HIGHLIGHTS OF THE RUSSIAN HEALTH STUDIES PROGRAM AND UPDATED RESEARCH FINDINGS

Abstract

Recognized for conducting cutting-edge science in the field of radiation health effects research, the Department of Energy's (DOE) Russian Health Studies Program has continued to generate excitement and enthusiasm throughout its 23-year mission to assess worker and public health risks from radiation exposure resulting from nuclear weapons production activities in the former Soviet Union. The three goals of the Program are to: (1) clarify the relationship between health effects and chronic, low-to-medium dose radiation exposure; (2) estimate the cancer risks from exposure to gamma, neutron, and alpha radiation; and (3) provide information to the national and international organizations that determine radiation protection standards and practices. Research sponsored by DOE's Russian Health Studies Program is conducted under the authority of the Joint Coordinating Committee for Radiation Effects Research (JCCRER), a bi-national committee representing Federal agencies in the United States and the Russian Federation. Signed in 1994, the JCCRER Agreement established the legal basis for the collaborative research between USA and Russian scientists to determine the risks associated with working at or living near Russian former nuclear weapons production sites. The products of the Program are peer-reviewed publications on cancer risk estimates from worker and community exposure to ionizing radiation following the production of nuclear weapons in Russia. The scientific return on investment has been substantial. Through 31 December 2015, JCCRER researchers have published 299 peer-reviewed publications. To date, the research has focused on the Mayak Production Association (Mayak) in Ozersk, Russia, which is the site of the first Soviet nuclear weapons production facility, and people in surrounding communities along the Techa River. There are five current projects in the Russian Health Studies Program: two radiation epidemiology studies; two historical dose reconstruction studies and a worker biorepository. National and international standard-setting organizations use cancer risk estimates computed from epidemiological and historical dose reconstruction studies to validate or revise radiation protection standards. An overview of the most important research results will be presented.

INTRODUCTION

The 14th International Congress of the International Radiation Protection Association Meeting was held at the International Convention Centre in Cape Town, South Africa from 9 to 13 May 2016. On May 10, Department of Energy (DOE) sponsored a special scientific session on the Russian Health Studies Program. The DOE Program Manager of the Office of Domestic and International Health Studies (AU-13) served as Chairperson of the special scientific session on the Russian Health Studies Program and delivered the lead presentation. Thirteen scientific abstracts for oral presentations were submitted and approved, along with 12 manuscripts for publication. One manuscript was published elsewhere. This paper provides an overview of the Russian Health Studies Program and leads the series of papers that will be published in this journal. The papers in this journal will follow the order in which the presentations were delivered during the special scientific session on May 10. Participation of US, Russian and UK researchers in the IRPA 14th International Congress showcased the most recent scientific results from projects within the Russian Health Studies Program and their impact on radiation protection standards and practices.

Current radiation protection standards are mainly based on high-quality data from studies of the Survivors of the Atomic Bombing in Japan and on patients who received medical radiotherapy treatments. For many years, DOE has been a leader in sponsoring extramural radiation health effects research, not only in Japan, but also in the Marshall Islands, Spain, Russia and Chernobyl.

BACKGROUND

The chernobyl nuclear power plant accident resulted in renewed interest in radiation health effects research

Thirty years ago this week, on 26 April 1986, the explosion at the Chernobyl Nuclear Power Plant northern Ukraine near the southern border of Belarus occurred. This accident caused reactor number 4 to burn for 10 days. As a consequence, over 10 million Curies of radiation from 50 tons of radioactive dust were dispersed over 140 000 square miles of Belarus, Ukraine, and Russia, and 4.9 million people were estimated to have been exposed to radiation. To date, this was the worst nuclear power plant accident in terms of environmental releases of radionuclides, especially ¹³¹iodine, ¹³⁷cesium, and ⁹⁰strontium. Seventy percent of the radionuclides went northeast towards Belarus and Russia. In addition to the general population, 600 000–800 000 Ukrainian remediation workers, known as liquidators, were exposed. These workers took part in abating the radioactive contamination at the site.

Of course, both the severity of the accident and the volume of radionuclide releases spurred renewed interest in the adverse health effects of ionizing radiation on human health. By its size, dose distribution and accessibility, the Chernobyl population provided an opportunity to consider the risks of developing thyroid cancer, leukemia and cataracts following exposure to radiation.

