- Email: [email protected]
International Consortium for Medical Care of Hibakusha and Radiation Life Science: a multidisciplinary program of Nagasaki University for the 21st Century Center of Excellence (COE) in Japan
International Congress Series 1258 (2003) 3 – 8
www.ics-elsevier.com
International Consortium for Medical Care of Hibakusha and Radiation Life Science: a multidisciplinary program of Nagasaki University for the 21st Century Center of Excellence (COE) in Japan Masao Tomonaga*,1 Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki 852-8523, Japan
Abstract. In October 2002, the Japanese Government started a new policy called Center of Excellence (COE) Project to selectively provide grants to universities for the promotion of their international contribution to education and research in the whole fields of science. Nagasaki University, the only university in the world that suffered the atomic bomb disaster in 1945, gained a COE grant for a multidisciplinary program that aims at combining three dimensions of research on the effect of radiation on humans; first, basic radiation biology, second, international medical care for people (Hibakusha) exposed to radiation and third, epidemiological research on atomic bomb survivors to reveal the molecular mechanism of radiation injury and induction of malignant diseases. Universities and institutions in the United Kingdom, the Netherlands, United States and former Soviet Union countries (Russia, Belarus, Ukraine and Kazakhstan) are engaged in this consortium and exchange young investigators and graduate students. Globally renowned investigators from these countries gather annually in Nagasaki to discuss the progress in the field of radiation life science. Our ultimate goal is to establish medical intervention of radiation-induced cancers and regenerative medicine for radiation victims through the development of molecular diagnostic technique, molecular targeting therapy and cell therapy. This COE program should offer a solution for the medical consequences of radio contamination in a globally widespread area on the Earth due to uncontrolled nuclear energy in the 20th century. D 2003 Published by Elsevier B.V. Keywords: Radiation life science; International medical care; Telemedicine; Tissue bank system; Radiation epidemiology
* Tel.: +81-95-849-7109; fax: +81-95-849-7113. E-mail address: [email protected] (M. Tomonaga). 1 Program Leader. 0531-5131/ D 2003 Published by Elsevier B.V. doi:10.1016/S0531-5131(03)01140-3
4
M. Tomonaga / International Congress Series 1258 (2003) 3–8
1. Introduction In October 2002, the Ministry of Education, Culture, Sports, Science and Technology (ECSST) of Japan selected 113 Center of Excellence (COE) Programs after a heated competition among 464 applications from the graduate schools of universities all over Japan. The COE project is a newly established policy of the Japanese Government on education and research that intends to extensively promote the international activities and contribution of Japanese universities in the 21st century. Nagasaki University won a COE grant as one of 113 programs and one of the 23 programs in the Multidisciplinary Area with the 13th largest grant among all programs selected. These COE programs will continue for 5 years and there will be another competitive selection for the next 5 years. 2. Structure and concept of the program The team for the COE program of Nagasaki University consists of 10 professors from Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, and Faculty of Environmental Studies. As shown in Fig. 1, the concept of our program, entitled ‘‘The International Consortium for Medical Care of Hibakusha and Radiation Life Science’’, is to efficiently combine three dimensions of research on radiation effect in humans; the first dimension is radiation life science as a basic research, the second is international medical care for radiation-exposed populations (Hibakusha) in radio-contaminated areas in the former Soviet Union countries and the third is epidemiological research on the three Hibakusha populations in Nagasaki, Chernobyl and Semipalatinsk. The international consortium of universities and institutions that are engaged in three dimensions has been established according to our program. In February 2003, we hosted the first international COE symposium on radiation life science in Nagasaki. Many leading international radiation biologists and physicians belonging to the consortium participated in the symposium and extensively discussed the concept of the program and agreed to start many projects as described in this volume. 3. Radiation life science Radiation life science will be promoted by a subgroup of this consortium consisting of several leading institutes such as Gray Cancer Institute of UK, Leiden University of the Netherlands, Columbia University and Michigan State University of USA. More universities and institutions will be invited to this group in the next year. All delegates from these COE member institutes agreed to exchange young researchers and graduate students. The consortium intends to overcome radiation-related injuries and late effects that are still serious problems in the radio-contaminated areas. In particular, elucidation of molecular mechanism of radiation oncogenesis in Hibakusha and subsequent developments of molecular diagnosis, molecular targeting therapy and cell therapy are the most important goal. 4. International medical care for radiation victims in former Soviet Union countries The second dimension consists of two major fields of radiation exposure due to nuclear power station accident or experimental detonations of nuclear weapons. Since 1991, in the
