------------------------------------------------------------------------ ------------------------------------------------------------------------ "Asleep at the Wheel": The Special Menace of Inherited Afflictions from Ionizing Radiation. Fall 1998. John W. Gofman, M.D., Ph.D., Professor Emeritus of Molecular & Cell Biology, University of California at Berkeley, and Egan O'Connor, Executive Director, CNR. ------------------------------------------------------------------------ ------------------------------------------------------------------------ * Part 1 -- "Asleep at the Wheel" due to a "Famous Failure" * Part 2 -- Dramatic Difference between Two Concepts * Part 3 -- Which Afflictions Are Irregularly Inherited? * Part 4 -- The Build-Up of Mutations during 1,000+ Years * Part 5 -- Inherent Limits of the A-Bomb Genetics Program * Part 6 -- Only 8 Inherited Effects Covered by Bomb Study * Part 7 -- "Fragile" Foundation Acknowledged by Neel and Colleagues * Part 8 -- The Health-Menace of a False Perception * Part 9 -- Why "The Radiation Concept" Is So Credible * Part 10 -- Can Natural Radiation Explain the Mutation Rate? * Part 11 -- The Specific Evidence from Low-Dose Radiation * Part 12 -- Is the Evidence "Screaming" at Humanity? * References ------------------------------------------------------------------ Part 1 * "Asleep at the Wheel" due to a "Famous Failure" 1a * The topic which consumes Parts 5, 6, 7 of this article is the famous failure to detect (at a statistically significant level) any extra frequency of inherited afflictions, in the Japanese children of the Atomic Bomb Survivors. 1b * The main importance of the "famous failure" has been its power to render much of the environmental and medical communities "asleep at the wheel," with respect to the menace of inherited afflictions caused by ionizing radiation. Some environmentalists even talk about "giving nuclear power a second chance." And some people in medicine are so relaxed, about low-dose radiation, that their customers have to fight in order to obtain shielding of their ovaries and testes from xray beams. 1c * We suspect that hardly one-percent of environmentalists and medical professionals know (a) that when the A-Bomb Genetics Program was initiated, it was already acknowledged that, in all probability, it would be inherently incapable of producing statistically significant results (see Para.5b), and (b) that very few inherited effects were even explored in that Program (see Part 6). One purpose of this article is to document statements (a) and (b). 1d * The other purpose of this article is to set forth a scientifically credible warning that ionizing radiation is probably the single most menacing mutagen to which people everywhere are exposed --- and by itself is probably the mutagen which accounts for one-quarter or more of humanity's inherited afflictions (Para.2b). This warning is tied to three types of relevant human evidence (Parts 9, 10, 11). ------------------------------------------------------------------ Part 2 * Dramatic Difference between Two Concepts 2a * The renowned British biologist, J.B.S. Haldane, suggested in 1948 that perpetual exposure to natural background radiation might account for most of humanity's accumulated burden of inherited afflictions (Haldane 1955, p.115). The great bulk of such afflictions are in the class called "Irregularly Inherited Disorders" (Part 3). 2b * A reality-check, on evidence accumulated since 1955, suggests that the share due to natural background radiation is very probably 25% or more --- maybe as high as 50%. So, it is time to consider the following scientifically credible proposition: "Natural background radiation is the mutagen which accounts for 25% or more of those cases of Irregularly Inherited Afflictions which occur because of inherited predisposition." For brevity in this article, we can refer to the proposition as "The Radiation Concept" (The Radiation Concept of Irregularly Inherited Afflictions). 2c * "The Radiation Concept" differs dramatically from a notion which became the operative concept during the "Atoms for Peace" program --- namely, that it would be inconsequential if nuclear pollution were to double the dose from natural background radiation. This operative notion is embedded in such numbers as a "permissible annual radiation dose" of 0.1 rad (100 milli-rads), and it is the premise of current discussions which refer to 0.1 rad per year as a dose too small to bother about at all (for instance, see Billen 1990 and Health Physics 1996). We and others call this "The De Minimis Concept. 