Reprogrammed Cells Earn Nobel Honor

Honored. John B. Gurdon and Shinya Yamanaka

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The discovery that cellular development is not a one-way street has earned this year's Nobel Prize in physiology or medicine. John B. Gurdon, a developmental biologist at the Wellcome Trust/Cancer Research UK Gurdon Institute at the University of Cambridge in the United Kingdom, and Shinya Yamanaka, a stem cell researcher at Kyoto University in Japan and the Gladstone Institute at the University of California, San Francisco, have won the prize for their discovery that mature cells can be reprogrammed to resemble the versatile cells of a very early embryo. These so-called pluripotent cells have the ability to become any of the body's tissues. The pair's work, which bridges two eras of modern biology, "revolutionised our understanding of how cells and organisms develop," the Nobel committee wrote in its award announcement.

The ability to reprogram adult cells has made it possible for researchers to study certain diseases in new ways and raises the possibility of someday growing replacement tissues or even organs in the lab. "I think everyone who works on developmental biology and on the understanding of disease mechanisms will applaud these excellent and clear choices for the Nobel prizes," says John Hardy, a neuroscientist the University College London. "Countless labs' work build on the breakthroughs they have pioneered."

In normal development, cells mature from their pluripotent state into various specialized cell types—a neuron, muscle cell, or skin cell, for example. For many years, developmental biologists thought that the cellular maturation process was irreversible. In 1962, however, John Gurdon, working at the University of Oxford, showed that under the right conditions, a mature cell nucleus could become developmentally young again. He replaced the nucleus of a frog egg with a nucleus taken from a cell in a tadpole's intestine. In a few cases, the egg cell was able to "reprogram" the DNA in the tadpole nucleus and the egg cell developed into an adult frog—the first animals cloned from mature cells*. Other researchers built on Gurdon's findings, most famously the team that cloned Dolly the sheep using a similar feat of nuclear transplantation. That breakthrough demonstrated that mammal cells could undergo the same transformation from mature to immature.

More than 4 decades later, Shinya Yamanaka showed that an egg cell wasn't necessary to reprogram a cell's DNA to pluripotency. Working with mouse cells, Yamanaka and his colleagues found that by adding extra copies of four genes to skin cells growing in a laboratory dish, they could prompt the cells to act like embryonic stem (ES) cells, the pluripotent cells taken from early embryos. A few years later, Yamanaka and other teams showed that a similar technique could work on human cells. That has allowed scientists to establish stable, growing populations of cells from patients with diseases such as amyotrophic lateral sclerosis (ALS). Researchers can study such cells, known as induced pluripotent stem (iPS) cells, for disease insights. In the case of ALS, they can prompt them to become muscle and nerve cells that mimic the problems seen in people with the condition. Yamanaka, who originally trained as an orthopedic surgeon, welcomed the Nobel honor with a note of caution about how quickly it might yield medical benefits. "I feel great joy, but at the same time a great responsibility. The iPS technology is new and we actually have not been able to apply these findings to the development of new therapies or drugs. I feel we have to continue research to make a contribution to society as early as possible."

Yamanaka's work was also welcomed because it offers researchers a potential alternative to human ES cells, which have been ethically and politically controversial given their source. Scientists are still working to understand exactly how cells reprogrammed by the addition of genes differ from the pluripotent cells that are found in embryos, and how those differences might affect the ways the cells can be used.

Gurdon released a statement highlighting how the two scientist's research had moved from basic science into medicine: "I am immensely honoured to be awarded this spectacular recognition, and delighted to be due to receive it with Shinya Yamanaka, whose work has brought the whole field within the realistic expectation of therapeutic benefits. ... It is particularly pleasing to see how purely basic research, originally aimed at testing the genetic identity of different cell types in the body, has turned out to have clear human health prospects."

At the press conference at Kyoto University today, Yamanaka said that he couldn't have carried out his work without the financial support he has received from the country." I really feel that Japan is receiving this prize." In 2009, he and Gurdon shared the Albert Lasker Basic Medical Research Award.

More background information from Science and ScienceNow:

* This article has been corrected to reflect that Gurdon's frogs were not the first cloned animals, but rather the first animals cloned from mature cells.

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