Summary
Ionizing radiation occurs in a wide range of medical, industrial, military, and commercial settings, and the number of individuals exposed or potentially exposed to radiation in these settings is increasing. There are longstanding concerns that exposures in these settings, even at low doses (defined as doses below 100 milligray [mGy]) or low dose rates (delivered at rates below 5 mGy/h), can adversely affect human health. Today, these concerns influence patient acceptance of medical diagnostic procedures, U.S. government decisions related to the future of nuclear power and clean energy policies, continuing efforts to assess the full range of radiogenic health outcomes of legacy exposures to fallout from nuclear weapons production, testing, and waste sites, management of nuclear waste, and plans for responding to radiological threats. These concerns also raise questions as to whether the public and workers are adequately protected from current environmental and occupational radiation exposures and from potential new sources of exposure such as rare earth element and lithium mining to support green energy and long-term energy policies in the United States.
Low-dose and low-dose-rate radiation effects on human health outcomes and the biological mechanisms of these effects are not fully understood. Cancer is the health outcome most commonly studied for its association with low doses of radiation, and heritable genetic effects are assumed to be associated with low-dose exposures, despite minimal evidence to date of such effects in humans. There is also increasing evidence that low-dose radiation exposure may be associated with non-cancer
health outcomes such as cardiovascular disease, neurological disorders, immune dysfunction, and cataracts. For some of these health outcomes, experts rely on risk estimates from studies of individuals who were primarily exposed to higher doses. As a result, the uncertainties associated with current estimates of adverse health effects that result from low-dose and low-dose-rate exposures of relevance to the U.S. population are considerable. Advances in epidemiological study design and analysis, radiation biology research, and biotechnology and research infrastructure make it possible to obtain more direct information on health effects that result from exposures to low-dose and low-dose-rate radiation. The increasing low-dose radiation exposures and the improved capabilities to quantify health risks and study the underlying mechanisms make it both urgent and feasible to improve understanding of the adverse human health effects from exposures to doses and dose rates of relevance to the U.S. population.
Research in low-dose and low-dose-rate radiation in the United States is currently limited and fragmented, lacking leadership and an overarching prioritized strategic research agenda. The Consolidated Appropriations Act, 2021 (Public Law 116-260) directed the Secretary of Energy to enter into an agreement with the National Academies of Sciences, Engineering, and Medicine (the National Academies) to develop a long-term strategic and prioritized research agenda for low-dose radiation research within the Department of Energy. A separate congressional directive (American Innovation and Competitiveness Act of 2017, Public Law 114-329) aims to develop a strategy for coordination of low-dose radiation research conducted across federal agencies. This congressional directive tasks the National Science and Technology Council within the White House’s Office of Science and Technology Policy with the coordination strategy.
The National Academies appointed an expert committee to define the essential components and to set priorities to guide research for a multidisciplinary coordinated low-dose radiation program that is developed neutrally in terms of the impact of the research on assessment of radiation health risk and consequently its potential impact on radiation protection policy and practice in the United States. The proposed program as outlined in this report involves the broad research enterprise and goes beyond the resources of any one federal agency. This summary contains the complete list of the committee’s findings and recommendations in response to the seven charges of the Statement of Task (see Box S.1).
IMPACT OF A MULTIDISCIPLINARY LOW-DOSE RADIATION PROGRAM
The following three findings address the goals and impact of a multidisciplinary low-dose radiation program in the United States (see Chapters 2 and 3).
Finding 1: A coordinated multidisciplinary low-dose radiation research program in the United States can improve understanding of adverse human health effects from exposures to radiation at doses and dose rates of relevance to the U.S. population. In addition, this program can identify mechanisms for induction of these health effects, develop
improved risk models for doses and dose rates at which direct measurement of risks is not currently possible, and ultimately develop more individualized risk estimates.
Finding 2: Comprehensive understanding of adverse human health effects emerging from the multidisciplinary low-dose radiation program will enable better assessment of whether current risk estimates (primarily for cancer) at low doses and low dose rates are accurate, underestimated, or overestimated and provide improved risk estimates for other adverse health outcomes. This assessment may impact radiation protection by confirming that current regulations and guidance sufficiently protect human health or by supporting either more restrictive or less restrictive regulations and guidance.
Finding 3: The committee is unable to quantify the low-dose radiation program’s economic impacts because comprehensive estimates of overall costs to comply with current radiation standards are unavailable. Additionally, any changes to the current estimates will depend on new information on adverse health effects that will be generated by the low-dose radiation research program. When adjustments in radiation protection standards and guidance are proposed based on new information, agencies can estimate the economic impacts of the changes and perform benefit-cost and cost-effectiveness analyses of alternative measures.
