Accounting for Unfissioned Plutonium from the Trinity Atomic Bomb Test.

The Trinity test device contained about 6 kg of plutonium as its fission source, resulting in a fission yield of 21 kT. However, only about 15% of the Pu actually underwent fission. The remaining unfissioned plutonium eventually was vaporized in the fireball and after cooling, was deposited downwind from the test site along with the various fission and activation products produced in the explosion. Using data from radiochemical analyses of soil samples collected postshot (most many years later), supplemented by model estimates of plutonium deposition density estimated from reported exposure rates at 12 h postshot, we have estimated the total activity and geographical distribution of the deposition density of this unfissioned plutonium in New Mexico. A majority (about 80%) of the unfissioned plutonium was deposited within the state of New Mexico, most in a relatively small area about 30-100 km downwind (the Chupadera Mesa area). For most of the state, the deposition density was a small fraction of the subsequent deposition density of Pu from Nevada Test Site tests (1951-1958) and later from global fallout from the large US and Russian thermonuclear tests (1952-1962). The fraction of the total unfissioned Pu that was deposited in New Mexico from Trinity was greater than the fraction of fission products deposited. Due to plutonium being highly refractory, a greater fraction of the Pu was incorporated into large particles that fell out closer to the test site as opposed to more volatile fission products (such as Cs and I) that tend to deposit on the surface of smaller particles that travel farther before depositing. The plutonium deposited as a result of the Trinity test was unlikely to have resulted in significant health risks to the downwind population.

Methods and Findings on Diet and Lifestyle Used to Support Estimation of Radiation Doses from Radioactive Fallout from the Trinity Nuclear Test.

The Trinity nuclear test was detonated in south-central New Mexico on 16 July 1945; in the early 2000s, the National Cancer Institute undertook a dose and cancer risk projection study of the possible health impacts of the test. In order to conduct a comprehensive dose assessment for the Trinity test, we collected diet and lifestyle data relevant to the populations living in New Mexico around the time of the test. This report describes the methodology developed to capture the data used to calculate radiation exposures and presents dietary and lifestyle data results for the main exposure pathways considered in the dose reconstruction. Individual interviews and focus groups were conducted in 2017 among older adults who had lived in the same New Mexico community during the 1940s or 1950s. Interview questions and guided group discussions focused on specific aspects of diet, water, type of housing, and time spent outdoors for different age groups. Thirteen focus groups and 11 individual interviews were conducted among Hispanic, White, and Native American participants. Extensive written notes and audio recordings aided in the coding of all responses used to derive ranges, prevalence, means, and standard deviations for each exposure variable for various age categories by region and ethnicity. Children aged 11-15 y in 1940s or 1950s from the rural plains had the highest milk intakes (993 mL d), and lowest intakes were among 11- to 15-y-olds in mountainous regions (191 mL d). Lactose intolerance rates were 7-71%, and prevalence was highest among Native Americans. Meat was not commonly consumed in the summer in most communities, and if consumed, it was among those aged 11-15 y of age or older who had relatively small amounts of 100-200 g d. Most drinking and cooking water came from covered wells, and most homes were made of adobe, which provided more protection from external radiation than wooden structures. The use of multiple approaches to trigger memory and collect participant reports on diet and other factors from the distant past seemed effective. These data were summarized, and together with other information, these data have been used to estimate radiation doses for representative persons of all ages in the main ethnic groups residing in New Mexico at the time of the Trinity nuclear test.

The Likelihood of Adverse Pregnancy Outcomes and Genetic Disease (Transgenerational Effects) from Exposure to Radioactive Fallout from the 1945 Trinity Atomic Bomb Test.

