John W. Gofman, M.D., Ph.D., Spring 1992
- Part 1 -- "Permissible" Doses Established in an Ocean of Ignorance
- Part 2 -- "Genetic" versus "Inherited," and Some Other Terms
- Part 3 -- The Pre-Cytogenetic Era, up to 1956
- Part 4 -- The Establishment of Cytogenetics, 1956-1959
- Part 5 -- The Pre-Banding Era of Cytogenetics, 1959-1970
- Part 6 -- The Banding Era of Cytogenetics, 1970-1985
- Part 7 -- The Era of Molecular Cytogenetics, 1985 Onward
- Part 8 -- What Else Will the New Technologies Reveal?
- Reference List
Chromosomes are the structures, in the nuclei of our cells, which are composed of helical, double-stranded DNA and associated proteins. The DNA molecules encode our human and individual genetic heritage. Two types of genetic injury which are readily caused by ionizing radiation at very low doses and low dose-rates are chromosomal deletions and translocations.
Recent evidence links a great variety of chromosomal deletions and translocations with devastating birth defects and mental handicaps. Nonetheless, pressure to "forgive" more nuclear pollution --- and thus "forgive" more involuntary exposures to ionizing radiation --- is reviving in a big way. One consequence of additional exposure would be additional injury of the population's chromosomes, our library of genetic information.
1 * "Permissible" Doses Established in an Ocean of Ignorance
The chromosome story is a classic example of how "permissible" levels of radiation and other pollutants are recklessly established under the "prove harm" doctrine before technologies even exist for proving which agents can be the cause of dreadful health effects.
This CNR paper describes the evidence which links chromosomal deletions and translocations with mental handicap and structural defects of the heart, kidneys, digestive tract, skeleton, and genitalia, and it also describes the limits of technology which have delayed this evidence for so long.
The essay is a non-technical introduction to just a small part of the story of chromosomal injuries, for it omits any consideration of health consequences such as cancer, schizophrenia, and metabolic diseases (for instance, diabetes, hyper-lipidemia, cystic fibrosis). My next book, in 1994 (Chernobyl Accident: Radiation Consequences for This and Future Generations (Russian Language)), will provide detailed evidence and analysis of the under-estimated health effects which can arise from radiation-induced chromosome damage. The information also has implications far beyond nuclear pollution, to the extent that chemicals and viruses (and possibly other types of radiation) may induce permanent chromosome injuries too.
The fact that ionizing radiation can break chromosomes has been "answered" between 1970 and the present day by questioning the health effects (see the three boxes , ,  in this essay). With respect to this and many other pollutants, the "prove harm" proponents see nothing wrong about establishing "permissible" levels of involuntary exposure, despite an ocean of ignorance regarding the potential, miserable consequences --- some of which are identified in this essay.
2 * "Genetic" versus "Inherited," and Some Other Terms
Among the permanent genetic injuries which can be inflicted by ionizing radiation are three types:
- Single-gene damage:Chromosome damage confined to a segment of DNA representing a single gene.
- Deletions:Breakage of a chromosome, followed by permanent loss of part of a chromosome carrying some or many entire genes, or just part of one gene.
- Translocations:Breakage of one or more chromosomes, followed by permanent removal of some or many genes (and partial genes) from their normal place in the DNA chain; these relocated DNA segments can end up in an abnormal place within the same DNA chain or within the DNA of an entirely different chromosome.
All three types of permanent chromosomal injury are now called "genetic mutations," and types (B) and (C) are also called "structural chromosome aberrations."
The terms "genetic" and "inherited" are not synonymous. Genetic injuries or mutations can occur in cell-nuclei
Before conception, in an ancestor's germ cells (sperm or ova).
After conception, during the person's gestation (in-utero).
Anytime during childhood and adulthood.
When genetic mutations occur before conception (inherited) or during early gestation (not inherited), the health consequences can be virtually identical. Distinctions are poorly defined between "genetic diseases," "irregularly inherited disorders," "constitutional diseases," "chromosomal disorders," "congenital diseases," and "birth defects" or "anomalies."
An explosion of new information on these topics has occurred. Indeed, a large share of all bio-medical research in recent years has been devoted to the genetic basis of disease and health, and existing results await coherent assembly and analysis. Part of the explosion is generated by the Human Genome Project, in which the U.S. Department of Energy is extremely active.
