Thresholds for radiation induced mutation? The Muller-Evans debate: A turning point for cancer risk assessment

Abstract

In 1949 Robley Evans [1] published a paper in Science supporting a threshold dose response for ionizing radiation-induced mutation, contradicting comments of Hermann Muller during his 1946 Nobel Prize Lecture [2] and subsequent presentations. Evans sent a final draft [3] prior to publication to over 50 leading geneticists/radiologists, including Muller, with this correspondence being generally extremely supportive, including letters from the radiation geneticists Curt Stern, James Neel and Donald Charles. Of interest is that Muller engaged in a dispute with Evans, with Evans dismissing Muller's comments as containing "a few points of scientific interest, and many matters pertaining to personalities and prejudices." A foundation of the Evans threshold position was the study by Ernst Caspari, which was done under the direction of Curt Stern, at the University of Rochester/Manhattan Project, and for which Muller was a paid consultant, thereby having insider knowledge of the research team, results and internal debates. Muller published a series of articles after the Evans Science publication that marginalized the Caspari findings, claiming that his control group was aberrantly high, which caused his threshold conclusion to be incorrect. Internal correspondence in 1947 between Muller and Stern reveals that Muller supported the use of the Caspari control group based on consistency with his own laboratory data. This correspondence shows that Muller reversed his position three years later, soon after the Evans publication. In that same 1947 correspondence with Stern, Muller also claimed that the mutational findings of Delta Uphoff, who was replicating the Caspari study, could not be supported because of aberrantly low control group values only to reverse himself to support the LNT model. The present paper links Muller's threshold rejection/LNT supporting actions to the timing of the debate with Evans concerning Evans' use of the Caspari data to support the threshold model. It is of historical significance that the duplicitous actions of Muller were rewarded, with his newly expressed reversed views becoming generally accepted (while his previously documented contrary views were hidden/remained private). At the same time, the marginalizing of the Caspari findings greatly impacted recommendations to support LNT by major advisory committees.

Keywords: Cancer; Dose response; Manhattan project; Mutation; Radiation; Risk assessment.