The potential health consequences of the Trinity nuclear weapon test of 16 July 1945 at Alamogordo, New Mexico, are challenging to assess. Population data are available for mortality but not for cancer incidence for New Mexico residents for the first 25 y after the test, and the estimates of radiation dose to the nearby population are lower than the cumulative dose received from ubiquitous natural background radiation. Despite the estimates of low population exposures, it is believed by some that cancer rates in counties near the Trinity test site (located in Socorro County) are elevated compared with other locations across the state. Further, there is a concern about adverse pregnancy outcomes and genetic diseases (transgenerational or heritable effects) related to population exposure to fallout radiation. The possibility of an intergenerational effect has long been a concern of exposed populations, e.g., Japanese atomic bomb survivors, survivors of childhood and adolescent cancer, radiation workers, and environmentally exposed groups. In this paper, the likelihood of discernible transgenerational effects is discounted because (1) in all large-scale comprehensive studies of exposed populations, no heritable genetic effects have been demonstrated in children of exposed parents; (2) the distribution of estimated doses from Trinity is much lower than in other studied populations where no transgenerational effects have been observed; and (3) there is no evidence of increased cancer rates among the scientific, military, and professional participants at the Trinity test and at other nuclear weapons tests who received much higher doses than New Mexico residents living downwind of the Trinity site.

Estimated Radiation Doses Received by New Mexico Residents from the 1945 Trinity Nuclear Test.

The National Cancer Institute study of projected health risks to New Mexico residents from the 1945 Trinity nuclear test provides best estimates of organ radiation absorbed doses received by representative persons according to ethnicity, age, and county. Doses to five organs/tissues at significant risk from exposure to radioactive fallout (i.e., active bone marrow, thyroid gland, lungs, stomach, and colon) from the 63 most important radionuclides in fresh fallout from external and internal irradiation were estimated. The organ doses were estimated for four resident ethnic groups in New Mexico (Whites, Hispanics, Native Americans, and African Americans) in seven age groups using: (1) assessment models described in a companion paper, (2) data on the spatial distribution and magnitude of radioactive fallout derived from historical documents, and (3) data collected on diets and lifestyles in 1945 from interviews and focus groups conducted in 2015-2017 (described in a companion paper). The organ doses were found to vary widely across the state with the highest doses directly to the northeast of the detonation site and at locations close to the center of the Trinity fallout plume. Spatial heterogeneity of fallout deposition was the largest cause of variation of doses across the state with lesser differences due to age and ethnicity, the latter because of differences in diets and lifestyles. The exposure pathways considered included both external irradiation from deposited fallout and internal irradiation via inhalation of airborne radionuclides in the debris cloud as well as resuspended ground activity and ingestion of contaminated drinking water (derived both from rivers and rainwater cisterns) and foodstuffs including milk products, beef, mutton, and pork, human-consumed plant products including leafy vegetables, fruit vegetables, fruits, and berries. Tables of best estimates of county population-weighted average organ doses by ethnicity and age are presented. A discussion of our estimates of uncertainty is also provided to illustrate a lower and upper credible range on our best estimates of doses. Our findings indicate that only small geographic areas immediately downwind to the northeast received exposures of any significance as judged by their magnitude relative to natural radiation. The findings presented are the most comprehensive and well-described estimates of doses received by populations of New Mexico from the Trinity nuclear test.

The Methodology Used to Assess Doses from the First Nuclear Weapons Test (Trinity) to the Populations of New Mexico.

Trinity was the first test of a nuclear fission device. The test took place in south-central New Mexico at the Alamogordo Bombing and Gunnery Range at 05:29 AM on 16 July 1945. This article provides detailed information on the methods that were used in this work to estimate the radiation doses that were received by the population that resided in New Mexico in 1945. The 721 voting precincts of New Mexico were classified according to ecozone (plains, mountains, or mixture of plains and mountains), and size of resident population (urban or rural). Methods were developed to prepare estimates of absorbed doses from a range of 63 radionuclides to five organs or tissues (thyroid, active marrow, stomach, colon, and lung) for representative individuals of each voting precinct selected according to ethnicity (Hispanic, White, Native American, and African American) and age group in 1945 (in utero, newborn, 1-2 y, 3-7 y, 8-12 y, 13-17 y, and adult). Three pathways of human exposure were included: (1) external irradiation from the radionuclides deposited on the ground; (2) inhalation of radionuclide-contaminated air during the passage of the radioactive cloud and, thereafter, of radionuclides transferred (resuspended) from soil to air; and (3) ingestion of contaminated water and foodstuffs. Within the ingestion pathway, 13 types of foods and sources of water were considered. Well established models were used for estimation of doses resulting from the three pathways using parameter values developed from extensive literature review. Because previous experience and calculations have shown that the annual dose delivered during the year following a nuclear test is much greater than the doses received in the years after that first year, the time period that was considered is limited to the first year following the day of the test (16 July 1945). Numerical estimates of absorbed doses, based on the methods described in this article, are presented in a separate article in this issue.

