The Genetic Effects of Radiation - 2

further alter the relative “goodness” or “badness” of certain gene
patterns.
Thus, over the past million years, for example, the human brain has,
through mutations and appropriate shifts in emphasis within the gene
pool, increased notably in size.

Genetic Load
Some gene mutations produce characteristics so undesirable that it is
difficult to imagine any reasonable change in environmental conditions
that would make them beneficial. There are mutations that lead to the
nondevelopment of hands and feet, to the production of blood that will
not clot, to serious malformations of essential organs, and so on. Such
mutations are unqualifiedly bad.
The badness may be so severe that a fertilized ovum may be incapable of
development; or, if it develops, the fetus miscarries or the child is
stillborn; or, if the child is born alive, it dies before it matures so
that it can never have children of its own. Any mutation that brings
about death before the gene producing it can be passed on to another
generation is a _lethal mutation_.
A gene governing a lethal characteristic may be dominant. It will then
kill even though the corresponding gene on the other chromosome of the
pair is normal. Under such conditions, the lethal gene is removed in the
same generation in which it is formed.
The lethal gene may, on the other hand, be recessive. Its effect is then
not evident if the gene it is paired with is normal. The normal gene
carries on for both.
When this is the case, the lethal gene will remain in existence and
will, every once in a while, make itself evident. If two people, each
serving as a _carrier_ for such a gene, have children, a sperm cell
carrying a lethal may fertilize an egg cell carrying the same type of
lethal, with sad results.
Every species, including man, includes individuals who carry undesirable
genes. These undesirable genes may be passed along for generations, even
if dominant, before natural selection culls them out. The more seriously
undesirable they are, the more quickly they are removed, but even
outright lethal genes will be included among the chromosomes from
generation to generation provided they are recessive. These deleterious
genes make up the _genetic load_.
The only way to avoid a genetic load is to have no mutations and
therefore no gene pool. The gene pool is necessary for the flexibility
that will allow a species to survive and evolve over the eons and the
genetic load is the price that must be paid for that. Generally, the
capacity for a species to reproduce itself is sufficiently high to make
up, quite easily, the numbers lost through the combination of
deleterious genes.
The size of a genetic load depends on two factors: The rate at which a
deleterious gene is produced through mutation, and the rate at which it
is removed by natural selection. When the rate of removal equals the
rate of production, a condition of _genetic equilibrium_ is reached and
the level of occurrence of that gene then remains stable over the
generations.
Even though deleterious genes are removed relatively rapidly, if
dominant, and lethal genes are removed in the same generation in which
they are formed, a new crop of deleterious genes will appear by mutation
with every succeeding generation. The equilibrium level for such
dominant deleterious genes is relatively low, however.
Deleterious genes that are recessive are removed much more slowly. Those
persons with two such genes, who alone show the bad effects, are like
the visible portion of an iceberg and represent only a small part of the
whole. The heterozygotes, or carriers, who possess a single gene of this
sort, and who live out normal lives, keep that gene in being. If people
in a particular population marry randomly and if one out of a million is
born homozygous for a certain deleterious recessive gene (and dies of
it), one out of five hundred is heterozygous for that same gene, shows
no ill effects, and is capable of passing it on.
It may be that the heterozygote is not quite normal but does show some
ill effects—not enough to incommode him seriously, perhaps, but enough
to lower his chances slightly for mating and bearing children. In that
case, the equilibrium level for that gene will be lower than it would
otherwise be.
It may also be that the heterozygote experiences an actual advantage
over the normal individual under some conditions. There is a recessive
gene, for instance, that produces a serious disease called sickle-cell
anemia. People possessing two such genes usually die young. A
heterozygote possessing only one of these genes is not seriously
affected and has red blood cells that are, apparently, less appetizing
to malaria parasites. The heterozygote therefore experiences a positive
advantage if he lives in a region where the incidence of certain kinds
of malaria is high. The equilibrium level of the sickle-cell anemia gene
can, in other words, be higher in malarial regions than elsewhere.
Here is one subject area in which additional research is urgently
needed. It may be that the usefulness of a single deleterious gene is
greater than we may suspect in many cases, and that there are greater
advantages to heterozygousness than we know. This may be the basis of
what is sometimes called “hybrid vigor”. In a world in which human
beings are more mobile than they have ever been in history and in which
intercultural marriages are increasingly common, information on this
point is particularly important.

