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The Mystery of Skin Pattern Formation and Blinking -- Unraveling a Life System Riddle

Animal Shapes and Skin Pigment Patterns are Made by a Wave

HIRANO Both of you paid attention to the wonder of living things other researchers didn't notice and achieved research results. You look like you enjoy research itself. First, Professor Kondo, would you talk about your research?
KONDO I was interested in how complex shapes in animals and skin patterns were generated, and for the last 20 years, I researched pigment patterns on the skin of fish. I'm going to spoil the riddle for you, but the pattern is made by a wave. As shown in ripple marks on water and sand, patterns by waves can be seen everywhere in nature.
In the animal body as well, regular vibration caused by intercellular chemical reaction spreads the surrounding area and causes waves. I published my thesis verifying this in the British science magazine Nature, which made me a professor. I don't think it's an exaggeration to say that that's all there is to my career.
HIRANO You mean that animal skin patterns are generated not by genes but by a chemical reaction?
KONDO That's right. Alan Mathison Turing (1912~1954), a British scientist, mathematically predicted this. It may sound a bit difficult, but if two chemical substances expand while reacting with each other, differences in their concentration may make waves. Turing thought that such waves create animal shape and skin pigment patterns and expressed waves in an equation and demonstrated that that could produce patterns similar to animal skin patterns. Skin pattern created by this equation is called the Turing pattern and actually when drawn using computer simulation, stripes, spots, leopard patterns, and giraffe patterns can be easily produced. However, there was no proof.
I found that stripes and skin patterns in fish move as predicted by Turing's theory and verified the existence of the Turing pattern for the first time in the world.

Proving the Theory of Autonomous Creation of Skin Pigment Patterns through Fish

HIRANO What do you mean by "the stripe pattern moves"?
KONDO When a striped angelfish grows, the number of stripes increases, but the spacing between the stripes remains the same. How does the number increase? To tell the truth, a line splits into two and opens little by little as a zipper does. Even fish experts didn't know this secret. The stripe pattern moves just 1cm in three months, so one cannot see that unless one examines them closely. However, if you know Turing's theory, you can predict the change using computer simulation. Then, all you have to do is take up your stand near the water tank with camera in hand and wait patiently. The moment I confirmed that the pattern moved was the happiest moment of my life.
HIRANO  Why did you get interested in shape and skin patterns in the first place?
KONDO Because it was incomprehensible. When I was a high school student, I learned that newts regrow lost limbs from Nikkei Science, the Japanese version of Scientific American and became interested.
Around that time, people began to understand about genes and it was the beginning of an age when people thought if one knew genes, one could know everything. Call me contrary, but I intuitively thought I would address the challenges that one cannot solve even if all genes are decoded. Generation is such an issue.
Since genes determine characteristics of only one protein molecule, it's a little bit of a stretch for us to think that genes determine the shape of a huge, complex, and sophisticated structure of an individual. But I didn't know how and what to study, so I learned biology at university for a while and waited for a chance. Some 15 years later, I encountered Turing's theory advocating that animal skin patterns were formed using chemical reactions. I thought ‘This is it!’ This theory was not accepted at all at that time, but I thought this was a chance.

Elucidating Brain Mechanisms through Blink Research

HIRANO Professor Nakano, you're examining neural mechanisms for blink control and systems for cognition and behavior in autism spectrum disorders, aren't you?
NAKANO I want to clarify the brain mechanism and behavior through blink research. We blink every three seconds, 20 blinks a minute on average. There are three types of blinks: Reflexive Blinking caused by stimuli such as sound, light, and wind; Voluntary Blinking by closing eye lids intentionally; and Spontaneous Blinking occurring without any reasons. For humans, spontaneous blinking occurs most frequently. It is said that spontaneous blinking is for lubricating the front surface of the eye; however, research regarding the surface of the eye shows that blinking three times a minute is enough for lubrication alone. Then, why do we blink so frequently? In order to elucidate this mechanism, I performed experiments to examine the timing of blinks by getting subjects to watch two types of video stories without sound.

Making Units of Information by Blinking

HIRANO Why did you pay attention to the timing of blinks?
NAKANO I guessed that blinking was involved in information processing in the brain and wondered if individuals watching the same video stories would blink with the same timing. I measured eye blinks of people who were watching Mr. Bean, a British sitcom, in which different stories were being played one after another. It was found that people blinked at implicit breaks of information such as the end of the protagonist's action and repeated presentations of a similar scene. In other words, we find units of information unconsciously and blink at scene breaks.
Then, I examined brain activities while the subjects were blinking with fMRI, a measuring device of brain blood flow. While neural network activities paying outward attention temporarily decreased, brain activities in the default mode network, which was believed to be related to inward information processing, increased.
From these facts, I think blinking functions to divert one's attention from the object one is watching by switching antagonistic neural network activities in the brain and make units of information.
HIRANO You're also researching cognitive behavior of people with autism. How is that related to blinking?
NAKANO Blinking of patients with autism do not synchronize with those of other people even if they are watching the same video stories. I think they have their own way of information processing and their way of seeing the world is different from others so their blinking does not synchronize with others.
HIRANO I hear that you returned to the research world after working at a company.
NAKANO Researching became fun while I was writing my graduation thesis, but I had already determined to work outside. So I entered a major brewing company and got a marketing job. But I didn't get the same pleasure of finding things on my own that I got through research. In the research world, even if one is thought to be one's own person, if he/she gets results, he/she is recognized. I couldn't forget this pleasure research brings. That’s why I returned to the graduate school of my alma mater.

