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Shinya Yamanaka
 
Shinya Yamanaka
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Shinya Yamanaka Interview

Embryonic Stem Cell Research

July 6, 2008
Kailua-Kona, Hawaii

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  Shinya Yamanaka

At the 2008 International Achievement Summit in Kailua-Kona, Hawaii, Dr. Yamanaka participated in a panel discussion of genetics in medicine. An excerpt from his remarks on that occasion precedes the text of this interview.

Dr. Yamanaka, you've been exploring a new form of stem cell research. How did you become involved in this work, and what do you see as the promise of stem cell research?


Shinya Yamanaka: It may be surprising, but I was a surgeon, like 20 years ago. And I found I was terrible in the operating room. So I thought, "Well, I won't help people by doing this!" That's why I decided to move to basic science, and I hope it's working. So, for the last -- let me see -- for the last 12 years I have been working on embryonic stem cells, ES cells. And I think probably... so please raise your hand if you know about ES cells. Oh, not all. Okay. Embryonic stem cells are stem cells which scientists generated from fertilized eggs. It was first derived from the mouse embryo in 1981, so 27 years ago. ES cells have two properties, very important properties. The first one: you can increase -- you can culture -- ES cells as much as you want, almost forever. The second, very important point of ES cells is that you can induce, you can make any types of cells from ES cells. Including cardiac cells, neural cells, blood cells, and also germ cells. That means you can prepare any cells, in any quantity, any time. Because of that, mouse embryonic stem cells -- ES cells -- gave rise to a new technology called "knockout mouse" technology. Which is a super technology in understanding the gene function, and as you may know, knockout mouse technology was awarded the Nobel Prize last year. Then in 1998, Dr. James Thomson developed ES cells from human blastocysts. That opened up a completely new way in regenerative medicine.


Because of his success, we have new opportunities to prepare cardiac cells and neural cells to transplant into patients. So when I saw his paper, I thought, "Wow! It's just amazing." But after that, I realized some problems with human ES cells.


You have to use human embryos to prepare human ES cells. And some people do not like that idea, including the president of your country. And also, because ES cells are not the patients' own cells, we have to deal with immune rejections after transplantation. So we decided to start a new project of our laboratory, in which we tried to generate ES-like stem cells, not from embryos, but from patients' own cells. We thought the project would be very, very risky, challenging, and it would take 20 or 30 years. But it turned out it took only five years to achieve that goal in a mouse. So we were able to publish the generation of new stem cells -- which were designated "iPS cells," induced pluripotent stem cells -- from mouse skin cells in 2006. And last year we were able to translate that technology to the human. So we and James Thomson, almost at the same time, were able to report that we can make ES-like stem cells without using embryos. We can convert a patient's skin cells directly to ES-like stem cells.


Could you clarify the significance of ES cells for us?


Shinya Yamanaka: ES cells have two important properties. The first one: we can proliferate -- we can culture ES cells as much as we want. So from a single ES cell we can have a million, billion or more ES cells within a certain period of time. The other important property of ES cells is something called pluripotency. So pluripotency means that we can make any types of cells that exist in our body. We have more than 200 types of cells in our body. So we can make those 200 types of cells from ES cells. So that's the second important property of ES cells.


Let's take a moment to really define what your stem cell breakthrough is, and we'll go from there to the impact it has on the future of medicine. Instead of using embryonic stem cells, you have taken skin cells, and what have you done with them?


Shinya Yamanaka: Because of this technology, iPS technology, now we can prepare many types of human cells. For example, heart cells -- cardiac cells -- or neural cells from patients. So you can easily imagine that without this technology, it's impossible to take cardiac cells from patients who have some kinds of cardiac diseases. If the patient dies, we may be able to get a small amount of cardiac cells from that patient, but those cells do not proliferate, so we cannot increase the number. But with this technology, all we need is a small piece of skin from that patient, and by making iPS cells, we can increase the number of cells as much as we want. And then we can make cardiac cells from those iPS cells. So I think for the first time in the history of medicine, we now have an opportunity to prepare many, many cardiac or neural cells directly from patients, and those cells should be very, very useful, to understand why those patients become sick. And to search for very effective drugs for that patient, and also to study -- to predict -- any side effect for that particular patient. So that is the most beautiful approach -- I mean application -- of this iPS cell technology.


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