Costs for complying with radiation protection standards and guidelines, administering radiation compensation programs, or for using technologies that utilize radiation in medical and other applications are balanced with the health, societal, and other benefits based on current scientific understanding of low-dose radiation health effects. To the committee’s knowledge, comprehensive estimates of overall costs to federal agencies and the society to comply with current radiation protection standards and guidelines are unavailable. Similarly, comprehensive estimates for the overall cost savings for protecting the U.S. population’s health by implementing these standards and guidelines are also unavailable. Without these current estimates as a starting point, preparing comprehensive estimates of overall costs to comply with prospective radiation protection standards or guidelines is not possible.
PROPOSED RESEARCH AGENDA PRIORITIES
Epidemiological and biological research of low-dose and low-dose-rate radiation faces several challenges. These arise because the effects of low-dose and low-dose-rate radiation exposures are assumed to be subtle and
difficult to distinguish from those caused by other stressors or “spontaneous” changes that adversely affect the normal functions of cells, tissues, and organs. Moreover, a full understanding of possible effects may be complicated by change in the magnitude of observed effect with dose, dose rate, type of radiation, and duration of exposure.
The following three findings and one recommendation address the proposed research agenda priorities (see Chapter 5).
Finding 4: Epidemiological studies have played a crucial role in identifying risks (primarily for cancer) from medical, occupational, and environmental radiation exposures at low doses. Existing epidemiological studies are unable to address a number of outstanding questions of low-dose and low-dose-rate exposures of concern to the U.S. population including the full range of potential adverse health effects, risks associated with doses around 10 milligray, and the potential impacts of genetic, lifestyle, environmental, and other factors that may also affect radiation-related risk estimates. Epidemiological studies designed to overcome these limitations can better elucidate adverse health effects of radiation exposure at low doses and low dose rates relevant to the U.S. population today.
Finding 5: Radiation biology studies have contributed to the mechanistic understanding of the effects of radiation on molecular pathways and intra- and extracellular processes. The application of novel and developing technologies will enable more precise definition of the cellular and molecular processes that are affected by low-dose and low-dose-rate exposures. Integration of this information with that from epidemiological studies will enable better quantification of the adverse health effects from low-dose and low-dose-rate exposures relevant to the U.S. population, increase understanding of the involved mechanisms, and inform on the most appropriate risk assessment models to be used.
Finding 6: Advances in biotechnology and research infrastructure have been driven by the vast research and development enterprise in the United States. These include new observational and experimental systems, tools for measurement and genetic manipulation, increased computational power, improved interpretative algorithms, and shared data access systems. These advances have enabled innovation and breakthroughs in many scientific areas including cancer research and treatment, environmental health effects research, and vaccine production. A revitalized low-dose radiation research program can likewise leverage and further develop these capabilities to enable scientific innovation and breakthroughs in radiation biology and epidemiology.
Recommendation A: Agencies responsible for the management of the multidisciplinary low-dose radiation program should fund low-dose and low-dose-rate radiation research in the 11 high-priority research topics identified by the committee and can address the scopes outlined in Finding 1. (See Table S.1 for listing and approach for addressing the recommended priorities.) These research priorities are broadly classified as epidemiological research, biological research, and research infrastructure and are of equal importance.
Criteria used to identify priorities for low-dose and low-dose-rate research included (1) existing human, laboratory model, and cellular evidence for adverse health effects resulting from radiation exposure; (2) limitations in the current radiation protection system in the United States; (3) feasibility of improving low-dose and low-dose-rate risk estimation models given newly available technologies and resources as well as increased understanding of human disease mechanisms; and (4) issues of concern for exposed populations.
The proposed research will address cancer and non-cancer health outcomes including cardiovascular disease, neurological disorders, immune dysfunction, cataracts, and heritable genetic effects for both internal and external exposures. The committee strongly emphasizes the need for integration across the research lines and anticipates that the most impactful research projects will include work in more than one research line and will be carried out by multidisciplinary teams. The specific tactics for addressing the recommended priorities and for integrating the research lines will be developed with input from the extended research community and other stakeholders. Importantly, the list of priorities will likely evolve as biological understanding and research tools advance and as the research community and other stakeholders are engaged with the program.
Finding 7: Significant investments over a sustained period spanning several decades are necessary to develop and maintain a multidisciplinary low-dose radiation research program in the United States that leverages existing and developing research infrastructure that will achieve the goals outlined in Finding 1. The committee’s best estimate is that the investments required during the first 10–15 years of the program are at the level of $100 million annually and periodic reassessments are required as large epidemiological studies and necessary research infrastructures are established.
