Received by the Atomic Bomb Survivors in 1945 Japan
By, Dr. Wesley Bolch, Distinguished Professor
A little background of the discovery and immediate medical uses of ionizing radiation
Ionizing radiation has been used in medical imaging and radiotherapy virtually since the time of its discovery. In December of 1895, Wilhelm Roentgen announced details of what was later termed “x-rays” produced by a cathode-ray tube constructed in his laboratory at the University of Wuerzburg in Germany. Later that same month, he produced the world’s first radiograph – that of his wife Bertha’s hand visualizing her hand bones and wedding ring. In January of 1896, x-rays were used in the first ever treatment of breast cancer in the United States, while concurrently in France, x-rays were used in the first ever treatment of stomach cancer. In 1989, radioactive atoms in uranium ore were discovered by Henri Becquerel, which were later denoted as “radioactivity” by Marie Curie, who herself went on to discover the element radium in 1898. In 1901, Henri Danlos and Eugene Bloch used radium in the treatment of a tuberculous skin lesion, and in 1913, Frederick Proescher published the first ever study on the intravenous injection of radium for the treatment of various diseases including arthritis.
The need to balance beneficial uses and harmful effects of ionizing radiation
Over the early decades of the 1900s, however, the medical and industrial uses of radiation and radioactivity unveiled the associated hazards of radiation exposure to include skin ulceration, leukemia, and for high intakes of radium, bone cancer and even skeletal fractures. These observations accelerated the science and engineering of radiological protection beginning in the1920s which lead to the fundamental principles of time, distance, and shielding to lower exposures, and to the construction of ionization chambers which allowed the safe measure of rates of radiation energy deposition in both air and tissue. It quickly became apparent that the life-saving beneficial uses of radiation and radioactivity in medical imaging and therapy had to be optimized to avoid life-threatening acute and long-term biological effects of radiation exposure. Questions arose, however, regarding what were “safe” levels of radiation tissue dose and how do radiation risks change with the exposed person’s age and sex? Also, how did these risks vary with the individual organs exposed? Animal experimentation could answer some of these questions, yet the study of populations of humans accidentally or intentionally exposed – radiation epidemiology studies – would be the most definitive means by which these questions would be answered, and that in turn their study results would lead to systems of radiological protection that struck a balance between benefit and risk.
The role of radiation epidemiology studies in quantifying radiation cancer risks / Atomic Bombings
Radiation epidemiology studies include a range of scenarios by which humans have been exposed to various forms of radiation. These have included studies of nuclear power plant workers, populations living in unusually high levels of natural background radiations, patients treated with early forms of external and internal radiation sources, and populations exposed to radionuclides released from nuclear reactor accidents such as at Chernobyl in northern Ukraine. Nevertheless, it is widely acknowledged that the “gold standard” radiation epidemiology study – one used as a comparator for all other studies of radiation cancer risk – is the multi-decade follow-up study of the survivors of the atomic bombings in Hiroshima and Nagasaki, Japan, in August 6 and 9, 1945, respectively. That study includes 93,741 children and adults that survived the initial bombings at both cities, and 2,355 surviving pregnant females. While the moral, strategic, and political reasons and justifications for these bombings have long been and continue to be debated, the scientific knowledge of radiation’s ability to induce cancer gained from the careful and compassionate medical surveillance of the survivors has led to the more proper use of ionizing radiation in the advancement of disease detection, and ironically, the eradication of cancer itself in hundreds of millions of patients worldwide. The power of the atomic bomb survivor study managed by the Radiation Effects Research Foundation (RERF) in Hiroshima, Japan – which is jointly funded by the Japanese and the United States governments – derives from the fact that the survivors included males and female of all ages, including those exposed in-utero, and owing to the distance from the bomb hypocenter to the location of their exposure, these survivors experienced a large range of radiation doses, even down to the levels currently used in medical CT imaging. Medical follow up of the survivors – now over 7 decades in extent – include reporting of a range of time-dependent cancer diagnoses, but also radiation-induced cataracts, and most recently, radiation-induced cardiovascular disease.
Brief history of US-Japan efforts to go back in time and estimate survivor organ doses
The ultimate goal of these studies is to quantify the risk of biological effect as a function of the organ irradiated and individual-specific parameters such as sex, age at exposure, and attained age at time of bioeffect. A key feature of these biostatistical analyses is therefore answering the question – “what was the radiation dose to each organ in each survivor delivered acutely at the time of bomb detonation in December 1945?” To answer this question, U.S. and Japanese researchers have undertaken several major attempts at going back in time to reconstruct individual survivor organ doses.