DOE's Chernobyl Radiation Health Effects Research Program

Under the auspices of the Joint Coordinating Committee for Civilian Nuclear Reactor Safety (JCCCNRS) between the United States and the former Soviet Union, DOE sponsored the Chernobyl Radiation Health Effects Research Program. The JCCCNRS was established by a bilateral agreement signed on 26 April 1988 between the United States and the former Soviet Union to study the health consequences of the Chernobyl accident on 26 April 1986. After the dissolution of the Soviet Union in 1991, the United States signed separate agreements with Belarus and Ukraine to continue these projects.

The research projects in this Program focused on people living in areas affected by the plume in northern Ukraine and Belarus and in Ukrainian liquidators. With the US National Cancer Institute (NCI), DOE co-sponsored a thyroid study in Belarus and a parallel study in Ukraine in those who were less than 18 at the time of the Chernobyl accident in 1986 and a leukemia study in the Ukrainian liquidators. These three studies were managed by NCI. In addition, DOE independently sponsored and managed an ocular cataract study in Ukrainian liquidators⁽¹⁾, the results of which led to recommendations from the International Council on Radiation Protection (ICRP) and the National Council for Radiation Protection and Measurements (NCRP) to reduce the annual worker dose limit of the beta dose to the lens of the eye.

The goal of the research from these four projects was to provide information on radiation effects with the aim of developing guidance for radiation protection and public health policies near operational nuclear reactors. Knowledge gained from these studies helped to provide guidance for radiation protection and public health policies for DOE workers and communities around DOE sites and commercial nuclear reactors.

DOE'S RUSSIAN HEALTH STUDIES PROGRAM

Background

The magnitude of the releases and exposures from the Chernobyl accident let to increased interest in the adverse effects of ionizing radiation on human health and the environment, not just around nuclear power plants, but also around nuclear weapons production plants. After the dissolution of the former Soviet Union in 1991, there began a renewed interest in studying adverse health effects at former Soviet nuclear weapons production sites, which had been studied since the early 1950s by scientists at the Federal Medical Biophysical Center (FMBC) in Moscow, the Southern Urals Biophysics Institute (SUBI) in Ozersk, and at the Urals Research Center for Radiation Medicine (URCRM) in Chelyabinsk.

For many years, DOE funded research across DOE former weapons production sites in the United States, but no consistent pattern of cancer emerged across the sites either in workers or in residents in communities surrounding these sites. This was primarily due to lower exposure levels and therefore lower observed cancer risks. Thus, a decision was made to study the risks of ionizing radiation which occurred from occupational and environmental exposures from Mayak, the first Soviet nuclear weapons production facility located in the formerly secret and still closed city of Ozersk in the Southern Urals region of Russia. Mayak workers had occupational exposures 100 to 1000 times higher than US weapons production and commercial nuclear power plant workers. Residents in communities along the Techa River had chronic exposures to low doses from liquid radioactive waste releases into the river and airborne releases from Mayak stacks from 1948 to 1982, an explosion of a liquid radioactive waste cooling tank in 1957, and resuspension of radionuclides from a dry lakebed during a tornado in 1967.

The role of epidemiology and dosimetry

Epidemiology is the study of the distribution and causes of diseases in groups of people. It is both an art and a science to determine whether causal relationships exist between an exposure to an agent and the subsequent development of illness or disease in a host. To that end, epidemiologists employ a variety of tools in their armamentarium to assess the statistical likelihood of relationships between exposures and diseases. The higher the radiation dose, the greater the likelihood of detecting adverse effects. In addition, in order to generate accurate cancer risk estimates, it is imperative to reconstruct as accurately as possible individual worker and Techa River resident doses and to determine the uncertainty about those individual dose estimates. Because DOE is responsible for protecting the health and safety of the DOE workforce and people living around DOE nuclear facilities, DOE has focused its research on the adverse health effects of ionizing radiation with respect to cancer as an endpoint, which is of greatest concern to the workers and to the public. National and international standard-setting organizations use data from epidemiology and historical dose reconstruction studies of various cohorts to compute radiation-related cancer risk estimates for revising radiation protection standards.

The Joint Coordinating Committee for Radiation Effects Research (JCCRER)

On 14 January 1994, the United States and the Russian Federation signed the bi-national JCCRER Agreement, which provides the legal framework for US and Russian scientists to collaboratively study the effects of ionizing radiation on workers and the public at any Russian former nuclear weapons production sites. The JCCRER's major role is to coordinate scientific research on the health effects of exposure to ionizing radiation in Russia from the production of nuclear weapons.

