Year : 2017 | Volume
: 40 | Issue : 2 | Page : 51--59
Radiation protection policies and practice rest on a thin sheet of ice called linear, no-threshold hypothesis
Distinguished Fellow, M.S. Swaminathan Research Foundation, Taramani, Chennai, Tamil Nadu, India
P C Kesavan
Distinguished Fellow, M.S. Swaminathan Research Foundation, Taramani, Chennai, Tamil Nadu
|How to cite this article:|
Kesavan P C. Radiation protection policies and practice rest on a thin sheet of ice called linear, no-threshold hypothesis.Radiat Prot Environ 2017;40:51-59
|How to cite this URL:|
Kesavan P C. Radiation protection policies and practice rest on a thin sheet of ice called linear, no-threshold hypothesis. Radiat Prot Environ [serial online] 2017 [cited 2017 Dec 16 ];40:51-59
Available from: http://www.rpe.org.in/text.asp?2017/40/2/51/210577
Soon after the twin discoveries of X-rays and radioactivity, made only a few months apart, a few years before the close of the 19th century, cancer incidence, initially skin cancers and then leukemia among the radiation workers became evident. Careful observations revealed that skin cancers among the radiation workers occurred mainly where the exposure to about 600r (6 Gy) had caused erythema (reddening of skin). In 1928, the National Committee for Radiation Protection and Measurement, USA fixed the tissue “tolerance dose” as 1/100th of erythema dose (600r) spread over 30 days (i.e. 6 rad spread over 30 days) or 0.2r/day (in the S.I system it is about 1.86 mGy/day or 680 mGy/year). The “tolerance dose” was thus prescribed within the limits of doses, which cause specific “deterministic” effects.
In the year 1927, Muller and Stadler both of the USA working with fruitfly (Drosophila melanogaster) and maize, respectively showed that X-rays induced mutations (i.e. heritable changes in traits). Both of them were basically geneticists, but that DNA is the genetic material was not known until 1953. Muller's paper  published in Science was not only slightly ahead of Stadler's but also substantially unequivocal. Muller had done a marvelous piece of chromosome engineering with the result that any mutation induced by X-rays on the X-chromosome of the irradiated males will result in the total absence of grandsons in the M2 generation resulting from mating of pairs of males and females of the M1 generation. The M1 generation is derived from mating of irradiated male flies (called C1B) with virgin female flies. The lethal mutations induced by X-rays are called the “sex-linked recessive lethals” (SlRl). The SlRl in 1927 was considered as “point mutations,” but later, these have been found to be 'deletions' of segments of varying lengths from the irradiated X-chromosome.
From the point of radiation protection, the SlRl induced by X-rays remained purely academic until after the detonation of atomic bombs in August 1945 over Hiroshima and Nagasaki in Japan. The A-bombs ended the World War II, but triggered a battle on the radiation protection policy based until then on the “deterministic” dose. Muller was not lauded immediately after his epoch-making discovery in 1927 about the mutagenic properties of ionizing radiation. He remained largely unnoticed during 1927 and until after the A-bombs detonation over Hiroshima and Nagasaki in August 1945. After the detonation of A-bombs in 1945, Atomic Bomb Casuality Commission was formed and during its work, the discovery of the mutagenic action of ionizing radiation in 1927 by Muller came to light. The immediate concern was about the mutagenic action of ionizing radiation in general, and of the A-bombs exposed survivors and their descendants, in particular. It is this concern that led to the recognition of Muller, and his meteoric rise to new heights in science; he was also awarded the Nobel Prize in medicine in 1946. He was also much sought after in the United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR), Biological Effects of Ionizing Radiation (BEIR) of USA, International Commission of Radiological Protection (ICRP), National Science Academies, USA and several other important decision-making bodies.
The rather unfortunate turning point for the radiation protection policies occurred on the 12th December 1946 when Muller delivered his Nobel Lecture. Despite the lack of scientific data to support his ideology, Muller declared that there is “no escape from the conclusion that there is no threshold” for the induction of genetic changes (i.e. mutation) by the ionizing radiation. In fact, the full sentence from Muller's Nobel Lecture  reads as follows:
“In our more recent work with Raychaudhuri (1939, 1940) these principles have been extended to total doses as low as 400r, and rates as low as 0.01r per minute, with gamma rays. They leave, we believe, 'no escape from the conclusion that there is no threshold dose', and the individual mutations result from individual 'hits,' producing genetic effects in their immediate neighbourhood.” He calls these “hits” as “point mutations.”
