Shimadzu Corporation 150th Anniversary Website

150 YEARS SPECIAL DIALOGUE

SPECIAL PROJECT

Recipe for Innovation

Nobel Prize Winners' Dialogue

Executive Research Fellow
Shimadzu Corporation

Koichi Tanaka

Professor, Director Emeritus
Center for iPS Cell Research and
Application, Kyoto University

Shinya Yamanaka

Shinya Yamanaka, Director Emeritus of the Center for iPS Cell Research and Application (CiRA), Kyoto University, was the first in the world to successfully generate induced pluripotent stem cells (iPS cells), which paved the way for regenerative medicine to treat many intractable diseases and injuries. Koichi Tanaka of Shimadzu Corporation developed the laser ionization mass spectrometer and engages in research related to proteins, which play important roles in the structure and function of living organisms. In this Special Dialogue, these two Nobel Prize-winning researchers discuss how they create innovation. We hope their discussion will motivate future researchers.

Shinya Yamanaka

Professor, Director Emeritus
Center for iPS Cell Research and
Application, Kyoto University

Born in 1962, Dr. Yamanaka is a native of Osaka Prefecture. He is a graduate of Kobe University School of Medicine and completed his doctorate at the Graduate School of Medicine, Osaka City University. After serving as a professor at the Institute for Frontier Medical Sciences, Kyoto University, among others, he assumed the post of Director for the Center for iPS Cell Research and Application at Kyoto University in 2010 and became Director Emeritus in 2022. He was awarded the Nobel Prize in Physiology or Medicine in 2012. Dr. Yamanaka also serves as the President of the CiRA Foundation.

Koichi Tanaka

Executive Research Fellow
Shimadzu Corporation

Born in 1959, Tanaka is a native of Toyama Prefecture. After graduating in 1983 from the Department of Electrical Engineering, School of Engineering, Tohoku University, he joined Shimadzu Corporation and was posted to the Central Research Laboratory. In 2002, he was awarded the Nobel Prize in Chemistry for developing the soft laser desorption ionization method. Since 2003, he has been engaged in research and development promotion as General Manager of the Koichi Tanaka Mass Spectrometry Research Laboratory.

Discoveries that started a new chapter in the history of science

— Teamwork has gotten us this far

Tanaka: You first announced the successful generation of iPS cells in 2006. The subsequent two decades seem to have passed quickly.

Yamanaka: I remember the discovery as if it were yesterday, but circumstances have changed significantly since then. We had a small lab at the time, and even though we developed the iPS cell technology, it was definitely impossible to make that technology available to patients on our own.
We received government support and initiated joint research with multiple research groups. Today, more than ten projects have reached the stage of clinical trials in Japan, and the benefits of this research are reaching patients little by little. I like marathons, and if I compare these efforts to a citizens’ marathon, no one has dropped out, and research teams have gotten this far. It’s truly gratifying.

Tanaka: I’ve always admired you. Just as stamina is necessary to complete a marathon, I think leaders of long-term projects are called on to set long-term goals and work toward them with tenacity. I think your strong will as a team leader communicates itself to the several hundred people involved in the research and serves as a motive force to keep moving forward.

Yamanaka: In fact, I have learned a lot from marathons. Runners prepare themselves for a race with more than a year of training. They do this every year, and in that way, they improve their time little by little until they can run a good race. Research and development require a far longer timescale than marathon training, but the accumulation of diligent effort is sure to take you closer to your goal, one step at a time. Like any race, the middle and end stages are very tough, but no one around you is taking it easy. That’s why we encourage each other as we pursue the goal. You lead a team in your own work at the Mass Spectrometry Research Laboratory, so I’m sure you can appreciate this.

— The joy of team accomplishments

Tanaka: I’m not the leader type, so perhaps I look at it in a slightly different way. It’s been 20 years since I was appointed to head the Mass Spectrometry Research Laboratory, which is an internal Shimadzu unit. To be honest, as director, I’m not so much managing the organization as I am enjoying doing experiments with my subordinates. The joy of making new discoveries never changes, and when things don’t go well, we discuss the possible reasons collectively, since we believe that failures often point to new discoveries. I nurture a culture of not fearing failure, and thanks to this, we’ve been able to conduct research without restrictions. I believe this has also led to a number of major discoveries.

Yamanaka: It’s truly wonderful that you can still enjoy experiments. In my case, a graduate-level experiment was the reason I decided to go into research. My graduate advisor told me how he believed the experiment would turn out, but in fact, the result was completely different. When I saw this unexpected outcome, I was surprised by how much it excited me. What could be more exciting, I thought? Until that point, I had been planning to become a clinical physician, but in that instant, I realized that research was my true calling. If not for that moment, I might never have encountered iPS cells.