The committee’s research agenda extends for 15 years, through 2037. By that time, several of the biological research priorities (e.g., development
of model systems [Priority B1] and development of biomarkers for radiation-induced adverse health outcomes [Priority B2]) and research infrastructure priorities (e.g., tools for detection and precise characterization of aberrant cell and tissue states [Priority I1] and dosimetry for low-dose and low-dose-rate exposures [Priority I3]) are expected to be completed or to be approaching completion and providing critical information. However, it is likely that the epidemiological research priorities will extend further into the future, based on progress with improving dosimetry for epidemiological studies (Priority I3), further establishment of database infrastructure (Priority I2), and advances on the most biologically important components of low-dose and low-dose-rate radiation (e.g., through research on Priorities B2 and B4).
The committee estimates that funding needed for the program is on par with the congressionally authorized funds for 2023 and 2024, that is, at the level of $30 million and $40 million, respectively, but needs to rise to the level of $100 million annually thereafter and remain at that level through 2037. Although the committee recognizes that the exact form of the program will be determined by the funding agency after consultation with stakeholders, it provided a prototypical program that comprises interacting hubs focusing on basic and translational biology, analytical and computational technologies, and epidemiology, intended to justify the $100 million annual funding level. The committee also notes that appropriations at the level of $5 million per year are not adequate to even initiate a meaningful low-dose radiation research program—as seen in 2021 and 2022 when funds for the program were at that level and the program was not initiated. Inadequate funding for the program will lead to continued scientific and policy debates about risks of low doses of radiation to the possible detriment of adequate protection of patients, workers, and members of the public from the adverse effects of radiation.
ELEMENTS OF A SUCCESSFUL LOW-DOSE RADIATION RESEARCH PROGRAM
The following two findings and one recommendation address the essential elements of a successful low-dose radiation research program (see Chapter 6).
Finding 8: The Department of Energy’s (DOE’s) Office of Science has a long history leading and supporting radiation research at national laboratories and universities to advance knowledge of radiation health effects and mechanisms of these effects. However, since about 2016, the Office’s focus has been directed away from radiation health effects research, resulting in a lack of leadership and scientific activity in this
TABLE S.1 Committee-Recommended Research Priorities for Low-Dose and Low-Dose-Rate Radiation Research
| Priority Research Goal Epidemiological Research |
|---|
| E1 Develop and deploy analytical tools for radiation epidemiology. |
| E2 Improve estimation of risks for cancer and non-cancer health outcomes from low-dose and low-dose-rate external and internal radiation exposures. |
| E3 Determine factors that modify the low-dose and low-dose-rate radiation-related adverse health effects. |
| Biological Research |
| B1 Develop appropriate model systems for study of low-dose and low-dose-rate radiation-induced health effects. |
| B2 Develop biomarkers for radiation-induced adverse health outcomes. |
| B3 Define health-effect dose-response relationships below 10 mGy and below 5 mGy/h. |
| B4 Identify factors that modify or confound estimation of risks for radiation-induced adverse health outcomes. |
| Research Infrastructure |
| I1 Tools for sensitive detection and precise characterization of aberrant cell and tissue states. |
| I2 Harmonized databases to support biological and epidemiological studies. |
| I3 Dosimetry for low-dose and low-dose-rate exposures. |
| I4 Facilities for low-dose and low-dose-rate exposures. |
a The broader field of “-omics” includes genomics, transcriptomics, proteomics, metabolomics, and radiomics.
NOTES: Examples of integration across the priorities are described in Chapter 5. mGy = milligray.
