Now also this week, big news for Cambridge University, we won another Nobel Prize. Well not we, personally - someone who works at the Gurdon Institute. In fact, it is Embryologist Sir John Gurdon. He learned on Monday that the Physiology and Medicine Nobel award had come his way and it was in recognition of his discovery using frogs, that if the DNA and the nucleus are specialised cells from say the intestine or the skin of an adult, is then put into an egg cell, which had its own genetic material removed, you can get a new frog which is genetically identical to the first one. This is of course, the basis of the cloning process which eventually enabled scientists in the ‘90s to clone Dolly the sheep. At the age of almost 80, Sir John Gurdon is still doing experiments and I went to see him in his lab this week to find out how he made this dramatic breakthrough.
John - The story leading to this award – well of course, that goes back right to almost the beginning of life. My mother and aunt could see I – at a very early age like 6 or 7 – I liked to catch butterflies and they encouraged that. That encouragement went on during my teenage years when I was at school and I used to infuriate my housemaster’s school by growing caterpillars as much as I could in my room, which he thought was a waste of time and stupid.
Chris - How did that turn into the work that then lead to you winning the Nobel Prize?
John - I was started on science at school at the age of 15. In those days, we didn’t do any science until you were at that age. And then I did one term of science being taught by a biology master and he gave me an absolutely crippling report, essentially saying I was absolutely unsuited to science, at which point in time was removed from science in the rest of my time at school, and was put on to ancient Greek and Latin. And then when I finished school, my mother and family could see what I really was interested in was actually biology in one form or another. And they, having paid very expensive private school fees until the age of 18, they were then asked if they would spend another 2 years, having me trained to get into science, which they very generously did and then I ended up being accepted for the zoology course in Oxford University. And then the career really took off when I was a graduate student with a wonderful supervisor in that department.
Chris - So, how did you then translate with that into an interest in the work that then lead to where you are now?
John - Well, when I needed to start a PhD, the person who kindly invited me to become a student of his, he was an embryologist and I did think that was an extremely interesting subject, as to how a plant seed turns into a plant, or an egg turns into an animal with no guidance from outside, particularly if you think of frogs, that egg just sits there in a pond and somehow it knows on its own, how to turn into a tadpole, amazing phenomenon. So, I was delighted to be accepted for a PhD work in what was called embryology.
Chris - And how did you progress that? What were the big questions when you started your PhD?
John - That’s a really good point. The primary question I was concerned with was whether all the different cell types of the body have the same sets of genes or not, and one has to go back a step and remember that in the late 1800s, people were very curious about whether the formation of different cells meant that something is lost from the cells that don’t need it. For example, brain genes being lost from skin or heart genes being lost from the liver, or if not lost, at least permanently put out of action.
Chris - So people thought that when a cell turns fro say, a primitive cell in an egg into what becomes skin that in becoming skin, it in some way throws away some of the genes that would enable it to do anything else. So, for the rest of its life, it has to stay as a skin cell.
John - That’s exactly right and there's a person whose name was August Wiseman who actually proposed that that is how development works. It would make good sense really that you throw what you don’t want, and you end up keeping what is needed for the particular cell type you are trying to make.
Chris - Seems pretty logical to not keep stuff. So you were very much swimming against the tide. If you were trying to disprove that, you're going a completely different the opposite direction to what people thought at that time.
John - In a way, it was swimming against the tide, but really, the point was – this was a question being asked. It wasn’t as if they said, “We know this happens. You have to kind of prove it.” It was thet saying, “Is that how development works?” and there is a piece of background that’s important. The technique of introducing a nucleus from a cell into an egg was actually invented by 2 Americans called Briggs and King. And they did that in 1952 and they found that if you take the nucleus of a very early embryo cell and put it into an egg whose own genes have been removed, they did indeed get normal-looking tadpoles. However, they found that if they took a nucleus from a little bit later embryo, an embryo at a day later, that no longer happened. And so, they concluded, as indeed I would have done if I have done that experiment, that something is being lost or permanently inactivated that is needed to enable the whole organism to be formed. So, I was in the position of being invited by my supervisor to try and do the same work, albeit on different species.
Chris - How did you actually do that and how many embryos did you have to throw away before you realised what was actually going on?
John - So, the Briggs and King had invented this clever method and we tried that and it absolutely wouldn’t work at all. So, that turned out to be because the kind of frog we were using has an extraordinary elastic jelly coat, which makes it totally impenetrable. By a piece of luck, my boss had recently bought a fancy ultraviolet microscope for UV microscopy and an extraordinary piece of luck was that that particular wavelength of ultraviolet light also destroyed this jelly coat, meaning it was possible to actually penetrate this egg with a micropipette. Sometimes it works absolutely perfectly and the combination of the transplanted nucleus and egg will make a completely normal adult frog. Other times, it doesn’t something goes wrong and the more advanced the cell from which you take the nucleus, the more likely it is to go wrong, but it works from time to time.
Chris - So, that led you to be able to conclude that regardless of how specialised a cell is, there is a complete compliment of DNA in that cell which if you put it back into an egg can recapitulate an entire animal again. So you get that result, your whole life changes presumably because you have suddenly rewritten biology.
John - Yes, it did really because it seem to prove that – we now believe it to be true – that all cells of the body, almost all have the same set of genes, and from then onwards which was roughly 50 years ago, I've been trying to discover how that happens, what has the egg got that can set the whole programme back to the beginning again. And some people say, “Gurdon did an interesting experiment when he was a student and he spent the next 50 years doing nothing useful at all.”
Chris - do you agree?
John - I like to think not because we actually do understand a reasonable amount, don’t understand everything. That’s my next aim, to try and fully understand how this is done.
Chris - John Gurdon who won the 2012 Nobel Prize for Physiology in Medicine chatting with me early this week, and I've put a full version of that interview in which he talks about what he’s doing today as a special edition Naked Scientists podcast on our website. If you go thenakedscientists.com and follow the links to our special podcasts, you will find that there.