Thursday, July 30, 2020

Strongly unified belief in the linear non-threshold model among panel members and their refusal to acknowledge that a low dose of radiation could exhibit a threshold, & an excessive degree of self-interest

The Muller-Neel dispute and the fate of cancer risk assessment. Edward J.Calabrese. Environmental Research, July 23 2020, 109961. https://www.sciencedirect.com/science/article/abs/pii/S0013935120308562

ABSTRACT: The National Academy of Sciences (NAS) Atomic Bomb Casualty Commission (ABCC) human genetic study (i.e., The Neel and Schull, 1956a report) showed an absence of genetic damage in offspring of atomic bomb survivors in support of a threshold model, but was not considered for evaluation by the NAS Biological Effects of Atomic Radiation (BEAR) I Genetics Panel. The study therefore could not impact the Panel's decision to recommend the linear non-threshold (LNT) dose-response model for risk assessment.1 Summaries and transcripts of the Panel meetings failed to reveal an evaluation of this study, despite its human relevance and ready availability, relying instead on data from Drosophila and mice. This paper explores correspondence among and between BEAR Genetics Panel members, including James Néel, the study director, and other contemporaries to assess why the Panel failed to use these data and how the decision to recommend the LNT model affected future cancer risk assessment policies and practices. This failure of the Genetics Panel was due to: (1) a strongly unified belief in the LNT model among panel members and their refusal to acknowledge that a low dose of radiation could exhibit a threshold, a conclusion that the Néel/Schull atomic bomb study could support, and (2) an excessive degree of self-interest among panel members who experimented with animal models, such as Hermann J. Muller, and feared that human genetic studies would expose the limitations of extrapolating from animal (especially Drosophila) to human responses and would strongly shift research investments/academic grants from animal to human studies. Thus, the failure to consider the Néel/Schull atomic bomb study served both the purposes of preserving the LNT policy goal and ensuring the continued dominance of Muller and his similarly research-oriented colleagues.


6. Conclusion

Human genetic data from over 25 years of the ABCC study (i.e., 1946–1972) demonstrated support for a threshold model for radiation-induced genetic damage in humans, but that information were both ignored and then rejected by the BEAR I and BEIR II Genetics Committees, respectively. The findings, now nearly 50 years later (Grant et al., 2015), have consistently continued to contradict a linear dose response, supporting a threshold response for a complex array of endpoints of genetic damage in humans. Furthermore, the decision to base the LNT recommendation on the male mouse data of Russell is now seen as flawed (Calabrese, 2017a,b), providing no support for the BEIR (1972) decision in favor of LNT.

The failure to assess the human genetic study of Neel and Schull (1956a) at this most crucial time in risk-assessment history represents a profound abrogation of responsibility by the NAS leadership and the BEAR Genetics Panels. This affirmative “failure of responsibility” appears to have been a goal of Muller as it would ensure the adoption of LNT and the continued professional dominance of Muller and his like-thinking and similar research-oriented colleagues. The adoption of LNT occurred during a “perfect storm” consisting of: heightened societal fear of nuclear confrontation; continuing nuclear fallout from atmospheric testing; ideologically based policy and scientific leadership of the Rockefeller Foundation and the US NAS; and a handpicked, highly LNT-biased Genetics Panel that was dominated by an even more-determined Hermann Muller to ensure adoption of the LNT. This history should represent a profound embarrassment to the US NAS, regulatory agencies worldwide, and especially the US EPA, and the risk-assessment community whose founding principles were so ideologically determined and accepted with little if any critical reflection.


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