Mutation Rates
It is easier to observe the removal of genes through death or through
failure to reproduce than to observe their production through mutation.
It is particularly difficult to study their production in human beings,
since men have comparatively long lifetimes and few children, and since
their mating habits cannot well be controlled.
For this reason, geneticists have experimented with species much simpler
than man—smaller organisms that are short-lived, produce many offspring,
and that can be penned up and allowed to mate only under fixed
conditions. Such creatures may have fewer chromosomes than man does and
the sites of mutation are more easily pinned down.
An important assumption made in such experiments is that the machinery
of inheritance and mutation is essentially the same in all creatures and
that therefore knowledge gained from very simple species (even from
bacteria) is applicable to man. There is overwhelming evidence to
indicate that this is true in general, although there are specific
instances where it is not completely true and scientists must tread
softly while drawing conclusions.
The animals most commonly used in studies of genetics and mutations are
certain species of fruit flies, called _Drosophila_. The American
geneticist, Hermann J. Muller, devised techniques whereby he could study
the occurrence of lethal mutations anywhere along one of the four pairs
of chromosomes possessed by _Drosophilia_.
A lethal gene, he found, might well be produced somewhere along the
length of a particular chromosome once out of every two hundred times
that chromosome underwent replication. This means that out of every 200
sex cells produced by _Drosophilia_, one would contain a lethal gene
somewhere along the length of that chromosome.
[Illustration: _Geneticist Hermann J. Muller studying_ Drosophila _in
his laboratory. Dr. Muller won a Nobel Prize in 1946 for showing that
radiation can cause mutations. (See page 34.)_]
That particular chromosome, however, contained at least 500 genes
capable of undergoing a lethal mutation. If each of those genes is
equally likely to undergo such a mutation, then the chance that any one
particular gene is lethal is one out of 200 × 500, or 1 out of 100,000.
This is a typical mutation rate for a gene in higher organisms
generally, as far as geneticists can tell (though the rates are lower
among bacteria and viruses). Naturally, a chance for mutation takes
place every time a new individual is born. Fruit flies have many more
offspring per year than human beings, since their generations are
shorter and they produce more young at a time. For that reason, though
the mutation rate may be the same in fruit flies as in man, many more
actual mutations are produced per unit time in fruit flies than in men.
This does not mean that the situation may be ignored in the case of man.
Suppose the rate for production of a particular deleterious gene in man
is 1 out of 100,000. It is estimated that a human being has at least
10,000 different genes, and therefore the chance that at least one of
the genes in a sex cell is deleterious is 10,000 out of 100,000 or 1 out
of 10.
Furthermore, it is estimated that the number of gene mutations that are
weakly deleterious are four times as numerous as those that are strongly
deleterious or lethal. The chances that at least one gene in a sex cell
is at least weakly deleterious then would be 4 + 1 out of 10, or 1 out
of 2.
Naturally, these deleterious genes are not necessarily spread out evenly
among human beings with one to a sex cell. Some sex cells will be
carrying more than one, thus increasing the number that may be expected
to carry none at all. Even so, it is supposed that very nearly half the
sex cells produced by humanity carry at least one deleterious gene.
Even though only half the sex cells are free of deleterious genes, it is
still possible to produce a satisfactory new generation of men. Yet one
can see that the genetic load is quite heavy and that anything that
would tend to increase it would certainly be undesirable, and perhaps
even dangerous.
We tend to increase the genetic load by reducing the rate at which
deleterious genes are removed, that is, by taking care of the sick and
retarded, and by trying to prevent discomfort and death at all levels.
There is, however, no humane alternative to this. What’s more, it is, by
and large, only those with slightly deleterious genes who are preserved
genetically. It is those persons with nearsightedness, with diabetes,
and so on, who, with the aid of glasses, insulin, or other props, can go
on to live normal lives and have children in the usual numbers. Those
with strongly deleterious genes either die despite all that can be done
for them even today or, at the least, do not have a chance to have many
children.
The danger of an increase in the genetic load rests more heavily, then,
at the other end—at measures that (usually inadvertently or
unintentionally) increase the rate of production of mutant genes. It is
to this matter we will now turn.