M. Tomonaga / International Congress Series 1258 (2003) 3–8
Fig. 1. Structure and concept of the COE program of Nagasaki University. 5
6
M. Tomonaga / International Congress Series 1258 (2003) 3–8
field of Chernobyl Nuclear Power Plant accident, we have conducted medical screening for over 200 000 children for early detection of thyroid cancer in collaboration with the Ministries of Health and academic institutes in Russia, Belarus and Ukraine. More recently, since 1999, the Telemedicine System has started because the long distance between Japan and these radio-contaminated areas is a geographical barrier. The system was established and operated by Professor Yamashita and his team consisting of many doctors and specialists from Chernobyl and Semipalatinsk areas as well as Nagasaki University. Tremendous amounts of medical informations, such as ultrasonic images of thyroid gland and cytological and histological images of biopsied/surgical specimens, have been sent to Nagasaki University via satellite network from Gomel Specialized Medical Dispensary of Belarus and Semipalatinsk Medical Academy of Kazakhstan. Many cases of childhood thyroid cancer have been diagnosed and successfully treated. Delegates from these countries participated in this symposium and presented updated data obtained through the Telemedicine System. This system has further developed into a WHO project. Recently, Nagasaki University was nominated as one of the research and educational centers of the Chernobyl Thyroid Tissue Bank Project that promotes tissue collection, storage and DNA/RNA extraction from Hibakusha’s specimen. The international medical care activity in Semipalatinsk, where more than a half million Kazakhstan people have been exposed to low to moderate dose of radiation, started in 1995 with financial aid from the Ministry of ECSST of Japan. Later on, the Tokyo International Congress on Kazakhstan Issue adopted resolutions to support this country to overcome radio contamination and solve health problem. Since then, the Japanese Government began to support an epidemiological investigation on the cohort of 20 000 people. In addition, Nagasaki University has been playing a major role in the Ministry of Foreign Affairs-based ODA-JICA project of Japan to strengthen medical infrastructure of Kazakhstan as well as mass health survey for radiation-exposed population in collaboration with Hiroshima University. A longitudinal epidemiological study on the fixed cohort, tissue bank establishment for molecular epidemiology and development of a reliable dosimetry system are the most important subjects. These studies should reveal the real risk of the late effects of radioactive fallout from the repeated atomic bomb explosion tests in air. The epidemiological study on cancer risks especially by low dose radiation is the most important subject to be accomplished within 5 years. It must be emphasized that studies of molecular epidemiology have been conducted on the cohort of about 30 000 children around Chernobyl. Case-control study of thyroid cancer, study of molecular genetics based on the tissue bank and risk study on the other endocrine cancers are the major subjects. These studies must deal with difficult radiation exposure status resulting from external as well as internal exposure and chronic low-dose rate exposure. 5. Epidemiological study and medical care of the atomic bomb survivors The third dimension is the epidemiological research and the field of medical care of the atomic bomb survivors (Hibakusha) in Nagasaki. Since 1950, we have conducted a longterm epidemiological survey in collaboration with Radiation Effects Research Foundation
M. Tomonaga / International Congress Series 1258 (2003) 3–8
7
(RERF) to collect basic data on the basis of a fixed cohort and estimates of radiation risk in humans. Exposure status was rather simple in atomic bomb survivors. Only external radiation was the major source of radiation exposure with various degrees of shielding. We have also been conducting biannual mass health survey for all survivors to promote disease detection especially by focusing on early diagnosis of cancers. In addition to these investigations, we have accomplished a large-scale study on the psychological effects of the atomic bombing experience on Hibakusha after almost a half century by using Goldberg’s General Health Questionnaire for evaluating mental health conditions. We were surprised to see an apparent persistence of such effects on mental health over 50 years. For the atomic bomb survivors cohort of about 60 000 in Nagasaki, we have been focusing on the incidence and mortality rate of cancers. In collaboration with RERF epidemiologists, we revealed apparent linear dose-dependent increases of leukemia and cancer risks in a relatively high dose range from 200 mSv to 4 Sv. More recently, we have become interested in an increased frequency of observing more than one cancer in Hibakusha individuals since they tend to have been cured of the first cancer and lived longer due to early diagnosis and successful treatment. Although cancer incidence has been established by organ-based epidemiological study on the RERF Life Span Study cohort, such a lifelong risk of single dose exposure in individual Hibakusha has never been thoroughly studied. Moreover, it