Biophysics in Japan, its Past, Present and Future
Professor Emeritus, National Institute for Physiological Science
KOSHIBA
Next Speaker is Dr. Setsuro Ebashi, who is Professor Emeritus of National Institute for Physiological Sciences. He served as Professor of Pharmacology, Faculty of Medicine of the University of Tokyo, Professor and Director General of National Institute for Physiological Science, and President of Okazaki National Research Institutes. He received many awards including the Imperial Prize from Japan Academy and the First Order of the Sacred Treasure, and was decorated with a Order of Cultural Merit from the Emperor. Professor Ebashi, please.
EBASHI
Thank you very much, Professor Koshiba, distinguished guests, ladies and gentlemen! It is my great pleasure and honor to have a chance to give a talk on this very memorable occasion. Before going into my main subject, I would like to introduce myself and my institute.
My institute is located in Okazaki, near Nagoya. Okazaki, perhaps most of you do not know, is a small city. Its population is less than four hundred thousands, but it is famous because Shogun Tokugawa (Iyeyasu) was born in this city.
The Okazaki National Research Institutes is composed of three institutes. One is the Institute for Molecular Science, built in 1975. It is known world-wide because of its excellent research on the orbit calculation of organic substances. Two years later, two other institutes were started, i.e., the National Institute for Basic Biology and the National Institute for Physiological Sciences. Each Institute has its own Director General, who is empowered more so than the dean of the faculty of national university (the dean cannot carry out his duties without the approval of faculty members, but the director is not necessarily required to obtain the consensus of professors -- something like the American way). We have a president of the three institutes who nominally supervises all the institutes, but actually has no power according to my experience.
An important duty of each institute is to accept the scientist in another institution as a collaborator(s) if he or she is qualified. It is, in a sense, an open institute.
The important thing is that we are in collaboration with some other national institutes of similar nature, we have settled graduate courses, and we have the Graduate University for Advanced Studies, which can offer doctoral degrees to students independently of other universities. This is very much indebted to the efforts of Mr. H. Osaki, when he was a staff member of the Ministry of Education, Science and Culture, and also to Prof. S. Nagakura, who was the President of the Okazaki Institutes at that time, then the first President of the University.
Now I will go into my task. First one: What is biophysics? This is a very sharp question, and I am quite at a loss. Biophysics itself is a very strange term, and if you scrutinize names of the departments of U.S. universities, there are only a few departments which primarily have this name, department of biophysics. But there are many cases using it as the second term, for example, department of physiology and biophysics, department of pharmacology and biophysics, and so on. Biophysics is used as a kind of accessory. Perhaps this word sounds elegant and implies some intelligent atmosphere. This is a nice term to use as an annex.
Then what is the definition of biophysics? The Webster dictionary says: 1) Physics of living organisms; this is too simple and means almost nothing; 2) Application of physical principle and method to biological system. If you consult with other Western encyclopedias, much the same definitions are given. However, according to the encyclopedia Nipponica (Japonica), biophysics aims at fundamental and integrated understanding of biological phenomena on the basis of thoughts and principle of physics. This is more sophisticated than the above. I will refer to this problem later.
The original title given by Prof. Koshiba was to talk about the present and future, but I dared to add "past" to it. Since biophysics, at least in Japan, is in a critical stage, I thought it was necessary to go back to the past.
It is very difficult to identify one person as the pioneer biophysicist, but I nominate Hooke (1635-1703), a famous physicist. He invented, as you know, the microscope. As is well known, almost at the same time Leeuwenhock (1632-1723) also invented a microscope, but his one, though superfine, was actually a magnifier. As a physicist, Hooke made his microscope on a more theoretical basis, and it is the real ancestor of today's microscope. He was interested in biological materials. Using his microscope, Hooke introduced to people the fine structure of many biological materials. There are many candidates to be nominated as the second, but I would like to mention one person, i.e., Helmholtz (1821-1894). He was a surgeon and from his experience, he wondered how the food digestion, putrefaction, and burning of wood was different from one another. Eventually, he came to the conclusion that all depended on the same principle. In this way, he became one of the pioneers or founders of thermodynamics. And, I think, he is perhaps the last person who was the king in both fields, medicine and physics. This may be an original form of biophysicist.