Projected Cancer Risks to Residents of New Mexico from Exposure to Trinity Radioactive Fallout.

The Trinity nuclear test, conducted in 1945, exposed residents of New Mexico to varying degrees of radioactive fallout. Companion papers in this issue have detailed the results of a dose reconstruction that has estimated tissue-specific radiation absorbed doses to residents of New Mexico from internal and external exposure to radioactive fallout in the first year following the Trinity test when more than 90% of the lifetime dose was received. Estimated radiation doses depended on geographic location, race/ethnicity, and age at the time of the test. Here, these doses were applied to sex- and organ-specific risk coefficients (without applying a dose and dose rate effectiveness factor to extrapolate from a population with high-dose/high-dose rates to those with low-dose/low-dose rates) and combined with baseline cancer rates and published life tables to estimate and project the range of radiation-related excess cancers among 581,489 potentially exposed residents of New Mexico. The total lifetime baseline number of all solid cancers [excluding thyroid and non-melanoma skin cancer (NMSC)] was estimated to be 183,000 from 1945 to 2034. Estimates of ranges of numbers of radiation-related excess cancers and corresponding attributable fractions from 1945 to 2034 incorporate various sources of uncertainty. We estimated 90% uncertainty intervals (UIs) of excess cancer cases to be 210 to 460 for all solid cancers (except thyroid cancer and NMSC), 80 to 530 for thyroid cancer, and up to 10 for leukemia (except chronic lymphocytic leukemia), with corresponding attributable fractions ranging from 0.12% to 0.25%, 3.6% to 20%, and 0.02% to 0.31%, respectively. In the counties of Guadalupe, Lincoln, San Miguel, Socorro, and Torrance, which received the greatest fallout deposition, the 90% UI for the projected fraction of thyroid cancers attributable to radioactive fallout from the Trinity test was estimated to be from 17% to 58%. Attributable fractions for cancer types varied by race/ethnicity, but 90% UIs overlapped for all race/ethnicity groups for each cancer grouping. Thus, most cancers that have occurred or will occur among persons exposed to Trinity fallout are likely to be cancers unrelated to exposures from the Trinity nuclear test. While these ranges are based on the most detailed dose reconstruction to date and rely largely on methods previously established through scientific committee agreement, challenges inherent in the dose estimation, and assumptions relied upon both in the risk projection and incorporation of uncertainty are important limitations in quantifying the range of radiation-related excess cancer risk.

Risk of lung adenocarcinoma from smoking and radiation arises in distinct molecular pathways.

KRAS mutations of lung adenocarcinoma (LADC) are associated with smoking but little is known on other exposure-oncogene associations. Hypothesizing that different inciting agents may cause different driver mutations, we aimed to identify distinct molecular pathways to LADC, applying two entirely different approaches. First, we examined clinicopathologic features and genomic signatures of environmental exposures in the large LADC Campbell data set. Second, we designed a molecular mechanistic risk model of LADC (M3LADC) that links environmental exposure to incidence risk by mathematically emulating the disease process. This model was applied to incidence data of Japanese atom-bomb survivors which contains information on radiation and smoking exposure. Grouping the clinical data by driver mutations revealed two main distinct molecular pathways to LADC: one unique to transmembrane receptor-mutant patients that displayed robust signatures of radiation exposure and one shared between submembrane transducer-mutant patients and patients with no evident driver mutation that carried the signature of smoking. Consistently, best fit of the incidence data was achieved with a M3LADC with two pathways: in one LADC risk increased with radiation exposure and in the other with cigarette consumption. We conclude there are two main molecular pathways to LADC associated with different environmental exposures. Future molecular measurements in lung cancer tissue of atom-bomb survivors may allow to further test quantitatively the M3LADC-predicted link of radiation to transmembrane receptor mutations. Moreover, the developed molecular mechanistic model showed that for low doses, as relevant e.g. for medical imaging, smokers have the same radiation risk compared with never smokers.

