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

When you began your work with human cells, how likely did it seem to you that the same three or four genes that reprogrammed skin cells in mice could do the same thing in humans?

Get the Flash Player to see this video. Shinya Yamanaka: Well, we have mouse ES cells and human ES cells. They are common, in that they are pluripotent. But they are different, so different in many aspects. They look different. The morphology of mouse ES cells and human ES cells are totally different, and the culture condition of mouse and human ES cells are also different. So from those substantial differences, I thought that the same three or four factors may not work on human cells. But it turned out the same factors can generate human iPS cells, so it was rather surprising to us.

It seems like you were taking a very large risk.

Shinya Yamanaka: The real risk was to start this project in mice, because we knew that chance is very, very small, and we thought it might take 20 -- or maybe 30 -- years. So moving from mouse to human was not so big a step. The first step was the highest step for us.

What were some of the challenges in working with the mice? Is it true that the mice had to be interbred, and then the cells had to be infected with a virus carrying the gene?

Get the Flash Player to see this video. Shinya Yamanaka: It must be infected by viruses having those four factors -- three or four factors. So viruses function as a so-called vector to deliver genes into cells. It's just like a gene therapy. In gene therapy, you use retrovirus to transfer one gene into patients. So we use the same retroviral system in order to transfer -- deliver -- three genes into skin cells. As you may recall, gene therapy to immune-deficient children was very effective in the beginning. But unfortunately, more than 50 percent of those patients who got gene therapy developed tumors, leukemia, after the treatment. That was because of the retroviral integration into a host genome.

So we have to worry about the same type of tumor, leukemia, in iPS cell technology.

What kind of setbacks have you had to deal with along the way, and what have you learned from them?

Get the Flash Player to see this video. Shinya Yamanaka: Failure is very important. Failure is kind of a beginning of success. Even in my own scientific experiments, I had many, many failures. But in many cases, those negative results gave me many insights into new directions, as you go. You know, in Japan we have a short sentence which -- in Japanese it's stem batoh. That means if you fell down seven times, you have to wake up [get up] eight times, then you can succeed. So I think that's very true in science.

In this country, a lot of funding for scientific research is controlled by the federal government. Have you seen any negative results or obstruction because of the current administration's views on funding for this field of science?

Shinya Yamanaka: Funding is essential. Without funding you cannot continue a long project.

Get the Flash Player to see this video. Since this project was risky, everybody can tell that it won't work, so I had a hard time to get enough funding. But back in Japan, I was very lucky to have a five-year period of relatively big funding by the Japanese government. But that program was -- how to say? One very famous Japanese scientist was handling that funding program. I presented our data and our project to him and he told me that, "I knew this wouldn't work." But he said he thought this was a good challenge to be funded. So I was very lucky to get some good funding. So I think I really need that kind of person who can predict which risky project would be funded. It's a very difficult job, but I think that kind of person would be essential.

Your work is at the frontier of cell research right now. Where do you think the frontier will be 25 years from now?

Shinya Yamanaka: Treating cancers is still very difficult, but I hope that within the next 15 or 25 years, most of the cancers will be cured. Right now it's still very difficult.

What would you like to leave as your legacy? What mark would you like to leave?

Shinya Yamanaka: As a scientist who developed this iPS technology, I hope to see that technology used in clinics. That's my hope. At the same time, if this technology is not good, I'd like to say no to this technology myself. Right now I have to be very neutral. Again, this technology is still very young. We have very good hopes, but there are many, many hurdles as well. So I really have to say yes or no to this technology myself, that's my hope.

What encouragement would you give to students and future scientists?

Shinya Yamanaka: There are many diseases which we cannot cure with the current medical technologies, and it is basic science which can cure those diseases and those patients. So I hope many, many talented, young students will be scientists.

Thank you Dr. Yamanaka.

Shinya Yamanaka: Thank you very much.

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