Authors: Rachel Carson
Although the committee did not say so, its decision meant that the public was to act as guinea pigs, testing the suspected carcinogen along with the laboratory dogs and rats. But laboratory animals give more prompt results, and after the two years it was evident that this miticide was indeed a carcinogen. Even at that point, in 1957, the Food and Drug Administration could not instantly rescind the tolerance which allowed residues of a known carcinogen to contaminate food consumed by the public. Another year was required for various legal procedures. Finally, in December 1958 the zero tolerance which the Commissioner had recommended in 1955 became effective.
These are by no means the only known carcinogens among pesticides. In laboratory tests on animal subjects, DDT has produced suspicious liver tumors. Scientists of the Food and Drug Administration who reported the discovery of these tumors were uncertain how to classify them, but felt there was some "justification for considering them low grade hepatic cell carcinomas." Dr. Hueper now gives DDT the definite rating of a "chemical carcinogen."
Two herbicides belonging to the carbamate group, IPC and CIPC, have been found to play a role in producing skin tumors in mice. Some of the tumors were malignant. These chemicals seem to initiate the malignant change, which may then be completed by other chemicals of types prevalent in the environment.
The weed-killer aminotriazole has caused thyroid cancer in test animals. This chemical was misused by a number of cranberry growers in 1959, producing residues on some of the marketed berries. In the controversy that followed seizure of contaminated cranberries by the Food and Drug Administration, the fact that the chemical actually is cancer producing was widely challenged, even by many medical men. The scientific facts released by the Food and Drug Administration clearly indicate the carcinogenic nature of aminotriazole in laboratory rats. When these animals were fed this chemical at the rate of 100 parts per million in the drinking water (or one teaspoonful of chemical in ten thousand teaspoonfuls of water) they began to develop thyroid tumors at the 68th week. After two years, such tumors were present in more than half the rats examined. They were diagnosed as various types of benign and malignant growths. The tumors also appeared at lower levels of feeding—in fact,
a level that produced no effect was not found.
No one knows, of course, the level at which aminotriazole may be carcinogenic for man, but as a professor of medicine at Harvard University, Dr. David Rutstein, has pointed out, the level is just as likely to be to man's disfavor as to his advantage.
As yet insufficient time has elapsed to reveal the full effect of the new chlorinated hydrocarbon insecticides and of the modern herbicides. Most malignancies develop so slowly that they may require a considerable segment of the victim's life to reach the stage of showing clinical symptoms. In the early 1920's women who painted luminous figures on watch dials swallowed minute amounts of radium by touching the brushes to their lips; in some of these women bone cancers developed after a lapse of 15 or more years. A period of 15 to 30 years or even more has been demonstrated for some cancers caused by occupational exposures to chemical carcinogens.
In contrast to these industrial exposures to various carcinogens the first exposures to DDT date from about 1942 for military personnel and from about 1945 for civilians, and it was not until the early fifties that a wide variety of pesticidal chemicals came into use. The full maturing of whatever seeds of malignancy have been sown by these chemicals is yet to come.
There is, however, one presently known exception to the fact that a long period of latency is common to most malignancies. This exception is leukemia. Survivors of Hiroshima began to develop leukemia only three years after the atomic bombing, and there is now reason to believe the latent period may be considerably shorter. Other types of cancer may in time be found to have a relatively short latent period, also, but at present leukemia seems to be the exception to the general rule of extremely slow development.
Within the period covered by the rise of modern pesticides, the incidence of leukemia has been steadily rising. Figures available from the National Office of Vital Statistics clearly establish a disturbing rise in malignant diseases of the blood-forming tissues. In the year 1960, leukemia alone claimed 12,290 victims. Deaths from all types of malignancies of blood and lymph totaled 25,400, increasing sharply from the 16,690 figure of 1950. In terms of deaths per 100,000 of population, the increase is from 11.1 in 1950 to 14.1 in 1960. The increase is by no means confined to the United States; in all countries the recorded deaths from leukemia at all ages are rising at a rate of 4 to 5 per cent a year. What does it mean? To what lethal agent or agents, new to our environment, are people now exposed with increasing frequency?
