Takashi Sugimura: In Memoriam (1926–2020)–A Personal Perspective

Abstract

Takashi Sugimura was a pioneer in cancer research and a figure recognized internationally for his seminal contributions to the understanding of mutagenicity and chemical carcinogenesis. Rather than focusing on the many accolades, honors, and influential positions that he held, the authors wish to present a more personal perspective on Dr. Sugimura’s life. In particular, we focus on his early research activities from 1950 to the late 1970s, when the author Susumu Nishimura first came to know him, with additional descriptions of his major scientific accomplishments from 1980 to recent years, through the eyes of the authors. Dr. Sugimura’s research was very much driven by his independent nature and unwavering pursuit of research findings over many decades. While working as an intern in the late 1950s at the Radiation Department in the School of Medicine of the University of Tokyo (Bunkyo–ku, Tokyo, Japan), Dr. Sugimura came to the realization that the treatment of many patients with cancer by radiation was of little benefit and instead was contributing to adverse events. He redirected his focus to basic research to gain a greater understanding of human cancer etiology. Toward achieving this aim,Dr. Sugimuramoved to the Cancer Institute of the Japanese Foundation for Cancer Research, a private cancer institute in Tokyo, Japan, which was the only cancer institute that existed in Japan at the time. The director of the Cancer Institute was Dr. Waro Nakahara, a mentor and collaborator of Dr. Sugimura, whose research outlook and personal interaction proved to be of great influence. Indeed, Dr. Nakahara was an extraordinary person in his own right. He had studied at Cornell University (Ithaca, NY) under the supervision of Dr. W.A. Riley, who was the department director. While there, Dr. Nakahara met and married Dorothy, a U.S. national who served at the time as secretary to Dr. Riley. Dr. Nakahara moved to the Rockefeller Institute (New York, NY), following the recommendations byDr. Riley, andworked under the supervision ofDr. PeytonRous.His immersion in U.S. culture truly influenced Dr. Nakahara’s research style and personality in an era when distinct differences existed between Japanese and Western cultures. After he returned to Japan, the impact of his excellent experience overseas was reflected in the staff of the Cancer Institute, who had freedom to follow individual research pursuits. Indeed, Dr. Nakahara himself worked in the laboratory alongside his research trainees. Dr. Sugimura also worked closely with Dr. Nakahara at this time and collaborated on investigating the carcinogenicity of 4-nitroquinoline N-oxide (4NQO; ref. 1). Subsequently, Dr. Sugimura traveled to the United States as a postdoctoral fellow and worked from 1957 to 1960, first at the NCI (Bethesda, MD) under Dr. J.P. Greenstein and then at the Case Western Reserve University (Cleveland, OH). This experience contributed markedly to Dr. Sugimura’s style of research. In 1960, he returned to the Cancer Institute in Tokyo, Japan, and became acquainted with Dr. Nishimura. Dr. Nishimura was immediately struck by Dr. Sugimura’s passion and scientific ability, and through the years, the two friends and colleagues had innumerable research discussions that continued over a lifetime. In 1962, the Japanese government established the National Cancer Center (NCC) in Tsukiji, Tokyo, Japan, andDr. Nakahara was selected to be the director. After the research institutes became aligned under the Ministry of Welfare, a number of researchers considered that greater career opportunities existed in the new NCC, and they were enticed by the possibility of working with their former mentor, Dr. Nakahara. Dr. Sugimura was one of the people who moved and was appointed as the director of the Division of Biochemistry. From 1958 to the late 1970s, Dr. Sugimura and his colleagues made numerous impactful discoveries, including the identification of novel carcinogenic heterocyclic amines produced by the cooking of meats. Anecdotally, it is said that Dr. Sugimura came to the realization of a link between cooked foods and carcinogenic risk factors while watching his wife cook in their modestly sized house and observing the large amount of smoke that cooking generated on a pivotal Sunday in 1976 (2). This moment encapsulated his highly inquisitive character, and mutagenic heterocyclic amines subsequently were established as multi-organ carcinogens in rodent bioassays. These accomplishments reinforced the human relevance of naturally occurring environmental mutagens and carcinogens and inspired numerous other scientists at the national and international level to enter the field of genotoxicology (3). Equally of note was the discovery of poly(ADP)-ribosylation, which is now known to contribute to DNA damage signaling, inflammation, and cancer. This research avenue became a long-standing scientific interest of Dr. Sugimura and his many colleagues (4). Dr. Sugimura’s inquisitive nature never allowed him to put this project to one side, as it arose from his own research efforts, despite it being many University of Tsukuba, Tsukuba, Ibaraki, Japan. National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.