3 * The Pre-Cytogenetic Era, up to 1956
The field of chromosome study, broadly, is called cytogenetics. Although the existence of chromosomes has been known for over a century, very little progress was made for a long time.
Chromosomes are not visible, unless you "catch" a cell which is preparing to divide. Then the very long, string-like chromosomes "condense" by folding themselves into enormously shorter and thicker objects. Ordinary stains used in biology showed their existence, but the objects appeared entangled with each other, and no one was even able to establish the correct number of human chromosomes per cell-nucleus during the pre-cytogenetic era.
In 1953, Hsu developed a simple but enormously powerful technical advance in chromosome studies. When cells are bathed in a solution with salt-concentration lower than their own salt-concentration, the cells swell. The chromosomes in cells preparing to divide become so well separated that quite a few details of individual, separated chromosomes can be noted, when the division is halted by a chemical inhibitor and the cells are flattened on a glass slide. Hsu's advance in laboratory techniques would soon establish the field of cytogenetics.
The year 1953 was also the year in which Watson and Crick announced the structure of the gene and DNA helix. The required technologies for that kind of very sophisticated analysis had become available before the availability of techniques which would permit us merely to count the number of structures which carry the genes.
4 * The Establishment of Cytogenetics, 1956-1959
Within three years of Hsu's low-salt cell-preparations, Tjio and Levan were able to establish conclusively, in 1956, that the normal number of human chromosomes per cell-nucleus is 46.
The father contributes 23 chromosomes and the mother also contributes 23 chromosomes to the fertilized ovum, from which the 46 are replicated in the cell-nuclei of all the descendant cells --- when everything goes well. There are 22 matched pairs called autosomes, grouped by letters A-G (for instance, paternal and maternal B-5 chromosomes). In addition, each cell has a pair of sex chromosomes which are not necessarily matched (X+X makes the child female; X+Y makes the child male). Each chromosome has a region somewhere along its length called the centromere, which divides the chromosome into a shorter arm (called the p-arm) and a longer arm (q-arm).
Each pair of undamaged autosomes provides the cell with two copies of each gene on the autosome --- a full set of this genetic information from the father and a full set from the mother. In 1956, we were yet to learn that there can be severe consequences for the children who have either more than two complete copies or fewer than two complete copies of the genetic information on both arms of each chromosome. But in 1959, our ignorance on this matter began to retreat.
5 * The Pre-Banding Era of Cytogenetics, 1959-1970
Banding is a technique which will be described in Part 6. Here we will summarize some insights which were gained in the pre-banding era.
In Part 2, we described two types of structural chromosome aberrations (deletions and translocations). There are also numerical chromosome aberrations. When an extra copy of one complete chromosome is present in cells, so that the cells contain 47 instead of 46 countable or "free" chromosomes, the condition is called a trisomy. When one complete copy of a chromosome is missing, so that cells have 45 instead of 46 countable chromosomes, the condition is called a monosomy. Of course, neither condition could be verified until the normal number of chromosomes was discovered in 1956.
In 1959, the cause of Down's Syndrome was discovered by Lejeune and Jacobs to be the presence of a third copy of the G-21 chromosome in a child's cells. Individuals with Down's Syndrome almost all suffer from mental handicap and characteristic facial features, and about 28% also suffer from a congenital heart defect. Approximately 1 per 700 liveborn children is a Down's child.
At first, it was assumed that Down's Syndrome required the trisomy-21 to involve a third copy of the full chromosome in every cell. We can call this an all-cell, full-chromosome trisomy-21. It accounts for about 92% of all cases of Down's Syndrome. The rest of the cases arise from two other types of trisomy-21. Although we will explain them here, with the pre-banding era, these other types were not discovered as early as all-cell, full-chromosome trisomy.
In-Utero Events: Mosaicism
When an infant has 47 chromosomes in every cell, it means that the numerical aberration was present in the fertilized ovum. But when only some fraction of a child's cells has 47 chromosomes, it means that the numerical aberration occurred in a cell which was ancestral to only some of the child's cells. Thus, the aberration occurred during gestation, in-utero. Individuals with two types of cells (some with 46 chromosomes, some with 47) are mosaics, and they have a some-cell, full-chromosome trisomy. For Down's Syndrome, mosaicism accounts for about 2.7% of the cases.
