Radiation Effects Research Foundation News and Views
Hiroshima and Nagasaki, Japan
Volume 14, Issue 1, Spring 2003

Table of Contents
RERF NewsThe 37th Board of Directors Meeting ........................................................................... 1
The 29th Scientific Council Meeting ............................................................................ 2
Staff News .......................................................................................................................... 4
Current Status of the New Study of Children of A-Bomb Survivors ................... 4
Current Status of Dosimetry Revision ......................................................................... 5

ArticlesTen Thousand Days Atop Hijiyama: Part 2, by Akio Awa ..................................... 7
The Way to DS02: Resolving the Neutron Discrepancy ....................................... 17
by Harry M. Cullings and Shoichiro Fujita
Facts and Figures .................................................................................................................... 24
In Memoriam
Gilbert W. Beebe, 1912–2003 ........................................................................................ 25
Abraham Kagan, 1922–2003 ......................................................................................... 26
Research Protocols and Publications
Research Protocols ........................................................................................................... 27
Recent Publications ......................................................................................................... 30

This newsletter is published by the Radiation Effects Research Foundation (formerly the Atomic
Bomb Casualty Commission), established in April 1975 as a private, nonprofit Japanese foundation.
It is supported equally by the government of Japan through its Ministry of Health, Labour andWelfare and that of the United States through the National Academy of Sciences under contract
with the Department of Energy.
RERF conducts research and studies—for peaceful purposes—on the medical effects of radiation
on humans with a view toward contributing to the maintenance of the health and welfare of atomicbomb survivors and to the enhancement of the health of all mankind.
Editor: Donald Pierce, Department of Statistics
Technical Editor: Yuko Ikawa, Editorial & Publications Section
Editorial Policy
Contributions to Update receive editorial review only and do not receive scientific peer review.
The opinions expressed herein are those of the authors only and do not reflect RERF policies orpositions.
Contact: Mailing address: RERF Editorial & Publications Section, 5-2 Hijiyama Park,
Minami-ku, Hiroshima 732-0815 Japan
Telephone: 81-82-261-3131; Facsimile: 81-82-263-7279
Internet: update@rerf.jp

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RERF NewsThe 37th Board of Directors Meeting
The 37th meeting of the Board of Directors washeld at the National Academy of Sciences (NAS) in
Washington, D.C., U.S.A. on June 19 and 20, 2002.
Twenty-three people including directors, supervisors,and observers attended the meeting, and animateddiscussions took place concerning RERF management.
In his opening address, Dr. Burton G. Bennett said,“RERF’s mission is to study radiation effects in Abomb survivors. We hope to maintain theFoundation’s scientific excellence and fulfill our social obligations in terms of the welfare of A-bomb
survivors.” The Board then approved the minutes ofthe previous Board meeting (36th, Hiroshima), andproceeded to report on the status of RERF. In thestatus report, Dr. Bennett used a slide presentation to
introduce various aspects of the RERF research activities. Dr. Bennett expressed in the report his
intention of continuing to work for the accomplishment of the following goals: to enhance congeniality
and trust among all the staff, strengthen epidemiology, and restore a balance in the U.S.-Japanesemanagement of RERF. A report on the health studyof children of A-bomb survivors was presented by
Dr. Senjun Taira, who explained the history of the
expansion of sample size in the study. Dr. Taira statedthat full-scale health examinations would start in July
2002.
In his report on the agreement on joint courses
with Hiroshima University and results of applications
for the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Grant-in-Aid for
Scientific Research, Dr. Eiichi Tahara noted the highstanding accorded to research conducted at RERF.
Other items of report included “present personnel
status,” “FY2001 salary revision,” “FY2002 labormanagement negotiations,” and “international
collaboration.”In the discussion of issues proposed by the members of the Board, Dr. Bennett suggested regarding
the “directorship balance” that the previous numberof permanent U.S. directors be restored. This issue
is to be deliberated further by the governments ofJapan and the U.S. In the area of “future planning,”
Dr. Tahara explained the results of each department’s
brainstorming sessions and further discussions at
Future Planning Committee meetings. It was projected that the future plans would be developed andcompleted within two years. Concerning the issue of
relocation of the Hiroshima Laboratory, Dr. Tairastated that relocation is an issue that RERF cannot

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avoid, and that he would like the issue, along withthe future plans, to be considered.
Among the items for deliberation, a summary of“recommendations of the 29th meeting of the Scientific Council” was presented by Dr. Joe W. Gray. In
the responses of RERF to the recommendations of
the Scientific Council, Dr. Tahara said, “We appreciate the Scientific Council’s recommendation that
RERF must continue to broaden its research basebeyond a strict focus on radiation effects, considering the importance of RERF as a joint institution
supported by the U.S. and Japan. We will continue
the brainstorming approach for the establishment of
future plans.” Following this, deliberations were carried out on the “FY2001 research activities reportand audit,” “FY2001 settlement of accounts and audit,” “FY2002 working budget,” and “FY2003
provisional budget plan,” and all of the items wereapproved by the Board of Directors.
As regards the “election/appointment of directors
and others,” it was concluded that Mr. Kazuaki Arichi
and Dr. Jonathan M. Samet would continue to serve
as directors until successors are decided. Concerning Scientific Councilors, Dr. Toshitada Takahashi,
Director of the Aichi Cancer Center Research Institute, and Dr. Joel S. Bedford, Professor of Colorado
State University, were elected as successors to Dr.
Shinichiro Ushigome and Dr. Joe W. Gray, respectively. It was decided that the next Board meeting
would be held at the Hiroshima Laboratory on June
18–20, 2003.
List of Participants
Permanent Directors:
Burton G. Bennett, Chairman
Senjun Taira, Vice Chairman
Eiichi Tahara, Permanent Director and Chief of Research
Visiting Directors:
Kazuaki Arichi, Councilor, Japan Institute of International Affairs (submitted a letter of attorney forboth days)
Takefumi Kondo, Professor, Department of Preventive Medicine and Public Health, Keio University
School of Medicine
Hiromichi Matsudaira, Consultant, Radiation Effects
Association
John E. Burris, President, Beloit College
Jonathan M. Samet, Professor and Chairman, Department of Epidemiology, School of Hygiene and
RERF Update Volume 14, Issue 1, Spring 2003

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RERF News
Public Health, Johns Hopkins University (submitted a letter of attorney for the 1st day)
Richard B. Setlow, Senior Biophysicist, Biology
Department, Brookhaven National Laboratory,
Adjunct Professor, Biochemistry and Cell Biology Department, State University of New Yorkat Stony Brook
Supervisors:
Tomio Hirohata, Professor Emeritus, Department of
Public Health, Faculty of Medicine, Kyushu University
David Williams, Senior Financial Advisor, National
Academy of Sciences (NAS)

Health, Labour and Welfare
Steven V. Cary, Deputy Assistant Secretary for HealthStudies, U.S. Department of Energy (DOE)
Joseph F. Weiss, Japan Program Manager, Office of
Health Studies, DOE
Libby White, Office of Health Studies, DOE
Warren R. Muir, Executive Director, Division on
Earth and Life Studies, National Research Council (NRC), NAS
Evan B. Douple, Director, Board on Radiation Effects Research, Division on Earth and Life
Studies, NRC, NAS
Catherine S. Berkley, Administrative Associate,
Board on Radiation Effects Research, Division
on Earth and Life Studies, NRC, NAS

Scientific Councilor:
Joe W. Gray, Professor of Laboratory Medicine andRadiation Oncology, Program Leader, Cancer
Genetics and Breast Oncology, Comprehensive
Cancer Center, University of California, San Francisco

Secretariat:
Charles A. Waldren, Chief Scientist
Masaharu Yoshikawa, Chief of Secretariat
Richard D. Sperry, Administrative Advisor, Secretariat

Representatives of Supporting Agencies:
Shigeki Shiiba, Deputy Director, General Affairs
Division, Health Service Bureau, Ministry of

Observer:Seymour Abrahamson, former RERF Vice Chairman
and Chief of Research

The 29th Meeting of RERF Scientific Council
The 29th meeting of the Scientific Council washeld on April 16–18, 2002, in Hiroshima. The meeting was co-chaired by Drs. Joe W. Gray and Yasuhito
Sasaki. After RERF Chairman Dr. Burton G. Bennett
extended greetings and introductory remarks, Chiefof Research Dr. Eiichi Tahara presented a generalreport of RERF research. Dr. Tahara also presented
a report of the Future Planning Committee of the
RERF based on internal brain-storming sessions
among department members and chiefs of the departments throughout the past year, listing several
possibilities that were suggested as future directions.
Dr. Tahara further proposed a set of policies on theuse of biological samples developed by the Working
Group on Ethical Policy for Biological Samples,
based on recently established ethical guidelines set
forth by the Japanese government for the protectionof human rights and privacy of study participants.
Present status and trends in the U.S. were introducedby American councilors.
Drs. Gen Suzuki and Masazumi Akahoshi presented a response to the Multinational Peer Reviewof the Departments of Clinical Studies. Presentations
were then made by all departments. In addition to
overviews given by department chiefs, the following
more specific presentations were made:Return to Table of Contents• Adult Health Study (AHS) Report 8 (Michiko

Yamada, Clinical Studies)• Cataract study (Kazuo Neriishi, Clinical Studies)• Thyroid disorders (Misa Imaizumi, Clinical Stud-ies, Nagasaki)• Microarray-based comparative genomic hybrid-ization (CGH) (Norio Takahashi, Genetics)• Epilation, chromosome aberrations, and dose bias

(Yoshiaki Kodama, Genetics)• Clonal chromosome aberrations (Nori Nakamura,

Genetics)• Cancer and noncancer mortality (Yukiko Shimizu,

Epidemiology)• F1 mail survey (Akihiko Suyama, Epidemiology,

Nagasaki)• Projections regarding Life Span Study (LSS)/F1

cohorts (Eric Grant, Epidemiology)• Plan for molecular epidemiology (Hidetaka

Eguchi, Epidemiology)• Molecular basis of A-bomb induced carcinogen-esis (Yuko Hirai, James Cao, Kiyohiro Hamatani,
Radiobiology)• T-cell homeostasis (Seishi Kyoizumi, Radiobiology)• LSS cancer incidence (Dale Preston, Statistics)• Describing and interpreting radiation effects(Donald Pierce, Statistics)
RERF Update Volume 14, Issue 1, Spring 2003

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RERF News• Probability of radiation causation (John Cologne,

Statistics)• F1 cancer and noncancer mortality (Shizue Izumi,
Statistics)• Dosimetry revision status (Shoichiro Fujita, Statistics)
The Scientific Council affirmed continued support for the core mission of RERF, but also supported
expansion of this core mission in a manner based on
thorough evaluation of research priorities, fundingbases, and resources. The Council’s general recommendations are summarized as follows:
Long term planning. The Council encourages continued departmental brainstorming on future plans,and supports the idea that RERF must broaden its
research base beyond a strict focus on radiation effects. In this, continuation of RERF as a joint
U.S.-Japanese effort is important. RERF is encouraged to obtain blood, serum, and tumor samples fromas many LSS and F1 members as possible, including
those who have moved away. Collection should more
involve representatives of local physicians and research communities. Patients should be asked forconsent to use of specimens in international collaborations. The Council supports development ofinternational and private sector collaborations. Increased involvement should be achieved withorganizations representing LSS and F1 cohorts in thedevelopment of strategic plans and molecular epidemiology studies. Efforts should be made to increase
the value to cohort members of the RERF studies, inorder to encourage their maximal participation. The
public should be better shown that RERF work is thefoundation of international radiation protection, andthat refinements will come from future work. The
policy on intellectual property should be reconsidered and revised to encourage collaborations withacademia and the private sector.
Cohort and tissue resources. As the cohort andspecimens are unique and highly valuable for research, every effort should be made to maintain thecohorts and increase the number of subjects contributing specimens. Further effort should be made toincrease the F1 study with persons whose parents were
exposed to high doses, even though not living locally. A better system of prioritization and protectionof specimens is needed. Production of microarrays
is recommended, and immortalization of nucleic acids should be attempted.
Collaboration. Collaboration is needed both to promote high-quality work and improve the reputationof RERF in Japan. Special efforts should be made tocollaborate with organizations having advanced analytical capabilities. Policies for collaboration and

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sharing of biosamples should be reviewed. International and private sector collaborations should be
developed. Involvement in Millenium Project shouldbe evaluated.
Organizational and management issues. Online
journal access should be enhanced. External peer
review is needed for projects involving highly technical methods. Scientific and fiscal policies areneeded for external grants. MEXT (Ministry of Education, Culture, Sports, Science and Technology)
proposals using RERF facilities should only be forprojects relevant to the broadly defined mission of
RERF. There needs to be more rapid review for clinical RPs, and renewal reviews should be made every
1–3 years. More publication in high-impact journals
is needed. The Department of Clinical Studies should
become more involved in cancer studies, integratingwith the Epidemiology Department. There should be
increased support for IT activities. Investigators areencouraged to seek statistical advice during study
design, and to take advantage of pilot studies. The
Council supports annual alternation of regular meeting and departmental/program peer review.
Extensive evaluations and recommendations werealso made for each research department.
Members of the Scientific Council
Takefumi Kondo, Professor, Department of Preventive Medicine and Public Health, Keio University
School of Medicine
Yusuke Nakamura, Director, Human Genome Center, Institute of Medical Science, University ofTokyo (Absent)
Ohtsura Niwa, Director and Professor, Radiation
Biology Center, Kyoto University
Yasuhito Sasaki, President, National Institute of Radiological Sciences
Shinichiro Ushigome, Visiting Professor, Jikei University School of Medicine (Absent)
J. Martin Brown, Professor and Division Chairman,
Division of Radiation Biology, Department ofRadiation Oncology, Stanford University Schoolof Medicine (Absent)
Joe W. Gray, Professor of Laboratory Medicine andRadiation Oncology, University of California, San
Francisco
Gloria M. Petersen, Professor of Clinical Epidemiology, Mayo Medical School
Theodore L. Phillips, Professor and Chairman, Radiation Oncology, Cancer Center, School of
Medicine, University of California, San Francisco
Clarice R. Weinberg, Chief, Biostatistics Branch,
Environmental Diseases and Medicine Program,
National Institute of Environmental Health Sciences

RERF Update Volume 14, Issue 1, Spring 2003

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RERF News

Staff News
Dr. Kazunori Kodama, formerly RERF Chief ofClinical Studies, rejoined RERF in July 2002 as Chiefof Epidemiology. During his time away from RERF
he was Professor, Institute of Health Sciences,
Hiroshima University. Drs. Shuhei Nakanishi andNobuaki Hattori joined the Department of ClinicalStudies in April 2002. Dr. Nakanishi was before thata medical student at Hiroshima University and Dr.
Hattori comes from the Gastroenterology Departmentof Oda Municipal Hospital, Shimane Prefecture. Alsoin April 2002 Dr. Masataka Taga joined the Department of Radiobiology, following his position as
Lecturer, Kyoto University Radiation Biology Center. Dr. Asao Noda joined the Department of Genetics
in September 2002, having been Lecturer, Depart-

ment of Molecular and Cellular Biology, Kobe University.
Dr. Kei Nakachi moved in July 2002 from being
RERF Chief of Epidemiology to Chief of the Department of Radiobiology/Molecular Epidemiology.
Dr. Donald MacPhee vacated the position as Chiefof Radiobiology due to mandatory retirement age,and continues at RERF as Research Advisor. Drs.
Kazue Imai and Hidetaka Eguchi, of Dr. Nakachi’smolecular epidemiology research group, followed
him in that departmental change. Dr. Fumiyoshi
Kasagi moved in August 2002 from the RERF Department of Statistics to the Department of
Epidemiology.

Current Status of the New Study of Children of A-Bomb Survivors
A mail survey and clinical study of the RERF F1
cohort was initiated in recent years; some information was provided in the Spring-Summer 2001 issueof Update. This is a major RERF program to supplement studies of this cohort when they were children,and the continuing surveillance of their mortality andcancer incidence. Study design resulted in a mail survey cohort to obtain lifestyle information, with theclinical study comprising those respondents expressing interest in participating. A primary aim of theclinical study is to ascertain any excess risk for multifactorial diseases such as hypertension, diabetes,and cardiovascular diseases as this cohort reaches
middle age.
A primary aspect of progress in the past two years
has been to expand the size of the initially selectedmail survey and clinical study cohorts. The main pointof this was to further include those for whom one
parent has a positive dose estimate but there is no
RERF information on the other parent (which very
likely means they were unexposed). This resulted inadding 6,600 persons to the original mail survey cohort of about 18,000. Notably, the number of persons
for whom at least one parent had a dose of 5–500
mSv was thereby doubled, and the corresponding
number for dose >500 mSv was increased by 50%.

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Exceptional care is being taken to carry out thisstudy in a scientifically and ethically most appropriate manner, and to assure the public and F1 populationthat this is being done. During 2000–2003 there wereseven meetings of the Scientific Committee and six
meetings of the Ethics Committee, both of these being external committees established for this study.
Separate informed consent procedures were established for the clinical examination and forpreservation of serum plasma, urine, and blood cells
for future molecular biology studies. A pilot clinicalstudy of 500 persons was conducted in 2002, and thefull-scale clinical study began in July 2002. Approximately 10,000 F1 cohort members are expected toparticipate in the clinical study over a four-year period. This is about 60% of those successfully
contacted in the mail survey.
The success of this study will not hinge on whether
a statistically significant radiation effect for multifactorial diseases is found. The purpose is to estimate
whatever risk there may be, and in the initial planning of the study it was determined that the precisionof such an estimate will be high enough for the study
to be scientifically useful. Upper confidence limits
on the true risk will be important whether or not there
is found a statistically significant effect.

