Vol. 35
Lifetime fascination with chiral science: Leading from applied physics to material science and bioscience
Toru AsahiProfessor, Faculty of Science and Engineering, Waseda University (Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering)
■Success through devotion to developing solid chiral measurement techniques I have been involved with Waseda University since I was an undergraduate student. However, my department affiliations and research themes have changed a number of times; I have been in the Department of Applied Chemistry of the School of Science and Engineering, the Kakumu Memorial Technical Research Institute (Zaiken), Waseda Research Institute for Science and Engineering, the Consolidated Research Institute for Advanced Science and Medical Care (ASMeW), and am now in the Department of Life Science and Medical Bioscience's School of Advanced Science and Engineering. Every time I made a change I found I could approach my research with a fresh mind.
When I was a fourth year undergraduate, I studied in Professor Jinzo Kobayashi's lab. While conducting research on structural phase transitions of ferroelectric substances there, I used a unique device, the high accuracy universal polarimeter (HAUP), invented by Prof. Kobayashi in 1983 to determine the optical nature of solid matter. This led me to an interest in research on substances which have a special structural characteristic called ‘chirality.’ Chirality refers to things whose mirror images and real images do not match. Two examples of chiral phenomena are humans' right and left hands, and clockwise and anticlockwise helices (see Figure 1).
Chiral pairs sometimes have completely different bioactive characters and functions. For example, sometimes when we eat something, one part of it is sweet and another is bitter. Likewise, there are two different variants of thalidomide, a drug which can cause serious harm: R (Rectus) and S (Sinister) type. It is known that R has medicinal benefits such as sleep enhancement, while S tends to induce birth abnormalities. However, it is not such a simple matter that we can say that if there were no S variant of the drug, there would be no health disaster. It has been pointed out that some complicated situation might arise such as R turning into S at a certain temperature or pH.
It is said that thalidomide has some benefit in the treatment of leprosy, AIDS and cancer, so I hope it can be used successfully once we have understood its mechanism. In Japan the use of thalidomide has been banned for a long time, but it was reported recently that clinical thalidomide trials started four years ago. Although thalidomide use could be harmful if researchers make an error with the formula, if possible thalidomide should be used to help people who suffer from incurable diseases. Therefore chirality research is also important for the safe use of medicine.
It is extremely difficult to divide things according to their chirality. Even when the structure and bioactive characteristics are different, some physical characteristics such as melting point and boiling point are not. There are two methods for determining chirarity. One is to use the ‘optical rotary power’ characteristic: when light which is vibrating in a linear manner (linearly polarized) is applied, the direction of the straight lines turns in two different directions, clockwise and anticlockwise. The other method is to use the ‘circular dichroism' characteristic: when linearly polarized is applied, the polarization vibrates in an elliptical manner in two directions, clockwise and anticlockwise.
It is thought that using these ‘chiral optical properties’ makes it easier to understand the essential characteristics of chirality. So far, there has been considerable research on liquid solutions but none on solid substances such as crystal and glass, since it is difficult to determine chiral optical properties. Professor Kobayashi saw that HAUP measurement method could be applied to such research, and I was convinced as well.
At first, we surveyed the changes in the symmetrical properties of a structure involved in phase transition and observed its transition mechanism by measuring its ‘optical rotary power’ using HAUP. With a subtle difference in temperature, a structure phase transition occurs in a substance and the crystalline structure changes. At that time, an atom could shift slightly, and an atomic arrangement with a clockwise or anticlockwise chirality could emerge and the symmetrical property of the crystal could change. HAUP was developed as a device to study whether such a symmetrical shift occurred or not, and how electron arrangement changes due to such shifts. However, I came to think that it would be wasteful if we only used this equipment for that purpose, and that this technology was potentially useful for the study of solid chirality.
At that time, there were almost no researchers in Japan who were interested in the development of measurement devices for chiral optics, even though results had been presented at the Physical Society of Japan. Several years before Prof. Kobayashi retired and closed his research lab, I proposed to him that it would be fruitful to do research on a new theme: chirality of amino acids. I felt dejected when he asked me, ‘Do you think that will result in a proper research paper? It might be worthwhile if it were focused on protein, though.’ In the end, I acted on my thinking and shifted my research base from crystallography to chiral optics, and extended my research interests to various other materials. After I moved from the Department of Applied Chemistry of the School of Science and Engineering to the Kakumu Memorial Technical Research Institute (Zaiken) to conduct research on ceramics and magnetic thin films, I took up bio-field topics such as the application of magnetic thin films to single cell trap technologies.
Meanwhile, I developed G-HAUP (Generalized HAUP), a device which can measure not only optical rotary power but also circular dichroism. I was attracted to chiral optics and gave myself entirely to that research, and somewhere along the line I found myself to be a world-class researcher of the development of chiral optical measurement methods. Eminent international researchers started offering me joint research projects since the study of that theme requires that particular measurement device.
