From Oxygenase to Sleep

I graduated fromOsaka University School of Medicine in 1942 at the age of 22 and then served in the Japanese Navy as a medical officer until the end of the SecondWorldWar. On a dreary cold afternoon in the late autumn of 1945, I returned home to Osaka, where I saw that the entire city had been almost completely destroyed by air raids and that my family’s house had disappeared without a trace. Under the circumstances, I decided to joinmy parents, who had evacuated to their rural home village of Ejiri, perhaps to help my father with his medical practice. Before leaving Osaka, I visited my former mentor, Professor Tenji Taniguchi, to tell him of my plans. He listened to me attentively and then asked me if I knew the old Japanese saying, “Take a seed of persimmon rather than a ball of rice. ” I was puzzled and speechless for a moment. In those days, food was scarce, and rice was rationed. A ball of white rice would be a feast! On the other hand, the seed of a persimmon would grow into a tree in 10 or 20 years and then bear plenty of flowers and fruits, which would in turn yield numerous new seeds that would grow to produce yet more trees. Standing at a crossroad of my life at the age of 25, I was faced with the following question: “Should I become a clinical doctor and practice medicine like my father, or should I become a research scientist like Professor Taniguchi? ” After pondering over the Professor’s remarks and discussing the situation withmy father for several days, I finally decided to join Professor Taniguchi’s department and started my career as a rookie microbiologist in the Department of Bacteriology, Osaka University, my almamater. However, it was obviously not a rational decision. Believe it or not, my starting salary was only 60 yen permonth, equivalent to 20 cents, not even one dollar amonth! Life was miserable and so were the conditions in the laboratory. Research funds were almost nonexistent, and even if we had had money, there were no sources of chemicals, experimental animals, or other needed commodities. The facilities were outdated, and the supply of electricity, gas, and even water was limited, so it looked almost impossible to start any experimental research. One day, I was visited quite unexpectedly by Dr. Yashiro Kotake, Professor Emeritus of Osaka University and a world-renowned biochemist in prewar Japan. He gave me several grams of tryptophan as a gift and encouraged me to use this amino acid for my research. I was very grateful to him but, frankly, did not know what to do with this precious material. At that time, tryptophan metabolism had already been investigated by numerous biochemists, including Kotake and coworkers. Tryptophan had been shown to be metabolized to kynurenic acid, anthranilic acid, and xanthurenic acid and secreted into the urine of rats and other mammals, including humans. Kotakewas famous for this discovery and for the identification of kynurenine, the key intermediate of tryptophan metabolism. In 1934–1935, he wrote two solicited review articles on this subject in theAnnual Review of Biochemistry (Volumes 3 and 4). Because Kotake’s lifework had been carried out with the animal systems and because of the poor existing conditions of our laboratory, I decided to try microorganisms. I went out into the back yard of the University building, took a spoonful of scorched soil, mixed it with a trace amount of Kotake’s tryptophan and water in a test tube, and simply waited. Several days passed, and then a faint white cloudiness appeared in the supernatant in the test tube containing tryptophan, whereas nothing happened in the test tube without the amino acid. This cloudiness slowly increased after several days, and by transferring the THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 283, NO. 28, pp. 19165–19175, July 11, 2008 © 2008 by The American Society for Biochemistry and Molecular Biology, Inc. Printed in the U.S.A.