2d * "The Radiation Concept" can neither be validated nor invalidated by the A-Bomb Genetics Program --- as we will explain --- but three OTHER types of evidence make it a very credible warning, scientifically (Part 9). ------------------------------------------------------------------ Part 3 * Which Afflictions Are Irregularly Inherited? 3a * Inherited afflictions and inherited mutations are not the same thing, of course. Mutations are a cause, afflictions are a result. Many different kinds of mutations may result in the same affliction. 3b * Inherited mutations can be loosely divided by their consequences: (1) Those which confer a certainty of some affliction (for instance, a malformed heart, a mental handicap, or a disease like hemophilia), (2) those which confer an elevated chance of negative consequences --- a predisposition, vulnerability, susceptibility, (3) those which are biologically inconsequential, and (4) those which are beneficial. With respect to group (4), the BEIR Committee of the National Research Council has stated the "general wisdom" in this field: "It must be emphasized again that virtually all mutations have harmful effects" (BEIR 1990, p.69). 3c * Group (2), above, is the key to a vast group of afflictions --- from mild to devastating --- called "Irregularly Inherited Disorders" (also called, "Disorders of Complex Etiology"). 3d * What are some of the Irregularly Inherited Afflictions? They range from dyslexia to Alzheimer's Disease. By 1990, the BEIR Committee included the following afflictions as an illustrative selection of Irregularly Inherited Disorders (BEIR 1990, p.70, p.89): 3e * Heart disease, cancer, diabetes mellitus, schizophrenic psychoses, affective psychoses (uni-polar and bi-polar), multiple sclerosis, epilepsy, glaucoma, asthma, psoriasis, rheumatoid arthritis, Grave's disease, gout, allergic rhinitis, idiopathic procto-colitis, gallstones, and mineral deposits in the kidneys. There are many, many more. The Irregularly Inherited Disorders are so common that every person is thought to have at least one (BEIR 1990, p.70). Logic insists that inherited predisposing mutations create problems in every major system: immune, endocrine, reproductive, nervous, respiratory, digestive, urinary ... 3f * No one yet knows (a) what share of cases of the Irregularly Inherited Afflictions occurs because of predisposing inherited mutations and (b) what share of cases of the same afflictions would happen "anyway." Estimates of (a) have been 50% or lower, in reports sponsored by the government (history in BEIR 1990 + NRC 1991). We predict that nearly all cases require some predisposing mutations (Gofman 1994, Chapter 7, Part 2). However, "The Radiation Concept" is independent of that prediction. Whatever the share turns out to be, "The Radiation Concept" (Para.2b) says that 25% or more of such cases are the result of humanity's perpetual exposure to natural background radiation. 3g * So, when we speak of Irregularly Inherited Afflictions, we mean all the cases which occur because of an inherited predisposition and not cases which would have occurred "anyway" under the same circumstances. ------------------------------------------------------------------ Part 4 * The Build-Up of Mutations during 1,000+ Years 4a * By definition, an inherited mutation is present in every cell of an offspring's body --- including the lymphocytes circulating in the blood. Some inherited mutations are so harmful that the recipient always dies before ever having any children. Because such mutations can not be passed along to the next generation, they never accumulate in the population. By contrast, most inherited mutations never cause EARLY death, and so they can be passed along to the next generation. These are the mutations which ACCUMULATE in a population. People inherit so many mutations that it is an enormous task (now in its early stages) to figure out which inherited mutations produce harmful consequences and which ones are biologically inconsequential (Para.3b). 4b * If an offspring inherits a particular mutation, and the same mutation is NOT found in the lymphocytes of one of the parents, it means that the mutation occurred newly in a germ cell of a parent who did NOT inherit it from his or her ancestors. (Germ cells are the precursors of "eggs" and sperm.) Such a mutation in the offspring is called a "de novo" mutation. By contrast, if the same mutation is found in the lymphocytes of one of the parents, the offspring's mutation is called a "parental mutation" --- meaning that one parent has it in EVERY cell. Many, many earlier generations may have had it in every cell, too. 4c * Suppose that Paul has inherited three parental mutations called A,B,C, plus one de novo mutation called D. Suppose that his wife Mary has inherited three parental mutations E,F,G, plus one de novo mutation called H. Their daughter Alice may inherit A,B,D,H as parental mutations plus J as a de novo mutation, while her brother Edward may inherit C,E,F,G as parental mutations plus K as a de novo mutation. In this "scenario," de novo mutations keep adding to the inventory. And indeed, de novo mutations are the only possible source of humanity's accumulated inventory of inherited parental mutations. 