Translocations and Partial Trisomies
It has been shown that Down's Syndrome can be caused also by a structural chromosome aberration --- one which is readily induced by ionizing radiation. We mean the translocation (see Part 2). An estimated 5.8% of all cases are due to a translocation in one ancestor of a child. Although a thorough explanation would require more space than we have here, Figures 1 and 2 may convey a sense of the problem.
Figure 1 depicts a normal E-18 chromosome and a normal B-5 chromosome. Figure 2 depicts their possible status after a translocation. When a chromosome carries a mixture of information belonging to more than one chromosome, its name is set by the information around its centromere (depicted by the black area). In Figure 2, the chromosome on the left is called the E-18, and B-5 is on the right.
The condition of partial trisomy arises for a child as follows.
Suppose that both the mother and father transmit normal E- 18 chromosomes to their child. But suppose that in the transmission of B-5 chromosomes, one parent transmits the damaged B-5 chromosome from Figure 2. It carries translocated genes belonging to the q-arm of the E-18 chromosome. The child, whose numerical count of separate chromosomes is the normal 46, will nonetheless have three copies of part of the genetic information on the q-arm of the E-18 chromosome. The child will have a partial trisomy-18. This structural aberration can be described as an all-cell 18q trisomy.
Translocations and Partial Monosomies
In the example above, the child simultaneously has a partial monosomy because the child has received a B-5 chromosome which lacks part of its p-arm and lacks the genetic information which was on it. Even though the other parent sends the child a normal B-5 with a complete p-arm, the child will have only one copy (instead of the normal two copies) of some genetic information belonging to the p-arm. This condition can be described as an all-cell 5p monosomy. Because the chromosome-count will be the normal 46 per cell, this is not a numerical aberration.
Emphasis belongs on the fact that the effect of a partial monosomy is no different from an inherited deletion (see Part 2). The net effect is an all-cell deficit of chromosomal information. The deficit may or may not be limited to genes which code for specific enzymes. The deficit will often include (A) some segments of DNA which have presently unknown but presumably important functions, and (B) some chromosomal proteins whose functions are presumably important too.
The Discovery of Trisomies Additional to Down's Syndrome
In 1960, Patau presented the first clinical observation of a full-chromosome trisomy-13 patient. Since then, the frequency has been estimated between 1 case per 4,000 and 1 case per 10,000 live births. The clinical features of trisomy-13 include (percentage of cases): Mental handicap 100%, undescended testicles 89% of the males; abnormally small jaw 87%; eye defects 88%; low-set or malformed ears 85%; heart defects 79%; apparent deafness 77%; cleft palate 77%; extra fingers 77%; kidney defects 66%; seizures 41%.
And also in 1960, Edwards described the first patient with a full-chromosome trisomy-18. The frequency is now estimated at 1 case per 8,000 live births. The clinical features of trisomy-18 include (percentage of cases): Mental handicap 98%; undescended testicles in 77% of males; abnormally small jaw 95%; low-set or malformed ears 95%; congenital heart defects 95%; kidney defects 60%; prominent heel-bone 74%; elongated (front to back) skull 87%.
Box #1, A Contrast in Warnings:
Examples from 1969-1970
o -- On October 29, 1969, at the IEEE Symposium on Nuclear Science, Gofman and Tamplin upset the nuclear community by their call for an immediate 90% reduction in the radiation guidelines set in 1960 by the Federal Radiation Council (FRC) for members of the public. These were "permissible" doses of 0.17 to 0.5 rem each year. A few months later, Gofman and Tamplin challenged the government's authority to legalize involuntary radiation doses at any level.
o -- In testimony presented to Congress in June 1970, Gofman and Tamplin posed a series of detailed questions for the FRC chairman concerning genetic injuries from the permissible dose.
"We are just beginning to learn the meaning of a variety of chromosomal anomalies, including deletions and translocations for numerous aspects of human health and disease . . . Does it make you feel at all uneasy that this spectacular field of human cytogenetics is now in its infancy, after all the decisions had been made which led to the setting of FRC guidelines for radiation exposure of populations?" (Gofman and Tamplin 1970, p.1554).
o -- On August 5, 1970, Dr. John Totter, director of the Bio-Medical Division of the Atomic Energy Commission (AEC), was asked about radiation-induced chromosome injury during his testimony before a Senate hearing chaired by Sen. Mike Gravel.
