The Genetic Effects of Radiation - 3

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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 Mutation
Where radiation is insufficient to render a cell incapable of division,
it may still induce mutations, and it is in this fashion that skin
cancer, leukemia, and other disorders may be brought about.[6]
[Illustration: _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._]
[Illustration: Four-winged male with a double thorax]
[Illustration: Three-winged fly with partial double thoraxes]
[Illustration: 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, it will not matter that there are
999,999 perfectly good sex cells that might have been used—it was the
damaged cell that _was_ used. That is why there is no threshold in the
genetic effect of radiation and why there is no “safe” amount of
radiations insofar as genetic effects are concerned. However small the
quantity of radiation absorbed, mankind must be prepared to pay the
price in a corresponding increase of the genetic load.
[Illustration: 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 mutations plus 1 radiational, we would have 99 plus 3.
The total number of mutations would increase from 100 to 102—an increase
of 2%, not an increase of 200% that one would expect if all spontaneous
mutations were caused by background radiation.
RADIATION EXPOSURES IN THE UNITED STATES[7]
Millirems[8]
Natural Sources
A. External to the body
1. From cosmic radiation 50.0
2. From the earth 47.0
3. From building materials 3.0
B. Inside the body
1. Inhalation of air 5.0
2. Elements found naturally in human tissues 21.0
Total, Natural sources 126.0
Man-made Sources
A. Medical Procedures
1. Diagnostic X rays 50.0
2. Radiotherapy X ray, radioisotopes 10.0
3. Internal diagnosis, therapy 1.0
Subtotal 61.0
B. Atomic energy industry, laboratories 0.2
C. Luminous watch dials, television tubes, 2.0
radioactive industrial wastes, etc.
D. Radioactive fallout 4.0
Subtotal 6.2
Total, man-made sources 67.2
Overall total 193.2

Dosage Rates
Another 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 in the saving of life and the mitigation of suffering. Still,
X rays ought not to be used lightly, or routinely as a matter of course.
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 Mammals
Although 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.
[Illustration: _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 and interesting, much research remains to be carried out.
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.

Conclusion
It 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.
[Illustration: _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.[9]
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 that the alternative of abandoning radiation
technology altogether will cause still greater suffering.
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 house—and he
would not be able to afford a second mortgage.
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.


SUGGESTED REFERENCES

Books
_Radiation, Genes, and Man_, Bruce Wallace and Theodosius Dobzhansky,
Holt, Rinehart and Winston, Inc., New York 10017, 1963, 205 pp., $5.00
(hardback); $1.28 (paperback).
_Genetics in the Atomic Age_ (second edition), Charlotte Auerbach,
Oxford University Press, Inc., Fair Lawn, New Jersey 07410, 1965, 111
pp., $2.50.
_Atomic Radiation and Life_ (revised edition), Peter Alexander, Penguin
Books, Inc., Baltimore, Maryland 21211, 1966, 288 pp., $1.65.
_The Genetic Code_, Isaac Asimov, Grossman Publishers, Inc., The Orion
Press, New York 10003, 1963, 187 pp., $3.95 (hardback); $0.60
(paperback) from the New American Library of World Literature, Inc.,
New York 10022.
_Radiation: What It Is and How It Affects You._ Ralph E. Lapp and Jack
Schubert, The Viking Press, New York 10022, 1957, 314 pp., $4.50
(hardback); $1.45 (paperback).
_Report of the United Nations Scientific Committee on the Effects of
Atomic Radiation_, General Assembly, 19th Session, Supplement No. 14
(A/5814), United Nations, International Documents Service, Columbia
University Press, New York 10027, 1964, 120 pp., $1.50.
_The Effects of Nuclear Weapons_, Samuel Glasstone (Ed.), U. S. Atomic
Energy Commission, 1962, 730 pp., $3.00. Available from the
Superintendent of Documents, U. S. Government Printing Office,
Washington, D. C. 20402.
_Effect of Radiation on Human Heredity_, World Health Organization,
International Documents Service, Columbia University Press, New York
10027, 1957, 168 pp., $4.00.
_The Nature of Radioactive Fallout and Its Effects on Man_, Hearings
before the Special Subcommittee on Radiation of the Joint Committee on
Atomic Energy, Congress of the United States, 85th Congress, 1st
Session, U. S. Government Printing Office, 1957, Volume I, 1008 pp.,
$3.75; Volume II, 1057 pp., $3.50. Available from the Office of the
Joint Committee on Atomic Energy, Congress of the United States,
Senate Post Office, Washington, D. C. 20510.
_Genetics, Radiobiology, and Radiology_, Proceedings of the Midwestern
Conference, Wendell G. Scott and Evans Titus, Charles C. Thomas
Publisher, Springfield, Illinois 62703, 1959, 166 pp., $5.50.

Articles
Genetic Hazards of Nuclear Radiations, Bentley Glass, _Science_, 126:
241 (August 9, 1957).
Genetic Loads in Natural Populations, Theodosius Dobzhansky, _Science_,
126: 191 (August 2, 1957).
Radiation Dose Rate and Mutation Frequency, W. L. Russell and others,
_Science_, 128: 1546 (December 19, 1958).
Ionizing Radiation and the Living Cell, Alexander Hollaender and George
E. Stapleton, _Scientific American_, 201: 95 (September 1959).
Radiation and Human Mutation, H. J. Muller, _Scientific American_, 193:
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