  The danger to the individual as a result of overexposure to high-energy radiation was understood fairly soon but not before some tragic experiences were recorded. One of the early workers with radioactive materials, Pierre Curie, deliberately exposed a patch of his skin to the action of radioactive radiations and obtained a serious and slow-healing burn. His wife, Marie Curie, and their daughter, IrÈne Joliot-Curie, who spent their lives working with radioactive materials, both died of leukemia, very possibly as the result of cumulative exposure to radiation. Other research workers in the field died of cancer before the full necessity of extreme caution was understood. The damage done to human beings by radiation could first be studied on a large scale among the survivors of the nuclear bombings of Hiroshima and Nagasaki in 1945. Here marked symptoms of radiation sickness were observed. This sickness often leads to death, though a slow recovery is sometimes possible. In general, high-energy radiation damages the complex molecules within a cell, interfering with its chemical machinery to the point, in extreme cases, of killing it. (Thus, cancers, which cannot safely be reached with the surgeon’s knife, are sometimes exposed to high-energy radiation in the hope that the cancer cells will be effectively killed in that manner.) The delicate structure of the genes and chromosomes is particularly vulnerable to the impact of high-energy radiation. Chromosomes can be broken by such radiation and this is the main cause of actual cell death. A cell that is not killed outright by radiation may nevertheless be so damaged as to be unable to undergo replication and mitosis. If a cell is of a type that will not, in the course of nature, undergo division, the destruction of the mitosis machinery is not in itself fatal to the organism. A creature like Drosophila, which, in its adult stage, has very few cell divisions going on among the ordinary cells of its body, can survive radiation doses a hundred times as great as would suffice to kill a man. In a human being, however—even in an adult who is no longer experiencing overall growth—there are many tissues whose cells must undergo division throughout life. Hair and fingernails grow constantly, as a result of cell division at their roots. The outer layers of skin are steadily lost through abrasion and are replaced through constant cell division in the deeper layers. The same is true of the lining of the mouth, throat, stomach, and intestines. Too, blood cells are continually breaking up and must be replaced in vast numbers. If radiation kills the mechanism of division in only some of these cells, it is possible that those that remain reasonably intact can divide and eventually replace or do the work of those that can no longer divide. In that case, the symptoms of radiation sickness are relatively mild in the first place and eventually disappear. Past a certain critical point, when too many cells are made incapable of division, this is no longer possible. The symptoms, which show up in the growing tissues particularly (as in the loss of hair, the misshaping or loss of fingernails, the reddening and hemorrhaging of skin, the ulceration of the mouth, and the lowering of the blood cell count), grow steadily more severe and death follows. Radiation and MutationWhere radiation is insufficient to render a cell incapable of division, it may still induce mutations, and it is in this Studies at the California Institute of Technology furnish information on the nature of radiation effects on genes. The experiments produced fruit flies with three or four wings and double or partially doubled thoraxes by causing gene mutation through X-irradiation and chromosome rearrangements. A is a normal male Drosophila; B is a four-winged male with a double thorax; and C and D are three-winged flies with partial double thoraxes. Four-winged male with a double thorax Three-winged fly with partial double thoraxes Three-winged fly with partial double thoraxes Mutations can be brought about in the sex cells, too, of course, and when this happens it is succeeding generations that are affected and not merely the exposed individual. Indeed, where the sex cells are concerned, the relatively mild effect of mutation is more serious than the drastic one of nondivision. A fertilized ovum that cannot divide eventually dies and does no harm; one that can divide but is altered, may give rise to an individual with one of the usual kinds of major or minor physical defects. The effect of high-energy radiation on the genetic mechanism was first demonstrated experimentally in 1927 by Muller. Using Drosophila he showed that after large doses of X rays, flies experienced many more lethal mutations per chromosome than did similar flies not exposed to radiation. The drastic differences he observed proved the connection between radiation and mutation at once. Later experiments, by Muller and by others, showed that the number of mutations was directly proportional to the quantity of radiation absorbed. Doubling the quantity of radiation absorbed doubled the number of mutations, tripling the one tripled the other, and so on. This means that if the number of mutations is plotted against the amount of radiation absorbed, a straight line can be drawn. It is generally believed that the straight line continues all the way down without deviation to very low radiation absorptions. This means there is no “threshold” for the mutational effect of radiation. No matter how small a dosage of radiation the gonads receive, this will be reflected in a proportionately increased likelihood of mutated sex cells with effects that will show up in succeeding generations. In this respect, the genetic effect of radiation is quite different from the somatic effect. A small dose of radiation may affect growing tissues and prevent a small proportion of the cells of those tissues from dividing. The remaining, unaffected cells take up the slack, however, and if the proportion of affected cells