Sen. Gravel: "What happens to cells [if they receive 10 rads]?"
Dr. Totter: "You would see chromosome breakage."
Sen. Gravel: "Would that be significant in your terms?"
Dr. Totter: "Well, it is undoubtedly significant, but what significance it has, we don't know" (Totter, p.677).
Nonetheless, the AEC vigorously opposed any reduction in the permissible dose (AEC Oct. 31, 1969, pp.203-209 --- an example of many subsequent statements). Unofficially, there was talk of increasing the permissible dose. Back then, the AEC had ambitious plans to build "a plutonium economy," to license 800 to 1000 large nuclear power plants by the year 2000 (AEC 1970, p.685), and to loosen natural gas in the Rocky Mountains by exploding hundreds of underground nuclear bombs.
The plans and the public's exposure to the permissible dose would probably have become a reality, if it were not for rising public concern in the 1970s over the potential health effects.
Later, with the advance of technology, it was discovered that both trisomy-13 and trisomy-18 --- like trisomy-21 --- also can occur as mosaics (in-utero) and as partial trisomies (inherited as a result of translocations).
The Linking of Cause with Consequence
No one is claiming that all individuals who have the health effects listed above are cases of trisomy-13, -18, or -21. Many additional genetic causes of these health problems have been discovered, and it is possible that some cases arise without any genetic injury at all. Then how can anyone be sure that a trisomy causes the problems of trisomic individuals?
Whenever a variety of causes might produce the same health effect, two types of study can establish causation.
In a prospective cohort study, you start with a suspected cause and then you measure the occurrence of presumed consequences. You measure the health of one group which has trisomic cells (a presumed cause of the listed health effects) and another group which does not have trisomic cells, and you discover which group has the higher rate of the health effects. The frequency of mental handicap, for example, approaches 100% in the trisomic individuals, while the frequency is certainly lower in the general population.
In a retrospective case-control study, you start with presumed health consequences and then you measure the occurrence of a suspected cause. You measure the rate of trisomic cells in one group which has the health effects (a presumed consequence of trisomy) and in another group which does not have these health effects, and you find out which group has the greater frequency of trisomic cells (a presumed cause). There is no doubt that the frequency of 47 chromosomes is higher among the persons who have the health effects listed above. Indeed, the rate of full-chromosome trisomy among persons who lack such health effects is so low that we are unaware of a single known case.
The First Discoveries of Deletion Syndromes
All-cell, full-chromosome trisomies were open to study in the early era, since this was a matter of just counting chromosomes. But the opposite possibility --- namely, a deficit of certain chromosomal information --- was not nearly so easily studied, since only arm-lengths and centromere positions were available to identify such losses.
Cri-Du-Chat Syndrome. Nonetheless, by 1963 progress was underway when Lejeune and co-workers described the first three cases of the 5p partial monosomy or deletion syndrome. It was called Cri du Chat Syndrome because infants with it have a peculiar, cat-like mewing cry. Hundreds of cases were subsequently reported, and they are missing 30% to 85% of the short arm of the B-5 chromosome. The disorder is severe. Besides the cry, clinical features in most cases include profound mental handicap, small head, low-set ears, and growth failure.
Box #2, A Contrast in Warnings:
Examples from 1980-1981
o -- The BEIR Committee replaced the Federal Radiation Council. In 1980, what sort of warning did it issue concerning radiation-induced chromosome damage? First, it grouped "small deletions" with single-gene mutations, and then stated: "Disorders due to chromosomal aberrations . . . will amount to fewer than 10 anomalies per million liveborn, and most subcommittee members felt that the true value may be near zero. (BEIR-3, Chapter 4 Summary). Instead of any warning flag, a strong suggestion of no effect was produced.
o -- In 1981, the book Radiation and Human Health (Gofman 1981) bristled with warnings in its last 150 pages of analysis. For instance:
- "The author's opinion is that small deletions occurring in-utero produce mosaicism which will prove to be an important basis for congenital anomalies. This is an opinion, not a fact. It is a fact that the technology for studying this question is not currently available" (p.721-22).