In 1957, the very first estimates of survivor radiation dose were made using theoretical models of the intensities, energies, and directions of gamma-rays and neutrons emerging from the two atomic bombs. Next, researchers estimated the dose to air at each survivor location based on knowledge of the ground distance from the bomb detonation site, with some consideration of local shielding of houses and buildings.
The next major update of organ doses to the atomic bomb survivors was made in 1965 where heavy reliance was made of experimental measurements of radiation dose in the United States southwestern desert. A pulsed nuclear reactor perched upon a tall scaffold was used to mimic the in-air atomic bomb detonation, with radiation dose measurement devices inserted within human mannikins placed at various distances within reconstructed Japanese houses. One problem with this approach was the lack of air humidity present in the US Southwest which was present over 1945 Japan. Water vapor can significantly slow down neutrons emitted from the atomic bombs and thus energies of the neutrons reaching the atomic bomb survivors
The next major update of organ doses in the atomic bomb survivors was in 1986. This dosimetry system – DS86 – was a momentous achievement in that all organ doses were estimated for the first time, not primarily by experiment as in 1965, but through the use of modern Monte Carlo radiation transport models. The DS86 system had four modules. The first simulated the atomic bomb explosions and both the prompt and delayed release of gamma-rays and neutrons, along with their emission directions and energies. The second module, also by computer simulation, followed those gamma-rays and neutrons through the air and local terrain including hills and mountains. The third module then computationally followed the radiation fields through building materials to include houses in both cities, and in Nagasaki, the factories where torpedoes and other weapons were being assembled. The fourth and final module followed the radiation fields into the body tissues and organs of the survivors themselves
In the 1980s, radiation transport simulations were slow (by today’s standards) and they were costly (one had to actually pay for each CPU-hour of computer time). Consequently, the 3D computerized anatomic models of the atomic bomb survivors used at the time were what are termed stylized models in which the outer body contours and even the internal organ surfaces are descriptively limited to 3D geometric shapes such as spheres, ellipsoids, toroids, and truncated cones (see Figure 1). Furthermore, only three such models were employed by DS86 as shown in Figure 1 – a 55 kg model representing all survivors from age 12 years to adults, a 19.8 kg model representing all survivors ages 3 to 12 years, and a 9.7 kg model representing newborns to 3 year-olds. Furthermore, each of these stylized models were hermaphrodites – that is, they included both sets of sex organs and were used both for male and female survivors in those age ranges. Note that a very important survivor category was missing – the pregnant female. No such model was developed nor used, and thus the radiation dose to the fetus within an exposed pregnant female was assessed using the uterine wall as a dose surrogate in the adult non-pregnant stylized model.
The last major update to the RERF official database of organ doses for the atomic bomb survivors was made in 2002 – the DS02 dosimetry system. In this joint US-Japan study, many lingering questions were addressed such as (1) what was the height above the ground in Hiroshima and Nagasaki when the atomic weapons were detonated, (2) how can we improve our modeling of the housing and factory structures that provided local shielding of some of the survivors within these structures, and (3) how can we use more recent data on neutron-induced radioactivity – Eu-152 and Co-60 in building materials – to validate our assumptions on the gamma and neutron yields of the two atomic bombs? All of these questions were addressed in the moving from the DS86 to the DS02 dosimetry system. However, due to lack of funding and time, that fourth module – the one that followed these radiation particles into the computerized anatomic models of the survivors – was not updated but instead was carried forward to DS02 from DS86 system.
New anatomic models of the atomic bomb survivors developed at UF and NCI
Which brings us to the present day. In 2017, RERF established a Working Group on Organ Dose to provide an update to the DS02 dosimetry system in terms of more modern and anatomically realistic 3D models of the human bodies of the 1945 Japan atomic bomb survivors. The Working Group was Chaired by Professor Wesley Bolch of the J. Crayton Pruitt Family Department of Biomedical Engineering. Joining the Working Group was Choonsik Lee of the National Cancer Center (NCI) (former postdoctoral researcher in the Bolch Laboratory) and Tatsuhiko Sato of the Japan Atomic Energy Agency (JAEA). For the course of a three-year period, the Working Group – to include Bolch doctoral students Colin Paulbeck, Sean Domal, and Camilo Correa-Alfonso – developed a series of hybrid computational phantoms – male and female of ages 0, 5, 10, 15, and 35 years (adults) – that matched known mean heights and weights of the mid-century Japan population (see Figure 2). Furthermore, in work lead by Colin Paulbeck and later extended by Sean Domal – four new adult pregnant females phantoms were created at 8-week, 15-week, 25-week, and 38-week post-conception (see Figures 3 and 4). The fetal models themselves are state-of-the-art and include all major internal organs and tissues, to include developing fetal bone. The Working Group has documented their development and demonstrated that the movement from the three hermaphrodite stylized phantoms to the full complement of J45 adult, children, and pregnant female phantoms will have significant impact on the estimates of internal organ and fetal dose needed to establish dose-dependent cancer risk models moving forward.