is small enough, symptoms are not visible and never become visible. There is thus a threshold effect: The radiation absorbed must be more than a certain amount before any somatic symptoms are manifest. Matters are quite different where the genetic effect is concerned. If a sex cell is damaged and if that sex cell is one of the pair that goes into the production of a fertilized ovum, a damaged organism results. There is no margin for correction. There is no unaffected cell that can take over the work of the damaged sex cell once fertilization has taken place. Suppose only one sex cell out of a million is damaged. If so, a damaged sex cell will, on the average, take part in one out of every million fertilizations. And when it is used, Percent lethal chromosomes vs. Amount of x radiation, r If the straight line obtained by plotting mutation rate against radiation dose is followed down to a radiation dose of zero, it is found that the line strikes the vertical axis slightly above the origin. The mutation rate is more than zero even when the radiation dose is zero. The reason for this is that it is the dose of man-made radiation that is being considered. Even when man-made radiation is completely absent there still remains the natural background radiation. It is possible in this manner to determine that background radiation accounts for considerably less than 1% of the spontaneous mutations that take place. The other mutations must arise out of chemical misadventures, out of the random heat-jiggling of molecules, and so on. These, it can be presumed, will remain constant when the radiation dose is increased. This is a hopeful aspect of the situation for it means that, if the background radiation is doubled or tripled for mankind as a whole, only that small portion of the spontaneous mutation rate that is due to the background radiation will be doubled or tripled. Let us suppose, for instance, that fully 1% of the spontaneous mutations occurring in mankind is due to background radiation. In that case, the tripling of the background radiation produced in the United States by man-made causes (see Table) would triple that 1%. In place of 99 non-radiational
Dosage RatesAnother difference between the genetic and somatic effects of radiation rests in the response to changes in the rate at which radiation is absorbed. It makes a considerable difference to the body whether a large dose of radiation is absorbed over the space of a few minutes or a few years. When a large dose is absorbed over a short interval of time, so many of the growing tissues lose the capacity for cell division that death may follow. If the same dose is delivered over years, only a small bit of radiation is absorbed on any given day and only small proportions of growing cells lose the capacity for division at any one time. The unaffected cells will continually make up for this and will replace the affected ones. The body is, so to speak, continually repairing the radiation damage and no serious symptoms will develop. Then, too, if a moderate dose is delivered, the body may show visible symptoms of radiation sickness but can recover. It will then be capable of withstanding another moderate dose, and so on. The situation is quite different with respect to the genetic effects, at least as far as experiments with Drosophila and bacteria seem to show. Even the smallest doses will produce a few mutations in the chromosomes of those cells in the gonads that eventually develop into sex cells. The affected gonad cells will continue to produce sex cells with those mutations for the rest of the life of the organism. Every tiny bit of radiation adds to the number of mutated sex cells being constantly produced. There is no recovery, because the sex cells, after formation, do not work in cooperation, and affected cells are not replaced by those that are unaffected. This means (judging by the experiments on lower creatures) that what counts, where genetic damage is in question, is not the rate at which radiation is absorbed but the total sum of radiation. Every exposure an organism experiences, however small, adds its bit of damage. Accepting this hard view, it would seem important to make every effort to minimize radiation exposure for the population generally. Since most of the man-made increase in background radiation is the result of the use of X rays in medical diagnosis and therapy, many geneticists are looking at this with suspicion and concern. No one suggests that their use be abandoned, for certainly such techniques are important It might seem that X rays applied to the jaw or the chest would not affect the gonads, and this might be so if all the X rays could indeed be confined to the portion of the body at which they are aimed. Unfortunately, X rays do not uniformly travel a straight line in passing through matter. They are scattered to a certain extent; if a stream of X rays passes through the body anywhere, or even through objects near the body, some X rays will be scattered through the gonads. It is for this reason that some geneticists suggest that the history of exposure to X rays be kept carefully for each person. A decision on a new exposure would then be determined not only by the current situation but by the individual’s past history. Such considerations were also an important part of the driving force behind the movement to end atmospheric testing of nuclear bombs. While the total addition to the background radiation resulting from such tests is small, the prospect of continued accumulation is unpleasant. What’s more, whereas X rays used in diagnosis and therapy have a humane purpose and chiefly affect the patient who hopes to be helped in the process, nuclear fallout affects all of humanity without distinction and seems, to many people, to have as its end only the promise of a totally destructive nuclear war. It is not to be expected that the large majority of humanity that makes up the populations outside the United States, Great Britain, France, China, and the Soviet Union can be