This author notes that during the 1940s, 1950s, and 1960s, the scientists, in general, mostly focused on their own narrow areas of specialization and seldom sought to understand the developments across closely related areas. Muller was no exception. In basing his ideological concept of linear, no-threshold hypothesis, he referred to the “hit theory” of the 1920s which assumed that “photon” like a bullet hit a very vital constituent of the cell and that caused mutation and even death. However, that the “hit theory” would not be valid at least for low linear energy transfer (LET) X- and gamma rays should have been inferred by the demonstration of “oxygen effect” in radiobiology by Petri. The oxygen effect is that molecular oxygen in the cells and tissues enhance the radiobiological damage induced by low-LET ionizing radiation by a factor of about 1.5–2.5. In dry seeds and spores, it could be as high as 5.0–6.0. That later became the central dogma in low LET radiobiology for radiotherapy. Much earlier, two French physicians, Bergonie, and Tribondeau  had shown that rapidly dividing cells with significant mitotic activity were far greatly more sensitive to ionizing radiation than nondividing cells. Had Muller known these, he probably would not have implicated the “hit” theory. Or else, he could also have deliberately not cited them as he had done so with respect of a few papers published before his Nobel Lecture, which did not support the linear relationship between the dose and mutation frequency.
Muller Ignored Science and Established His Ideology of LNT
Atleast two papers of Calabrese , clearly unravel that Muller ignored the scientific papers that showed a “threshold dose” for mutation induction in D. melanogaster and cited only those which supported his ideology. The citations made by Muller in his Nobel Lecture indeed confirm that he was selective in choosing the references (i.e. research papers of other scientists). Just to provide an example, Muller had cited Oliver, Hanson and Heys, and Timofeeff–Ressovsky, who all had used high doses and dose-rates and found linearity. He did not cite the papers of Hanson and Heys, Weinstein, Stadler, Serebrowsky and Dubinin, which did not support linearity at low doses and low dose-rates. Had Muller cited both the supporting as well as opposing sets of research publications, he could not have declared, “no escape from the conclusion that there is no threshold.”Calabrese  has elegantly documented that Muller let down the “science” to promote his ideology about radiation-induced genetic damage at low doses and dose-rates. He has followed up this paper with more details in a subsequent paper.
As of today, the absence of linearity between dose and mutation frequency in the germ cells of the fruitfly (D. melanogaster) has been unequivocally settled. Radiation genetic studies of Koana et al. have demonstrated a significant reduction of background (spontaneous) mutation rates by low doses (0.2 Gy) of X-rays; the spontaneous (unirradiated) mutation rate was 0.33% whereas a dose of 0.2 Gy reduced it to 0.07%. This is the radiation hormesis or the beneficial effects of low doses of ionizing radiation. However, a higher dose (10.0 Gy) enhanced the mutation frequency to 0.79% as to be expected. These authors had earlier reported a threshold at 1.0 Gy (100r) for the somatic mutation rates in the same organism.
From Fruitflies to Mice, to Human Beings
Late, Alexander Hollaender and Oak Ridge National Laboratory, USA, are synonyms with unraveling several phenomena and mechanisms in radiobiology during the 1950s and 1960s. In particular, Russell of Oak Ridge National Laboratory, introduced mice in place of fruitfly for basic research in radiation biology. Mice are much closer to human beings in the evolutionary history, or the genealogy than the fruitflies (D. melanogaster). Russell et al. devised a useful testing system in mice called the Russell's mouse “specific locus test” (SLT); the seven loci (i.e. genes expressing specific traits) were located on seven pairs of nonhomologous chromosomes, and therefore, there was no question of genetic linkage among two or more of the 7 loci. It was an elegant system to assess the mutations induced by a variety of physical and chemical mutagens. By 1960, the U.S. National Academy of Sciences had concluded that all radiation was dangerous, and the radiobiological effects were cumulative and irreparable. Therefore, the paper by Russell et al. introducing the “dose-rate effect” (i.e. reduction in the mutation rates, when the radiation dose is delivered at low dose-rates) challenged the notion that radiobiological damage is irreparable. Calabrese  points out that Russell's sustained, respected, and painstaking work in observing and documenting the effects of radiation on mice indicated that the rate at which radiation dose was administered made a major difference in the measured mutation rate for the identical total dose. The implication of this research is that lower dose-rates reduced mutation rates by factors of 3 and 20 in certain germ cells of male and female mice, respectively. It also revealed that fundamental beliefs/assumptions of the radiation geneticists from the 1940s through the 1950s concerning the induction by ionizing radiation of mutations in germ cells of mammals (i.e. especially in mouse spermatogonia and cocytes) were incorrect. These observations signaled serious flaws in the LNT model but could not be brought out in the open owing to Muller's dominance and unwillingness to accept the mice data!.
