The Genetic Effects of Radiation - 1

The Genetic Effects of Radiation

By ISAAC ASIMOV and THEODOSIUS DOBZHANSKY


Contents

THE MACHINERY OF INHERITANCE 1
Introduction 1
Cells and Chromosomes 2
Enzymes and Genes 5
Parents and Offspring 8
MUTATIONS 10
Sudden Change 10
Spontaneous Mutations 13
Genetic Load 16
Mutation Rates 19
RADIATION 22
Ionizing Radiation 22
Background Radiation 27
Man-made Radiation 30
DOSE AND CONSEQUENCE 32
Radiation Sickness 32
Radiation and Mutation 33
Dosage Rates 37
Effects on Mammals 40
Conclusion 43
SUGGESTED REFERENCES 47

THE COVER
[Illustration: The cover design embodies a radiation symbol, a stylized
karyotype of human chromosomes, and a genealogical table.]
THE AUTHORS
[Illustration: ISAAC ASIMOV received his academic degrees from Columbia
University and is Associate Professor of Biochemistry at the Boston
University School of Medicine. He is a prolific author who has written
over 65 books in the past 15 years, including about 20 science fiction
works, and books for children. His many excellent science books for the
public cover subjects in mathematics, physics, astronomy, chemistry, and
biology, such as _The Genetic Code_, _Inside the Atom_, _Building Blocks
of the Universe_, _The Living River_, _The New Intelligent Man’s Guide
to Science_, and _Asimov’s Biographical Encyclopedia of Science and
Technology_. In 1965 Dr. Asimov received the James T. Grady Award of the
American Chemical Society for his major contribution in reporting
science progress to the public.]
[Illustration: THEODOSIUS DOBZHANSKY was graduated from Kiev University
and is now a professor at the Rockefeller University. He has done
research in genetics and biological evolution on every continent except
Antarctica. Among his distinguished published works are _Radiation,
Genes, and Man_, _Heredity and the Nature of Man_, _Mankind Evolving_,
and _Evolution, Genetics, and Man_. Mr. Dobzhansky received the Daniel
G. Elliot Prize and Medal and the Kimber Genetics Award from the
National Academy of Sciences in 1958, and the National Medal of Science
awarded by the President of the United States, in 1965.]


The Genetic Effects of Radiation


THE MACHINERY OF INHERITANCE

Introduction
There is nothing new under the sun, says the Bible. Nor is the sun
itself new, we might add. As long as life has existed on earth, it has
been exposed to radiation from the sun, so that life and radiation are
old acquaintances and have learned to live together.
We are accustomed to looking upon sunlight as something good, useful,
and desirable, and certainly we could not live long without it. The
energy of sunlight warms the earth, produces the winds that tend to
equalize earth’s temperatures, evaporates the oceans and produces rain
and fresh water. Most important of all, it supplies what is needed for
green plants to convert carbon dioxide and water into food and oxygen,
making it possible for all animal life (including ourselves) to live.
Yet sunlight has its dangers, too. Lizards avoid the direct rays of the
noonday sun on the desert, and we ourselves take precautions against
sunburn and sunstroke.
The same division into good and bad is to be found in connection with
other forms of radiation—forms of which mankind has only recently become
aware. Such radiations, produced by radioactivity in the soil and
reaching us from outer space, have also been with us from the beginning
of time. They are more energetic than sunlight, however, and can do more
damage, and because our senses do not detect them, we have not learned
to take precautions against them.
To be sure, energetic radiation is present in nature in only very small
amounts and is not, therefore, much of a danger. Man, however, has the
capacity of imitating nature. Long ago in dim prehistory, for instance,
he learned to manufacture a kind of sunlight by setting wood and other
fuels on fire. This involved a new kind of good and bad. A whole new
technology became possible, on the one hand, and, on the other, the
chance of death by burning was also possible. The good in this case far
outweighs the evil.
In our own twentieth century, mankind learned to produce energetic
radiation in concentrations far surpassing those we usually encounter in
nature. Again, a new technology is resulting and again there is the
possibility of death.
The balance in this second instance is less certainly in favor of the
good over the evil. To shift the balance clearly in favor of the good,
it is necessary for mankind to learn as much as possible about the new
dangers in order that we might minimize them and most effectively guard
against them.
To see the nature of the danger, let us begin by considering living
tissue itself—the living tissue that must withstand the radiation and
that can be damaged by it.

