Shinya Yamanaka Interview (page: 3 / 6) Embryonic Stem Cell Research	Print Interview

Did you ever see being a doctor as a fallback plan, if other things didn't work out?

Shinya Yamanaka: Yes, because I had a medical license. Although I'm not so good at seeing patients, because I only did two-year residency in orthopedic surgeon. I think having a medical license is kind of a backup. I can always go back to clinics and do a training again. That did help me to do some very risky projects in science.

Where did you take these risks? Were they in the lab? How was risk important in what you were doing in the lab?

Get the Flash Player to see this video. Shinya Yamanaka: In order to achieve something, it's very important that it should be very risky, because if it's not risky, that means it's very easy, many people can achieve that. But if you really want to solve very tough questions, or very difficult goals, you really have to take risks.

In your field, what is a risk? Could you give us an example?

Get the Flash Player to see this video. Shinya Yamanaka: For the last ten years or so I have been working on stem cells, especially embryonic stem cells, ES cells. When I started working on ES cells, most people were trying to generate some kind of cells such as cardiac cells or neurocells from ES cells. So that kind of project was not so risky, because many people are trying to do that. To me, at that time, the most risky project was the reverse. Instead of making some special cells from ES cells, I wanted to make ES cells from, like, skin cells. So it's the opposite direction, and I knew it would be very risky. The chance is very small.

Did you find more collaboration in the lab at Nara than at Osaka?

Shinya Yamanaka: Yes. In Osaka I almost worked by myself. I used many, many mice. I had almost 1,000 mice for my own project, and I had to take care of all of them by myself. So it was a lot of work. After I moved to Nara, I had many, many technicians and students who helped me. So I was not alone, that's very important for me.

Did the direction of your work change when you came to the second lab?

Get the Flash Player to see this video. Shinya Yamanaka: When I went to my second lab, in Nara, it was my first time to be the so-called "principal investigator." So I became independent for the first time in my scientific career. That means I will have to have many students and many post-docs, so I thought I really have to have some wonderful research project in my own lab to attract as many people as possible. So I thought what the goal should be, and I thought making stem cells from patients' own cells should be my goal. That was the beginning of my full research.

[ Key to Success ] Vision

Did it attract students as you'd hoped?

Shinya Yamanaka: Actually it worked, yes. I got more then 20 or 30 applicants that year. I could only afford three students, so I was able to select the three best students out of those 30 applicants, and they did very well.

The dominant trend in research at the time was trying to make different kinds of cells from stem cells. It's surprising to hear that there was so much interest in your work, when you were trying to do the reverse, make stem cells from ordinary cells. Did it surprise you that you would have that kind of response?

Shinya Yamanaka: Well no, actually. I thought that kind of idea should attract many young scientists.

In these induced pluripotent stem cells, iPS cells, how do you maintain pluripotency, and why is it important?

Shinya Yamanaka: iPS cells and ES cells are indistinguishable in many aspects. We have good conditions for mouse and human ES cells to maintain pluripotency. We can use exactly the same conditions to maintain mouse and human iPS cells. So it is not so difficult. Pluripotency is the most important property of ES and iPS cells, because with the pluripotency, we can make many types of cells from stem cells.

Can you describe the process of reprogramming adult cells to revert to an embryonic state?

Shinya Yamanaka: It's very simple. All we have to do is to put three genes -- namely Oct-3/4, SOX2 and Klf4 -- into adult skin cells, and those three genes can convert skin cells into stem cells.

When we read about your work a few months ago, you were using four genes, weren't you? How did you get it down to three?

Shinya Yamanaka: That's a good point. Originally we thought four genes are required and one of the four genes is very dangerous because it's c-Myc. It's a famous cancer-causing gene. By modifying our protocol, we were able to omit the usage of c-Myc. So now we only need three genes, not four genes.

A couple of months ago, wasn't it thought that two of the genes were perhaps cancer-causing? Is it only the one gene?

Shinya Yamanaka: Yes, actually. One of the three genes, Klf4, had some relationship with cancer, but compared to c-Myc, the risk is much, much smaller.

Now that it's only three genes, has it reduced this risk?

Shinya Yamanaka: Yes.

So it's gone from a 50/50 ratio to one out of three?

Shinya Yamanaka: Yeah.

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