Feature: Changing Fates – Sir John Gurdon
Among the clutter of John Gurdon’s brightly lit Cambridge office sits a picture frame, displaying a small scrap of browning paper from an early school report. It reads: “I believe he has ideas about becoming a scientist…this is quite ridiculous…it would be a sheer waste of time, both on his part and of those who have to teach him.”
Professor Sir John Gurdon is now a knight of the realm, a Fellow of the Royal Society, a former Governor of the Wellcome Trust and the scientist who kickstarted the field of cloning.
That he should have so utterly disproved his schoolteacher’s assessment is testimony to his passion for science – and to an element of luck.
“There’s a saying: ‘Luck favours the prepared mind’,” he says. “Ninety per cent of the time things don’t work, but when they do you have to seize the opportunity.”
Change of direction
Had history taken a different turn, John Gurdon wouldn’t even be a scientist. Educated at Eton, he was on course to study classics, only to receive a surprising offer from an Oxford admissions tutor who had neglected to fill all the places at his college. Fate, if a scientist believes in such things, led the young John to follow his childhood interests and read Zoology at Christ Church.
A PhD followed in 1962, and there again fate intervened. Challenged with working on transplanting a nucleus from one cell to another, John successfully ‘cloned’ the South African frog Xenopus laevis from a tadpole’s intestinal cell (“a pivotal piece of luck,” he says) by transplanting the nucleus into an empty Xenopus egg cell. The result was an organism genetically identical to the tadpole before. This proved that cells can be ‘reprogrammed’ to start anew.
The discovery caused shockwaves around the scientific community, not least because a mere graduate student had disproved previously held dogma developed by more famous and established scientists.
“In the 1950s, no one knew if all cells in the body had the same genes,” says John. “The hypothesis was that as cells grew they lost the genes they didn’t need.” His finding proved that cells all carry the same genes, with other factors telling the cell which to use. The biologist John Haldane dubbed John’s achievement ‘cloning’, borrowing a term from plant biology, and a new field was born.
“If you take a skin cell nucleus and put it into an egg cell which has had its own genes removed, you can get a normal animal,” John explains. “The question then was: how can it do it?””
Get with the reprogram
John’s current research, funded by three successive Wellcome Trust grants, focuses again on the Xenopus egg cell. His research group is working to tease out the molecules and mechanisms through which they reverse specialisation. If they can work this out, it may one day be possible to create an endless supply of embryonic stem cells from adult cells.
“It’s remarkable that an egg cell – this single cell – has every instruction it needs to turn itself into a complex organism,” says John. “It knows how to go through this remarkable process; that is an amazing phenomenon. Yet there are very few people worldwide trying to work out what the components of eggs are.”
There are two things you need to do to reprogram a cell: reactivate suppressed genes and activate other genes.
John says: “In a specialised cell, a lot of genes are switched off by suppressor molecules. We want to find out what these suppressors are and how the egg removes them in reprogramming. The other thing is when you start up an embryo, certain genes need to be activated – we want to identify these and how they work.”
His great hope is that we can one day generate banks of replacement heart, brain, blood, skin or other cells that are grown from our own cells and thus avoid the problems of rejection and immunosuppression that come with current tissue and organ transplants. And, unlike new methods such as induced pluripotent stem cells, reprogramming of egg cells remains, he says, the most “natural” method, harnessing an inherent property of egg cells and creating stem cells most amenable to clinical transplantation.
Prospects for regeneration
We sit in his ecletically decorated office on the second floor of the Gurdon Institute, formerly the Wellcome Trust – Cancer Research UK Institute of Cancer and Developmental Biology, renamed in his honour (“A great honour but a strange feeling…like a coded message that you should be dead but have failed to do so!”). John founded the centre in 1989 with his colleague Ron Laskey and chaired it for 12 years.
“We started with two groups and now there are 18. It means we can have a greater diversity of work in roughly the same field. And being in Cambridge is hugely beneficial – if we want to do something there’s almost always someone nearby doing something like it.
“The future of cloning and stem cells excites him and, though realising the vision of regenerating entire organs is still some way away, John believes that regenerating individual cells is on the horizon. He points to the work of Professor Pete Coffey, Director of the London Project to Cure Blindness and Professor of Cellular Therapy and Visual Sciences, who has managed to regenerate retinal epithelial cells from stem cells to treat macular degeneration in mice.
“Progress in replicating individual kinds of cells is really quite hopeful, and treatments are feasible if you think of neurological diseases such as Parkinson’s disease where certain cells are defective. It’s difficult but it will happen.”
At the age of 77, he is fuelled by the same curiosity and passion that took him to Oxford in the 1950s, work that still spurs him to arrive early in the lab.
“I once asked Dame Miriam Rothschild [the British zoologist and author] what it is like when you reach an older age. She said to me: ‘You just have to focus more and more on what you really know about.’ So if you focus down, one can still get a lot done, even in your later years.”
In that fateful school report, his teacher wrote that the young John “will not listen, but will insist on doing his work in his own way”. How fortunate.
- Gurdon JB. The developmental capacity of nuclei taken fromintestinal epithelium cells of feeding tadpoles. J Embryol Exp Morphol 1962;10:622-40.
- Gurdon JB, Colman A. The future of cloning. Nature2000;402:743-6.
- Gurdon JB, Byrne JA. The first half-century of nuclear transplantation. Proc Natl Acad Sci USA 2003;100:8048-52.
- Gurdon JB. From nuclear transfer to nuclear reprogramming: the reversal of cell differentiation. Ann Rev Cell Dev Biol 2006;22:1-22.
- Gurdon JB, Melton DA. Nuclear reprogramming in cells. Science 2008;322:1811-5.
Image: Sir John Gurdon. Credit: Wellcome Images.