JCCRER member organizations

The JCCRER consists of six Federal agencies in the United States and five in Russia. The US JCCRER consists of DOE, which is the US Executive Agent, the Department of Defense (DoD), including the Armed Forces Radiobiology Research Institute (AFRRI), the Department of Health and Human Services (DHHS), including the Centers for Disease Control and Prevention (CDC), the Environmental Protection Agency (EPA), the National Aeronautics and Space Administration (NASA), and the Nuclear Regulatory Commission (NRC). The Russian JCCRER consists of the Federal Medical-Biological Agency (FMBA), which is the Russian Executive Agent, the State Research Center-Burnasyan Federal Medical Biophysical Center (BFMBC), the State Atomic Energy Corporation (Rosatom), the State Scientific Center – Institute of Medical and Biological Problems of the Russian Academy of Sciences (IBRAE), and Mayak.

The Russian Health Studies Program

The subset of JCCRER projects funded by DOE comprise the Russian Health Studies Program. The Program's name helped avoid confusion with JCCCNRS, which focused on assessing the effects of radiation from the Chernobyl nuclear power plant accident of 1986.

Purpose and objectives

The Russian Health Studies Program assesses worker and public health risks from radiation exposure resulting from nuclear weapons production activities in the former Soviet Union. The three goals of the Program are to: (1) clarify the relationship between health effects and chronic, low-to-medium dose radiation exposure; (2) estimate the cancer risks from exposure to gamma, neutron and alpha radiation; and (3) provide information to the national and international organizations that determine radiation protection standards and practices. To date, the research has focused at Mayak and residents in surrounding communities along the Techa River. Mayak is the site of the first Soviet nuclear weapons production facility and is comparable to DOE's Hanford site in Richland, Washington. For many years, researchers gathered clinical data from medical records and dosimetry information from archived doses, whole body counts, and bioassays in workers and in residents in surrounding communities affected by liquid radioactive wastes released into the Techa River and airborne releases from Mayak stacks.

History

Since the Program's inception in 1994, three phases have been completed. Phase I entailed coordinating, planning, building infrastructure, and facilitating links between US and Russian researchers. Phase II entailed conducting feasibility studies of 12–18 months and preservation of paper records in microfiche, microfilm, and electronic format. In Phase III, feasibility studies deemed scientifically meritorious resulted in multi-year projects. Currently, the Program is in Phase IV. Researchers are refining dosimetry, uncertainty, and cancer risk estimates. For additional historical details, please see Seligman⁽²⁾, Fountos and Rabovsky⁽³⁾, the Russian Health Studies Program website at http://energy.gov/ehss/russian-health-studies-program, and the JCCRER website at http://energy.gov/ehss/russian-health-studies-program-joint-coordinating-committee-radiation-effects-research-jccrer.

Current radiation protection standards

The NRC Annual Whole Body Dose Limit for workers is 50 mSv (5 rem) and for the public is 1 mSv (0.1 rem), which is 50 times less. Radiation health effects researchers consider 0–100 mSv (0–10 rem) per year to be low doses. The most crucial issue in radiation research is to determine whether it is possible to identify effects on human health of exposures of less than 50 mSv (5 rem) per year. The reason for this is that such exposures are more likely to have been received by DOE workers and surrounding populations.

Rationale for conducting Mayak worker and Techa River population studies

The data characteristics, the research focus, and its application and relevance to radiation protection standards and practices made the Mayak workers and Techa River well-suited for conducting radiation health effects research. For over 50 years, Russian scientists kept detailed health and exposure records and closely examined the health and doses of Mayak worker and Techa River residents. The workers were relatively stationary, as were many members of the exposed Techa River population. There were both external and internal exposures of chronic duration over a wide range of doses in both sexes. All of these characteristics facilitated the conduct of epidemiological studies with the goal of producing research results relevant to understanding radiation risks experienced by nuclear weapons production workers, commercial nuclear workers, and residents of surrounding communities.

Scientific oversight

Since the inception of the Program and as required by the JCCRER Agreement, there has been ongoing scientific oversight, which is a critical and vital element of the Program. There are external Scientific Review Groups (SRGs) in the United States and in Russia consisting of eminent US and Russian radiation effects research scientists with expertise in relevant fields, including radiation epidemiology and dosimetry, occupational and environmental historical dose reconstruction, radiation measurements and shielding, health physics, medicine, public health and biostatistics. Each SRG meets separately every 6 months to review semi-annual technical progress reports and proposals. In addition, the work is conducted according to 5-year plans containing a detailed research agenda.

Current projects

The JCCRER Agreement contains three directions: (1) population studies; (2) worker studies and (3) emergency response and training. The purpose of this paper is to present an overview of the activities in Directions 1 and 2. There are five current projects in the Program:

• 1.1: Techa River Population Dosimetry;

• 1.2b: Techa River Population Cancer Morbidity and Mortality;

• 2.2: Mayak Worker Cancer Mortality;

• 2.4: Mayak Worker Dosimetry; and

• 2.8: Russian Human Radiobiology Tissue Repository.