RERF Update Volume 14, Issue 1, Spring 2003

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RERF News

Current Status of Dosimetry Revision
Previous issues of RERF Update have reported
progress towards a revised RERF dosimetry system.
The new system DS02 to replace DS86 was given
final approval on 15 March 2003 by the Joint U.S.Japanese Senior Review Group, chaired by Dr.
Warren Sinclair and Dr. Wataru Mori. The Final Report is essentially finished in draft form, and RERF
is starting to prepare the publication of it.
As with previous systems, the implementation of
DS02 to compute dose estimates for survivors in
RERF cohorts is a subsequent project, which we expect to complete by about the end of May 2003.
Presently, the efforts in that project involve movingfrom the free-in-air kerma estimates for each survivor, which have now been computed, to calculationof shielding from terrain and structures and then computation of organ doses.
An article by Drs. Harry M. Cullings and Shoichiro
Fujita in this issue of RERF Update provides insight
into the history leading up to the project, basic considerations during the development of the new system,
and indications of the changes in free-in-air kerma
for gamma-rays and neutrons in each city. Subsequent
publications in the scientific literature and in RERF
Update will document the changes in shielded kerma,organ doses, and risk estimates for cancer and othereffects.
Following is a news release prepared by the Senior Review Group, and the impressive list ofscientists involved in the dosimetry review and revision project.
A major reassessment of the system used at theRadiation Effects Research Foundation (RERF), Japan to determine radiation doses for atomic-bomb
survivors has resolved the long-standing problems
with the system that has been in place since 1986,
and has defined the parameters for a replacement
dosimetry system for survivor dose calculation. Overthe past two years, a Joint U.S.-Japan Working
Group, chaired by Dr. Robert Young and Dr. Hiromi
Hasai, has undertaken a comprehensive evaluationof the calculations that comprise the RERF dosimetry system and the measurements that are used toverify these calculations. At a meeting in Tokyo on
March 14–15, 2003, a Joint U.S.-Japanese Senior
Review Group, chaired by Dr. Warren Sinclair and
Dr. Wataru Mori, approved DS02 (Dosimetry System 2002), which was developed by the Joint Working
Group.

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The dosimetry reassessment was mandated andsupported by the U.S. Department of Energy (DOE)
and the Japanese Ministry of Health, Labour andWelfare (MHLW), which are jointly responsible for
the RERF, in an effort to resolve the apparent discrepancy between neutron activation calculated by
the existing DS86 system and as measured in material exposed to neutrons at the time of the bombing.
During the course of this reassessment, the working
groups, with members and associates from American, German, and Japanese universities and national
laboratories, have recomputed all aspects of theHiroshima and Nagasaki radiation calculations,
made new fast-neutron and low-background thermalneutron measurements, upgraded the calculation of
the radiation shielding provided by terrain and large
buildings, and conducted a comprehensive reassessment of all radiation measurements in activatedmaterial. The new calculations produced during thisreassessment agree with both gamma and neutron
measurements out to distances from the detonations
at which sample measurements become indistinguishable from background, effectively resolving thelong-standing neutron dose discrepancy. The calculations that produce this agreement are the basis forthe new RERF dosimetry system, DS02.
The RERF is supported by the DOE Office of
Health Studies (Environment, Safety and Health; EH6) and the dosimetry reassessment effort in the U.S.
was funded both by the DOE Office Biological andEnvironmental Research (SC-72) and EH-6. The
current reassessment was made possible largely by
the development of techniques such as accelerator
mass spectrometry for the measurement of traceamounts of neutron activation remaining from 1945,
and by the availability of massively-parallel computing capacity that permits three-dimensional
calculation of a problem as vast and complex as an
atomic detonation.
The new calculations and measurements produced
during this reassessment have confirmed the yieldand epicenter for the Nagasaki detonation while refining both these values for Hiroshima. Current
measurements and calculations confirm a 21-kiloton-yield for the Nagasaki bomb and a burst point
to within 2 meters of previous assessments. In
Hiroshima, the estimated yield has been increased
from 15 kilotons to 16 kilotons and the epicenter has
been repositioned 20 meters higher and 15 meters
to the west. While supercomputing technology maderecalculation of the nuclear explosions possible, application of current geographic information systems
RERF Update Volume 14, Issue 1, Spring 2003

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RERF News
technology has reconciled the exact hypocenter locations on new, more accurate maps with World War
II vintage maps. The new dosimetry system will be
implemented at RERF as quickly as possible. Although significant changes in risk estimates are notexpected, the improved calculation and refinedshielding considerations should reduce the uncertainties and provide much confidence in the validityof risk assessments.
Joint Senior Review Group:
Warren K. Sinclair, President Emeritus, National
Council on Radiation Protection
Harold L. Beck, Environmental Measurements Laboratory (retired)Richard E. Faw, Kansas State University (retired)
Nolan E. Hertel, Professor, Georgia Institute of Technology
Wataru Mori, President, Japanese Association of
Medical Sciences
Tatsuji Hamada, Consultant, Japan Radioisotope
Association
Hiromi Hasai, President, Hiroshima International
Gakuin University
Ohtsura Niwa, Director, Kyoto University Radiobiology Center
Joint Working Group:
Robert W. Young, Defense Nuclear Agency (retired)George D. Kerr, Oak Ridge National Laboratory (retired)
Robert F. Christy, President Emeritus, California Institute of Technology
Harry M. Cullings, Radiation Effects Research Foundation
Stephen D. Egbert, Science Applications International
Corporation

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Alexandra R. Heath, Los Alamos National Laboratory
Dean C. Kaul, Science Applications International
Corporation
Robert T. Santoro, Oak Ridge National Laboratory
Tore Straume, University of Utah
Paul P. Whalen, Los Alamos National Laboratory
Stephen W. White, Los Alamos National Laboratory
Shoichiro Fujita, Radiation Effects Research Foundation
Masaharu Hoshi, Hiroshima University
Toshiso Kosako, University of Tokyo
Takashi Maruyama, National Institute of Radiological Sciences
Yasuo Nagashima, Tsukuba University
Yutaka Okumura, Nagasaki University
Tokushi Shibata, High Energy Accelerator Research
Organization
Kiyoshi Shizuma, Hiroshima University
Contributing Associates:
Joe V. Pace, John M. Barnes, Yousry Y. Azmy, Charles
O. Slater, Richard A. Lillie, Oak Ridge National
Laboratory
Alfredo A. Marchetti, Jeffrey E. McAninch,
Lawrence Livermore National Laboratory
James A. Roberts, Science Applications International
Corporation
Werner Ruehm, Ludwig Maximilians Universitaet,
MunichGunther Korschinek, Technical University of Munich
Satoru Endo, Hiroshima University
Tetsuji Imanaka, Seiichi Shibata, Kyoto University
Kazuo Iwatani, Kazuo Kato, Hiroshima Prefectural
College of Health Sciences
Kazuhisa Komura, Takashi Nakanishi, Kanazawa
University

RERF Update Volume 14, Issue 1, Spring 2003

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Ten Thousand Days Atop Hijiyama: Part 2

Ten Thousand Days Atop Hijiyama
Part 2. Genetics Program
Akio Awa
1. Introduction
In 1927, Dr. H. J. Muller devised a way to detectmutations in germ cells of Drosophila (fruit flies),and demonstrated that ionizing radiation can inducesuch heritable mutations.1 Subsequently, many scientists performed radiation experiments using
various animals and plants, confirming Dr. Muller’s
findings. For this achievement, Dr. Muller wasawarded in 1946 the Nobel Prize in Physiology andMedicine.
As evident from the above, research for elucidating the genetic effects of A-bomb radiation has
become an increasingly important scientific projectof our institution. Thus the genetics project was
launched in early days of the Atomic Bomb Casualty
Commission (ABCC) and has been continued to dateat the Radiation Effects Research Foundation(RERF). Before describing our F 1 cytogenetics
project, I will briefly describe below an outline of
the early genetics programs at ABCC, i.e., the “Untoward Pregnancy Outcome Study” started in 1948and “Mortality Study” in 1958.
A. Untoward Pregnancy Outcome Study—
Malformations and Other Abnormalities at BirthIn 1948, Dr. James V. Neel, an internationallyknown human geneticist who served as Acting
Director of ABCC at the time of its inception, initiated a large-scale study of genetic effects of atomic
radiation in cooperation with Dr. William J. Schull,and many U.S. and Japanese collaborators.2 The objective of this study, that enrolled about 80,000
newborn babies, was to scrutinize from epidemiological and statistical point of view a variety of genetic
endpoints, such as congenital malformations
among newborns andstillbirth, and neonatal
mortality rate. Medical
check-ups were also performed nine months
after birth to determine
whether there were any
abnormalities that had
been either overlooked
or not yet manifested at
the time of physical examinations at birth.

Because of a shortage of food immediately afterWorld War II, pregnant women who registered theirpregnancy at a public office were granted the privilege of having an increased ration of rice. Therefore,
almost all women who were in the fifth month of pregnancy would be officially registered. This made it
possible to accurately confirm the state of pregnancy.
Based on this pregnancy registration, pregnant
women were interviewed by the ABCC field workers regarding whether they and their spouses were
exposed to A-bomb radiation. For the exposed, theirdistance from the hypocenter and shielding status
were verified and documented.
In those days, most women in Japan delivered
babies at home. It is worth strongly emphasizing thatthe midwives in Hiroshima and Nagasaki had playeda very important role in this study.
Since there was no system for estimating radiation doses for A-bomb survivors, newborns weredivided into 25 categories, five for mothers and fivefor fathers on the basis of their parental exposure
status (distance from the hypocenter, presence orabsence of shielding, etc.). Comparisons were madeof the rates of malformations, stillbirth, and mortality at birth. The study was finished in 1954. As
shown in the literature cited at the end of this report, 2,3 the amount of research findings wasenormous and extensive. Their findings indicatedthat no statistical evidence of relationship with parental exposure was observed for any of the genetic
markers under study.
In parallel with this investigation, the sex ratio of
the children of A-bomb survivors was also studied.
In the general human population, males and females
are born with an equal probability. It was theoretically anticipated that the parental radiation exposure
would result in a change of the sex ratio of the offspring. Although there was some expectation of adecrease of females born to exposed fathers and adecrease of males born to exposed mothers, statistical analyses of the actual findings failed to support
this hypothesis.

Dr. James V. Neel [taken
in 1983]

B. Mortality Study
In 1958, Kato et al.4 initiated, through the Koseki
surveys, a study of the mortality of the children of Abomb survivors. Using the F1 cohort of A-bomb
survivors who were registered in the Neel study, theReturn to Table of Contents

RERF Update Volume 14, Issue 1, Spring 2003

Ten Thousand Days Atop Hijiyama: Part 2
Mortality Study population was newly founded. The
number of deaths and the causes of death among theF1 children were ascertained through the Koseki
checks, and comparisons of death rates were madebetween the exposed and control (both non-exposedand distally exposed) groups.
This study, covering about 54,000 children, also
failed to demonstrate evidence of genetic effects ofparental radiation exposure.5,6 It also failed to verify
any increase in the mortality rate due to congenital
childhood cancer in the exposed group.7 A followup mortality study has been continued to date, by
expanding the sample size of up to 80,000 F1 children.
As mentioned above, none of the early genetic
study series provided any positive evidence of thegenetic effects of A-bomb radiation. The results ofthe past genetic studies at ABCC seem in conflictwith those of studies performed by Muller and his
followers using various animals and plants. In particular, the mutation studies of Russell et al,8
conducted in the 1950’s using tens of thousands ofirradiated mice at Oak Ridge National Laboratory,
were not in line with the human studies at ABCC. If
genetic effects of radiation in various animals andplants are real, why did the ABCC studies fail to prove
the increased mutation rates in the human population? This problem has not been resolved as yet, andit still remains an important issue to be investigated.

2. F1 Cytogenetics Study: 1967–1984
A. Initial Studies: 1967–1968
The purpose of the chromosome study, termed F1
cytogenetics, was to evaluate genetic effects of Abomb radiation on humans using the then novel
technique of chromosome analysis. More specifically,
this study was designed to answer the question ofwhether parental exposure to A-bomb radiation would
increase the frequency of children carrying radiationinduced chromosome aberrations. In other words, if
the chromosome aberrations were produced de novo
in the germ-line cells of the exposed parents (bothsperm in the male and ova in the female), then theincreased genetic risk with radiation-related chromosome aberrations would be anticipated among theoffspring of survivors. As already described in Part
1, there are two types of chromosome aberrations,(i) abnormalities of chromosome number (aneuploidy), and (ii) structural aberrations of chromosomes,
as represented by reciprocal translocations. The
former type of chromosome aberrations are in general characterized by phenotypic abnormalities ofvarying degree of severity. Down’s syndrome, featured by the presence of an extra chromosome 21, isa typical example of this category. Structural chromosome aberrations were considered as the mostsuitable marker for the evaluation of genetic effectsof ionizing radiation.

Return to Table of Contents&

The structural rearrangements of chromosomes arefurther classified into two groups; one where there is
no loss or gain of chromosome material (geneticallybalanced rearrangements), and the other being associated with either loss or gain of parts of certain
chromosomes (genetically unbalanced rearrangements). The carriers of the former aberrations looksuperficially normal. In other words, the carrier’s
phenotype is normal, though his (or her) genotype isabnormal. Carriers of reciprocal translocations arefound to predominate in this category of aberrations,so that they are often called “translocation heterozygotes.” In contrast, the latter type of unbalanced
rearrangements would result in the serious phenotypic impairments of the carrier, often leading todeath.
The proportion of persons having translocation
heterozygotes in the general human population isestimated to be about 1 in 1,000. This rate does notseem to be influenced by racial or ethnic differences.
Family studies have confirmed that about 80% of thetranslocation heterozygotes are inherited from either
one of the carrier parents. The remaining one-fifth of
the translocation heterozygote children was found toborn to genetically normal parents due to a de novo
mutation produced in germ-line cells in either of theparent.9
In our proposal, we adopted use of the frequencyof translocation heterozygotes as an indicator of thegenetic effects. If the increased rate of the translocation carriers is statistically significant in the exposedgroup as compared with the controls, then we candeduce that the increase would be ascribed to the exposure of the parents to atomic radiation. When thesechromosome aberrations are detected in the childrenof A-bomb survivors, their parents as well as siblings must be investigated to determine the origin of
the aberrations.
In the early spring of 1967, we prepared a pilot
study project.10 The study subjects were chosen fromthe children born to exposed women enrolled in the
Fertility Study population.11 The samples were further divided into four groups: children born before
the atomic bombing (Group I), children whose motherwas exposed to the bomb (Group II), children whose
father was exposed (Group III), and children whoseparents were both exposed (Group IV). Group I constituted as a comparison group, while Groups II–IV
were the exposed. Our proposal was submitted andapproved immediately by ABCC.
A pilot study started in the spring of 1967, andwas completed in the fall of the same year. Somatic
chromosomes analysis was performed on a total of
185 individuals in Hiroshima and Nagasaki, comprising 128 in the exposed group (born between 1946
and 1963), and 57 controls (born from 1940 through1946). There was no instance of children with inRERF Update Volume 14, Issue 1, Spring 2003

Ten Thousand Days Atop Hijiyama: Part 2born chromosome error, except for one case in the
exposed group showing a sex chromosome mosaicism
of 45, X / 47, XXX. Because of the small sample
size, no proof of genetic effects was attained.12
B. Extended Study: 1969–1984
In 1968, we again started planning a full-scale F1
cytogenetics study in cooperation with the Statistics
Department staff. Study subjects under study wereselected on the basis of the F1 Mortality Study of
Kato et al .4 Advantages in use of this population were
two-fold; (i) exposed categories are well defined, and(ii) dosimetry (T65D) information was available forsome parents. After exclusion of deceased cases(about 5%) and individuals having moved away from
Hiroshima and Nagasaki (35%), about 22,000 children born after 1 May 1946 were found to be eligible
for study. All of these were found to reside in the twocities, whom ABCC staff members could easily contact. Young students and others who temporarily
moved away from their parents’ address were contacted during summer or winter school vacations.
Those who lived separately from their parents because of marriage or other reasons but who lived
within the cities were also included in the population. About a half of the 22,000 individuals were bornto parents either one or both of whom had been exposed to the bomb within 2 km from the hypocenter,with T65D estimated dose of 1 rad or more. The remaining children were born to either non-exposed or
distally exposed parents, with estimated dose of lessthan 0.5 rad, serving as a comparison group for the
exposed.
There were some social and ethical problems we
had to resolve prior to the realization of the project.
The most serious issue was the dark image of words“hereditary diseases.” In those days, there was a tendency to discriminate against people afflicted withsuch diseases and to segregate them from the society. Under these circumstances, the words “heredity”
and “hereditary diseases” were taboos. Some of thehuman geneticists were skeptical as to whether thegeneral public could correctly understand the meaning of the words “hereditary disease.” In order toobtain agreement to our research, we decided to visit
the homes of the study participants, and to fully explain them and the parents (or close relatives) the
purpose of our research. Prior to the initiation of thework, it was absolutely necessary to reach mutual
understandings between the examinees (study participants) and examiners (ABCC), and to obtain theircooperation. This was indeed a key to a success ofour study.
Today, genetic knowledge has been widely disseminated among the public, though in a limited way,
and genetic counseling provided by certified physicians or experts in human genetics has become aroutine procedure. However, about 30 years ago, physicians who specialized in human genetics were rare
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9in Japan. In addition, there were neither adequate
guidelines nor manuals available for genetic counseling. Since none of us in ABCC were physicians,
we needed help from experts in the Japanese Societyof Human Genetics regarding this issue. Prior to theinitiation of our project, we were able to obtain agreat deal of knowledge on genetic counseling fromthe Society members. It should be noted here that we
received a remarkable support from Dr. Koso Ohama,a staff member of the Department of Obstetrics andGynecology at Hiroshima University School of Medicine, in establishing measures to carefully take when
hereditary diseases were detected.
The cytogenetics study was thus launched withall involved being determined to walk a tightrope,
coping with difficult problems we had never encountered before. As a first step, public health nurses andmedical social workers at the Clinical Contacting
Section of the Department of Medical Sociology (currently belonging to the Department of ClinicalStudies) visited homes of the participants and theirparents. They explained our genetics study in easyterms. When understanding was either unavailable
or a more detailed explanation was requested by them,
I visited their home accompanying a social worker
in charge, and gave them further detailed explanations. Some of the participants hesitated about
participating in our study. In this case, we were cautious not to forcibly persuade them to participate, andalways followed their own judgment.
Our public health nurses, Mss. Chie Yanagawa,
Miyoko Kamisako, and Midori Kamouchi, willingly
committed to this program and worked very hard,
helping our study to become a great success. I now
can imagine how difficult it must have been for thesemembers to perform all their duties without any previous experience. Mr. Kanjuro Hidada (former
Administrative Assistant Chief of the Departmentof Clinical Studies) and other staff of the ClinicalContacting Section took a heavy burden of contacting the participants by home visit. The staff in the
Medical Records and Coding Section of the Statistics Department (currently in the Department ofClinical Studies) provided great help with necessary backup support. We owe a debt of gratitude tothese people for the smooth operation of our study.
Although belatedly, I would like to express my sincere appreciation to those involved.
The citizens of Hiroshima and Nagasaki became
increasingly interested in our study through coverage by the mass media. As I well knew, many of the
A-bomb survivors seemed to have concerns about
genetic effects of radiation in their offspring. They
were also anxious about the genetics study itself.
Those who opposed the study were much concerned
about the possible consequences of genetic effectsof radiation among the children of A-bomb survivors.
None of us had any idea about what to do if any eviRERF Update Volume 14, Issue 1, Spring 2003



Ten Thousand Days Atop Hijiyama: Part 2
dence of genetic effects was demonstrated. For thisreason, some people did not want to conduct the study.
Those who supported the study wished that any genetic problems should be scientifically clarified andsettled the issue as soon as possible. Two opposite
opinions seemed to be well represented in the resultsof a large-scale public opinion poll carried out in the
Chugoku Shimbun on July 31, 1972.13

nized. Data analysis of our results was postponed until
the new dosimetry reassessment system (DS86) was
finalized. Even under the DS86 system, however, radiation-dose-related analyses were difficult becauseof the paucity of dose information with regard to parental reproductive organ doses, which remains until
now unavailable for some of the parents of F1 children.

