14. One in Every Four
THE BATTLE of living things against cancer began so long ago that its origin is lost in time. But it must have begun in a natural environment, in which whatever life inhabited the earth was subjected, for good or ill, to influences that had their origin in sun and storm and the ancient nature of the earth. Some of the elements of this environment created hazards to which life had to adjust or perish. The ultraviolet radiation in sunlight could cause malignancy. So could radiations from certain rocks, or arsenic washed out of soil or rocks to contaminate food or water supplies.
The environment contained these hostile elements even before there was life; yet life arose, and over the millions of years it came to exist in infinite numbers and endless variety. Over the eons of unhurried time that is nature's, life reached an adjustment with destructive forces as selection weeded out the less adaptable and only the most resistant survived. These natural cancer-causing agents are still a factor in producing malignancy; however, they are few in number and they belong to that ancient array of forces to which life has been accustomed from the beginning.
With the advent of man the situation began to change, for man, alone of all forms of life, can create cancer-producing substances, which in medical terminology are called carcinogens. A few man-made carcinogens have been part of the environment for centuries. An example is soot, containing aromatic hydrocarbons. With the dawn of the industrial era the world became a place of continuous, ever-accelerating change. Instead of the natural environment there was rapidly substituted an artificial
one composed of new chemical and physical agents, many of them possessing powerful capacities for inducing biologic change. Against these carcinogens which his own activities had created man had no protection, for even as his biological heritage has evolved slowly, so it adapts slowly to new conditions. As a result these powerful substances could easily penetrate the inadequate defenses of the body.
The history of cancer is long, but our recognition of the agents that produce it has been slow to mature. The first awareness that external or environmental agents could produce malignant change dawned in the mind of a London physician nearly two centuries ago. In 1775 Sir Percivall Pott declared that the scrotal cancer so common among chimney sweeps must be caused by the soot that accumulated on their bodies. He could not furnish the "proof" we would demand today, but modern research methods have now isolated the deadly chemical in soot and proved the correctness of his perception.
For a century or more after Pott's discovery there seems to have been little further realization that certain of the chemicals in the human environment could cause cancer by repeated skin contact, inhalation, or swallowing. True, it had been noticed that skin cancer was prevalent among workers exposed to arsenic fumes in copper smelters and tin foundries in Cornwall and Wales. And it was realized that workers in the cobalt mines in Saxony and in the uranium mines at Joachimsthal in Bohemia were subject to a disease of the lungs, later identified as cancer. But these were phenomena of the pre-industrial era, before the flowering of the industries whose products were to pervade the environment of almost every living thing.
The first recognition of malignancies traceable to the age of industry came during the last quarter of the 19th century. About the time that Pasteur was demonstrating the microbial origin of many infectious diseases, others were discovering the chemical origin of cancer—skin cancers among workers in the new lignite industry in Saxony and in the Scottish shale industry, along with other cancers caused by occupational exposure to tar and pitch. By the end of the 19th century a half-dozen sources of industrial carcinogens were known; the 20th century was to create countless new cancer-causing chemicals and to bring the general population into intimate contact with them. In the less than two centuries intervening since the work of Pott, the environmental situation has been vastly changed. No longer are exposures to dangerous chemicals occupational alone; they have entered the environment of everyone—even of children as yet unborn. It is hardly surprising, therefore, that we are now aware of an alarming increase in malignant disease.
The increase itself is no mere matter of subjective impressions. The monthly report of the Office of Vital Statistics for July 1959 states that malignant growths, including those of the lymphatic and blood-forming tissues, accounted for 15 per cent of the deaths in 1958 compared with only 4 per cent in 1900. Judging by the present incidence of the disease, the American Cancer Society estimates that 45,000,000 Americans now living will eventually develop cancer. This means that malignant disease will strike two out of three families.
The situation with respect to children is even more deeply disturbing. A quarter century ago, cancer in children was considered a medical rarity. Today, more American school children die of cancer than from any other disease. So serious has this situation become that Boston has established the first hospital in the United States devoted exclusively to the treatment of children with cancer. Twelve per cent of all deaths in children between the ages of one and fourteen are caused by cancer. Large numbers of malignant tumors are discovered clinically in children under the age of five, but it is an even grimmer fact that significant numbers of such growths are present at or before birth. Dr. W. C. Hueper of the National Cancer Institute, a foremost authority on environmental cancer, has suggested that congenital cancers and cancers in infants may be related to the action of cancer-producing agents to which the mother has been exposed during pregnancy and which penetrate the placenta to act on the rapidly developing fetal tissues. Experiments show that the younger the animal is when it is subjected to a cancer-producing agent the more certain is the production of cancer. Dr. Francis Ray of the University of Florida has warned that "we may be initiating cancer in the children of today by the addition of chemicals [to food]... We will not know, perhaps for a generation or two, what the effects will be."
