John Gurdon: A laureate against all odds

Professor John Gurdon and Professor Shinaya Yamanaka were awarded the Nobel Prize in Medicine or Physiology 2012 for the discovery that mature cells can be reprogrammed to become pluripotent. A paradigm-shifting concept which has changed our view on cellular specialization forever.

I met with Professor Gurdon at the Grand Hotel two days before the Nobel festivities. Although tired from a hectic Nobel week in Stockholm he was happy and engaged when he spoke about his discovery and his research.

The godfather of cloning

Gurdon’s part of the discovery could in short be described as the beginning of cloning, and he is sometimes also referred to as “the godfather of cloning”. The starting point for his finding was when he started as a PhD student in Professor Fischberg’s group at Oxford. He was encouraged to try to achieve nuclear transplantation in Xenopus frogs. By implanting the nucleus of an adult frog cell into a frog egg that had its nucleus removed Gurdon showed that the result could be a functional, cloned tadpole. Hence, that the specialization of cells is reversible. His landmark study was published in the Journal of Embryology and Experimental Morphology in 1962. 

However Gurdon’s results contradicted earlier views and were widely scrutinized. Many people in the field were reluctant to accept the conclusions of a graduate student over the earlier findings of senior scientists Briggs and King. 

“Their experiments concluded that irreversible nuclear changes do take place as cells begin to differentiate,” explains Gurdon. “They reached the conclusion that genes were being lost or permanently inactivated.”

And their results were entirely correct for the kind of frog they tested, Rana pipiens. It turned out that Xenopus was a better model for these experiments.

“The top researchers in the field concluded otherwise, so of course I encountered a lot of skepticism,” Professor Gurdon agrees. “At the time I did not realize the full impact of the finding.”

Gradually people started to conclude that the experiments were correct. Professor Fischberg found a genetic marker which was able to show that the resultant embryo or animal carried the genetic marker of the introduced nucleus, rather than the marker of the egg whose own nucleus that was intended to have been removed. This marker was very crucial for Gurdon’s work. Later he and his colleagues were also able to obtain normal feeding-stage larvae from a wide range of adult organs, such as kidney, lung and skin, and the general principle of genome conservation during cell differentiation was established.

A waste of time

Skepticism was not new to John Gurdon. He actually encountered it already at the age of 15. His interest in biology came early on. His fascination for insects came from an aunt who used to catch him butterflies and he liked to set them and find out what they were. His parents were very supportive and had enough money to send him to the well renowned private school Eton. Gurdon had only completed one term when his master wrote a report saying that “Gurdon wanting to be a scientist was a total waste of time”. He was taken out of science and sent to study classics instead. “Luckily my parents were still very encouraging and supported me in my wish to become a scientist,” says Gurdon. 

Luckily my parents were still very encouraging and supported me in my wish to become a scientist.

Through family connections an interview was arranged with a professor of zoology in Oxford and his parents paid for another year of private tuition in elementary science.“Compared to my first teacher I now had a very good mentor, who was very supportive,” he says.

Therapeutic benefit

Like every professor Gurdon has to cope with the time consuming task of applying for grants and funding for his research. When it comes to basic science it could be quite difficult.

“Having a clinical application is easier. But I hope this will change, it is so important to support basic science, it often happens that therapeutic benefit come quite a long time after the initial discovery,” he says. And in the case of his discovery, it has. 

I had no expectations about therapeutic benefit at the time of my finding. This came gradually from the 1980s onwards with technical advancements and with the cloning of sheep Dolly 1996.” And then came Professor Yamanaka’s finding in 2006. His finding showed that intact, adult cells can be rebooted into so called induced pluripotent stem (iPS) cells, which can give rise to many different cell types. “I was actually at the meeting in Toronto where he presented his result. It was amazing, and then others repeated it and then it was evident,” Gurdon says.

The technique reduces the need for controversial and difficult to acquire embryonic stem cells. These iPS cells allow researchers to study disease and development in the lab by, for example, generating disease models from the skin of patients with neurodegenerative disorders. The cells are also showing promise in cell replacement therapies to treat various illnesses. Gurdon sees potential in several areas, in disease models as well as in transplantation in the case of neural damage and macular degeneration.

I believe patients should be allowed to make their own informed decisions about the treatments they receive.

The field has made a lot of progress over the last few decades but has also encountered, again, a lot of skepticism and controversy. There are ethical debates and countries are restricting the field. “I believe patients should be allowed to make their own informed decisions about the treatments they receive,” states Gurdon. 

Don’t give up

John Gurdon is today 79 years old and currently group leader at the Gurdon Institute in Cambridge. His research is focused on the reprogramming of gene expression by nuclear transfer; analyzing intracellular signaling factors involved in cell differentiation and studying mechanisms involved in reprogramming the nucleus in transplantation experiments, including the role of histone variants and demethylation of the transplanted DNA. Gurdon still enjoys doing experiments and spending time in his laboratory. “I have never been tempted to work in industry, it is too restricted,” he says. 

I have never been tempted to work in industry, it is too restricted.

His advice for a young researcher today starting his or her career is “Be interested in what you do. Put everything into what you do and then build a career. Do not give up. Experiment and try different things. A bad start is no reason to give up your dream.” 

And he should know. Gurdon still keeps his report card from Eton up on his wall in his Cambridge office, perhaps now next to his Nobel Prize Diploma.