FRONT MATTER: HISTORY Temperature 2:3, 310--315; July/August/September 2015; Published with license by Taylor & Francis Group, LLC

History of thermal and environmental physiology in : the heritage of Yas Kuno

Taketoshi Morimoto* Department of Physiology; Kyoto Prefectural University of Medicine; Kawaramachi Hirokoji; Kamigyoku, Kyoto, Japan

r. Yas Kuno was a pioneer in the Kokichi Ohara and Teruo Nakayama. sweating from human skin. A celluloid Dfield of sweat gland physiology. He Many students joined the laboratories run dish attached to the skin was ventilated by trained many research scientists who by that first generation, comprising the dry air and connected to a U-tube filled formed the first generation of thermal second generation of thermal and environ- with calcium chloride. Sweat from the physiologists. In turn, these investigators mental physiologists in Japan. Further- skin was trapped by the U-tube, and the recruited qualified investigators, forming more, the students of the second sweat rate was determined from the weight the second and third generations of ther- generation form the third and fourth gen- change of the U-tube measured every mal physiologists. At present, the third erations of thermal and environmental 5 minutes. Based on the systematic and and fourth generations of investigators physiologists who are actively working at extensive sweating activity measurements are actively engaged in research, expand- the present. taken with this method, he classified ing their interests to neurophysiology, Avoiding sectionalism, Kuno stressed sweating into 2 categories: “thermal chronobiology and exercise physiology. the importance of creative and cooperative sweating,” resulting from heat accumula- research. He also felt it was important to tion in the body, and “mental sweating,” share ideas and encourage each other stimulated by mental stress. He also stud- Historical Background through scientific meetings. His philoso- ied the development of secretory activity phy became a tradition that is now hon- in the sweat glands, together with their The first scientific publication in the ored by Japanese physiologists in this field. innervation and humoral control, as well field of temperature regulation from Japan The following is a review of each of as the physiological significance of thermal was The Physiology of Human Perspiration, these generations of thermal and environ- sweating in body temperature regulation. published by Churchill in 1934 by Yas mental physiologists in Japan, with The results of those studies were published Kuno. An extended edition, titled Human emphasis on their cooperative works and as The Physiology of Human Perspiration1 Perspiration, was published as a mono- the international meetings they organized. in 1934. graph in American Lectures in Physiology In 1939, he assumed a post as a Professor by CC Thomas in 1956. of Physiology at University School The first generation of thermal and The Legacy of Yas Kuno of Medicine, where he extended his work on environmental physiologists in Japan who (1882–1977) sweating and covered further details of the worked together with Kuno include Kore- sweating mechanism, including hemi- hiro Ogata, Shinji Itoh, Hisato Yoshi- Yas Kuno was born on March 30, hidrotic response, pulsatile secretion of mura, and Kentaro Takagi, as well as 1882, in Aichi Prefecture. After graduat- sweating, the effects of thermal sweating on ing from Aichi Medical School, the fore- water and salt metabolism, and the related Keywords: environmental physiology, runner of the Nagoya University School pathophysiology. The results of those studies history, Japan, thermal physiology, Yas of Medicine, he studied physiology at the were summarized in Human Perspiration2 as Kuno University of and then at Kyoto a monograph in American Lectures in Physi- © Taketoshi Morimoto University until 1911, when he was ology in 1956. *Correspondence to: Taketoshi Morimoto; appointed Professor of Physiology at Nan- After retiring from Nagoya Univer- Email: [email protected] man Medical School of Medicine. In sity in 1955, he continued his studies Submitted: 04/28/2015 1913, he went to Leipzig to study physiol- on human sweating at the Kyoto Pre- Revised: 05/26/2015 ogy and then moved to the University fectural University of Medicine. The College London to study the physiology final presentation of his life-long work Accepted: 06/24/2015 of circulation with Prof. Ernest Starling. wasmadeintoaspeciallecturetitled http://dx.doi.org/10.1080/23328940.2015.1066920 After returning to Japan, he initiated his The Mechanism of Human Sweat Secre- This is an Open Access article distributed under studies on the physiology of sweating, tion at the XXIII International Congress the terms of the Creative Commons Attribution- Non-Commercial License (http://creativecom which became his life work. He noticed of Physiology in Tokyo in 1965. In mons.org/licenses/by-nc/3.0/), which permits that heavy sweating in cold northern dis- that lecture, he presented a hypothesis unrestricted non-commercial use, distribution, trict leads to frostbite in the hands and that the neural control of human sweat and reproduction in any medium, provided the feet. To analyze sweating mechanisms, he apparatus has developed into cholinergic original work is properly cited. The moral rights devised a new method for obtaining con- innervation from the adrenergic inner- of the named author(s) have been asserted. tinuous measurements of the rate of vation of the sweat glands of primitive