- "With respect to both deletions and translocations, the author would like to warn the reader about a very poor practice in a great deal of the medical and scientific literature. The technology for recognizing and measuring relatively small deletions and translocations is most appropriately described as primitive, even after taking the new banding techniques into account. The large majority of small deletions and translocations can not possibly be recognized with the use of available technology. Yet many authorities treat these injuries as though they simply do not occur" (p.766).
- "The extent to which the genetic-chromosomal effects of radiation are under-estimated, just on the basis of a total absence of appreciation of the deletion problem, can not be known. Any guesstimate would be highly speculative. But the author of this book would not be at all surprised if future evidence showed that the `deletion cost' from radiation exceeds most of the costs which have been estimated already" (p.843).
Wolf-Hirschhorn Syndrome. In 1965, the 4p partial monosomy or deletion syndrome was discovered by Wolf. Between 10% to 80% of the short arm of chromosome B-4 is missing. Clinical features of this Wolf-Hirschhorn Syndrome include severe mental handicap, seizures, delayed psychomotor development, pre-natal and post-natal growth failure, and multiple malformations such as cleft palate, cleft lip, congenital heart malformations, genital abnormalities in males, defects of the urinary tract, skeletal abnormalities of fingers, hips, spine. As we shall see in Part 7, special facial features are associated with Wolf-Hirschhorn Syndrome, too. About 40% of infants who are born with the 4p deletion syndrome die in infancy or childhood.
6 * The Banding Era of Cytogenetics, 1970-1985
The banding era began around 1970, when special stains made it possible to start differentiating segments (or bands) along chromosomal arms. Gradually it became possible to distinguish about 400 pairs of bands (total) among the 46 chromosomes. Advanced, high-resolution banding techniques today extend the total to over 800 pairs. The naming of each band begins with the number of the chromosome, then the arm (p or q), and then single digits indicating large regions. Number 1 is always the region closest to the centromere, and then additional digits indicate sub-sections of specific regions.
Banding made it possible to start finding and correctly identifying translocations and deletions. In the pre-banding era, the true identity of the injured chromosomes was easily mistaken, because they acquired new shapes and sizes.
Thanks to the development and improvement of banding techniques, de Grouchy and Turleau were able to publish a second edition of their remarkable Clinical Atlas of Human Chromosomes in 1984. Based on the worldwide literature of reported cases, the Atlas demonstrates the discovery of partial trisomies or partial monosomies (deletion syndromes) involving every autosome. There is not enough space here even to list them all --- over 70 types known by 1984.
Are these structural chromosomal aberrations associated with important health effects? Mental handicap at various levels is one feature shared by almost all 70 types. A few examples follow:
- For chromosome 3, for instance, there is a partial trisomy involving the 3q2 region. It is associated with severe mental handicap, heart defects in about 33% of cases, abnormalities of kidneys and digestive tract "frequently," skeletal abnormalities at "many sites," and genital abnormalities in males "always" and in females "most cases."
- For chromosome 3 also, there is a partial trisomy of the p-arm from 3p2 to the distal end. This is associated with severe mental handicap, heart defects in about 75% of reported cases, skeletal abnormalities at many sites, and genital abnormalities in all males.
- On chromosome 3 also, there is a partial monosomy involving the 3p2 region. This is associated with very severe mental handicap skeletal abnormalities at several sites, and genital abnormalities in both sexes.
The Issue of Causation
This type of evidence in the Atlas, accompanied by some photos of the infants, is virtually screaming at the world: CAUTION ! Structural chromosome aberrations --- readily inducible by ionizing radiation --- can cause extremely serious mental handicap and other birth defects. And yet, in some circles, denial or "we don't know the meaning" is still heard (Box #3).
Thus, we expect a challenge from some circles to the presumption that the chromosome aberrations are causing the handicaps described in the Atlas --- a presumption which is made in the Atlas and elsewhere, and a presumption which I predict will be systematically validated in the future.
Consider that there is a continuum of genetic mutations. At one end, we learned that an all-cell full-chromosome trisomy causes serious handicaps. At the other end, we know that a single-gene mutation can cause devastating health effects, such as cystic fibrosis and Huntington's Disease. Every few weeks now, the genetic basis of an additional disease is announced. Would it make sense for anyone to deny that partial trisomies and partial monosomies, which lie in the realm between single-gene mutations and full trisomies, have a causal relationship with the associated health effects described in the Atlas?
