Sir John Gurdon’s ancestry at www.nobelprize.org could easily be mistaken for a crash course in English history. From the arrow of Bertram de Gurdon, which killed Richard Lionheart in 1199, to Sir Adam de Gurdon, a likely model for Robin Hood, and Sir John Gurdon of Assington, who had Oliver Cromwell as his guest in 1648. Their descendant John Bertrand Gurdon was the first to successfully clone an animal - a frog - in 1958. "Scientifically speaking, the cloning was almost a minor detail."
We were able to interview Sir John Gurdon (85) after his keynote lecture at the Annual Meeting of the Belgian Society for Stem Cell Research. Twenty years after he officially retired, he’s still working full-time in the Cambridge laboratory that was named after him, and active at the bench.
And he’s travelling around the world to deliver lectures. "I still receive about 200 invitations per year. But I don’t accept all of them - not even close." Fortunately for us, he did accept the invitation for today. "I have a strong connection with Belgium through the famous Professor Jean Brachet (a mid-twentieth-century professor at Université libre de Bruxelles and a key figure in the field of molecular biology - ed.). His help has been invaluable for my research. And Professor Vincent Pasque, who is now affiliated with KU Leuven, completed his PhD in my lab."
The importance of Gurdon’s 1958 discovery can hardly be overestimated. He showed that cells carry the potential to grow into any type of cell. Up to then, scientists had always assumed that, say, intestinal cells were fundamentally different from lung cells. This discovery was rewarded with a Nobel Prize in 2012, which he shared with Shinya Yamanaka, who had succeeded in reprogramming mature cells into stem cells.
As a child, Gurdon was interested in collecting insects - particularly moths - and breeding caterpillars. And yet, even the start of his scientific career was a close call. At the age of fifteen, when he was at Eton College, he came bottom out of 250 students in biology. His report card said it was quite ridiculous for him to even think of doing science. He was put on to learning Greek and Latin. After he left school, Gurdon’s parents paid for one extra year of teaching in elementary biology. This allowed him to pass the entrance exam: he was able to enrol as a student of zoology at Oxford.
The report from Eton is now in a frame, adorning the wall of his office at Cambridge. "It reminds me that it’s worth persisting if you find something that really interests you, even if the odds are against you."
New species discovered
Fortunately for science, that’s exactly what Gurdon did. His initial plan was to pursue a PhD in entomology, but he was rejected, possibly because he had offended the professor: when walking in the forests around Oxford, he had accidentally discovered an unknown insect species, which had thus far escaped the notice of the zoology department. "Luckily, another excellent professor took me on for a PhD in developmental biology. He gave me a challenging assignment: repeating an experiment that had previously been designed and executed by two American scientists, albeit without success: nuclear transfer, whereby you remove the nucleus from one cell and replace it with the nucleus of another cell."
Gurdon set to work - exactly sixty years ago - with the eggs of the South African clawed frog: "This frog makes eggs each month, while the frog that King and Briggs had been experimenting with only makes eggs two months per year. So that’s an advantage I had."
Where two renowned scientists didn’t have any luck, the twenty-five-year-old Gurdon succeeded. After quite a few failed attempts, he eventually managed to transfer the nucleus of a tadpole’s intestinal cell into an egg, which then grew into a normal tadpole. Without even meaning to, he had cloned a frog. "The real point of the experiment was to show that the nucleus of a mature cell contains all the necessary genes to make a complete individual or to produce any type of tissue. The cloning was sort of a by-product."
His discovery revolutionised cell biology. Did he already realise that at the time? "Yes. At that point, of course, we didn’t know how the field would develop. Much later, it became clear what the possibilities were and the interest in the subject gradually increased."
New eye cells
Gurdon completed his PhD, took a year off to do something completely different at Caltech, and then returned to find his frogs still in good health: "In those days, you could still take your time. So I only wrote the work up as a paper in 1962. After that, it still took about ten years before people actually accepted my results as correct."
Who is Sir John Bertrand Gurdon?
- ° 1933 in Dippenhall, United Kingdom
- Studies zoology at Oxford and successfully clones a South African claw frog in 1958.
- Obtains his PhD in 1960 and starts working as a postdoctoral researcher at Caltech.
- 1962-1971: affiliated with the faculty of zoology at the University of Oxford.
- 1972-1983: affiliated with the MRC Laboratory of Molecular Biology (University of Cambridge).
- Since 1983: affiliated with the Department of Zoology (University of Cambridge).
- Since 1991: affiliated with the Gurdon Institute (University of Cambridge).
- Knighted in 1995.
- Winner of the Wolf Prize in Medicine (1989), the Copley Medal (2003) and the Albert Lasker Award for Basic Medical Research (2009), among others.
- Awarded the Nobel Prize for Physiology or Medicine in 2012, together with Shinya Yamanaka.
It even took the Nobel Prize committee more than fifty years to recognise his research... "That’s a bit long, indeed (laughs). I think they waited until the therapeutic applications became more evident. When Dolly was cloned with the same technique in 1997, it became clear that you could apply nuclear transfer to mammals - and possibly even human beings."
And then there was the work of Shinya Yamanaka, with whom he shares his Nobel Prize. "He developed a method to make mature cells revert to the embryonic stage. This makes it possible to, for instance, turn skin cells into cells for the eye. I estimate that, in three or fours years, such reprogrammed cells will be a solution for macular degeneration, a condition that may lead to blindness. Amazing. Human cells will also be reprogrammable to test drugs. And all that goes back to that one key observation: all different cells in the body have the same genes."
Will we ever be able to clone human beings - should we want to, that is? "Experiments with nuclear transfer still often result in animals with malformations or disorders, so human cloning is not appropriate yet. Perhaps in the future, with genetic correction... But most people don’t consider it a very useful aim."
"Growing new organs’ That’s not science fiction, although I’m not sure about the time frame. You know, when I’d cloned that frog, a journalist asked me how long it would be before we’d be able to clone a mammal. I said it could be anything between ten and a hundred years. It turned out to be about forty, so I was proven right (laughs). It’s all very much a guess."
Meanwhile, he still spends his days in his lab at Cambridge. His current focus is on unravelling the precise mechanism of cloning: "Something in eggs, whether from frogs or from mammals, can reset the genetic expression of a nucleus. I would very much like to know in detail how that works."