310 Temperature Volume 2 Issue 3 Table 1. Cooperative Research Projects on Thermal and Environmental Physiology in Japan Years Title Organizer or Author

1946–1953 Physiological Response to Seasonal Variations Y Kuno 1956–1958 Physiological Response to Cold Weather Y Kuno 1956–1957 Disorders due to Cold Weather H Yoshimura 1964–1965 Adaption to Climate H Yoshimura 1966–1972 International Biological Program H Yoshimura 1966–1972 Heat and Cold Tolerance H Yoshimura 1966–1972 Adaptability of Ama (Diving women) S Kobayashi 1969–1970 Circadian Rhythm K Ogata 1973–1978 Central and Peripheral Adaptation to Temperature K Ohara 1979–1981 Process of Adaptation to Heat and Cold T Nakayama 1982–1984 Regulatory Mechanisms of Body Temperature N Murakami 1986–1988 Heat Adaptation of the aged T Ogawa 1988–1989 The Role of Bioactive Substances in Adaptation T Hori 1990–1992 Analysis of Adaptation System T Morimoto 1992–1994 Analysis of Factors to Modify Temperature Sensitivity M Kosaka 1995–1998 Analysis of Sweating Mechanism during Heat Acclimatization M Kosaka

animals to maintain cutaneous blood In 1960, his students edited a book generation of Japanese physiologists in this flow, avoiding adrenergic vaso- titled Essential Problems in Climatic Physiol- field. In Table 2, Japanese physiologists in constriction. ogy3 as a tribute to Prof. Yas Kuno in cele- this field are listed: Dr. Kuno’s students In addition to these research activi- bration of his 77th birthday. This book who formed the first generation are listed ties, as a member of the Science Coun- covered “Physiological Responses to Heat” in the first line, and the second and third cil of Japan, he presented a proposal to by S Itoh, “Physiological Responses to generations are shown in the lower cases. the Japanese Government for the pro- Cold” by K Ogata, and “Acclimatization motion of cooperative research activities to Heat and Cold,” including seasonal in various fields, and the Ministry of change in body fluid by H Yoshimura. Education therefore organized a funding “Problems Related to Thermal Regulation” system for cooperative scientific research were also dealt with, which included skin groups. Cooperative research activities temperature, morphology of sweat glands, summarized in Table 1 were supported sex differences in sweating, axon-reflex by the Ministry of Education, which sweating, shivering, the mechanism of contributed to the progress of research hemi-hidrotic sweating, heat stroke, and activities of this field over an extended the treatment of frostbite. Figure 1 is a time period. photo of Dr. Kuno from this book. The Japanese Journal of Physiology In 1972, a book titled Advances in Cli- (renamed as the Journal of Physiological matic Physiology4 was edited by his stu- Science in 2006) was founded by dents in celebration of his 88th birthday, Dr. Kuno in 1951, which he edited and including contributions by Drs EF published until 1970, when its publication Adolph, J Achoff, DB Dill, OG Edholm, was handed over to the Physiological Soci- F Halberg, JD Hardy, SM Horvath, F ety of Japan. In recognition of his brilliant Sargent, E Simon, M Smolensky, R Tha- work, the Japanese Government awarded uer, as well as contributions by the second Dr. Kuno with the Academy Prize in and third generations of Japanese physiol- 1941, followed by the highest decoration ogists in this field. in the field of cultural achievements, the Dr. Kuno passed away on December Order of Cultural Merits in 1963 and the 30, 1977, and his contributions to the Order of the Sacred Treasure in 1976. He physiology of human perspiration stimu- was appointed as a member of the Japan lated the development of thermal and envi- Academy in 1949 and also received honor- ronmental physiology in Japan—in which Figure 1. Yas Kuno. The phot is from the book ary memberships in the Physiological Soci- his coworkers and pupils, including H “Essential Probles in Climatic. Physiology: A ety of Great Britain, the American Yoshimura, K Ogata, S Itoh, K Ohara, K Tribute to Prof. Kuno in Celebration of his Sev- enty Seventh Birthday.” Edited by Y. Yoshi- Physiological Society and the Physiological Takagi and T Nakayama—played leading mura et al., Nonkodo Publishing Co., Kyoto, Society of the Federal Republic of roles. Furthermore, the heritage of Dr 1960. Germany. Kuno has now descended to the present

www.tandfonline.com Temperature 311 Table 2. Japanese Thermal and Environmental physiologists K Ogata S Itoh H Yoshimura Kyoto K Ohara Nagoya T Nakayama K Takagi Y Toda M Iriki Kumamoto Univ Hokkaido Univ Pref Univ Med City Univ Univ Nagoya Univ Kobe Univ Yamanashi Univ

