Knowing that DDT and other (perhaps all) chlorinated hydrocarbons stop the energy-producing cycle by inactivating a specific enzyme or uncoupling the energy-producing mechanism, it is hard to see how any egg so loaded with residues could complete the complex process of development: the infinite number of cell divisions, the elaboration of tissues and organs, the synthesis of vital substances that in the end produce a living creature. All this requires vast amounts of energy—the little packets of ATP which the turning of the metabolic wheel alone can produce.
There is no reason to suppose these disastrous events are confined to birds. ATP is the universal currency of energy, and the metabolic cycles that produce it turn to the same purpose in birds and bacteria, in men and mice. The fact of insecticide storage in the germ cells of any species should therefore disturb us, suggesting comparable effects in human beings.
And there are indications that these chemicals lodge in tissues concerned with the manufacture of germ cells as well as in the cells themselves. Accumulations of insecticides have been discovered in the sex organs of a variety of birds and mammals—in pheasants, mice, and guinea pigs under controlled conditions, in robins in an area sprayed for elm disease, and in deer roaming western forests sprayed for spruce budworm. In one of the robins the concentration of DDT in the testes was heavier than in any other part of the body. Pheasants also accumulated extraordinary amounts in the testes, up to 1500 parts per million.
Probably as an effect of such storage in the sex organs, atrophy of the testes has been observed in experimental mammals. Young rats exposed to methoxychlor had extraordinarily small testes. When young roosters were fed DDT, the testes made only 18 per cent of their normal growth; combs and wattles, dependent for their development upon the testicular hormone, were only a third the normal size.
The spermatozoa themselves may well be affected by loss of ATP. Experiments show that the motility of bull sperm is decreased by dinitrophenol, which interferes with the energy-coupling mechanism with inevitable loss of energy. The same effect would probably be found with other chemicals were the matter investigated. Some indication of the possible effect on human beings is seen in medical reports of oligospermia, or reduced production of spermatozoa, among aviation crop dusters applying DDT.
For mankind as a whole, a possession infinitely more valuable than individual life is our genetic heritage, our link with past and future. Shaped through long eons of evolution, our genes not only make us what we are, but hold in their minute beings the future—be it one of promise or threat. Yet genetic deterioration through man-made agents is the menace of our time, "the last and greatest danger to our civilization."
Again the parallel between chemicals and radiation is exact and inescapable.
The living cell assaulted by radiation suffers a variety of injuries: its ability to divide normally may be destroyed, it may suffer changes in chromosome structure, or the genes, carriers of hereditary material, may undergo those sudden changes known as mutations, which cause them to produce new characteristics in succeeding generations. If especially susceptible the cell may be killed outright, or finally, after the passage of time measured in years, it may become malignant.
All these consequences of radiation have been duplicated in laboratory studies by a large group of chemicals known as radiomimetic or radiation-imitating. Many chemicals used as pesticides—herbicides as well as insecticides—belong to this group of substances that have the ability to damage the chromosomes, interfere with normal cell division, or cause mutations. These injuries to the genetic material are of a kind that may lead to disease in the individual exposed or they may make their effects felt in future generations.
Only a few decades ago, no one knew these effects of either radiation or chemicals. In those days the atom had not been split and few of the chemicals that were to duplicate radiation had as yet been conceived in the test tubes of chemists. Then in 1927, a professor of zoology in a Texas university, Dr. H. J. Muller, found that by exposing an organism to X-radiation, he could produce mutations in succeeding generations. With Muller's discovery a vast new field of scientific and medical knowledge was opened up. Muller later received the Nobel Prize in Medicine for his achievement, and in a world that soon gained unhappy familiarity with the gray rains of fallout, even the nonscientist now knows the potential results of radiation.
Although far less noticed, a companion discovery was made by Charlotte Auerbach and William Robson at the University of Edinburgh in the early 1940's. Working with mustard gas, they found that this chemical produces permanent chromosome abnormalities that cannot be distinguished from those induced by radiation. Tested on the fruit fly, the same organism Muller had used in his original work with X-rays, mustard gas also produced mutations. Thus the first chemical mutagen was discovered.
Mustard gas as a mutagen has now been joined by a long list of other chemicals known to alter genetic material in plants and animals. To understand how chemicals can alter the course of heredity, we must first watch the basic drama of life as it is played on the stage of the living cell.
The cells composing the tissues and organs of the body must have the power to increase in number if the body is to grow and if the stream of life is to be kept flowing from generation to generation. This is accomplished by the process of mitosis, or nuclear division. In a cell that is about to divide, changes of the utmost importance occur, first within the nucleus, but eventually involving the entire cell. Within the nucleus, the chromosomes mysteriously move and divide, ranging themselves in age-old patterns that will serve to distribute the determiners of heredity, the genes, to the daughter cells. First they assume the form of elongated threads, on which the genes are aligned, like beads on a string. Then each chromosome divides lengthwise (the genes dividing also). When the cell divides into two, half of each goes to each of the daughter cells. In this way each new cell will contain a complete set of chromosomes, and all the genetic information encoded within them. In this way the integrity of the race and of the species is preserved; in this way like begets like.