Now, Japan. Who used the term of biophysics first? That would be K. Hashida (1882-1945), professor of physiology, Tokyo Imperial University, now University of Tokyo, in early Showa era, i.e., around 1930. He was at the same time, a philosopher, eventually concerned with the educational administration or politics. Physiology, for him, was the highest biological science, comparable to physics; he used special Japanese, seikigaku (
), a term which the young generation of Japan may not know. He divided it into two areas: one was biophysics and the other biochemistry. The latter is now so popular and no one has any question about it. Biophysics, he called, is nothing but physiology according to ordinary persons. He published a journal under the title "Biophysik"; contributed papers should be written, in principle, in German. The first issue was published in 1932, but it was an assembly of papers submitted from 1929 to 1931. The final one was published in 1942, during the Second World War II. He wanted to continue it, but unfortunately, he became the Minister of Education in 1940 and could not continue this journal. After the War, of course, it was not possible to revive it, not because of the loss in his relation with science, but because of his commitment of suicide, feeling it was his responsibility during the War.
Actually, however, biophysics according to him was nothing but electrophysiology. At that time, Japanese medical sciences were following the tradition of German physiology, in which the nerve physiology had been most important. They tacitly assumed, I suppose, that clarification of the electrical mechanism of the nerve would solve the secret of the mind or would present a crucial suggestion to it. Therefore, at that time, so many excellent people graduated from medical schools, they entered physiological laboratories and worked on nerve physiology, namely electrophysiology of nerves. That was an unusual atmosphere from nowadays' point of view. They were requested to be well trained in mathematics and physics, especially electromagneticism. The use of "biophysics" in this way was only done by Hashida, and his followers, except a few, did not use his classification. They called their science just physiology.
Looking back at the attitude of Japanese physicists, they were not interested much in biological subjects, except philosophical consideration. Perhaps the first person who was deeply interested in biological matters was Torahiko Terada (1878-1935). He was also an excellent essayist and very popular among common people, particularly young students. But he was not appreciated by his colleagues, professors of physics, in the Tokyo Imperial University. His colleagues rather looked down upon him because he was so much concerned with common affairs and had many novelist and poet friends. He was, however, an excellent physicist. In 1912, reading the Laue's paper, he immediately reached the conditions for diffraction, almost at the same time as Bragg (1890-1971). Since he was so modest, he never insisted on receiving proper recognition. He was truly an admirable person. But his colleague professors in the Tokyo Imperial University did not allow such attitude; scientists should devote themselves only to science and not be concerned with common people. This was a tragedy to Terada.
Now, the next generation of biophysicists. Motoyoshi Sugita and Shoten Oka, graduates from Tokyo Imperial University, were interested in phenomena in living organisms or substances. They did not stay at the Tokyo Imperial University; instead they served at the private institute, Kobayashi Riken, or Kobayashi Institute of Physical Science, sponsored by a company. What they mainly wanted to do was to apply mathematics to biological systems and some success was obtained. However, most physicists at that time did not appreciate their way of thinking and attitude. Physics were the supreme subject among many sciences, not comparable with any other. A physicist honestly confessed his real mind; he wanted to formulate the "life equation". He thought that there must be an equation something like Schrodinger's equation, from which important things of life would be derived. He wanted to become a person in Biophysics comparable to Schröinger (1887-1961). Other physicists might not be so naive, but still he represents their inner psychology at that time.
