Produced by Stephen Hutcheson and the Online Distributed
Proofreading Team at http://www.pgdp.net









                    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
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
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:
  58 (November 1955).

Ionizing Radiation and Evolution, James F. Crow, _Scientific American_,
  201: 138 (September 1959).


Motion Pictures

_Radiation and the Population_, 29 minutes, sound, black and white,
  1962. Produced by the Argonne National Laboratory. This film explains
  how radiation causes mutations and how these mutations are passed on
  to succeeding generations. Mutation research is illustrated with
  results of experimentation on generations of mice. A discussion of
  work with fruit flies and induced mutations is also included. This
  film is available for loan without charge from the AEC Headquarters
  Film Library, Division of Public Information, U. S. Atomic Energy
  Commission, Washington, D. C. 20545 and from other AEC film libraries.

The following films were produced by the American Institute of
  Biological Sciences and may be rented from the Text-Film Division,
  McGraw-Hill Book Company, 330 West 42nd Street, New York 10036.

_Mutation_, 28 minutes, sound, color, 1962. This film discusses
  chromosomal and genetic mutations as applied to man. Muller’s work in
  inducing mutations by X rays is described.

These three films are 30 minutes long, have sound, are in black and
  white, and were released in 1960. They are part of a 48-film series
  that is correlated with the textbook, _Principles of Genetics_, (fifth
  edition), Edmund W. Sinnott, L. C. Dunn, and Theodosius Dobzhansky,
  McGraw-Hill Book Company, 1958, 459 pp., $8.50.

_Mutagen-Induced Gene Mutation._ The narrator of this film is Hermann J.
  Muller, who won a Nobel Prize in 1946 for his work in the field of
  genetics. The measurement of X-ray dose in roentgens and the dose
  required to double the spontaneous mutation rate in _Drosophila_ and
  mice are discussed. The magnitude and meaning of permissible doses of
  high-energy radiation are discussed. Other mutagenic agents
  (ultraviolet light and chemical substances) are discussed, concluding
  with comments on the importance of gene mutation in the present and
  future.

_Selection, Genetic Death and Genetic Radiation Damage._ The narrator of
  this film is Theodosius Dobzhansky, the coauthor of this booklet.
  Genetic death is discussed in detail, as are examples of how genetic
  loads are changed subsequent to radiation exposure. While it is
  generally agreed that the great majority of mutants are harmful when
  homozygous, more evidence is needed about the beneficial and
  detrimental effects of mutants when heterozygous. In the case of
  sickle cell anemia, heterozygotes are adaptively superior to normal
  homozygotes. This makes for balanced polymorphism, by which a gene is
  retained in the population despite its lethality when homozygous
  because of the advantage it confers when heterozygous.

_Gene Structure and Gene Action._ The lecturer of this film is G. W.
  Beadle of Cornell University. The Watson-Crick structure of DNA is
  discussed in terms of mutation. Several tests of the chain separation
  hypothesis for DNA replication are described (experiments with heavy
  DNA, radioactive chromosomes, and the replication of DNA in vitro).
  This working hypothesis is presented: The coded information in DNA is
  transferred to RNA, which serves as a template for polypeptide
  synthesis.

                              PHOTO CREDITS

  Dr. Asimov’s photograph by David R. Phillips, courtesy _Chemical and
  Engineering News_

    Page

  4         James German, M.D.
  6         Bausch & Lomb, Inc.
  12        James German, M.D.
  20        Indiana University
  24        Robert C. Filz, Air Force Cambridge Research Laboratories
  25        J. K. Boggild, Niels Bohr Institute, Copenhagen University
  26        Brookhaven National University
  28, 31    Herman Yagoda, Air Force Cambridge Research Laboratories
  41        Oak Ridge National Laboratory




                               Footnotes


[1]For more detail about cell division, see _Radioisotopes and Life
    Processes_, another booklet in this series.

[2]This is more commonly known as “Mongolism” or “Mongolian idiocy”
    though it has nothing to do with the Mongolian people.

[3]Actually, all waves have some of the characteristics of particles and
    all particles have some of the characteristics of waves. Usually,
    however, the radiation is predominantly one or the other and little
    confusion arises under ordinary circumstances in speaking of waves
    and particles as though they were separate phenomena.

[4]For more about this subject, see _Radioisotopes in Industry_ and
    _Radioisotopes in Medicine_, companion booklets in this series.

[5]For more about this subject, see _Fallout from Nuclear Tests_,
    another booklet in this series.

[6]For details on _somatic_ effects of radiation, see _Your Body and
    Radiation_, a companion booklet in this series.