Such world-famous institutions as the Mayo Clinic admit hundreds of victims of these diseases of the blood-forming organs. Dr. Malcolm Hargraves and his associates in the Hematology Department at the Mayo Clinic report that almost without exception these patients have had a history of exposure to various toxic chemicals, including sprays which contain DDT, chlordane, benzene, lindane, and petroleum distillates.
Environmental diseases related to the use of various toxic substances have been increasing, "particularly during the past ten years," Dr. Hargraves believes. From extensive clinical experience he believes that "the vast majority of patients suffering from the blood dyscrasias and lymphoid diseases have a significant history of exposure to the various hydrocarbons which in turn includes most of the pesticides of today. A careful medical history will almost invariably establish such a relationship." This specialist now has a large number of detailed case histories based on every patient he has seen with leukemias, aplastic anemias, Hodgkin's disease, and other disorders of the blood and blood-forming tissues. "They had all been exposed to these environmental agents, with a fair amount of exposure," he reports.
What do these case histories show? One concerned a housewife who abhorred spiders. In mid-August she had gone into her basement with an aerosol spray containing DDT and petroleum distillate. She sprayed the entire basement thoroughly, under the stairs, in the fruit cupboards and in all the protected areas around ceiling and rafters. As she finished the spraying she began to feel quite ill, with nausea and extreme anxiety and nervousness. Within the next few days she felt better, however, and apparently not suspecting the cause of her difficulty, she repeated the entire procedure in September, running through two more cycles of spraying, falling ill, recovering temporarily, spraying again. After the third use of the aerosol new symptoms developed: fever, pains in the joints and general malaise, acute phlebitis in one leg. When examined by Dr. Hargraves she was found to be suffering from acute leukemia. She died within the following month.
Another of Dr. Hargraves' patients was a professional man who had his office in an old building infested by roaches. Becoming embarrassed by the presence of these insects, he took control measures in his own hands. He spent most of one Sunday spraying the basement and all secluded areas. The spray was a 25 per cent DDT concentrate suspended in a solvent containing methylated naphthalenes. Within a short time he began to bruise and bleed. He entered the clinic bleeding from a number of hemorrhages. Studies of his blood revealed a severe depression of the bone marrow called aplastic anemia. During the next five and one half months he received 59 transfusions in addition to other therapy. There was partial recovery but about nine years later a fatal leukemia developed.
Where pesticides are involved, the chemicals that figure most prominently in the case histories are DDT, lindane, benzene hexachloride, the nitrophenols, the common moth crystal paradichlorobenzene, chlordane, and, of course, the solvents in which they are carried. As this physician emphasizes, pure exposure to a single chemical is the exception, rather than the rule. The commercial product usually contains combinations of several chemicals, suspended in a petroleum distillate plus some dispersing agent. The aromatic cyclic and unsaturated hydrocarbons of the vehicle may themselves be a major factor in the damage done the blood-forming organs. From the practical rather than the medical standpoint this distinction is of little importance, however, because these petroleum solvents are an inseparable part of most common spraying practices.
The medical literature of this and other countries contains many significant cases that support Dr. Hargraves' belief in a cause-and-effect relation between these chemicals and leukemia and other blood disorders. They concern such everyday people as farmers caught in the "fallout" of their own spray rigs or of planes, a college student who sprayed his study for ants and remained in the room to study, a woman who had installed a portable lindane vaporizer in her home, a worker in a cotton field that had been sprayed with chlordane and toxaphene. They carry, half concealed within their medical terminology, stories of such human tragedies as that of two young cousins in Czechoslovakia, boys who lived in the same town and had always worked and played together. Their last and most fateful employment was at a farm cooperative where it was their job to unload sacks of an insecticide (benzene hexachloride). Eight months later one of the boys was stricken with acute leukemia. In nine days he was dead. At about this time his cousin began to tire easily and to run a temperature. Within about three months his symptoms became more severe and he, too, was hospitalized. Again the diagnosis was acute leukemia, and again the disease ran its inevitably fatal course.