Now I will come to the Western current. I should first mention Bohr (1885-1962), who was perhaps the first modern physicist deeply interested in biological subjects. He tried to apply his concept, "complementality" to biological systems. Delbrük was very much impressed with Bohr's attitude and eventually he himself became a molecular biologist. On the other hand, Schrödinger's famous book "What is Life" influenced so many, both biologists and physicists. Needless to say, diffraction studies in Cavendish were a great contribution. Thus, physicists played an unparalleled role in opening today's molecular biology.
In the United Kingdom, no discrimination was made between molecular biology and biophysics. The research in the famous MRC Molecular Biology Laboratory, Hills Road, Cambridge, truly deserves the term biophysics. But in other countries, molecular biology and biophysics were separated somehow.
Influenced by Western current, particularly U.S's one, Masao Kotani (1906-1993) , he was almost the same age as Sugita and Oka), Professor of Physics, University of Tokyo, was a famous theoretical physicist who did many nice things in basic physics. He opened the stage of Japanese biophysics. He was a real expert of physics of the condensed matter and perhaps one of the pioneers of quantum chemistry.
Masao Kotani was very short, and his letters written on the blackboard was so small the students could not see them. He had very soft manner and always spoke quietly, but inwardly had a definite mind which could not be altered by any means. He suddenly decided to form the Biophysical Society of Japan. He organized a preparing committee in the summer of 1960, and in December, the establishment of biophysical society was announced (actual activities including business started in 1962). This was very early even compared to Western countries. In the United States, the biophysical society began around 1957 and the International Union of Pure and Applied Biophysics (IUPAB) was established in 1961. Kotani naturally played an important role in founding and organizing this Union.
Every society in Japan has some kind of ideal or constitution. The Biophysical Society's one said that biophysics should aim at the fundamental understanding of the phenomenon of the living organism; it has no reference to physics. Why? During the time of preparation of the Biophysical Society mentioned above, the molecular biology group, excited with the success of DNA model, dashed into the preparing committee. They thought that the idea of molecular biology itself, strictly speaking, molecular genetics was physics, and, therefore, it was not necessary to refer to physics. Serious discussions were made in that meeting, and eventually they reached the above ideal. This has remained to be a live coal in the Society.
Now we come back to the Japanese encyclopedia's definition mentioned before. It is very similar to this definition, and, I think, this writer was very much influenced by the idea of molecular biologists at that time. After the start of the Society, everything went rather smoothly and the sixth International Congress of Biophysics was held in Kyoto in 1978; naturally Prof. Kotani was its President. This meeting was attended by nearly 2,000 participants and its international reputation was very high. In view of the contribution of Japanese biophysicists, represented by Prof. Kotani, the position of Japanese Biophysical Society in the international community of biophysics had been rather high. IUPAB has always included a Japanese as one of its staff members, including the cases of a President and a Vice-President.
Up to this point, Japanese biophysics seemed to go rather smoothly. However, the molecular biology group who had made serious discussion before the start of the Society, finally decided to withdraw from the Biophysical Society to form an independent society in 1978. That was a very serious problem for the Japanese Biophysical Society. Today the number of its members has not increased so much, now about three thousands, but the newly established Molecular Biology Society has already more than six thousand members. Biochemical Society of Japan, for example, has become a gigantic organization, totalling twenty-three thousand members. The number of the members may not mean so much, but in a sense it indicates the influence of each society on the scientific community.
As a consequence of the separation of molecular biology, the Biophysical Society lacks the impact from the biological side concerning not only biology in general, but also structural analysis, which was one of the most important subjects of the Biophysical Society. At that time, some biophysicists were not disappointed by the divorce, but rather pleased with this change; “now we have become free from demands of molecular biologists who always made troublesome noises by requesting many tasks different from our interest, but now we can pursue our own hobby". To some extent, however, the research needs some kinds of enforcement from the outside. Without such kind of compulsory influence, the study itself would become very narrowed, though theoretically refined. This really happened in the Society. This was and still is a very serious problem for the Japanese Biophysical Society.
