This year’s Nobel Prize for Medicine was shared by Professor Sir Martin Evans of Cardiff University and two American scientists, Professor Oliver Smithies and Professor Mario Capecchi, for their work on gene targeting in mice and isolating embryonic stem cells.
Professor Allan Bradley, Director of the Welcome Trust Sanger Institute, who was Martin Evans’ final-year undergraduate student, PhD student and postdoc, said:
“This is wonderful news that recognizes the development of ES cell technology. The use of ES cells to modify genes in the mouse by gene targeting and other technologies has transformed our ability to evaluate gene function and test the role of genetic variants in health and disease. These technologies were developed in parallel and brought together in the late 1980s.
“The concepts developed in Martin’s, Mario’s and Oliver’s laboratories allow researchers worldwide to examine gene activity in mice and other organisms.”
Sir Leszek Borysiewicz, MRC chief executive, said:
“Both personally and professionally I am delighted that Sir Martin’s work has been recognised with a Nobel prize. MRC support for his work spanned three decades, his research is an example of excellent science leading to wider applications which will be of benefit to human health in the long-term.”
Professor Robin Lovell-Badge, Head of the Developmental Genetics Division, MRC National Institute for Medical Research, said:
“This is excellent news! It is long overdue, but it must have been a very difficult decision for the Nobel Committee, in part because of the involvement of many others in the work that led up to the discoveries. However, all three clearly deserve this honour. Martin Evans discovered Embryonic Stem cells in the mouse, which can be manipulated in cell culture and then returned back into early embryos where they will contribute to all cell types of the resulting mouse. Meanwhile, Mario Capecchi and Oliver Smithies independently worked on gene targeting, a method used to create specific alterations in gene sequences within the genome of cells. It was the combination of the two that allowed genes to be mutated or modified at will in mice. ES cells have many other uses, however, both in other ways to manipulate the genome and as a source of cells for cell-based therapies. Gene targeting relies on introducing pieces of DNA isolated in the lab back into cells such that they can find matching sequences within the genome and recombine with them. This occurs at high frequency in organisms such as yeast, where it was used long before the work of Cappechi and Smithies, but they showed that it can also work in mammalian cells, albeit at low frequencies, and developed ways to find the rare cells where the targeting took place.”
Dr Duncan Baird, University of Cardiff, said:
“By providing powerful tools to allow us to understand the contribution that genes play in human disease, the development of gene targeting was a significant advance, that has had a broad ranging impact on biomedical research worldwide.”
Professor Farzin Farzaneh, Professor of Molecular Medicine at King’s College London, said:
“In terms of medical genetics, this news is most welcome. This is a well deserved and timely prize for these scientists, who have made significant contributions to the understanding of the genetic basis of a number of human diseases.
“They have discovered some of the fundamental mechanisms involved in gene function. They have also developed techniques for the selective destruction of specifically targeted genes, in a technique called gene knockout.
“This technology has enabled the selective destruction of specific genes in mouse stem cells, thus allowing the creation of mouse models of human genetic disorders.
“These models have helped the understanding of the detailed mechanisms involved in the development of these disorders and have therefore helped the development of suitable treatments for them.
“The vital work of these scientists will continue to have a significant impact on many aspects of medicine for years to come.”
Professor Paul Sharpe, Head of Craniofacial Development at King’s College London, said:
“This is great news and long overdue. Together this trio of people developed methodologies that have revolutionised the way we study gene function in mammals.
“Gene targeting, a way of altering gene structure and hence function, in animals, provides a direct way to investigate the role of particular genes. In addition, genes can be altered in animals to reproduce mutations found in human diseases and thus provide genetic animal models of human diseases.
“The impact of their pioneering work cannot be overstated since it changed the way all areas of mammalian biology and medicine are studied.”
Jo Tanner, Chief Executive, Coalition for Medical Progress, said:
“This award acknowledges the fact that if we are ever going to find cures for genetic conditions such as Muscular Dystrophy and Cystic Fibrosis, scientists will need to work on animal models, identifying the genetic defects responsible and correcting them in animals before trialling potential treatments in humans. This group’s work has given hope to many thousands of people currently suffering from incurable genetic conditions.”
Professor Steve Brown, Director of the Medical Research Council Mammalian Genetics Unit, said:
“The fundamental techniques developed by Martin Evans and his fellow winners have allowed scientists to unravel how genes work in mammals. Together, they figured out how to remove one gene from a mouse at a time allowing us to study how the loss of a gene might disrupt diverse biological processes from development to the function of the brain. As mouse and human genomes are almost identical this approach is having an enormous impact on our understanding of human disease. The ability to study how individual genes might cause disease, leads to enormous opportunities for the development of new approaches to therapeutics and treatment.”
Professor Kay E Davies, MRC Functional Genetics Unit, University of Oxford, said:
“The award of this Prize is long overdue. The creation of transgenic models is a vital tool in the understanding of disease as well as being central for the provision of in vivo models for the design of new therapies. The impact of their work on biology and medicine has been immense and promises to continue to be so.”
Dr Wolf Reik, Head of the Laboratory of Developmental Genetics and Imprinting, at the Babraham Institute, said:
“This is excellent news. Martin Evans paved the way to targeted genetic manipulation in mammals by isolating ES cells (embryonic stem cells which by the way also stimulated the stem cell revolution we see today). Smithies and Cappechi developed technologies for accurate targeting of specific genes in these cells. The cells can then be reintroduced into animals (such as mice) resulting in permanently genetically altered organisms. This technology is particularly powerful to establish the function of every gene in the mammalian genome, and to create animal models of human diseases, leading to new treatments.”
Professor Stephen O’Rahilly, Head of the Department of Clinical Biochemistry, University of Cambridge, said:
“The development of gene targeting technology in the mouse has had a profound influence on medical research. Thanks to this technology we have a much better understanding of the function of specific genes in pathways in the whole organism and a greater ability to predict whether drugs acting on those pathways are likely to have beneficial effects in disease.”
Dr Bill Colledge, University of Cambridge, who worked in Prof Marin Evans’ lab from 1988 to 1995, said:
“This award is an acknowledgment of the outstanding contribution that Martin Evans played in developing the technology that allows us to study the function of genes in a whole animal.”
Martin Rees, President of the Royal Society, said:
“This is a fitting recognition of Sir Martin’s ground-breaking research on embryonic stem cells. He a world leader in mammalian genetics and his research has undoubtedly increased our understanding of human diseases. Stem cell research has immense potential. It is a field to where UK scientists such as Martin, have made pioneering contributions and maintain a powerful presence.”
N.B. Sir Martin Evans was elected a Fellow of the Royal Society in 1993.