Figure 1: Examples of chiral structure
The above: Clockwise helix and anticlockwise helix
The below: The two crystals are mirror images of each other
■Breakthrough on the gamma problem in second year graduate school I was enthusiastic about the activities of the sports club which I had established with my friends in the school, so when I joined the research lab I was seen as a sort of maverick. However, I am very grateful to professor Kobayashi for his strict discipline, both official and private, which led me to become a devoted researcher. There were times when I was in tears over the difficulty of a challenge. One time he scolded me during my seminar presentation, saying “This in not a school play!” However, I am convinced that I benefited greatly from his strict approach. At one year-end party, I asked my senior, “Why does Prof. Kobayashi give me so much more severe discipline than the others?” My friend tried to comfort me by telling a story about two great baseball stars. He said, “The Giants’ manager, Kawakami, developed Wáng Zhēnzhì by praising him and Shigeo Nagashima by criticizing him.” I do not know if this is true or not but I tried to think positively from that point on, imagining myself in the same situation as Nagashima.
There were a number of coincidences and fortunate circumstances on the way to my decision to be a researcher. One of those events was a trigger: when I was in second year graduate school I discovered an unexpected solution to a problem and gave my first presentation at an international academic conference.
In those days, it was said that it would be impossible to do the general measurement of the optical rotary power of any solid material without first solving the difficult ‘gamma problem.’ Mr. Takahashi, my colleague at the lab, and I repeated various experiments; I tried to think of all the possibilities while Mr. Takahashi approached the problem from the theoretical side. We stayed overnight in the lab many times, continuing our experiments and discussions intensely, seeking ways to solve the issue.
One day at lunch time during that period, we were eating in the school cafeteria, discussing the possibility of finding a solution. Suddenly both of us shouted simultaneously. It was such a dramatic moment. By chance we had both come up with the same idea at the same time. We immediately conducted experiments based on that idea and subsequently showed the results to Prof. Kobayashi. He recognized it as a good idea and encouraged us to write a paper.
After several months of work under the guidance of Prof. Kobayashi, we completed the paper and presented it as a poster session at the International Union of Crystallography conference in Perth. It was my first experience of flying, and of going abroad. During the conference, a number of world class researchers dropped in at our booth and praised us. We were so impressed and inspired. At that time I realized that in other countries, if one demonstrates originality one can be recognized.
Prior to that, when I was a fourth year undergraduate, I considered taking a job in the humanities. It was the bubble economy time, and even a person in the sciences could get a high paying job in sectors such as banking, security and the service industry. My idea was that once I got a job, I wanted to devote myself to something I could pursue for my whole life. On the other hand, I was receiving Prof. Kobayashi’s tutelage at the time, and I thought I might regret quitting my studies and taking a job. I had second thoughts and decided to continue with my studies.
When I was in second year graduate school, I went job hunting again; I visited thriving companies of various sorts, including think tanks, advertising agencies and manufacturers. However, I could not forget the HAUP. In the meantime, I succeeded in solving the gamma problem, which had defied even brilliant senior researchers. Subsequently I found myself involved in exciting research activities. I felt confident that I could go ahead even in the face of difficulties. After thorough consideration of other career paths, I made up my mind to proceed to doctoral studies and become a researcher.
Photo: Prof. Asahi (second from the right) when he joined the lab as a fourth
year undergraduate, seen here with other members after a midnight study session.
■ A new science leadership image, the super technology officer (STO) I was one of the first six people granted the new super technology officer (STO) qualification in October 2007. The STO curriculum is the science and technology human resources development program offered by Waseda’s Consolidated Research Institute for Advanced Science and Medical Care (ASMeW), which was established as a Super COE Program*. This is a groundbreaking approach which has attracted attention from both inside and outside of Japan. (*MEXT Center of Excellence for Strategic Research on Business Projects)
This program is intended to create world leading human resources from students with science and technology doctorates and the competence to conduct advanced research. These people are expected to obtain qualifications and skills such as 1) an MBA, 2) sufficient leadership capability to be a driving force in fusion research, 3) the ability to negotiate with international leaders over matters such as research agreements, 4) the ability to convey one’s thoughts logically and accurately, and 5) the ability to manage organizations. I myself studied at Waseda’s business school for two years and obtained an MBA with my master's thesis on the theme, ‘Proposal for a Biosensor Business Model.’ It was a very useful opportunity for me to learn extensively through activities such as group discussions and joint presentations with motivated persons who aimed to improve their career and with aspiring entrepreneurs who wished to take on new challenges.
In Japan, there has long been a climate of prejudice in which people in the humanities are respected while those in science and technology are thought poorly of, partly due to the fact that science and technology professionals excel in specialized fields but cannot easily obtain leading positions in society or in organizations. For example, please consider how government officials mostly come from the humanities. In order to break through such a prejudicial atmosphere, it is necessary to establish a new image for people in science and technology. I believe that we should eliminate such bias and create a society which can make full use of all talents.
