From tadpole guts to Nobel Prize: John Gurdon’s UCL Prize Lecture in Clinical Science

Written by James Arrich and Isobel Weinberg, both UCL PhD students

Do all the cells of the body possess the same set of genes? This was the question facing a young John Gurdon as he embarked upon his PhD 60 years ago. His research has transformed the way we understand biology in a way that holds promise for the treatment of many common diseases. He received the Nobel Prize in 2012 and on 10 November he visited UCL to give the UCL Prize Lecture in Clinical Science and receive the accompanying medal.

John Gurdon made an unpromising start to his scientific career: at school, he was ranked last out of 250 students for Biology, and was required to give up science and study Classics. Nevertheless, he later chose to switch his degree from Classics to Zoology and then embark on a PhD in cell development.

Ground-breaking work soon followed. His PhD centred upon the technique of nuclear transplantation.

That is, he would transplant the nucleus of one cell into an egg cell whose own nucleus had been removed (it had been ‘enucleated’) and then watch to see how this egg (with its transplanted nucleus) developed.

In a famous set of experiments, he took a specialised gut cell from a tadpole and transplanted the cell’s nucleus into an enucleated egg. Astonishingly, he demonstrated that such eggs (with their transplanted ‘gut’ nuclei) could develop into healthy frogs. That is, the nucleus of a gut cell that was wholly specialised to absorb nutrients still possessed all the genes required to make an entire new frog.

The implications were huge. Not only did all the cells of an organism possess the same genes, but clearly some factors in the egg cell could revert an adult, specialised cell into a stem cell capable of generating any other cell type. The phenomenon was termed nuclear reprogramming and Gurdon has spent the rest of his career unravelling the mechanisms that underlie it.

It wasn’t until 2006 that Shinya Yamanaka, the man who shared the 2012 Nobel Prize with Gurdon, identified the cocktail of factors required to revert any adult cell back to this stem cell state. As a result it is now possible to take some skin cells from your forearm, culture them with these factors and then form them into any cell you like, whether spindly nerve cells or beating heart muscle cells.

The UCL Prize Lecture in Clinical Science is awarded for basic science that has the potential to translate to future patient care. Many of the diseases that plague modern medicine are degenerative in nature; that is, they result from the loss of specialised cells that the body is unable to replace. Thus, the ability to make new and healthy cells for a particular individual has vast therapeutic potential.

In his lecture, Gurdon highlighted age-related macular degeneration as a potential first step for therapy. This is a common cause of blindness that results from the loss of specialised cells that lie at the back of the eye. Gurdon described how, by adopting Yamanaka’s approach, a few patients with macular degeneration are currently having sheets of these specialised cells grafted into the backs of their eyes.

The technique has been highly successful in animals and Gurdon‘s frustration at the regulatory and legal caution that is hampering the transfer to humans was palpable. Once honed, this therapeutic approach could be extended to bigger problems, perhaps replacing the heart muscle that dies following a heart attack, or the neurons lost in those with dementia.

Before the lecture, a group of the current UCL MBPhD students met Gurdon for tea. Despite his eminence, he expressed interest in our views on everything from how cells detect a concentration gradient to Scottish independence. Gurdon described how, since childhood, he had been fascinated by how cells produce colourful patterns on moths’ wings, and how this had spurred his interest in developmental biology. The enthusiasm with which he posed to us the fundamental questions in his field showed his scientific curiosity is undimmed by a lifetime’s research.

The authors are both students on the UCL MBPhD, a programme designed for students who would like to pursue a clinical career that embodies a substantial research component.