No Surprise Here Then

The announcement that the 2012 Nobel Prize in Physiology or Medicine had gone to John Gurdon – jointly with Shinya Yamanaka – might well enter the Guinness Book of Records as the least surprising in history. Certainly in Cambridge, where Gurdon has worked since 1971, for as long as I can remember it has always been a matter of ‘when’ not ‘if.’ I guess having The Institute for Cell Biology and Cancer named after you, as it was in 2004, is a bit of a clue to his standing.

Sir John Gurdon, FRS

Sir John Gurdon, FRS

The work that launched Gurdon’s career in the 1960s showed, in effect, that the nucleus of every cell in the body contains the same genes – that is, the complete sequence of the individual’s DNA. The basic method was to use frogs, replacing the nucleus of an egg cell with that of a mature cell taken from the intestine. The fact that the modified egg turns into a normal tadpole shows that all the information needed to make the animal is retained in the DNA code of fully developed cells.

Frog eggs

Frog eggs

Many years ago (over 30, I’m abashed to calculate) I was lucky enough to receive a personal demo of how to manipulate frog eggs in Gurdon’s lab from a friend who worked with him. As everyone knows, the eggs are quite big – about 1 mm in diameter – so you don’t need a microscope to see them – and in her hands fiddling with their nuclei looked pretty easy. It’s not, of course, which is why Gurdon’s early experiments caused controversy: not only were the results completely unexpected but quite a few people failed to reproduce them until sufficiently skilled hands had a go.

Shinya Yamanaka, working in Kyoto, followed this up by unveiling the specific genes that are needed to make ‘pluripotent’ cells – cells that have the capacity to develop into any of the many cell types that make up a body. In a series of the most elegant molecular biology manipulations, he started with a large panel of genes previously implicated in controlling embryonic stem cells. From these he teased out four that, when ‘switched on’ to make their encoded proteins, can confer pluripotentcy.

Dr. Shinya Yamanaka

Dr. Shinya Yamanaka

Their work has already had massive consequences. It’s founded a new branch of science – stem cell biology. Most famously, this has produced Dolly the Sheep – the first mammal to be cloned from an adult cell – but it has also led to skin being grown in the lab for use as grafts to repair burns and, even more astonishingly, to the creation of entire organs (e.g., bladder) from the patient’s own cells to provide a transplant that will not give rise to an immune response and hence rejection.

It has also had an impact on cancer – perhaps unsurprisingly given that the genes identified by Yamanaka can rejuvenate cell growth, and abnormal proliferation lies at the heart of the disease. Two of the pluripotent genes he identified are ‘oncogenes’, that is, they can help to drive tumour development (Myc and Klf4). This has generated the ‘cancer stem cell hypothesis’ that arises from the fact that some of the cells in tumours have features similar to those found in embryonic stem cells (e.g., they can be distinguished because they make the some of the same surface proteins). The significance, of course, is that working out how to control pluripotency may also reveal ways of targeting cancer cells.

So none would argue the award is overdue – Gurdon’s former schoolteacher, who wrote that ‘his ideas about becoming a Scientist’ are ‘on his present showing … quite ridiculous’ and whose report he still keeps, is presumably imparting his perception in the classroom in the sky.

But how has the Prize affected Sir John, you might wonder? Well, not detectably in that he has commented that‘It isn’t going to be particularly productive to clear off to some exotic place and I don’t have a yacht’ and indeed, most days you can still spot a tall, distinctive figure walking determinedly along Tennis Court Road, where The Gurdon Institute lives, usually with woolly hat pulled firmly down against the elements, at 79 years young the very embodiment of what science is really about.

References

Gurdon, J. B.; Elsdale, T. R.; Fischberg, M. (1958). “Sexually Mature Individuals of Xenopus laevis from the Transplantation of Single Somatic Nuclei”. Nature 182, 64–65.

Gurdon, J. B. (1962). “The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles”. Journal of Embryology and Experimental Morphology 10, 622–640.

http://www.nobelprize.org/nobel_prizes/

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