Always embracing new challenges in my life from Nagasaki onward

On this unique occasion celebrating the 100^th anniversary of the founding of the Japan Endocrine Society (JES), it is a great honor and pleasure for me to have this deeply appreciated opportunity to introduce to the junior and young members my modest background and reasons for aspiring to Endocrinology.

First, I would like to refer to the famous proverb, “When you drink water, think of its source,” an idiomatic translation for “Don’t forget where your happiness comes from.” The Dutch physician J.L.C. Pompe van Meerdervoort (1829–1908) established the “Igakudenshusho” and “Nagasaki Yojosho” in 1857 and 1861, respectively, which were the first modern western-style medical school and hospital in Japan. He similarly said: “The physician should realize the nature of this vocation, once he has made his choice, he is accountable to the suffering, not to himself. If it is not his wish, then he should choose another profession.” Two famous novels were inspired by this interesting period of history: Kocho no yume (A butterfly dream) written in Japanese by Ryotarou Shiba and Akatsuki no tabibito (A traveler at break of day) written in Japanese by Akira Yoshimura, both of which introduced the break of dawn of western-style medicine from Nagasaki focusing on Dr. Ryoujun Matsumoto and other young challengers.

I myself had learnt medicine with high ideals and beliefs at Nagasaki University School of Medicine, which has a long history and tradition described elsewhere. Tragically, our Medical School was destroyed and burnt to ashes on August 9, 1945, by the second Atomic Bombing. After graduation in March 1978, I entered the First Department of Internal Medicine, Nagasaki University Hospital, where many active and attractive senior doctors influenced me especially about the logical thinking way through seeing various patients with a wide spectrum of endocrine disorders. These were busy days from early morning to midnight filled with clinical and research work, yet a precious and even enjoyable opportunity to learn many things from different and difficult patients who were all my teachers. Then at some point I realized that it was problematic to understand the essence of things and to improve my limited knowledge of Medicine if I was to be very busily occupied with daily clinical practice. Nevertheless, I greatly appreciated the very comfortable working environment surrounded by good teachers and colleagues who all worked very hard until late at night. Also, it was indeed due to my wife and family who permitted me and supported my daily life to work hard to master the way of Medicine, especially Endocrinology, as was my wont, without any concern over monetary reward.

When I was in the up-and-coming era of clinical graduate student, Professor Shigenobu Nagataki (1932–2016), a well-known thyroid expert, came to Nagasaki University as the third chairman of our Department after the Second World War. He moved from the Third Department of Internal Medicine, Tokyo University School of Medicine, to give us wonderful leadership and guidance. Another mentor was Dr. Motomori Izumi who gave me a chance to learn the establishment of radioimmunoassay (RIA) for serum thyroglobulin measurement, primary cell cultures from human, porcine and rat thyroid glands, and a bioassay for measurement of thyroid stimulating antibodies from the sera of patients with Graves’ disease. These RIAs and bioassay technologies looked somewhat like home-manufactured experiments through trial and error. From the beginning of experimental research, we prepared for and mastered basic knowledge and biochemical and cell biology techniques, including the wide application of radioactive tracers such as ³H, ¹⁴C, ³²P, ³⁵S, ¹²⁵I and ¹³¹I. During the graduate student period, our team also challenged an advanced clinical application of targeted radioisotope therapy using anti-thyroglobulin antibody labeled with ¹³¹I against refractory thyroid cancer. Such clinical trials were exciting and encouraged me to further understand thyroid carcinogenesis.

The honorable late Professor Nagataki sometimes requested me to write review articles or chapters, in Japanese or English, either for his requested manuscripts or as stand-alone ones. These were really big opportunities to collect, summarize, and learn from the textbooks and papers related to various topics on endocrine disorders, strengthening and widening my own basic knowledge base. Such experiences later came into fruition as several English textbooks, the most recent is one of the chapters in the Oxford Textbook of Endocrinology and Diabetes of 2022.

