Background radiation and cancer risks: A major intellectual confrontation within the domain of radiation genetics with multiple converging biological disciplines

Abstract

This paper assesses the judgments of leading radiation geneticists and cancer risk assessment scientists from the mid-1950s to mid-1970s that background radiation has a significant effect on human genetic disease and cancer incidence. This assumption was adopted by the National Academy of Sciences (NAS) Biological Effects of Atomic Radiation (BEAR) I Genetics Panel for genetic diseases and subsequently applied to cancer risk assessment by other leading individuals/advisory groups (e.g., International Commission on Radiation Protection-ICRP). These recommendations assumed that a sizeable proportion of human mutations originated from background radiation due to cumulative exposure over prolonged reproductive periods and the linear nature of the dose-response. This paper shows that the assumption that background radiation is a significant cause of spontaneous mutation, genetic diseases, and cancer incidence is not supported by experimental and epidemiological findings, and discredits erroneous risk assessments that improperly influenced the recommendations of national and international advisory committees, risk assessment policies, and beliefs worldwide.

Keywords:

• Cancer risk assessment
• chemical risk assessment
• dose-response
• mutation
• radiation
• linear dose-response

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

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Notes

1 Based on numerical linear extrapolation, Muller (1955) asserted there was background mutation incidence due to radiation in his fruit fly model. Yet, other researchers, such as Stadler (1930), had provided plant dose-response data using nine doses with the lower three having no treatment effect, leading to his suggestion of a threshold. Likewise, Giles (1940) administered radiation some 1,000-fold greater than the background without detecting any genetic damage increase above the background in Tradescantia. He also showed that this same high dose had no impact on plants with very low or very high background mutation rates. Giles (1940) concluded that “natural radiation is very rarely involved in the production of spontaneous chromosome aberrations”. Several groups of researchers supported the findings of Giles (1940) using the fruit fly model of Muller. In these studies, Warren P. Spencer (1935), who later was a key collaborator with Muller and Curt Stern on the Manhattan Project radiation genetics mutation research, reported that the feeding of fruit flies with a diet of very high levels of carnotite, a radioactive ore, failed to induce mutation in extensive studies. Also, in other experiments, fruit flies were transported from 70,000-100,000 feet above the earth to enhance the exposure to cosmic rays for 6-16 hours, increasing the exposure rates by about five-fold. These exposures failed to increase the frequency of either recessive lethals or translocations, and they found no breaks in the X-chromosome (Pipkin and Sullivan 1959; Reddi and Rao 1964), thereby not supporting the background radiation assumption of Muller (1955).

2 Readers interested in assessing comprehensively the historical foundations for why the LNT model was adopted should see Calabrese (2019).

3 Muller was one of nine radiation geneticists who provided estimates of radiation-induced mutations from 10 R to the BEAR I Genetics Panel in February 1956. A copy of Muller’s (1956a) analysis dated 25 February 1956 provides a detailed estimate of the number of mutations per 160,000,000 people, the approximate US population at that time. The report of Muller to the BEAR Panel was a seven-page, single-spaced detailed assessment of this issue, providing far greater detail than the Muller (1955) paper. Based on the Muller (1955) paper and his letter to the BEAR I Genetics Panel (Muller 1956a), both of which strongly promoted the doubling dose (DD) concept, there is the unavoidable, yet tentative, conclusion that Muller’s views strongly influenced the BEAR I Genetics Panel DD concept, even though the Panel report (NAS/NRC, 1956) did not cite Muller’s article/letter or other possible sources of influence. At the core of the DD concept was the long-standing belief in the radiation geneticist community that induced mutations by radiation and other causes were not repairable (Muller 1929). In fact, the LNT single-hit model of Timofeeff-Ressovsky et al. (1935) failed to include a repair component. The belief in a lack of genetic damage repair was first challenged by Russell et al. (1958) in their groundbreaking paper on mouse spermatogonia and oocytes.

4 Note that the BEAR I Genetics Panel refused to evaluate the major study of genetic mutation in the offspring of survivors of the atomic bomb explosions in Japan that was offered to the Panel by Panelist James V. Neel. See Calabrese (2020) for a detailed assessment of this matter. Furthermore, the 15-fold greater sensitivity of the male mouse was later shown to be based on a control group error of 120% (Calabrese 2020b). Correction for this error at that time would likely have had a major impact on Panel estimates, leading to a threshold model. The reader is directed to a recently published paper on the Russell mouse mutational historical foundations, errors, and their risk assessment implications (Selby and Calabrese 2023).

5 The dose-rate discovery was considered a major development since before that paper, it was long believed that all radiation-induced damage was cumulative, irreversible, and unrepairable (Calabrese 2019). So significant were these findings perceived that they prompted Hermann Muller to change his laboratory research direction to assess this dose-response phenomenon in fruit flies. In 1972, the NAS BEIR I Genetics Committee (1972) acknowledged the need to incorporate the dose rate concept into risk assessment based on Russell et al. (1958) and subsequent findings.

6 In a 1997 follow-up paper (Russell and Russell 1997), Russell and Russell acknowledged an error in their 1996 PNAS paper (Russell and Russell 1996) by publishing a correction factor to account for their earlier failure to report and deal with large clusters of mutations. As explained in a recently published paper (Selby and Calabrese 2023), the required correction factor is likely to be at least 160% instead of the 120% proposed by Russell and Russell.

Additional information

Funding

EJC acknowledges longtime support from the US Air Force (AFOSR FA9550-19-1-0413) and ExxonMobil Foundation (S18200000000256).