4d * The "mutation rate" in a population refers to the rate of DE NOVO mutations per generation, and NOT to the population's very much higher incidence rate of parental mutations, already accumulated during 50 or 100 previous generations. The ratio of "de novo to parental" mutations is low, and this unfavorable "signal to noise ratio" has been an obstacle to conclusive epidemiologic research in this field. ------------------------------------------------------------------ Part 5 * Inherent Limits of the A-Bomb Genetics Program 5a * One of the most important statements, in the world's professional literature on inherited afflictions, was published by the National Academy Press in 1991 (Neel 1991). The statement occurs in the "Orientation" section (at p.2) of the 518-page book entitled The Children of Atomic Bomb Survivors: A Genetic Study, edited by James V. Neel and William J. Schull --- two of the principal investigators in that study: 5b * "In 1946, knowledge both of the doses of radiation sustained by survivors [of the atomic bombings] and the sensitivity of the mammalian genome to radiation was far inferior to the present situation. Nevertheless, as the preliminary data on post-atomic bomb Hiroshima and Nagasaki emerged, it became very likely, given the number of survivors in the two cities and their probable gonadal doses, as well as the indicators one would be forced to pursue in any study, that even a very major effort would not yield a statistically significant difference between the children of survivors receiving increased radiation at the time of the bombings (ATB) and the children of suitable controls. 5c * In other words, when the study was initiated, it was expected in advance that such a study would be inherently incapable of detecting the radiation-induction of inherited afflictions at any statistically significant level. The famous negative "findings" were built-in before the study began. And yet the negative findings were described in 1990 as follows --- in the highly influential journal Science: 5d * "The [A-Bomb Study] researchers have found no evidence of any genetic effects at all in the children who were conceived after the blast --- no genetic diseases, cancer, or congenital abnormalities. And they have scoured the data with a fine-toothed comb, even scanning protein sequences for any telltale variation that would indicate a genetic mutation" (Roberts 1990). 5e * Readers of the Roberts description could easily say "Case closed." But the researchers who did the work have quite a different view. Seven leading analysts in the A-Bomb Genetics Program wrote in 1990 (Neel 1990, p.1061): 5f * "We take it as a given that the exposure [to the atomic bombs] resulted in mutations in some survivors of the atomic bombings, inasmuch as, without exception, under controlled laboratory conditions, ionizing radiation has produced mutations in every properly studied plant and animal species." And (Neel 1990, p.1063): "Again we reiterate the point that, unless humans differ from every other properly studied animal, as well as from plants, mutations must have been produced by this exposure." See also Para.7a. 5g * These statements are emphatic warnings --- widely unknown or ignored --- that of course ionizing radiation (regardless of its source) contributes to inherited human afflictions. ------------------------------------------------------------------ Part 6 * Only 8 Inherited Effects Covered by Bomb Study 6a * If one appreciates the vast range of afflictions, to which inherited mutations contribute, then one can better appreciate the limitations of the A-Bomb Genetics Program with respect to radiation-induced inherited afflictions in offspring of A-Bomb Survivors. Only the following eight "indicators" were studied, in an effort to detect a statistically higher rate of de novo mutation in offspring having at least one parent exposed to bomb radiation, compared with offspring having neither parent exposed to bomb radiation (details in Neel 1990). As predicted (Para.5b), for none of the eight indicators was a statistically significant difference found (Neel 1990, p.1053). 1 - Untoward pregnancy outcome (an infant stillborn and/or exhibiting major congenital malformation and/or dying within the first 2 weeks of life expectancy). 