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Nessa Carey

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Toads and Mice and the Sheep in Between: The 2012 Nobel Prize in Physiology or Medicine

Posted: 10/19/2012 8:57 am

A quintessential English gentleman educated at Eton and a Japanese orthopedic surgeon. Not the most likely of traveling companions, you might think. But very soon the two of them will be journeying to Stockholm to collect the Nobel Prize for Physiology or Medicine, for research carried out on different continents, using different animal species and decades apart, yet intimately linked. The work of both men is elegant and beautiful and has one of the features that characterizes the truly revolutionary in biology -- as soon as you understand it, it seems so self-evident that it's hard to believe no one had ever thought of it or done it before.

Sir John Gurdon is in his seventies and is still an active researcher, seemingly unfazed by the fact that his laboratory at the University of Cambridge is now in a building named after him. For over twenty years from the 1960s onwards he carried out a long series of research programs using a wonderfully ugly toad, called Xenopus laevis, which lays lots of very big eggs outside her body.

Gurdon harvested these and carefully removed the nucleus from an egg. The nucleus is the part of the cell that contains all the genetic information, the DNA. He put into this "empty" egg a nucleus that he'd taken out of a different type of toad cell, for example from the gut, and let the egg develop. And it did, leading to the production of tadpoles. It was the first example of cloning, taking a cell from the body and using its nucleus to create a whole new organism

Now this is the forerunner to the production of Dolly the Sheep many years later when Keith Campbell and Ian Wilmut performed a conceptually similar technique to create the first cloned mammal. And Gurdon's work would be important for that alone, but the real reason why he has won the Nobel Prize is because he solved a very big mystery in biology. Animals reproduce when an egg is fertilized by a sperm. The large cell that is produced has the potential to form all the cells of the body. It divides to form two cells, these divide to form four and so on, resulting in the fifty trillion cells or so in a human, for example. But as all these cells are created, they become more and more specialized, becoming different cell types. And they stay as those specialized cell types. It's why we don't get hearts in our brains or teeth in our eyeballs.

The big question was why these cells stay so specialized. There was a perfectly sensible theory that suggested that the cells jettisoned or permanently inactivated any genes they didn't need. A brain doesn't need to produce the proteins that are used when your biceps contracts (no matter how many times people say it in self-help books, the brain is not another muscle) and your ear has no need of the genes for eye color. Perhaps cells just got rid of genes they didn't need?

John Gurdon's research showed that this wasn't the case. Because he could create new toads using the nucleus from the specialized cells of older animals, it was clear that these cells kept all the genetic material required to re-create life. They just weren't using it.

Shinya Yamanaka was just a small boy in Japan when John Gurdon performed many of his key experiments. He became fascinated by stem cells, the ones which have the potential to form all the tissue types in the body. These include that starting cell created when an egg and sperm fuse, those cells created by John Gurdon that could generate entire tadpoles, and also the famous embryonic stem cells. Over twenty genes had been identified that were required for the function of stem cells and virtually everyone working in the field assumed that these would act in an almost impossibly complex network. But Yamanaka took an incredible gamble. He began testing combinations of these genes to see if they would turn specialized mouse cells into stem cells. He was attempting to achieve for thousands of cells simultaneously in a culture dish the same thing that Gurdon had done laboriously with individual toad eggs. Incredibly, Yamanaka found that he could create stem cells, simply by forcing the specialized cells to express really high levels of just four particular genes.

At first no one really believed this could be right. It was like setting off on a quest for the Holy Grail and finding it in the second place you looked, behind the bag of frozen peas in the icebox. But soon other labs repeated the finding and a whole new field of research began. This work went from "you can't be serious" to the Nobel Prize in six years -- that's how transformational it is.

Yamanaka's work is the driving force not just for a greater understanding of cell fate, but also for the generation of entire new industries. Using his techniques scientists can now create effectively unlimited supplies of stem cells from any individual. These can in turn be converted into potentially any cell type in the body. Imagine the possibilities. We could replace cells lost in diseases, from those that produce insulin in the pancreas of patients with type 1 diabetes, to the brain cells destroyed in Parkinson's disease. We could produce unlimited banks of red blood cells for transfusions for trauma patients. And we'd have none of the ethical controversies associated with embryonic stem cells, and no immune rejection because we could make cells specific to an individual patient.