In those days, more than 20 years had alreadyelapsed after the atomic bombings. As the childrenof A-bomb survivors became older, they began moving out from Hiroshima and Nagasaki to othermegalopolitan areas such as Kanto and Kansai districts. The major reasons for this move were (i) toreceive better education, and (ii) to get much betterjob opportunities. This tendency irritated me a greatdeal. I believed that, as time goes by, the chance ofconducting genetic studies would become smaller andsmaller. It occurred to me that early 1970’s would be
the last opportunity for us to conduct a large-scale
genetics survey.

Of the 16,298 individuals whose chromosomes
were studied, autosomal structural aberrations wereascertained in 23 out of 8,322 individuals of the exposed group, and in 27 of 7,976 in the comparisongroup. Sex chromosome aberrations identified included 19 individuals in the exposed group and 24 in
the comparison group. Thus no statistically significant difference was obtained between the proximallyand distally exposed groups in terms of the frequencies of carriers having structurally rearranged
chromosomes, or in terms of chromosome aneuploidy. Although the frequencies of these aberrations
were lower in the exposed group than in the comparison group, no statistical significance wasdemonstrable between the exposed and control
groups.14

In the course of cytogenetic study, I was deeply
indebted to Dr. Hiroshi Maki, then Associate Director of ABCC (who passed away on October 23, 1998),
in the realization of the genetics study. Caught between the one-sided claim of mine and the generally
difficult situation that ABCC faced at that time, Dr.
Maki must have worried greatly. I feel sorry for Dr.
Maki now, and continue to respect him and appreciate his efforts toward this study.
For some five years from the spring of 1969 to
1974, about 4,000 cases in two cities, about 2,300 in
Hiroshima (60%), and about 1,700 (40%) in
Nagasaki, could be examined cytogenetically. This
amounted to 720 individuals per year. This meantthat the medical social workers would have met participants of approximately 3,400 in Hiroshima and2,300 in Nagasaki in this period.
In the fall of 1974, our study was temporarily suspended. This was due in part to introduction of a newresearch project proposed by Dr. James V. Neel, thedetails of which are described in the later section ofthis article. In short, the existing organizational structure for routine working procedures was inadequate
for the realization of a new project. It was thus urgently needed to establish a new internal structure in
the ABCC. After several months of lengthy discussions by the ABCC managerial staff concerned, we
could somehow settle this difficult task by sharing
new working loads among all department members.
Thus we were able to resume the cytogenetics survey in the summer of 1975.
The F1 Cytogenetics Study was terminated in thefall of 1984, 15 years after its initiation. A total of
16,298 individuals in both cities, 9,828 in Hiroshima
and 6,470 in Nagasaki, were cytogenetically scrutiReturn to Table of Contents

Mention must be made that the participation rateof this study was unexpectedly high, being 74%
throughout this study; 70% in Hiroshima and nearly
80% in Nagasaki. In both cities, the participation rate
was slightly higher in the proximally exposed groupthan the distally exposed group. Among those who
visited ABCC-RERF, many wanted to be given amore detailed explanation. Although my memory is
now vague and inaccurate, during the entire study
period I interviewed at least several hundred participants in Hiroshima at the time of their visit to ourinstitute. This gives an idea of how the children of
the exposed people positively participated in the genetics program, and how deep was their concern about
their health problems.
I would like to close this chapter by citing part of
the acknowledgements described in our F1 paper 14
as follows:“We are grateful to the Hiroshima and Nagasaki
citizens for their willingness to voluntarily participate in this survey. Without their cooperation thisstudy would not have been possible.”

3. Dr. Neel and Biochemical Genetics
Study: 1971–1984
Dr. Neel visited Hiroshima in the fall of 1971,
with a plan of initiating a new genetics study to be
conducted at ABCC. That was the time when a newtechnology of electrophoresis had become practicallyavailable for protein (and enzyme) analysis. Proteinsthat are the end-points of the gene products show
differing electric charges. When a gene mutates, itmay, or may not, induce an alteration of electric
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Ten Thousand Days Atop Hijiyama: Part 2
charges of the same protein. Thus this method wasthought useful to detect some forms of the protein
variants by identifying the electric charges that are
deviated from the normal pattern. A small amount ofserum or plasma in the blood is required for analysis. Aliquots of sample are placed in starch gel arrays.
When electric current is applied to the gel, proteinsmove along within the arrays. Depending on the electric charges, proteins would stop at a specific array
position. The gel is stained with dye to visualize theposition of proteins, and thus the mobility of proteins under study is measured. If the position of atarget protein deviates from expectation, the protein
is considered as a variant or a mutant. This technique
is also capable of measuring a large number ofsamples at a time. A drawback is of this technique isthat mutated proteins are not necessarily associatedwith changes in the electric charges.
Dr. Neel, bringing this new technology with him,came to Japan with the intention of initiating a study
at ABCC for clarifying the relationship between radiation dose and gene mutation frequency using thistechnique. As soon as Dr. Neel arrived in Hiroshima,
he started working hard by attending various meetings, to make briefings and discuss the feasibility of
new electrophoretic technique with those concernedin and outside ABCC. He also worked energeticallyto make the general public aware of his project throughthe mass media. All the events and happenings in thosedays were described in detail in his book.15
ABCC had, since its inception, always received
criticisms from A-bomb survivors and the mass media, insisting that the victims of the atomic bombings
had been handled at ABCC as guinea pigs, and for
not providing medical treatment. The same held true
for Dr. Neel’s research proposal; the news media weremore or less bitter towards him. There was an escalated view against this plan saying that ‘ABCC should
know that to examine the blood of the children of Abomb survivors is more costly than to produce anatomic bomb.’ Although opinions and criticisms ofthis kind were publicly open, a key issue in the success of the new project depended on whether ABCC
could obtain understanding and support of A-bomb
survivors and the local community.
Many Japanese scientists also were aware of thesituation of A-bomb studies, and held views similar
to those of the mass media in Japan. I regretted inthose days that this unique and important genetics
project had not been conducted under the initiativeof Japanese scientists funded by the Japanese government. It was my belief that it was a responsibilityof Japanese scientists to conduct a study of genetic
effects of the atomic bombings. In fact, funds fromthe Japanese government were very limited regarding research of the A-bomb effects. Consequently,
ABCC was the only institution that could conduct
genetic studies.
Despite Dr. Neel’s efforts and great excitement,
his project did not easily get started. Based on discussions with those concerned at ABCC, it was
decided that Dr. Neel should conduct a feasibility
study as to whether the technology would be applicable. A full-scale study was indeed launched three
and a half years later, after ABCC was reorganized
into RERF. Thereafter, Dr. Neel visited Hiroshima at
least once a year without fail, and stayed here for amonth, or as long as 2–3 months, to check the
progress of the project, and to put relevant researchsupplies in order.
The Biochemical Genetics Laboratory, abbreviatedas “BGS” Lab, was established in the Department ofClinical Laboratories. Since Dr. Neel was not permanently assigned to RERF, the laboratory was placed
under the administrative supervision of Dr. Howard
B. Hamilton, Chief of the Department of Clinical Laboratories. To set up routine laboratory procedures, Drs.
Robert Tanis and Robert Ferrell from the Universityof Michigan came to Hiroshima and worked hard everyday in the laboratory. Drs. Naoki Ueda (Yamaguchi
University), Shinya Kishimoto (Hiroshima University),and Shigeo Akaiwa (Tokyo Medical and Dental University) were newly recruited to the laboratory. Several
technicians were transferred from other sections of thedepartment. Since then, many research associates havebeen recruited from time to time. This included Dr.
Chiyoko Sato (former Chief of the Department of Genetics) and others such as, to name just a few, Drs.
Takeshi Kageoka, Kazuaki Goriki, Norio Takahashi,
Jun-ichi Asakawa, Mikio Fujita, and Keiko Hiyama.

4. Beginning of Biochemical Genetics
Study: 1975–1984

Dr. Neel and the author [taken in 1988]
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The years 1974 and 1975 were the time of preparation of ABCC’s reorganization. The ABCC issue
became a subject of diplomatic deliberations between
the U.S. and Japanese governments, and ultimately
the two countries reached to an agreement stipulatRERF Update Volume 14, Issue 1, Spring 2003

Ten Thousand Days Atop Hijiyama: Part 2
ing that ABCC would become a Japanese juridical
person foundation.
On the morning of Tuesday, April 1, 1975, undera clear blue sky, the opening ceremony of the new
Radiation Effects Research Foundation was held in
the front yard of the main entrance. Four people wereappointed as directors of the new organization: Dr.
Hisao Yamashita (former professor of Keio University) as Chairman; Dr. LeRoy R. Allen (former ABCC
director) as Vice Chairman; Dr. Gilbert W. Beebe as
Chief of Research (formerly called Chief Researcher);and Dr. Masuo Takabe as a Permanent Director. Thatsummer, Dr. Beebe resigned from RERF and returnedto the United States. Dr. Stuart C. Finch assumed theposition of Chief of Research.
The Crow Committee, which was convened justprior to the reorganization, recommended that in addition to the Life Span Study (LSS), the Adult HealthStudy (AHS), and the Pathology Study, RERF initiate
the Biochemical Genetics Study as a top priority. Basedon this recommendation, a comprehensive genetics
research program was approved as the RERF Platform
Protocol, and endorsed by the Board of Directors inlate 1975.16 This included the Mortality Study, Cytogenetics Study, and Biochemical Genetics Study as
major genetic components of the platform protocol.
After approval of the protocol, the initiation of
the Biochemical Genetics Study (BGS) was officiallyannounced. The actual work, however, did not get
underway. This was due to a lack of a research leader
who could coordinate overall administrative and routine works in order. The true responsible investigator
was Dr. Neel, but he was not permanently stationed
at RERF. The research associates just assigned to
RERF had no idea how to operate the daily work in
the laboratory.
I talked with Dr. Finch, who also was a newcomerof RERF as Chief of Research, and who had been irritated by the delay of BGS program, about how toproceed with getting the BGS program in motion. We
agreed the following items: (i) Current administrativeand operational structures of RERF were adequate only
for conducting the currently ongoing LSS, AHS, andPathology Study projects, and thus there was no leeway for conducting the BGS project, (ii) In order toinitiate the BGS program, a project leader was indispensable for the coordination of all necessary works,and (iii) The vertical organizational structure was suited
only for top-down work, but not horizontal collaboration with the members in other departments.
The role of coordinator of the study fell on me.
Since I brought up the issues, I guess that was what I
had to deserve. After I became a coordinator of the
BGS program, I solicited of all department chiefs
and supervisors to support BGS research activity andto share the newly added working load caused by
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this program. Through more than ten weekly meetings, we could reach an agreement establishing new
supporting systems for the BGS program through thelending of hands from other department members,
adding to their own daily routine work. All members, key persons of RERF attending the meetings,
agreed voluntarily, or somewhat reluctantly, to accept extra burden of work for this purpose. Some of
the major changes in the work procedures at ABCCRERF are as follows.
For realization of the F1 BGS project, it was understood that support was required from members
from all departments; especially from the clinicalresearch staff, Department of Medicine (currently
Department of Clinical Studies). Until that time, clinical members did not participate in the F1 cytogenetics
program, but this was successfully changed. Emphasis should be made that this arrangement was madepossible by the effort of the late Dr. Hisao Sawada,
then Assistant Chief of the Department of Medicine,to whom our thanks are dedicated.
Because the proposed study subjects would be
expected to include young people, we decided not todraw blood for safety and health purpose from children below 12 years of age, or pupils of the primaryschool. For this we would better wait until theyreached that age. Occasionally, the parents of thestudy participants visited RERF bringing all children,some of who were enrolled in our study cohort, andasked us to do medical checkups for all of them. Whenrequested by the parents, blood was drawn even under age of 12 years for routine genetic tests.
Due to the geographical location of ABCC, whichstood on the top of Hijiyama, arrangements weremade to use taxis for transporting the participants.
Dispatchers then played a new role in this project.
An institution-wide work sharing system for genetic
study was thus established. After many trials and errors, a new working system finally proved to besmoothly workable.
In those days, we had a weekly clinical night shift(from 1:00 p.m. to 8:00 p.m) on Thursdays at
Hiroshima and Wednesdays at Nagasaki. We thought
this arrangement would be efficient and also convenient for those participants who are unable to come to
RERF clinic during daytime of the weekdays. Nearly
half of the participants visited RERF to receive medical check-ups including blood drawing relied on thosenight clinics. When a variant was discovered, a physician or a research scientist in charge made an interview
with the variant carrier to explain the result of tests indetail, and ask permission together with his (or her)parents for further family studies. After obtaining
agreement from them, a family study was performed
in order to verify the origin of the variant. Thanks to
the devoted efforts of the entire RERF staff, the BGS
project was finally in order.
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Ten Thousand Days Atop Hijiyama: Part 2
The BGS project was initiated in 1975 simultaneously with the Cytogenetics program. Bothprograms were successfully completed in 1984. At
the time of completion of the BGS study, the numberof children totaled 23,661, 11,364 in the proximally
exposed group and 12,297 in the distally exposed or
unexposed group as control. The number of gene locianalyzed was 544,779 for the exposed and 589,506
for the comparison group, respectively. The numbersof mutated genes that were confirmed through family studies were two in the proximally exposed group,and four in the distally exposed group.17
None of these genetic studies have provided thebasis for verifying genetic effects of atomic radiation. In order to verify the observed negative findings,
a further genetic study with the aid of much refinedtechnology would be desirable. I understand that acouple of new F1 study projects have been approved
and are currently ongoing. If further genetic researchis to continue in the future, it will be associated witha human genome project that is a collaborative research involving scientists from all over the world.

5. Unforgettable People
Over my thirty years of scientific career at ABCCRERF, I have encountered a great number of
unforgettable people who have rendered an immense
help to me. Not to mention the chairmen and directors of the institution, a great many colleagues havesupported me in various ways. I now feel guilty that
I caused a lot of troubles that influenced to a great
extent a number of goodwilled people. Whenever I
met troubles, I used to ask Dr. Hiroshi Maki for his
help. He did help me all the time in many ways. I still
remember Dr. Maki’s warm face with smile, and used
to say: “Don’t worry. This is my job.”
Mention must be made of Dr. Howard B.
Hamilton, Chief of the Department of Clinical Laboratories, who would keep me under control when I
started to stampede. Kanze-school Noh performance
was more than just a hobby for Dr. Hamilton. In thespring of each year, he dedicated a Noh play to theGods at Itsukushima Shrine. He also was an expert(from left) Dr. Hiroshi Maki, Dr. William J. Schull, Mrs.
Victoria Schull, Mrs. Chie Maki [taken in 1996]
Return to Table of Contentsof Kabuki, and was acquainted with many famous
Kabuki actors. His collection of “Kumadori (makeups of famous Kabuki actors copied directly to thesheet of paper taken immediately after the actual performance)” is nothing but a treasure. He now lives in
Virginia, in a suburb of Washington D.C.
Due to space limitation, I will describe below myrecollections of only a few people.