Yet, the epoch-making papers by Russell et al. and Russell and Kelly  remained quiescent and did not make any impact on the LNT model. The reason was the most influential and dominant Muller. Calabrese  explains the reasons. It is that Russell was acutely aware of the confrontational nature of Muller and his capacity to challenge others and generate professional hostility, having witnessed it first hand as a member of the BEAR II Genetics Panel. It was well-known that Neel a distinguished geneticist associated with the Radiation Effects Research Foundation (RERF) and Muller had very deeply strained relationship as Muller could not accept the RERF's findings on the absence of genetic effects in the children of the A-bombs survivors. The conflict between Muller and Neel (who was 25 years younger than Muller) started by Muller's response to a presentation by Neel at the WHO Study Group Meeting on the “Effects of Radiation on Human Heredity” held in Denmark in August 1956. Based on his decade-long studies of atomic bomb survivors, Neel criticized a number of assumptions about radiation dose and mutation rates, thereby challenging the foundation of the LNT dose-response model. Muller took it as an attack on his life's work. Muller tried to pressure both Neel and conference leaders not to present the findings of genetic effects on the A-bomb survivors and this led other scientists to threaten to not participate should Muller have his way! The situation became so disruptive that Alexander Hollaender, the Conference Session Chair and Russell's supervisor arranged for Muller and Neel to meet later in Oak Ridge, hoping that the acrimonious situation could be resolved. That meeting held on January 6,1957 at Oak Ridge did not result in reconciliation, though Alexander Hollaender acting as the referee tried his best. Later, Neel reminisced that Muller could not accept that a human geneticist has turned around and pointed out some of the limitations and difficulties in working with Drosophila. Calabrese  also refers to the letter that Neel wrote to Stern about how impossible it was to have a rational scientific discussion with Muller on scientific points of dispute, with Muller often responding in highly emotional ways. It is surmised that this type of behavior and intimidation by Muller may well have contributed to the reluctance of Russell to directly challenge Muller on the LNT concept with his dose-rate findings. However, after the death of Muller in April of 1967, Russell became more eager to discuss his mega-mouse SLT research, and its implications for the LNT model. With the reactivation of Russell's earlier studies on the dose-rate effects and radiation-induced mutation frequencies in the SLT, an oversight in computing the spontaneous mutation frequencies came to be noticed a few decades later.
It turns out that there was also a long-standing problem of the Russell's not reporting spontaneous mutations arising as clusters of spontaneous mutations during the perigametic interval. Selby  took it up with Russell and after some initial dispute, both agreed that an adjustment upward for the spontaneous (control) mutation frequency was needed to correct the long-standing error. Thus, an increase in the mutation rate of 1.7-fold for males and a 2.2-fold for males and females combined was recommended by the Russells, while Selby suggested an increase of 4.8-fold for males and 7.3-fold for males and females combined. Such increases observed in the control (i.e. unirradiated) groups in comparison with mutation frequencies induced at low doses and low-dose rates categorically dismissed the LNT model. Both the suggestions categorically dismissed the LNT model. What happens due to the corrections are as follows: The Russell's correction essentially converted a linear dose response to a threshold dose response while Selby's correction showed the possibility of a J-shaped dose-response, suggestive of radiation hormesis at low-dose rates.
While mouse is a far more relevant test system than Drosophila, there is yet vast difference between mouse and humans. Extensive analyses of the data generated by the RERF Japan have led to the conclusion that atomic bomb radiation has not caused any genetic changes in the children of the parents exposed to varying doses of ionizing radiation of differing LET values. The absence of the “expected” and “greatly feared” genetic and teratogenic effects in the children of the highly exposed atomic bomb survivors is described in a simple and sophisticated statement of Neel et al.,. This is as follows:
“The children of the most highly irradiated population in the world's history provide no statistically significant evidence that mutations were produced in their parents. In particular, the studies should prove reassurance to that considerable group of exposed Japanese and their children, without whose significant cooperation these studies would have been impossible and who have over the years been subjected to a barrage of exaggerations concerning the genetic risks involved.” For additional information on this issue, the readers are referred to Kondo. The author discusses several radiobiological mechanisms which repair the radiation-induced DNA damage and also those which eliminate the cells with irreparable damage to facilitate their replacement with normal stem cells. The elimination of damaged cells by necrosis or apoptosis is well known., These have also been briefly discussed by Kesavan.
Radiobiology Never Supported the LNT Model; Instead it Consistently Rejected it
It is astonishing that a few radiobiologists refer to the LNT model as just “controversial.” On the other hand, it is quite expected that radiobiologists with a “systems biology” approach to interpreting data derived from voluminous radiobiological research, especially that involving low doses and low dose-rates would outright reject the LNT model. There have been others, not necessarily radiobiologists, who have noted that LNT is governed by nonscientific influences. In fact, Taylor  in his 1980 Sievert Lecture stated that “some non-scientific influences prevail over scientific facts on radiation protection standards.” Wrixon  wrote, “Radiation protection is not 'Pure Science;' it is based on science, but also relies on assumptions that are necessary to the application of scientific knowledge to real life issues.” This statement is rather vague, and it needs to be explained.
Yet, one should know what the hardcore low-dose radiobiological studies actually reveal.
