A series of 12 papers published over the past decade have revealed that the June 12, 1956, recommendation of the US National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Committee, Genetics Panel, to switch from a threshold to a linear, non-threshold (LNT) dose–response model was the most significant risk assessment policy change ever made. This recommendation was soon generalized from genetic risk to cancer risk and rapidly adopted by highly influential national and international advisory committees and would determine the setting of exposure standards for ionizing radiation and chemical carcinogens in the United States and throughout the world down to the present time.
This same genetic risk prediction of course applies to all environmental toxicants, including all therapeutic agents. As Paracelsius said several years ago: “Alles ist Gift.” “Everything is toxic at some dose,” the Corollary being (in pharmacogenomics) “There is a drug dosage level that results in therapeutic failure, a level that is efficacious, and a level that is toxic.” This is true for every drug. And each drug, as well as each patient being treated, can show variations in response.
The attached paper represents a brief personal account of how Edward Calabrese stumbled upon the LNT falsification of data. His interest in the history of the LNT is fairly new, starting about 5 years ago as part of research into the history of the hormetic dose–response curve. During the course of writing a manuscript on the origins of the LNT, a preliminary draft was criticized by a senior genetic toxicologist who suggested that Calabrese had neglected the role of Hermann Muller (1890-1967) in shaping the field on this topic. Taking the advice of a reviewer, Calabrese devoted considerable effort to learn about Muller, his life, career, publications, controversies, achievements, and final years. It was during the detailed historical assessment of Muller that unexpected irregularities in the scientific record on mutation risk assessment began to emerge, all potentially troubling and yet feeding interest to get to the bottom of the story.
There was no inherent desire to challenge Muller, his radiation geneticist colleagues, or the NAS. In fact, most of what has been recently reported is material in the historical record –– citing their own words, via correspondence, memos, and similar documents. In other words, these reports tend to let the subjects of this historical tale tell the story in their own way.
Toxicol_Res_Appl_LNTgate_2~1.pdf (128 KB)