is still unclear what the low dose range exposure actually brought about to Hibakusha due to relatively small population size. Compared with this atomic bomb survivor cohort, Semipalatinsk seems to have a much larger cohort. To gain insight into low-dose effects of radiation, the cohort study in the latter will be of great importance. Although chromosome studies on Hibakusha have indicated an apparent dose-dependent increase in stable-type karyotypic abnormalities in blood cells obtained from individual Hibakusha, and many experiments have demonstrated chromosomal and genetic instability in animal cells exposed to radiation, there is no established theory for the induction of human cancers and leukemias with recurrent cytogenetic/genetic abnormalities like Philadelphia chromosome translocation or BCR/ABL fusion gene in chronic myeloid leukemia (CML) that was a prototype of leukemia occurring in atomic bomb survivors. BCR/ABL fusion gene is a hallmark of CML diagnosis, and transfection of mouse blood cells with this fusion gene can cause human CML-like leukemia in transplanted mice. Another example is the frequent occurrences of ret oncogene rearrangement in radiation-induced thyroid cancer. Thus, there seems a lack of knowledge about how such recurrent gene rearrangements eventually ensue after cytogenetic/genetic instabilities induced by radiation. To understand fully such molecular processes underlying the induction of actual human leukemias or cancers are prerequisite for the development of molecular diagnosis of early onset of leukemia and cancer, and molecular targeting drugs that can intervene preleukemic or pre-cancerous clones. To understand more thoroughly the cytogenetic/genetic instability at cellular level, we need to introduce the microbeam technology and to use human cells such as hematopoietic stem cells. The so-called bystander effect is not well studied in human cells. Professor Watanabe hosted an international symposium in February 2001 in Nagasaki on low dose effects of radiation. Many participating radiation biologists exchanged their views on the
8
M. Tomonaga / International Congress Series 1258 (2003) 3–8
bystander effect. This COE symposium invited the same participants who concluded the necessity of performing possible experiments on human cells to further promote our understanding of early events and late events inducing malignant cells. In order to observe development of malignant clone, it will be essential in future to transplant radiationdamaged human stem cells to common g-chain-knock out mice that are deficient in T/B lymphocytes as well as NK cells. To irradiate individual stem cells, we are going to introduce a soft X-ray microbeam irradiator from Gray Cancer Institute in the second year. Another important question about the health effects of atomic bomb irradiation on second-generation children (F1) born to Hibakusha parents has to be answered. RERF is now conducting a large-scale epidemiological survey on F1 population. This problem profoundly relates to the future generations of humans exposed to radiation because of the huge number of such exposed population due to worldwide use of nuclear energy in the 20th century. In this respect, we need to keep in mind evidence of trans-generation effect of radiation, namely germ line transmission of radiation-induced mutation, first reported on the basis of mouse experiments and also recently recognized by a molecular study on three generations of Semipalatinsk Hibakusha population. 6. Exchange of young researchers and graduate students Our program mainly deals with the radio-contaminated areas in the former Soviet Union countries as shown in Fig. 1. These countries need international aid in the form of manpower as well as medical facilities. Education of postgraduate students and young researchers is one of the most important projects in our program. Graduate students from Nagasaki University can join and experience various medical care and field research such as tissue bank. Exchange of researchers and students are essential for the future advancement in research and medical care in these countries. All outcomes from this exchange program will be presented in the annual international symposium of this consortium for further improvement. Such radio-contaminated areas are not restricted in this area but are scattered over the earth. Overcoming such environmental contamination with radioactive materials is most important for human survival in the 21st century. 7. Conclusion Our COE program apparently stands on the remarkable results of past investigations conducted in the three major fields of radio contamination in the world that brought about tremendous progress in the management of Hibakusha not only in atomic bomb survivors of Nagasaki and Hiroshima, but also in the international Hibakusha population. Our program intends to combine basic research on radiation biology with epidemiological research and medical care on Hibakusha by aiming at clarifying the mechanism of the effects of low dose irradiation to human bodies, one of the most difficult problems remaining in the 21st century. We must overcome the negative legacy of the 20th century. This will become possible only by bringing in the world leaders in the research field of radiation life science, whether basic or clinical. This is the most difficult but also the most meaningful work for human beings in overcoming environmental contamination of the earth with radioactive materials.
