Cloning and Stem Cell Discoveries Earn Nobel in Medicine

Cloning and Stem Cell Discoveries Earn Nobel in MedicineBy NICHOLAS WADE

Published: October 8, 2012 28 Comments

A pair of landmark discoveries in cell biology made more than 40 years apart have earned the 2012 Nobel Prize in Physiology or Medicine for John B. Gurdon of the University of Cambridge in England and Shinya Yamanaka of Kyoto University in Japan. The prize was announced in Stockholm on Monday.

The 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.

Both men made 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 no 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.

Biologists have pushed ahead nonetheless, believing that manipulations like these may lead to regenerative medicine, the hope of repairing or replacing stricken organs with the body’s own cells.

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 is 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.

Many biologists hope that Dr. Yamanaka’s technique will be the gateway toward generating replacement tissues 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.”

After this verdict, the 15-year old John Gurdon had to spend the rest of his school time studying Latin and Greek. But spurred by a fascination with the color patterns on the wings of butterflies and moths, he did not forget his interest in the mystery of how animals develop, and in 1956 he got himself accepted for graduate work in the embryology department at Oxford University.

There a more encouraging mentor, the Latvian scholar Michail Fischberg, 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. Earlier experiments in the United States had suggested the genome did change as an animal developed, implying it would never be possible to clone an animal from a single cell, as can be done with plants.

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