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Nobel Prize in Medicine and Physiology 2012

The 2012 Nobel Prize in Physiology or Medicine is awarded to Dr. John B. Gurdon and Dr. Shinya Yamanaka for their discovery that mature, differentiated cells can be reprogrammed to a pluripotent stem cell state.

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Cellular differentiation appears to be a unidirectional process, where un-differentiated cells mature to various specialized cell fates, such as neurons, muscle and skin cells. The prevalent view during the first half of the 20th century was that the mature cells were permanently locked into the differentiated state, and unable to return to a fully immature, pluripotent stem cell state. In 1962, John B. Gurdon changed this view by demonstrating that the nucleus from a differentiated frog intestinal epithelial cell was capable of generating a fully functional tadpole upon transplantation to an enucleated egg. This discovery proved that cellular differentiation is not a uni-directional process.

Gurdon’s discovery was only the beginning for cloning endeavors in various organisms. However, the question remained whether an intact differentiated cell could be fully reprogrammed to become pluripotent. In 2006, by a very simple procedure, Shinya Yamanaka proved that introduction of a small set of transcription factors into a differentiated cell was sufficient to revert the cell to a pluripotent state. The resulting cells were called Induced Pluripotent Stem cells (iPS). They have demonstrated that the usually very stable differentiated state can be brought back because it harbors a potential for reversion to pluripotency. This discovery has introduced new research areas, and offers exciting new opportunities to study disease mechanisms.

In summary, the concept that mature, differentiated cells can be reprogrammed to a pluripotentstem cell state is a paradigm-shifting discovery. This insight has influenced essentially all areas of medicine or physiology. The discoveries made by John Gurdon and Shinya Yamanaka clearly stand out as truly fundamental and have introduced an entirely new research field.

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