Dr. Sajiro Makino (1906–1989):
Dr. Makino, my mentor, devoted his lifetime tothe human and animal chromosome research, thatcovered all animal kingdom. He was very active andproductive while working with classic techniques,using an old-fashioned Leitz microscope without any
support of advanced technology that is available today. He received the Japan Genetics Society Awardin 1944 for his research on mouse chromosomes.
Then he turned to chromosomal research of transplantable ascites tumors of rats, such as Yoshidasarcoma. He was the first to discover what is known
as the “stem-line cell theory.” The theory indicatedthat each tumor cell line has a specific, and thus
unique, karyotypic pattern, and that such a cell line
plays a central role in the proliferation of tumors.
For this theory he was conferred the Japan Academyof Sciences Award in 1958. In the mid-1950’s, hemoved into a new area of human cytogenetics, andpaved the way for this research field in Japan. Hisname became widely known both nationally and internationally as an authority on human andmammalian cytogenetics. This was the reason why
ABCC asked help from Dr. Makino in the conductof new research on radiation cytogenetics. In 1973,
he was elected as a member of the Japan Academy of
Sciences. Immediately after his retirement from university, Dr. Makino received an honor as Professor
Emeritus of Hokkaido University.
Dr. Makino was a very eager mentor for young researchers who eventually became active scientists.
None of his disciples could escape from his loud voicein scolding. Dr. Masao Sasaki, currently Professor
Emeritus of Kyoto University, who served until recently as Scientific Council of RERF, is one of themost excellent students trained by Dr. Makino. Dr.
Makino always advised his disciples to write scientific papers in English. He kept saying: “That is the
only means to be internationally evaluated by the scientists of the world.” He himself published over 700
papers, including co-authored works, and 20 monographs and books, most of which were written in
English. He practiced what he preached to his students.
Despite the fact that I had long been one of his students, after all, I have been nothing but a packhorse.
For more than 40 years since I first received training
from Dr. Makino in 1958, and began wandering into
the world of “chromosomes,” what I have learned fromthe microscopic works is: “Chromosomes never lie.”
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Ten Thousand Days Atop Hijiyama: Part 2
Dr. James V. Neel (1915–2000):
Together with Dr. Schull, Dr. James V. Neel, Professor Emeritus of the University of Michigan
Medical School, was a founder of the Japan Societyof Human Genetics. I am sure that many of the Japanese human geneticists never forget their names.
In the spring of 1968, annual meeting of the Japan Society of Human Genetics was held at the
Hideyo Noguchi Commemorative Auditorium of
Keio University in Tokyo. It was there that I first met
Dr. Neel. He was invited as a guest speaker for the
keynote lecture of the Society. During the conference,
I had a chance to talk with him about our F1 cytogenetics program. Dr. Neel listened intently to me withfurrowed brows. I still remember vividly what he said
after I finished my talk. He said; “I think you knowthat we did conduct a large-scale genetic study in
1948, and the subject is still extremely important for
the elucidation of the genetic effects of radiation. But
you must also realize that this indeed is a difficult
task to perform and to interpret.”Dr. Neel and I first started working together in
1971, when Dr. Neel brought the idea of initiating
the BGS program. Although he kept saying; “Research is my hobby,” his attitude toward research wasvery strict and he never allowed any compromise.
In the years of 1968 and 1969, in the AHS study,
and in 1969, in the F1 study, we discovered an extremely rare type of cells in cultured lymphocytes
from AHS and F1 participants. It showed an uncountable number of complex chromosomal aberrations
so that karyotype analysis was impossible. The discoverer of the cell was Dr. Toshio Sofuni, who was
our research associate during the period between
1967 and 1979. Apparently, the aberrant cell was
unrelated to any radiation exposure. We could notunderstand why such an incredible cell was produced
and present in the body of a healthy non-irradiatedperson. In any case, we named it “a cell with multiple chromosome aberrations.” We recorded thephenomenon in detail in our data books. Some of theresults were published in our AHS paper in 1978.18
Almost at the same time of our discovery, a researchteam headed by Dr. Neel carried out human genetics
studies on the native Venezuelan people in SouthAmerica. They also discovered the same kind of aberrant cells in Yanomama tribe residents. They
reported the results in 1968.19
Around the mid-1980’s, when Dr. Neel came toHiroshima as his routine visit, I showed him some ofcells with multiple chromosome aberrations that we
had encountered in our F1 study subject. He was surprised and extremely pleased by the conformity withhis own experience in South America. We immediately conducted epidemiological analysis on the F1
members in whom at least one or more of cells withextremely aberrant chromosomes were detected. The
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results of analysis were then published.20
Dr. Neel recommended in the report that the cellwith multiple chromosome aberrations be called a“rogue cell.” I learned that the term “rogue” means“scoundrel,” “villain,” and an expression like “a rogueelephant.” In the report, the term was used in the classical biological sense of a “marked deviant from thetypical observations.”15
Since we published the report, there have been
many papers that have dealt with the rogue cell phenomenon, discovered all over the world. Many
cytogeneticists in European countries and, in particular, scientists from the former USSR, observed
instances of rogue cells in the course of chromosome
screenings on the sufferers of the Chernobyl nuclear
plant accident. For this reason, a symposium on“rogue cells” was held in early 1990’s in Obninsk,
Russia. In a chromosomal study of those exposed in
the Chernobyl accident undertaken at RERF, we also
observed many rogue cells derived from the residents
living in uncontaminated areas.21 Dr. Neel’s interest
was shifted toward the elucidation of the mechanism
by which the rogue cells are produced. Later on, hehypothesized the possibility of an interaction between
host cells and tumorigenic/teratogenic viruses.22,23
In a very unfortunate turn of events, Dr. Neelpassed away on February 1, 2000. In the Christmas
card I received from him one year prior to his death
he had written the words:“The rogue cell story is getting more and more
exciting.”
This was to be the last message that I would receive from him in his own writing.

Dr. William Jackson Schull:
Dr. Schull and his wife, Victoria, have had alongstanding relationship with ABCC as well as RERF.
He first came to Japan in 1949. Since he participatedin the Child Health Study as Dr. Neel’s right-hand man,so to speak, his contribution to the Japan Society of
Human Genetics have been significant, starting with
the initial genetic study at ABCC followed by the
Hirado consanguineous marriage study.24 He worked
hard not only in research but also in the administrative
operations after ABCC was reorganized into RERF.
He served as Vice Chairman (from 1978 to 1981),
Director (from 1990 to 1992), and again as Vice Chairman and Chief of Research (from 1996 to 1997). I
always call him Jack, in a familiar manner. I still feel
he is “mon oncle (my uncle).”When Jack came to Japan as the Vice Chairmanof RERF in 1996, he was in the office next to me.
When 5:00 p.m. rolled around, Jack asked me to walkhome together, since our destinations were more orless the same. We walked down Hijiyama together,
RERF Update Volume 14, Issue 1, Spring 2003

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Ten Thousand Days Atop Hijiyama: Part 2
crossed the Tsurumi Bridge, rambled on the westernbank of the Kyobashi River, and then headed north.
There was always a flavor of the four seasons aroundthe bank of the river. While strolling along, we would
talk on various topics. Jack was truly erudite. Even
being a Japanese, I was in the position of being taught
from him things about the history of Japan, such as
hidden Japanese Christians in western part of Japan,
various habits in the consanguineous area, and so on.
We would sometimes drop in at a hotel standing near
the river’s bank, and enjoy one or two drinks ofwhisky and water. However, due to a lack of enzyme,
aldehyde dehydrogenase, my face would quickly turnbright red even after one drink of weak whiskey andwater. It was always an enjoyable end of the day’s
work.

opportunity to express my sincere gratitude to him.
Whatever words I choose, it is beyond my ability
to express my feeling of gratitude to my colleagues
at ABCC-RERF who have worked together with me.
All I can do now is to document all of their names
listed below in the chronological order without honorific. These people worked with us between 1967
and 1994.
Hiroshima:
Professional staff
Nanao Kamada, Hiromu Okada, Takeo Honda(transferred to Nagasaki), Toshio Sofuni, Hachiro
Shimba, Kazuo Ohtaki, Richard A. King, Mimako
Nakano, Yoshiaki Kodama, Sadayuki Ban, Nori
Nakamura.

Our Staff:
My long story now comes to an end. During the
10,000 or more days of research life on top of thehill, I welcomed here many scientists from overseas
to receive training at RERF. In the summer of 1980,
Dr. Jin Cuizhen from the Chinese Institute of Radiation Medicine in Beijing came to Japan for a periodof one year, and her passion for work really left astrong impression on me. Even after the retirement,
she still is active as a leader of the chromosome aberration research in China.
At the end of December 1993, before reaching
mandatory retirement age, I resigned from the post of
Chief of the Genetics Department. As I wrote in Part
1, Dr. Nori Nakamura, who had served as the Assistant Chief of the Radiobiology Department, wasappointed as my successor. I find Dr. Nakamura’s efforts highly respectable as he and his colleagues havepublished many papers amid the harsh research environment, and he holds a strong scientific leadership
position both in and out of RERF. I want to take thisTechnical staff
Shozo Iida, Kazumi Tanabe, Setsuko Furubayashi,
Tatsuo Mandai, Sumie Murata, Akiko Kido, Takeshi
Abe, Sadamaru Ichiyama (deceased in 1975),
Masashi Hiramoto, Junso Naruto, Junko Takabayashi(deceased), Junso Takayama, Kyoko Ozaki, Mayumi
Utaka, Mieko Nakamura, Yoshiko Watanabe, Miwa
Miura, Kaori Muramoto, Miyuki Tsuchiyama,
Hiroyuki Ryukaku, Tomoko Matsumoto.
Nagasaki:Professional staff
Shotaro Neriishi (deceased in 2002), Tetsuya Iseki,
Michihiro Yoshida, Masahiro Itoh (transferred toHiroshima), Sei Okimoto.
Technical staff
Keiichi Ohki (deceased), Yoko Urakawa, Nobuko
Okazaki, Nobuaki Taira, Mankichi Tagami, Hiroyuki
Miyaji, Osamu Kusumi, Fukiko Kondo, Mikiko
Mizogoshi, Yukihiro Inada, Kazuhiko Tagawa.

References
1. Muller HJ: Artificial transmutation of the gene. Science 66:84–7, 1927
2. Neel JV, Schull WJ: The Children of Atomic Bomb Survivors: A Genetic Study. National Academy Press,
Washington DC, 1991
3. Nakamura N: Genetic effects of atomic-bomb radiation: Past, present and future (Review). Hoshasen Seibutsu
Kenkyu [Radiat Biol Res Commun] 34:153–69, 1999
4. Kato H, Schull WJ, Neel JV: A cohort-type study of survival in the children of parents exposed to atomic
bombings. Am J Hum Genet 18:339–73, 1966
5. Neel JV, Kato H, Schull WJ: Mortality in the children of atomic bomb survivors and controls. Genetics 76:311–
36, 1974
6. Otake M, Schull WJ, Neel JV: Congenital malformations, stillbirths, and early mortality among the children of
atomic bomb survivors: A reanalysis. Radiat Res 122:1–11, 1990
7. Yoshimoto Y, Neel JV, Schull WJ, Kato H, Soda M, Eto R, Mabuchi K: Malignant tumors during the first 2
decades of life in the offspring of atomic bomb survivors. Am J Hum Genet 46:1041–52, 1990
8. Russell WB: X-ray-induced mutations in mice. Cold Spring Harbor Symp Quant Biol 16:327–36, 1951
9. Jacobs PA: Mutation rates of structural chromosome rearrangements in man. Am J Hum Genet 33:44–54, 1981
10. Bloom AD, Neriishi S, Awa AA, Archer PG, Hamilton HB: A cytogenetic study of the offspring of atomic bomb

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RERF Update Volume 14, Issue 1, Spring 2003

$

Ten Thousand Days Atop Hijiyama: Part 2
survivors, Hiroshima and Nagasaki. ABCC Research Protocol 7-67, 1967

11. Sawada H, Finch SC: Fertility study Hiroshima and Nagasaki: Provisional research plan. ABCC Technical
Report 18-62, 1962
12. Awa AA, Bloom AD, Yoshida MC, Neriishi S, Archer PG: Cytogenetic study of the offspring of atomic bomb
survivors. Nature 218:367–8, 1968
13. Chugoku Shimbun: Poll on the health problem of the children of A-bomb survivors, 1972
14. Awa AA, Honda T, Neriishi S, Sofuni T, Shimba H, Ohtaki K, Nakano M, Kodama Y, Itoh M, Hamilton HB:
Cytogenetic study of the offspring of atomic bomb survivors, Hiroshima and Nagasaki. In: Cytogenetics (Obe G,
Basler A, eds). Springer-Verlag Berlin Heidelberg, 1987. pp.166–83
15. Neel JV: Physician to the Gene Pool. John Wiley & Sons, Inc., New York, 1994
16. Radiation Effects Research Foundation: Research plan for RERF studies of the potential genetic effects ofatomic radiation; Hiroshima and Nagasaki (Platform Protocol), RERF Research Protocol 4-75, 1975
17. Neel JV, Satoh C, Goriki K, Asakawa J, Fujita M, Takahashi N, Kageoka T, Hazama R: Search for mutations
altering protein charge and/or function in children of atomic bomb survivors: Final report. Am J Hum Genet
42:663–76, 1988
18. Awa AA, Sofuni T, Honda T, Itoh M, Neriishi S, Otake M: Relationship between the radiation dose and chromosome aberrations in atomic bomb survivors of Hiroshima and Nagasaki. J Radiat Res 19:126–40, 1978
19. Bloom AD, Neel JV, Choi KW, Iida S, Chagnon N: Chromosome aberrations among the Yanomamma Indians.
Proc Natl Acad Sci USA 66:920–7, 1970
20. Awa AA, Neel JV: Cytogenetic “rogue” cells: What is their frequency, origin, and evolutionary significance?
Proc Natl Acad Sci USA 83:1021–5, 1986
21. Neel JV, Awa AA, Kodama Y, Nakano M, Mabuchi K: “Rogue” lymphocytes among Ukrainians not exposed toradioactive fall-out from the Chernobyl accident: The possible role of this phenomenon in oncogenesis, teratogenesis, and mutagenesis. Proc Natl Acad Sci USA 89:6973–7, 1992
22. Neel JV, Major EO, Awa AA, Glover T, Burgess A, Traub R, Curfman B, Satoh C: Hypothesis: “Rogue cell”type chromosomal damage in lymphocytes is associated with infection with the JC human polyoma virus andhas implications for oncopenesis. Proc Natl Acad Sci USA 93:2690–5, 1996
23. Neel JV: An association, in adult Japanese, between the occurrence of rogue cells among cultured lymphocytes(JC virus activity) and the frequency of “single” chromosomal damage among the lymphocytes of persons
exhibiting these rogue cells. Am J Hum Genet 63:489–97, 1998
24. Schull WJ: Song among the Ruins. Harvard University Press, Cambridge, MA, 1990

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RERF Update Volume 14, Issue 1, Spring 2003

%RERF Dosimetry Revision

The Way to DS02:
Resolving the Neutron Discrepancy
Harry M. Cullings and Shoichiro Fujita
Department of Statistics
DS86 should be updated and revised. At about thesame time the U.S. Department of Energy formed aworking group of scientists that collaborated with apre-existing Japanese group on an intensive new program of calculations and measurements, culminatingin the forthcoming publication of a report recommending a new dosimetry system, DS02.

In 1987, RERF published the final report on DS86,
which was a new and fundamentally different type of
dosimetry system for the A-bomb survivors. DS86
used detailed calculations of the interactions of neutrons and gamma rays, rather than an adaptation of
empirical results of atomic weapons tests and associated measurements. This gave DS86 more power
and flexibility than its predecessors, which sufferedfrom difficulties when trying to generalize from results of specific bombs, test conditions, and shielding
experiments.

Contrary to expectations, DS02 does not produce
very large changes from its predecessor DS86 in either the free-in-air neutron or gamma-ray doses at
distances relevant to survivors, even though its development addressed in a cogent manner the
motivating neutron discrepancy. As will be discussed
elsewhere, DS02 will result in some importantchanges in shielded survivor doses, because of improved capabilities to address terrain and structural
shielding. But the more central part of the story, relating to the neutron discrepancy and affecting all
survivor doses, concerns the free-in-air gamma ray
and neutron fluences and kerma that are calculatedby the dosimetry system as a function of distance fromthe hypocenter. The changes in free-in-air kerma produced by DS02 are shown in the figure. In theremainder of this communication a discussion is givenof the causes of these changes and their significance,
including their relationship to the neutron discrepancy.