T Sasaki T Hiroshige Y Toda M Kosaka T Hori T Ogawa T Araki M Shibata N Murakami A Kuroshima T Morimoto Y Isobe M Shibata* J Sugenoya* Y Inoue M Nagai A Morimoto* H. Ohinata* H Nose* H Satho T Kiyohara* T Nagasaka N Kondo S Nomoto T Watanabe* Y Agishi A Takamata* F Furuyama S Aou* O Shido* M Shibasaki M Hashimoto K Doi S Nakai* T Nakajima* K Hirata* K Honma K Nagashima* K Kanosue S Sakurada* S Homma S Hori K Matsumura M Kosaka K Moriya K Shiraki H Tanaka T Matsumoto* K Miki* K Niwa M Sugawara* F Yamazaki* Y Ohnuki T Hori K Yagita T Midorikawa K Nakamura

*Indicates a student of the name above

Thermal and Environmental Biological Program (IBP) was started, and at Yamaguchi University, where he Physiology in Japan he organized the International Sympo- extended his work with Dr. Akio Mori- sium Human Adaptability and its Method- moto and Dr. Tatsuo Watanabe. Unfortu- Dr. Hisato Yoshimura (1907–1990) ology in Kyoto (Fig. 2), and the result was nately, Dr. A Morimoto passed away at covered a wide range of research topics, compiled as the IBP Handbook: Human the age of 39 (see Supplemental materi- including the acid-base balance of body Biology: A Guide to Field Methods.Asan als). Dr. T Watanabe is now working on fluid, protein nutrition, sport anemia, the organizer of the Human Adaptability sec- the effect of angiotensin II and atrial natri- cold induced vasodilation test, seasonal tion of the IBP in Japan, he recruited uretic peptide on body temperature regu- variations in body fluid and basal metabo- more than 100 scientists and led the proj- lation as a Professor of Physiology at lism at Kyoto Prefectural University of ect to great success during the period of Tottori University. Medicine. Dr. Yoshimura contributed 1966–1972. Dr. S Itoh, Dr. K Ohara and T greatly to organize cooperative research Korehiro Ogata (1905–1979) worked Nakayama worked with Dr. Kuno at projects in the field of environmental together with Dr. Kuno at Nanman Uni- Nagoya University. Dr. Shinnji Itoh physiology. He supported the projects versity as an Assistant Professor. In 1947, (1912–2003) moved to Hokkaido Uni- conducted by Dr. Kuno as a manager and he became a Professor at Kumamaoto versity, where Dr. Tsutomu Hiroshige, organizing many projects himself. In University, where he worked on the sea- Dr. Kenichi Honma and Dr. Sato Honma 1962, he was elected as the President of sonal variation of basal metabolism and did extensive work on chronobiology, the Japanese Society of Biometeorology, circadian rhythm of body temperature while Dr. Akihiro Kuroshima and Dr. which was founded by the first generation with Dr. Takashi Sasaki, and thermoregu- Katsuhiko Doi worked on BAT and non- of thermal and environmental physiolo- lation and fever with Dr. Naotoshi Mura- shivering thermogenesis in relationship gists in Japan. In 1965, the International kami. Dr. Murakami became a Professor with cold tolerance.

Figure 2. International Symposium on Human Adaptability and its Methodology. By H Yoshimura at Kyoto, 1965.

312 Temperature Volume 2 Issue 3 Figure 3. International Symposium on Thermoregulatory Mechanism. By T Nakayama at Osaka, 1982.