The problem that concerns us here is whether any of the chemicals we are using in our attempts to control nature play a direct or indirect role as causes of cancer. In terms of evidence gained from animal experiments we shall see that five or possibly six of the pesticides must definitely be rated as carcinogens. The list is greatly lengthened if we add those considered by some physicians to cause leukemia in human patients. Here the evidence is circumstantial, as it must be since we do not experiment on human beings, but it is nonetheless impressive. Still other pesticides will be added as we include those whose action on living tissues or cells may be considered an indirect cause of malignancy.
One of the earliest pesticides associated with cancer is arsenic, occurring in sodium arsenite as a weed killer, and in calcium arsenate and various other compounds as insecticides. The association between arsenic and cancer in man and animals is historic. A fascinating example of the consequences of exposure to arsenic is related by Dr. Hueper in his Occupational Tumors, a classic monograph on the subject. The city of Reichenstein in Silesia had been for almost a thousand years the site of mining for gold and silver ores, and for several hundred years for arsenic ores. Over the centuries arsenic wastes accumulated in the vicinity of the mine shafts and were picked up by streams coming down from the mountains. The underground water also became contaminated, and arsenic entered the drinking water. For centuries many of the inhabitants of this region suffered from what came to be known as "the Reichenstein disease"—chronic arsenicism with accompanying disorders of the liver, skin, and gastrointestinal and nervous systems. Malignant tumors were a common accompaniment of the disease. Reichenstein's disease is now chiefly of historic interest, for new water supplies were provided a quarter of a century ago, from which arsenic was largely eliminated. In Cordoba Province in Argentina, however, chronic arsenic poisoning, accompanied by arsenical skin cancers, is endemic because of the contamination of drinking water derived from rock formations containing arsenic.
It would not be difficult to create conditions similar to those in Reichenstein and Cordoba by long continued use of arsenical insecticides. In the Unit
ed States the arsenic-drenched soils of tobacco plantations, of many orchards in the Northwest, and of blueberry lands in the East may easily lead to pollution of water supplies.
An arsenic-contaminated environment affects not only man but animals as well. A report of great interest came from Germany in 1936. In the area about Freiberg, Saxony, smelters for silver and lead poured arsenic fumes into the air, to drift out over the surrounding countryside and settle down upon the vegetation. According to Dr. Hueper, horses, cows, goats, and pigs, which of course fed on this vegetation, showed loss of hair and thickening of the skin. Deer inhabiting nearby forests sometimes had abnormal pigment spots and precancerous warts. One had a definitely cancerous lesion. Both domestic and wild animals were affected by "arsenical enteritis, gastric ulcers, and cirrhosis of the liver." Sheep kept near the smelters developed cancers of the nasal sinus; at their death arsenic was found in the brain, liver, and tumors. In the area there was also "an extraordinary mortality among insects, especially bees. After rainfalls which washed the arsenical dust from the leaves and carried it along into the water of brooks and pools, a great many fish died."
An example of a carcinogen belonging to the group of new, organic pesticides is a chemical widely used against mites and ticks. Its history provides abundant proof that, despite the supposed safeguards provided by legislation, the public can be exposed to a known carcinogen for several years before the slowly moving legal processes can bring the situation under control. The story is interesting from another standpoint, proving that what the public is asked to accept as "safe" today may turn out tomorrow to be extremely dangerous.
When this chemical was introduced in 1955, the manufacturer applied for a tolerance which would sanction the presence of small residues on any crops that might be sprayed. As required by law, he had tested the chemical on laboratory animals and submitted the results with his application. However, scientists of the Food and Drug Administration interpreted the tests as showing a possible cancer-producing tendency and the Commissioner accordingly recommended a "zero tolerance," which is a way of saying that no residues could legally occur on food shipped across state lines. But the manufacturer had the legal right to appeal and the case was accordingly reviewed by a committee. The committee's decision was a compromise: a tolerance of 1 part per million was to be established and the product marketed for two years, during which time further laboratory tests were to determine whether the chemical was actually a carcinogen.
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.