For various technical reasons we aren't ready to use these cells to treat patients yet, but banks of them are being created to help scientists investigating specific diseases, and for testing new drugs.

Gurdon and Yamanaka have transformed the biological landscape with research that was conceptually beautiful, and technologically at the limits of what could be achieved at the time. The Nobel committee has made a fabulous choice.

 

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A quintessential English gentleman educated at Eton and a Japanese orthopedic surgeon. Not the most likely of traveling companions, you might think. But very soon the two of them will be journeying t...
A quintessential English gentleman educated at Eton and a Japanese orthopedic surgeon. Not the most likely of traveling companions, you might think. But very soon the two of them will be journeying t...
 
 
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01:31 AM on 11/02/2012
"The nucleus is the part of the cell that contains all the genetic information, the DNA." Not all the genetic information in a cell is contained in the nucleus. Some is contained in the mitochondria. It is because of this difference that humans inherit their mitochondrial DNA only from their mothers.
QuietLightTraveler
Scientist, Teacher, Naturalist, Photographer
06:17 PM on 10/22/2012
Fantastic work. Just fantastic. Absolutely a wonderful contribution and achievement. There is something related to this story about Dr. Gurdon that is very amusing. It was posted recently somewhere. It was a report from his college biology teacher claiming that his work at school was absolutely dreadful, that his grades were horrible, that he placed last in his class of 18, and that he was incapable of learning the facts of biology. She went further to say that she learned he wanted to be a scientist but that such an idea was utterly absurd - that it would be a total waste of effort and time for both him and those who tried to teach him. Surprise Ms. Biology teacher ! He is now Sir John Gurdon, winner of a Nobel Prize, the highest and most prestigious recognition in all of science. Let that be a lesson to all you school failures out there. No one knows what they can do until they actually try. Never let anyone define you.
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HUFFPOST SUPER USER
cvermeulen9
And you thought it could never happen!
08:47 AM on 10/21/2012
I wonder if we will ever see it used to repair human organs. If so.... when? I hope it is in my lifetime. It would be wonderful to ..for instance grow a new heart or lungs OR new limbs and eyes.
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HUFFPOST SUPER USER
Chipher
06:12 PM on 10/20/2012
One more reason to fight for your 'right' to afford transgenetic medicine, and leave the pill popping and prayer to the poor plebians. Oh, this is a Brave Renewable World we will live in ... if you can afford it!!
11:06 PM on 10/19/2012
I never quite understood the DNA concept. Good to know the things I didn't understand weren't a stupid question after all. I mean everything is built on the cell level, so... how do cells know what form to take where and when? And stem cells without embryos, way cool.
10:57 PM on 10/19/2012
LOL, I enjoy reading science articles, but am severely under-educated regarding science. I could never wrap my mind around DNA or RNA. This helped address some of my confusion, like why each cell contained all DNA rather than just what is needed to make the cell and how a cell ends up in the right place and the right type. Glad that wasn't a stupid question. This has been known for years but news to me. Stem cells without the infant factor. Very cool.
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02:44 AM on 10/20/2012
". This helped address some of my confusion, like why each cell contained all DNA rather than just what is needed to make the cell and how a cell ends up in the right place and the right type"

That certainly isn't a stupid question but a very interesting one as the Nobel Committee have confirmed with it's award. To my mind the fact that every cell (with some exceptions like red blood cells in mammals) in the body has all the DNA needed to make a complete organism is powerful evidence for evolution. Surely a well designed organism would have cells which got rid of the redundant DNA? But a creature which had evolved from a single cell organism might well keep the DNA in all it's cells and evolve methods of shutting down the DNA which is not required. Which is exactly what does happen.
QuietLightTraveler
Scientist, Teacher, Naturalist, Photographer
06:37 PM on 10/22/2012
Evolution is written all over the genomes of various organisms. Only the ignorant try to discredit evolution. I saw on the news the other day that some GOP representative said recently, that the theory of evolution was directly from "the pit of Hell". And now the even more amazing part. He is a physician and is on one the science committees in Congress. He is a southerner of course, I forget from which state. Shame on Congress and whatever bastion of bible thumping ignorance this guy comes from.