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iPS cell research and the drive for cures(1) -All 4 episodes-

Prof. Shinya Yamanaka

Photo:Prof. Shinya Yamanaka

Prof. Shinya Yamanaka
speaks in his office at CiRA
at Kyoto University, Kyoto, Japan.

We took this opportunity to sit down with Prof. Shinya Yamanaka, the father of iPS cell research and director of the Center for iPS Cell Research and Application (CiRA), Kyoto University. CiRA was inaugurated in May 2010 as a new base for iPS cell research spanning the fundamental biology to preclinical studies and the development of clinical applications. And Yamanaka holds positions in both Japan and the United States, where he leads pioneering work in the field. We asked about the world state of R&D in this exciting field of science, and his views on how to move applications forward in the future.

Rapid uptake of iPS cells in research in the U.S.

Interviewer :
In the past, you remarked that ``Japan has one win and 10 losses in iPS cell research.'' How does that compare with other parts of the world? I know you hold a concurrent position at the Gladstone Institute of Cardiovascular Disease in San Francisco, so I was hoping you'd speak a bit about the differences in iPS cell research styles between Japan and the U.S.

Prof. Shinya Yamanaka(Sketch by Katsuaki Sato)

Prof. Shinya Yamanaka
(Sketch by Katsuaki Sato)

Yamanaka :
Well, this isn't limited just to iPS cells, but I think there are clear cultural differences. Japanese scientists tend to favor a linear mode of research with an emphasis on carrying on tradition, and people tend to be a bit embarrassed about jumping into whatever field happens to be hot. But in the U.S., it's more of a rotating model. If a new tool appears, many researchers quickly try to find ways of using it in their own field of interest. I can't say that one of these styles is better than another, but it seems difficult for Japanese researchers to keep up with a new technology when it appears.

Take knockout mice or DNA microarrays for example. Soon after the techniques were developed, you saw them being used everywhere in the U.S. I moved to the U.S. in 1992 to work on knockout mice, as at that time, there were few labs in Japan that made use of them. Similarly, around the time when I left for Japan in 1996, DNA microarrays(an analytical tool consisting of several thousand types of DNA sequences as DNA probes attached to a solid surface by semi-conductor micro-engineering) came into popular use in the U.S. It seems that in the U.S., people quickly jump into new technologies, and then there's a lag of two to three years before Japan catches up.

Japan has been on the sidelines in iPS cell research as well. When I used that line about "one win and ten losses" in media interviews, I was referring to the large number of people who have started using the technique in the U.S. There were scientists and engineers who were continuing their resesarch on human embryonic stem (ES) cells, having gotten funding from private sources, despite the restrictions on federal support, and they were quickly able to make the switch to iPS cells.
Since two years, I've been traveling to San Francisco every month, and I see the new progress that's been made every time I'm there. Even people who have never worked with stem cells are using iPS cells in their labs, trying new things. Japan will need to strengthen its game if it hopes to compete in the future of this field. There's a lot of ground to make up.

An emphasis on the creativity of young scientists

CiRA research building was completed in February.Sketch by Dr. Katsuaki Sato

CiRA research building was completed in February.
Sketch by Dr. Katsuaki Sato

Interviewer :
It was a very creative approach that led you to develop the first iPS cell techniques, and I understand you want to promote that same creativity in your new institute. What do you think of researchers of younger generations in Japan?

Yamanaka:Unfortunately, we haven't seen many young scientists coming up with new ideas on how to use this technology. I'd like to think that the younger scientists would be quicker to take it up, but so far there have not been many. I think it should be possible to propose novel, interesting applications for using iPS cells as a tool, but so far I haven't heard that many. It seems people are stuck in their habits of thinking.
At our new institute, about half of the 19 labs are headed by people in their thirties, many of them younger than 35. I'm hopeful that all this young energy will lead to new ideas.

When I was in my 30s, a famous scientist told me that “Great discoveries come about when young scientists disagree with their bosses and set out to have their own way.” I'm now in a leadership position, so I have to take care not to interfere with or stand in the way of anyone who wants to try something that runs contrary to my own habitual ways of thinking.
One serious problem, though, is that even young scientists are facing the limit of 5-year term or 3-year funding period, meaning that they have to show some productivity in the short term, and as a result, many people choose safe routes that they think are certain to yield publishable findings.

Photo:Researchers work at an open laboratory at the CiRA research building. (Left) People have discussions at communication space. (Right)

Researchers work at an open laboratory at the CiRA research building. (Left) People have discussions at communication space. (Right)


Interview by Miwako Homma, supervisor of iPS Trend website, and Katsuaki Sato and Bisei Watanabe from the Japan Science and Technology Agency.

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Shinya Yamanaka, M.D., Ph.D.

Director, Center for iPS cell Research and Application (CiRA), Kyoto University Senior Investigator, Gladstone Institute of Cardiovascular Disease

After graduating from the Kobe University School of Medicine in 1987, and doing his residency at National Osaka Hospital, Yamanaka received his Ph.D. in medical science from Osaka City University Graduate School of Medicine in 1993. He moved to the Gladstone Institute of Cardiovascular Disease in San Francisco that same year as a postdoctoral fellow. He became a Japan Society for the Promotion of Science special postdoctoral fellow in 1996, and an assistant professor in the department of pharmacology at Osaka City University the same year. He moved to the Nara Institute of Science and Technology as associate professor in 1999 and was appointed professor in 2003. He took a professorship at the Institute for Frontier Medical Sciences, Kyoto University in 2004, moving to the Institute for Integrated Cell-Material Sciences (iCeMS) at the same university in 2007, and named director of CiRA,iCeMS Kyoto University in 2008. He is the director of CiRA, Kyoto University since April 2010.

Major Awards

2004 Tokyo Techno Forum 21 Gold Medal (Japan)
2008 Robert-Koch Prize (Germany)
2008 Shaw Prize in Life Science and Medicine (Hong Kong)
2008 Medal of Honor with Purple Ribbon 2008 (Japan)
2009 Canada Gairdner Foundation International Award (Canada)
2009 Albert Lasker Basic Medical Research Award (U.S.)
2010 Imperial Prize of the Japan Academy (Japan)
2012 The Nobel Prize in Physiology or Medicine
etc.

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