expected to accept stoically the risk of even limited quantities of genetic damage, out of any feeling of loyalty to nations not their own. Even within the populations of the three major nuclear powers there are strong feelings that the possible benefits of nuclear testing do not balance the certain dangers. Public opinion throughout the world is a key factor, then, in enforcing the Nuclear Test Ban Treaty, signed by the governments of the United States, Great Britain, and the Soviet Union on October 10, 1963. Effects on MammalsAlthough genetic findings on such comparatively simple creatures as fruit flies and bacteria seem to apply generally to all forms of life, it seems unsafe to rely on these findings completely in anything as important as possible genetic damage to man through radiation. During the 1950s and 1960s, therefore, there have been important studies on mice, particularly by W. L. Russell at Oak Ridge National Laboratory, Oak Ridge, Tennessee. While not as short-lived or as fecund as fruit flies, mice can nevertheless produce enough young over a reasonable period of time to yield statistically useful results. Experimenters have worked with hundreds of thousands of offspring born of mice that have been irradiated with gamma rays and X rays in different amounts and at different intensities, as well as with additional hundreds of thousands born to mice that were not irradiated. Since mice, like men, are mammals, results gained by such experiments are particularly significant. Mice are far closer to man in the scheme of life than is any other creature that has been studied genetically on a large scale, and their reactions (one might cautiously assume) are likely to be closer to those that would be found in man. Almost at once, when the studies began, it turned out that mice were more susceptible to genetic damage than fruit flies were. The induced mutation rate per gene seems to be about fifteen times that found in Drosophila for comparable X ray doses. The only safe course for mankind then is to err, if it must, strongly on the side of conservatism. Once we have decided what might be safe on the basis of Drosophila studies, we ought then to tighten precautions several notches by remembering that we are very likely more vulnerable than fruit flies are. Counteracting the depressing nature of this finding was that of a later, quite unexpected discovery. It was well established that in fruit flies and other simple organisms, it was the total dosage of absorbed radiation that counted and that whether this was delivered quickly or slowly did not matter. Arrangement for long-term low-dose-rate irradiation of mice used for mutation-rate studies at Oak Ridge National Laboratory. The cages are arranged at equal distances from a cesium-137 gamma-ray source in the lead pot on the floor. The horizontal rod rotates the source. This proved to be not so in the case of mice. In male mice, a radiation dose delivered at the rate of 0.009 rad per minute produced only from one-quarter to one-third as many mutations as did the same total dose delivered at 90 rads per minute. In the male, cells in the gonads are constantly dividing to produce sex cells. The latter are produced by the billions. It might be, then, that at low radiation dose rates, a few of the gonad cells are damaged but that the undamaged ones produce a flood of sperm cells, “drowning out” the few produced by the damaged gonad cells. The same radiation dose delivered in a short time might, however, damage so many of the gonad cells as to make the damaged sex cells much more difficult to “flood out”. A second possible explanation is that there is present within the cells themselves some process that tends to repair damage to the genes and to counteract mutations. It might be a slow-working, laborious process that could keep up with the damage inflicted at low dosage rates but not at high ones. High dosage rates might even damage the repair mechanism itself. That, too, would account for the fewer mutations at low dosage rates than at high ones. To check which of the two possible explanations was nearer the truth, Russell performed similar tests on female mice. In the female mouse (or the female human being, for that matter) the egg cells have completed almost all their divisions before the female is born. There are only so many cells in the female gonads that can give rise to egg cells, and each one gives rise to only a single egg cell. There is no possibility of damaged egg cells being drowned out by floods of undamaged ones because there are no floods. Yet it was found that in the female mouse the mutation rate also dropped when the radiation dose rate was decreased. In fact, it dropped even more drastically than was the case in the male mouse. Apparently, then, there must be actual repair within the cell. There must be some chemical mechanism inside the cell capable of counteracting radiation damage to some extent. In the female mouse, the mutation rate drops very low as the radiation dose rate drops, so that it would seem that almost all mutations might be repaired, given enough time. In the male, the mutation rate drops only so far and no farther, so that some mutations (about one-third is the best estimate so far) cannot be repaired. If this is also true in the human being (and it is at least reasonably likely that it is), then the greater vulnerability of our genes as compared with those of fruit flies is at least partially made up for by our greater ability to repair the damage. This opens a door for the future, too. The workings of the gene-repair mechanism ought (it is to be hoped) eventually to be puzzled out. When it is, methods may be discovered for reinforcing that mechanism, speeding it, and increasing its effectiveness. We may then find ourselves no longer completely helpless in the face of genetic damage, or even of radiation sickness. On the other hand, it is only fair to point out that the foregoing appraisal may be an over-optimistic view. Russell’s experiments involved just 7 