However, an issue still unresolved when DS86 waspublished was a discrepancy between some measured
neutron activation levels, e.g. in building materials,
and levels calculated from DS86. After publicationof the DS86 Final Report (RERF 1987), various committees and individual investigators continued to
examine the problems identified in that report. By
the mid-1990’s, further measurements and discussion
greatly raised the level of interest in what popularly
became known as the “neutron discrepancy.” Thestory of DS02 is in many ways a story of the neutron
discrepancy and its resolution.
In May 2001, a committee of the National Research Council Board on Radiation Effects Research,that was formed in 1996, published a report (NRC2001) with specific recommendations about how

Percent Changes from DS86 to DS02 as a Function of Ground Distance30

30

Neutron Free-in-Air Kerma

Hiroshima

10
0
-10

Nagasaki-20-30

Gamma Free-in-Air Kerma

20

Percent Change

Percent Change

20

Nagasaki

100

Hiroshima

-10
-20

0

500

1000

1500

Ground Distance (m)Return to Table of Contents

2000

-30

0

500

1000

1500

2000

Ground Distance (m)RERF Update Volume 14, Issue 1, Spring 2003

RERF Dosimetry Revision
All retrospective measurements of neutron doserelated quantities in Hiroshima and Nagasaki involve
activation products in materials that were present at
the time of the bombings. These are traces of radioactive isotopes produced by neutrons from the bombs,
in nuclear reactions with normal isotopes of various
elements in rocks and other building materials. The
strategy of such measurements is to find an elementthat had a high probability of interacting with bomb
neutrons to create a radioisotope with a reasonably
long half-life. That is, long enough to be still present
years later at the time of measurement but shortenough to emit sufficient radiations per unit time tobe detected. The investigator uses physical andchemical techniques to enrich a sample in the activation product radioisotope. Then, radiation emission
counting, using techniques that detect only the characteristic radiations emitted by the particularradioisotope of interest, is used to make very sensitive measurements.
Japanese investigators made the first measurements of neutron activation products in 1945, withina few weeks of the bombings. They realized that“fast,” i.e. high energy, neutrons react with sulfur tocreate a radioisotope of phosphorous, P-32, and thatthe porcelain insulators on electrical power lines contained a paste of pure elemental sulfur. They made anumber of such measurements, although the detection technology available at the time allowed
measurements with useful precision only at locations
very close to the hypocenter. These measurements
could not be repeated in later years because P-32 has
a half-life of 14.3 days and was gone within a few
months after the bombings. It would not be until thetime leading up to DS02, some 50 years later, that a
new technique would be devised to make retrospective measurements of fast neutrons, which are theportion of the neutron spectrum most closely related
to survivor neutron doses. In the meantime, a different type of measurement would have to be made.
Because of the difficulty of finding suitable activation products for fast neutrons, investigators turnedto the activation products associated with “slow” or“thermal,” i.e. low energy, neutrons. Thermal neutrons have only the minimal energy associated withrandom thermal motion at the temperature of theirsurroundings: they started out as faster neutrons but
lost their energy and directionality in scattering interactions with air and ground materials before theyreached the sample. Thus the thermal neutrons thatcreated activation in a sample were not neutrons thattraveled straight from the bomb, and the shielding
considerations that affect levels of thermal neutrons
in a measured sample are not the same as those that
affect the fast neutrons that delivered most of thesurvivor dose. As a consequence, measurements ofthermal neutrons activation products are subject todifficulties of interpretation and depend on detailed
calculations to establish a proportionality between
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&the numbers of fast and thermal neutrons at a sample’s
location.
Japanese investigators made the first measurements of thermal neutron activation in the 1960’s,
using the cobalt radioisotope Co-60, which was produced by the interaction of thermal neutrons withsmall amounts of cobalt typically present in iron andsteel. As noted, the notion of a neutron discrepancy
had its beginnings in the DS86 Final Report, in thetime period when neutron measurement of this typewas still a relatively developing field. Although investigators in the mid-1980’s had recently begun
making a new type of thermal neutron activation
measurement with an isotope of the rare earth element europium, the main results available for DS86
were the measurements of Co-60 that had been madesome twenty years earlier by investigators of the Japanese National Institute of Radiological Sciences(JNIRS) (Hashizume 1967). The chapter on Measurements of Neutron Fluences in the DS86 Final
Report began its Summary and Conclusions with thisparagraph:
The sulfur activation by neutrons above 3 MeV
and the europium activation by thermal neutrons
show no important discrepancy with calculations.
Cobalt activation, however, contradicts the calculated values by an ever-increasing factor that is fiveat 1000 m. If the measured cobalt activations were
accepted as correct representations of thermal
fluences and the assumption is then made that thecalculated fluences on the ground are low by a factor that applies to all energies, then the proportionof neutron kerma in the mixed radiation field beyond 1000 m at Hiroshima would change frominsignificant to significant.
This chapter of the DS86 Final Report further
emphasized that the europium measurements available at the time were insufficient to either confirm or
deny the cobalt discrepancy.
The cobalt discrepancy thus defined in DS86 itself contained all the essential elements of the neutron
discrepancy that would give rise to the dosimetry reevaluation and the DS02 system. The measured
values suggested an obvious trend: calculated values
appeared substantially above measured values near
the hypocenter and below measured values at longer
distances.
In the ten years following the publication of DS86,
Japanese and U.S. investigators made many more
thermal neutron activation measurements. Additional
cobalt measurements were published in 1990 (Kerret al, Kimura et al), 1992 (Shizuma et al), and 1993
(Kimura and Hamada, Shizuma et al). Even larger
numbers of measurements were made using europium, which is present in all rocks at very low
concentrations, typically on the order of a few parts
RERF Update Volume 14, Issue 1, Spring 2003

RERF Dosimetry Revision
per million, but has a great affinity for activation by
thermal neutrons. Due to europium’s ubiquity,
samples that were in known locations at the time of
the bombing, e.g., in structural materials, were easier
to find than iron or steel samples necessary for cobalt. By 1993 Japanese investigators had madeeuropium measurements at dozens of additional locations, extending to ground distances as far as 1370
m in Hiroshima (Hoshi et al 1989, Nakanishi et al
1991, Shizuma et al 1993).
In addition to europium, the new technique of accelerator mass spectrometry (AMS) was applied tomeasuring neutron activation products (Straume etal 1990). Because AMS counts atoms of a particularisotope by ballistically separating them as ions by
their charge-to-mass ratio, rather than by waiting forthem to decay and counting their characteristic radiations, it opened the door to low level measurementsof activation products with very slow radioactive
decay. It was applied to the chlorine isotope Cl-36,
and was extended down to concentrations approaching the order of one Cl-36 atom per 1015 atoms ofchlorine.
In 1992 (Straume et al), an influential paper basedon Cl-36 measurements and summarizing other measurements of thermal neutron activation suggested
that measured values were “a factor of two to ten, ormore” higher than calculated values at distances beyond 1 km in Hiroshima. The extensive series of
Eu-152 measurements published in 1993 (Shizuma
et al) appeared to add further support to this trend.
Meanwhile, work was being done in the realm of
calculations, including re-calculation in 1993 of thedelayed radiations from the bombs, using new physical constants and adjustments to the energy groupings,
to try to resolve the discrepancy. At a conference on
the Hiroshima Dosimetry Discrepancy Study in1994,
papers were presented that reported on the updatingof DS86 to include newer interaction probabilities
between neutrons and air (Hale et al), on the DS86
source term (Whalen), and on efforts to explain themeasurements by devising ad hoc sources to replacethose from the calculations based on physical principles of nuclear explosions (Rhoades et al). An
influential paper (Kaul et al) made a multivariate
analysis of the problem and asserted that no reasonable bomb source term could simultaneously explain
all of the available measurements.
A major assumption underlying much of the debate in the 1990’s relating to the neutron discrepancy
was that the problem was the Hiroshima source termof DS86, as opposed to its transport calculations.
The models for calculating the transport of radiations
over distances of hundreds of meters through air had
been proven elsewhere in atomic weapons tests.
These models establish the quantitative relationshipbetween the fluences in the source term and those at
Return to Table of Contents'the location of interest. Moreover, the Hiroshimabomb was a unique type of design not measured elsewhere in such tests, as the Nagasaki bomb had been.
Hence the most logical cause of the discrepancy
seemed to be the calculation of the types and numbers of radiations emitted in various directions at
various energies by the Hiroshima bomb: theHiroshima source term.
The ongoing debate about the neutron discrepancy
in the 1990’s was hampered by a lack of an agreedupon quantitative definition of the trend in thediscrepancy as a function of distance. This was particularly problematic at longer distances, where themeasurements become increasingly imprecise as they
approach natural or “background” levels, i.e., allmeasurements have finite levels unrelated to the bombradiations, whose natural variability is a limiting factor in measurement precision. In general, a modelwith neutron fluences lower than DS86 near the hypocenter and higher than DS86 at longer distances
required a more penetrating neutron spectrum. To
explain such a difference from DS86, concomitantlywith the increasing concern created by the neutron
discrepancy, some investigators suggested theories
based on an unplanned sequence of events in the explosion of the Hiroshima bomb. They suggested thatthe bomb might have had breaches in its heavy metalcase before the fission chain reaction of the nuclear
material occurred, which would have allowed theescape of unattenuated neutrons in certain directions,
resulting in larger numbers of neutrons at further distances than calculated by DS86.
Many of the models proposed to explain the discrepancy attempted only to explain a trend vs.
distance in thermal neutron activation that was more
like the apparent trend in the thermal neutron measurements than that in DS86, and did not address otherradiations and their measurements completely. Oneof the major theoretical concerns about attempts tomake any such alternative model was the question of
how much of a departure from the trend in DS86 was
physically obtainable from any feasible source term,even one with a totally unshielded “bare fission” neutrons escaping in some directions, if it wereconstrained to originate from a localized source at
the height above ground of the Hiroshima bomb.
Despite the complexities involved, it seems fair tosay that, in general, the observation made in 1994
had merit: the physically plausible models under consideration prior to the reassessment effort were notable to satisfactorily and simultaneously explain allof the measurements, including the 1945 sulfur measurements of fast neutrons and the gamma ray
thermoluminescent dosimetry (TLD) measurements.
This was the general situation when the National
Research Council’s Board on Radiation Effects Research charged its committee on RERF dosimetry,
beginning in 1996, to prepare a report on the probRERF Update Volume 14, Issue 1, Spring 2003

RERF Dosimetry Revisionlem, which was published in 2001. In 2000, the U.S.
Department of Energy formed a U.S. working group
to work in concert with the existing Japanese working group on the dosimetry reassessment that resulted
in DS02. The U.S. funding allocated for DS02 focused strongly on the re-evaluation of both the source
term and the transport calculations of DS86 and theresulting free-in-air (i.e., unshielded) kerma values.
Complete new calculations were performed using thelatest weapon simulation codes available at Los
Alamos National Laboratory. Relative to DS86, the
new calculation made many improvements:• the newest data on physical constants were used,• the entire bomb up to and including the tail fins
was modeled,• a finer time and spatial resolution was used,• finer discrete subdivisions of energy and angle
were used, and• the calculation, which must consider events that
occur at times well below the microsecond level,
was carried out to a full second, much longer
than the DS86 calculation.
In addition to the source term calculation, which
fully and dynamically models the transmission ofneutrons through the bomb casing as the bomb isexploding, the Little Boy replica, made of unused
parts identical to the Hiroshima bomb, was subjected
to new experimental measurements of transmissionof neutrons through the case. These measurements,using a wide-energy-spectrum, accelerator-based
neutron source at Los Alamos, provided new empirical verification of the source term.
New transport calculations were performed using
two complementary methods, Monte Carlo and discrete ordinates, and were found to agree. The latest
values for physical constants, particularly the interaction probabilities for neutrons of various energies
colliding with atomic nuclei of the nitrogen and oxygen in air, were used. Again, as with the source term,
no major surprises emerged.
None of these efforts led to results that could provide a satisfactory explanation of the neutron
discrepancy. Furthermore, although many details of
the Hiroshima bomb’s design specifications remainclassified, the Los Alamos group provided cogent
assurances that the bomb could not have exploded
with a lack of integrity in the case, because if it had
done so the yield of the explosion would not havebeen in the range that clearly occurred.
How, then, has the neutron discrepancy been resolved?
The resolution resulted primarily from• reconsideration of and changes to the estimatedheight of burst and yield of the Hiroshima bomb,• better calculations of the relationship between
free-in-air quantities and the quantities existing
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in samples in situ,
better understanding of the natural variability
among measurements at different sites due tophysical irregularities in the real city that are
not practical to model, and• a better understanding of the limitations of distal measurements.
•

One of the troubling aspects of the neutron discrepancy was the disagreement near the hypocenter,
where measurements are at their best due to the strong
signal, and calculated values exceeded measured
values for most types of measurements. When it became clear that neither the new source term
calculations nor the new transport calculations werelikely to explain this aspect of the discrepancy, theworking groups were compelled to consider the“bomb parameters,” particularly the interrelated
quantities of bomb yield and height of burst.
To tackle this problem, all known measurements
made to date were assembled in a large spreadsheet
and the calculated activation for each measured
sample was specified as a function of the burst heightand yield. These calculated values include corrections such as the “transmission factor” relating the
calculated free-in-air value at a sample’s distance tothe calculated in situ value in the sample based on its
size, composition, and geometrical configuration. In
many cases, this involved new, detailed, Monte Carlocalculations using a model of the entire building inwhich the sample resided at the time of the bombing.
Such calculations are also the best way to address
the question discussed earlier, of establishing the relationship between numbers of fast and thermal
neutrons at a given location. Because thermal neutrons are more like a diffusing cloud of gas and do
not have the directionality of fast neutrons, the things
such as shielding that affect the relationship between
the free-in-air fluence and the fluence in the sample
are different for thermal than for fast neutrons. The
entire ensemble of measurements was combined withappropriate statistical weighting in a calculation todetermine the yield and height of burst that would
best fit the totality of available measurements. The
yield and height-of burst values implied by the measurements were carefully considered in light of all of
the other lines of evidence bearing on those parameters, such as the yield range implied by the newsource term calculations, and all of the older data
relating to sightings, shadows of thermal burns, blast
canisters, and so on. A change was made, and was a
key improvement in the agreement of measurements
and calculations at short distances.
In Hiroshima, the yield was increased from 15 kt
to 16 kt, producing an essentially uniform, proportional increase of about 6.7% in all fluences, all otherthings being equal. In addition, the height of burst
was raised from 580 m to 600 m, which tends to decrease the fluences near the hypocenter but has a
RERF Update Volume 14, Issue 1, Spring 2003

RERF Dosimetry Revision
diminishing effect at longer distances. The most important other factor affecting the unshielded gamma
kerma in Hiroshima is an increase in the “prompt”
portion of the gamma ray fluence in the source term,
which increase is due to the newer values for physical constants (“cross-sections”) that were used in theDS02 calculations The total prompt gamma ray
fluence per kiloton of yield in the source term increased by 31% in Hiroshima, but the effect on kerma
is much smaller because only a small fraction (about4%) of the total kerma is due to prompt gamma rays.
(The remainder is delayed gamma rays emitted by
the radioactive materials in the fireball and by thecapture of neutrons by nitrogen in the air near thefireball.) The overall effect of these changes, alongwith others due to the newer cross-sections and improvements in computational capability, is that the
gamma ray kerma, shown in the right panel of the
figure for Hiroshima, is slightly reduced near the
hypocenter, where the effect of the increased heightof burst predominates. At distances beyond about 500
m the other effects begin to predominate, and the
kerma is increased by a factor approaching 10% at
longer distances.
After careful consideration of the available evidence in Nagasaki, the working groups concluded
that the yield and height of burst should remain unchanged. The predominant factor affecting gamma
ray kerma is an increase of about 37% in prompt
gamma rays per kiloton of yield, similar in proportion and for the same reasons as the increase in prompt
gamma rays in Hiroshima. The kerma values are more
uniformly increased because the height of burst isunchanged, and the effect is more pronounced thanin Hiroshima because prompt gamma rays produce alarger proportion (about 25%) of the total gamma
ray kerma in Nagasaki. This factor, combined withothers related to the newer cross-sections and improvements in computational capability, results in therelatively uniform increase in gamma kerma over theentire distance range shown in the figure.
In Hiroshima the DS02 neutron kerma is lower
than DS86 near the hypocenter, increases to values
slightly more than 10% above DS86 at distances on
the order of 1 km slant range, and falls off to values
less than DS86 at distances beyond about 2 km. The
trend in thermal neutron activation vs. distance issimilar but not identical to what is shown here forkerma. As with gamma rays, the change in fluence isessentially proportional to yield. The effect of theincreased height of burst is similar but somewhat
stronger than for gamma rays because neutrons are
more strongly attenuated by the same distancethrough air. The other features seen in the plottedcurve are due to changes in cross-sections and improvements in computational capability. The
reduction near the hypocenter is more important toimproving the agreement with measurements than theslight increase at somewhat longer distances.
Return to Table of Contents
The most marked change arising from the new
calculations is the substantial overall reduction in
neutron kerma in Nagasaki, although the effect onsurvivor doses is negligible because the neutron
kerma there was already so small in relation to gamma
kerma. This is primarily attributable to carrying out
the source calculation to much longer times than werefeasible in DS86, which results in more down-moderation of the neutrons by the hydrogenous materials
in the high explosive of the Nagasaki bomb. This
down-moderation, a reduction overall in the energyof neutrons leaving the nuclear explosion, results in
fewer neutrons at distances relevant for survivors.
In summary, the primary effect on total kerma andhence on survivor doses in contrast to DS86 is a very
modest increase of 5 to 10% in both cities, which isprimarily due to gamma rays and is thus illustrated
by the gamma ray kerma values in the plots beyond
about 1000 m ground distance, where most survivors are located. But what of the more important
aspect of the neutron discrepancy, particularly withrespect to survivor dose—the trend at longer distancesby which the measurements appeared to increasingly
exceed the calculated values? It is clear from the figure that DS02 calculated values of neutron kerma in
Hiroshima do not greatly exceed DS86 estimates atlonger distances, although there is some minor increase at distances from about 700 to 1500 m, wheremost of the discrepant measurements were located.
The range from about 700 to 1500 m is the portion of the discrepancy whose resolution has more to
do with the understanding of the measurements, andtheir relationship to the calculated “free in air” values of the dosimetry system, than does thediscrepancy close to the hypocenter. Investigators inthis realm have long understood the difficulties ofinterpreting measurements that begin at some point
to approach limits of detection because the signal ofinterest is too weak to reliably separate from “noise”
or “background.” And there is genuine room for disagreement about matters such as, for instance, theacceptable, statistically defined error rates that one
will agree to tolerate in distinguishing signal fromnoise.
But the most important understandings relate topeculiar, technical aspects of the measurements.
These measurements require special methods to detect levels much lower than similar measurements
made for routine purposes, such as radiation protection in the vicinity of an operating nuclear facility.
Furthermore, the investigators in this case are not only
compelled to peer back in time over several decades
or more, but are forced to find ways to use natural
materials rather than designed and specially prepared
dosimeters.
One example is the measurement of Eu-152, which
is detected and quantified by the characteristic gamma
RERF Update Volume 14, Issue 1, Spring 2003