2 - Death (except from cancer) before an average age of 28.8 Years (age in Neel 1991, p.403); age 39 was the oldest. 3 - Occurrence of malignancy before age 20 (age at p.1057, Neel 1990). 4 - Frequency of de novo chromosomal translocations and inversions: Blood samples were taken from offspring at an average age of 23-24 years (Awa 1987, p.346). Searches for balanced translocations (reciprocal and Robertsonian) and pericentric inversions were done without any molecular techniques, such as "FISH." 5 - Frequency of sex-chromosome aneuploidy (wrong number of sex chromosomes). 6 - Frequency of de novo mutation in 30 selected protein-coding genes (Neel 1988 + Neel 1990, p.1059-1060): Out of an estimated 50,000 to 100,000 genes in the genome, 30 were selected for study, indirectly. The protein products of 30 genes were studied electrophoretically, for alteration of electric charge, and a subset of nine enzymes was examined for a partial loss of activity (Neel 1988, pp.664-66). 7 - Sex-ratio among children of exposed mothers. 8 - Height, weight, circumference of head, chest. ------------------------------------------------------------------ Part 7 * "Fragile" Foundation Acknowledged by Neel and Colleagues 7a * What do Neel and co-workers conclude from their eight specific indicators? They acknowledge (Neel 1990, p.1063) that "Each of the eight estimators of a genetic effect of the bombs which we have been able to generate is associated with a relatively large error term, and individually these estimators are fragile reeds on which to lean in building a case. 7b * Nonetheless, Neel and co-workers combine five of their eight indicators (#1, 2, 3, 5, 6, from above), and calculate an estimate of the dose of bomb-radiation which would double the mutation rate for these five indicators. Their estimate (Neel 1990, p.1064 text): About 200 rems (approx. 200 rads). Since the error-term on each of the five indicators is larger than its slope (Neel 1990, Table 5), their estimate of 200 rems is consistent with very different values. Neel and co-workers decline, appropriately, to suggest any specific confidence limits (Neel 1990, p.1064). ------------------------------------------------------------------ Part 8 * The Health-Menace of a False Perception 8a * After responsible people become familiar with the BASIS of the estimated 200-rem doubling dose, they will recognize how unreliable and virtually irrelevant it is. This is not the fault of Neel and colleagues. From the outset, their study was expected to be inherently unable to produce any meaningful evaluation of the impact of ionizing radiation on inherited afflictions (Para.5b). What is such a menace to human health is the PERCEPTION that the results are meaningful when they are NOT. 8b * Neel and co-workers partly acknowledge the irrelevancy of their 5-indicator estimate, when they state (Neel 1990, p.1063; emphasis is in the original): "Ideally, the genetic doubling dose is calculated as that amount of radiation which increases the TOTAL impact of spontaneous [de novo] mutation by 100%. 8c * That statement is correct. And we add that the Irregularly Inherited Disorders represent the overwhelming share of the potential impact. When the A-Bomb Study addressed cancer before age 20 (very rare), it essentially addressed the issue of inherited predisposition to cancer NOT AT ALL. As for the multitude of other Irregularly Inherited Afflictions (Para.3e), the A-Bomb Genetics Program has addressed only the very rare disorders which were FATAL before an average age of 28.8 years of age. The overwhelming share, of the potential impact from exposure to ionizing radiation, is simply not addressed by that Program. ------------------------------------------------------------------ Part 9 * Why "The Radiation Concept" Is So Credible 9a * "The Radiation Concept" was defined in Paragraph 2b. It assigns a very large role to natural background radiation --- an assignment based on three types of human evidence. 9b * First is the fact that today's incidence rate of Irregularly Inherited Afflictions (Para.3g) is the result of many centuries of build-up, because the responsible mutations rarely kill their carriers before child-bearing age (Para.4a). Therefore, the chemical "revolution" after World War Two can not explain very much of humanity's current incidence of such inherited afflictions. A very large share of the current incidence has to be explained by mutagens which have "always been with us." Natural background radiation certainly qualifies on that requirement. 