Setsuro Ebashi, a pioneer of muscle research, died on July 17, 2006 at the age of 83 years. He was an exceptional scientist and had an outstanding personality. Dr Ebashi was born in Tokyo on August 31, 1922. In September 1944, he graduated as Doctor of Medicine from the Faculty of Medicine of the University of Tokyo, where he spent most of his professional life. In June 1954, he obtained the Doctor of Medical Sciences (PhD) degree from the same university. From January to December 1959, he was Guest Investigator of the Rockefeller Institute in the laboratory of Fritz Lipmann, Nobel Laureate in Medicine. In May 1959, he was offered the Chair of Pharmacology in the Faculty of Medicine of the University of Tokyo and kept this position until March 1983. From May 1971 to March 1983, he was also Chair of Biophysics at the Faculty of Sciences of the University of Tokyo. After retiring from the University of Tokyo and becoming Professor Emeritus, he was offered a professorship in the National Institute for Physiological Sciences in Okazaki. In April 1985, he became Director-General of the National Institute for Physiological Sciences. Prof Ebashi left this position in March 1991, after being nominated as President of Okazaki National Institutes. After retiring from this position, he became Professor Emeritus of the National Institute for Physiological Sciences in March 1993.
While preparing his PhD thesis under the supervision of Prof H. Kumagai, he purified choline-acetylase and took special pride in the study of the “relaxing factor,” discovered by B.B. Marsh in 1951, which in the presence of adenosine triphosphate (ATP) relaxed glycerinated muscles of rabbits. Ebashi found that this factor existed in particulates with Mg-activated ATPase. He demonstrated that the fractions that strongly took up Ca2+ in the presence of ATP consisted of fragmented sarcoplasmic reticulum, suggesting a regulatory function for the calcium pump of the sarcoplasmic reticulum. This built upon Emil Bozler's observation that sequestration of Ca by EDTA caused muscle relaxation. W.H. Hasselbach and Anne-Marie Weber, who explained how the endoplasmic reticulum (ER) could accumulate Ca2+, confirmed the importance of intracellular Ca2+ pumps associated with the endomembranes. At the same time, the first indications of ER-residing regulated ion channels, which could provide a means of Ca2+ release, were reported by Clara Franzini-Armstrong.
In the early 1940s, Heilbrunn in the United States and Kamada in Japan demonstrated the role of Ca2+ as a contraction signal. In the early 1960s, studying actomyosin prepared directly from whole muscle, Setsuro Ebashi discovered that in the absence of Ca ions, no contractile reaction occurs, even when ATP is added to the myosin-actin system, but that with even a minute amount of calcium (on the order of 1 μmol), ATP induces a vigorous sensitivity to actomyosin. Clearly, the muscle extracts contained a factor that conferred Ca2+ sensitivity to actomyosin. This factor turned out to be the tropomyosin-troponin complex. Ebashi's concept of Ca receptor protein was extended to other cell types, for instance, with calmodulin, which plays a role in various cellular regulations from muscle to nerve cells.
Setsuro Ebashi presented a clear picture for factors regulating onset and offset of the Ca2+ signal in skeletal muscles. He reported that Ca2+-related regulatory processes were different in the various types of muscles. This elucidation of the role of the calcium ion in mechanisms that regulate muscle contraction-relaxation and the demonstration of differences among muscles paved the way for studies of the pharmacological control of the Ca2+ signal that emerged as a therapeutic principle. A by-product of his research included studies related to alterations of calcium regulatory mechanism and proteins dysfunction in muscle pathologies such as muscular dystrophy and malignant hyperthermia.
His seminal research attracted a large number of research fellows and associates, a pattern that continued after his move from Tokyo to Okazaki, thus allowing Japanese scientific research to become a world leader. At the risk of leaving out numerous associates who benefited from his creative critical scientific approach, I would like to mention the following people who are well known in the fields of skeletal muscle and cardiovascular research as well as neuroscience: Masanori Otsuka, Makoto Endo, Yosiaki Nonomura, Tomoh Masaki, Iwao Ohtsuki, Yoshiki Hotta, Yasuo Ogawa, Eijiro Ozawa, and Takeyuki Wakabayashi.
From 1978-1981, Setsuro Ebashi was President of the International Union for Pure and Applied Biophysics (IUPAB), but his major international activity was devoted to IUPHAR, the International Union of Pharmacology (now the International Union of Basic and Clinical Pharmacology). He organized and chaired the Eighth World Congress of Pharmacology held in Tokyo in July 1981. This Congress is considered an international model because of its perfect organization and the high quality of its scientific program. Dr Ebashi was elected president of IUPHAR for the period 1990-1994 and officiated as Immediate Past-President until December 1998. During this time, he devoted himself to fundraising for IUPHAR, and because of his commitment, the Japanese Pharmacological Society initiated an increase of Member Society contributions to IUPHAR with the purpose of allowing the establishment and the development of scientific research activities operated by the Union (eg, Receptor Characterization and Classification, which has become a major receptor database).
Dr Ebashi was awarded the Order of Cultural Merit (Bunka-Kunsho) and received numerous major honors from diverse scientific and civic organizations and academies throughout the world. A few of these stand out: the 1965 Prize of the Yamaji Science-Promoting Foundation, the 1968 Asahi Prize (issued by Asahi Newspaper Publishing Co), and the 1972 Imperial Prize of the Japan Academy. In 1999, he was awarded the International Prize for Biology for outstanding developments in biomedical sciences and fundamental developments in the field of calcium's role in the physiological regulation of skeletal muscle. Dr Ebashi was very proud that the awards ceremony was attended by the Emporer and Empress of Japan.
Setsuro Ebashi was a member of the Japan Academy and a foreign member of several academies including the Deutsche Akademie Leopoldina, the Royal Academy of Medicine of Belgium, the American Academy of Arts and Sciences, the National Academy of Sciences (US), the Academia Europaea, and the Royal Society of London. He was also an honorary professor at the Shanghai Institute of Biochemistry, Chinese Academy of Sciences.
Bob Furchgott introduced me to Setsuro Ebashi in 1969. Since then, I met him several times around the world. I met with him more regularly during the period 1990-1998. He was a modest person with a rich and complex personality. As a scientist, he proved to be rational and imaginative. He had a great memory even for small details; this allowed him to identify existing connections between facts apparently disparate. His scientific creativity was enhanced by his rejection of any dogmatism. He sometimes appeared imposing. In fact, Setsuro Ebashi was unusual in being outspoken; when he was critical about something or somebody, he said so. Yet, he was among the most cultured scientists I have ever met, able to sing a capella Bach chorals.
When writing about Setsuro Ebashi, it is not possible to forget his wife, who provided him with great support. In the early years, she was efficiently active in his laboratory. At the end of his life, she had been vigilant, maintaining an affectionate environment and contacts with his friends abroad.
Dr Setsuro Ebashi made many lifelong friendships. His many friends from many different continents will miss him dearly.