By convention, population studies begin with the number 1; worker studies begin with the number 2. As required by the JCCRER Agreement, all projects are jointly conducted, each with a US and a Russian Principal Investigator (PI).

Techa River Population Dosimetry and Techa River Cancer Morbidity and Mortality

The Techa River Dosimetry System (TRDS) developed in Project 1.1 provides point estimates (TRDS-D) and Monte Carlo distributions (TRDS-MC) of organ doses for Project 1.2b, Techa River Population Cancer Morbidity and Mortality, and NCI and European Commission (EC)-funded studies. EC-funded research was conducted under the auspices of the Epidemiological Studies of Exposed Southern Urals Populations (SOLO) Program, which was completed in March 2015, and its predecessor Southern Urals Radiation Risk Research (SOUL) Program, which was completed in December 2009. For further details on research conducted with EC sponsorship, please refer to the SOLO Program website at http://www.solo-fp7.eu.

More specifically, the TRDS provides individual dose estimates for internal, external and medical exposures for four environmentally-exposed cohorts:

• The Techa River Cohort (TRC), which consists of 29 719 persons born before the start of contamination.

• The Techa River Incidence Cohort (TRIC), which consists of 17 435 persons born before the start of contamination.

• The East Urals Radioactive Trace Cohort (EURTC), which consists of 9500 evacuees from the ‘Kyshtym explosion’ in 1957 as well as 13 000 who remained in the fringes of the plume, totaling 22 500 persons.

• Post-natal doses to the Techa River Offspring Cohort (TROC), which consists of 24 243 persons born after the start of contamination (conducted under SOLO Program).

Project 1.2b and companion Project 1.1 address cancer incidence and mortality in residents downstream from Mayak. Residents exposed to both internal and external radiation (less than 10 mSv or 1 rem per year) over a long period (20–30 years). The TRC follow-up through 12-31-2007 is very good: 13% were lost to follow-up (due to migration from the catchment area); vital status is known for 92% of the non-migrants. At the end of 2007, 25% were alive; 75% were known to have died. Of these, cause of death was known for 91% of the decedents. Researchers found statistically significant dose-responses for solid cancer mortality⁽⁴⁾ with an Excess Relative Risk (ERR) per 100 mGy of 0.061 [95% CI (0.004–0.13)]; solid cancer incidence adjusted for smoking⁽⁵⁾ with an ERR/100 mGy of 0.10 [CI (0.0013–0.15)]; and non-chronic lymphocytic leukemia (non-CLL) incidence⁽⁶⁾ with an ERR/100 mGy of 0.22 [CI (0.08–0.54)]. There was no evidence of a radiation effect for CLL and no statistically significant differences between solid cancer⁽⁴⁾ and leukemia ERR estimates⁽⁶⁾ in the Techa River cohort (chronic low dose-rate exposures) and those for the A-bomb survivors (acute high dose-rate exposures).

Mayak Worker Cancer Mortality and Mayak Worker Dosimetry

Project 2.2 and companion Project 2.4 address cancer mortality in Mayak workers. The Mayak Worker Cohort (MWC) is the largest Pu-exposed cohort ever studied. The MWC consists of 25 757 workers who worked at any time between 1948 and 1982; 25% were female. Of note, workers were exposed to both internal and external radiation in reactor complex, radiochemical plant, plutonium production plant or auxiliary departments, had protracted low dose-rate exposure similar to that of interest for radiation protection, and there was extensive Pu exposure (many Sv per year) for many radiochemical and plutonium plant workers. Project 2.2 was the first study to demonstrate in humans significantly increased incidence of lung, liver, and bone cancer related to internal deposition of plutonium. This had been demonstrated earlier in studies of beagle dogs. The MWC follow-up through 12-31-2008 is very good: 23% were lost to follow-up (due to migration from Ozersk); vital status is known for is known for all Ozersk residents and most pre-2004 migrants. At the end of 2008, 37% were alive; 63% were known to have died. Of these, cause of death was known for 99% of the decedents. In those exposed to Pu for 5 or more years since first exposure, researchers found statistically significant increases from lung cancer⁽⁷⁾ in men [ERR/100 mGy = 0.74 (0.5–1.1)] and in women [ERR/100 mGy = 2.4 (1.1–5.6)], from liver cancer⁽⁸⁾ in men [ERR/100 mGy = 0.26 (0.07–0.60)] and in women [ERR/100 mGy = 2.9 (1.0–9.5)], and bone cancer⁽⁸⁾ in women [ERR/100 mGy = 0.34 (0.04–2.0)]. The statistically significant sex effects from Pu doses for bone, lung and liver cancer have not yet been explained. For both sexes combined, researchers found statistically significant increases in lung cancer⁽⁷⁾ [ERR/100 mGy = 0.024 (0.008–0.044)], other solid cancers⁽⁹⁾ [ERR/100 mGy = 0.016 (0.007–0.026)] and non-CLL leukemia (unpublished data from Mikhail Sokolnikov, Russian PI for Project 2.2) both after 2–4 years [ERR/100 mGy = 0.69 (0.29–1.5)] and 5 or more years [ERR/100 mGy = 0.045 (0.01–0.11)] since first gamma exposure.