The term hormesis describes the beneficial effects at low concentrations/doses of substances/agents which at high doses are toxic. Hormesis means, “to excite in small amounts;” Greek “Hormoligosis.” It could be physiological effect that occurs at low doses, and which cannot be anticipated by extrapolating from toxic effects noted at high doses. Luckey  has presented a comprehensive list of studies by several authors, showing that low doses of ionizing radiation produce beneficial effects in organisms and are “hormetic.” Sagan  has pointed out that radiation hormesis received scant respect because it conflicts with the conventional radiation science paradigm.
There are several experimental studies which show that suboptimal levels of radiation impairs cell multiplication and growth by Planel  and Kawanishi et al. These justify the depiction of radiobiological effects from very low to high doses as complete dose-response curve by Kesavan.
Contrary to the general assumption that radiation doses delivered over a period of time act in a cumulative manner, (i.e. a dose of 0.1 Gy given first and another dose of 0.9 Gy given later would produce a biological effect equivalent to 0.1 Gy + 0.9 Gy = 1.0 Gy), a lower dose given first often protects the cells and organisms against a subsequent higher dose exposure. This is the phenomenon of radio-adaptation. The low doses that are effective in inducing radioadaptive responses are known as priming doses. Radioadaptive responses have been observed in multiple biological end-points such as unscheduled DNA synthesis, micronuclei, chromosomal aberrations, gene mutations, and cell survival. Jayashree et al. have compiled a few of the very early reports on radio adaptation. Radioadaptation as a phenomenon of valid consideration has been recorgnized by UNSCEAR. Adaptive responses have been documented in humans following occupational exposure  and in people living in very high natural background areas by Ghiassi-nejad et al. The radioadaptation clearly negates the LNT model.
Differential Gene Expression Induced by Low and High Doses
Jayashree et al. were among the first to discuss how the phenomenon of “differential gene expression” at low and high doses negates the LNT hypothesis. Kesavan  has cited more recent articles on this subject and has drawn attention to the fact that cellular response to low and high doses of ionizing radiation is qualitatively different. More recently, Kesavan  has argued that since the gene products induced at low and high doses are qualitatively different, it is absurd to draw a linear line from low to high doses or make backward extrapolation of genetic damage from high to low doses.
Strange but True
In 2005, the U.S. National Research Council, notwithstanding the low-dose radiobiological phenomena described above, concluded that current scientific evidence is consistent with the linear, no-threshold dose-response relationship. On the other hand, Tubiana et al. for the French National Academies of Science and Medicine concluded the opposite. These contradictory conclusions are atleast partly because of an emphasis on epidemiological vis-a-vis low-dose radiobiological data. The BEIR  does not consider the low-dose radiobiological phenomena, whereas the French National Academies of Science and Medicine  give due-importance to radiobiological mechanisms. Ulsh  describes that the epidemiological data and the radiobiological data represent a “top-down” versus “bottom up” approach, respectively. He has also argued how the ionizing radiation, even at high doses and dose-rates, is a relatively weak carcinogen. That this view is correct is clearly evident from the absence of heritable genetic disorders in the children of the A-bombs survivors by Neel  Kondo. The epidemiological data which BEIR largely depends on has serious limitations discussed by Taubes. Further, as has been elaborated by Luckey, several of the epidemiological studies involving nuclear workers, general public exposed to nuclear accidents, etc., suffer from “credibility gap” between data analyzed, and inferences drawn. What is, however, far worse is the interpretation of the epidemiological data, revealing prejudice against radiation hormesis.
Luckey  has analyzed all the seven BEIR reports. Of these, only two of them directly relevant to the genetic effects attributed to radiation exposures are discussed here: (i) The 1990 BEIR V  report states (p. 252), ” The risks of acute leukemia and chronic myeloid leukemia are increased by irradiation of the hemopoietic cells, the magnitude of increase depending on the dose of irradiation.” This concept is not supported by the data of Shimuzu, et al. on the cancer risk and mortality among the A-bombs survivors. In addition, the relative risk of colon cancer was significantly lower in the dose-range of 10–19 rad than at 0 rad (ii) There are also discrepancies between actual data on the health effect of ionizing radiation among the A-bombs survivors in Hiroshima and Nagasaki and the conclusions drawn by the 2006 BEIR VII report. The summary for BEIR VII states: “The main studies establishing the health effects of ionizing radiation are those analysing survivors of the Hiroshima and Nagasaki atomic bombings in 1945” (p. 19 of the report). Luckey  points out that the data show unexpected benefits from acute exposure to low-dose irradiation. He has reproduced the data of Mine et al., who found apparently beneficial effect of low to intermediate doses of A-bombs radiation on human lifespan. The data show significant reduction in the relative risk for total mortality in Japanese atomic bombs survivors from 1950 to 1985. Yet, the BEIR VII (2005, p. 19) is “that the preponderance of information indicates, that there will be some risk, even at low doses.” Luckey  goes on to state that the committee failed to recognize the significant decrease (P points out a prejudice against radiation hormesis in a study by Cardis et al. This study by Cardis et al. presents the results of internationally combined analyses of cancer mortality data on 95, 673 radiation workers (84.5% men) monitored for external exposure to ionizing radiation during their employment for 6 months or longer in the nuclear industry in any of the three countries (the U.S., the U.K, and Canada). These analyses, the authors say, were undertaken to obtain a more precise direct assessment of the carcinogenic effects of protracted low-level exposure to external, predominantly gamma-irradiation. The authors conclude, “Although they are lower than the linear estimates obtained from studies of atomic bomb survivors, they are compatible with a reduction of risk at low doses to risks twice those on which current radiation protection recommendations are based. Overall, the results of this study do not suggest that current radiation risk estimates for cancer at low levels of exposure are appreciably in error”. A prejudice against radiation hormesis at low doses is evident from the statement (p. 119), “As there was no reason to suspect that exposure to radiation would be associated with a decrease in risk of any type of cancer, one-sided tests are presented throughout.” Luckey  has reworked on the data of Cardis et al. and shown reduced cancer mortality rates (i.e. hormesis) for the 32,000 exposed nuclear workers as compared to 45, 825 unexposed (control) nuclear workers. The cancer mortality was found substantially reduced for those exposed in the dose range of 1–7 cGy Figure 29, P.59 of Luckey].