In 1984 after finishing graduate school at Nagasaki University, I went to the United States as the first postdoc fellow of the young talented mentor, Dr. Shlomo Melmed at the Endocrinology Division of Internal Medicine at the Cedars-Sinai Medical Center-UCLA in Los Angeles. There I was heavily involved in research on the negative-feedback mechanism of pituitary growth hormone gene regulation by insulin-like growth factor-I. I was deeply interested in understanding homeostasis, especially hormonal regulation of gene expression. Thanks to the wonderful mentorship of Dr. Melmed, I had luckily published more than 10 peer-reviewed papers (Table 1) during my three-year stay at Cedars-Sinai Medical Center through learning and applying the most advanced molecular biology techniques. This was the happiest time for me where I could enjoy, not only basic research but also quality time with my family in the United States, making for a highly satisfactory period in my life.

Table 1

Publication list on GH Gene Regulation (1984–87)

After my return to Japan in 1987, the notion that destiny is a strange overlap came into force. I changed my career from clinical endocrinologist to more basic researcher after being elected as Professor of the Atomic Bomb Disease Institute, Nagasaki University at the age of 38 years old. Since then, “Radiation exposure and Thyroid cancer” has been my lifework. My research career and achievements are beyond the scope of this article, however, and after the age of 40, I spent most of my time on education, intellectual interaction, and international cooperation mostly concentrating on global outlook issues such as medical aid projects targeting the former Soviet Union such as Belarus, Russia, Ukraine, and Kazakhstan, particularly in the field of radioactive contaminated lands.

Here, I wish to briefly introduce my deep commitment to the Chernobyl Sasakawa Medical Cooperation Project from 1991 over the period of 10 years. In its frame, health surveillance was provided to more than 200,000 children at the time of the Chernobyl Nuclear Power Plant (NPP) accident at five centers in the three contaminated countries. I was working on this difficult joint project, interacting with the health ministries, health bureaus, research institutes, and local clinics of the affected areas (Fig. 1).

Fig. 1

Achievement of Chernobyl Sasakawa Medical Cooperation Project from 1991 to 2001 in the former Soviet Union; Belarus, Russia and Ukraine.

Initially, the visits of the Japanese experts to the Soviet Union were supervised by the KGB in the major cities of Kiev (Kyiv), Minsk, and Moscow and in rural areas where the health checks covered large farms and village schools and clinics of kolkhozes and sovkhozes. During the severe winter months, the activities continued in heated garages or hangars of the designated centers. Each year, the appointed specialists from the five centers in charge of thyroid screening, blood tests, and whole-body counter examination underwent education and training, and also attended progress reporting sessions held in the local areas. Annual reports both in Japanese and Russian languages were published. As a result, after the demise of the Soviet Union, standardized diagnostic accuracy and data management were maintained in the three countries; Belarus, Russia and Ukraine. An international conference was organized in Kiev (Kyiv) in the fifth year of the project, and Chernobyl: A Decade (Elsevier, 1997), a summary of that phase of activities was published. In fact, during this period of medical assistance, the additional introduction of thyroid ultrasound-guided fine needle aspiration cytology in the five centers made accurate thyroid diagnosis possible, and together with long term preservation of blood smear specimen and serum, has laid the ground for the future international thyroid research, such as ongoing to this day through the Chernobyl Tissue Bank (CTB) (https://www.chernobyltissuebank.com).

As a part of our activities, during my professorship period in Nagasaki University, we succeeded in establishing academic cooperative agreements with Belarusian State Medical University; Belarusian Medical Academy of Post-Graduate Education; Gomel State Medical University in Belarus; A. Tsyb Medical Radiological Research Center; Endocrine Research Center; North-Western State Medical University named after I.I. Mechnikov in the Russian Federation; V.P. Komisarenko Institute of Endocrinology and Metabolism; National Research Center for Radiation Medicine; Ukrainian Radiation Protection Institute in Ukraine; Semey Medical University; Center for Nuclear Medicine and Oncology in Semey; Scientific Research Institute of Radiation Medicine and Ecology; and Kazakh National Medical University in Kazakhstan. I am very proud that my young colleagues succeeded my jobs, and actively show wonderful achievements in thyroid cancer molecular epidemiology, international public health, and radiation research. However, it is very sad to see that Russia launched a military offensive against Ukraine in February 2022. As one of the men who knows the Chernobyl areas and has many friends in the affected locations, I am strongly against the Russian military invasion of Ukraine and would like to demand that Russia cease all acts of hostility, including attacks on the nuclear facilities in Ukraine and solve the conflict peacefully as soon as possible.

