inline imageProfessor. Nakao Ishida (1923–2009)
Medical scientist, microbiologist, immunologist, entrepreneur,
educator, and administrator

Our Japanese research communities recently lost a great mentor and friend, Professor Nakao Ishida on December 4, 2009. Late Professor Nakao Ishida, M.D. was born in 1923 at Nigata prefecture, Japan. He entered and graduated from Tohoku University Medical School, Sendai, Japan, in 1946 and pursued the academic track since then at Tohoku University. He was a Fulbright scholar at the Virus Institute of University of Michigan School of Public Health (1954–1956) under Professor Thomas Francis Jr. M.D. Professor Ishida became a full professor of the Department of Bacteriology, Tohoku University Medical School, Sendai in 1960 and served the professorship till 1985.

Professor Ishida discovered Sendai virus in 1951 from a pediatric patient. This paramyxovirus not only became an indispensable tool in cell fusion, but also provided a basic concept of protease driven promotion of viral infectivity. The mechanism of proteolytic activation of the viral infectivity through cleaving F-protein was elegantly elucidated by Morio Homma of Ishida's group in Sendai. This mechanism provided a clue to analyze the similar mechanism of HA cleavage of influenza virus, which confers the virus infectivity, as demonstrated by Hans-D. Klenk et al in Germany.

At the front of active viral research in his Department of Bacteriology, Professor Ishida as a chairman of the department, played a key role in the discovery of adenovirus type 11 as a causative agent of infantile acute hemorrhagic cystitis by Yoshio Numazaki et al, and also in the discovery of rotavirus, a causative agent of infantile gastroenteritis in the pediatric patients, by Tasuke Konno et al of Tohoku University. It was about the same time independently of the discovery of rotavirus by Ruth Bishop et al in Australia. Professor Ishida's other research interest in virology include hepatitis virus B and C as well as influenza virus.

In the Ishida's Department of Bacteriology, the research project on antibiotics was one of major efforts since 1943, the day of his predecessor Professor Chairman Masahiko Kuroya. Collaboration between the department and pharmaceutical companies was a routine scene, and screening program for antiviral and antitumor agents were undertaken in addition to antibacterial agents where many companies sent their scientists for training. Among numbers of newly discovered antibiotics, a proteinaceous antitumor agent named neocarzinostatin (NCS) was a successful case that became an approved drug used in clinics. This neocarzinostatin became the first prototype protein antitumor agents, among others such as actinoxanthin of Prof. A. Khovlove, Science Academy of Soviet Union, or macromomycin of Prof. Hamao Umezawa, University of Tokyo.

Extensive investigation of NCS was carried out under the leadership of Professor Nakao Ishida. Namely, antitumor activity was elucidated by Katsuo Kumagai, the mechanism of action in molecular biology using bacteria as DNA degradation and inhibition of DNA synthesis was established by Yasushi Ono, and subsequently, Kenzo Ohtsuki detailed molecular mechanism further. The chemistry, biochemistry, pharmacological properties, including amino acid sequence, in vivo half life, subcellular action were clarified by Hiroshi Maeda. The chemical structure of the unique endyene chromophore associated with NCS was established by Kiyoto Edo. The development for commercialization was undertaken by Kayaku Antibiotics Laboratories, Ltd, Tokyo, led by Yasuo Koyama, Shigehiro Matsumoto, Kazuso Toriyama et al. NCS was later conjugated with styrene-co-maleic acid polymer named SMANCS by Hiroshi Maeda, and it became the first polymeric drug approved by regulatory agency (1993), and opened up a new field of polymer therapeutics in cancer therapy.

Professor Ishida's research interests were limitless, and immunology was another area. He was intrigued by that child-bearing mother who is immunologically tolerant to the baby, even though the baby is apparently non-self. Keiji Tamura pursued a plasma component that might suppress immune reaction under Professor Ishida's direction, that is intriguing analogy between the host (cancer patients)–cancer relationship. So the effort to purify the plasma or ascitic fluid component from cancer patients revealed an immunosuppressive acidic protein (IAP). Later IAP was turned out to be an isoform of α1-acid glycoprotein. IAP was then found useful as a prognostic marker after surgery or chemotherapy of cancer patients. In the field of immunology in the Department, Kazuo Sugamura, who succeeded the Professor and Chairmanship of the Department after Professor Ishida, discovered and clarified the common cytokine receptor, γc-chain expressed on T-cells. He was also a student of Professor Ishida.

The Department of Bacteriology under Professor Ishida's Chairmanship was one of the most active laboratory in Japan at that time, and yielded more than fifty professors. This means he was a great teacher with warm personality and wide scope of interests, and truly multidisciplinary person. His friends range from academia to industry, from artists to historians and classic poets. He also served as a Dean of Tohoku University Medical School, and President of Tohoku University (1983–1989) and contributed greatly to the Medical School and the University. He received numerous awards such as highly prestigious Academy Prize of Japan Academy (1987), the First Orders of the Sacred Treasure (1996), from the Emperor of Japan, and National Order of Merit. Degree of Commander from the President of the Republic of Ecuador (1980). Professor Ishida organized the VIth International Virology Conference as the President (Takusaburo Ebina as the Secretariat) in Sendai in 1984, in addition to numerous other meetings in Japan.

Dr. Ishida was also keen to realize the importance to foster interaction between academia and industry. For this purpose he established a think-tank organization with help of the business circle, law-makers, and academicians. The organization is named Tohoku Intelligent Cosmos Organization, which encompasses seven prefectures of northeastern Japan.

Professor Ishida died of pneumonia at the age of 86, leaving his wife Harue, two sons, Toshio and Norio who is a Distinguished Principal Investigator of National Institute of Advanced Industrial Science & Technology, and an Adjunct Professor of Tsukuba University, and a daughter, Kazuko. He was loved by so many, not only his students and colleagues, but also by many other people in different disciplines all over Japan.

Professor Ishida was a person of passion who inspired students, colleagues, and new comers with his great vision, warmth, enthusiasm and strong leadership. All his students have lost a giant and the light-house who covered a wide range of microbiology, bioscience subjects, and beyond.

Winter, 2010