RERF Dosimetry Revisionrays that it emits at certain discrete energies. Rocksand building materials contain many other, naturally
occurring radioactive isotopes that emit gamma rays
at energies too close to the Eu-152 gammas to becompletely distinguished by even the most modern
detectors. Extremely low-level measurements rely
upon both sophisticated chemical processing andspectral methods to reduce the natural interferences.
They also require a very careful quantitative assessment of the “non-bomb-related counts” from theinterferences that remain, and from the spectral continuum of ambient x rays and system noise. The
working group held workshops on the special statistical and quantitative methods needed for suchproblems. Other related topics were addressed indetail, such as the properties of samples themselves(e.g., content of hydrogen and other elements withstrong neutron interaction probabilities) that affectthe amount of activation for a given number of bomb
neutrons impinging on the sample.
Another example relates to chlorine 36. New understanding emerged from differences between
measurements in granite vs. those in concrete. Reports of measurements in granite became importantin working group meetings circa 2000, whereas thosein concrete had been reported since about 1990. Because of the 300,000-year half-life of Cl-36, naturallevels in rock were produced as it sat in the earth fortimes on the order of a million years or more before
being quarried by humans, by neutrons from cosmic
rays and spontaneous fissions of natural uranium andthorium in the rock. Much of the chlorine in concrete, on the other hand, has been in the hydrosphere,
particularly the earth’s oceans, where there is typically less shielding of the cosmic ray fluence but alsoless natural uranium and thorium, for much of its “recent” history on the geological time scale. Thus thenatural Cl-36 levels that affect measurements at medium to long distances are determined differently inconcrete and in various types of rocks, including thepebbles that are often present in concrete.
Another consideration is that chloride ion, in contrast to the chemical forms of cobalt or europium inmeasured samples, is substantially mobile in somematerials, and much more so in concrete than granite. Some advances related to understanding potential
sources of misleading results in concrete samples
taken near the surface of a wall or other structure.
Artifacts can result from infiltration of rainwater witha Cl-36 level different from the level in the surface
concrete, or from the existence of surface concretethat was added to exterior walls after the war, among
other causes.
One useful endeavor of the current work has been
an organized program of chemical processing of eightlarge samples of granite from various distances, by aspecialized, contracted laboratory at the Japan Chemical Analysis Center, followed by measurements ofReturn to Table of Contents

Eu-152 in a special, low-background counting facility located in a deep underground tunnel in Japan.
The same samples were also measured for Cl-36 by
three different laboratories, in Japan, Germany, andthe United States, as part of a designed intercomparison among different activations products,
laboratories, and methods.
In another development, new techniques for measuring the isotope nickel 63 were developed in theyears leading up to DS02, which allowed the firstmeasurements of fast neutrons since 1945. Nickel 63
atoms are produced by the interaction of fast neutrons with copper. A new and very sensitive method
uses special chemical processing to completely separate nickel from the copper, followed by accelerator
mass spectrometry with (AMS) a special gas-filled
magnet detector in Munich, Germany. Japanese investigators have also shown that radiation counting
methods based on beta emissions of nickel 63 may
also be feasible with special sample preparation, incases where large enough samples of copper are available. The capability of making direct, newmeasurements of the numbers of fast neutrons produced by the bombs is a major development, and the
AMS measurements of nickel 63 have added confidence to the dosimetry assessment.
All available measurements made since 1945, including the original Japanese measurements of fastneutron activation in sulfur, were re-evaluated forDS02. This included a re-evaluation of sample map
coordinates and hypocenter locations. Map work wasdone with modern geographical information system
software, using both war-era maps and newer, moreaccurate maps in conjunction with war-era aerial
photographs and other sources of information. TLD
measurements of gamma ray dose as well as the neutron activation measurements were re-evaluated,
including all of the newer TLD measurements madesince DS86. Bounding calculations were done as partof the transport calculations to evaluate the effect onradiation transport of assumptions differing from theidealized DS86 assumption that the radiations weretransported over an earth surface consisting of flat,level ground of uniform composition and moisture
content. All of these improvements and many more
contributed to the new understanding of calculations
and measurements that emerged in DS02.
The above descriptions, of course, cover only
some of the more salient aspects in which DS02 represents substantial improvements in both calculations
and measurements. In the final analysis, the working groups concluded that the existing body ofmeasurements is consistent with DS02 calculations,from the hypocenters out to distances at which individual types of measurements become insufficiently
reliable for validation of the calculations, due to theirtechnical limitations. This is a very important improvement over the situation that existed with DS86.
RERF Update Volume 14, Issue 1, Spring 2003

!

RERF Dosimetry Revision
In addition to what has been discussed here, substantial improvements have been made in the area ofshielding calculations. This includes shielding by terrain and neighboring structures not accounted for in
DS86, and what should be substantial improvements

for Nagasaki factory workers where shielding bybuildings and equipment have long been problematical. These further issues will be discussed insubsequent publications.

The discussion given here represents only the personal views of the authors and not those of the
Joint U.S.-Japan working group, the RERF, the U.S. Department of Energy, or the Japanese Ministryof Health, Labour and Welfare. The authors gratefully acknowledge the assistance of the Update
Editor and Dale Preston, which was invaluable in preparing a readable discussion.

References
1. Hale GM, Young PG, Chadwick MB, Chen ZP: R-matrix analysis for nitrogen and oxygen. Proceedings of the
8th International Conference on Radiation Shielding, Arlington, Texas, April 24–28, 1994
2. Hashizume T, Maruyama T, Shiragai A, Tanaka E, Izawa M, Kawamura S, Nagaoka S: Estimation of the air
doses from the atomic bombs in Hiroshima and Nagasaki. Health Phys 13:149–69, 1967
3. Hoshi M, Yokoro K, Sawada S, Shizuma K, Iwatani K, Hasai H, Oka T, Morishima H, Brenner D: Europium152 activity induced by Hiroshima atomic bomb neutrons: Comparison with the 32P, 60Co, and 152Eu activities in
Dosimetry System 1986 (DS86). Health Phys 57(3):831–7, 1989
4. Kaul DC, Woolson WA, Egbert SD, Straume T: A brief summary of comparisons between the DS86 A-bomb
survivor dosimetry system and in-situ measurements in light of new measurements, revised nuclear data andimproved calculational methods. Proceedings of the 8th International Conference on Radiation Shielding, Arlington, Texas, April 24–28, 1994
5. Kerr GD, Dyer FF, Emery JF, Pace III JV, Brodzinski RL, Marcum J: Activation of Cobalt by Neutrons from theHiroshima Bomb. Oak Ridge, Tennessee: Oak Ridge National Laboratory; ORNL-6590, 1990
6. Kimura T, Takano N, Iba T, Fujita S, Watanabe T, Maruyama T, Hamada T: Determination of specific activity ofcobalt (60Co/Co) in steel samples exposed to the atomic bomb in Hiroshima. J Radiat Res 31:207–13, 1990
7. Kimura T, Hamada T: Determination of specific activity of 60Co in steel samples exposed to the atomic bomb in
Hiroshima. Radioisotopes 42:17–20, 1993
8. Nakanishi T, Ohtani H, Mizouchi R, Miyaji K, Yamamoto T, Kobayashi K, Imanaka T: Residual neutron-induced radionuclides in samples exposed to the nuclear explosion over Hiroshima: Comparison of the measured
values with the calculated values. In: A review of forty-five years study of Hiroshima and Nagasaki atomic bomb
survivors. J Radiat Res 32(Suppl.):69–82, 1991
9. National Research Council: Status of the Dosimetry for the Radiation Effects Research Foundation (DS86).
National Academy Press, Washington, DC, 2001
10. Rhoades WA, Barnes JM, Santoro RT: An explanation of the Hiroshima activation problem. Proceedings of the
8th International Conference on Radiation Shielding, Arlington, Texas, April 24–28, 1994
11. Roesch WC, ed.: US-Japan Joint Reassessment of Atomic Bomb Radiation Dosimetry in Hiroshima and Nagasaki,
Final Report, Vol. 1 and 2. Radiation Effects Research Foundation, Hiroshima, Japan, 1987
12. Shizuma K, Iwatani K, Hasai H, Oka T, Morishima H, Hoshi M: Specific activities of 60Co and 152Eu in samples
collected from the Atomic Bomb Dome in Hiroshima. J Radiat Res 33:151–62, 1992
13. Shizuma K, Iwatani K, Hasai H, Hoshi M, Oka T, Morishima H: Residual 152Eu and 60Co activities induced byneutrons from the Hiroshima bomb. Health Phys 65(3):272–82, 1993
14. Shizuma K, Iwatani K, Hasai H, Oka T, Hoshi M, Shibata S, Imamura M, Shibata T: Identification of 63Ni and60
Co produced in a steel sample by thermal neutrons from the Hiroshima atomic bomb. Nucl Instrum Meth Phys
Res A384:375–9, 1997
15. Shizuma K, Iwatani K, Hasai H, Oka T, Endo S, Takada J, Hoshi M, Fujita S, Watanabe T, Imanaka T: Residual60
Co activity in steel samples exposed to the Hiroshima atomic-bomb neutrons. Health Phys 75:278–84, 1998
16. Straume T, Finkel RC, Eddy D, Kubik PW, Gove HE, Sharma P, Fujita S, Hoshi M: Use of accelerator mass
spectrometry in the dosimetry of Hiroshima neutrons. Nucl Instrum Meth Phys Res B52:552–6, 1990
17. Straume T, Egbert SD, Woolson WA, Finkel RC, Kubik PW, Gove HE, Sharma P, Hoshi M: Neutron discrepancies in the DS86 Hiroshima dosimetry system. Health Phys 63:421–6, 1992
18. Whalen PP: Source and replica calculations. Proceedings of the 8th International Conference on Radiation
Shielding, Arlington, Texas, April 24–28, 1994

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RERF Update Volume 14, Issue 1, Spring 2003

"

Facts and Figures

Facts and Figures
Department of Statistics
Projections of Radiation-Related Mortality in the LSS
RERF reports clearly indicate that atomic bombradiation exposure has a significant and continuing
impact on cancer and noncancer death rates in theLife Span Study (LSS). It is generally well known
that slightly more than half of the members of the
RERF LSS cohort had died by the late 1990’s. However, it is less well known that most of theradiation-related deaths in the LSS are expected tooccur in the future. The figure presents estimates of
the annual number of radiation-associated cancer andnoncancer deaths in the LSS for the follow-up to dateand projections for the future. The meaning of “excess deaths” here is the same as in LSS reports, bothfor the current follow-up and projected lifetime risks.
In particular, for a specific cause this includes thosehastened by radiation exposure even though theymight have occurred later in the absence of exposure.

at the exposure. There is of course some uncertainty
in the future projections, and also for the past since
the excess deaths are not directly observable. Estimates of the number of radiation-related noncancer
deaths are considerably less precise than those forsolid cancer or leukemia, since the nature of both the
low dose noncancer risks and age-time patterns in
the noncancer are poorly characterized.
These calculations are based on the current agespecific risk estimates for solid cancer and noncancer
disease mortality of LSS Report 13, which will appear shortly. The leukemia risk estimates were
described in the previous LSS Report 12. For cancer, age-specific excess risks depend on both attained
age and exposure age, and as noted these are highest
for those exposed as children. For noncancer diseases,
the exposure-age variation is presently less clear andnone is used for calculations here.

We estimate that between 1950 and 1997 there
were about 450 excess solid cancer deaths, 100 excess leukemia deaths, and 250 excess noncancer
deaths in the LSS. Our projections suggest that thesenumbers will increase to well over 1,000 for solidcancers and 500 for noncancer diseases, with little
increase in the number of radiation associated leukemia deaths. The large projected increase in solidcancer deaths reflects the observation that excess risks
are highest for those exposed as children or young
adults, and about half of the cohort was under age 25

The remaining follow-up will provide better understanding of the crucially important age-time
patterns of radiation-related risk for both solid cancer and noncancer mortality. It is difficult with eventhe current 50 years of follow-up to distinguish between variations with exposure age and attained age.
For noncancer mortality important further information will be obtained regarding risk at under about
0.5 Sv, which is at this time rather unclear.

Past and Projected Radiation-Related Mortality in the LSS

Excess Deaths per Year

30
Solid Cancer
20

10

Noncancer Diseases
Leukemia

0
1945

Return to Table of Contents

1965

1985

2005

2025

RERF Update Volume 14, Issue 1, Spring 2003

25

In Memoriam

In Memoriam: Gilbert W. Beebe, 1912–2003
After a long a productive life, Dr. Gilbert W.
Beebe, who played a central role in the organizationand continuing success of the Atomic Bomb Casualty Commission (ABCC) and the Radiation Effects
Research Foundation (RERF), died on March 3rd in
Washington, D.C. He was 90 years old. Dr. Beebe issurvived by his wife, Ruth, four children, and five
grandchildren.
As all of those who knew him can attest, Dr. Beebe
was an outstanding scientist and an excellent manager. Prior to World War II, Dr. Beebe, who wastrained as a sociologist and statistician, worked onstudies of contraception and family planning. From
1942 through 1946 he managed the Statistical Analysis Branch in the Office of the Surgeon General for
the US Army. Following the war, Dr. Beebe, together
with the famous heart surgeon Dr. Michael DeBakey,
led the efforts to organize a large-scale follow-up
study of the health US war veterans. Their efforts
resulted in the creation of the National Academy of
Sciences (NAS) Medical Follow-up Agency (MFUA)
in 1946. Under Dr. Beebe’s leadership the MFUA,
which is still active today, carried out many important studies.
As the MFUA was being created, U.S. President
Truman directed the NAS to organize and manage
health effects studies of the atomic bomb survivors.
Dr. Beebe played a key role in recruiting scientists
and overseeing research at ABCC. By the mid-1950’s
there was a feeling that, with the decline in the rates
of radiation-induced leukemia and the lack of apparent effects on children born to the survivors, further
studies of the atomic bomb survivor studies were notnecessary. To counter this misconception and improve
the quality of ABCC research, Dr. Beebe, together
with Seymour Jablon, organized the Francis Committee to review the ABCC program and makerecommendations regarding its future. The
committee’s 1955 report laid the foundation for thecreation and follow-up of the Life Span Study (LSS),
Adult Health Study, and F1 cohort. The first of Dr.
Beebe’s three terms as Chief of the Department of
Statistics at ABCC lasted from 1958 through 1960.
During this crucial period he organized the Department of Statistics, guided the creation of the LSS andF 1 cohorts, helped organize the Hiroshima andNagasaki Tumor Registries, and established the basic mortality and incidence follow-up methods thatare still in use today. Dr. Beebe returned to ABCC
for two years from 1966, the period during which
the T65D dosimetry was introduced. Dr. Beebe’s third
term of service at ABCC began in 1973. He stayed at
RERF through 1975 serving as the last Chief of the
Department of Statistics at ABCC and as a Director
Return to Table of Contents

and the first Chief of Research at RERF. Following
his return to the U.S., Dr. Beebe continued to oversee RERF and direct the MFUA until 1977.
After leaving NAS, Dr. Beebe went to work in theClinical Epidemiology Branch of the U.S. National
Cancer Institute (NCI). Following the Russian
Chernobyl accident in 1986, he organized and managed the successful efforts to establish follow-up
studies of clean-up workers and children exposed toradiation as a result of the accident. He was actively
involved in this work until the time of his death. He
also continued to take an active interest in RERF research, most recently working on the analysis andreporting of our liver cancer incidence studies with
Dr. John Cologne, Dr. Shoji Tokuoka, and other
RERF scientists.
Over the years, Dr. Beebe arranged for many
young Japanese researchers to obtain training andexperience in the U.S. through fellowships at NCI
and other research institutions. Dr. Beebe’s legacy at
RERF will continue in many ways, including the
newly created Gilbert W. Beebe Fellowship. This
program, which is being managed by NAS, provides
support for visiting researchers (including Japanesescientists) to work on joint NCI-RERF research
projects.
When I came to RERF in 1981 six years had
passed since Dr. Beebe worked at RERF, however
his impact on the scientists and staff was still readily
apparent as hardly a day went by without several references to the near-legendary Dr. Beebe. Over thelast 15 years as I had the chance to meet and workwith him I developed an even greater appreciation

Dr. Gilbert W. Beebe in 1966 (photo courtesy ofArchives Office, Department of Information
Technology)
RERF Update Volume 14, Issue 1, Spring 2003

26

In Memoriam
for his kind, insightful, though sometimes demanding, advice and support. Last year, as I prepared atalk for a special symposium in Dr. Beebe’s honor, I
asked former RERF staff members for recollections
and remembrances and received a surprisingly large
number of heartfelt comments. As expected, I again
heard the tales of Gil’s tireless and hard-driven work
habits, especially his ability to produce an amazing
amount of well-written reports and memos (easily
keeping a small group of secretaries fully engaged in
preparing manuscripts). However, without exception,
those who worked with Dr. Beebe also noted how
they were inspired and encouraged by his actions,
support, and example.
Dr. Beebe was a conscientious and energetic scientist with a unique talent for the organization ofimportant, large-scale, research projects and a special ability to guide and inspire others. Dr. Beebe
was motivated by a desire to advance knowledge and,despite his numerous major accomplishments, neversought to focus attention on his own crucial contributions.
Though few people at RERF today worked with,or even knew, Dr. Beebe, I hope that all of us will be
inspired by Dr. Beebe’s quiet but effective style andwill work to keep his spirit alive through the conductof ethical, innovative research that benefits the atomic
bomb survivors and all of humanity. All of us at RERF
should be proud to play a role in Dr. Beebe’s continuing legacy.
Dale L. Preston

In Memoriam: Abraham Kagan, 1922–2003
Dr. Abraham Kagan, our mentor and one of theworld’s pioneers in epidemiology research on circulatory diseases, passed away on February 1 this year.
I take this opportunity to express my regret over his
death.
Dr. Kagan played a central role in the NI-HONSAN Study, which was initiated in 1965. Thisrenowned international collaborative study has
proven epidemiologically that, among Japanese descendents spending many years in the West in Hawaii
and San Francisco, the rate of cerebral stroke has
decreased whereas that of heart diseases has increased. This study therefore pointed out that
improvement of lifestyle is essential for the prevention of heart diseases and stroke. Because theJapanese organization responsible for this study was
ABCC, the Department of Epidemiology and Statistics and the Department of Medicine were actively
engaged in the study around 1974, when I first joined
ABCC. I was naturally involved, as I was aiming tobecome a physician specializing in circulatory diseases. Dr. Kagan, who was responsible for this studyin Honolulu, was the organizer of the Honolulu Heart
Program and lived there. I visited Honolulu several
times because of my involvement in the study, and I
vividly remember his warm hospitality as if it were
yesterday. Also, when I organized the 30th anniversary symposium of the NI-HON-SAN Study held in
Hiroshima in September 1996, he visited Hiroshima
with his colleagues, including Drs. Katsuhiko Yano,David Curb, and Beatriz Rodriguez, and participatedin fruitful discussion over a span of two days.
My specialty has somehow changed from internal medicine of circulatory diseases to epidemiology
on circulatory diseases, but over these 30 years since
I graduated from medical school, Dr. Kagan has been
my model, on whom I have tried to pattern myself.
Currently in Japan, prevention and care of lifestylediseases such as heart diseases and stroke is one of
the most important issues in health management. We
should cope with health problems in the 21st century
on the basis of Dr. Kagan’s many achievements including the NI-HON-SAN Study.