For young Endocrinologists, I want to emphasize the importance of benefits of studying abroad when young, where you can experience new places and cultures, make friends from around the world, and gain a global perspective. Of course, your research interest and career would be stimulated, yet you could also expect to develop additional highly valued by-products and skills such as intercultural communication, foreign languages, adaptability, and problem-solving. For example, my first paper presentations at the international conferences were at the Third World Congress of Nuclear Medicine and Biology in Paris and subsequently at the annual meeting of the European Thyroid Association in Brussels in August 1982. I was very nervous and hesitated to communicate in my poor English at both meetings, but for most Europeans, English was not their mother language either, and we were all at the same level of the so-called not-native speakers. It was the most important to think forward and overcome the problem known from a famous proverb, “The frog in the well doesn’t know the ocean.” Therefore, it is true that you need to “toss your fears before you try something new.” I was very lucky because my mentors were all active and open-minded, and always encouraged me to challenge new things.

As a result, I served 40 years in Nagasaki University and spent my professorship for 27 and a half years keeping in mind that my leadership role is intended to create the environment where many young doctors and researchers from Japan and abroad would grow up in a cultural milieu of freedom. Among them, nearly 70 obtained their Ph.D. degrees, and more than 10 professors were brought up from my small department. Furthermore, owing to making good choice and concentrating on my work, I could perform thyroid cancer research from clinical to basic with wonderful colleagues, especially through various international joint projects on Chernobyl. One that I was deeply committed to was the establishment and management of the CTB for more than 20 years. The CTB possesses valuable bio-samples and relevant clinical data from the operated thyroid cancer patients.

My modest experience and knowledge were suddenly utilized on large scale in response to the completely unexpected and unprecedented accident at the Fukushima NPP after the Great East Japan Earthquake and Big Tsunami on March 11, 2011. Unfortunately, the consequences of the Fukushima accident were tremendous and remain a great concern for the future because of the anxiety and fear of radiation exposure, and distrust and doubt towards Science and Technology in Society. The impact was not really so much a health crisis but much more an industrial crisis and a source of social confusion beyond our control. Without knowledge of radiation health effects and rules of radiation protection, it was difficult to explain the risk and stochastic effects integrating the international consensus on radiation protection.

In the middle of chaos and calamity, I had to work as a member of nuclear disaster medicine expert group dispatched from Nagasaki to Fukushima. Initially I assumed responsibility for establishing the Fukushima Health Management Survey and then recently became the Director of Advanced Clinical Research Center at Fukushima Medical University as of August 2022, aiming at developmental research of new diagnostic technologies and nuclear medicine diagnosis and therapies firstly against neuroendocrine tumors focusing on malignant pheochromocytomas, paragangliomas, and neuroblastoma, as well as more common cancers.