And then there is the case of a Swedish farmer, strangely reminiscent of that of the Japanese fisherman Kuboyama of the tuna vessel the
Lucky Dragon.
Like Kuboyama, the farmer had been a healthy man, gleaning his living from the land as Kuboyama had taken his from the sea. For each man a poison drifting out of the sky carried a death sentence. For one, it was radiation-poisoned ash; for the other, chemical dust. The farmer had treated about 60 acres of land with a dust containing DDT and benzene hexachloride. As he worked puffs of wind brought little clouds of dust swirling about him. "In the evening he felt unusually tired, and during the subsequent days he had a general feeling of weakness, with backache and aching legs as well as chills, and was obliged to take to his bed," says a report from the Medical Clinic at Lund. "His condition became worse, however, and on May 19 [a week after the spraying] he applied for admission to the local hospital." He had a high fever and his blood count was abnormal. He was transferred to the Medical Clinic, where, after an illness of two and one half months, he died. A post-mortem examination revealed a complete wasting away of the bone marrow.
How a normal and necessary process such as cell division can become altered so that it is alien and destructive is a problem that has engaged the attention of countless scientists and untold sums of money. What happens in a cell to change its orderly multiplication into the wild and uncontrolled proliferation of cancer?
When answers are found they will almost certainly be multiple. Just as cancer itself is a disease that wears many guises, appearing in various forms that differ in their origin, in the course of their development, and in the factors that influence their growth or regression, so there must be a corresponding variety of causes. Yet underlying them all, perhaps, only a few basic kinds of injuries to the cell are responsible. Here and there, in research widely scattered and sometimes not undertaken as a cancer study at all, we see glimmerings of the first light that may one day illuminate this problem.
Again we find that only by looking at some of the smallest units of life, the cell and its chromosomes, can we find that wider vision needed to penetrate such mysteries. Here, in this microcosm, we must look for those factors that somehow shift the marvelously functioning mechanisms of the cell out of their normal patterns.
One of the most impressive theories of the origin of cancer cells was developed by a German biochemist, Professor Otto Warburg of the Max Planck Institute of Cell Physiology. Warburg has devoted a lifetime of study to the complex processes of oxidation within the cell. Out of this broad background of understanding came a fascinating and lucid explanation of the way a normal cell can become malignant.
Warburg believes that either radiation or a chemical carcinogen acts by destroying the respiration of normal cells, thus depriving them of energy. This action may result from minute doses often repeated. The effect, once achieved, is irreversible. The cells not killed outright by the impact of such a respiratory poison struggle to compensate for the loss of energy. They can no longer carry on that extraordinary and efficient cycle by which vast amounts of ATP are produced, but are thrown back on a primitive and far less efficient method, that of fermentation. The struggle to survive by fermentation continues for a long period of time. It continues through ensuing cell divisions, so that all the descendant cells have this abnormal method of respiration. Once a cell has lost its normal respiration it cannot regain it—not in a year, not in a decade or in many decades. But little by little, in this grueling struggle to restore lost energy, those cells that survive begin to compensate by increased fermentation. It is a Darwinian struggle, in which only the most fit or adaptable survive. At last they reach the point where fermentation is able to produce as much energy as respiration. At this point, cancer cells may be said to have been created from normal body cells.
Warburg's theory explains many otherwise puzzling things. The long latent period of most cancers is the time required for the infinite number of cell divisions during which fermentation is gradually increasing after the initial damage to respiration. The time required for fermentation to become dominant varies in different species because of different fermentation rates: a short time in the rat, in which cancers appear quickly, a long time (decades even) in man, in whom the development of malignancy is a deliberate process.