Dr. Abraham Kagan in 1984 (photo courtesy ofArchives Office, Department of Information
Technology)
Return to Table of Contents

In closing, I offer my prayers for the soul of Dr.
Kagan.
Kazunori Kodama

RERF Update Volume 14, Issue 1, Spring 2003

Research Protocols
Research Protocols Approved 2002
RP 1-02 Health Effects Study of the Childrenof A-bomb Survivors: Clinical Health Study
Fujiwara S, Suzuki G, Yamada M, Takahashi N,
Akahoshi M, Hakoda M, Neriishi K, Soda M, Hida
A, Imaizumi M, Suyama A, Koyama K, Nakachi K,
Katayama H, Pierce DA, Preston DL, Taira S
The objectives of the clinical health study on thechildren of A-bomb survivors (F1 Clinical Study[FOCS]) are (1) to elucidate epidemiologically theeffects of parental exposure to A-bomb radiation on
the development of multifactorial diseases among thechildren of A-bomb survivors, (2) to preserve blood
samples for the future molecular biological studies,and (3) to contribute to the health and welfare of theF1 population via health examinations and healthguidance.
The F1 Clinical Study will be carried out over four
years. A study cohort of about 17,500 has been identified, and each year one-fourth of those will be
invited to participate. This will be done by including
them each year in a mail survey, which will explain
the study and determine their willingness to participate. There was a pilot mail survey of 300 persons inwhich about 50% of 300 persons (75% of the pilot
mail survey respondents) expressed willingness toparticipate in a clinical study. Thus it can be expected that around 9,000 of the mail survey cohort of
17,500 will agree to participate.
There will be a pilot clinical study involving about
500 people, both cities together, chosen from thoseexpressing willingness to participate in the pilot mailsurvey and first year of the full mail survey. The objectives of the pilot clinical study are to evaluate theusefulness and validity of the study forms and procedures, method of contacting subjects, and to review
the organizational structure and costs of the healthexamination.
In the F1 Clinical Study, upon obtaining informed
consent from the participants, the health examination including interviews, medical examinations,anthropometric measurements, blood pressure measurements, urinalysis, hematological tests, occultstool blood reaction tests, electrocardiogram (ECG),
abdominal ultrasonography, and radiological examination for stomach and so on will be conducted. Also,
gynecological examinations, and detailed examinations will be conducted if necessary. Multifactorialdiseases detected via these examinations and various measurements will be analyzed in relation toradiation exposure of their parents, taking into consideration confounding factors. Blood drawn fromthose who gave their consent will be preserved for
future molecular biological studies.
The F1 Clinical Study will contribute to the healthmanagement of the children of A-bomb survivors by
feeding back the clinical results of the health examiReturn to Table of Contents

27
nation to them and by giving them appropriate guidance.
As a rule, the procedure and contents of the healthexamination, the ethical issues, data management, andso on are the same in the pilot and full-scale clinicalstudies. However, when some additions and modifications are indicated by the pilot clinical study, an
addendum to this research protocol will be submitted for the full-scale clinical study. Molecularbiological studies will be conducted after a separate
detailed research protocol is prepared and approved
following the institutional procedures of RERF.

RP 2-02 Studies on Skin Cancer Incidence
among the RERF Life Span Study Cohort,
Hiroshima and Nagasaki (Addendum to RP 291)
Kishikawa M, Koyama K, Iseki M, Yonehara S,
Tokuoka S, Soda M, Mabuchi K, Ron E, Preston DL,
Suyama A, Nakachi K
The aim of this study is to describe and quantify
the risk of skin cancer in the Life Span Study cohort.
The findings obtained from the previous skin cancer
study (RP 2-91) completed during the study period
from 1950 to 1987 suggest an increase of skin cancer risk by radiation, but for further assessment ofradiation effect on skin cancer, this study proposes
to review, together with previously obtained data, skincancer cases newly developed in 1988 and after.
RP 3-02 Health Effects Study of the Childrenof A-bomb Survivors: Mail Survey
Koyama K, Suyama A, Grant EJ, Nakachi K,
Watanabe T, Fujiwara S, Suzuki G, Preston DL,
Taira SA mail survey is being planned in the RERF F1
cohort to obtain baseline epidemiological information that will be used for ongoing mortality and cancer
incidence studies at RERF and the establishment ofa sub-cohort for a clinical health examination program.
The mail survey will be sent to approximately
24,000 people. This includes 17,698 surviving members of the F1 mortality cohort whose koseki is in
Hiroshima or Nagasaki and whose current address isin or near the cities. In addition, we expect 6,000–
7,000 members whose koseki is in either city or
surrounding areas but whose current address information is not available will be subjects of the mailsurvey cohort. In order to minimize the time between
the receipt of the survey and the scheduling of theclinical examinations conducted at the Departmentof Clinical Studies, RERF, the survey will be carriedout over four years with the questionnaire being sent
to one-quarter of the sample subjects per year.
The questionnaire and associated documents are
virtually identical to those used in the “Pilot Mail
Survey of the Children of Atomic Bomb Survivors”
RERF Update Volume 14, Issue 1, Spring 2003

Research Protocols(RP 4-00) that were sent to 300 members of the mailsurvey sample between May and July 2000. The
material included in this survey will also include an
additional brochure that provides a detailed description of the planned health examination.
The results of the pilot study suggest that we can
expect a 70% response rate with about 8% of the
non-responses resulting from outdated addresses.
About 75% of the respondents indicate some willingness to participate in the clinical examination.
This suggests that the mail survey will identify
12,000–12,500 potential clinical program participants.
Scientific and ethical issues related to the designand conduct of this study have been reviewed by thethird-party committees established by RERF specifically for consideration of this survey and the related
clinical examination program. These committees
have indicated their support of the plans for the mailsurvey.

RP 4-02 Perturbation of T-cell Homeostasis in
Atomic-bomb Survivors
Kusunoki Y, Kyoizumi S, Hayashi T, Hakoda M,
Suzuki G, Kasagi F, Fujita S, Kodama Y, MacPhee
DG
We wish to examine the proposition that radiation exposure can seriously perturb one or more of
the mechanisms responsible for T-cell homeostasis
in man. Our approach leans heavily on a number ofrecently-developed techniques which we believe will
help us to learn a great deal about the history of the
T-lymphocyte populations which are of vital importance to the immunological defense activities ofatomic-bomb (A-bomb) survivors. The nature andextent of any substantial impairment (or in some situations unbalancing) of their immunological defense
systems may well be an important element in theirexcessive (and ongoing) cancer and non-cancer disease histories.
Our basic strategy involves studying the blood
leukocytes of about one thousand A-bomb survivors
who are current or recent participants in the Adult
Health Study (AHS) population to determine (1) the
numbers of T lymphocytes that contain T-cell receptor-rearrangement excision circles (TRECs) and(2) the average lengths of telomere repeats in T lymphocytes and other immunity-determining cell
populations.
TRECs are circular DNA molecules generated inthymocytes during the T-cell receptor (TCR) generearrangement process in the thymus, and an individual’s ability to produce T lymphocytes in thethymus can be evaluated by determining how manyof his or her T cells contain TRECs as a fraction of
the total T-cell population. Assuming that A-bombradiation is almost certain to have increased the rate
at which age-dependent thymus dysfunction occurs
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28(as has been suggested by several previous studies),
we can expect to find that the numbers of T cellswith TRECs will be somewhat lower in A-bomb
exposed survivors than in age-matched but non-exposed controls.
The lengths of telomere repeats in peripheral
blood memory and naïve T lymphocytes will also
be measured to provide us with an indication of how
many cycles of cell division these T-cell populations
have undergone prior to being sampled. If it is supposed that T lymphocytes are required to divide more
frequently during the recovery process from A-bombradiation-induced cell loss than are the T lymphocytes of the appropriate unexposed controls, it ought
to be possible to detect greater reductions in telomere lengths in cells from both the naïve and memory
T-lymphocyte populations of exposed individuals
than are seen in concurrent T lymphocyte populations from unexposed controls. Moreover, given thatthe recovery to near normal of the peripheral T-cellpool from A-bomb damage is thought to result inlarge part from an expansion in the population ofmemory T cells that survived exposure to A-bomb
irradiation, we ought to be able to detect a more pronounced shortening of telomere length in the memory
T-cell population of any given exposed survivor thanin his or her naïve T-cell population.
We believe that the results of these types of measurement will provide us with a reasonable indicationof the extent to which abnormalities of the immune
functions (including, but not exclusively, the defense
functions) of A-bomb survivors have been causal incertain of the diseases that appear to be more common in A-bomb exposed survivors. We will therefore
carry out a detailed investigation of any possible
relationships between the perturbations in lymphocyte-dependent immune function we have describedunder RPs 3-87 and 1-93 and the inferences concerning mechanism(s) that we hope to be able to draw
from our measurements of TREC-bearing CD4 Tcell numbers and T-lymphocyte telomere lengths.
Clinical laboratory data including blood test results
and records of inflammatory disease(s) will be assessed to determine how they relate to TREC-bearing
CD4 T-cell numbers and telomere lengths. Fromthese analyses, we hope to be in a position to determine whether A-bomb radiation has perturbed thenormal processes of T-cell homeostasis, as well as
whether any such perturbations are directly involved
in disease development or disease status in A-bomb
survivors.
To gain a better understanding of the mechanisms
involved in radiation-induced perturbation of T-cell
homeostasis, we also plan to investigate the processes of T-cell reconstitution following radiation-induced
damage using a number of potentially valuable animal models. By reconstituting irradiated mice with apopulation of mouse T cells that carry a stable genetRERF Update Volume 14, Issue 1, Spring 2003

Research Protocols
ic marker along with functional TCRs that differ fromthose of the irradiated mice, we intend to examine
many of the parameters that help to restore and maintain T-cell production and memory in irradiated hosts.
Once we have made solid progress in the mouse/mouse system, we are planning to reconstitute theimmune systems of immunodeficient mice with human rather than mouse T cells, and to investigate
whether we can use such a system to better characterize some of the mechanisms involved in the controlof human T-cell memory in both control and irradiated animals.

RP 5-02 Papillary Thyroid Carcinomas in Residents of Hiroshima and Nagasaki Who Were
Exposed to A-bomb Radiation as Children: A
Study of RET Gene Rearrangements and OtherDNA Changes Potentially Responsible for theOrigins and/or Development of These Tumors
Hamatani K, Hirai Y, MacPhee DG, Koyama K, Soda
M, Katayama H, Preston DL, Tokuoka S, Fukuhara T,
Hayashi Y, Fujihara M, Tsuda N, Mabuchi K, Ron E
Rearrangements of the RET proto-oncogene havebeen found to occur in the thyroid tumors of a considerable number of patients with histories ofradiotherapy as well as in children who lived in the
Chernobyl contaminated area. Radiation-associatedthyroid cancers with relatively short latencies and/or
the histological pattern of a solid variant mainly seemto contain rearrangements of the RET/PTC3 type andrather fewer of the RET/PTC1 type. By contrast, tumors with relatively long latencies and/or
morphologically typical papillary features seem tocontain predominantly RET/PTC1-type rearrangements. The elevated risk of papillary thyroid
carcinoma that is known to have occurred amongpeople who were exposed to the Hiroshima/Nagasaki atomic bombs (A-bombs) as children is also
believed to be due in the main to the induction of
RET gene rearrangements, and in particular to the
induction of RET/PTC1 rearrangements, by A-bombradiation. We now plan to use the reverse transcription-polymerase chain reaction (RT-PCR) techniquetogether with RNA samples derived from paraffinembedded blocks of tumor tissue to determine whichof several possible rearranged RET gene transcripts
can be detected in the thyroid tumors of a carefullyselected group of A-bomb survivors. Our aim is todetermine which of the known gene-activating rearrangements of the RET proto-oncogene are most
likely to have been involved in the development ofpapillary thyroid carcinomas in those A-bomb survivors with an exceptionally high excess relative risk
(ERR) who were still very young at the time of thebombing. However, we do not expect to be able toexplain all thyroid tumors among A-bomb survivors
on the basis of rearrangement-induced RET gene
expression. We are therefore planning to carry out a
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29
later-stage screen of all otherwise uncharacterizedtumor tissues for DNA sequence-based evidence of
putatively causative mutant genes, and to do so withthe best techniques that are available at the time.

RP 6-02 A Nested Case-Control Study of Breastand Endometrial Cancer in the Cohort of Japanese Atomic Bomb Survivors
Sharp GB, Neriishi K, Hakoda M, Suzuki G,
Akahoshi M, Cologne JB, Imai K, Eguchi H, Nakachi
K, Key TJ, Stevens RG, Kabuto M, Land CE
A nested case-control study of breast and endometrial cancer in the Adult Health Study (AHS) is
proposed which builds upon the results of the Kabuto and associates study which was recently published.
The initial study provided evidence for an association of free estradiol level in serum prior to diagnosis
and subsequent risk of breast cancer. Although originally designed to examine a possible interaction ofradiation and hormones, the number of cases was too
small to address this question. The Kabuto and associates study included breast cancer cases diagnosedin the AHS cohort through 1983. The proposed new
study will additionally include cases diagnosed since
this time, resulting in a combined study group thatwill be more than four times larger than that used in
the original study. Because risk factors for endometrial and breast cancer are similar, this research projectwill also investigate the etiology of endometrial cancer. Controls will be matched to breast cancer cases,
and endometrial cancer cases will be compared tothe pool of breast cancer controls. The proposed study
will examine a series of hormone-related serum measurements, including total estradiol, bioavailable
estradiol, testosterone, sex hormone binding globulin (SHBG), progesterone, insulin-like growth factors
1, 2, and binding protein-3 (IGF-1, IGF-2, and IGFBP-3), and prolactin. The study will also investigate
the role played by phytoestrogen in the etiology ofthese diseases and, based on data available from the
AHS interviews, will also take into account confounders and other risk factors. Because elevated bodyburden of iron may increase susceptibility to breastor endometrial cancer and because of evidence of
biologic interaction between iron and estrogen, we
will also measure serum ferritin, as an indication ofbody iron level, and protein-carbonyl, as an indicator of oxidative stress. Estrogen burden is believed
to be closely related to lifetime risk of breast andendometrial cancer, and there is reason to hypothesize that the effect of estrogen varies with ferritin
level in the etiology of these diseases. A diet rich in
phytoestrogens may reduce risk.
RP 7-02 Measurement of Thyroid Autoantibodies in Atomic-bomb Survivors (Addendum
to RP 2-99)
Imaizumi M, Neriishi K, Akahoshi M, Maeda R, Soda
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30

Recent Publications
M, Suzuki G, Fujiwara S, Yamada M, Nakashima E
This research protocol is an addendum to RP 299. The primary objective of RP 2-99 is to study theeffect of atomic-bomb radiation on thyroid disease
incidence. With this addendum protocol, diagnosis
of autoimmune thyroid disease among the subjectsof the thyroid study (RP 2-99) will be made by a newly developed thyroid autoantibody measurement
method, which enables diagnosis of autoimmune thyroid disease with increased sensitivity. This projectis indispensable for studying the relationship between
autoimmune thyroid disease incidence and radiationdose.

RP 8-02 Ophthalmologic Study of Children of
Atomic Bomb Survivors (Addendum to RP 102)
Minamoto A, Kumagami T, Yoshitani N, Mishima
HK, Amemiya T, Nakashima E, Neriishi K, Hida A,
Fujiwara S, Suzuki G, Akahoshi M
Cataracts are a multifactorial disease that stems
from a combination of environmental and genetic
factors. Animal experiments have suggested the possibility of an increase in the incidence of congenital
cataracts in the offspring of A-bomb survivors. However, the number of cases is expected to be too small
for this purpose in this study. For congenital cataract
cases, if found, its relationship with radiation will be
investigated as a case report. Our research will quantitatively investigate the opacity of eye lenses andretinal arteriolosclerosis in the offspring of such survivors who are at least 50 years of age at the time of
examination. It is designed to investigate the association of lens opacity with multifactorial diseases andthe radiation dose to which the parents were exposed.
Lens opacity and retinal arteriolosclerosis are to be
graded with the Lens Opacity Classification System
II (LOCS II) and Scheie classification, respectively,
and regression analysis conducted after incorporating a variety of risk factors. Lens and retina
photographs will be stored permanently in our computers as digital images.