RADIATION

Ionizing Radiation
Our modern technological civilization exposes mankind to two general
types of genetic dangers unknown earlier: Synthetic chemicals (or
unprecedentedly high concentrations of natural ones) absent in earlier
eras, and intensities of energetic radiation equally unknown or
unprecedented.
Chemicals can interfere with the process of replication by offering
alternate pathways with which the cellular machinery is not prepared to
cope. In general, however, it is only those cells in direct contact with
the chemicals that are so affected, such as the skin, the intestinal
linings, the lungs, and the liver (which is active in altering and
getting rid of foreign chemicals). These may undergo somatic mutations,
and an increased incidence of cancer in those tissues is among the
drastic results of exposure to certain chemicals.
Such chemicals are not, however, likely to come in contact with the
gonads where the sex cells are produced. While individual persons may be
threatened by the manner in which the environment is being permeated
with novel chemicals, the next generation is not affected in advance.
Radiation is another matter. In its broadest sense, radiation is any
phenomenon spreading out from some source in all directions. Physically,
such radiation may consist of waves or of particles.[3] Of the wave
forms the two best-known are sound and electromagnetic radiations.
Sound carries very low concentrations of energy. This energy is absorbed
by living tissue and converted into heat. Heat in itself can increase
the mutation rate but the effect is a small one. The body has effective
machinery for keeping its temperature constant and the gonads are not
likely to suffer unduly from exposure to heat.
Electromagnetic radiation comes in a wide range of energies, with
visible light (the best-known example of such radiation because we can
detect it directly and with great sensitivity) about in the middle of
the range. Electromagnetic radiations less energetic than light (such as
infrared waves and microwaves) are converted into heat when absorbed by
living tissue. The heat thus formed is sufficient to cause atoms and
molecules to vibrate more rapidly, but this added vibration is not
usually sufficient to pull molecules apart and therefore does not bring
about chemical changes.
Light will bring about some chemical changes. It is energetic enough to
cause a mixture of hydrogen and chlorine to explode. It will break up
silver compounds and produce tiny black grains of metallic silver (the
chemical basis of photography). Living tissue, however, is largely
unaffected—the retina of the eye being one obvious exception.
Ultraviolet light, which is more energetic than visible light,
correspondingly can bring about chemical changes more easily. It will
redden the skin, stimulate the production of pigment, and break up
certain steroid molecules to form vitamin D. It will even interfere with
replication to some extent. At least there is evidence that persistent
exposure to sunlight brings about a heightened tendency to skin cancer.
Ultraviolet light is not very penetrating, however, and its effects are
confined to the skin.
Electromagnetic radiations more energetic than ultraviolet light, such
as X rays and gamma rays, carry sufficient concentrations of energy to
bring about changes not only in molecules but in the very structure of
the atoms making up those molecules.
Atoms consist of particles (electrons), each carrying a negative
electric charge and circling a tiny centrally located nucleus, which
carries a positive electric charge.
Ordinarily, the negative charges of the electrons just balance the
positive charge on the nucleus so that atoms and molecules tend to be
electrically neutral. An X ray or gamma ray, crashing into an atom,
will, however, jar electrons loose. What is left of the atom will carry
a positive electric charge with the charge size proportional to the
number of electrons lost.
An atom fragment carrying an electric charge is called an _ion_. X rays
and gamma rays are therefore examples of _ionizing radiation_.
Radiations may consist of flying particles, too, and if these carry
sufficient energy they are also ionizing in character. Examples are
_cosmic rays_, _alpha rays_, and _beta rays_. Cosmic rays are streams of
positively charged nuclei, predominantly those of the element hydrogen.
Alpha rays are streams of positively charged helium nuclei. Beta rays
are streams of negatively charged electrons. The individual particles
contained in these rays may be referred to as _cosmic particles_, _alpha
particles_, and _beta particles_, respectively.
[Illustration: _Cosmic ray and trapped Van Allen Belt energetic
particles produced the dark tracks in this photo of a nuclear emulsion
that had been carried aloft on an Air Force satellite. The energetic
particles cause ionization of the silver bromide molecules in the
emulsion._]
[Illustration: _Alpha particles emitted by the source at right leave
tracks in a cloud chamber. Some tracks are bent near the end as a result
of collisions with atomic nuclei. Such collisions are more likely at the
end of a track when the alpha particle has been slowed down._]
[Illustration: _Beta particles originating at left leave these tracks in
a cloud chamber. Note that the tracks are much farther apart than those
of alpha particles. As the particle slows down, its path becomes more
erratic and the ions are formed closer together. At the very end of an
electron track the proximity of the ions approximates that in an
alpha-particle track._]
Ionizing radiation is capable of imparting so much energy to molecules
as to cause them to vibrate themselves apart, producing not only ions
but also high-energy uncharged molecular fragments called _free
radicals_.
The direct effect of ionizing radiation on chromosomes can be serious.
Enough chemical bonds may be disrupted so that a chromosome struck by a
high-energy wave or particle may break into fragments. Even if the
chromosome manages to remain intact, an individual gene along its length
may be badly damaged and a mutation may be produced.
[Illustration: _Effects of ionizing radiation on chromosomes: Left, a
normal plant cell showing chromosomes divided into two groups; right,
the same type of cell after X-ray exposure, showing broken fragments and
bridges between groups, typical abnormalities induced by radiation._]
If only direct hits mattered, radiation effects would be less dangerous
than they are, since such direct hits are comparatively few. However,
near-misses may also be deadly. A streaking bit of radiation may strike
a water molecule near a gene and may break up the molecule to form a
free radical. The free radical will be sufficiently energetic to bring
about a chemical reaction with almost any molecule it strikes. If it
happens to strike the neighboring gene before it has disposed of that
energy, it will produce the mutation as surely as the original radiation
might have.
Furthermore, ionizing radiations (particularly of the electromagnetic
variety) tend to be penetrating, so that the interior of the body is as
exposed as is the surface. The gonads cannot hide from X rays, gamma
rays, or cosmic particles.
All these radiations can bring about somatic mutations—all can cause
cancer, for instance.
What is worse, all of them increase the rate of genetic mutations so
that their presence threatens generations unborn as well as the
individuals actually exposed.

