Cardiff School of Biosciences Biomedical Building Museum Avenue PO Box 911 Cardiff CF10 3US UK Tel: +44 (0)29 20 874120 Fax: +44 (0)29 20 874116 Email: Martin Evans is Director of the School of Biosciences and Professor of Mammalian Genetics of Cardiff University. After graduating from Cambridge in 1963 I decided on a career studying the genetic control of vertebrate development and undertook research for my PhD at University College London in the department of Anatomy and Embryology. During this early research on changes of messenger RNA profile during neural induction in Xenopus I was using pioneering techniques of agarose gel electrophoresis and metabolic double labelling. These experiences led to a realisation of the need for a tractable experimental system to study development in isolation from the whole embryo and with the possibilities of genetic manipulation and I therefore chose to explore the use of cultures of mouse teratocarcinoma stem cells in tissue culture systems. I was the first to maintain these cells in tissue culture under conditions where their ability to differentiate was retained indefinitely. Studies from my laboratory showed extensive differentiation of these cells in culture and the means whereby this happened was shown to be that corresponding to organisation of a normal mouse embryo. Moreover these cells would participate extensively in normal development in combination with a normal embryo and give rise to adult mice. These studies showed the close relationship between these "EC" cells and normal mouse embryos but it was not until 1981 after my return to Cambridge that together with Matt Kaufman he was able to isolate similar cells from normal mouse embryos. Subsequently we rapidly demonstrated, together with my student and post-doc Liz Robertson and student Allan Bradley, that these cells which became known as "Embryonic Stem Cells" (ES cells) were able to be used to fully regenerate fertile breeding mice from the tissue culture cells and that these could therefore carry mutations introduced and selected or screened for in culture. This is now the basis of all the mouse knockout and targetted genetic manipulation. Since pioneering these fundamental developments which created new routes to experimental mammalian genetics and hence functional genomics, I have been exploiting them using gene knockout and gene trap methods both for novel discovery and to create animal modes of human disease. From my laboratory came the first demonstration of gene therapy to cure the deficit in Cystic Fibrosis in the whole animal and recently, from a mutated mouse model, insights into the breast cancer gene BRCA2 function. I have published 124 scientific papers, including the following. I am a Fellow of the Royal Society and a founder Fellow of the Academy of Medical Sciences, Doctor of Philosophy and Doctor of Science.