Every person begins as just one cell — a fertilized egg. That cell rapidly divides, forming a cluster of cells that will eventually become all the types of cells in all the organs needed to create a whole human being. This cluster of embryonic stem cells has the unique ability to differentiate into any kind of cell in the body, such as brain cells or skin cells.
Scientists had long believed that once stem cells turned into a specific type of cell, they were mature and forever locked in that role. But this year’s Nobel Prize winners in physiology or medicine, John B. Gurdon and Shinya Yamanaka, disproved this dogma by discovering that specialized, fully developed cells can be reprogrammed back into undifferentiated states.
This discovery has revolutionized the understanding of human development and holds great promise for future medical treatments.
Fifty years ago, Gurdon was an assistant lecturer of zoology at the University of Oxford and began experimenting with eggs from a frog species called Xenopus. He destroyed the nucleus of a Xenopus egg with ultraviolet light and then transferred into that cell the nucleus of a fully differentiated frog intestinal cell. He wondered if the nucleus from the differentiated intestinal cell retained the information for pluripotency, the ability to form all cell types and subsequent tissues. If so, the egg would still grow into a tadpole. But if the information was irreversibly lost when a stem cell became specialized, then the egg would not be able to develop further.
Amazingly, the egg became a tadpole. This proved that fully differentiated cells retain all the necessary information to produce a complete living organism.
The scientific world did not immediately embrace this shocking and controversial discovery. However, as others used and refined Gurdon’s techniques the method became known as somatic cell nuclear transfer, which was used to produce the first cloned mammals like Dolly the sheep.
Years later — and thousands of miles away — Yamanaka, a professor with the Institute for Frontier Medical Sciences in Kyoto, Japan, took the idea one step further by questioning whether a fully differentiated cell could be reprogrammed back to a pluripotent state. In a remarkable set of experiments, he transferred the genes for 24 transcription factors, specialized proteins which in this case were active in embryonic stem cells, into mouse skin cells called fibroblasts. As a result, some of these cells changed to a shape and size similar to stem cells.
Next, he painstakingly reduced the transcription factors one by one to identify the four key factors required for cellular reversion, proving these factors could induce pluripotent embryonic stem cells.
Despite spanning decades and continents, these two discoveries together will pave the way for treating diseases with regenerative medicine, replacing damaged human organs or tissues with new, functioning ones.
In addition, this will allow scientists to work with induced stem cells without facing the ethical concerns of harvesting stem cells from human embryos.
Doctors Gurdon and Yamanaka were honored in Stockholm on Saturday.