9c * Second is the emerging evidence --- thanks to recently developed laboratory techniques in "molecular" cytogenetics --- that structural chromosomal mutations are extremely important causes of inherited diseases and "birth defects" (as we predicted in Gofman 1970 and 1981). We have described some of the evidence and references elsewhere (Gofman 1992, 1994). Such chromosomal mutations are often called "I/D/R events" in the biomedical literature. 9d * How important are they? In 1989, Mohrenweiser and 2 co-workers stated (Mohrenweiser 1989, p.242): "[Recent] molecular studies of human genetic diseases indicate that insertion/deletion/re-arrangement [I/D/R] events are the molecular basis for many genetic alterations ... The latter group of variants may be of greater health significance than base substitutions as most of the mutations in the I/D/R class, if they involve functional loci, should result in the loss of a functional gene product" --- the same point made in Gofman 1981 (p.787). Elsewhere, Neel and 7 co-workers acknowledge: "... a surprising frequency of spontaneous mutations are being found to be deletions" (Neel 1988, p.666). Hemophilia-A is an example. Youssoufian reported in 1987 that more deletions than point mutations have been identified as causing hemophilia-A (Youssoufian 1987, p.3772). 9e * Third is the evidence --- some of it available for decades (e.g., Kucerova 1972, Evans 1978) --- that ionizing radiation is a "champion clastogen." Clastogen means "chromosome breaker." Breakage of BOTH opposing strands of DNA, in the double helix, is the key requirement for production of all varieties of structural chromosomal mutations --- including dicentric translocations, insertions, and deletions. There are many mutagens beside ionizing radiation which can cause SINGLE strand breaks, but ionizing radiation can also deliver the biologically unnatural amounts of energy which readily break BOTH strands (discussion of the uniquely violent properties of ionizing radiation, in Gofman 1997, Part 4). The double-strand breaks are far more difficult for a cell to repair correctly than single-strand breaks. 9f * Not only is ionizing radiation a particularly potent chromosome breaker, but also chromosomal mutations are more likely --- per mutation --- to have biological consequences than non-chromosomal mutations. For instance, one of the most common chromosomal mutations (the deletion) actually removes segments of the genetic code, whereas a single base-change does not. Even the smallest deletion can scramble the genetic code along major segments of DNA. 9g * It is scientifically very credible to predict that chromosomal mutations cause at least half of humanity's current incidence of Irregularly Inherited Afflictions (with the other half caused by non-chromosomal mutations such as base-changes, etc.) AND that ionizing radiation causes at least half of the de novo chromosomal mutations (Part 11). ------------------------------------------------------------------ Part 10 * Can Natural Radiation Explain the Mutation Rate? 10a * We have proposed "The Radiation Concept (Para.2b) because there is ENOUGH dose from natural background radiation to cause 25% or more of the Irregularly Inherited Afflictions (details in Part 11). 10b * At sea-level, natural background radiation exposes everyone to about 0.1 rad per year of absorbed radiation dose (the dose is is slightly higher at higher altitudes). This means that, ever since the beginning of humanity, the germ cells in our ancestors have accumulated a radiation dose of about 0.1 rad per year. At what age did people have children in the past? We can not ignore past practices (Para.9b). If we say that ages 15-20 (or 17.5 years on the average) have been common, then the average accumulated gonadal dose would be about 1.75 rads for each parent. 10c * So, the question becomes: Could an average gonadal dose of only 1.75 rads suffice to account for half of the de novo mutation rate for chromosomal mutations? By accounting for half of all chromosomal mutations, natural background radiation would account for one-fourth of all the afflictions --- if half of the afflictions are due to non-chromsosomal mutations (Para.9g). 10d * This question can be explored by study of chromosomal mutations in human blood. Such studies are highly relevant, because every chromosomal mutation inflicted by ionizing radiation on lymphocytes can also be inflicted by radiation on the chromosomes of human germ cells. Blood-studies have been done for decades. Although the methods reveal only the easily visible mutations, the non-detected chromosomal mutations occur in proportion to the detected ones, since all types begin with chromosome breakage. 