Selection of reference groups in the Life Span Study of atomic bomb survivors.

In cohort studies, unbiased estimation of exposure-outcome associations requires selection of an appropriate reference group of unexposed individuals. We illustrate strategies for analyzing cohort data with multiple potential reference groups. We analyzed the association between radiation exposure and incidence of first primary solid cancer among 105,444 participants of the Life Span Study (Hiroshima and Nagasaki, Japan, 1958-2009). Potential reference groups included zero-dose survivors at different ground distances from the hypocenter (internal) and city residents who were not in either city at the time of the bombings (external). DS02R1 weighted absorbed colon doses were estimated by the DS02 dosimetry system. Piecewise constant hazard models estimated excess relative risks of first primary solid cancer. We focused on sex-averaged excess relative risks and the shape of the dose-response curve. A model with internal standardization provided a sex-averaged excess relative risk of 0.510, 95% confidence interval: (0.414, 0.612) per gray of weighted absorbed colon dose, as well as strong evidence of a curvilinear dose response among males (P = 0.008). Selection of not-in-city residents as the reference group resulted in a larger excess relative risk of 0.560, 95% confidence interval: (0.467, 0.657) per gray, and reduced evidence of a curvilinear dose response among males (P = 0.042). These differences were particularly apparent at weighted absorbed colon doses < 1 gray. In cohort studies, selection of an appropriate reference group requires understanding of the nature of unmeasured confounding to which the results could be sensitive.

Solid Cancer Incidence among the Life Span Study of Atomic Bomb Survivors: 1958-2009.

This is the third analysis of solid cancer incidence among the Life Span Study (LSS) cohort of atomic bomb survivors in Hiroshima and Nagasaki, adding eleven years of follow-up data since the previously reported analysis. For this analysis, several changes and improvements were implemented, including updated dose estimates (DS02R1) and adjustment for smoking. Here, we focus on all solid cancers in aggregate. The eligible cohort included 105,444 subjects who were alive and had no known history of cancer at the start of follow-up. A total of 80,205 subjects had individual dose estimates and 25,239 were not in either city at the time of the bombings. The follow-up period was 1958-2009, providing 3,079,484 person-years of follow-up. Cases were identified by linkage with population-based Hiroshima and Nagasaki Cancer Registries. Poisson regression methods were used to elucidate the nature of the radiation-associated risks per Gy of weighted absorbed colon dose using both excess relative risk (ERR) and excess absolute risk (EAR) models adjusted for smoking. Risk estimates were reported for a person exposed at age 30 years with attained age of 70 years. In this study, 22,538 incident first primary solid cancer cases were identified, of which 992 were associated with radiation exposure. There were 5,918 cases (26%) that occurred in the 11 years (1999-2009) since the previously reported study. For females, the dose response was consistent with linearity with an estimated ERR of 0.64 per Gy (95% CI: 0.52 to 0.77). For males, significant upward curvature over the full dose range as well as restricted dose ranges was observed and therefore, a linear-quadratic model was used, which resulted in an ERR of 0.20 (95% CI: 0.12 to 0.28) at 1 Gy and an ERR of 0.010 (95% CI: -0.0003 to 0.021) at 0.1 Gy. The shape of the ERR dose response was significantly different among males and females (P = 0.02). While there was a significant decrease in the ERR with increasing attained age, this decrease was more rapid in males compared to females. The lowest dose range that showed a statistically significant dose response using the sex-averaged, linear ERR model was 0-100 mGy (P = 0.038). In conclusion, this analysis demonstrates that solid cancer risks remain elevated more than 60 years after exposure. Sex-averaged upward curvature was observed in the dose response independent of adjustment for smoking. Findings from the current analysis regarding the dose-response shape were not fully consistent with those previously reported, raising unresolved questions. At this time, uncertainties in the shape of the dose response preclude definitive conclusions to confidently guide radiation protection policies. Upcoming results from a series of analyses focusing on the radiation risks for specific organs or organ families, as well as continued follow-up are needed to fully understand the nature of radiation-related cancer risk and its public health significance. Data and analysis scripts are available for download at: http://www.rerf.or.jp .