Background Radiation
Ionizing radiation in low intensities is part of our natural
environment. Such natural radiation is referred to as _background
radiation_. Part of it arises from certain constituents of the soil.
Atoms of the heavy metals, uranium and thorium, are constantly, though
very slowly, breaking down and in the process giving off alpha rays,
beta rays, and gamma rays. These elements, while not among the most
common, are very widely spread; minerals containing small quantities of
uranium and thorium are to be found nearly everywhere.
In addition, all the earth is bombarded with cosmic rays from outer
space and with streams of high-energy particles from the sun.
Various units can be used to measure the intensity of this background
radiation. The _roentgen_, abbreviated _r_, and named in honor of the
discoverer of X rays, Wilhelm Roentgen, is a unit based on the number of
ions produced by radiation. Rather more convenient is another unit that
has come more recently into prominence. This is the _rad_ (an
abbreviation for “radiation absorbed dose”) that is a measure of the
amount of energy delivered to the body upon the absorption of a
particular dose of ionizing radiation. One rad is very nearly equal to
one roentgen.
Since background radiation is undoubtedly one of the factors in
producing spontaneous mutations, it is of interest to try to determine
how much radiation a man or woman will have absorbed from the time he is
first conceived to the time he conceives his own children. The average
length of time between generations is taken to be about 30 years, so we
can best express absorption of background radiation in units of _rads
per 30 years_.
[Illustration: _Natural radioactivity in the atmosphere is shown by this
nuclear-emulsion photograph of alpha-particle tracks (enlarged 2000
diameters) emitted by a grain of radioactive dust._]
The intensity of background radiation varies from place to place on the
earth for several reasons. Cosmic rays are deflected somewhat toward the
magnetic poles by the earth’s magnetic field. They are also absorbed by
the atmosphere to some extent. For this reason, people living in
equatorial regions are less exposed to cosmic rays than those in polar
regions; and those in the plains, with a greater thickness of atmosphere
above them, are less exposed than those on high plateaus.
Then, too, radioactive minerals may be spread widely, but they are not
spread evenly. Where they are concentrated to a greater extent than
usual, background radiation is abnormally high.
Thus, an inhabitant of Harrisburg, Pennsylvania, may absorb 2.64 rads
per 30 years, while one of Denver, Colorado, a mile high at the foot of
the Rockies, may absorb 5.04 rads per 30 years. Greater extremes are
encountered at such places as Kerala, India, where nearby soil, rich in
thorium minerals, so increases the intensity of background radiation
that as much as 84 rads may be absorbed in 30 years.
In addition to high-energy radiation from the outside, there are sources
within the body itself. Some of the potassium and carbon atoms of our
body are inevitably radioactive. As much as 0.5 rad per 30 years arises
from this source.
Rads and roentgens are not completely satisfactory units in estimating
the biological effects of radiation. Some types of radiation—those made
up of comparatively large particles, for instance—are more effective in
producing ions and bring about molecular changes with greater ease than
do electromagnetic radiations delivering equal energy to the body. Thus
if 1 rad of alpha particles is absorbed by the body, 10 to 20 times as
much biological effect is produced as there would be in the absorption
of 1 rad of X rays, gamma rays, or beta particles.
Sometimes, then, one speaks of the _relative biological effectiveness_
(RBE) of radiation, or the _roentgen equivalent, man_ (rem). A rad of X
rays, gamma rays, or beta particles has a rem of 1, while a rad of alpha
particles has a rem of 10 to 20.
If we allow for the effect of the larger particles (which are not very
common under ordinary conditions) we can estimate that the gonads of the
average human being receive a total dose of natural radiation of about 3
rems per 30 years. This is just about an irreducible minimum.

