The Nobel Prize: J B Gurdon

the nobel prize

Sir John Gurdon was awarded the 2012 Nobel Prize in Physiology or Medicine, jointly with Shinya Yamanaka,‘for the discovery that mature cells can be reprogrammed to become pluripotent’. Here he writes about the start of his career in research:

After completing the Department of Zoology course at Oxford in 1956, I was invited to do a PhD with Dr Michail Fischberg, the Oxford University lecturer who taught developmental Biology.

Fischberg suggested to me that I should try to carry out somatic cell nuclear transfer in Xenopus, a procedure for this having been recently published by Briggs and King (1952). Once the technical obstacles had been overcome, largely as a result of good luck and hard work, the work proceeded extraordinarily fast. By the end of my PhD I had succeeded in obtaining normal development of intestinal epithelium cell nuclei transplanted to enucleated eggs of Xenopus. When these tadpoles had eventually reached sexual maturity, I was able to publish a paper entitled ‘Fertile intestine nuclei’. This was the first decisive evidence that all cells of the body contain the same complete set genes, answering a longstanding and important question in the field of Developmental Biology. However it also showed very clearly, as was commented on in my papers at the time, the remarkable ability of eggs to reprogramme somatic cell nuclei back to an embryonic state. This phenomenon attracted increasingly large interest, and led to the idea of cell replacement using accessible adult cells, such as skin cells. A key

future discovery was that of Martin Evans (Nobel Prize 2006) that a permanently proliferating embryonic stem cell could be established from mouse embryos. Under appropriate conditions these cells could be caused to differentiate into different cell types. The combination of this work on somatic cell nuclear transfer and the derivation of embryonic stem cells in mammals made it realistic to think of cell replacement for human diseases. A huge boost for this idea was later provided by Takahashi and Yamanaka (2006), with the discovery that the over - expression of certain transcription factors can also yield embryonic stem cells from adult somatic tissues.

Design of a somatic cell nuclear transfer experiment using unfertilised eggs as first designed by Briggs and King (Briggs and King, 1952) for Rana pipiens and as used subsequently in Xenopus; in Rana, enucleation is by hand with a needle, and in Xenopus by ultraviolet light irradiation (Gurdon, 1960a)

Photo: Jonathan Player

Photos: Alastair Downie

Sir John Gurdon’s Nobel Prize medal

Sir John Gurdon delivered his Nobel lecture entitled ‘The egg and the nucleus: a battle for supremacy’ on 12 December 2012 at the Karolinska Institute in Sweden. The concluding paragraph of his lecture ‘overviews and prospect’ is reproduced below:

The process of nuclear reprogramming by eggs and oocytes can be seen as a conflict between the cytoplasm of an egg, whose components are designed to promote rapid DNA replication and then transcription, and the components of differentiated cell nuclei, whose function is to maintain a stable state. The cytoplasm of an egg is specially designed to activate the highly condensed and specialized nucleus of sperm, with 100% efficiency. Not surprisingly, the same components are effective at activating the nucleus of a somatic cell. The difference is that a somatic cell nucleus has become, during the process of cell differentiation, highly resistant to activation by egg cytoplasm in a way that is different from sperm nuclei. These nuclei of differentiated cells are provided with molecules that stabilise their differentiated state and resist reversal or rejuvenation. If differentiated cell nuclei could be too easily switched to an embryonic state, this could permit the reversal of differentiation and lead to cancer.

The experimental work described here has centred on the use of amphibian eggs and oocytes because of the abundance of material and ready availability offered by them, an advantage that was very clear to developmental biologists up to the 1950s. The general principles that have emerged from work on amphibia seem also to apply to mammals and other vertebrate species. A full understanding of nuclear reprogramming by amphibian eggs and oocytes may well facilitate nuclear reprogramming in mammals, including humans, and hence contribute to the eventual therapeutic application of cell replacement.