10e * The dicentric translocation is the chromosomal mutation on which blood-studies generally rely most heavily. With the use of common methods, about 1 dicentric is detected in 1,000 cells from an adult blood-donor. This frequency reflects the fact that the dicentric mutation occurred after conception --- because the same dicentric would have to appear in EVERY cell if it were inherited. There is no question that blood-studies are counting DE NOVO dicentrics. 10f * What we really would like to count, with respect to "The Radiation Concept," is the frequency of de novo dicentrics typically found in the blood of people at age 17.5 years, when their accumulated gonadal dose from natural background radiation is about 1.75 rads. Then, we would irradiate samples of their blood with an extra 1.75 rads. If we found that the experimental dose of 1.75 EXTRA rads doubled the pre-experimental count of de novo dicentrics, we would have to conclude that natural background radiation caused ALL of the pre-experimental dicentrics in the blood. 10g * Why? If 1.75 extra rads can ADD as many de novo dicentrics as were already present BEFORE the extra 1.75 rads --- in other words, if 1.75 rads can DOUBLE the frequency of dicentrics --- this would be evidence that 1.75 rads from natural background radiation are sufficient to cause ALL of the pre-experimental de novo dicentrics. There would be no "room" for a contribution, to the pre-experimental count of dicentrics, by any other clastogen EXCEPT the inescapable natural background radiation. 10h * Moreover, because natural background radiation has access to the gonads, we could reasonably infer that natural background caused all of the de novo chromosomal mutations in the germ cells, too. 10i * Suppose such studies establish that an extra dose of 3.5 rads is required in order to double the pre-experimental number of de novo dicentrics at age 17.5 years? Then we would conclude that natural radiation causes about HALF of the de novo chromosomal mutations which accumulate during the child-bearing years (Para.10c). ------------------------------------------------------------------ Part 11 * The Specific Evidence from Low-Dose Radiation 11a * We quote from the BEIR-5 Report (BEIR 1990, p.385): "In areas of high natural background radiation, an increased frequency of chromosome aberrations has been noted repeatedly. 11b * In 1983, Tonomura and 2 co-workers at the Tokyo Medical and Dental University reported their blood-study of 96 adults (49 females; 47 males) who had neither previously received any exposure to ionizing radiation from their jobs nor any significant exposure from medical procedures, as well as of 23 newborn infants whose mothers had NOT received medical radiation during pregnancy. The age-distribution of the blood-donors and the number of cells examined were (Tonomura 1983, Tables 28-1 and 28-2): Age 20: 12,495 cells from 13 donors. Age 30: 20,322 cells from 20 donors. Age 40: 21,560 cells from 22 donors. Age 50: 18,546 cells from 21 donors. Age 60: 19,544 cells from 20 donors. Newborn: 15,325 cells from 23 donors. 11c * Tonomura et al report (p.605) that "the incidence of dicentrics showed a linear increase with age." The frequency detected in newborns was zero. The frequency at age 20 --- when about 2.0 rads of gonadal dose have accumulated from natural background radiation --- was 0.0007 (9 de novo dicentrics in 12,495 cells). The frequency at age 40 (when an additional 2.0 rads of gonadal dose from natural background radiation have accumulated) was 0.0012 (25 dicentrics in 21,560 cells). Because the additional 2 rads added 70% to the rate of 0.0007 already present at age 20, it is credible that less than 2 rads could account for 50% or more of the dicentrics observed at age 17.5. 11d * "The Radiation Concept" and the Tonomura data are therefore in harmony (see Para.10i). It would be very enlightening to have some larger studies of the Tonomura type, but we are unaware of any. We note that in 1979, Evans also reported that de novo chromosomal mutations increase with age. Citing "unpublished evidence" and one 1968 Russian study, Evans writes (1979, p.532): "We have evidence from studies on a variety of populations for an increase in the spontaneous frequency of [chromosomal] aberrations --- in the absence of known radiation exposure [other than natural background] --- with increasing age. 11e * In 1992, results were published from one of the largest and most reliable blood-studies (Lloyd 1992). Blood samples were drawn from 20 donors of various ages, with an average age of 30.1 years (Lloyd 1992, Table 8). Two of the 20 donors were smokers. Each blood sample was divided into four portions: One portion (the control) received no extra radiation. The second portion received an extra radiation dose of 0.482 rad (4.82 mGy). The third portion received an extra dose of 2.85 rads (28.5 mGy). The fourth received an extra dose of 28 rads (280 mGy). The blood was irradiated with xrays of defined quality (169 keV ISO wide series) produced by an xray machine operated at 250 kVp with a half-value layer of 4.3 mm Cu (Lloyd 1992, p.336). 