The Mayak Worker Dosimetry System (MWDS) developed in Project 2.4 provides the dosimetric data for companion Project 2.2. MWDS-2013 deals explicitly with shared and unshared uncertainties in the models used to calculate doses from both external and internal sources. A novel Bayesian approach has been developed to interpret the bioassay measurement data. Probability distributions for external gamma, external high energy neutron, external low-energy neutron and medical exposures and probability distributions for organ doses following inhalation of plutonium have been completed. This is the first time a complete uncertainty analysis has been performed for both internal and external doses. Of note, a state-of-the-art model of the respiratory tract is being developed, the impact of DTPA administration taken into account and the addition of americium component of dose underway. The extra-thoracic model of the respiratory tract that was developed in Project 2.4 has now been adopted by ICRP⁽¹⁰⁾ and will be used in the forthcoming revision of dose coefficients for workers and members of the public. Collaborative work with SOLO and US Transuranium and Uranium Registries has demonstrated a bound fraction of inhaled Pu material. Researchers found that worker doses were high in the early years; external gamma and internal Pu were of the same magnitude; and neutrons and medical exposures were less important than originally thought.

Russian Human Radiobiological Tissue Repository

The Russian Human Radiobiological Tissue Repository, also known as the Mayak Worker Tissue Repository, is the first and only facility in Russia to preserve and make available to the scientific community unique biospecimens of Russian nuclear facility workers. The repository preserves samples of biological tissues of employees from the first Russian domestic nuclear enterprise, Mayak, which was created at a time when its workers had no experience in operating such facilities. Mayak employees were exposed to prolonged external gamma radiation and/or internal alpha radiation due to Pu-239 in a wide range of doses. For each donor, there is information on occupational exposure history, as well as detailed medical and biological information. Real-time information about the contents is searchable online. The current inventory consists of about 283 790 biological specimens from 8027 registrants in storage, including samples from 6986 Mayak workers and 1324 Ozersk residents without occupational exposure to ionizing radiation. The contents facilitate molecular epidemiology studies designed to assess the relationship between disease and radiation exposure.

OBSERVATIONS

Studies of Mayak workers and Techa River residents are valuable because both cancer and non-cancer effects have been observed. Radiation effects are commensurate with those from the Japanese LSS. Radiation effects appear to be linear. Doses delivered at low dose rates appear to be as effective in producing cancer as doses delivered at high dose rates. Dose and dose-rate effectiveness factor is about 1; this was not widely anticipated. The Program fills data gaps in radiation research. The MWC is a unique resource for evaluating the risk of cancer from long-term internal exposure to plutonium and long-term external gamma exposure. The TRC is a unique resource for evaluating long-term environmental exposures, such as those in communities surrounding DOE nuclear facilities. Data from the research, especially on plutonium in workers, has provided critical information to help answer the question about cancer risks following the way a person accrues his or her doses.

CONCLUSIONS

The results of the Russian Health Studies Program have been significant in terms of observing risks at low doses in worker and residents exposed to ionizing radiation for protracted periods over a wide range of doses. The excess bone, lung and liver cancers in MWC provide confirmatory evidence of results observed from animal studies following the inhalation of Pu. The return on DOE's investment, as measured by 299 peer-reviewed publications is 23 years, has been very high.

FUNDING

This work was conducted as part of the Joint Coordinating Committee for Radiation Effects Research (JCCRER) under the auspices of the JCCRER Agreement of 1994 between the United States and the Russian Federation. It was jointly funded by the Russian Health Studies Program of the US Department of Energy (DOE) and by the Federal Medical Biological Agency (FMBA) of the Russian Federation. Past US JCCRER funding organizations included the US Department of Health and Human Services/National Institutes of Health/National Cancer Institute, the US Environmental Protection Agency, the US National Aeronautics and Space Administration, and the US Nuclear Regulatory Commission.