Man-made Radiation
Man began to add to the background radiation in the 1890s. In 1895, X
rays were discovered and since then have become increasingly useful in
medical diagnosis and therapy and in industry. In 1896, radioactivity
was discovered and radioactive substances were concentrated in
laboratories in order that they might be studied. In 1934, it was found
that radioactive forms of nonradioactive elements (_radioisotopes_)
could be formed and their use came to be widespread in universities,
hospitals, and industries.[4]
Then, in 1945, the nuclear bomb was developed. With the uranium or
plutonium fission that produces a nuclear explosion, there is an
accompaniment of intense gamma radiation. In addition, a variety of
radioisotopes are left behind in the form of the residue (_fission
fragments_) of the fissioning atoms. These fission fragments are
distributed widely in the atmosphere. Some rise high into the
stratosphere and descend (as _fallout_) over the succeeding months and
years.[5]
It is hard to try to estimate how much additional radiation is being
absorbed by human beings out of these man-made sources. Fallout is not
uniformly spread over the earth but is higher in those latitudes where
nuclear bombs have been most frequently tested. Then, too, people in
industries and research who are involved with the use of radioisotopes,
and people in medical centers who constantly deal with X rays, are
likely to get more exposure than others.
These adjuncts of modern science and medicine are more common and
widespread in technologically advanced countries than elsewhere, and
nuclear bombs have most often been exploded in just those latitudes
where the advanced countries are to be found.
Attempts have been made to work out estimates of this exposure. One
estimate, involving a number of technologically advanced countries
(including the United States) showed that an average of somewhere
between 0.02 and 0.18 rem per year was absorbed, as a result of
radiations (usually X rays) used in medical diagnosis and therapy.
Occupational exposure added, on the average, not more than 0.003 rem,
though the individuals constantly exposed in the course of their work
would naturally absorb considerably more than this overall average.
[Illustration: _Man-made radioactivity in the atmosphere produced this
nuclear-emulsion photograph. This radiation source is a fission product
produced in a nuclear explosion. The enlargement is 1200 diameters.
Compare this with the natural radioactivity depicted on page 28._]
On the whole, the highest absorption was found, as was to be expected,
in the United States.
If these findings are expanded to cover a 30-year period, assuming the
absorption will remain the same from year to year, it turns out that the
average absorption of man-made radiation in the nations studied varies
from 0.6 rem to 5.5 rems per 30 years per individual.
Considering the higher figure to be applicable to the United States, it
would seem that man-made radiation from all sources is now being
absorbed at nearly twice the rate that natural radiation is. To put it
another way, Americans are just about tripling their radiation dosage by
reason of the human activities that are now adding man-made radiation to
the natural supply. By far the major part of this additional dosage is
the result of the use of X rays in searching for decayed teeth, broken
bones, lung lesions, swallowed objects, and so on.


DOSE AND CONSEQUENCE

Radiation Sickness
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