7 * The Era of Molecular Cytogenetics, 1985 Onward
Very strong evidence in favor of causality is provided by a medical mystery whose solution was described during 1991 by Michael Altherr and co-workers in the American Journal of Human Genetics. The solution depended not only on human tenacity, but also on the availability of the new laboratory technologies in molecular biology such as RFLP (Restriction Fragment Length Polymorphism) and FISH (Fluorescence In-Situ Hybridization) --- which we will not attempt to describe in this paper.
The mystery involved a female child with the facial features of the Wolf-Hirschhorn Deletion Syndrome noted at birth. Serious additional abnormalities included a septal defect between the cardiac auricles. On the basis of the facial features, the diagnosis of Wolf-Hirschhorn was considered, but an ordinary chromosome analysis detected no abnormality of chromosome 4.
At age one, the child had heart surgery, and as she grew older, her facial features increasingly had the characteristics of Wolf-Hirschhorn Syndrome. So a high-resolution chromosome analysis was performed on her and on both parents. But even the best banding technologies in cytogenetics could not provide a conclusive answer (see Box #2).
Altherr persevered. First he tried RFLP, with DNA probes for seven different segments within the most distal band of chromosome 4's p-arm. These DNA probes were able to establish that the child did not inherit a maternal copy for two of the segments. When Altherr also used FISH on the mother's chromosomes, he discovered that she had a small part of 4p translocated onto the p-arm of chromosome 19. When she transmitted only 23 chromosomes to her daughter, the daughter received the copy of B-4 which was missing some information, but not the copy of chromosome 19 which carried the missing information --- and which spared the mother from the obvious health effects.
Which is the more reasonable conclusion from this story: (A) the very small 4p deletion in this child caused the characteristic abnormalities observed in other cases of Wolf-Hirschhorn 4p Deletion Syndrome, or (B) the very small 4p deletion was present in this particular child just by coincidence?
Box #3. A Contrast in Warnings: Examples from 1988 to Now
o -- Depreciation of chromosome aberrations occurs in Dr. Thomas Luckey's 1991 book, the thesis of which is that good health requires more radiation exposure, not less. Going even further than Dr. Totter (Box #1), Dr. Luckey says, "Although chromosomal aberrations are proportional to radiation dose and appear after very low doses of radiation, no medical diseases are associated with these changes" (p.77).
o -- In 1990, the BEIR-5 Committee made some major moves toward realism with respect to admitting high spontaneous rates of genetically-related diseases and afflictions. On the other hand, when it came to assigning responsibility to radiation, the BEIR-5 Report sent mixed messages. For instance:
"Although chromosome aberrations can be induced by relatively low doses of radiation . . . the health implications, if any, of an increase in the frequency of such aberrations in circulating lymphocytes is uncertain" (p.34).
Uncertain? If aberrations increase in a population's lymphocytes because of whole-body irradiation (from either natural or man-made sources), the aberrations also increase in all other cells, including the germ cells. "Health implications" are described in the text.
o -- Analysts at RERF write extensively about the Hiroshima-Nagasaki children who were in-utero during the bombings and who showed an elevated frequency of mental handicaps. RERF is the foundation which controls the A-Bomb Study for the U.S. Dept. of Energy and the Japanese Ministry of Health. In five papers published in 1988 through 1991, the RERF analysts speculate for pages about how radiation could have caused the mental handicaps --- without even mentioning radiation-induction of chromosome injuries.
o -- The contrast is stunning between the depreciation of chromosome injuries in some circles, versus the evidence described in this 1992 essay.
Altherr and co-workers comment (1991, p.1235), "This provides the first evidence, in chromosome 4p, of a molecular deletion due to a subtle, inherited translocation leading to the Wolf-Hirschhorn phenotype. Such subtle translocations may become an important mechanism for some recurrent genetic defects." We could hardly have conjured up a better-matching and independent agreement with our own warnings and predictions of 1970 and 1981.
8 * What Else Will the New Technologies Reveal?