Concerning the health consequences after the Fukushima NPP accident, although the risk of radiation-associated diseases is very low or negligible, the psycho-social impact is tremendously large, especially manifesting as a wrong interpretation of the second-coming Chernobyl-like increased risk of childhood thyroid cancers in Fukushima. Recent UNSCEAR (United Nations Scientific Committee on the Effects of Atomic Radiation) reports of 2013 and 2020 clearly demonstrated no evidence of radiation-induced health consequences in Fukushima. However, a high prevalence of childhood and adolescent thyroid cancers detected by a population-based screening negatively aggravates radiation fear and anxiety. It is, therefore, critically important for endocrinologists as well as radiation protection members/administrative officers to correctly explain the current prevalence of thyroid cancers in Fukushima to the public as a screening effect but not as an epidemic due to direct linkage to radiation exposure. To learn more correctly and understand the clinicopathological characteristics of thyroid cancers whether or not radiation-related, we collaborated with international experts and re-evaluated the Chernobyl cases in comparison with the Fukushima data and published several monographs (Fig. 2) besides our original papers. Long-term strategies for thyroid monitoring after nuclear accidents were also recommended from an Expert Group convened by the International Agency for Research on Cancer (IARC) in 2018 in order to maximize benefit and minimize harm at any health intervention. Endocrinologists should learn a natural history of the different types of thyroid cancers and develop more suitable approaches of their diagnosis and treatment in addition to other endocrine tumors.

Fig. 2

Lessons learnt from Chernobyl to Fukushima; achievement of international academic collaboration from 2001 to 2017.

After the accident, a long-term health surveillance is now ongoing in Fukushima, and our goals include overcoming the consequences of this nuclear disaster, changing and reforming our difficult and discordant psychological situation, and leading Fukushima in transforming in the future into the “Number one prefecture of longevity in Japan.” It is exactly the spirit of “Let’s change our tragedy into a miracle.”

From the standpoint of the above slogans, for patient-oriented gentle treatment integrating Endocrinology and Nuclear Medicine, the newly developed targeted radioisotope (²¹¹At)-based therapies for advanced and metastatic cancers are highly promising in the modern aging society. More precisely we are now taking up the challenge of how to implement “Radio-theranostics” at Fukushima Medical University. However, it is difficult to ensure appropriate communication of radiation risk in nuclear medicine diagnosis and treatment without accurate knowledge and understanding of radiation and radioactivity. For example, in Fukushima after the accident, there are still problems that need to be solved such as environmental radio-contamination, existence of difficult-to-return areas, and how to release the massive volumes of tritium water stockpiled at the accident site. It is, therefore, essentially necessary to prepare appropriate human resources from among different experts on radiation and even endocrinology education in Fukushima.

Like the developments in any field of knowledge, Medicine, including Endocrinology, has also undergone a remarkable evolution owing to the progress in science and technology. My humble experience that I have just introduced here touches on how to realize health risks imposed by the nuclear accidents and radiation exposure. However, we are always surrounded by many unpredictable risks. It is, therefore, ideal that from a broad perspective, without pursuing immediate benefit, we should honestly and seriously seek for the mystery of life, including the homeostasis mechanism and the sheer wonderfulness of human beings, through learning Endocrinology.

Thanks to Professor Seiichi Takenoshita, the President of Fukushima Medical University, after my official retirement from Nagasaki University in March 2018, I immediately moved to Fukushima again challenging the problems of Fukushima’s negative legacy, with the idea that Endocrinology is my backbone of the academic credentials determining my code of conduct, and I strongly believe in my heart that “out of evil comes good.”

Finally, I sincerely pray for the future advancement of junior and young endocrinologists through learning from the patients in front, and also for the magnificent development and bright future of the JES.

Biographies

Shunichi Yamashita

Honorary Member

Professor Emeritus, Nagasaki University

Vice-President, Fukushima Medical University

Director General, National Institute of Radiological Sciences, National Institutes for Quantum Science and Technology

Email: [e-mail]

Careers in JES

2022– Honorary Member

2018– Senior Councilor

2011–2017 Auditor

2008–2010 President for Kyushu Regional Branch

2007–2011 Director (Public Relations and Collaboration)

2001–2005 Director (General Affairs)

1991– Councilor

1980– Member

Activities in JES

2010 Chair, 28^th JES Summer Seminar on Endocrinology & Metabolism

2002 Chair, 2^nd Kyushu Naibunpi Taisha Forum (Annual Meeting of JES Kyusyu Regional Branch)

JES Awards

2019 Distinguished Endocrinologist Award

Contributions to EJ

2009–2018 Associate Editor-in-Chief