[7]Estimated average exposures to the gonads, based on 1963 report of
    Federal Radiation Council.

[8]One thousandth of a rem.

[9]Nevertheless, it should be pointed out that the precautions taken in
    the atomic energy industry are such that absorption of radiation is
    not as severe a problem as one might suspect. Fully 95% of those
    engaged in this work receive less than 1 rem a year. Only 1% receive
    more than 5 rems.


UNITED STATES ATOMIC ENERGY COMMISSION

  _Dr. Glenn T. Seaborg, Chairman_
  _James T. Ramey_
  _Dr. Gerald F. Tape_
  _Dr. Samuel M. Nabrit_
  _Wilfrid E. Johnson_

_ONE OF A SERIES ON
UNDERSTANDING THE ATOM_

Nuclear energy is playing a vital role in the life of every man, woman,
and child in the United States today. In the years ahead it will affect
increasingly all the peoples of the earth. It is essential that all
Americans gain an understanding of this vital force if they are to
discharge thoughtfully their responsibilities as citizens and if they
are to realize fully the myriad benefits that nuclear energy offers
them.

The United States Atomic Energy Commission provides this booklet to help
you achieve such understanding.

                  [Illustration: Edward J. Brunenkant]

  Edward J. Brunenkant
  Director
  Division of Technical Information


This booklet is one of the “Understanding the Atom” Series. Comments are
invited on this booklet and others in the series; please send them to
the Division of Technical Information, U. S. Atomic Energy Commission,
Washington, D. C. 20545.

Published as part of the AEC’s educational assistance program, the
series includes these titles:

  NUCLEAR POWER AND MERCHANT SHIPPING
  PLUTONIUM
  OUR ATOMIC WORLD
  NUCLEAR ENERGY FOR DESALTING
  CONTROLLED NUCLEAR FUSION
  WHOLE BODY COUNTERS
  PLOWSHARE
  POPULAR BOOKS ON NUCLEAR SCIENCE
  SNAP, NUCLEAR SPACE REACTORS
  NUCLEAR REACTORS
  ATOMS, NATURE, AND MAN
  MICROSTRUCTURE OF MATTER
  SYNTHETIC TRANSURANIUM ELEMENTS
  COMPUTERS
  RESEARCH REACTORS
  GENETIC EFFECTS OF RADIATION
  POWER FROM RADIOISOTOPES
  NONDESTRUCTIVE TESTING
  RARE EARTHS
  FOOD PRESERVATION BY IRRADIATION
  FALLOUT FROM NUCLEAR TESTS
  RADIOACTIVE WASTES
  RADIOISOTOPES IN INDUSTRY
  ATOMS AT THE SCIENCE FAIR
  RADIOISOTOPES AND LIFE PROCESSES
  ATOMIC FUEL
  ATOMIC POWER SAFETY
  DIRECT CONVERSION OF ENERGY
  CAREERS IN ATOMIC ENERGY
  RADIOISOTOPES IN MEDICINE
  ACCELERATORS
  NUCLEAR TERMS, A BRIEF GLOSSARY
  NEUTRON ACTIVATION ANALYSIS
  ATOMS IN AGRICULTURE
  POWER REACTORS IN SMALL PACKAGES

Single copies of any booklet may be obtained free by writing to:

           USAEC, P. O. BOX 62, OAK RIDGE, TENNESSEE    37830

Requests for more than three titles generally can not be honored.

Complete sets of the series are available to school and public
librarians, and to teachers who can make them available for reference or
for use by groups. Requests should be made on school or library
letterheads and indicate the proposed use.

Students and teachers who need publications on specific topics related
to nuclear science, or references to other reading material, may also
write to the Oak Ridge address. Requests should state the topic of
interest exactly, and the use intended.

_IMPORTANT_: All requests should include the “Zip Code” in the address
to which the material is to be mailed.


                Printed in the United States of America


USAEC Division of Technical Information Extension, Oak Ridge, Tennessee
                             September 1966




                          Transcriber’s Notes


--Retained publication information from the printed edition: this eBook
  is public-domain in the country of publication.

--Where possible, UTF superscript and subscript numbers are used; some
  e-reader fonts may not support these characters.

--In the text version only, underlined or italicized text is delimited
  by _underscores_.

--In the text version only, superscript text is preceded by caret and
  delimited by ^{brackets}.

--In the text version only, subscripted text is preceded by underscore
  and delimited by _{brackets}.

--In the text version only, added a brief label to each illustration;
  and for graphs, provided tabular summaries of the data where possible.