Sir John B Gurdon has won the Nobel Prize in Physiology or Medicine 2012 for his discovery at the University of Oxford that the specialisation of cells is reversible, challenging the dogma that mature cells are irreversibly committed to their fate.
He wins the award jointly with Shinya Yamanaka for the discovery that mature, specialised cells can be reprogrammed to become immature cells capable of developing into all tissues of the body.
Their findings have revolutionised our understanding of how cells and organisms develop, said the Nobel Assembly at Karolinska Institutet in a press release announcing the award.
Sir John B Gurdon was born in 1933 in Dippenhall, UK. He did his undergraduate degree at Christ Church, Oxford, starting off studying Classics but switching to Zoology. He received his doctorate from the University of Oxford in 1960 and was a postdoctoral fellow at California Institute of Technology. He returned to Oxford as Assistant Lecturer in Zoology at the Department of Zoology in 1962.
A classic experiment
It was while he was at Oxford's Department of Zoology that he carried out a classic experiment published in 1962.
He hypothesised that the genome of a mature cell might still contain all the information needed to drive its development into all the different cell types of an organism. He replaced the immature cell nucleus in an egg cell of a frog with the nucleus from a mature intestinal cell. This modified egg cell developed into a normal tadpole. The DNA of the mature cell still had all the information needed to develop all cells in the frog.
Gurdon's landmark discovery was initially met with scepticism but became accepted when it had been confirmed by other scientists.
It initiated intense research and the technique was further developed, leading eventually to the cloning of mammals, the Nobel Assembly says.
Oxford stem cell biologist Professor Sir Richard Gardner, who knows Sir John and his research well, says the Nobel Prize for work that began in Oxford is 'entirely warranted'. He says: 'He’s been a highly regarded leader in the field for many, many years.'
Sir Richard explains that, after it was shown that DNA was the genetic material, it was realised that an embryo would need all the genetic information contained in our DNA to develop into all the tissues of the body. But an adult liver cell would only need a subset of genes, and a nerve cell would need a different subset. The question was what happened in the nerve cell to the DNA that was not needed?
'John showed that the genes were still there but inactive, and could be made active again,' says Sir Richard, who came to Oxford from Cambridge soon after Sir John went the other way. 'It showed us how cell specialisation happened: cells retained expression of some genes, but suppressed others.
'The key thing he showed was that as cells specialise, genes are not lost and that they are potentially accessible ... It’s also vitally relevant to the current excitement around regenerative medicine.'
Cloning 'became a reality'
Professor Chris Graham of Oxford University's Department of Zoology, one of Sir John's first students who worked with him at Oxford in the 1960s, says:
'He showed that you could take several nuclei from one individual and produce genetically-identical animals – that was his great achievement. People had talked about cloning a good deal but with John Gurdon’s work it became a reality.
'The importance of this work was immediately recognised: the early 1970s saw a substantial number of books about the ethical and biological consequences of cloning.
'The work that he did then is marvellous, but he has my admiration for the series of experiments he has done throughout his career. For instance, in 1971 at Oxford his was the first group to translate messenger RNA from a mammal into a protein – he showed that what was believed to be rabbit haemoglobin messenger RNA did indeed carry a message.'
Ethics & regenerative medicine
Julian Savulescu, Uehiro Professor of Practical Ethics at Oxford says:
'This is not only a giant leap for science, it is a giant leap for mankind. Yamanaka and Gurdon have shown how science can be done ethically. Yamanaka has taken people’s ethical concerns seriously about embryo research and modified the trajectory of research into a path that is acceptable for all. He deserves not only a Nobel Prize for Medicine, but a Nobel Prize for Ethics.
'Before Yamanaka’s breakthrough, which built on Gurdon’s work, this research could only be done on cells derived from live human embryos. Many people objected to the creation of embryos for research, describing it as cannibalizing human beings. They even objected to the use of embryos no longer required for IVF. This led GW Bush to introduce laws that retarded the field for years. Yamanaka was able to overcome all those objections and resuscitate the field.
'Yamanaka has opened the door to a completely new kind of medicine: regenerative medicine. Until now, dead or damaged tissue and organs, for example in the brain or heart, have been replaced by scar tissue. This results in loss of function, such as inability to talk or walk after a stroke, or heart failure after a heart attack.
'Regenerative medicine offers the prospect of replacing dead or damaged human parts with new functioning ones. It also opens a radically new way of studying the origin of disease: by creating tissue with disease, it can be experimented on in the laboratory, instead of in humans and animals. This is good for humans and good for non-human animals used in experiments. This is as significant at the discovery of antibiotics. Given the millions, or more lives, which could be saved, this is a truly momentous award.'
Sir John joined Cambridge University in 1972 and has served as Professor of Cell Biology and Master of Magdalene College. Gurdon is currently at the Gurdon Institute in Cambridge.
Legacy: modern stem cell research
Sir John has worked on frog embryology all his career, continuing to go into the labs in Cambridge 50 years on from the work he began in Oxford.
Shinya Yamanaka discovered in 2006 how intact mature cells in mice could be reprogrammed to become immature stem cells. Surprisingly, by introducing only a few genes, he could reprogram mature cells to become 'induced pluripotent stem cells' or iPS cells: immature cells that are able to develop into all types of cells in the body.
Research during recent years has shown that iPS cells can give rise to all the different cell types of the body. These discoveries have also provided new tools for scientists around the world and led to remarkable progress in many areas of medicine.
For instance, skin cells can be obtained from patients with various diseases, reprogrammed, and examined in the laboratory to determine how they differ from cells of healthy individuals. Such cells constitute invaluable tools for understanding disease mechanisms and so provide new opportunities to develop medical therapies.