Dr. Kokichi Ohara (1922–1986) stud- appointed to the post of Professor of Phys- Dr. Mitsuo Kosaka became a professor ied physiology in the laboratory of Profes- iology at Nagoya University after the at Nagasaki University, where he worked sor Kuno at Nagoya University. In 1957, retirement of Dr. Kuno. He studied the on heat shock proteins and ethnic differ- he moved to Nagoya City University, and mechanism of hemihidrotic sweating. In ence of sweating activity with Dr. Takaaki then he went to West Germany and stud- that study, he found that during a period Matsumoto. Dr. Tetsuro Hori worked ied the physiology of body temperature where pressure was applied on one side of extensively on the central mechanisms of regulation in the laboratory of Prof. Tha- the body, the sweat rate of oppressed side thermoregulation, especially hypothalamic uer at the Max-Planck Institute. He visited of the body was decreased, and the sweat neurons with Dr. Nakayama at Osaka Indiana University in 1964 and worked rate of the other half of the body was dou- University. Later, he assumed a post as a with Prof. Sid Robinson. He found that bled. Thereafter, he extended his studies professor at Saga University and contin- monkeys can sweat when they are exposed to the mechanism of acupuncture. Many ued his work with Drs. Masaki Shibata, to heat repeatedly. He also succeeded in talented research scientists joined his lab, Toshikazu Kiyohara and Toshihiro Naka- breeding a heat tolerant rat by successive including Dr. T Ogawa, Dr. T Nagasaka, shima, and then at Kyushu University crossbreeding, with Dr. F Furuyama. Dr. M Kosaka and Dr. T Hori. with Shuji Aou. Dr. T Hori passed away Dr. Teruo Nakayama (1927–1989) Dr. Tokuo Ogawa visited Indiana Uni- in 2009, and Dr. Blatteis contributed a joined Dr. Kuno’s laboratory in 1950. He versity and worked on sweating activity reminiscence of Dr. Hori to Fever Lab. visited Dr. JD Hardy at the John Pierce devising continuous determination of net. Lab from 1960 to 1963 and found warm- sweating from a small area of skin with In April of 2015, Nagoya University sensitive neurons in the anterior hypothal- Prof. S Robinson and Prof. B Bullard appointed Dr. Kazuhiro Nakamura as the amus. The results of his studies were using ventilation capsule and hygrometer. Professor of Physiology, where he is work- reported in Science in 1961. Returning to As a professor at Aichi Medical School, he ing on the neural network of thermoregu- Japan, he moved to Osaka University, extended his work on sweating with Dr. lation. Thus, the long history and where he extended his work together with Masami Asayama and Dr. Junnichi traditions inspired by Dr. Kuno in the Dr. Tetsuro Hori and with his students Sugenoya. field of thermal physiology have been Dr. Kazuyuki Kanosue, Dr. Kiyoshi Mat- Dr. Tetsuo Nagasaka moved to Kana- revived at Nagoya University. sumura and many other talented thermal zawa University, where he worked on cir- Dr. Yoshiaki Toda (1915–1989), physiologists. He edited many textbooks culation and thermoregulation and also after studying in Kyoto with Dr. H in the field of thermal physiology and brain cooling with Dr. Osamu Shido and Yoshimura, moved to Kobe University played an important role in the progress others. Dr. O Shido is now working on asaProfessor.AthisLab,Dr.Yoshi- of thermal physiology in Japan. In 1982, the central mechanism of heat acclimation mitsu Inoue, now working at Osaka he organized an International Symposium as a Professor of Shimane University. In International University, studied the on Temperature Regulation, as shown in 2009, he sponsored the 3rd International development of sweating activity during Figure 3. Symposium on Physiology and Pharma- childhood and deterioration of sweating Dr. Nakayama passed away at the age cology of Temperature Regulation, with activity with aging. of 62 (see Supplemental materials). many participants from all over the world Dr. Masami Iriki graduated Tokyo Dr. Kentaro Takagi (1910–1990) was (Fig. 4). University, and he later went to West

www.tandfonline.com Temperature 313 Figure 4. International Symposium on Physiology and Pharmacology of Temperature. Regulation. By O. Shido at Izumo, 2009.

Figure 5. Man in Stressful Environment, Thermal and Work Physiology. By K Shiraki at Kitakyushu, 1986.