www.ics-elsevier.com
International Consortium for Medical Care of Hibakusha and Radiation Life Science: a multidisciplinary program of Nagasaki University for the 21st Century Center of Excellence (COE) in Japan Masao Tomonaga*,1 Department of Hematology, Atomic Bomb Disease Institute, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto 1-12-4, Nagasaki 852-8523, Japan
Abstract. In October 2002, the Japanese Government started a new policy called Center of Excellence (COE) Project to selectively provide grants to universities for the promotion of their international contribution to education and research in the whole fields of science. Nagasaki University, the only university in the world that suffered the atomic bomb disaster in 1945, gained a COE grant for a multidisciplinary program that aims at combining three dimensions of research on the effect of radiation on humans; first, basic radiation biology, second, international medical care for people (Hibakusha) exposed to radiation and third, epidemiological research on atomic bomb survivors to reveal the molecular mechanism of radiation injury and induction of malignant diseases. Universities and institutions in the United Kingdom, the Netherlands, United States and former Soviet Union countries (Russia, Belarus, Ukraine and Kazakhstan) are engaged in this consortium and exchange young investigators and graduate students. Globally renowned investigators from these countries gather annually in Nagasaki to discuss the progress in the field of radiation life science. Our ultimate goal is to establish medical intervention of radiation-induced cancers and regenerative medicine for radiation victims through the development of molecular diagnostic technique, molecular targeting therapy and cell therapy. This COE program should offer a solution for the medical consequences of radio contamination in a globally widespread area on the Earth due to uncontrolled nuclear energy in the 20th century. D 2003 Published by Elsevier B.V. Keywords: Radiation life science; International medical care; Telemedicine; Tissue bank system; Radiation epidemiology
* Tel.: +81-95-849-7109; fax: +81-95-849-7113. E-mail address: [email protected] (M. Tomonaga). 1 Program Leader. 0531-5131/ D 2003 Published by Elsevier B.V. doi:10.1016/S0531-5131(03)01140-3
4
M. Tomonaga / International Congress Series 1258 (2003) 3–8
1. Introduction In October 2002, the Ministry of Education, Culture, Sports, Science and Technology (ECSST) of Japan selected 113 Center of Excellence (COE) Programs after a heated competition among 464 applications from the graduate schools of universities all over Japan. The COE project is a newly established policy of the Japanese Government on education and research that intends to extensively promote the international activities and contribution of Japanese universities in the 21st century. Nagasaki University won a COE grant as one of 113 programs and one of the 23 programs in the Multidisciplinary Area with the 13th largest grant among all programs selected. These COE programs will continue for 5 years and there will be another competitive selection for the next 5 years. 2. Structure and concept of the program The team for the COE program of Nagasaki University consists of 10 professors from Atomic Bomb Disease Institute, Graduate School of Biomedical Sciences, and Faculty of Environmental Studies. As shown in Fig. 1, the concept of our program, entitled ‘‘The International Consortium for Medical Care of Hibakusha and Radiation Life Science’’, is to efficiently combine three dimensions of research on radiation effect in humans; the first dimension is radiation life science as a basic research, the second is international medical care for radiation-exposed populations (Hibakusha) in radio-contaminated areas in the former Soviet Union countries and the third is epidemiological research on the three Hibakusha populations in Nagasaki, Chernobyl and Semipalatinsk. The international consortium of universities and institutions that are engaged in three dimensions has been established according to our program. In February 2003, we hosted the first international COE symposium on radiation life science in Nagasaki. Many leading international radiation biologists and physicians belonging to the consortium participated in the symposium and extensively discussed the concept of the program and agreed to start many projects as described in this volume. 3. Radiation life science Radiation life science will be promoted by a subgroup of this consortium consisting of several leading institutes such as Gray Cancer Institute of UK, Leiden University of the Netherlands, Columbia University and Michigan State University of USA. More universities and institutions will be invited to this group in the next year. All delegates from these COE member institutes agreed to exchange young researchers and graduate students. The consortium intends to overcome radiation-related injuries and late effects that are still serious problems in the radio-contaminated areas. In particular, elucidation of molecular mechanism of radiation oncogenesis in Hibakusha and subsequent developments of molecular diagnosis, molecular targeting therapy and cell therapy are the most important goal. 4. International medical care for radiation victims in former Soviet Union countries The second dimension consists of two major fields of radiation exposure due to nuclear power station accident or experimental detonations of nuclear weapons. Since 1991, in the
