Biohistory Jyournal, Autumn, 2004
Scientist Library: Index > Genetics of behavior-Search for the new theory
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Genetics of behavior - Search for the new theory
Yoshiki Hotta,
Professor Emeritus, The University of Tokyo
Professor Emeritus, National Institute of Genetics
Professor Emeritus, the Graduate University for Advanced Studies
Director, the Research Organization of Information and Systems
photograph by Naruaki Onishi
I was interested in the radio during my childhood.
That's why my interest in living creatures is the mechanism.
The basis of the human being and the fly are the same--DNA.
I was drawn to genetics, which tell us it.
Then, I tried to unravel the mystery of the brain.
My interest now is how to understand the diverse and complex phenomenon of life while it remains so complex.
The time has come for the boy interested in insects and the radio to tackle this.

 My encounter with genetics
    I was raised in the Hotta home from my childhood, but my relationship to them was not one of parents and child. Genetics gave me with the opportunity to discover this. When I was in primary school, I was interested in blood type heredity, which was covered in my science book. I quickly distributed a questionnaire to my classmates asking them to write the blood type of their parents, their siblings, and themselves. I found several combinations including mine that did not conform to the rules in the book. When I declared that the book was mistaken, the teacher, who had turned pale, took away my questionnaire. I realized that the rule was correct after all.
    When I was even younger, I thought it was fascinating that a voice could come out of a speaker. I thought there had to be a person inside, and I pried it open. I was a child that would immediately begin examining things and taking them apart if I was interested in them.

 Brain research starts with electrophysiology
    In high school, I thought I would like to become a doctor and help people, so I enrolled at the University of Tokyo. Unfortunately, I disliked biology. On the biology portion of the test for admission to the School of Medicine, I wrote, "I cannot answer these stupid questions. I will certainly fail the examination. Yoshiki Hotta." I turned in a blank sheet. Somehow, I wound up passing the examination. Professor Junnosuke Nakai (Quarterly Biohistory Journal, Issue #4) had written the questions for the test. Though he was angry with me, he took a liking to me.
    I later found out about the new research in biology into such subjects as molecular genetics and the analysis of cerebellum circuits, and I took the basic medicine course. Many talented people had gathered under Professor Setsuro Ebashi (Quarterly Biohistory Journal, Issue #12), and the atmosphere was very open. I wasn't interested in the lab's research topic of muscle contraction mechanism, and I was self-centered enough to announce that I wanted to study the brain. I was told that electrophysiology would be important if I wanted to do research into the brain, so I was given the research topic of measuring the action potential of unstriated muscle. The work combined pharmacology and physiology, and my research results appeared in Nature and Science.
    While conducting research into the muscular system, I wondered if I could conduct brain research using genes, and I searched for an animal whose genes I could use. Then I heard from the United States that Seymour Benzer, the leading figure in fuzzy molecular genetics, had begun studies of brain genetics by examining the activity of Drosophila. I heard that he was looking for someone knowledgeable about electrophysiology. When I wrote him a letter, he replied that he had created a mutant incapable of the normal activity of walking toward light, and that he was looking for the causative gene. I thought, "How interesting!" I had no job even after finishing graduate school, so I went to the United States.

 Studying the Drosophila mutant
    From measurements of the electric potential of the retina, we found that many of the mutants that would not face the light were blind. Abnormal eye function was not limited to abnormal genes functioning in the eye, however. As a Vitamin A deficiency causes poor eyesight, vision can deteriorate due to a different cause, even with normal genes in the eye. This was a difficult problem.
    After thinking it over, I solved the problem creating a mosaic that had the mutant gene only in the eye, not in the body. Mosaic analysis has been a stimulus for many researchers and created a new area for drosophila researchers.
    After returning to Japan, I began work in physics (actually biophysics) at the University of Tokyo. Neither the Biology Department nor the Medical School expressed interest for me. Thanks to them, I taught genetics to physics students, which resulted in the development of many interesting researchers. In addition to my activities, I began studying generation, and my attention was drawn to the process in which nerve circuits are created. I discovered a mutant in which the neuroglial cells had disappeared from the brain, and in which there were only nerve cells. The separation of the nerves and glia from the neural stem cell was a clear result indicating that a switch was turned off and on in one gene. I was very happy to make this discovery.

 The next thing to come after DNA /
 Expectations for theoretical biology
    Gene-centered research into the brain has been achieved, but the mechanism of the brain cannot be elucidated. The phenomenon of life is diverse and complex, and we must think about understanding it in its complex state. This requires a grand unifying theory rivaling the principle that DNA functions the same in all living creatures. This theory could predict which experiments should be conducted. I insist this would require a research organization capable of pursuing the science of information and the science of systems, including complex interaction. As the head of this "information and systems research organization", linked to research in genetics, information, polar research, and statistics and mathematical research, I would aim to create a true theoretical biology.
    The reorganization of science on the axis of the life sciences is likely to be the final stage in modern science. The people aiming for a future career in the sciences will require talents completely different than those of the people of our era. We are now in a period of searching. I hope that this research organization will be useful in that search.
(Text: Atsushi Yamagishi)
1. As a new junior high school student.
2. As a child, I liked evidence-based physics.
"Electricity for Young Engineers" had the greatest impression on me at that time.
3. During my graduate student days. At Dr. Ebashi's Lab.
4. The members of Dr. Benzer's Lab. (I am in the center.)
5. A commemorative photo with Dr. Benzer just before I returned to Japan. The results of the mosaic analysis are written on the blackboard behind us.
6. With my co-workers at the biophysics laboratory (I am at the extreme right.)
7. At the International Biophysics Conference in Kyoto in 1978
From left: Fumio Osawa (Professor Emeritus, Nagoya University, Osaka University), Hirokazu Hotani, (Professor Emeritus, University of Nagoya), Akiyoshi Wada (Professor Emeritus, University of Tokyo; currently the director of the Yokohama Science Center), Yasushi Hiromi (Currently at the National Institute of Genetics), Me.
8. My retirement from the University of Tokyo. I'm holding the record of attendance, which I never used even once.
8. Professors' meeting at the National Institute of Genetics. The day I last served as chairman.
9. Party at the National Institute of Genetics commemorating the 50th anniversary of the DNA double helix structure and the decoding of the human genome.

Yoshiki Hotta
Born in Tokyo (it seems)
Graduated from School of Medicine, the University of Tokyo
Awarded an M.D.
Ph.D. researcher in the Biology Division of the California Institute of Technology
Lecturer at the University of Tokyo School of Science
Assistant professor at the same school
Professor at the same school
Director of the National Institute of Genetics
Director of genetics studies, the Graduate University for Advanced Studies
Director, Research Organization of Information and Systems
The Matsunaga Prize / Inoue Academic Prize / Kihara Prize, Genetics Society of Japan / Takeda Medical Prize / Medal of Honor with Purple Ribbon
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