Intensity of Attacks between Pro- and Anti-LNT Groups
During 2015 and 2016, papers have been published that go beyond the expression of views and making interpretations of low-dose radiobiological data to result in highly acerbic statements. In a recent paper, Beyea  refers to an earlier paper by Calabrese  on the origins of linear, no-threshold (LNT).
Scientists for Accurate Radiation Information Comes in
There is now a growing demand world over to reject the LNT and put in its place a science-based model for evolving appropriate policies and standards for radiation protection of the general public as well as the radiation workers. In fact, the US-based “Scientists for Accurate Radiation Information” (SARI) formed about 4 years ago, has several leading radiation biologists, radiation medical physicists, radiotherapists, and policy experts and outstanding intellectuals from most parts of the world. Through emails, the members exchange their views on the subject and explore the best ways and means to put radiation protection standards on a firm scientific basis. The unwanted fear of radiation (i.e. the radiophobia) leading to mental illnesses in case of exposed survivors as well as the unexposed people in the neighborhood of nuclear accidents (e.g. Chernobyl, Fukushima) have caused enormous health and socioeconomic problems for no valid reasons at all. The fact that people living in the high level natural background Areas are healthy and as normal as those living in the normal level natural background areas exerts little favorable impact on these people because LNT-based estimations of the number of people who will die of cancers over a period of time (i.e. the fear)overwhelms any reassurances. In this regard, Taylor was so right when he referred to LNT and its impact in the Sievert Memorial Lecture 1980. He, “No one has been identifiably injured by radiation while working within the first numerical standards (0.2r/day) set by the NCRP and then the ICRP in 1934.” He goes on, “An equally mischievous use of the number game is that of calculating the number of people who will die as a result of having been subjected to diagnostic X-ray procedures. An example of such calculations are those based on a linear, non-threshold, dose-effect relationship, treating the concept as a fact rather than a theory --- These are deeply immoral uses of our scientific knowledge.”
An unreasonable offshoot of the LNT is the absurd concept and use of “collective dose.” It assumes the final biological outcome will be the same whether 1 person is exposed to a total whole body dose of 5 Gy or if 50,000 persons are varyingly exposed to 5 Gy that gives a mean exposure rate of 0.0001 Gy per person. To say the least, it is absurd from scientific point of view. In fact, such non-scientific, assumptions-based estimations are largely responsible to promote radiophobia and unfounded fear of radiation.
Hence, SARI is endeavoring to restoring scientific rationality into the evolution of radiation protection standards.
Biological Effects Following Acute Vis-A-Vis Chronic Exposures
As had been mentioned earlier, the rate at which the radiation dose is delivered to reach a given total dose forms the tissue of dose-rate. Even at the time of Muller's Nobel Lecture in December 1946, it was noted that low dose-rates reduced the mutation frequency in the fruit fly D. melanogaster. The significance of dose-rate became much amplified with the mouse SLT studies by Russell et al. As stated earlier, at low doses and dose-rates, there was no linearity but a “threshold' or even J-shaped curve indicating hormesis at low doses and low dose-rates.