Cells and Chromosomes
The average human adult consists of about 50 trillion _cells_—50
trillion microscopic, more or less self-contained, blobs of life. He
begins life, however, as a single cell, the _fertilized ovum_.
After the fertilized ovum is formed, it divides and becomes two cells.
Each daughter cell divides to produce a total of four cells, and each of
those divides and so on.
There is a high degree of order and direction to those divisions. When a
human fertilized ovum completes its divisions an adult human being is
the inevitable result. The fertilized ovum of a giraffe will produce a
giraffe, that of a fruit fly will produce a fruit fly, and so on. There
are no mistakes, so it is quite clear that the fertilized ovum must
carry “instructions” that guide its development in the appropriate
direction.
These “instructions” are contained in the cell’s _chromosomes_, tiny
structures that appear most clearly (like stubby bits of tangled
spaghetti) when the cell is in the actual process of division. Each
species has some characteristic number of chromosomes in its cells, and
these chromosomes can be considered in pairs. Human cells, for instance,
contain 23 pairs of chromosomes—46 in all.
When a cell is undergoing division (_mitosis_), the number of
chromosomes is temporarily doubled, as each chromosome brings about the
formation of a replica of itself. (This process is called
_replication_.) As the cell divides, the chromosomes are evenly shared
by the new cells in such a way that if a particular chromosome goes into
one daughter cell, its replica goes into the other. In the end, each
cell has a complete set of pairs of chromosomes; and the set in each
cell is identical with the set in the original cell before division.
[Illustration: Mitosis]
Interphase
Prophase
Metaphase
Anaphase
Telophase
Interphase
[Illustration: _To study chromosomes, scientists begin with a cell that
is in the process of dividing, when chromosomes are in their most
visible form. Then they treat the cell with a chemical, a derivative of
colchicine, to arrest the cell division at the metaphase stage (see
mitosis diagram on preceding page). This brings a result like the
photomicrograph above; the chromosomes are visible but still too tangled
to be counted or measured. Then the cell is treated with a
low-concentration salt solution, which swells the chromosomes and
disperses them so they become distinct structures, as below._]
[Illustration: Cell after treatment with salt solution]
[Illustration: _The separate chromosomes in a dividing cell are
photographed and then can be identified by their overall length, the
position of the centromere, or point where the two strands join, and
other characteristics. The photomicrograph can then be cut apart and the
chromosomes grouped in a karyotype, which is an arrangement according to
a standard classification to show chromosome complement and
abnormalities. The karotype below is of a normal male, since it shows X
and Y sex chromosomes and 22 pairs of other, autosomal, chromosomes. By
contrast, the cells in the upper pictures are abnormal, with only 45
chromosomes each._]
In this way, the fundamental “instructions” that determine the
characteristics of a cell are passed on to each new cell. Ideally, all
the trillions of cells in a particular human being have identical sets
of “instructions”.[1]