Lung, Laryngeal and Other Respiratory Cancer Incidence among Japanese Atomic Bomb Survivors: An Updated Analysis from 1958 through 2009.

The Life Span Study (LSS) of Japanese atomic bomb survivors is comprised of a large, population-based cohort offering one of the best opportunities to study the relationship between exposure to radiation and incidence of respiratory cancers. Risks of lung, laryngeal and other cancers of the respiratory system were evaluated among 105,444 LSS subjects followed from 1958 to 2009. During this period, we identified 2,446 lung, 180 laryngeal and 115 other respiratory (trachea, mediastinum and other ill-defined sites) first primary incident cancer cases. Ten additional years of follow-up, improved radiation dose estimates, revised smoking data, and updated migration information were used to investigate the joint effects of radiation and smoking using Poisson regression methods. For nonsmokers, the sex-averaged excess relative risk per Gy (ERR/Gy) for lung cancer (at age 70 after radiation exposure at age 30) was estimated as 0.81 (95% CI: 0.51, 1.18) with a female-to-male ratio of 2.83. There was no evidence of curvature in the radiation dose-response relationship overall or by sex. Lung cancer risks increased with pack-years of smoking and decreased with time since quitting smoking at any level of radiation exposure. Similar to the previously reported study, which followed cohort members through 1999, the ERR/Gy for lung cancer was significantly higher for low-to-moderate smokers than for heavy smokers, with little evidence of any radiation-associated excess risk in heavy smokers. Of 2,446 lung cancer cases, 113 (5%) could be attributed to radiation exposure. Of the 1,165 lung cancer cases occurring among smokers, 886 (76%) could be attributed to smoking. While there was little evidence of a radiation effect for laryngeal cancer, a nonsignificantly elevated risk of other respiratory cancers was observed. However, significant smoking effects were observed for both laryngeal (ERR per 50 pack-years = 23.57; 95% CI: 8.44, 71.05) and other respiratory cancers (ERR per 50 pack-years = 1.21; 95% CI: 0.10, 3.25).

DS02R1: Improvements to Atomic Bomb Survivors' Input Data and Implementation of Dosimetry System 2002 (DS02) and Resulting Changes in Estimated Doses.

Individual dose estimates calculated by Dosimetry System 2002 (DS02) for the Life Span Study (LSS) of atomic bomb survivors are based on input data that specify location and shielding at the time of the bombing (ATB). A multi-year effort to improve information on survivors' locations ATB has recently been completed, along with comprehensive improvements in their terrain shielding input data and several improvements to computational algorithms used in combination with DS02 at RERF. Improvements began with a thorough review and prioritization of original questionnaire data on location and shielding that were taken from survivors or their proxies in the period 1949-1963. Related source documents varied in level of detail, from relatively simple lists to carefully-constructed technical drawings of structural and other shielding and surrounding neighborhoods. Systematic errors were reduced in this work by restoring the original precision of map coordinates that had been truncated due to limitations in early data processing equipment and by correcting distortions in the old (WWII-era) maps originally used to specify survivors' positions, among other improvements. Distortion errors were corrected by aligning the old maps and neighborhood drawings to orthophotographic mosaics of the cities that were newly constructed from pre-bombing aerial photographs. Random errors that were reduced included simple transcription errors and mistakes in identifying survivors' locations on the old maps. Terrain shielding input data that had been originally estimated for limited groups of survivors using older methods and data sources were completely re-estimated for all survivors using new digital terrain elevation data. Improvements to algorithms included a fix to an error in the DS02 code for coupling house and terrain shielding, a correction for elevation at the survivor's location in calculating angles to the horizon used for terrain shielding input, an improved method for truncating high dose estimates to 4 Gy to reduce the effect of dose error, and improved methods for calculating averaged shielding transmission factors that are used to calculate doses for survivors without detailed shielding input data. Input data changes are summarized and described here in some detail, along with the resulting changes in dose estimates and a simple description of changes in risk estimates for solid cancer mortality. This and future RERF publications will refer to the new dose estimates described herein as "DS02R1 doses."

