Daily Archives: August 8, 2015

Linear No-Threshold Extrapolation for Ionizing Radiation: Let the Sacred Cow Die

Two very important papers detailing the history behind the default assumption of linear no-threshold for extrapolation of ionizing radiation cancer risk assessment were published in 2013 by Ed Calabrese. His work on hormesis is well-established.

Edward J. Calabrese. How the US National Academy of Sciences misled the world community on cancer risk assessment: new findings challenge historical foundations of the linear dose response. Archives of Toxicology, 2013; DOI: 10.1007/s00204-013-1105-6

This paper extends several recent publications indicating that Hermann J. Muller: (1) Made deceptive statements during his Noble Prize Lecture on December 12, 1946, that were intended to promote the acceptance of the linear dose-response model for risk assessment for ionizing radiation and (2) that such actions of Muller were masked by a series of decisions by Muller’s long-time colleague and esteemed radiation geneticist Curt Stern, affecting key publications in the mutation literature. Such actions further enhanced acceptance of the linearity dose-response model while preventing Muller’s deceptions from being discovered. This paper provides documentation that Muller reinforced such practices within the scientific literature in the early 1950s, by supporting scientifically questionable actions of Stern. Detailed documentation is provided that demonstrates how these actions affected national and international risk assessment policy for ionizing radiation and chemical carcinogens via the recommendations of the National Academy of Sciences Biological Effects of Atomic Radiation committee in 1956, to adopt the linear dose-response model.

Edward J. Calabrese. Origin of the linearity no threshold (LNT) dose–response concept. Archives of Toxicology, 2013; DOI: 10.1007/s00204-013-1104-7

This paper identifies the origin of the linearity at low-dose concept [i.e., linear no threshold (LNT)] for ionizing radiation-induced mutation. After the discovery of X-ray-induced mutations, Olson and Lewis (Nature 121(3052):673–674, 1928) proposed that cosmic/terrestrial radiation-induced mutations provide the principal mechanism for the induction of heritable traits, providing the driving force for evolution. For this concept to be general, a LNT dose relationship was assumed, with genetic damage proportional to the energy absorbed. Subsequent studies suggested a linear dose response for ionizing radiation-induced mutations (Hanson and Heys in Am Nat 63(686):201–213, 1929; Oliver in Science 71:44–46, 1930), supporting the evolutionary hypothesis. Based on an evaluation of spontaneous and ionizing radiation-induced mutation with Drosophila, Muller argued that background radiation had a negligible impact on spontaneous mutation, discrediting the ionizing radiation-based evolutionary hypothesis. Nonetheless, an expanded set of mutation dose–response observations provided a basis for collaboration between theoretical physicists (Max Delbruck and Gunter Zimmer) and the radiation geneticist Nicolai Timoféeff-Ressovsky. They developed interrelated physical science-based genetics perspectives including a biophysical model of the gene, a radiation-induced gene mutation target theory and the single-hit hypothesis of radiation-induced mutation, which, when integrated, provided the theoretical mechanism and mathematical basis for the LNT model. The LNT concept became accepted by radiation geneticists and recommended by national/international advisory committees for risk assessment of ionizing radiation-induced mutational damage/cancer from the mid-1950s to the present. The LNT concept was later generalized to chemical carcinogen risk assessment and used by public health and regulatory agencies worldwide.