Science Talk

The 2012 Nobel Prize in Physiology or Medicine


Podcast Transcription

Steve:       Welcome to the Scientific American podcast Science Talk, posted on October 8th, 2012. I am Steve Mirsky. Just after 5:30 this morning Eastern time, Göran Hansson of the Karolinska Institute and Nobel Committee for Physiology or Medicine stepped to the microphone in Stockholm.

Hansson:   The Nobel assembly has concluded its meeting and made the decision. I'll read the announcement. The Nobel assembly at the Karolinska Institutet has today decided to award the Nobel Prize in Physiology or Medicine 2012 jointly to John B. Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogramed to become pluripotent. And with that I would like to ask Professor Thomas Perlmann of the Nobel Committee to present the science behind the prize.

Perlmann:          John Gurdon from Great Britain is a professor at the University of Cambridge and the Gurdon Institute. Shinya Yamanaka, born in Japan and a professor at Kyoto University. This year's Nobel Prize awards the discovery that has changed the way we understand how cells in the body become specialized, and it has provided entirely new tools for effective development of drugs and new therapies. A fertilized egg develops first into an embryo and then into an adult human with all its specialized cells, such as muscles, nerves and skin. As we all know, this process always moves in the same direction, from immature cells in the embryo to specialized cells in the adults. A common metaphor for this process visualizes how cells move downhill in a landscape to finally reach their destinations as specialized mature cells at the bottom of the valleys. Scientists believe for a long time that our genes are likely altered in this process, in ways so that this journey could never be set in reverse; and it seemed impossible for mature cells to travel back, all the way to the immature state at the top of the mountain. Now John Gurdon changed this view by a ground-breaking experiment in frog cells. He thought that if a gene's, contrary to the common view, were intact in mature cells, its nucleus should be able to develop when moved into the cellular context of an egg. So, he destroyed the nucleus of an egg and used a fine pipette to transfer and replace it with a nucleus from a mature intestinal cell from a tadpole. In most cases, this modified egg could not develop, but in a few cases, it developed into normal swimming tadpoles and later adult frogs. At first many were skeptical and surprised by this result, but this paradigm shifting discovery was confirmed. And we now know that the same experiment works to clone mammals, the first being Dolly the sheep, but later also mice, cows, pigs and other animals. Gurdon had shown that a nucleus of a mature cell retains all genetic information that is required to generate an animal. But could this also be done in intact cells, without dissecting out the cell nucleus and using a pipette like Gurdon did, and placing it in an egg. Shinya Yamanaka, over 40 years later, made a discovery that also whole intact mature cells can be reprogrammed and that this could be achieved by surprisingly simple procedure. Now Yamanaka, he studded genes that are important for the function of pluripotent stem cells. Pluripotent stem cells are found in the early embryo and can develop into all different types of mature cells in the body. And he thought that some stem cell genes may induce pluripotency if they would be transferred into mature cells in a mouse. Twenty-four candidate stem cell genes were selected. This target cell was the skin cell from a mouse. Now usually scientists transfer genes into other cells one by one, but in a strikingly bold experiment, all of these 24 genes were introduced in one single step into the skin cells, and a few cells became reprogrammed into cells that could generate all the mature cells in a mouse. They had now become pluripotent. Further experiments demonstrated that only four genes were needed for this induction of pluripotency. He named these cells induced pluripotent stem cells, or iPS cells. The iPS cell technique is a truly groundbreaking discovery that has opened up whole new research areas in cell biology and medicine. For example, iPS cells can now be generated from patients with disease and from these iPS cells, mature cells can be cultured so that we now have a procedure that gives success to new cell models for disorders that previously have been very difficult to study. Thanks to these two scientists, we now know that development is not strictly a one way street.

Hansson:   Thank you Thomas. So we are now ready for questions.

Boyce:       I'm Karen Boyce from the Swedish daily Dagens Nyheter; and how far away do you think those iPS cells are from treatment for people?

Hansson:   I'll ask Urban Lendahl, chairman of the Nobel Committee, to comment.

Lendahl:    So, it is difficult to give an exact time prediction for when things and stem cells of any kind move into cell therapy, but what is a more imminent area is actually to use them as platforms for drug screening and actually to learn about disease; because this is the first time where we can generate large number of cells and differentiate them into specific cell types, and often they actually recapitulate critical parameters of a disease. So that's where we are right now. But to give an exact time axis for when they reach cell therapy, I think that's beyond what we want to do today.

Louise:      Hi, Louise from the AP. I was wondering if you've been able to get a hold of the winners and how their reactions were?

Hansson:   Yes. This year, I spoke to both of the laureates on the phone and they were equally happy and are looking forward to coming to Stockholm later this year.

Louise:      I was wondering the exact age of the two laureates, and also how this can be applied for someone who doesn't really know what pluripotent means?

Hansson:   John Gurdon is 79 years old and Shinya Yamanaka, 50 this year—I don't know if he has had his birthday yet, but he was born in 1962. How to explain it? Who would like to take a shot at that? Yeah, Urban.

Lendahl:    I think we've always viewed development as going from the undifferentiated to the differentiated state, and I think it's such an important notion that all differentiated cells encapsulate a possibility to go back to the undifferentiated state; and I think that is very remarkable. And I think that that was very much an uphill battle, originally, from Gurdon to, sort of, prove the concept and then I think with the discovery that it was simple in the sense that it required a very limited set of genes, to actually do this in an intact cell from Yamanaka’s experience. I think both these discoveries really, sort of, sent shockwaves into the world and really, sort of, challenged and shattered dogma.

Landis:       Avan Landis with The Local. I was wondering if you could reflect a bit upon or elaborate how these discoveries affect the moral debate around stem cells in certain countries and how these advances affect that debate going forward?

Hansson:   Anna Wedell, professor of clinical genetics.

Wedell:     Well, of course, there can be different views on moral issues but in general in science, we have a very open debate and we, the Nobel Committee, does not really participate in that. But we as individual scientists and physicians do, and I think regulations evolve according to a general consensus in society—what is acceptable and what is not acceptable—and also another point is that every great discovery in biology that has applications in humans needs to be discussed, every individual application, and I think that is being done. That debate is continuously going on. We try to contribute to the best of our knowledge to that.

Landis:      How would you describe the main obstacles to therapy with iPS?

Hansson:   Therapy with stem cells, as of course, I mean, it's already used for hemapoietic stem cells in therapy, but the type of stem cells we're talking about here, pluripotent stem cells, we're still at a very early stage. I mean, there's a lot of promise and excitement and difficult disorders such as neurodegenerative disorders like Alzheimer's and perhaps more likely Parkinson's disease are very interesting targets. But we have to remember that we're at an early phase, even with pluripotent stem cells that have been known for quite a while. iPS cells can in theory solve the problem, the immunological problem, surrounding therapy with stem cells, but we have to remember that there are many obstacles and many of them are associated with safety. We have to be certain that pluripotent stem cells that are grafted, when they are, that they are totally safe and will not cause tumors and other problems. And we are not there yet, but for sure there is hope that it will progress.

The Press Release from the Nobel Assembly at Karolinska Institute

The Nobel Prize in Physiology or Medicine 2012 goes jointly to John B. Gurdon and Shinya Yamanaka for the discovery that mature cells can be reprogrammed to become pluripotent






Life – a journey towards increasing specialisation


Frogs jump backwards in development



A roundtrip journey – mature cells return to a stem cell state




From surprising discovery to medical use






Key publications:

Gurdon, J. B. (1962). The developmental capacity of nuclei taken from intestinal epithelium cells of feeding tadpoles. Journal of Embryology and Experimental Morphology 10:622-640.


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