The Altherr report confirms a logic which may be self-evident to many objective analysts in this field: If single-gene mutations can cause drastic health consequences, then surely small, sub-visible deletions (either inherited or occurring early in gestation) can also cause them. In my opinion, if any radiation expert today were to say "We do not know the significance of small deletions and translocations," it would be a strangeness lasting 20 years too long.
Readers may consider the estimate of Dallapiccola and Forabosco (1987, p.25): "A chromosome contains about 100 million base-pairs of DNA. Any visible deletion of a chromosome involves at least 2% to 5% of a chromosome. A deletion would involve enough space for 2 million base pairs, or about 50 genes (a gene typically takes up about 40,000 base pairs of space)." The point is that chromosome injuries can delete multiple genes and still be completely undetectable by the best banding technologies.
If readers consider the limitless variety of micro-deletions and translocations which may exist --- undetected --- in today's population, then they may agree with our prediction:
The new discoveries being made with molecular biological techniques will confirm that a large part of the congenital defects of unknown origin, and a large part of the irregularly inherited diseases of unknown origin, are really consequences of deletions and translocations at the sub-microscopic level. The Altherr report is only the very tip of an iceberg which will be seen more fully in the next decade.
This "iceberg" should be taken into account today when people discuss "permissible" levels of involuntary exposures to possible chromosome-breakers and to proven chromosome-breakers such as ionizing radiation.
AEC 1969 (October 31).
James T. Ramey and Dr. Theos J. Thompson, both commissioners of the U.S. Atomic Energy Commission, in Environmental Effects of Producing Electric Power, Hearings Part 1: October 31, 1969 before the Joint Committee on Atomic Energy, 91st Congress, first session, pp.203-209. 1969. Their testimony opposing any reduction in the permissible dose is also quoted in Gofman + Tamplin 1971, pp.133-140.
AEC 1970 (August 5).
Clarence E. Larson and James T. Ramey, both commissioners of the U.S. Atomic Energy Commission, in Underground Uses of Nuclear Energy, Hearings Part 2 on Bill S.3042: August 5, 1970 before the Subcommittee on Air and Water Pollution of the Committee on Public Works, U.S. Senate, 91st Congress, second session, p.685. 1970.
Michael R. Altherr + 7 co-workers, "Molecular Confirmation of Wolf-Hirschhorn Syndrome with a Subtle Translocation of Chromosome 4," American Journal of Human Genetics Vol.49: 1235-1242. 1991.
BEIR 1980, or BEIR-3.
The BEIR-3 Report, sponsored by the U.S. Government and authored by the Committee on the Biological Effects of ionizing Radiations (Edward P. Radford, Chairman). The Effects on Populations of Exposure to Low Levels of Ionizing Radiation. (National Academy Press, 2101 Constitution Avenue, NW, Washington DC 20418, USA.) No index. 1980.
BEIR 1990, or BEIR-5.
The BEIR-5 Report, sponsored by the U.S. Government and authored by the Committee on the Biological Effects of ionizing Radiations (Arthur C. Upton, Chairman). Health Effects of Exposure to Low Levels of Ionizing Radiation. 421 pages. ISBN 0-309-03995-9. (National Academy Press, 2101 Constitution Avenue, NW, Washington, DC 20418, USA.)
B. Dallapiccola + A. Forabosco, "Human Micro-Cytogenetics," Acta Medica Auxologica Vol. l9: 5-33. 1987.
De Grouchy 1984.
Jean de Grouchy (M.D.) + Catherine Turleau (M.D.), Clinical Atlas of Human Chromosomes, Second Edition. 487 pages. A Wiley Medical Publication. (John Wiley and Sons, New York City NY, USA.) 1984.
Gofman + Tamplin 1969 (October 29).
John W. Gofman + Arthur R. Tamplin, "Low Dose Radiation and Cancer," paper presented at the IEEE Nuclear Science Symposium, San Francisco. In IEEE Transactions on Nuclear Science, Vol. NS-17 Number 1, Feb. 1970: 1-9. (Institute of Electrical and Electronics Engineering, New York City NY, USA.)
Gofman + Tamplin 1970 (April 22).
