Why Yamanaka Will Win the Nobel Prize

Stem cells are almost magical in their power. It is possible to turn stem cells into all other cell types of the body, including brain, heart and kidney. This is why they offer so much promise for the regeneration and repair of diseased and damaged organs. But the most powerful stem cells, those able to make the most cell types, have historically come from early embryos. Hence the ethical controversy, since it has been necessary to kill human embryos to make human stem cells.

Yamanaka changed all of that. He discovered a way to take adult cells, for example from the skin, and to turn them into extremely potent stem cells, indeed able to give rise to all cell types. This discovery has absolutely revolutionized stem cell research. We don’t need stem cells from human embryos anymore, so the key ethical objections to this research have been eliminated. And now it is possible to take skin cells from a patient and to make stem cells that are an exact genetic match. This means that there would no longer be any immune rejection problems for stem cell treatments.

How is it done? How can we convert a differentiated adult cell into the functional equivalent of a cell from a very early embryo? The answer lies in the manipulation of gene expression patterns.

When an egg is fertilized by a sperm their two sets of genes are united, creating the unique genetic combination of that individual. During development, as that single cell, the fertilized egg, proceeds to make a person, exact copies of every gene are made before every cell division. The end result is that every cell of the body carries the same complement of genes. But different cell types use their genes differently. Brain cells will have a set of brain genes active, while a liver cell will have a unique combination of liver genes active. The cell is sort of like a computer. It carries many gene programs capable of doing many different things, but only uses one program at a time.

But not all genes are created equal. Some are much more powerful than others. Fruit fly geneticists discovered about 100 years ago that mutations in some genes had amazingly profound effects. For example, an alteration of a gene named Antennapedia resulted in a fruit fly that had legs coming out of the head where the antennae were supposed to be! What a crazy fly, with an extra pair of legs coming out of its head. Mutation of another gene, bicoid, gave a true butt head fly, with an extra butt where its head was supposed to be. Genes of this sort were dubbed master switch genetic regulators because of their incredible effects.

How do they do it? These genes function by regulating the activities of other genes. And some of the genes they activate are additional regulator genes. It is easy to see how switching on one of these genes can initiate a genetic cascade, changing the expression levels of hundreds or even thousands of downstream genes, thereby controlling the developmental destinies of cells.

The genius of Yamanaka was to realize that there might be such master switch genes capable of converting adult cells into stem cells. Who would think this is possible? Turning a skin cell, for example, into the equivalent of an embryonic cell! But Yamanaka proved it was indeed possible. It was technically very challenging because a special combination of four master switch genes had to be turned on simultaneously to make it happen. Figuring out how many were necessary, and which ones, out of the over twenty thousand genes present, was a technical tour de force. But, to his great credit, he and his coworkers did it.

And so the stem cell revolution takes a giant leap forward. You need a bone marrow transplant? Why not be your own perfectly matched donor? Take skin cells, turn them into embryonic stem cells and then convert those into blood stem cells. Maybe you need a complete replacement organ, like a heart, liver or kidney. Remarkable progress is being made in turning stem cells into organs. Further, think quadriplegics that can walk again, the blind that can see again, the deaf that can hear again, and a cure for diabetes. We are clearly at the beginning stage of a new era in medicine. Doctors of the future will have a new set of mind-boggling tools for the treatment of a host of diseases involving diseased or worn out organs.

This is why Yamanaka will win the Nobel Prize.

About the Author: Steve Potter, PhD, is a Professor of Pediatrics, in the Division of Developmental Biology, at Children’s Hospital Medical Center in Cincinnati. He has authored Designer Genes: A New Era in the Evolution of Man, published by Random House 2010. In addition he has written over one hundred science papers, and co-authored the third edition of the medical school textbook, Larsen’s Human Embryology.

Eveloce: A term coined in Designer Genes: A New Era in the Evolution of Man. It refers to self accelerating evolution. For example, in the not too distant future people will be able to genetically engineer offspring with increased intelligence, who in turn will be better equipped to make offspring that are still smarter. It is easy to see how this kind of evolution could go explosive.


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