Now, I will briefly refer a little bit to what the Biophysical Society is doing. To avoid misinterpretation, I would like to confine my talk to the field with which I am somehow acquainted. It is strange that in Japan muscle research is very popular. I do not know why. As a consequence of this trend, the fundamental part of the today's Ca2+ concept, Ca2+ is the most important regulatory factor of intracellular processes, which had been fostered in Japan. This was indebted to the pleasant atmosphere of the Society free of any restriction and tradition. This cartoon represents the exterior and interior distribution of inorganic ion in the cell, including prokaryote, one of the most common features of living organisms. However, Ca2+ does not play its regulatory role in prokaryote. This means that prokaryote does not know how to utilize Ca2+. This might have something to do with very much retarded evolution of prokaryote, virtually no change during past 4 x 109 years. On the other hand, eukaryote has made a remarkable development, the science of which is one of the most important fields of biological sciences, "evolution". It may then not so absurd to assume that the begin of evolution coincided with acquiring the ability to utilize Ca2+. There is no wonder the skeletal muscle, the most differentiated tissue, has fully utilized Ca2+ as a tool for performing its function.
Among many excellent studies on muscle contraction, I would like to quote the work of Prof. T. Yanagida of Osaka University. He was a student of Prof. Fumio Osawa who also contributed a great deal not only to muscle science and cell motility, but also to the development of Biophysical Society (without him today's Biophysical Society could not have existed.) Everyone thinks that one ATP would be split during one cycle of the interaction of one actin molecule and a head of one myosin molecule. But now Yanagida showed that at least several cycles, sometimes ten, could be performed by one ATP. That is unbelievable, but now we have realized that the principle of chemical reaction on the macroscale would not be applicable to a reaction in a very small area accompanied with the conversion of energy form (conversion of energy form associated with important biological phenomena is another important theme of biophysics).
Now I have to speak about the future. A solution is to reunite with Molecular Biological Society. If possible, it is all right, but I think now it is almost impossible. For example, the International Union of Biochemistry has already included molecular biology in its name, thus becoming the International Union of Biochemistry and Molecular Biology. Even in the United States, the American Society of Biochemistry now has changed its name to the American Society for Biochemistry and Molecular Biology; molecular biology is now an important part of biochemistry. In Japan, the Biochemical Society has not included "molecular biology" in its name, but there is a strong movement to strengthen their cooperation. On the other hand, the Japanese Biophysics Society has scarcely touched molecular biology (molecular genetics) after its separation from the molecular biology group. It is tragic, I think.
The second possibility is that the Society will remain just as it is. Scientists in the Biophysical Society form a very nice group, having a very good atmosphere. People are very naive, enjoying the research itself and do not mind too much about publication. That is what I like very much. This is an unusual state retaining the atmosphere of scientific community thirty, forty years ago, and is in a sharp contrast to nowaday's general tendency. However, this does not help acquiring financial support from the outside. As emphasized above, structural analysis of macromolecules is the most important theme for orthodox biophysics and it is impotant to introduce research fund into biophysics. It is also a way to strengthen the relationship with the physics and physical community to find the new subjects of biophysics. In addition to these, there are many charming problems, though they cannot form a strong current. To include all of them, it might be a way to remain as a small society, in which everyone will enjoy his or her hobby. It is not so unreasonable to have such a pleasant and enjoyable Society of a relatively small scale at this greedy time, if circumstances would permit it.
Now I would like to briefly refer to the American Biophysical Society. As I said before, the American Biophysical Society began with a little relationship with molecular biology, and it still does. Thus, the present state of the Japanese and American Societies resemble each other to some extent. Further, in both societies, studies on muscle and cell motility and on membrane are popular. So I think they have a nice condition for cooperation to think over about the future of biophysics. This is my personal proposal, but I have not yet consulted with anyone of the Japanese Biophysical Society, but I think it deserves further consideration.
Now I should finish. Thank you very much.