Enzymes and Genes
Each cell is a tiny chemical factory in which several thousand different
kinds of chemical changes are constantly taking place among the numerous
sorts of molecules that move about in its fluid or that are pinned to
its solid structures. These chemical changes are guided and controlled
by the existence of as many thousands of different _enzymes_ within the
cell.
Enzymes possess large molecules built up of some 20 different, but
chemically related, units called _amino acids_. A particular enzyme
molecule may contain a single amino acid of one type, five of another,
several dozen of still another and so on. All the units are strung
together in some specific pattern in one long chain, or in a small
number of closely connected chains.
Every different pattern of amino acids forms a molecule with its own set
of properties, and there are an enormous number of patterns possible. In
an enzyme molecule made up of 500 amino acids, the number of possible
patterns can be expressed by a 1 followed by 1100 zeroes (10¹¹⁰⁰).
Every cell has the capacity of choosing among this unimaginable number
of possible patterns and selecting those characteristic of itself. It
therefore ends with a complement of specific enzymes that guide its own
chemical changes and, consequently, its properties and its behavior. The
“instructions” that enable a fertilized ovum to develop in the proper
manner are essentially “instructions” for choosing a particular set of
enzyme patterns out of all those possible.
The differences in the enzyme-guided behavior of the cells making up
different species show themselves in differences in body structure. We
cannot completely follow the long and intricate chain of
cause-and-effect that leads from one set of enzymes to the long neck of
a giraffe and from another set of enzymes to the large brain of a man,
but we are sure that the chain is there. Even within a species,
different individuals will have slight distinctions among their sets of
enzymes and this accounts for the fact that no two human beings are
exactly alike (leaving identical twins out of consideration).
Each chromosome can be considered as being composed of small sections
called _genes_, usually pictured as being strung along the length of the
chromosome. Each gene is considered to be responsible for the formation
of a chain of amino acids in a fixed pattern. The formation is guided by
the details of the gene’s own structure (which are the “instructions”
earlier referred to). This gene structure, which can be translated into
an enzyme’s structure, is now called the _genetic code_.
[Illustration: _Stained section of one cell from salivary gland of_
Drosophila, _or fruit flies, reveals dark bands that may be genes
controlling specific traits_.]
If a particular enzyme (or group of enzymes) is, for any reason, formed
imperfectly or not at all, this may show up as some visible abnormality
of the body—an inability to see color, for instance, or the possession
of two joints in each finger rather than three. It is much easier to
observe physical differences than some delicate change in the enzyme
pattern of the cells. Genes are therefore usually referred to by the
body change they bring about, and one can, for instance, speak of a
“gene for color blindness”.
A gene may exist in two or more varieties, each producing a slightly
different enzyme, a situation that is reflected, in turn, in slight
changes in body characteristics. Thus, there are genes governing eye
color, one of which is sufficiently important to be considered a “gene
for blue eyes” and another a “gene for brown eyes”. One or the other,
but not both, will be found in a specific place on a specific
chromosome.
The two chromosomes of a particular pair govern identical sets of
characteristics. Both, for instance, will have a place for genes
governing eye color. If we consider only the most important of the
varieties involved, those on each chromosome of the pair may be
identical; both may be for blue eyes or both may be for brown eyes. In
that case, the individual is _homozygous_ for that characteristic and
may be referred to as a _homozygote_. The chromosomes of the pair may
carry different varieties: A gene for blue eyes on one chromosome and
one for brown eyes on the other. The individual is then _heterozygous_
for that characteristic and may be referred to as a _heterozygote_.
Naturally, particular individuals may be homozygous for some types of
characteristics and heterozygous for others.
When an individual is heterozygous for a particular characteristic, it
frequently happens that he shows the effect associated with only one of
the gene varieties. If he possesses both a gene for brown eyes and one
for blue eyes, his eyes are just as brown as though he had carried two
genes for brown eyes. The gene for brown eyes is _dominant_ in this case
while the gene for blue eyes is _recessive_.

Parents and Offspring
How does the fertilized ovum obtain its particular set of chromosomes in
the first place?
Each adult possesses gonads in which _sex cells_ are formed. In the
male, sperm cells are formed in the testes; in the female, egg cells are
formed in the ovaries.
In the formation of the sperm cells and egg cells there is a key
step—_meiosis_—a cell division in which the chromosomes group into pairs
and are then apportioned between the daughter cells, one of each pair to
each cell. Such a division, unaccompanied by replication, means that in
place of the usual 23 pairs of chromosomes in each other cell, each sex
cell has 23 individual chromosomes, a “half-set”, so to speak.
In the process of fertilization, a sperm cell from the father enters and
merges with an egg cell from the mother. The fertilized ovum that
results now has a full set of 23 pairs of chromosomes, but of each pair,
one comes from the father and one from the mother.
In this way, each newborn child is a true individual, with its
characteristics based on a random reshuffling of chromosomes. In forming
the sex cells, the chromosome pairs can separate in either fashion (_a_
into cell 1 and _b_ into cell 2, or vice versa). If each of 23 pairs
does this randomly, nearly 10 million different combinations of
chromosomes are possible in the sex cells of a single individual.
Furthermore, one can’t predict which chromosome combination in the sperm
cell will end up in combination with which in the egg cell, so that by
this reasoning, a single married couple could produce children with any
of 100 trillion (100,000,000,000,000) possible chromosome combinations.
It is this that begins to explain the endless variety among living
beings, even within a particular species.
It only begins to explain it, because there are other sources of
difference, too. A chromosome is capable of exchanging pieces with its
pair, producing chromosomes with a brand new pattern of gene varieties.
Before such a _crossover_, one chromosome may have carried a gene for
blue eyes and one for wavy hair, while the other chromosome may have
carried a gene for brown eyes and one for straight hair. After the
crossover, one would carry genes for blue eyes and straight hair, the
other for brown eyes and wavy hair.
[Illustration: Meiosis]
Interphase
Prophase
Metaphase
Anaphase
Interphase
Metaphase
Interphase