Tanaka: That’s fascinating.

Yamanaka: I’m well acquainted with your respect for your team. Working alone can be exciting, but when collaborating with a team, one can achieve things that would be impossible working alone. And when it results in a discovery, there’s nothing more gratifying. You were quoted in a recent newspaper article, frankly stating how rewarding it can be to succeed as a team. You said, “Designation as an IEEE Milestone* is more rewarding to me than the Nobel Prize,” and I found myself strongly agreeing.

Tanaka: Thank you. At the time, I chose to say that the designation was “deeply significant” to place more importance on how this was an achievement for the entire team. Calling it “gratifying” would have made me feel guilty, given the many people involved [laughs]. To demonstrate that the method I discovered could be used for mass spectrometry of proteins, we had to sort the proteins by size, characterize them in terms of their electrical signals, measure those signals, and analyze them further. Each of these R&D processes would have been impossible without the cooperation of the entire team. We utilized each member’s expertise, conducted research in parallel, and ultimately commercialized the product. I think the IEEE Milestone recognition acknowledged the hard work on the part of everyone. That’s why I said it was significant.

*IEEE (the Institute of Electrical and Electronics Engineers) Milestone honors significant technological achievements at least 25 years after their introduction. In May 2024, Shimadzu Corporation’s LAMS-50K laser ionization mass spectrometer (launched in February 1988), developed by Koichi Tanaka and others, was recognized as an IEEE Milestone. It was the world’s first commercially available device that applied soft laser desorption ionization techniques, leading to new pharmaceuticals and diagnostic capabilities in the fields of molecular biology and medicine.

— The lineage of Mendel and Darwin

Yamanaka: The laser ionization mass spectrometer has greatly advanced molecular biology and medicine since you and your team developed it. A single instance of groundbreaking research has opened many new directions. In the same sense, we are still doing research based on Mendel’s laws of inheritance and Darwin’s theory of evolution. These theories continue to be vital and viable today. My own research may not even amount to a single page in the long history of science. Even so, seeing the next generation develop my work in ways I never imagined gives me a real sense that I’m supporting a part of history as a researcher, and that makes me happy.

Tanaka: You discovered that previously differentiated cells can be reprogrammed, completely overturning the conventional view. Using a book as an example, even an entire chapter might not be enough to cover your discovery. But you are absolutely right. At first, I felt very fortunate to have actually achieved something, but seeing many other researchers joining in and working to apply the discovery to molecular biology and medicine makes me excited for the future, and I realize that I need to work harder myself.

Curiosity as the foundation of discovery

— Applying interest in other domains to chemistry

Yamanaka: You majored in electrical engineering as an undergraduate. I imagine you’re often told that going from electrical engineering to chemistry was an unusual career move.

Tanaka: I am. Maybe it was unusual. But I think coming in as an outsider enabled me to make that discovery.

Yamanaka: Really? How so?

Tanaka: My hobby is photography, and in elementary school and junior high school, I liked to draw. If I saw a map, I loved to think about what kinds of fruit grew there and what the cities were like. In university, I majored in electrical engineering and did research into ways to suppress radio waves that strike and bounce off skyscrapers. Later, as an adult, I discovered the technology to ionize proteins using lasers. People thought I was letting my work go to waste, but at the time, I was able to go as far as I did because I took a schematic design I had in my mind, the same type of design I was interested in, and researched it as a university student and applied it to the entirely unrelated domain of chemistry. In other words, my interest in images, whether visual or schematic, led me to success.

Yamanaka: That’s very interesting.

Tanaka: Cameras and lasers both involve electromagnetic waves and both use lenses. When I needed a device that used lasers, of course, I was a complete beginner, but I was interested. Why? Because I was interested in cameras.

Yamanaka: So there was a common denominator.

Tanaka: Yes, and there are other ways that my hobby influenced me. Back then, cameras used film, as you know. When you take a color photo with film, a mixture of cyan, magenta, and yellow reproduces all the other colors. What interested me was why only certain colors are found in reflected white light. In a sense, this is also about chemistry.

Because I had this sort of basic curiosity, I could also be curious about something I’d never been involved with before, that is, ionizing a target with a laser. In that sense, I think having curiosity is the most important thing. Even expertise in an unrelated field will give you new perspectives for interpretation. Incorporating these new perspectives is always very interesting. It’s why I’ve never lost my interest in chemistry. I hope young people in particular will be sure to preserve their curiosity.

In addition, even with a separate domain that at first seems unrelated, it’s important to remember that your interest in that field may be something you can use, and this perspective can be useful in enabling you to continue your work or your research.

Yamanaka: That’s very true. Knowledge from other domains is important.

Creating opportunities to encounter other domains

— Do you assume you will fail?