John W. Gofman + Arthur R. Tamplin, "Can We Survive the Peaceful Atom?", paper GT-120 presented at the Environmental Teach-In of the First "Earth Day," University of Minnesota, Minneapolis. Reprinted in Earth Day --- The Beginning; A Guide For Survival, compiled and edited by the staff of Environmental Action, Washington, DC. Bantam Book number 553-05822-125. Arno Press, Inc., New York City, USA. Also available in Underground Uses of Nuclear Energy, Hearings Part 2 on Bill S.3042: August 5, 1970 before the Subcommittee on Air and Water Pollution of the Committee on Public Works, U.S. Senate, 91st Congress, second session, pp.1509-1522. 1970.
Gofman + Tamplin 1970 (June 29).
John W. Gofman + Arthur R. Tamplin, "Questions for Dr. Paul Tompkins, Director of the Federal Radiation Council," in Underground Uses of Nuclear Energy; the full reference is provided above in the April 1970 entry; pp.1538-1559. Warnings about the consequences of chromosome damage are also given in Gofman + Tamplin 1971 (especially Chapter 3).
Gofman + Tamplin 1971. Re-issued in 1979.
John W. Gofman and Arthur R. Tamplin, Poisoned Power: The Case Against Nuclear Power Plants. 353 pages. ISBN 0-87857-288-0. Rodale Press, Emmaus PA, USA. 1971, 1979.
John W. Gofman, Radiation And Human Health. 908 pages. ISBN 0-87156-275-8. (Sierra Club Books, 100 Bush Street, 13th floor, San Francisco, CA 94104, USA.) 1981.
Thomas D. Luckey, Radiation Hormesis. 306 pages. ISBN 0-8493-6159-1. (CRC Press, 2000 Corporate Blvd. NW, Boca Raton FL 33431, USA). 1991.
Otake 1988-a (May).
Masanori Otake + Hiroshi Yoshimaru + William J. Schull, Severe Mental Retardation Among The Prenatally Exposed Survivors Of The Atomic Bombing Of Hiroshima And Nagasaki: A Comparison Of The T65DR And DS86 Dosimetry Systems. RERF Technical Report TR-16-87, printed May 1988. (Radiation Effects Research Foundation. Hiroshima, Japan.) 1988.
Otake 1988-b (August).
Masanori Otake + William J. Schull + Yasunori Fujikoshi + Hiroshi Yoshimaru, Effect On School Performance Of Prenatal Exposure To Ionizing Radiation In Hiroshima: A Comparison Of The T65DR And DS86 Dosimetry Systems. RERF Technical Report TR-2-88. (Radiation Effects Research Foundation, Hiroshima, Japan.)
Masanori Otake + William J. Schull + Hiroshi Yoshimaru, "Brain Damage among the Prenatally Exposed," Journal of Radiation Research (TOKYO), Supplement 32: 249-264. 1991.
RERF analysts: Five papers on mental retardation.
William J. Schull + Stata Norton + Ronald P. Jensh, "Ionizing Radiation and the Developing Brain," Neurotoxicology And Teratology Vol.12: 249-260. 1990.
Totter 1970 (August 5).
John Totter, director of the Bio-Medical Division of the U.S. Atomic Energy Commission, in Underground Uses of Nuclear Energy Hearings Part 2 on Bill S.3042, August 5, 1970 before the Subcommittee on Air and Water Pollution of the Committee on Public Works. U.S. Senate. 91st Congress, second session, p.677. 1970.
Yamazaki 1990 (August 1).
James N. Yamazaki + William J. Schull, "Perinatal Loss and Neurological Abnormalities among Children of the Atomic Bomb: Hiroshima and Nagasaki Revisited 1949-1989," Journal Of The American Medical Assn. Vol.264, No.5: 605-609.
AUTHOR: JWG is chairman of CNR; professor emeritus of Molecular and Cell Biology at the University of California, Berkeley; founder in 1963 of the Bio-Medical Research Division of the Livermore National Laboratory; author of four scholarly books on health effects from ionizing radiation (1981, 1985, 1990, and 1994 in progress).
# # # # #
Committee for Nuclear Responsibility, Inc. (CNR)
A non profit educational organization since 1971.
Gifts are tax deductible.
Post Office Box 421993, San Francisco, CA 94142, USA.
This document is also available in fancy HTML and ASCII text formats
and can always be found at http://www.ratical.org/radiation/CNR/RICIP.html