| Approach | Integration Across Research Lines |
|---|---|
| Develop cohorts of sufficient size, with detailed health information and biosample collection and accurate dosimetry, to support epidemiological studies of radiation-induced health effects in medically, occupationally, and environmentally exposed U.S. populations. | B2–B4; I1–I3 |
| More precisely define health outcomes to enable exclusion of diseases caused by other effects, identifying easily measured signatures that can serve as disease surrogates, by improving dosimetry and identifying and compensating for confounding and modifying factors. | B1–B4; I1–I3 |
| Assess the impact of genetic makeup, epigenomic status, DNA repair efficacy, comorbidities, exposure history to radiation and other agents, lifestyle and psychosocial factors, and immune status on radiation-induced adverse health outcomes. | B1–B4; I1–I3 |
| Identify laboratory model systems in which molecular, cellular, and pathological features of radiation-induced health effects are similar to humans. | E2–E3; I1–I4 |
| Identify radiation-induced changes in cellular and molecular features that causally link to adverse health effects in appropriate model systems. | E1–E3; I1–I4 |
| Establish radiation dose-response curves for molecular and cellular endpoints and for associated early- and late-stage diseases at doses below 10 mGy and dose rates below 5 mGy/h. | E1–E3; I1–I4 |
| Assess the impact of genetic makeup, epigenomic status, DNA repair efficacy, comorbidities, exposure history to radiation and other agents, lifestyle factors, and immune status on low-dose and low-dose-rate radiation-induced adverse health effects and associated cellular and molecular response endpoints. | E1–E3; I1–I4 |
| Identify, develop, and deploy bulk and single-cell -omicsa and image measurement and computational analysis workflows to quantify disease-linked cellular and molecular signatures that are sufficiently sensitive, reliable, and low cost for wide-scale application. | E1–E3; B1–B4 |
| Develop accessible databases that document exposure levels, rates, types, and durations as well as cell, molecular, and health outcomes for human populations and experimental models. | E1–E3; B1–B4 |
| Elucidate biological localization of internalized radionuclides; directly measure radiation-induced damage and associated response mechanisms; develop high-fidelity anatomically and physiologically based dosimetry; develop and apply modern statistical and computational methods for dose reconstruction. | E1–E3; B1–B4 |
| Ensure access to low-dose and low-dose-rate exposure facilities, including those allowing internal exposure in model systems by a variety of routes (e.g., inhalation, ingestion) or invest in new facilities. | B1–B4 |
area. Separate offices within DOE and within other federal agencies and national and international organizations have relevant expertise and have supported and continue to support research in radiation health effects. Except for the National Aeronautics and Space Administration, radiation research carried out by these other entities has not been coordinated with that supported by DOE’s Office of Science.
DOE and its predecessor organizations have a long history of leading research on radiation effects in academia, national laboratories, and elsewhere, starting in the 1940s in support of the U.S. nuclear weapons program. From 1999 to 2016, DOE’s Office of Science Biological and Environmental Research (BER) managed the low-dose radiation program. The program took advantage of new technologies available at the time as well as advances in molecular and cell biology made by the Human Genome Project and expanded knowledge of molecular and cellular responses to radiation and helped better understand biological responses at low doses of radiation. The program was terminated owing to BER’s change of focus toward bioenergy and environmental research. National laboratories have traditionally been a vital component of DOE’s research capabilities, but since termination of the low-dose radiation research program, they have been refocused on research areas other than low-dose radiation mechanisms and effects.
A separate office within DOE, the Office of Health and Safety, supports research programs mandated by Congress or required by international agreement, including the Japan program that supports studies of the Japanese atomic bombing survivors of Hiroshima and Nagasaki carried out at the Radiation Effects Research Foundation. The Office of Health and Safety does not have available funds to support competitive external grants and contracts. A few other federal agencies within the United States (primarily the National Aeronautics and Space Administration, the National Institutes of Health [NIH], the Centers for Disease Control and Prevention, and the Department of Defense) have programs that support or conduct research on low-dose radiation relevant to the agency’s specific missions. Some offices within these agencies have relevant expertise but the research they support is primarily in higher doses and exposures.
Finding 9: Impacted communities exposed to radiation as a result of activities carried out as part of the U.S. nuclear weapons program (1942–1991) have strongly objected to the Department of Energy’s (DOE’s) management of the low-dose radiation program. They assert that the agency’s role in promoting nuclear technologies and its responsibility for management and cleanup of its nuclear sites conflict with its role as a manager of studies on low-dose and low-dose-rate radiation health
effects that may serve as the basis for exposure management decisions. This conflict, and the legacy of DOE’s history of problematic community interactions, is a source of distrust of the agency by these communities.
Impacted communities in the context of this report include Indigenous communities; atomic veterans; nuclear workers; uranium miners, millers, transporters, and their families; and individuals or communities impacted by radioactive contamination or nuclear fallout due to nuclear weapons testing, offsite radiation releases from nuclear weapons production sites, and nuclear waste cleanup activities. Much of the distrust of these impacted communities toward DOE’s management of the low-dose radiation program originates from DOE’s and its predecessor organization’s secrecy during the nuclear weapons program activities and cleanup operations. Based on the input from community representatives to the committee, it is apparent that there is continuing distrust toward the U.S. government, and there is a belief that the U.S. government has failed to accept responsibility for past radiation exposures and has failed to develop programs that adequately compensate all impacted communities.