Scholarship and Research are Intelligent Entertainment

HIRANO What drives you to perform research?
KONDO Isn’t it amazing that animals’ skin patterns are formed by a wave? I’m excited about discovering truths that no one knew that are different from how they used to be. I think that simply understanding things is very enjoyable form of intelligent entertainment.
NAKANO I want to conduct research about things that no one pays attention to but are actually very important.
HIRANO What do you think about the number of female researchers continuing to be so small?
NAKANO Being unique is a strength regardless of if you are a man or woman. Even if the time you have available is limited because of child-rearing, as is the case for me, if your research is unique, you can find your place.
KONDO I hope more women will be involved in research, but I think it’s better not to increase the number of female researchers across the board, but rather, to allow the number to increase naturally.
HIRANO Currently, researchers tend to be involved in research based on whether it will be helpful in society. What do you think about that?
KONDO I am involved in well-funded research so I don’t think that basic research is underestimated. However, universities need to take a decisive stance that the results of basic research will eventually contribute to society, no matter how many years it takes.
NAKANO Because I can spend the budget even on unusual research like mine, I’ m satisfied with systems such as Grant-in-Aid for Scientific Research. It's not possible to know what field of study a discovery will be made in advance, it's necessary to have diversity in research. If research is done for decisive objectives alone, I’m afraid Japan will succumb to foreign competition.

Further Elucidating Mysteries and Meanings

HIRANO Finally, tell me about your dreams.
KONDO Currently, I'm involved in bone research as part of shape research. I'd be happy if I could find my own theory, near-Tuning's theory. I also hope it will become possible to change bone shape at will in the future. For example, changing the shape of deer into that of a giraffe. If we can unravel the mystery of what living things did in their long process of revolution, I’m sure we can manipulate their shape, too. It's already possible to change skin pattern at will, for example, changing the pattern in zebrafish to a leopard pattern.
NAKANO I found that a dynamic change was caused in associated with blinking, so my next goal is to elucidate why one needs to change brain activities at the high frequency of once every 3 seconds. I hope that this will lead to the discovery of a new principle of a rhythm of information processing mechanisms in the brain beyond the blinking function.
HIRANO You are on the right track. I can count on you to do great things. Scholarship will never progress without researchers with strong characteristics like you. Thank you for your time today.

Scholarship and Research are Full of Dreams -- Comments from President Hirano after the Talk

We want to know unknown things, which is essential to human nature. Research and scholarship are full of dreams, and make society happy and spiritually rich. Osaka University aspires to become one of the world's top 10 research universities by our 100th anniversary in 2031. We’d like to contribute to a society facing a lot of challenges by improving the quality of scholarship and research. There is diversity in the world -- differences in race, culture, and religion. This diversity is essential for creating groundbreaking innovation, but it has also brought about negative results such as obstacles and conflicts. "Scholarship," a kind of language common to all humankind, can overcome such negative aspects of diversity. Osaka University creates harmonious diversity through scholarship and will shine into the 22nd century -- this is my great dream as a president.

Shigeru KONDO
A graduate of The University of Tokyo's School of Science in 1982, Professor KONDO graduated from Osaka University's Graduate School of Medicine in 1984. After graduating from Kyoto University's Graduate School of Medicine in 1988, he began serving as a researcher at the Biochemistry Course I at The University of Tokyo’s School of Medicine in the same year. In 1990, he became a cytobiology researcher at the Biocenter the University of Basel, and an assistant at the Kyoto University gene testing facility in 1993. He became a lecturer at Kyoto University’s School of Medicine In 1995 and a professor at the Faculty of Integrated Arts and Sciences, Tokushima University in 1997. He became a team leader of the RIKEN Center for Developmental Biology Laboratory for Positional Information in 2002 and a professor at the Graduate School of Science in 2003. He began at his current position as professor in August 2009. His research themes are “Experimental and mathematical analyses of biological pattern formation” and “Molecular level clarification of the mechanism for animal skin pattern formation.”

Tamami NAKANO
A graduate of The University of Tokyo’s Faculty of Education in 1999, Associate Professor NAKANO graduated from The University of Tokyo’s Graduate School of Education in 2009. She became a Fellow DC in 2007 and Fellow RPD in 2009 at the Japan Society for the Promotion of Science (JSPS). She became an assistant professor at Juntendo University’s School of Medicine in 2010 and an assistant professor at the Osaka University Graduate School of Frontier Biosciences in 2011. She began at her current position as associate professor at the same school in 2012. Her research themes are "Neural mechanisms underlying control of eye movements and blinking" and "Analysis of cognition and behavior in autism spectrum disorders."

Toshio HIRANO
A graduate of Osaka University's Faculty of Medicine in 1972, President HIRANO studied at NIH (U.S.) from 1973 through 1976. He became an assistant professor at Kumamoto University in 1980. He then became an assistant professor in 1984 and a professor in 1989 at Osaka University. Following that, he became the director of the Graduate School of Frontier Biosciences in 2004, and a director of the Graduate School of Medicine and the dean of the Faculty of Medicine in 2008. He assumed the the 17th presidency of Osaka University in August 2011. He served as Chairman for the Japan Society for Immunology from 2005 to 2006. He is also a member of the Council for Science, Technology and Innovation and The Science Council of Japan. He has a doctoral degree of medicine. His awards include the Sandoz Prize for Immunology, Osaka Science Prize, Academic Award of the Mochida Memorial Foundation, Medical Award, Fujiwara Prize, Crafoord Prize, Japan Prize, and Medal with Purple Ribbon by the Emperor of Japan.

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