It is not easy to provide research leadership and management and to continue patient research at the same time, but it is necessary to somehow achieve a good balance between management and scholarship. I myself am quite busy in management, holding several positions such as member of the ASMeW secretariat, deputy chief of Waseda's Postdoctoral Fellow Career Center and secretariat member of the Research and Education Center for Practical Chemical Wisdom (a Global COE program). Even off campus, I am involved as an organizer for academic meetings.
Sometimes a new human network is created through management work and new seeds for research are found: such merits are significant. The new campus of the ‘Advanced Life Medicine Center’ was opened in March 2008 near Tokyo Women’s Medical University in Kawada-cho. As full-scale advanced medical research has begun there, my educational activities will soon be in full swing, in addition to my fusion medical research activities.
Moreover, in the Postdoctoral Fellow Career Center, I am working to raise the awareness of postdoctoral fellows and also of the instructors. I am appealing to the instructors to avoid holding onto highly capable researchers for a long time and destroying their career opportunities. On the other hand, I also advise the postdoctoral fellows not to depend on established thought, but to accumulate knowledge and experience so as to be ready for challenging opportunities, and to be independent and proactive. For example, I offer training programs to enhance their intellectual assets and communication ability, and to support activities related to the creation of career paths. From one point of view, the STO curriculum is the most important of such training programs.
I think I have a good understanding of the situation and sentiment of postdoctoral fellows, since I was a fixed contract researcher for 14 years. I feel that recently there has tended to be to a negative climate in which postdoctoral work is seen in a poor light (this is called the ‘postdoctoral issue'). I am enthusiastic to transform such a social climate and system, which makes postdoctoral fellows feel insignificant. I would like to encourage postdoctoral fellows, who are struggling and pursuing their research very hard. I want to say to them, “You should not feel ashamed of being postdoctoral fellows nor should you accept negative comments. Although your situation may seem unstable given your fixed term contracts, please confidently devote yourself to creative research and discipline while at the same time being involved in other work and management.”
20 years ago, after obtaining my degree I joined the ‘21st Century Club,’ which is a pan-industry exchange society established by my university colleagues. Through this society I have been involved in exchanges with front-line business people from the humanities. The membership of this society includes management executives, politicians, government officials and professional athletes. The society has been sponsoring various activities including open college type lecture meetings, inviting politicians including former prime ministers Mr. Nakasone, Mr. Miyazawa and Mr. Koizumi, study meetings for discussions with guests from various fields, and sports lessons for children.
However, such pan-industry exchange activities are not particularly well received among people in the sciences. Science people tend to think that those involved in such societies are not seriously focusing on their research but rather are playing around. I used to downplay my involvement in such activities for that reason, but since I became a STO, I feel free to go and deepen exchanges with the outside world of researcher networks. At the same time, I would like to help the public to understand the daily activities of researchers of the sciences and see the importance of the promotion of science and technology.
In spite of all this, chirality research has been and always will be my lifetime work. There are right and left biases inside biological bodies. For example, DNA in a biological body is a double helix consisting of a polymer of the sugar deoxyribose, but it has only a clockwise helix. Protein only has an anticlockwise helix (called an ‘alpha helix’) consisting of an amino acid. Such bias in chirality is called homo-chirality, but the reason for it has not been found yet. There are various theories; one is that it occurs in parity nonconservation in elementary particles or in the process of the evolution of life; another is that it arose because the light that biological bodies receive from the sun was polarized either to the left or right. I would like to spend the rest of my life pursuing this romantic quest: the mystery of life and biological phenomena.
Figure 3: Super Technology Officer (STO) conferment ceremony.
Prof. Asahi is on the extreme left in the first row.
Profile:
Toru Asahi
Professor, Faculty of Science and Engineering, Waseda University (Department of Life Science and Medical Bioscience, School of Advanced Science and Engineering) Super Technology Officer
Prof. Asahi graduated from Waseda University's Department of Applied Chemistry of the School of Science and Engineering in 1986, and completed the master’s course in Physics and Applied Physics at Waseda’s Graduate School of Science and Engineering in 1988. He obtained his doctorate in Science in 1992 and his MBA in October 2007. Before taking his current position in April 2007, he was research associate in Waseda’s School of Science and Engineering, visiting associate professor at Waseda’s Kakumu Memorial Technical Research Institute (Zaiken) and at Waseda Research Institute for Science and Engineering and Waseda Graduate School of Science and Engineer Nano-Science Major, and visiting professor at the Consolidated Research Institute for Advanced Science and Medical Care (ASMeW). He is also a member of the ASMeW secretariat and deputy chief of Waseda's Postdoctoral Fellow Career Center. He was selected as one of the first Waseda STOs. His fields of expertise are chiral science, bio-solid state science and magnetic thin films.
Last revised:01.07, 2009 For inquiry：Research Promotion Division koho-rps@list.waseda.jp
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