into mouse blastocysts and develop into healthy mice with tissue contributions from the embryonic stem cells. Thus there was the realisation that embryonic stem cell differentiation was not abnormal but followed the normal pathways of early development.

Sir Martin recognised the possibility of transgenesis and mutagenesis with transgenes or mutations being incorporated in tissue culture prior to incorporation into mouse blastocysts. However, it was the parallel development of homologous recombination gene targeting that was developed by Smithies and Capecchi, together with the availability of cloned sequence for the target gene that was pivotal in the worldwide development of genetically manipulated mice and their use in medical research.