Gurdon and Yamanaka Win Nobel Prize for Stem Cell Research

Written By Unknown on Selasa, 09 Oktober 2012 | 13.57

Two scientists who were awarded the Nobel Prize in Physiology or Medicine on Monday helped lay the foundation for regenerative medicine, the hotly pursued though still distant idea of rebuilding the body with tissues generated from its own cells. They are John B. Gurdon of the University of Cambridge in England and Shinya Yamanaka of Kyoto University in Japan.

Kyodo/Reuters

Shinya Yamanaka, left, in April 2009, and John B. Gurdon.

Their discoveries concern the manipulation of living cells, and lie at the heart of the techniques for cloning animals and generating stem cells, the primitive cells from which the mature tissues of the body develop. Dr. Gurdon was the first to clone an animal, a frog, and Dr. Yamanaka discovered the proteins with which an adult cell can be converted to an egg-like state. The prize was announced in Stockholm.

Both men had to overcome false starts in life. Dr. Gurdon was told as a boy that he was wholly unsuited for biology, and Dr. Yamanaka trained as a surgeon only to find he was not so good at it.

The techniques they developed reach to the beginnings of life, and have generated objections from people who fear, on ethical or religious grounds, that scientists are pressing too far into nature's mysteries and the ability to create life artificially.

Dr. Gurdon's discovery came in 1962, when he produced living tadpoles from the adult cells of a frog. His work was at first greeted with skepticism, because it contradicted the textbook dogma that adult cells are irrevocably assigned to their specific functions and cannot assume new ones. (His prize was the first Nobel to be awarded to a cloner.)

Dr. Gurdon's technique was to extract the cell nucleus, containing the frog's DNA, from a mature intestinal cell and inject the nucleus into a frog egg whose own nucleus had been removed. The egg was evidently able to reprogram the introduced nucleus and direct its genes to switch from the duties of an intestinal cell to those appropriate to a developing egg.

But how did the egg cell body accomplish this reprogramming feat? The answer had to wait 44 years, while molecular biologists gained a more intimate understanding of genes and the agents that control them.

Working with mice, Dr. Yamanaka discovered in 2006 that the reprogramming can be accomplished by just four specific gene control agents in the egg. The agents, known to biologists as transcription factors, are proteins made by master genes to regulate other genes. By injecting the four agents into an adult cell, Dr. Yamanaka showed that he could walk the cell back to its primitive, or stem cell, form.

Stem cells generated by this method, known as induced pluripotent cells, or iPS cells, could then be made to mature into any type of adult cell in the body, a finding with obvious potential for medical benefits.

Biologists hope the technique will enable replacement tissues to be generated from a patient's own cells for use against a wide variety of degenerative diseases. For the moment, that remains a distant prospect. But the cells have already proved useful in studying the genesis of disease. Cells generated from a patient are driven to form the tissue that is diseased, enabling biologists in some cases to track the steps by which the disease is developed.

Dr. Gurdon's early academic career did not hint at what the future might hold. "I believe Gurdon has ideas about becoming a scientist; on his present showing this is quite ridiculous," his high school biology teacher wrote. "If he can't learn simple biological facts he would have no chance of doing the work of a specialist, and it would be a sheer waste of time, both on his part and of those who would have to teach him."

At Oxford University, a more positive mentor encouraged him to try transplanting the nucleus of adult cells into frog eggs. The idea was to see if the genome — the hereditary information — stayed unchanged during development or underwent irreversible changes. In producing living tadpoles from the nucleus of adult frog cells, Dr. Gurdon showed that the genome of both egg and adult cells remained essentially unchanged.

But the possibility that animals, including humans, could be cloned did not seriously impinge on the public imagination until his work was reproduced in mammals with the generation of Dolly, the cloned sheep, in 1997. The following year saw generation of the first human embryonic stem cells, which are derived from the early human embryo. Such cells are called pluripotent because they can develop into any of the mature tissues of the body.


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