Recent Publications(Japanese): the original article is in Japanese.
(Russian): the original article is in Russian.
(Bilingual): the original article is in both Japaneseand English.
(JTr): a Japanese translation is available.
Akahoshi M, Soda M, Nakashima E, Tominaga T,
Ichimaru S, Seto S, Yano K. The effects of bodymass index on age at menopause. International
Journal of Obesity and Related Metabolic Disorders 2002 (July); 26(7):961–8. (RERF Report 1500)
Amino N et al (RERF: Suyama A). Tatsumi N, ed.
Handbook of Reference Values of Clinical Tests,
2nd ed. Tokyo: Nankodo; 2003 (April) (Japanese)
Asakawa J, Kodaira M, Ishikawa N, Hirai Y, Nagataki
S, Moatamed F, Sugawara M. Two-dimensional
complementary deoxyribonucleic acid electrophoresis revealing up-regulated human epididymal protein-1 and down-regulated CL-100 in thyroid papillary carcinoma. Endocrinology 2002
(November); 143(11):4422–8. (RERF Report 802)
Awa AA. Mutation research at ABCC/RERF: Cytogenetic studies of atomic bomb exposed populations. Mutation Research 2003 (January);543(1):1–15.
Brimkulov NN, Nakamura N, Abdullina AA,
Toktosunov A. Retrospective reconstruction of theradiation doses in the Chernobyl NPs accident liquidators by EPR spectrometry of teeth enamel.
Kyrgyz-Russian Slavonic University Herald 2002;
2(1):68–72. (Russian)Cologne JB, Pawel DJ, Sharp GB, Fujiwara S. Probability of causation of liver disease for radiation
exposure: Impact of interaction with hepatitis-C
virus. AOCRP-1 Secretariat, ed. Proceedings ofthe First Asian and Oceanic Congress for Radiation Protection (AOCRP-1) [CD-ROM]. Seoul,
Korea: AOCRP-1 Secretariat; 2002 (October),
Session/OP-1B/OP-1B-5.
Fujiki H, Suganuma M, Okabe S, Kususu M, Imai
K, Nakachi K. Involvement of TNF-alpha changes
in human cancer development, prevention andpalliative care. Mechanisms of Ageing and Development. 2002 (November); 123(12):1655–63.
Fujita K, Nagatomi R, Hozawa A, Ohkubo T, Sato
K, Anzai Y, Sauvaget C, Watanabe Y, Tamagawa
A, Tsuji I. Effects of exercise training on physicalactivity in older people: a randomized controlled
trial. Journal of Epidemiology 2003 (March);
13(2):120–6.

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RERF Update Volume 14, Issue 1, Spring 2003

Recent Publications
Fujiwara S. Epidemiology: (1) Prevalence ofosteoprosis and fracture. Saishin Igaku [Modern
Medicine] 2002; Extra Issue:19–24. (Japanese)
Fujiwara S. Epidemiology of osteoporosis in Japan.
Spine fracture. Jikken Chiryo [Experiment andTherapy] 2002; No. 667:124–7. (Japanese)
Fujiwara S. Measurements of activities of daily living in the aged. Seikei Saigai Geka [Orthopaedic
Surgery and Traumatology] 2002 (June);
45(7):705–13. (Japanese)
Fujiwara S. Risk factors of osteoporosis. Rinsho-i[Medical Clinics of Japan] 2002 (August);
28(8):1790–1. (Japanese)
Fujiwara S, Sone T, Tomomitsu T, Fukunaga M. DXAof femoral neck. Osteoporosis Japan 2002 (July);
10(3):420–1. (Japanese)
Grant EJ, Preston DL, Kodama K. Accessing research
data: The ‘easy’ way. Current situation and prospects for the training and support system using
the IT technology and Internet. Japanese Association of Computer Science; 2003 (February), pp
42–3. (Proceedings of the 18th Scientific Annual
Meeting of the Japanese Association of Computer
Science). (Japanese)
Hakoda M. Prognostic factors in rheumatoid arthritis. Ryumachi-ka [Rheumatology] 2002 (February); 27 (Supplement 1):627–31. (Japanese)
Hall W, MacPhee DG. Cannabis use and cancer. Addiction 2002 (March); 97(3):243–7.
Hayashi T, Kusunoki Y, Hakoda M, Morishita Y,
Kubo Y, Maki M, Kasagi F, Kodama K, MacPhee
DG, Kyoizumi S. Radiation dose-dependent increases in inflammatory response markers in Abomb survivors. International Journal of Radiation Biology 2003 (February); 79(2):129–36.
(RERF Report 2-02)
Hoffmann GR, MacPhee DG. Editorial. Reflectionsof Edward Calabrese on hormesis. Mutation Research 2002 (July); 511(3):179.
Julius S, Majahalme S, Nesbitt S, Grant EJ, Kaciroti
N, Ombao H, Vriz O, Valentini MC, Amerena J,
Gleiberman L. A “gender blind” relationship oflean body mass and blood pressure in the
Tecumseh study. American Journal of Hypertension 2002 (March); 15(3):258–63.
Kakinuma S, Nishimura M, Sasanuma S, Mita K,
Suzuki G, Katsura Y, Sado T, Shimada Y. Spectrum of Znfn1a1 (Ikaros) inactivation and its association with loss of heterozygosity in radiogenic Tcell lymphomas in susceptible B6C3F1 mice. Radiation Research 2002 (March); 157(3):331–40.
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31
Katayama H. The present situation and problems of
the international collaboration. Current situationand prospects for the training and support systemusing the IT technology and Internet. : Japanese
Association of Computer Science; 2003 (February), pp 20–3. (Proceedings of the 18th Scientific
Annual Meeting of the Japanese Association ofComputer Science). (Japanese)
Katayama H, Matsuura M, Endo S, Hoshi M, Ohtaki
M, Hayakawa N. Reassessment of the cancer
mortality risk among Hiroshima atomic-bomb
survivors using a new dosimetry system,
ABS2000D, compared with ABS93D. Journal of
Radiation Research 2002 (March); 43(1):53–63.
Kodaira M. Genetic effects of radiation: Effects on
germline mutation rates at human minisatellite
loci. Hoshasen Seibutsu Kenkyu [Radiation Biology Research Communications] 2002 (September); 37(3):264–81. (Japanese)
Kodaira M. Genetic effects of atomic-bomb radiation: Analysis of minisatellite genes. Pinak M, ed.
Proceedings of the Workshop: Recognition of
DNA damage as onset of successful repair: Computational and experimental approaches. Tokaimura, Ibaraki: Dept of Health Physics, Tokai Research Establishment, Japan Atomic Energy Research Institute; 2002 (March), pp 43–57.
Koshurnikova NA, Gilbert ES, Shilnikova NS,
Sokolnikov M, Preston DL, Kreisheimer M, Ron
E, Okatenko PV, Romanov SA. Studies on the
Mayak nuclear workers: health effects. Radiationand Environmental Biophysics 2002 (March);
41(1):29–31.
Koshurnikova NA, Mushkacheva GS, Shilnikova NS,
Rabinovich EI, Petrushkina NP, Hall P,
Bolotnikova MG, Preston DL, Ron E. Studies on
the Ozyorsk population: health effects. Radiationand Environmental Biophysics 2002 (March);
41(1):37–9.
Kossenko MM, Preston DL, Krestinina LY, Degteva
MO, Startsev NV, Thomas T, Vyushkova OV,
Anspaugh LR, Napier BA, Kozheurov VP, Ron E,
Akleyev AV. Studies on the extended Techa rivercohort: cancer risk estimation. Radiation and Environmental Biophysics 2002 (March); 41(1):45–8.
Kuramoto K, Ban S, Oda K, Tanaka H, Kimura A,
Suzuki G. Chromosomal instability and radiosensitivity in myelodysplastic syndrome cells. Leukemia 2002 (November); 16(11):2253–8.
Kusunoki Y, Hirai Y, Hakoda M, Kyoizumi S. Uneven distributions of naïve and memory T cells in
the CD4 and CD8 T-cell populations derived froma single stem cell in an atomic bomb survivor:
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Recent Publications
Implications for the origins of the memory T-cell
pools in adulthood. Radiation Research 2002
(May); 157(5):493–9. (RERF Report 20-99)
Kusunoki Y, Yamaoka M, Kasagi F, Hayashi T,
Koyama K, Kodama K, MacPhee DG, Kyoizumi
S. T cells of atomic bomb survivors respond poorly
to stimulation by Staphylococcus aureus toxins
in vitro: Does this stem from their peripheral lymphocyte populations having a diminished naive
CD4 T-cell content? Radiation Research 2002
(December); 158(6):715–24. (RERF Report 3-02)
Kyoizumi S, Kusunoki Y, Hayashi T. Lymphocyte
lifespan and immunological memory—Recent
topics in studies of T-cell homeostasis. Rinsho
Meneki [Clinical Immunology] 2002 (August);
38(2):213–20. (Japanese)
Matsuyama S, Ohkura Y, Eguchi H, Kobayashi Y,
Akagi K, Uchida K, Nakachi K, Gustafsson J-A,
Hayashi S. Estrogen receptor beta is expressed inhuman stomach adenocarcinoma. Journal of Cancer Research and Clinical Oncology 2002 (June);
128(6):319–24.
Nakachi K, Eguchi H, Imai K. Can teatime increase
one’s lifetime? Ageing Research Reviews 2003
(January); 2(1):1–10.
Nakamura N. Germ cell mutations among people living near nuclear test sites in Semiparatinsk. Iden
[Heredity] 2002 (May); 56(3):21–4. (Japanese)
Nakashima E, Fujiwara S, Funamoto S. Effect of radiation dose on the height of atomic bomb survivors: A longitudinal study. Radiation Research
2002 (September); 158(3):346–51. (RERF Report10-01)
Neriishi K, Nakashima E. An analysis of persistent
inflammation among atomic bomb survivors withrespect to sex and age at the time of the bombings. Sugihara T, Nikaido O, Niwa O, eds. International Congress Series 1236. Amsterdam, Netherlands: Elsevier Science B.V.; 2002, pp 71–4.
(Proceedings of the International Symposium on
Radiation and Homeostasis).
Ohara T, Koyama K, Kusunoki Y, Hayashi T,
Tsuyama N, Kubo Y, Kyoizumi S. Memory functions and death proneness in three CD4+CD45RO+
human T cell subsets. Journal of Immunology 2002
(July 1); 169(1):39–48. (RERF Report 15-01)
Okumura N, Saji S, Eguchi H, Hayashi S, Saji S,
Nakashima S. Estradiol stabilizes p53 protein in
breast cancer cell line, MCF-7. Japanese Journalof Cancer Research 2002 (August); 93(8):867–
73.
Oue N, Motoshita J, Yokozaki H, Hayashi K, Tahara
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E, Taniyama K, Matsusaki K, Yasui W. Distinct
promoter hypermethylation of p16INK4a, CDH1,
and RAR-beta in intestinal, diffuse-adherent, anddiffuse-scattered type gastric carcinomas. Journalof Pathology 2002 (September); 198(1):55–9.
Pierce DA. Age-time patterns of radiogenic cancer
risk: their nature and likely explanations. Journalof Radiological Protection 2002 (September);22(3A):A147–54.
Pierce DA, Sharp GB, Mabuchi K. Joint effects ofradiation and smoking on lung cancer risk among
atomic bomb survivors. Radiation Research 2003
(April); 159(4):511–20. (RERF Report 17-02)
Preston DL, Mattsson A, Holmberg E, Shore RE,
Hildreth NG, Boice JD. Radiation effects on breast
cancer risk: A pooled analysis of eight cohorts.
Radiation Research 2002 (August); 158(2):220–35. (RERF Report 1-01)
Preston DL, Ron E, Yonehara S, Kobuke T, Fujii H,
Kishikawa M, Tokunaga M, Tokuoka S, Mabuchi
K. Tumors of the nervous system and pituitary
gland associated with atomic bomb radiation exposure. Journal of the National Cancer Institute2002 (October 16); 94(20):1555–63. (RERF Report 14-01)
Sasaki H, Wong FL, Yamada M, Kodama K. The effects of aging and radiation exposure on bloodpressure levels of atomic bomb survivors. Journal of Clinical Epidemiology 2002 (October);55(10):974–81. (RERF Report 9-00) (JTr)
Sauvaget C, Allen N, Hayashi M, Spencer E, Nagano
J. Validation of a food frequency questionnaire in
the Hiroshima/Nagasaki Life Span Study. Journalof Epidemiology 2002 (September); 12(5):394–
401. (RERF Report 4-02)
Sauvaget C, Yamada M, Fujiwara S, Sasaki H,
Mimori Y. Dementia as a predictor of functional
disability: A four-year follow-up study. Gerontology 2002 (July–August); 48(4):226–33. (RERF
Report 6-01)
Sharp GB. The relationship between internally deposited alpha-particle radiation and subsite-specific liver cancer and liver cirrhosis: an analysis
of published data. Journal of Radiation Research
2002 (December); 43(4):371–80. (RERF Report
6-02)
Sharp GB. Does radiation cause liver cancer? Comparison of radiation effects in atomic bomb survivors and other populations. International Congress
Series 1236. Amsterdam, Netherland: Elsevier
Science B.V.; 2002, pp 59–66. (Proceedings ofthe International Symposium on Radiation andHomeostasis)
RERF Update Volume 14, Issue 1, Spring 2003

Recent Publications
Suyama A, Shiota G. Utilization of statistical software: How to apply data correctly. EBM Journal
2002 (February); 3(2):236–44. (Japanese)
Suyama A, Soda M. Epidemiological index related
to radiation epidemiology: mortality, incidence,and prevalence rates. Hoshasen Kagaku [Radiological Sciences] 2003 (February); 46(2):38–43.
(Japanese)
Suzuki G, Akahoshi M, Fujiwara S, Neriishi K,
Yamada M, Hakoda M. Radiation effect on noncancer diseases among A-bomb survivors.
AOCRP-1 Secretariat, ed. Proceedings of the First
Asian and Oceanic Congress for Radiation Protection (AOCRP-1) [CD-ROM]. Seoul, Korea:
AOCRP-1 Secretariat; 2002 (October), Session/
OP-1c/OP-1c-1.

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Yamamoto Y, Ohta M, Urabe T, Hakoda M, Koyama
K, Nakaoka K, Shiraga K, Ogata S, Tokita D,
Shiroyama Y, Watanabe T, Shinoda H, Sumi K,
Fukushima T, Fukumoto J, Narui S, Sanada K.
Report on the results of the thirteenth medical
examination of atomic bomb survivors resident
in North America. Hiroshima Igaku [Journal of
the Hiroshima Medical Association] 2002 (May);
55(5):381–403. (Bilingual)Yokoyama N, Nagataki S, Uetani M, Ashizawa K,
Eguchi K. Role of magnetic resonance imaging
in the assessment of disease activity in thyroidassociated ophthalmopathy. Thyroid 2002
(March); 12(3):223–7.

Tahara E. Histone acetylation and retinoic acid receptor beta DNA methylation as novel targets for
gastric cancer therapy. Drug News and Perspectives 2002 (November); 15(9):1–5.
The Endogenous Hormones and Breast Cancer Collaborative Group (RERF: Neriishi K). Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. Journal of the National Cancer Institute 2002 (April 17); 94(8):606–16.
Tsuji I, Sauvaget C, Hisamichi S. Health expectancies in Japan: Gender differences and policy implications for women. Laditka SB, ed(s). Health
Expectations for Older Women: International Perspectives. New York: The Haworth Press; 2002,
pp 135–48
Vickers MA, Hoy T, Lake H, Kyoizumi S, Boyse J,
Hewitt M. Estimation of mutation rate at humanglycophorin A locus in hematopoietic stem cellprogenitors. Environmental and Molecular Mutagenesis 2002 (June); 39(4):333–41.
Yamada M, Izumi S. Psychiatric sequelae in atomic
bomb survivors in Hiroshima and Nagasaki two
decades after the explosions. Social Psychiatry andPsychiatric Epidemiology 2002 (September);37(9):409–15. (RERF Report 5-00)
Yamada M, Sasaki H, Kasagi F, Akahoshi M, Mimori
Y, Kodama K, Fujiwara S. Study of cognitive function among the Adult Health Study (AHS) population in Hiroshima and Nagasaki. Radiation Research 2002 (August); 158(2):236–40. (RERF
Report 12-01)
Yamada M, Wong FL, Suzuki G. Longitudinal trendsof hemoglobin levels in a Japanese population—
RERF’s Adult Health Study subjects. European
Journal of Haematology 2003; 70:129–35. (RERF
Report 15-02)
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RERF Update Volume 14, Issue 1, Spring 2003

Recent Publications

34

Publications Using RERF Data
The following publications represent research done
by non-RERF scientists based on the data publicly
available from RERF.
Little MP. Absence of evidence for differences in thedose-response for cancer and non-cancer endpoints by acute injury status in the Japaneseatomic-bomb survivors. International Journal of
Radiation Biology 2002; 78(11):1001–10.
Little MP. Cancer after exposure to radiation in thecourse of treatment for benign and malignant disease. Lancet Oncology 2001; 2:212–20.
Little MP. Comparison of the risks of cancer incidence and mortality following radiation therapy
for benign and malignant disease with the cancer
risks observed in the Japanese A-bomb survivors[published erratum appears in International Journal of Radiation Biology 2001; 77(6):745–60].
International Journal of Radiation Biology 2001;
77(4):431–64.
Little MP. Comparisons of lung tumour mortality riskin the Japanese A-bomb survivors and in the Colorado Plateau uranium miners: Support for the
ICRP lung model. International Journal of Radiation Biology 2002; 78(3):145–63.
Little MP. The proportion of thyroid cancers in theJapanese atomic bomb survivors associated withnatural background radiation. Journal of Radiological Protection 2002; 22(3):279–91.
McGeoghegan D, Binks K. The mortality and cancer morbidity experience of employees at theChapelcross plant of British Nuclear Fuels plc,
1955–95. Journal of Radiological Protection
2001; 21(3):221–50.
Radivoyevitch T, Hoel DG. Biologically-based risk
estimation for radiation-induced chronic myeloid
leukemia. Radiation and Environmental Biophysics 2000; 39(3):153–9.
Radivoyevitch T, Sachs RK, Nikiforov YE,
Nikiforova MN, Little MP. On target cell numbers in radiation-induced H4-RET mediated papillary thyroid cancer. Radiation and Environmental Biophysics 2001; 40:191–7.

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RERF Update Volume 14, Issue 1, Spring 2003