Program Description
Since its beginning in 1999, the focus of research has been to study cellular and molecular responses to doses of x- or gamma- radiation that are at or near current workplace exposure limits; in general, for total radiation doses that are less than 0.1 Sievert (10 rem). Currently about 55% of Program funds support projects at academic institutions and the remainder support Low Dose Scientific Focus Area research at the DOE National Laboratories. Research must focus on elucidating molecular mechanisms and pathways involved in normal radiobiological responses to low dose exposure. In general, supported research focuses on low Linear Energy Transfer (low LET) ionizing radiation (x- and gamma-rays; high-energy electrons and protons) exposures, and total radiation doses that are less than 0.1 Gray (10 rads). Some experiments involve selected exposures to higher doses of radiation for comparisons with previous experiments or for determining the validity of extrapolation methods previously used to estimate the effects of low doses of radiation from observations made at high doses. In some cases, a biological response of interest seen only at high doses may actually be absent (as opposed to simply undetectable) at low doses of radiation; evidence is also accumulating that biological responses after low dose exposure are qualitatively different from responses after high dose exposure. Therefore, research aimed at defining the dose where the mechanisms of response shift (dose-series and time-series experiments) has had high programmatic priority.Solicitations
The program is not presently soliciting research proposals. Future grant solicitation notices will be posted on the DOE Office of Science Grants and Contracts Web Site and at Grants.gov. Information about preparing and submitting applications, as well as the DOE Office of Science merit review process, may also be found on the DOE Office of Science Grants and Contracts Web Site.The most recently closed solicitation (Notices 08-20) was a highly focused joint DOE-NASA call for new research to develop a better scientific basis for understanding risks from exposures to low doses or low fluences of ionizing radiation. New research that focused on molecular and cellular responses within tissue- and higher levels of biological organization were offered higher priority. Experimental research of particular interest to this call included radio-adaptive responses; systems genetics of inter-individual variation; low dose and/or low dose-rate effects on: a) proteomic responses, b) the immune system, c) epigenetic regulation, and d) molecular and cellular hallmarks of aging. The Programs were also interested in funding new mathematical/risk modeling projects that would incorporate the latest low dose and low dose-rate biological research into mechanism-based models of tissue function. After a pre-application round, 57 final formal applications were received, and 20 of them were selected for funding.
Why the Program's Research is Important
Program research is supported that will help determine health risks from exposures to low levels of radiation. This information is critical to adequately and appropriately protect people while making the most effective use of our national resources. Over the next 100 years, radiation exposures associated with human activity are expected to be very low dose and low dose-rate radiation from medical tests, waste clean up, environmental isolation of materials associated with nuclear weapons and nuclear power production, and possibly terrorism events. The major type of radiation exposures to workers and the public will be low Linear Energy Transfer (LET) ionizing radiation (primarily X- and gamma-radiation) from fission products. The DOE Low Dose Radiation Research Program therefore concentrates on studies of low-LET exposures delivered at low total doses and low dose-rates.Data Sharing Policy
Any data and results generated through funded investigations that are appropriate to share with the broader scientific community should, where possible, be provided in a format amenable to deposition in widely held databases. Investigators are expected to effectively communicate research results through publication in peer-reviewed journals. Investigators are also encouraged to communicate with the wider community of concerned persons, so that current thinking and public debate are better able to reflect sound science.More Information about the Program and Its Accomplishments
Prior to the Low Dose Program, there was almost no scientific evidence to support regulatory standards for exposures less than 0.5 Sv (50 rem). Solid epidemiological data from populations receiving high doses at high dose rates (mainly the Japanese A-Bomb survivor Life Span Study) have shown that ionizing radiation increases rates of cancer in human populations, at a level of roughly 5 or 6% per 1 Sv (or 6% /100 rem). However, traditional epidemiology has never been able to demonstrate significantly higher cancer risks in humans exposed to lower doses (below 0.1 Sv or 10 rem), or to chronic low dose rate exposures at somewhat higher total doses. Therefore, mathematical models were needed to develop health risk estimates for low doses of radiation. In order to test the resulting biophysical risk estimate models, animal life span studies were conducted from the 1960’s to 90’s, measuring cancer incidence and cancer mortality in irradiated mice and dogs. As in human epidemiology, significantly higher cancer rates were not seen at the lower doses, only at the high dose exposures. Biological experiments were also undertaken using mammalian cell culture systems, but the majority of these only looked at initial biological damage. Until recently, the models of radiation action have assumed that ionization events acted independently in cells and tissues and that the single cell was the unit of function. The models also assume that every ionization event increases the probability of DNA breaks. Together, these physical/biological assumptions supported linear, no-threshold models of radiation risk and cancer. Historically, measurements of initial radiation damage such as cell death, chromosome aberrations, or micronuclei formation in cellular systems showed a fairly linear response with dose, but these experiments seldom encompassed doses lower than 0.5 Sv (50 rem), and they did not address human health risks such as carcinogenesis.New research from DOE’s Low Dose Program directly challenges the old fundamental assumptions. The new findings provide compelling evidence that ionization events in cells and tissues are not completely independent and that tissues have surveillance mechanisms that dramatically affect the development of cancer and the behavior of cancer cells. The research is establishing the tremendous importance of studying a tissue’s biological response to an exposure, rather than studying just the initial events within an individual cell. The Low Dose Program is supporting research to help in the development of new mechanistic models that would incorporate all aspects of radiation biology, from cellular and molecular actions within tissues, to the evolution of cancer as a multi-cellular disease. Ongoing research in the Low Dose Program and advances in systems biology hold promise in providing this modeling framework, which can facilitate moving new biological paradigms into the regulatory process. The Low Dose Program supported projects continue to expand current understanding of normal tissue responses to low doses of radiation. As of 2008, there were at least 550 peer-reviewed publications coming from the Low Dose Program projects, 100 of which were published in the last year. An Investigators’ Workshop is held every 18 months, and focused topical workshops are held as needed.
Program Manager
Noelle F. Metting, Sc.D.