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Tsuyoshi Kakefuda, 1929–2006: Bridging US–Japan cancer research

2006; Wiley; Volume: 97; Issue: 11 Linguagem: Inglês

10.1111/j.1349-7006.2006.00316.x

1349-7006

Haruo Sugano,

DNA Repair Mechanisms

Dr Tsuyoshi Kakefuda, an eminent cancer researcher, Honorary Member of the Japanese Cancer Association and former Executive Secretary for the US–Japan Cooperative Cancer Research Program, died of liver disease aged 77 at his home in Potomac, Maryland, on June 16, 2006. His obituary appeared in the July 1, 2006, issue of the Washington Post. Tsuyoshi Kakefuda dedicated himself to cancer research and to coordination of cancer research between the USA and Japan. We all praise him for his prominent contribution to US–Japan cancer research. We will miss this great person. We would like to express our sincere condolences on his death. After graduation from the Faculty of Medicine, University of Tokyo, in 1951, Kakefuda joined the Department of Pathology, University of Tokyo. He was trained in histo-anatomical pathology under the leadership of Professor Tomizo Yoshida and Professor Masashi Miyake. At the same time Kakefuda worked with the ultrastructure of cancer cells using the newly introduced electron microscope. He beautifully demonstrated plasma cells with electron micrographs and obtained his PhD from the University of Tokyo. In 1960, by the invitation of Ryojun Kinoshita, Director of the City of Hope Medical Center, Los Angeles, Kakefuda moved to California as a postdoctoral fellow to study the newly developing area of ultrastructural biology, and he was acquainted with excellent scientists, including Kinoshita, Susumu Ohno, and Alfred Knudson. In such an ideal scientific environment, Kakefuda enjoyed research with the use of a well equipped electron microscope. His early work involved looking at how carcinogens in cigarette smoke damaged DNA. In 1967, the National Cancer Institute (NCI), National Institutes of Health, offered Kakefuda the position of Senior Researcher at the Laboratory of Molecular Carcinogenesis, because of his excellent knowledge in electron microscopic technique. Kakefuda moved to Bethesda driving a station wagon with his wife, two children and a dog. Afterwards Kakefuda became Section Chief in the Nucleic Acids Section and later moved to the Office of International Affairs. He stayed with the NCI for 40 years. At the NCI, Kakefuda's work gradually shifted to molecular biology, which was then new and rapidly developing. His knowledge and insights into subcellular organelles of cells were highly regarded and excellent collaborative works were performed. For example, with Jun-ichi Tomizawa, Kakefuda beautifully demonstrated the origin of DNA replication. He also joined with Blumberg's hepatitis B virus (HBV) study group and proved HBV DNA replication precisely. These electron micrographs of DNA replication clearly indicated his skill and innovative ability in electron microscopic technology. The interaction of carcinogens with DNA and mutation was of course important in molecular carcinogenesis and his contribution to this area was also great. At that time Kakefuda was fully focused on his daily lab work. His research style was that of ‘running first then thinking’. Kakefuda was interested in only the questions at the forefront and approached them with sophisticated technologies. When projects were not satisfactory for him, Kakefuda threw them away without hesitation. In this sense Kakefuda was very aristocratic. In the USA in 1971, the National Cancer Program was established to conquer cancer. Thus President Nixon's ‘War on Cancer’ began. Frank Rauscher, Director of the NCI, and Tomizo Yoshida, Kakefuda's mentor and Director of the Cancer Institute, Japanese Foundation for Cancer Research (JFCR), met at the NCI in 1972 and agreed to establish a US–Japan cooperation in cancer research, and in 1974 the US–Japan Cooperative Cancer Research Program was inaugurated by the NCI and the JSPS (Japanese Society for Promotion of Sciences). From that time on, Kakefuda was deeply involved in the Program. His scientific knowledge and human networks in the USA and Japan were indispensable for the smooth development of the Program in both countries. Kakefuda carefully carried out his important work as an advisor for the Program in the early stages and then later as Executive Secretary from the USA. The Program consisted of three areas: workshops, short-term exchange of personnel, and exchange of research materials. To realize the Program there were numerous matters to consider. Through Kakefuda, both Institutes were able to communicate freely and exchange ideas and opinions frankly. At that time the emergence of a new horizon in cancer research was anticipated with the introduction of the oncogene hypothesis and recombinant DNA technology. Oncogene research and gene level studies were rapidly developed and cancer research itself changed drastically. Through the Program, results of such new studies were immediately disseminated to researchers in both countries. The Program has now continued successfully for over 30 years. During this period cancer research in Japan has developed markedly and this was mostly owing to the Program. Kakefuda's contribution to both countries, especially to Japan, was extremely great. Kakefuda was a man full of curiosity who was interested in many things; he liked pottery, tea bowls, coffee mills, woodprints, dogs, golfing, fishing, and drinking Sake. He also liked to talk with people. Everyone was happy with him, and he was beloved by people around the world. Many of his friends remember with deep appreciation Kakefuda and his wife's warmest hospitality at their home. Many young Japanese scientists studied in Bethesda and numerous visitors came to the NCI and NIH, including H.I.H. Prince Masahito Hitachi and Japanese scientists supported by the Program. Kakefuda generously took care of these visitors for many years; therefore they nicknamed him the village headman of a Japanese village in Bethesda. Kakefuda was really the ambassador of cancer research between the USA and Japan. Kakefuda often attended the annual JCA meetings. In 1994, Kakefuda was invited to the symposium held in Tokyo at the Commemoration of the 60th Anniversary of the Cancer Institute and Cancer Institute Hospital, JFCR. Kakefuda gave a lecture entitled ‘Dr Tomizo Yoshida: Bridging over the Pacific Ocean’, in which he talked about experiences of Yoshida and stressed the great contribution of Yoshida in creating a bridge between the USA and Japan in cancer research. His talk was impressive; however, I thought that Kakefuda himself, just like Yoshida, has been devoted to bridging over the Pacific Ocean. Kakefuda published two books in Japanese in the last years of his life: Tracking down the Oncogene (Bunshun Shinsho, 2000) and Life Science Strategies of NIH (Blue Backs Kodansha, 2004). They are widely distributed in Japan and give inspiring messages to all readers. Kakefuda had a wonderful family. His wife Fujiko is an artist, a Japanese painter. They have two children, a son Genichi and a daughter Mika, both working with bioscience as capable researchers in North Carolina and California, respectively. During Kakefuda's last months, his children and their spouses visited him every weekend and they spent much affectionate time with their father. I want to know the landscape that Kakefuda dreamed and outlined from the US–Japan bridge. Perhaps it would be a scene of the successful National Cancer Program in the USA on one side, and a successful cancer program in Japan on the other – the Comprehensive 10-year Strategy for Cancer Control initiated by Prime Minister Nakasone in 1984. We are most grateful to Kakefuda for his enduring efforts on the bridging the US–Japan divide. Kakefuda and I first met in 1952 at the Department of Pathology, University of Tokyo, where we learned pathology and electron microscopy, and later were together in the US–Japan Cooperative Cancer Research Program. I lost my old friend.