genes and it is possible that these are not representative of the thousands that exist altogether. While the work done so far is most suggestive If, then, we cannot help hoping that natural devices for counteracting radiation damage may be developed in the future, we must, for the present, remain rigidly cautious. ConclusionIt is unrealistic to suppose that all sources of man-made radiation should be abolished. The good they do now, the greater good they will do in the future, cannot be abandoned. It is, however, reasonable to expect that the present Nuclear Test Ban Treaty will continue and that nations, such as France and China, which have nuclear capabilities but are not signatories of the Treaty will eventually sign. It is also reasonable to expect that X ray diagnosis and therapy will be carried on with the greatest circumspection, and that the use of radiation in industry and research will be carried on with great care and with the use of ample shielding. A film badge (left) and a personal radiation monitor (right) record the amount of radiation absorbed by the wearer. These safety devices, worn by persons working in radiation environments, are designed to keep a constant check on each individual’s absorbed dose and to prevent overexposure. As long as man-made radiation exists, there will be some absorption of it by human beings. The advantages of its use in our modern society are such that we must be prepared to pay some price. This is not a matter of callousness. We have come to depend a great deal for comfort and even for extended life, upon the achievements of our technology, and any serious crippling of that technology will cost us lives. An attempt must be made to balance the values of radiation against its dangers; we must balance lives against lives. This involves hard judgments. Those working under conditions of greatest radiation risk—in atomic research, in industrial plants using isotopes, and so on—can be allowed to set relatively high limits for total radiation dosages and dose rates that they may absorb (with time) with reasonable safety, but such rates will never do for the population generally. A relative few can voluntarily endure risks, both somatic and genetic, that we cannot sanely expect of mankind as a whole. From fruit fly experiments it would seem that a total exposure of 30 to 100 rads of radiation will double the spontaneous mutation rate. So much radiation and such a doubling of the rate would be considered intolerable for humanity. Some geneticists have recommended that the average total exposure of human beings in the first 30 years of life be set at 10 rads. Note that this figure is set as a maximum. Every reasonable method, it is expected, will be used to allow mankind to fall as far short of this figure as possible. Note also that the 10-rad figure is an average maximum. The exposure of some individuals to a greater total dose would be viewed as tolerable for society if it were balanced by the exposure of other individuals to a lesser total dose. A total exposure of 10 rads might increase the overall mutation rate, it is roughly estimated, by 10%. This is serious enough, but is bearable if we can convince ourselves A 10% increase in mutation rate, whatever it might mean in personal suffering and public expense, is not likely to threaten the human race with extinction, or even with serious degeneration. The human race as a whole may be thought of as somewhat analogous to a population of dividing cells in a growing tissue. Those affected by genetic damage drop out and the slack is taken up by those not affected. If the number of those affected is increased, there would come a crucial point, or threshold, where the slack could no longer be taken up. The genetic load might increase to the point where the species as a whole would degenerate and fade toward extinction—a sort of “racial radiation sickness”. We are not near this threshold now, however, and can, therefore, as a species, absorb a moderate increase in mutation rate without danger of extinction. On the other hand, it is not correct to argue, as some do, that an increase in mutation rate might be actually beneficial. The argument runs that a higher mutation rate might broaden the gene pool and make it more flexible, thus speeding up the course of evolution and hastening the advent of “supermen”—brainier, stronger, healthier than we ourselves are. The truth seems to be that the gene pool, as it exists now, supplies us with all the variability we need for the effective working of the evolutionary mechanism. That mechanism is functioning with such efficiency that broadening the gene pool cannot very well add to it, and if the hope of increased evolutionary efficiency were the only reason to tolerate man-made radiation, it would be insufficient. The situation is rather analogous to that of a man who owns a good house that is heavily mortgaged. If he were offered a second house with a similar mortgage, he would have to refuse. To be sure, he would have twice the number of houses, but he would not need a second house since he has all the comfort he can reasonably use in his first What humanity must do, if additional radiation damage is absolutely necessary, is to take on as little of that added damage as possible, and not pretend that any direct benefits will be involved. Any pretense of that sort may well lure us into assuming still greater damage—damage we may not be able to afford under any circumstances and for any reason. Actually, as the situation appears right now, it is not likely that the use of radiation in modern medicine, research, and industry will overstep the maximum bounds set by scientists who have weighed the problem carefully. Only nuclear warfare is likely to do so, and apparently those governments with large capacities in this direction are thoroughly aware of the danger and (so far, at least) have guided their foreign policies accordingly. | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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