Archives of Toxicology

, Volume 87, Issue 9, pp 1621–1633 | Cite as

Origin of the linearity no threshold (LNT) dose–response concept

  • Edward J. CalabreseEmail author
Review Article


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.


Ionizing radiation Linearity Dose response Risk assessment Threshold dose response Target theory Eugenics LNT 



The research on the topic of hormesis has been supported by awards from the US Air Force and ExxonMobil Foundation over a number of years. Sponsors had no involvement in study design, collection, analysis, interpretation, writing and decision to submit.


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© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.Department of Public Health, Environmental Health SciencesUniversity of MassachusettsAmherstUSA

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