Dr. Gurdon earned the distinction of a Nobel for being the first to successfully clone a living organism, an achievement which he accomplished over fifty years ago. Gurdon pioneered the development of a technique which allowed him to generate live tadpoles from intestinal calls that had been harvested from an adult frog. By extracting the nucleus of an adult intestinal cell and injecting it into a frog egg in which the nucleus had been removed, he found that the adult nucleus and factors within the egg were sufficient to direct the development of an entire tadpole. The procedure Gurdon used to generate the tadpoles was the earliest prototype of modern day cloning, although at the time of the discovery his findings were controversial and met with widespread skepticism (Dr. Gurdon, 79, is currently affiliated with the Gurdon Institute in Cambridge, England and says he has no intention of retiring anytime soon).
The concept of cloning was revisited 35 years later, and before you know it, there’s Dolly (the sheep, that is). After the cloning of Dolly in 1997, it was theorized that a similar technique could be used for therapeutic purposes. By extracting the nucleus of an individual's skin cell and injecting it into a human egg, stem cells from the developing embryo could be harvested and transformed into cells which could be used to generate a new organ or tissue. Collecting these cells, however, meant destroying a human embryo. The concept stirred up a heated debate over the ethicality of the procedure, and so the use of stem cells taken from human embryos to generate human tissue and organs did not seem like a viable idea.
Such was the landscape of the nascent field of stem cell research six years ago when Shinya Yamanaka announced that he had managed to reprogram adult cells into stem cells which, by definition, retain the ability to turn into a number of different types of cells. Typically, fully mature (or differentiated) adult cells have more or less reached a biological dead end: once they’ve totally committed to a future as a certain kind of cell, there’s no going back. A small population of cells, however, retain the ability to turn into a number of different adult cells: heart, muscle, skin, you name it- these cells, of course, are the pluripotent stem cells that created quite a stir in the scientific community when Yamanaka’s paper was published in 2006. Dr. Yamanaka's work revolutionized the field of stem cell therapy, transforming it from an eerie sci-fi potential into a reality. Even better, it allowed researchers to bypass those pesky ethical issues and would serve as a platform for the major advances in stem cell research and therapeutics that followed. Stem cells to be used for therapeutic purposes could be generated using only a few skin cells from a patient, and the newly formed stem cells could be used to generate organs or tissues which would be specific to an individual- and therefore less likely to be rejected by their immune system.
Yamanaka began his work by identifying 24 genes coding for protein products known as transcription factors as promising candidates for inducing pluripotency. Transcription factors were the most likely suspects, as they have the capability of turning a number of other genes on and off. Even one transcription factor running amok in the nucleus can generate a flurry of gene activity, directing the entire cascade of events that follows. He then introduced each of the 24 genes individually into mouse skin cells. Yamanaka found that this method was not enough to achieve pluripotency; however, when all 24 were introduced into adult skin cells the cells were transformed into pluripotent stem cells. So he knew that somewhere in the mix was the right combination of cells to permit the conversion of adult cells into pluripotent stem cells, then it just became a matter of finding them. Yamanaka eventually narrowed it down to only four genes- Myc, Oct4, Sox2, and Klf4. Expression of these four genes was sufficient to turn adult skin cells into induced pluripotent stem cells (iPSCs), making the stem cell ‘vision’ a reality.
Yamanaka’s work was published a mere six years ago, which is a notably short period of time in Nobel Prize considerations- typically, the prize is awarded for work which was accomplished at least a decade earlier. Because science changes so rapidly, the results need to endure the test of time before they are considered prize-worthy.
This year's Nobel Prize came with a 1.2 million dollar award (8 million Swedish krona), a slight reduction since previous years but not too shabby nonetheless.
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