Circulating Hematopoietic Stem and Progenitor Cells in Aging Atomic Bomb Survivors.

It is not yet known whether hematopoietic stem and progenitor cells (HSPCs) are compromised in the aging population of atomic bomb (A-bomb) survivors after their exposure nearly 70 years ago. To address this, we evaluated age- and radiation-related changes in different subtypes of circulating HSPCs among the CD34-positive/lineage marker-negative (CD34(+)Lin(-)) cell population in 231 Hiroshima A-bomb survivors. We enumerated functional HSPC subtypes, including: cobblestone area-forming cells; long-term culture-initiating cells; erythroid burst-forming units; granulocyte and macrophage colony-forming units; and T-cell and natural killer cell progenitors using cell culture. We obtained the count of each HSPC subtype per unit volume of blood and the proportion of each HSPC subtype in CD34(+)Lin(-) cells to represent the lineage commitment trend. Multivariate analyses, using sex, age and radiation dose as variables, showed significantly decreased counts with age in the total CD34(+)Lin(-) cell population and all HSPC subtypes. As for the proportion, only T-cell progenitors decreased significantly with age, suggesting that the commitment to the T-cell lineage in HSPCs continuously declines with age throughout the lifetime. However, neither the CD34(+)Lin(-) cell population, nor HSPC subtypes showed significant radiation-induced dose-dependent changes in counts or proportions. Moreover, the correlations of the proportions among HSPC subtypes in the survivors properly revealed the hierarchy of lineage commitments. Taken together, our findings suggest that many years after exposure to radiation and with advancing age, the number and function of HSPCs in living survivors as a whole may have recovered to normal levels.

Developing a Nuclear Global Health Workforce Amid the Increasing Threat of a Nuclear Crisis.

This study argues that any nuclear weapon exchange or major nuclear plant meltdown, in the categories of human systems failure and conflict-based crises, will immediately provoke an unprecedented public health emergency of international concern. Notwithstanding nuclear triage and management plans and technical monitoring standards within the International Atomic Energy Agency and the World Health Organization (WHO), the capacity to rapidly deploy a robust professional workforce with the internal coordination and collaboration capabilities required for large-scale nuclear crises is profoundly lacking. A similar dilemma, evident in the early stages of the Ebola epidemic, was eventually managed by using worldwide infectious disease experts from the Global Outbreak Alert and Response Network and multiple multidisciplinary WHO-supported foreign medical teams. This success has led the WHO to propose the development of a Global Health Workforce. A strategic format is proposed for nuclear preparedness and response that builds and expands on the current model for infectious disease outbreak currently under consideration. This study proposes the inclusion of a nuclear global health workforce under the technical expertise of the International Atomic Energy Agency and WHO's Radiation Emergency Medical Preparedness and Assistance Network leadership and supported by the International Health Regulations Treaty. Rationales are set forth for the development, structure, and function of a nuclear workforce based on health outcomes research that define the unique health, health systems, and public health challenges of a nuclear crisis. Recent research supports that life-saving opportunities are possible, but only if a rapidly deployed and robust multidisciplinary response component exists.