Dose-Rate Problem in Extrapolation of A-Bombs Data to Estimation of Cancer Risk of Chronic Exposure Situations
Both based on the scientific literature and personal association with some of the outstanding radiobiologists in Japan, this author notes that the Japanese people who were devastated by the A-bombs in 1945 have now conquered the radiophobia. The recent Fukushima nuclear power reactor accident has not prevented the Japanese from continued dependence on nuclear fuel for power generation. Dr. Tanooka is among the world's leading radiobiologists and outstanding thinkers. With the backing of enormous amount of valid data, he disagrees with the dose and dose-reduction factor (DDREF) of just 2 for the extrapolation of cancer data from acute A-bombs exposure to chronic low environmental exposures. Tanooka  has shown that quantitative analysis of cancer risk of ionizing radiation is a function of dose-rate. Employing what he refers to as “non-tumour dose, Dnt.,” defined as the higher dose of radiation at which no statistically significant tumor increase is observed above the control (spontaneous), level, he found an inverse correlation between Dnt and dose-rate of the radiation. Dnt increases 20-fold with decreasing dose-rate from 1 to 10−8 Gy per minutes for whole body irradiation with low LET radiation. He has also estimated the dose-rate effectiveness factor to extrapolate the A-bomb data to cancer risk of environmental radiation as 16.5, presently the DDREF for cancer risk to extrapolate from A-bomb survivors data is just 2 (set by BEIR, UNSCEAR, ICRP, etc.).
From what have been aforementioned, the present policies and practice of radiation protection are in appreciable error. It needs to be corrected if the “radiophobia” of the general public is to be eliminated, and the peaceful applications of nuclear energy in power generation, medicine, and agriculture need to be enhanced.
Radiation Protection Policy based on “tolerance dose” as 1/100th of erythema dose spread over 30 days (i.e. 0.2r/day (in the S.I. system about 1.86 mGy/day) since 1928 was replaced in 1950s with “linear, no-threshold dose” (LNT) model based purely on the Nobel Laureate Muller's ideology. It has had no scientific evidence then or even today.When Muller proposed the LNT hypothesis in his Nobel Lecture delivered on 12th December 1946, the structure of the genetic material (i.e. DNA) was not known; in particular, its capacity to repair any damage caused to it by the physical and chemical genotoxins (i.e. DNA repair) or to eliminate by death of the cell(s) carrying extensive unreparable damage by cellular processes such as necrosis, mitotic catastrophe, or the more sophisticated apoptosis had not been known.The “target theory” that Muller depended on to support the LNT model, unfortunately regarded cellular organelles as nonliving, static entities; this assumption was totally erroneous as cells and organisms exhibit tenacity of life with a wide spectrum of defense and self-healing/self-repairing mechanisms.The LNT model assumes that radiation doses are cumulative which is proven wrong by “radioadaptive response.” In fact, the low doses confer beneficial effects referred to as “radiation hormesis.”Both “cell death” and mutagenesis (i.e. induction of mutations in somatic cells that may lead to cancer) are biological processes involving gene expression. In other words, ionizing radiation, chemical genotoxins do not kill or mutate by physical or chemical processes, but through the induction of molecular signaling for gene expression. Today, a large number of outstanding research papers deal with 'differential gene expression' at low and high doses. These data form a fatal blow to the LNT hypothesis.The LNT model that had been rigorously followed by several policy-making bodies, primarily ICRP, BEIR and to a lesser extent UNSCEAR has failed to explain why the radiation from the A-bombs detonated over Hiroshima and Nagaski in August 1945 did not result in any discernible increase in heritable mutations (leading to a diseased state) in the descendants of the exposed survivors. Further, there are reports of reduced incidence of different types of cancers in the Japanese population exposed to “low” whole body doses than in unexposed (control) population. A “J” – shaped curve and not a linear one is reported in plots linking cancer incidence with exposure doses.The use of “collective dose” for the estimation of radiation risks is scientifically wrong and socially immoral.There is an agreement among radiation biologists and radiation protection agencies that evacuation of large number of residents from the Chernobyl and Fukushima radiation accident sites based on assumption of highly exaggerated adverse health effects at around environmentally realistic or the “tolerance dose” has resulted in “mental” and not “somatic” illnesses. The false notion that even very low doses could induce cancers results in fear psychosis which leads to mental disturbance. When people are seriously affected mentally, somatic disorders (not necessarily cancers) can result. Reports of cardiovascular diseases following accidental exposures to ionizing radiation possibly have more to do with fear and anxiety than radiation-induced biological events.Carefully-designed rigorous radiobiological and epidemiological studies of the people living in world's high level natural background radiation areas in India and China do not show any increased incidence of diseases ascribable to higher levels of chronic exposures.Under these circumstances, as viewed by Taylor in his 1980 Sievert Memorial Lecture, the radiation safety policy makers and regulatory authorities should reexamine the validity of “tolerance dose.” There is also need to reckon with the fact that human environment and diet with ever-increasing nanoparticles, pesticides and electronic waste etc., pose serious health effects. Hence, it is wrong to put all the blame on low doses of ionizing radiation using the LNT model, and go on periodically reducing the maximum permissible exposure levels to the radiation workers and general public. The need of the hour is to sift facts from fallacies.
