British scientist John B. Gurdon and Shinya Yamanaka (MD, PhD!), a Japanese scientist now at the Gladstone Institutes in San Francisco, were awarded the Nobel Prize in Physiology or Medicine this morning, ”for the discovery that mature cells can be reprogrammed to become pluripotent.”
Briefly, Gurdon and colleagues showed that the genetic information from a mature, differentiated cell still had the ability to program an undifferentiated embryonic cell to develop into an adult organism. That is, an embryonic cell contains the chemical signals to use adult DNA to drive development of a new organism.
The work was done with the frog, Xenopus laevis, and the technique came to be known as “nuclear transfer.” In colloquial terms, this is “cloning.” Current press reports are citing Gurdon’s work as occurring in 1962 but studies appear to have been published in Nature as early as 1958.
Christen Brownlee composed a superb summary of nuclear transfer for the Classics section of the Proceedings of the National Academy of Sciences. Gurdon’s work stemmed from 1952 experiments of Robert Briggs and Thomas J. King with another frog, Rana pipens. Briggs died in 1983 and King in 2000 and could not be recognized with the Nobel. This fact relieved the Nobel committee, in my opinion, from having to decide which scientist would have been awarded the potential third slot for the prize. (Addendum 7:18 am EDT): I suspect that some argument will arise in support of UW-Madison’s James A. Thomson for the third slot as the Science paper from his group came out concomitantly with Yamanaka’s Cell paper. 8:21 am: The Guardian’s Alok Jha just reminded me that I overlooked Takahashi and Yamanaka’s earlier Cell paper from 2006. However, C&EN’s Carmen Drahl is now reporting this 2001 TIME magazine cover with Thomson.)
The conceptual originator of the technique, Germany’s Hans Spemann, was given the 1935 Nobel Prize in Physiology or Medicine for identifying how different parts of the embryo lead to each segment of the adult organism.
Shinya Yamanaka, now at the tender age of 50, had earlier led studies to convert adult human
cells back into the fully undifferentiated state. These are today called induced pluripotent stem cells or iPS. The term “pluripotent” means that the cells can divide into any other mature cell type: live, brain, muscle, etc.
In 2006 while at Kyoto University, Yamanaka’s group demonstrated that only four genes were required for reprogramming a skin cell into a pluripotent stem cell: SOX2, Oct-3/4, Klf4, and c-Myc. These four genes encoding proteins called transcription factors, regulators of specific patterns of genes to be turned on or off. The average science reader is likely to at least recognize c-Myc since its inappropriate activation is central to several human cancers. Klf4 is also considered to be an oncogene.
And, to this biologist, the pluripotent stem cells’ potential to also become cancerous has been a considerable technical and ethical barrier in human cloning. More will emerge today on the seminal papers and significance of the work behind the prize but I just wanted to get a brief description up before heading to work. (Addendum 7:30 am EDT: And my New Zealand colleague, Grant Jacobs, just informed me of his early analysis he put up before heading to sleep!)
Here’s your factlet for the day if you wish to sing the praises for model organism research: the genus name Xenopus is Hebrew for “medical frog.” (Click “Translate” if you’re using Google Chrome.)
Addendum 7:53 am EDT: The UK Guardian’s superb writer Alok Jha has a continuing thread on the prize developments as the day goes on.
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