Monday, October 08, 2012

The 2012 Nobel Prize in Physiology or Medicine

The Nobel Committee announced the awarding of the 2012 Nobel Prize in Physiology or Medicine to Sir John B. Gurdon and Shinya Yamanaka for their work on the reprogramming of mature cells to immature pluripotent cells.

It is rather amazing to think that the variety of different cells within our bodies start from a single cell. Those early cells that have the ability to turn into many different types of cells are called pluripotent stem cells. The cellular differentiation process is relatively well understood. But, is it possible for a mature cell to revert to its immature, pluripotent state, or is cellular differentiation a one-way street?

Fifty years ago Sir John Gurdon performed an experiment to test this idea. He replaced the nucleus of a frog egg with the nucleus of a mature cell from a tadpole intestine. This egg developed into a normal adult frog. After subsequent repetition of the experiment it became clear that the information for cellular differentiation still resided within the mature cell. In fact, cells do have the ability to go backward.

After this discovery, the question became, how does this happen? What are the keys to the underlying mechanism of differentiation? In the early 21st century, Shinya Yamanaka took genes thought to play a role in keeping cells in an immature state and injected them into mature cells in varying combinations looking for combinations that would turn those mature cells into immature cells. He and his colleagues did find a combination that reprogrammed these mature cells and surprisingly, it took only 4 genes to accomplish this remarkable task. They went on to show that these reprogrammed cells could differentiate into many different cell types.

The implications of this work are profound. Gurdon's original observation led to the cloning of mammals - Dolly the Sheep being the first success. The ability to reprogram cells by the introduction of just a few specific genes creates cellular tools that allow us to get a better understanding of the underlying processes, the study of changes in healthy versus diseased cells, and even the potential to use these findings to treat degenerative diseases.

There are many unanswered questions about the potential of these reprogrammed stem cells. Dolly the Sheep only lived 6 years and these genetically reprogrammed stem cells appear to have a propensity to form tumors. However, the two discoveries awarded this year's prize have opened up amazing possibilities.

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