I acknowledge the excellent support given by Ms. Sharmila Babu in typing the manuscript and setting the references. I would particularly like to thank Dr. D.D. Rao, Editor, Radiation Protection and Environment for valuable suggestions for improving the manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Muller HJ. Artificial transmutation of the gene. Science 1927;66:84-7.|
|2||Available from: http://www.nobelprize.org/nobel_prizes/medicine/laureates/1946/mu. [Last accessed on 2017 Mar].|
|3||Petri E. The conditions for the biological activity of Roentgen rays. Biochem Z 1921;119:23-44.|
|4||Kesavan PC, Trasi S, Ahmad A. Modification of barley seed radiosensitivity by posttreatment with caffeine. I. Effect of post-irradiation heat shock and nature of hydration. Int J Radiat Biol Relat Stud Phys Chem Med 1973;24:581-7.|
|5||Bergonie J, Tribondeau L. Interpretation of some results of radiotherapy and an attempt at determining a logical technique of treatment. PubMed. Gov., US National Library of Medicine, National Institute of Health. Radiat Res 1959; 11:587-8.|
|6||Calabrese EJ. Muller's Nobel Prize Lecture on Dose-response for ionizing radiation: Ideology or science? Arch Toxicol 2011;85:1495-8.|
|7||Calabrese EJ. Muller's Nobel prize lecture: When ideology prevailed over science. Toxicol Sci 2012;126:1-4.|
|8||Oliver CP. The effect of varying the duration of x-ray treatment upon the frequency of mutation. Science 1930;71:44-6.|
|9||Hanson FB, Heys F. Radium and lethal mutations in Drosophila; further evidence of the proportionality rule from the effects of equivalent doses differently applied. Am Nat 1932;66:335-45.|
|10||Timofeeff-Ressovsky NW, Zimmer KG, Delbruck M. Nachrichten von der gesselschaft der Wissenschaften zu Gottingen. Uber die nature der genmutation und der genstruktur. Biologie 1935;1:13.|
|11||Hanson FB, Heys F. An analysis of the effect of the different rays of radium in producing lethal mutations in Drosophila. Am Nat 1929; 63:201-13.|
|12||Weinstein A. The production of mutations and rearrangements of genes by x-rays. Science 1928;67:376-7.|
|13||Stadler LJ. Some genetic effects of X-rays in plants. J Hered 1930; 21: 3-19.|
|14||Serebrowsky AS, Dubinin NP. X-ray experiments with Drosophila. J Hered 1930;21:259-65.|
|15||Koana T, Okada MO, Ogura K, Tsujimura H, Sakai K. Reduction of background mutations by low-dose X irradiation of Drosophila spermatocytes at a low dose rate. Radiat Res 2007;167:217-21.|
|16||Calabrese EJ, Stanek EJ 3rd, Nascarella MA. Evidence for hormesis in mutagenicity dose-response relationships. Mutat Res 2011;726:91-7.|
|17||National Academy of Sciences. The Biological Effects of Atomic Radiation. Summary Reports. National Academy of Sciences, National Research Council, Washington D.C; 1906.|
|18||Russell WL, Russell LB, Kelly EM. Radiation dose rate and mutation frequency. Science 1958;128:1546-50.|
|19||Calabrese EJ. The threshold vs LNT showdown: Dose rate findings exposed flaws in the LNT model part 2. How a mistake led BEIR I to adopt LNT. Environ Res 2017;154:452-8. Doi: 10.1016/j. envres.2016-11-024.|
|20||Russell WL, Russell LB, Kelly EM. Dependence of mutation rate on radiation intensity. In: Buzzati-Traverso AA, editor. Immediate and Low Level Effects of Ionizing Radiation. London: Taylor & Francis Ltd; 1960. p. 311-20. [Also, International J Rad Biol 1960, Supplement:311-20.|
|21||Selby PB. Discovery of numerous clusters of spontaneous mutations in the specific-locus test in mice necessitates major increases in estimates of doubling doses. Genetica 1998;102-103:463-87.|
|22||Neel JV, Satoh C, Goriki K, Asakawa J, Fujita M, Takahashi N, et al. Search for mutations altering protein charge and/or function in children of atomic bomb survivors: Final report. Am J Hum Genet 1988;42:663-76.|
|23||Neel JV, Schull WJ, Awa AA, Satoh C, Kato H, Otake M, et al. The children of parents exposed to atomic bombs: Estimates of the genetic doubling dose of radiation for humans. Am J Hum Genet 1990;46:1053-72.|
|24||Kondo S. Health Effects of Low Level Radiation. Osaka, Madison, WI, USA: Kinki University Press, Japan and Medical Physics Publishing; 1993. p. 213.|
|25||Bauer G. Low dose radiation and intercellular induction of apoptosis: Potential implications for the control of oncogenesis. Int J Radiat Biol 2007;83:873-88.|