11f * Except for blood samples receiving 28 rads, 3,000 cells were "scored" at each dose-level from each of the 20 donors (for example, 60,000 cells were scored for the control group). Even though this was a much bigger study than Tonomura's, counts varied considerably from one donor to another, both before and after the extra irradiation (Lloyd Table 8) --- which illustrates the reason not to rely heavily on small studies. 11g * Because of "The Radiation Concept," our interest is in comparing the counts of de novo chromosomal mutations in the Control Group (which must have accumulated a dose from natural background radiation of about 3.0 rads by age 30) with the counts from the blood which received an EXTRA 3.0 rads (actually, 2.85 rads). The counts below, from the 20 donors combined, come from Lloyd 1992, Table 8. Dic=dicentrics. CR=centric rings. AF=acentric fragments. Control: 49 Dic. 1 CR 134 AF Extra 2.85 rad: 88 Dic. 12 CR 211 AF 11h * The extra 2.85 rads added 80% to the control's frequency of de novo dicentrics and added about 60% to the fragments. (We can ignore the centric rings, because a measurement of 1 is very unstable.) If we assume, reasonably, that the counts of dicentrics and fragments in the control samples would have been lower, if the average age had been 17.5 years instead of 30.1 years, then it would be very reasonable indeed to believe that (a) 2.85 rads is enough approximately to double such control values, and (b) that 1.75 rads of gonadal dose, received by age 17.5 years from natural background radiation, is enough to cause half of all the de novo chromosomal mutations. ------------------------------------------------------------------ Part 12 * Is the Evidence "Screaming" at Humanity? 12a * "The Radiation Concept" is in harmony with the Tonomura data and the Lloyd data on low-dose radiation. And that is because "The Radiation Concept" is not a mere speculation drawn from thin air. It is a scientifically credible concept BASED on relevant real-world evidence of the types described in Part 9. 12b * Ionizing radiation from any source (natural or man-made) is well-established as a particularly potent cause of chromosomal mutations and other complex genetic mutations. This is just not in dispute. And there are solid biological reasons for the unique mutagenic potency of ionizing radiation (discussion and references in Gofman 1997). 12c * A population dose of 0.1 EXTRA rad per year, due to human activities, would be the equivalent of doubling the annual gonadal dose from natural background radiation. We have shown above that such an annual increment, if received generation after generation, could ultimately add 25% to the incidence of the Irregularly Inherited Afflictions --- a consequence of breath-taking size. Indeed, adding that extra dose for just ONE generation would have a very large aggregate impact on future generations, because no one can issue "a recall" on the mutations, which are transmitted from that ONE generation to future generations (quantitative analysis in Gofman 1994, Chapter 7.) 12d * Moreover, if the extra dose comes from nuclear pollution, it is impossible to limit such dose to a single generation, because many of the radioactive species persist in the biosphere for centuries and millennia. For example, half of the carbon-14 created in nuclear power plants today will still be around 5,700 years from now. And half of the radium, already "liberated" by mining nuclear fuel, will still be around 1,600 years from now. 12e * The very low doubling-dose for radiation-induced chromosomal mutations, and confirmation of the importance of such mutations in inherited disorders, combine almost to scream at humanity: "Do not permit increases in nuclear pollution. At enormous expense, you can recapture only a small part of what you let loose. Irrevocable nuclear pollution inevitably increases humanity's rate of inherited afflictions." 12f * Responsible people will also consider the possibility that chromosomal mutations are the cause of MORE than half of humanity's inherited afflictions (Para.9g). Such a prospect is not rendered "improbable" by current knowledge. Moreover, the measurements discussed in Part 11 have error-bands, which means that natural background radiation could turn out to explain almost ALL the mutation rate for chromosomal mutations. In other words, today's evidence does not rule out the possibility that very low-dose ionizing radiation, from natural background, explains 50% or more of the inherited afflictions. 