This paper (2o17 publication in Environ Res; preprint attached) reveals that –– almost 25 years after the National Academy of Sciences (NAS), Biological Effects of Ionizing Radiation (BEIR) I Committee (1972) used Russell’s dose-rate data to support the adoption of the linear-no-threshold (LNT) dose response model for genetic and cancer risk assessment –– Russell acknowledged a significant under-reporting of the mutation rate of the historical control group. This error, which was unknown to BEIR I, had profound implications, leading it incorrectly to adopt the LNT model, which was a decision that has profoundly changed the course of risk assessment for radiation and chemicals from the 1950s to the present.
Several factors affected the application of, and the manner in which, the concept of the dose-rate effect for ionizing radiation could have changed cancer risk assessment during the second half of the 20th century. These include: the strong opposition from an aging Muller; a BEIR I Genetics Subcommittee led by Muller’s protégé James Crow that defaulted to the Precautionary Principle when the science supporting LNT became challenged; and an error in reporting mutations in the mouse specific locus test (SLT) that resulted in adoption of the LNT. The following six specific findings summarize the historic impact of the Russell mouse SLT model on assessing the risk of ionizing radiation and of chemical carcinogens:
• The discovery that a significant dose-rate effect on germ cell mutations for males and females in the mouse SLT challenged key assumptions of the LNT model
• The Russells’ research at Oak Ridge National Laboratory on effects of ionizing radiation was an unprecedented massive effort, involving well over two million mice over more than four decades.
• Russell determined that the underlying tenets of LNT, as recommended by the BEAR I Genetics Panel, did not apply to mouse spermatogonia and oocytes and that these germ cells had far more genetic relevance to somatic cells than mature spermatozoa, which lacked DNA repair capabilities.
• Whereas dose-rate effects in oocytes suggested a threshold response, those in spermatogonia were less extreme, permitting retention of the LNT dose-response model by BEIR I and enabling the subsequent creation of the dose-response effectiveness factor (DREF) to adjust for risk overestimation by the LNT dose response.
• An early error by Russell in reporting and estimating the mutation rate of the mouse control group (involving clusters of spontaneous mutations arising during the perigametic interval) affected all SLT-based risk assessments from the 1950s and was unknown until Selby reported it in the mid-1990s.
• If the error in control group mutation rate had been corrected –– prior to NAS/NRC BEIR I (1972) –– the course of cancer risk assessment might have been significantly affected, with consideration given to the threshold or hormetic dose-response models.
The attached paper concludes with a “seasoned” perspective by Professor James Crow (p 379 of Crow, 1987), an original member of BEAR I and Chair of BEIR I Genetics Subcommittee: “It is clear that Muller’s alarmist views of the hazards of radiation have prevailed… In my opinion, Muller was too effective in cautioning against radiation risks, with the result that the public now has an irrational fear of low-level radiation relative to other risks. The fear, I suppose, has resulted more from the assumption of “no threshold for carcinogenic effects” than from the dread of genetic effects. In any event, the battle that Muller waged was certainly won: The present standards for radiation safety are more stringent than even he dared advocate.”