Germany and studied the physiology of endogenous pyrogen and other subjects continued his work at Hyogo Medical body temperature regulation in the labora- with Dr. Masaaki Hashimoto and other School. Dr. Keizo Shiraki studied sports tory of Prof. R Thauer, as well as with coworkers. anemia and extended his work to diving Prof. E Simon at the Max-Planck Insti- At the laboratory of Dr. H Yoshimura physiology later at the University of Occu- tute. Returning to Japan, he became a at Kyoto, Dr. Seiki Hori worked on the pational and Environmental Health in Professor of Yamanashi Medical School, adaptation to hot climate and the assess- Kitakyushu. In 1986, he organized the where he studied fever syndrome, ment of heat tolerance. Later, he International Symposium on Physiology

Table 3. Publications and the International Symposium on Thermal and Environmental Physiology Years Title Organizer or Author

1934 The Physiology of Human Perspiration (Monograph) Y Kuno 1956 Human Perspiration (Monograph) Y Kuno 1960 Essential Problems in Climatic Physiology (Publication) H Yoshimura, K Ogata, S Itoh 1965 Human Adaptability and its Methodology (Symposium) H Yoshimura, JS Weiner 1972 Advances in Climatic Physiology ((Publication) S Itho, K Ogata, H Yoshimura 1975 Physiolofy of Cold Adapted Man (Monograph) S Itoh 1982 International Symposium on Thermoregulatory Mechanism (Symposium) T Nakayama 1983 Hyperbaric Medicine and Underwater Physiology (Symposium) K Shiraki, S Matsuoka 1984 International Symposium on Chronobiology (Symposium) T Morimoto 1986 Man in Stressful Environment, Thermal and Work Physiology (Symposium ) K Shiraki, MK Yousef 1987 Man in Stressful Environment, Thermal and Work Physiology (Publication ) K Shiraki, MK Yousef 1992 International Symposium on Space Medicine in Nagoya 1992 (Symposium ) N Matsui 1995 Body Temperature and Metabolism (Symposium) T Nagasaka, AS Milton 1997 Nagano Symposium on Sports Sciences (Symposium) H Nose, ER Nadel, T Morimoto 1999 Exercise, Nutrition, and Environmental Stress (Symposium) H Nose, CV Gisolfi, K Imaizumi 2000 Exercise, Nutrition, and Environmental Stress (Symposium) H Nose, LL Sprit, K Imaizumi 2009 International Symposium on Physiology and Pharmacology of Temperature Regulation (Symposium) O Shido

314 Temperature Volume 2 Issue 3 of Stressful Environment (Fig. 5) and the gene in peripheral cells, and they are now Disclosure of Potential Conflicts of Interest proceedings were published as Man in working on the mechanism of circadian No potential conflicts of interest were Stressful Environments, Thermal and Work clock development in mammalian cells. disclosed. Physiology.5 This book was edited as a trib- Some of publications and the interna- ute to Professor Hisato Yoshimura in cele- tional meetings related to thermal and bration of his 77th birthday. environmental physiology held in Japan Supplemental Material Succeeding Dr. H Yoshimura, Dr. are listed in Table 3. Supplemental data for this article can Taketoshi Morimoto worked on the effect Cooperation by thermal and environ- be accessed on the publisher’s website. of dehydration on thermoregulation with mental physiologists in Japan continues Dr. Hiroshi Nose, Professor of Shinshu even today. In 1996, the Environmental University, and other coworkers, and he Physiology Section of the Physiological References 1. Kuno Y. The Physiology of Human Perspiration. elucidated the mechanism of voluntary Society of Japan instituted the Yas Kuno London, Churchill, 1934. dehydration after sweating, which was first Memorial Award for Young Investigators. 2. Kuno Y. Human Perspiration. Charles C. Thomas: reported in the classical book by Dr. EF In addition, the heat wave attack is Springfield, IL; 1956. 3. Yoshimura H, Ogata K, Itoh S (eds.). Essential Problems Adolph, The Physiology of Man in the Des- increasing due to global warming and the in Climatic Physiology. Nankodo Pub. Co.: Kyoto, ert. Dr. Seiichi Nakai conducted an epide- incidence of heat stroke is also increasing. Japan; 1960. 4. Itoh S, Ogata K, Yoshimura H (eds.). Advances in Cli- miological survey of heat stroke casualties For the prevention of heat stroke death, matic Physiology: Igakushoin: Tokyo; 1972. in Japan and actively worked for the pre- we edited A Guidebook for the Prevention 5. Shiraki K, Yousef MK (eds.). Man in Stressful Environ- ments: Thermal and Work Physiology. Charles C. vention of heat stroke casualties. of Heatstroke during Sports Activity, and Thomas: Springfield, IL; 1987. At present, Dr. Kazuhiro Yagita, Profes- also Every Day Activity. Many of the ther- sor of Physiology at Kyoto Prefectural Uni- mal and environmental physiologists in versity of Medicine, is working on circadian Japan previously listed participate in proj- rhythm. Dr. Yagita’s group found a clock ects to prevent heat stroke casualties.

www.tandfonline.com Temperature 315