MUTATIONS

Sudden Change
Shifts in chromosome combinations, with or without crossovers, can
produce unique organisms with characteristics not quite like any
organism that appeared in the past nor likely to appear in the
reasonable future. They may even produce novelties in individual
characteristics since genes can affect one another, and a gene
surrounded by unusual neighbors can produce unexpected effects.
Matters can go further still, however, in the direction of novelty. It
is possible for chromosomes to undergo more serious changes, either
structural or chemical, so that entirely new characteristics are
produced that might not otherwise exist. Such changes are called
_mutations_.
We must be careful how we use this term. A child may possess some
characteristics not present in either parent through the mere shuffling
of chromosomes and not through mutation.
Suppose, for instance, that a man is heterozygous to eye color, carrying
one gene for brown eyes and one for blue eyes. His eyes would, of
course, be brown since the gene for brown eyes is dominant over that for
blue. Half the sperm cells he produces would carry a single gene for
brown eyes in its half set of chromosomes. The other half would carry a
single gene for blue eyes. If his wife were similarly heterozygous (and
therefore also had brown eyes), half her egg cells would carry the gene
for brown eyes and half the gene for blue.
It might follow in this marriage, then, that a sperm carrying the gene
for blue eyes might fertilize an egg carrying the gene for blue eyes.
The child would then be homozygous, with two genes for blue eyes, and he
would definitely be blue-eyed. In this way, two brown-eyed parents might
have a blue-eyed child and this would _not_ be a mutation. If the
parents’ ancestry were traced further back, blue-eyed individuals would
undoubtedly be found on both sides of the family tree.
If, however, there were no record of, say, anything but normal color
vision in a child’s ancestry, and he were born color-blind, that could
be assumed to be the result of a mutation. Such a mutation could then be
passed on by the normal modes of inheritance and a certain proportion of
the child’s eventual descendants would be color-blind.
A mutation may be associated with changes in chromosome structure
sufficiently drastic to be visible under the microscope. Such
_chromosome mutations_ can arise in several ways. Chromosomes may
undergo replication without the cell itself dividing. In that way, cells
can develop with two, three, or four times the normal complement of
chromosomes, and organisms made up of cells displaying such _polyploidy_
can be markedly different from the norm. This situation is found chiefly
among plants and among some groups of invertebrates. It does not usually
occur in mammals, and when it does it leads to quick death.
Less extreme changes take place, too, as when a particular chromosome
breaks and fails to reunite, or when several break and then reunite
incorrectly. Under such conditions, the mechanism by which chromosomes
are distributed among the daughter cells is not likely to work
correctly. Sex cells may then be produced with a piece of chromosome (or
a whole one) missing, or with an extra piece (or whole chromosome)
present.
In 1959, such a situation was found to exist in the case of persons
suffering from a long-known disease called Down’s syndrome.[2] Each
person so afflicted has 47 chromosomes in place of the normal 46. It
turned out that the 21st pair of chromosomes (using a convention whereby
the chromosome pairs are numbered in order of decreasing size) consists
of three individuals rather than two. The existence of this chromosome
abnormality clearly demonstrated what had previously been strongly
suspected—that Down’s syndrome originates as a mutation and is inborn
(see the figure on the next page).
[Illustration: _Karyotype of a female patient with Down’s syndrome
(Mongolism). During meiosis both chromosomes No. 21 of the mother,
instead of just one, went to the ovum. Fertilization added the father’s
chromosome, which made three Nos. 21 instead of the normal pair.
(Compare with the normal karyotype on page 4.)_]
Most mutations, however, are not associated with any noticeable change
in chromosome structure. There are, instead, more subtle changes in the
chemical structure of the genes that make up the chromosome. Then we
have _gene mutations_.
The process by which a gene produces its own replica is complicated and,
while it rarely goes wrong, it does misfire on occasion. Then, too, even
when a gene molecule is replicated perfectly, it may undergo change
afterward through the action upon it of some chemical or other
environmental influence. In either case, a new variety of a particular
gene is produced and, if present in a sex cell, it may be passed on to
descendants through an indefinite number of generations.
Of course, chromosome or gene mutations may take place in ordinary cells
rather than in sex cells. Such changes in ordinary cells are _somatic
mutations_. When mutated body cells divide, new cells with changed
characteristics are produced. These changes may be trivial, or they may
be serious. It is often suggested, for instance, that cancer may result
from a somatic mutation in which certain cells lose the capacity to
regulate their growth properly. Since somatic mutations do not involve
the sex cells, they are confined to the individual and are not passed on
to the offspring.

