Part 1

The Genetic Effects of Radiation

By ISAAC ASIMOV and THEODOSIUS DOBZHANSKY

Contents

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

THE COVER

THE AUTHORS

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.

Interphase Prophase Metaphase Anaphase Telophase Interphase

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_.

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.

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).

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.

Pleistocene and Recent Pliocene Miocene Oligocene Eocene