12g * The bottom line is: Even "The Radiation Concept" presented in this article (Para.2b) may rather severely underestimate the impact of low-dose ionizing radiation on inherited afflictions. It is far from prudent, for anyone in environmental or medical circles to be "asleep at the wheel." # # # # # >>>>> Reference List <<<<< --------------------------------- * Awa 1987 (Akio A.) + 9 colleagues: "Cytogenetic Study of the Offspring of Atomic Bomb Survivors," pp.344-361 in Neel 1991. * BEIR 1990: Committee on the Biological Effects of Ionizing Radiation, Health Effects of Exposure to Low Levels of Ionizing Radiation. National Academy Press. ISBN 0-309-03995-9. * Billen 1990 (Daniel): "Spontaneous DNA Damage and Its Significance for the `Negligible Dose' Controversy in Radiation Protection," Radiation Research 124: 242-245. Responses by Keith F. Baverstock and John F. Ward in 1991, Radiation Research 126: 383-387. * Evans 1978 (H.J.) + David C. Lloyd (editors), Mutagen-Induced Chromosome Damage in Man. University Press, Edinburgh. * Evans 1979 (H.J.) + 3 co-workers: "Radiation-Induced Chromosome Aberrations in Nuclear Dockyard Workers," Nature 277: 531-534. Feb. 15. * Gofman 1970 (John W.) + Arthur R. Tamplin: "Questions for Dr. Paul Tompkins, Director of the Federal Radiation Council," pp.1538-1559 in Underground Uses of Nuclear Energy, Hearings on S.3042 before Senate Committee on Public Works, Air & Water, August 5, 1970. See also Chapter 3 in Poisoned Power, 1971 by Gofman + Tamplin. ISBN 0-87857-004-7. * Gofman 1981 (John W.): Radiation and Human Health. ISBN 0-87156-275-8. Sierra Club Books. Still in print. * Gofman 1992 (John W.): Radiation-Inducible Chromosome Injuries: Some Recent Evidence on Health Consequences --- Major Consequences. On Internet at: http://www.ratical.org/radiation/CNR/RICI.html * Gofman 1994 (John W.): Chernobyl Accident: Radiation Consequences for This and Future Generations. Russian language. Vysheishaya Shkola Publishing House, Minsk. ISBN 5-339-00869-X. * Gofman 1997 (John W.): "The Free-Radical Fallacy about Ionizing Radiation: Demonstration That a Popular Claim Is Senseless." On Internet at: http://www.ratical.org/radiation/CNR/FreeRadFallacy.html * Haldane 1955 (John Burdon Sanderson): "Genetical Effects of Radiation from Products of Nuclear Explosions, Nature 176: 115. * Health Physics 1996: Position Statement of the Health Physics Society, "Radiation Risk in Perspective," by Kenneth F. Mossman + 5 colleagues, in Health Physics Newsletter, March 1996. * Kucerova 1972 (M.) + A.J.B. Anderson + K.E. Buckton + H.J. Evans, "Xray Induced Chromosome Aberrations in Human Peripheral Blood Lymphocytes," International Journal of Radiation Biology 21: 389-396. * Lloyd 1992 (David C.) + 10 co-workers: "Chromosomal Aberrations in Human Lymphocytes Induced in Vitro by Very Low Doses of Xrays," International Journal of Radiation Biology 61: 335-343. * Mohrenweiser 1989 (Harvey W.) + Robert D. Larsen + James V. Neel: "Development of Molecular Approaches to Estimating Germinal Mutation Rate," Mutation Research 212: 241-252. * Neel 1988 (James V.) + 7 co-workers: "Search for Mutations Altering Protein Charge and/or Function in Children of Atomic Bomb Survivors: Final Report," American Journal of Human Genetics 42: 663-676. Also in Neel 1991, pp.363-376. * Neel 1990 (James V.) + 6 co-workers: "The Children of Parents Exposed to Atomic Bombs: Estimates of the Genetic Doubling Dose of Radiation for Humans," American Journal of Human Genetics 46: 1053-1072. Also in Neel 1991, pp.431-450. * Neel 1991 (James V.) + William J. Schull, editors: The Children of Atomic Bomb Survivors: A Genetic Study. ISBN 0-309-04488-X. National Academy Press. * NRC 1991 (Nuclear Regulatory Commission): "Health Effects Models for Nuclear Power Plant Accident Consequence Analysis, Addendum One to Nureg/CR-4214. * Roberts 1990 (Leslie): "British Radiation Study Throws Experts into a Tizzy," Science 248: 24-25. April 6. * Tonomura 1983 (Akira) + Kunikazu Kishi + Fumiko Saito: "Types and Frequencies of Chromosome Aberrations in Peripheral Lymphocytes of General Populations," Chapter 28 (pp.605-616) in Radiation-Induced Chromosome Damage in Man, edited by Takaaki Ishihara + Masao S. Sasaki. ISBN 0-8451-2404-8. Pub: Alan R. Liss Inc, New York City. * Youssoufian 1987 (Hagop) + 5 co-workers: "Characterization of Five Partial Deletions of the Factor VIII Gene," Proceedings of the National Academy of Sciences (USA) 84: 3772-3776. # # # # # ------------------------------------------------------------------ Committee for Nuclear Responsibiity, Inc. (CNR) POB 421993, San Francisco, CA 94142, USA An educational group since 1971. 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