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For discovering that a cell’s fate is not set in stone, John B. Gurdon, 79, and Shinya Yamanaka, 50, will share the 2012 Nobel Prize in Physiology or Medicine. Gurdon and Yamanaka’s work showed that cells can be reprogrammed to become pluripotent—that is, capable of turning into any kind of cell in the body.
The discovery transformed understanding of developmental biology, created new ways to study the onset of disease, and now paves the way for therapies to combat a wide variety of diseases.
Winning the Nobel Prize is “a tremendous honor, especially since I heard I share the prize with John Gurdon,” said Yamanaka, a stem cell researcher at Japan’s Kyoto University and San Francisco’s Gladstone Institute of Cardiovascular Disease, at an Oct. 8 press conference. “I was able to initiate my project because of his experiments 50 years ago.”
In 1962, Gurdon, a developmental biologist at Cambridge University, published the results of an experiment in which he removed the nucleus from a frog embryo and replaced it with the nucleus from a tadpole’s intestinal cell (J. Embryol. Exp. Morphol. 1962, 10, 622). The modified embryo turned into a normal tadpole, showing that the genome—even from a differentiated cell—holds all of the information required for an organism to develop. This experiment was also the first time an animal was cloned.
Some 40 years later, Yamanaka was the first to turn a mouse skin cell into a pluripotent stem cell capable of turning into any kind of cell (Cell, DOI: 10.1016/j.cell.2006.07.024). In particular, Yamanaka showed this reprogramming required the activation of only four genes.
The discoveries of Yamanaka and Gurdon “revolutionized regenerative medicine,” comments Ian Wilmut, the University of Edinburgh researcher who famously cloned Dolly the sheep. One practical application of cellular reprogramming is in studies of disease development in the brain or other organs from which “you can’t take significant biopsies,” Wilmut says. By reprogramming skin cells into more primitive cells and then differentiating them into brain cells, researchers can observe the onset of disease, discover its molecular mechanisms, and screen for potential drugs.
“The work of Gurdon and Yamanaka is especially important from a chemist’s perspective since it opened an exciting frontier—small-molecule-mediated transdifferentiation,” says Stuart L. Schreiber, a chemical biologist at Harvard University and MIT’s Broad Institute. “Now chemists can explore whether they can impose their will on tissues in the body with new medicines” that convert an abundant cell type into another that is deficient as a result of disease, he says, such as dopamine-producing neurons to help cure Parkinson’s disease.
Yamanaka and Gurdon will split the $1.2 million prize.
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