M. Tomonaga / International Congress Series 1258 (2003) 3–8
Fig. 1. Structure and concept of the COE program of Nagasaki University. 5
6
M. Tomonaga / International Congress Series 1258 (2003) 3–8
field of Chernobyl Nuclear Power Plant accident, we have conducted medical screening for over 200 000 children for early detection of thyroid cancer in collaboration with the Ministries of Health and academic institutes in Russia, Belarus and Ukraine. More recently, since 1999, the Telemedicine System has started because the long distance between Japan and these radio-contaminated areas is a geographical barrier. The system was established and operated by Professor Yamashita and his team consisting of many doctors and specialists from Chernobyl and Semipalatinsk areas as well as Nagasaki University. Tremendous amounts of medical informations, such as ultrasonic images of thyroid gland and cytological and histological images of biopsied/surgical specimens, have been sent to Nagasaki University via satellite network from Gomel Specialized Medical Dispensary of Belarus and Semipalatinsk Medical Academy of Kazakhstan. Many cases of childhood thyroid cancer have been diagnosed and successfully treated. Delegates from these countries participated in this symposium and presented updated data obtained through the Telemedicine System. This system has further developed into a WHO project. Recently, Nagasaki University was nominated as one of the research and educational centers of the Chernobyl Thyroid Tissue Bank Project that promotes tissue collection, storage and DNA/RNA extraction from Hibakusha’s specimen. The international medical care activity in Semipalatinsk, where more than a half million Kazakhstan people have been exposed to low to moderate dose of radiation, started in 1995 with financial aid from the Ministry of ECSST of Japan. Later on, the Tokyo International Congress on Kazakhstan Issue adopted resolutions to support this country to overcome radio contamination and solve health problem. Since then, the Japanese Government began to support an epidemiological investigation on the cohort of 20 000 people. In addition, Nagasaki University has been playing a major role in the Ministry of Foreign Affairs-based ODA-JICA project of Japan to strengthen medical infrastructure of Kazakhstan as well as mass health survey for radiation-exposed population in collaboration with Hiroshima University. A longitudinal epidemiological study on the fixed cohort, tissue bank establishment for molecular epidemiology and development of a reliable dosimetry system are the most important subjects. These studies should reveal the real risk of the late effects of radioactive fallout from the repeated atomic bomb explosion tests in air. The epidemiological study on cancer risks especially by low dose radiation is the most important subject to be accomplished within 5 years. It must be emphasized that studies of molecular epidemiology have been conducted on the cohort of about 30 000 children around Chernobyl. Case-control study of thyroid cancer, study of molecular genetics based on the tissue bank and risk study on the other endocrine cancers are the major subjects. These studies must deal with difficult radiation exposure status resulting from external as well as internal exposure and chronic low-dose rate exposure. 5. Epidemiological study and medical care of the atomic bomb survivors The third dimension is the epidemiological research and the field of medical care of the atomic bomb survivors (Hibakusha) in Nagasaki. Since 1950, we have conducted a longterm epidemiological survey in collaboration with Radiation Effects Research Foundation
M. Tomonaga / International Congress Series 1258 (2003) 3–8
7
(RERF) to collect basic data on the basis of a fixed cohort and estimates of radiation risk in humans. Exposure status was rather simple in atomic bomb survivors. Only external radiation was the major source of radiation exposure with various degrees of shielding. We have also been conducting biannual mass health survey for all survivors to promote disease detection especially by focusing on early diagnosis of cancers. In addition to these investigations, we have accomplished a large-scale study on the psychological effects of the atomic bombing experience on Hibakusha after almost a half century by using Goldberg’s General Health Questionnaire for evaluating mental health conditions. We were surprised to see an apparent persistence of such effects on mental health over 50 years. For the atomic bomb survivors cohort of about 60 000 in Nagasaki, we have been focusing on the incidence and mortality rate of cancers. In collaboration with RERF epidemiologists, we revealed apparent linear dose-dependent increases of leukemia and cancer risks in a relatively high dose range from 200 mSv to 4 Sv. More recently, we have become interested in an increased frequency of observing more than one cancer in Hibakusha individuals since they tend to have been cured of the first cancer and lived longer due to early diagnosis and successful treatment. Although cancer incidence has been established by organ-based epidemiological study on the RERF Life Span Study cohort, such a lifelong risk of single dose exposure in individual Hibakusha has never been thoroughly studied. Moreover, it is still unclear what the low dose range exposure