Dose response and risk assessment: Evolutionary foundations.

The present paper indicates that the origin of the LNT concept for ionizing radiation was based on insufficient understanding of evolution, which precluded the possibility of repair of gene mutation. The denial of such repair processes had important implications, leading to a belief in a linear dose response and thus in Hermann J Muller's proclamation of a Proportionality Rule for ionizing radiation. The paper documents how the lack of repair concept dominated the radiation geneticist community to the 1960s leading to the establishment of the linear no threshold dose response (LNT) model for radiation and chemical reproductive and cancer risk assessment. Research from the late 1950s onward would establish the occurrence, generality, and efficacy of genetic and cellular repair processes. While the assumption of a lack of gene mutation repair was wrong, Muller was correct that dose-response concepts need to be founded on mechanistic understandings of evolution. Such mechanisms require the integration of constitutive and inducible adaptive and repair mechanisms that operate in the low-dose zone. This perspective reflects the comment of Dobzhansky (1973) that "nothing makes sense in biology except in light of evolution." While this is a powerful scientific dictum, it assumes a correct understanding of evolution, something that the origins of the LNT dose response lacked. Such modern mechanistic repair developments reveal that the historical foundations of LNT were flawed from the start. Nonetheless, they have been carried forward to the present time, principally by environmental health regulatory agencies that decoupled risk assessment policy from a sound evolutionary foundation.