Spontaneous Mutations
Mutations that take place in the ordinary course of nature, without
man’s interference, are _spontaneous mutations_. Most of these arise out
of the very nature of the complicated mechanism of gene replication.
Copies of genes are formed out of a large number of small units that
must be lined up in just the right pattern to form one particular gene
and no other.
Ideally, matters are so arranged within the cell that the necessary
changes giving rise to the desired pattern are just those that have a
maximum probability. Other changes are less likely to happen but are not
absolutely excluded. Sometimes through the accidental jostling of
molecules a wrong turn may be taken, and the result is a spontaneous
mutation.
We might consider a mutation to be either “good” or “bad” in the sense
that any change that helps a creature live more easily and comfortably
is good and that the reverse is bad.
It seems reasonable that random changes in the gene pattern are almost
sure to be bad. Consider that any creature, including man, is the
product of millions of years of evolution. In every generation those
individuals with a gene pattern that fit them better for their
environment won out over those with less effective patterns—won out in
the race for food, for mates, and for safety. The “more fit” had more
offspring and crowded out the “less fit”.
By now, then, the set of genes with which we are normally equipped is
the end product of long ages of such _natural selection_. A random
change cannot be expected to improve it any more than random changes
would improve any very complex, intricate, and delicate structure.
[Illustration: _Evolution of the horse (skull, hindfoot, and forefoot
shown). Note the changes over a 60-million-year period from the Eocene
era to the present._]
Pleistocene and Recent
Pliocene
Miocene
Oligocene
Eocene
Yet over the eons, creatures have indeed changed, largely through the
effects of mutation. If mutations are almost always for the worse, how
can one explain that evolution seems to progress toward the better and
that out of a primitive form as simple as an amoeba, for instance, there
eventually emerged man?
In the first place, environment is not fixed. Climate changes,
conditions change, the food supply may change, the nature of living
enemies may change. A gene pattern that is very useful under one set of
conditions may be less useful under another.
Suppose, for instance, that man had lived in tropical areas for
thousands of years and had developed a heavily pigmented skin as a
protection against sunburn. Any child who, through a mutation, found
himself incapable of forming much pigment, would be at a severe
disadvantage in the outdoor activities engaged in by his tribe. He would
not do well and such a mutated gene would never establish itself for
long.
If a number of these men migrated to northern Europe, however, children
with dark skin would absorb insufficient sunlight during the long winter
when the sun was low in the sky, and visible for brief periods only.
Dark-skinned children would, under such conditions, tend to suffer from
rickets.
Mutant children with pale skin would absorb more of what weak sunlight
there was and would suffer less. There would be little danger of sunburn
so there would be no penalty counteracting this new advantage of pale
skins. It would be the dark-skinned people who would tend to die out. In
the end, you would have dark skins in Africa and pale skins in
Scandinavia, and both would be “fit”.
In the same way, any child born into a primitive hunting society who
found himself with a mutated gene that brought about nearsightedness
would be at a distinct disadvantage. In a modern technological society,
however, nearsighted individuals, doing more poorly at outdoor games,
are often driven into quieter activities that involve reading, thinking,
and studying. This may lead to a career as a scientist, scholar, or
professional man, categories that are valuable in such a society and are
encouraged. Nearsightedness would therefore spread more generally
through civilized societies than through primitive ones.
Then, too, a gene may be advantageous when it occurs in low numbers and
disadvantageous when it occurs in high numbers. Suppose there were a
gene among humans that so affected the personality as to make it
difficult for a human being to endure crowded conditions. Such
individuals would make good explorers, farmers, and herdsmen, but poor
city dwellers. Even in our modern urbanized society, such a gene in
moderate concentration would be good, since we still need our
outdoorsmen. In high concentration, it would be bad, for then the
existence of areas of high population density (on which our society now
seems to depend) might become impossible.
In any species, then, each gene exists in a number of varieties upon
which an absolute “good” or “bad” cannot be unequivocally stamped. These
varieties make up the _gene pool_, and it is this gene pool that makes
evolution possible.
A species with an invariable set of genes could not change to suit
altered conditions. Even a slight shift in the nature of the environment
might suffice to wipe it out.
The possession of a gene pool lends flexibility, however. As conditions
change, one combination of varieties might gain over another and this,
in turn, might produce changes in body characteristics that would then