A special kind of cell division occurs in the formation of the germ cells. Because the chromosome number for a given species is constant, the egg and the sperm, which are to unite to form a new individual, must carry to their union only half the species number. This is accomplished with extraordinary precision by a change in the behavior of the chromosomes that occurs at one of the divisions producing those cells. At this time the chromosomes do not split, but one whole chromosome of each pair goes into each daughter cell.
In this elemental drama all life is revealed as one. The events of the process of cell division are common to all earthly life; neither man nor amoeba, the giant sequoia nor the simple yeast cell can long exist without carrying on this process of cell division. Anything that disturbs mitosis is therefore a grave threat to the welfare of the organism affected and to its descendants.
"The major features of cellular organization, including, for instance, mitosis, must be much older than 500 million years—more nearly 1000 million," wrote George Gaylord Simpson and his colleagues Pittendrigh and Tiffany in their broadly encompassing book entitled Life. "In this sense the world of life, while surely fragile and complex, is incredibly durable through time—more durable than mountains. This durability is wholly dependent on the almost incredible accuracy with which the inherited information is copied from generation to generation."
But in all the thousand million years envisioned by these authors no threat has struck so directly and so forcefully at that "incredible accuracy" as the mid-20th century threat of man-made radiation and man-made and man-disseminated chemicals. Sir Macfarlane Burnet, a distinguished Australian physician and a Nobel Prize winner, considers it "one of the most significant medical features" of our time that, "as a by-product of more and more powerful therapeutic procedures and the production of chemical substances outside of biological experiences, the normal protective barriers that kept mutagenic agents from the internal orga
ns have been more and more frequently penetrated."
The study of human chromosomes is in its infancy, and so it has only recently become possible to study the effect of environmental factors upon them. It was not until 1956 that new techniques made it possible to determine accurately the number of chromosomes in the human cell—46—and to observe them in such detail that the presence or absence of whole chromosomes or even parts of chromosomes could be detected. The whole concept of genetic damage by something in the environment is also relatively new, and is little understood except by the geneticists, whose advice is too seldom sought. The hazard from radiation in its various forms is now reasonably well understood—although still denied in surprising places. Dr. Muller has frequently had occasion to deplore the "resistance to the acceptance of genetic principles on the part of so many, not only of governmental appointees in the policy-making positions, but also of so many of the medical profession." The fact that chemicals may play a role similar to radiation has scarcely dawned on the public mind, nor on the minds of most medical or scientific workers. For this reason the role of chemicals in general use (rather than in laboratory experiments) has not yet been assessed. It is extremely important that this be done.
Sir Macfarlane is not alone in his estimate of the potential danger. Dr. Peter Alexander, an outstanding British authority, has said that the radiomimetic chemicals "may well represent a greater danger" than radiation. Dr. Muller, with the perspective gained by decades of distinguished work in genetics, warns that various chemicals (including groups represented by pesticides) "can raise the mutation frequency as much as radiation.... As yet far too little is known of the extent to which our genes, under modern conditions of exposure to unusual chemicals, are being subjected to such mutagenic influences."
The widespread neglect of the problem of chemical mutagens is perhaps due to the fact that those first discovered were of scientific interest only. Nitrogen mustard, after all, is not sprayed upon whole populations from the air; its use is in the hands of experimental biologists or of physicians who use it in cancer therapy. (A case of chromosome damage in a patient receiving such therapy has recently been reported.) But insecticides and weed killers are brought into intimate contact with large numbers of people.
Despite the scant attention that has been given to the matter, it is possible to assemble specific information on a number of these pesticides, showing that they disturb the cell's vital processes in ways ranging from slight chromosome damage to gene mutation, and with consequences extending to the ultimate disaster of malignancy.
Mosquitoes exposed to DDT for several generations turned into strange creatures called gynandromorphs—part male and part female.
Plants treated with various phenols suffered profound destruction of chromosomes, changes in genes, a striking number of mutations, "irreversible hereditary changes." Mutations also occurred in fruit flies, the classic subject of genetics experiments, when subjected to phenol; these flies developed mutations so damaging as to be fatal on exposure to one of the common herbicides or to urethane. Urethane belongs to the group of chemicals called carbamates, from which an increasing number of insecticides and other agricultural chemicals are drawn. Two of the carbamates are actually used to prevent sprouting of potatoes in storage—precisely because of their proven effect in stopping cell division. Another antisprouting agent, maleic hydrazide, is rated a powerful mutagen.
Plants treated with benzene hexachloride (BHC) or lindane became monstrously deformed with tumorlike swellings on their roots. Their cells grew in size, being swollen with chromosomes which doubled in number. The doubling continued in future divisions until further cell division became mechanically impossible.