Griffin K, Paulbeck CG, Bolch WE, Cullings H, Egbert S, Funamoto S, Sato T, Endo A, Hertel N, and Lee C, “Dosimetric impact of a new computational voxel phantom series for the Japanese atomic bomb survivors: children and adults”, Radiat Res 191: 369-379 (2019). [PMID: 30779693]
Paulbeck CG, Griffin K, Lee C, Cullings H, Egbert SD, Funamoto S, Sato T, Endo A, Hertel N, and Bolch WE, “Dosimetric impact of a new computational voxel phantom series for the Japanese atomic bomb survivors: Pregnant females”, Radiat Res 192: 538-561 (2019). [PMID: 31469615]
Sato T, Funamoto S, Paulbeck CG, Griffin K, Lee C, Cullings H, Egbert SD, Endo A, Hertel N, Bolch WE, “Dosimetric impact of a new computational voxel phantom series for the Japanese atomic bomb survivors: Methodological improvements and organ dose response functions”, Radiat Res 194: 390-402 (2020). [PMID: 33045092]
Griffin KT, Sato T, Funamoto S, Chizhov K, Domal SG, Paulbeck CA, Bolch WE, Cullings HM, Egbert SD, Endo A, Hertel N, and Lee C, “Japanese pediatric and adult atomic bomb survivor dosimetry using the J45 phantom series: Comprehensive source term modelling”, Radiat Env Biophys 61:73-86 (2022) – AOP October 30, 2021. [PMID: 34718851]
RERF decision to move forward with major update of organ dosimetry of the atomic bomb survivors
On April 8 of this year, the Working Group formally presented their work to key governmental representatives of the Japan Ministry of Health, Labor, and Welfare and the United States Department of Energy. Following this meeting, RERF made the decision to move forward with another major effort to refine their estimates of radiation organ dose received by these 96,000 atomic bomb survivors. In this new effort, all estimates of organ dose will be modeled using the anatomical models created at the University of Florida and the National Cancer Institute using new computational dosimetry methods pioneered at the Japan Atomic Energy Agency.
The world community continues to hold strong interest in learning what are the cancer risks of radiation exposure so that they may be properly balanced with the immense benefits of ionizing radiation in the imaging and cancer radiotherapy. Work by RERF in the coming years, with a revised and more accurate database on survivor organ dose, will have significant impacts across occupational, environmental, and medical radiological protection programs. It is the hope of all of us that the human race will never see again the use of atomic weapons, and thus we are immensely grateful for the scientific knowledge provided by these survivors of the Hiroshima and Nagasaki bombings.
Figure 1. Surface images of the three stylized hermaphrodite computational phantoms used to represent all Japanese Atomic Bomb Survivors – including the pregnant female – in both the 1986 and 2002 RERF studies of survivor organ dose. A total of only 15 organs and tissues were modeled within these three phantoms, and thus RERF cancer risk modelers have had over the decades to rely upon the use of surrogate organs (e.g., use of the urinary bladder wall as a dose surrogate for the male prostate gland).
Figure 2. Series of J45 human computational phantoms of adult and pediatric males and females developed at the University of Florida, in collaboration with the Radiation Epidemiology Branch of the National Cancer Institute, in use currently to reassess individual organ doses for all 96,000 atomic bomb survivors. Each of these phantoms now includes more than 80 different organs and tissues, thus negating the need to assign dose surrogate tissues – a major issue with the older stylized models.
Figure 3. Series of J45 pregnant female phantoms at four different stages of pregnancy post-conception. Each fetal model include 50 explicitly defined models of internal soft tissue organs and partially ossified bones of the skeleton.
Figure 4. Roughly one-third of all Atomic Bomb Survivors were in a kneeling posture at the time they were exposed to the radiations from the bomb detonations. The newer mesh-based modeling techniques of the J45 phantom series allows each member to be repositioned from its original standing posture to a realistic placement of the arms and legs of a kneeling posture.