Tanaka: You also often say that involvement in other domains is important for creating innovation.

Yamanaka: Yes. I belonged to the Faculty of Medicine at university and did my research at a medical research institute, so for 12 years, I focused on the medical field. In December 1999, I was hired as an assistant professor (now equivalent to an associate professor) at the Nara Institute of Science and Technology (NAIST). It was there that I had my first experience managing a research lab. It’s an interesting university where researchers from many different domains, such as physics, agricultural science, and engineering, work in the same building. This approach led to many important contacts.

At the time, I had just begun my research on generating pluripotent cells that could transform from somatic cells into any type of cell. To be honest, while I started with a great deal of enthusiasm, I was not convinced it was possible. At one point, I had the opportunity to present my research to others at the institute. I said, “I want to transform skin cells into pluripotent cells, but I am prepared for the difficulty of this challenge.” Afterward, another professor—a plant specialist—sought me out and said, “Plants are collections of pluripotent cells.”

For example, cherry trees can be propagated with cuttings because they produce pluripotent cells. It struck me that I had arbitrarily assumed that it would be too difficult. It was then that I thought, if plants can do it, animals ought to be able to do it as well.
About five years later, I succeeded in generating iPS cells. If I had never joined NAIST, I would never have met that plant specialist, and I might have given up before I reached my goal.

— Combining different domains

Tanaka: Masatoshi Koshiba (winner of the 2002 Nobel Prize in Physics for research into neutrinos) loved Mozart. Satoshi Omura (winner of the 2015 Nobel Prize in Physiology or Medicine for the discovery of ivermectin) is well-known as an art lover. Historically, many scientists have also had a deep appreciation of the arts. Perhaps that interest had something to do with their scientific discoveries. It’s an exciting thought.

Yamanaka: I like that. Exchanges between people with completely different backgrounds can lead to discoveries and new opportunities. This is indeed the case. On this floor where we are now conversing, we can see all the way across the floor. This design is based on the concept that many different types of people can interact. We had our institute, the Center for iPS Cell Research and Application, Kyoto University, designed to keep walls to a minimum and allow people to interact. Outside Japan, barriers between academic domains are even lower. Systems are set up to let people with all kinds of cultural backgrounds interact easily in every way imaginable, with many professional specialists designing buildings to facilitate this. In Japan, these initiatives have been progressing slowly. However, I recently visited the Center for Cancer Immunotherapy and Immunobiology of the Graduate School of Medicine, Kyoto University, headed by Dr. Tasuku Honjo (winner of the 2018 Nobel Prize in Physiology or Medicine for work in cancer immunotherapy). It was very eye-opening. I had a fixed image of research centers at national universities being square buildings, but this new research center, designed by Mr. Tadao Ando, is round. It gave me the feeling that the building would help researchers avoid fixed ideas and create new concepts.

Tanaka: That reminds me. The economist Joseph Schumpeter (1883-1950) said something interesting. When we think of innovation, we tend to assume that it requires a total technological revolution. But Schumpeter said, “Innovation is created out of new combinations.” I remember his words giving me considerable courage to think that I, too, could create innovation. To create the new, you don’t necessarily have to develop something totally new. It may be that anyone can create new ideas or developments by combining different domains. The important thing is to realize that it is possible.

— The courage to break the mold

Yamanaka: My understanding of innovation is that it involves “breaking the mold.” If you have a fixed framework and you do all your thinking in terms of it, new ideas won’t emerge. What’s important is how you can get outside the fixed framework. I once heard a very interesting talk by Mr. Tamasaburo Bando, the Kabuki actor, about his art. Bando devised many innovative forms of expression that did not previously exist in Kabuki. He said it was important to study the established forms thoroughly and then see if you can break the mold. If you fail to learn the established forms before attempting something new, it’s not the same as breaking the mold. It’s just formless. His words made a deep impression on me, and I was in complete agreement. For any domain, it’s important to learn the basics thoroughly, but don’t swallow them whole. Think about what you learned, then act. I think this will lead to true innovation. The Japanese education system has long struggled to accept deviations from established forms, but more and more young people are recently breaking free from conventional frameworks. Watching them, I believe Japan may well leap forward again over the next 30 years.

Tanaka: I hope they will have confidence. I feel that things have not gone well for Japan over the past 30 years. There’s a sense that hard work isn’t worth it, and more people are afraid of failure. To change that mindset, I think we have to keep taking on new challenges.

Recipe for Innovation

Nobel Prize
Winners' Dialogue

Executive Research
Fellow Shimadzu
Corporation

Koichi Tanaka

Professor, Director Emeritus
Center for iPS Cell Research and
Application, Kyoto University

Shinya Yamanaka