The herbicide 2,4-D has also produced tumorlike swellings in treated plants. Chromosomes become short, thick, clumped together. Cell division is seriously retarded. The general effect is said to parallel closely that produced by X-rays.
These are but a few illustrations; many more could be cited. As yet there has been no comprehensive study aimed at testing the mutagenic effects of pesticides as such. The facts cited above are by-products of research in cell physiology or genetics. What is urgently needed is a direct attack on the problem.
Some scientists who are willing to concede the potent effect of environmental radiation on man nevertheless question whether mutagenic chemicals can, as a practical proposition, have the same effect. They cite the great penetrating power of radiation, but doubt that chemicals could reach the germ cells. Once again we are hampered by the fact that there has been little direct investigation of the problem in man. However, the finding of large residues of DDT in the gonads and germ cells of birds and mammals is strong evidence that the chlorinated hydrocarbons, at least, not only become widely distributed throughout the body but come into contact with genetic materials. Professor David E. Davis at Pennsylvania State University has recently discovered that a potent chemical which prevents cells from dividing and has had limited use in cancer therapy can also be used to cause sterility in birds. Sublethal levels of the chemical halt cell division in the gonads. Professor Davis has had some success in field trials. Obviously, then, there is little basis for the hope or belief that the gonads of any organism are shielded from chemicals in the environment.
Recent medical findings in the field of chromosome abnormalities are of extreme interest and significance. In 1959 several British and French research teams found their independent studies pointing to a common conclusion—that some of humanity's ills are caused by a disturbance of the normal chromosome number. In certain diseases and abnormalities studied by these investigators the number differed from the normal. To illustrate: it is now known that all typical mongoloids have one extra chromosome. Occasionally this is attached to another so that the chromosome number remains the normal 46. As a rule, however, the extra is a separate chromosome, making the number 47. In such individuals, the original cause of the defect must have occurred in the generation preceding its appearance.
A different mechanism seems to operate in a number of patients, both in America and Great Britain, who are suffering from a chronic form of leukemia. These have been found to have a consistent chromosome abnormality in some of the blood cells. The abnormality consists of the loss of part of a chromosome. In these patients the skin cells have a normal complement of chromosomes. This indicates that the chromosome defect did not occur in the germ cells that gave rise to these individuals, but represents damage to particular cells (in this case, the precursors of blood cells) that occurred during the life of the individual. The loss of part of a chromosome has perhaps deprived these cells of their "instructions" for normal behavior.
The list of defects linked to chromosome disturbances has grown with surprising speed since the opening of this territory, hitherto beyond the boundaries of medical research. One, known only as Klinefelter's syndrome, involves a duplication of one of the sex chromosomes. The resulting individual is a male, but because he carries two of the X chromosomes (becoming XXY instead of XY, the normal male complement) he is somewhat abnormal. Excessive height and mental defects often accompany the sterility caused by this condition. In contrast, an individual who receives only one sex chromosome (becoming XO instead of either XX or XY) is actually female but lacks many of the secondary sexual characteristics. The condition is accompanied by various physical (and sometimes mental) defects, for of course the X chromosome carries genes for a variety of characteristics. This is known as Turner's syndrome. Both conditions had been described in medical literature long before the cause was known.
An immense amount of work on the subject of chromosome abnormalities is being done by workers in many countries. A group at the University of Wisconsin, headed by Dr. Klaus Patau, has been concentrating on a variety of congenital abnormalities, usually including mental retardation, that seem to result from the duplication of only part of a chromosome, as if somewhere in the formation of one of the germ cells a chromosome had broken and the pieces had not bee
n properly redistributed. Such a mishap is likely to interfere with the normal development of the embryo.
According to present knowledge, the occurrence of an entire extra body chromosome is usually lethal, preventing survival of the embryo. Only three such conditions are known to be viable; one of them, of course, is mongolism. The presence of an extra attached fragment, on the other hand, although seriously damaging is not necessarily fatal, and according to the Wisconsin investigators this situation may well account for a substantial part of the so far unexplained cases in which a child is born with multiple defects, usually including mental retardation.
This is so new a field of study that as yet scientists have been more concerned with identifying the chromosome abnormalities associated with disease and defective development than with speculating about the causes. It would be foolish to assume that any single agent is responsible for damaging the chromosomes or causing their erratic behavior during cell division. But can we afford to ignore the fact that we are now filling the environment with chemicals that have the power to strike directly at the chromosomes, affecting them in the precise ways that could cause such conditions? Is this not too high a price to pay for a sproutless potato or a mosquitoless patio?
We can, if we wish, reduce this threat to our genetic heritage, a possession that has come down to us through some two billion years of evolution and selection of living protoplasm, a possession that is ours for the moment only, until we must pass it on to generations to come. We are doing little now to preserve its integrity. Although chemical manufacturers are required by law to test their materials for toxicity, they are not required to make the tests that would reliably demonstrate genetic effect, and they do not do so.
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