actually brought about to Hibakusha due to relatively small population size. Compared with this atomic bomb survivor cohort, Semipalatinsk seems to have a much larger cohort. To gain insight into low-dose effects of radiation, the cohort study in the latter will be of great importance. Although chromosome studies on Hibakusha have indicated an apparent dose-dependent increase in stable-type karyotypic abnormalities in blood cells obtained from individual Hibakusha, and many experiments have demonstrated chromosomal and genetic instability in animal cells exposed to radiation, there is no established theory for the induction of human cancers and leukemias with recurrent cytogenetic/genetic abnormalities like Philadelphia chromosome translocation or BCR/ABL fusion gene in chronic myeloid leukemia (CML) that was a prototype of leukemia occurring in atomic bomb survivors. BCR/ABL fusion gene is a hallmark of CML diagnosis, and transfection of mouse blood cells with this fusion gene can cause human CML-like leukemia in transplanted mice. Another example is the frequent occurrences of ret oncogene rearrangement in radiation-induced thyroid cancer. Thus, there seems a lack of knowledge about how such recurrent gene rearrangements eventually ensue after cytogenetic/genetic instabilities induced by radiation. To understand fully such molecular processes underlying the induction of actual human leukemias or cancers are prerequisite for the development of molecular diagnosis of early onset of leukemia and cancer, and molecular targeting drugs that can intervene preleukemic or pre-cancerous clones. To understand more thoroughly the cytogenetic/genetic instability at cellular level, we need to introduce the microbeam technology and to use human cells such as hematopoietic stem cells. The so-called bystander effect is not well studied in human cells. Professor Watanabe hosted an international symposium in February 2001 in Nagasaki on low dose effects of radiation. Many participating radiation biologists exchanged their views on the
8
M. Tomonaga / International Congress Series 1258 (2003) 3–8
bystander effect. This COE symposium invited the same participants who concluded the necessity of performing possible experiments on human cells to further promote our understanding of early events and late events inducing malignant cells. In order to observe development of malignant clone, it will be essential in future to transplant radiationdamaged human stem cells to common g-chain-knock out mice that are deficient in T/B lymphocytes as well as NK cells. To irradiate individual stem cells, we are going to introduce a soft X-ray microbeam irradiator from Gray Cancer Institute in the second year. Another important question about the health effects of atomic bomb irradiation on second-generation children (F1) born to Hibakusha parents has to be answered. RERF is now conducting a large-scale epidemiological survey on F1 population. This problem profoundly relates to the future generations of humans exposed to radiation because of the huge number of such exposed population due to worldwide use of nuclear energy in the 20th century. In this respect, we need to keep in mind evidence of trans-generation effect of radiation, namely germ line transmission of radiation-induced mutation, first reported on the basis of mouse experiments and also recently recognized by a molecular study on three generations of Semipalatinsk Hibakusha population. 6. Exchange of young researchers and graduate students Our program mainly deals with the radio-contaminated areas in the former Soviet Union countries as shown in Fig. 1. These countries need international aid in the form of manpower as well as medical facilities. Education of postgraduate students and young researchers is one of the most important projects in our program. Graduate students from Nagasaki University can join and experience various medical care and field research such as tissue bank. Exchange of researchers and students are essential for the future advancement in research and medical care in these countries. All outcomes from this exchange program will be presented in the annual international symposium of this consortium for further improvement. Such radio-contaminated areas are not restricted in this area but are scattered over the earth. Overcoming such environmental contamination with radioactive materials is most important for human survival in the 21st century. 7. Conclusion Our COE program apparently stands on the remarkable results of past investigations conducted in the three major fields of radio contamination in the world that brought about tremendous progress in the management of Hibakusha not only in atomic bomb survivors of Nagasaki and Hiroshima, but also in the international Hibakusha population. Our program intends to combine basic research on radiation biology with epidemiological research and medical care on Hibakusha by aiming at clarifying the mechanism of the effects of low dose irradiation to human bodies, one of the most difficult problems remaining in the 21st century. We must overcome the negative legacy of the 20th century. This will become possible only by bringing in the world leaders in the research field of radiation life science, whether basic or clinical. This is the most difficult but also the most meaningful work for human beings in overcoming environmental contamination of the earth with radioactive materials.