Recommendation B: Agencies responsible for the management of the multidisciplinary low-dose radiation program should incorporate the following elements:
- Programmatic commitment to developing and maintaining a long-term multidisciplinary low-dose radiation research program that leverages the advances in U.S. research infrastructure and health effects research.
- Independent scientific advice and program evaluation by a trusted entity.
- Transparent management of the research process.
- A prioritized strategic research agenda developed with input from all relevant scientific, regulatory, and impacted stakeholder communities nationally and internationally.
- Research sponsorship mechanisms that support competitive research and infrastructure development projects and employ transparent peer review to select projects that are aligned with the program’s strategic research agenda.
- Training and research support for scientists of all career levels and relevant disciplines that promote equity, diversity, and inclusion.
- Commitment to engagement and communication with all relevant stakeholder communities.
- Coordination across federal agencies and other national and international organizations that carry out low-dose radiation
research or have relevant expertise and entities that carry out relevant (non-radiation) research.
Long-term commitment to the low-dose radiation program is needed to address the research priorities discussed by the committee in this report and to take advantage of the continuing technological and biological advances. Congress has assigned the management of the low-dose radiation program to DOE, but congressional staff told the committee that other government agencies could initiate their own low-dose radiation programs, carry out research that is dedicated to low-dose radiation, or have a low-dose radiation research component. Because the only entity at this point that Congress has tasked with a focused low-dose radiation program is DOE, the committee saw a role for DOE in coordinating low-dose radiation research within the United States. However, the committee also recognized the concerns raised by members of impacted communities about DOE’s inherent conflicts with leading low-dose radiation research and by the research community on DOE’s shortcomings related to management of the previous low-dose radiation program. In addition, the research agenda proposed by the committee extends beyond any single agency’s capabilities, and a partnership with an agency whose mission is to enhance health would be warranted.
Among various federal agencies with missions to enhance or protect health, NIH is widely trusted by the scientific community and members of the public and does not have any regulatory responsibilities related to setting or implementing radiation protection standards; therefore, it has no perceived conflict of interest with leading low-dose radiation research through a cross-institutional effort. In addition, it has well-established and transparent processes for soliciting, reviewing, and funding research. Within NIH, the National Institute of Allergy and Infectious Diseases’ (NIAID’s) Radiation and Nuclear Countermeasures Program (RNCP) could be suitable to support low-dose radiation research through a cross-institutional effort. Although RNCP currently supports research in moderate and high doses starting at about 1 gray and supports limited research on cancer (which is the primary focus of the National Cancer Institute [NCI]), the committee was impressed with the program management’s commitment and transparency as well as engagement with its stakeholder communities. NCI has processes similar to NIAID’s and by virtue of its mission it focuses on cancer research. The Advanced Research Projects Agency for Health (ARPA-H), a proposed agency tasked with building high-risk, high-reward capabilities to drive biomedical breakthroughs, could also contribute to innovative low-dose radiation research leadership.
DOE and NIH have traditionally supported most of the low-dose radiation research in the United States, and there is a precedent for a successful coordination by the two agencies to complete the Human Genome
Project. The committee supports a similar approach to be used to lead the coordination of low-dose radiation research, with DOE leading a portion of the strategic research agenda (e.g., on genome biology, computational, and modeling research, and support for facilities for low-dose and low-dose-rate exposures), and NIH, through a cross-institutional effort, leading the epidemiological and biological research, but with mechanisms in place to allow for integration of the different research lines.
The committee was not tasked with assessing the suitability of DOE to manage the low-dose radiation program or with recommending an alternative management structure. But congressional staff was interested in views and possible alternative options for the management of the low-dose program.
DOE does not currently meet important criteria for an effective managing agency, namely commitment to the program and absence of perceived conflicts with the research it supports. Among various federal agencies with experience with research funding, NIH is an example of a federal organization that meets these criteria.
The committee estimates that to initiate the new low-dose program, DOE could implement most of the essential elements identified by the committee within about 2 years given adequate funding. DOE’s progress with implementing the essential elements needs to be formally and transparently assessed. For example, Congress may use the scheduled Government Accountability Office review of the low-dose program mandated in the Consolidated Appropriations Act, 2021, § 11001. This review is scheduled to take place in 2023, 3 years after the enactment of the law. If Congress finds that DOE failed to adopt the research agenda and implement the essential elements recommended by this committee, it may consider alternatives for placement and management of the low-dose radiation program, for example within NIH, likely as a cross-institutional effort, for example, by NIAID and/or NCI and/or the newly conceptualized ARPA-H.
This page intentionally left blank.