|26||Portess DI, Bauer G, Hill MA. O'Neil P. Low dose radiation on non- transformed cells stimulates the selective removal of precancerous cells via intercellular induction of apoptosis. Cancer Res 2007;67:1246-53.|
|27||Kesavan PC. Linear, no threshold response at low doses of ionizing radiation: Ideology, prejudice and science. Curr Sci 2014;107:46-53.|
|28||Taylor LS. Some nonscientific influences on radiation protection standards and practice. The 1980 Sievert Lecture. Health Phys 1980;39:851-74.|
|29||Wrixon, AD. What can we tell people about health effects of radiation exposure. Radiat Prot Environ 2016;39:17-21.|
|30||Luckey TD. Radiation Hormesis. Boca Raton, FL: CRC Press; 1991. p. 239.|
|31||Sagan LA. What is hormesis and why haven't we heard about it before? Health Phys 1987;52:521-5.|
|32||Planel H, Soleilhavoup JP, Tixador R, Richoilley G, Conter A, Croute F, et al. Influence on cell proliferation of background radiation or exposure to very low, chronic gamma radiation. Health Phys 1987;52:571-8.|
|33||Kawanishi M, Okuyama K, Shiraishi K, Matsuda Y, Taniguchi R, Shiomi N, et al. Growth retardation of paramecium and mouse cells by shielding them from background radiation. J Radiat Res 2012;53:404-10.|
|34||Kesavan PC. Low dose radiation health hazards: Radiobiological mechanisms versus theoretical predictions based on Linear, Non-threshold model. In: Rajaraman R, editor. India's Nuclear Energy Programme – Future Plans, Prospects and Concerns. New Delhi: Published by Indian National Science Academy and Academic Foundation ; 2013. p. 89-109.|
|35||Jayashree B, Devasagayam TPA, Kesavan PC. Low dose radiobiology: Mechanistic considerations. Curr Sci 2001;80:515-23.|
|36||United Nations Scientific Committee on the Effects of Atomic Radiations Report; 2009.|
|37||Barquinero JF, Barrios L, Caballín MR, Miró R, Ribas M, Subias A, et al. Occupational exposure to radiation induces an adaptive response in human lymphocytes. Int J Radiat Biol 1995;67:187-91.|
|38||Ghiassi-nejad M, Mortazavi SM, Cameron JR, Niroomand-rad A, Karam PA. Very high background radiation areas of Ramsar, Iran: Preliminary biological studies. Health Phys 2002;82:87-93.|
|39||Kesavan PC. Linear, no threshold model in radiation protection and safety: Standards thrive on 'assumptions' and not on science-based evidence Curr Sci 2017;12:2349-50.|
|40||National Research Council, Committee Assess Health Risks from 'Exposure to Low Levels of Ionizing Radiation. Health Risks from Low Levels of Ionizing Radiation: BEIR VII, Phase 2. Washington, D.C.: The National Academies Press; 2006.|
|41||Tubiana M, Aurengo A, Averbeck D, Bonin A, Leguen B, Massee R, et al., editors. Dose-effect Relationships and Estimation of the Carcinogenic Effects of Low Doses of Ionizing Radiation. Academy of Medicine (Paris) and Academy of Science (Paris) Join Report No. 2; March 30, 2005.|
|42||Ulsh BA. The new radiobiology: Returning to our roots. Dose Response 2012;10:593-609.|
|43||Taubes G. Epidemiology faces its limits. Science 1995;269:164-9.|
|44||Luckey T D. Nuclear law stands on thin ice. Int J Nucl Law 2008;2: 33-65.|
|45||BEIR Committee. Health Effects of Exposure to Low Levels of Ionizing Radiation, National Academies Press, Washington D.C.; 1990.|
|46||Shimizu Y, Kato H, Schull WJ. Studies of the mortality of A-bomb survivors 9. Mortality, 1950-1985: Part 2. Cancer mortality based on the recently revised doses (DS86). Radiat Res 1990;121:120-41.|
|47||Mine M, Okumura Y, Ichimaru M, Nakamura T & Kondo S. Apparently Beneficial Effect of Low to Intermediate Doses of A-bomb Radiation on Human Lifespan. Int J Radiat Biol 1990;58: 1035-57.|
|48||Cardis E, Gilbert ES, Carpenter L, Howe G, Kato I, Armstrong BK, et al. Effects of low doses and low dose rates of external ionizing radiation: Cancer mortality among nuclear industry workers in three countries. Radiat Res 1995;142:117-32.|
|49||Beyea J. Response to, on the origins of the linear no-threshold (LNT) dogma by means of untruths, artful dodges and blind faith. Environ Res 2016;148:527-34.|
|50||Calabrese EJ. On the origins of the linear no-threshold (LNT) dogma by means of untruths, artful dodges and blind faith. Environ Res 2015;142:432-42.|
|51||Tanooka H. Meta-analysis of non-tumour doses for radiation-induced cancer on the basis of dose-rate. Int J Radiat Biol 2011;87:645-52.|