THE cancer cell, to borrow a phrase from Schopenhauer, has the will to live. That is to say, it is able to defy those forces which restrain the multiplication of normal cells and so preserve a just proportion among the various parts of the organism.
Growth is not a function of the adult human body, apart from what an engineer would call maintenance and repair, and it is a dramatic event indeed when some of its cells suddenly acquire the faculty of ungovernable proliferation. The new capacity may add itself in any degree, from that possessed by the lowly and benign wart, which increases but slowly in size and does no harm save to the aesthetic sense of its bearer, up to that of the most highly malignant cancer, which is capable of destroying life in a period so brief as to be reckoned in months.
No matter whether its character be malignant or benign, a group of cells that succeeds in escaping the restrictions ordinarily imposed is called a tumor. Many varieties are recognized by the pathologist, but only the sarcoma and the carcinoma need be kept in mind for the present purpose. These differ in source, the former developing from the connective tissues, which occupy the interior of the body, the latter from the epithelium, a protective layer of cells that covers the surface of the organism and lines its ducts and cavities.
Both the tumors just named are malignant, and both are often included for convenience under the term ‘cancer,’ as they will be in the following article, although more specifically a cancer is a tumor of epithelial cells.
Cancer was recognized centuries before the opening of the Christian Era, and endeavors were made to explain it, many of them not much more fantastic than some comparatively recent attempts. Thus, about the middle of the past century it was noticed that cancer was not so common in prisons as elsewhere, and it was proposed that this was because prisoners received less food, and less meat in particular, than other persons. The suggestion was heard with respect, and even to-day enjoys serious consideration in some quarters, though the true explanation of the discrepancy is that the average age of a jail population lies considerably below thirty-five, the period of life at which cancer usually begins to appear. Prisoners are protected by their youth rather than by enforced abstinence.
Furthermore, since that suggestion was advanced it has become common knowledge that cancer affects vegetarian races; nay, more, it attacks the lower animals, without predilection for the Carnivora. Meat can therefore be eliminated from consideration, as can all diets and customs peculiar to man, except in so far as these are associated with chronic irritation, while the frequent occurrence of the disease in fishes ought to discourage the idea that soil or climate operates to cause it.
The germ hypothesis comes and goes, like the Cheshire cat, and, though not yet discarded, it is in disfavor at the present time. The cancer villages and cancer belts that have been so often reported can be accounted for by a disproportionately large number of inhabitants of the cancer age. As for cancer houses, a distinguished pathologist dismissed them years ago by appeal to the law of chance; for one house in a thousand may fortuitously show an excess of cases of cancer — or of twin births — over the ordinary run of houses. No single case has yet been reported which would prove beyond any doubt the transfer of cancer from one person to another, and when the high mortality of physicians and nurses from demonstrably infectious diseases is considered it is doubly significant that no attendant on a cancer patient has yet contracted the disease as a result of the exposure.
Most of the remaining efforts to account for the origin of cancer are so technical as to interest only the scholar, and may therefore be dismissed with but few words. They have been proved either wholly fallacious or, at the best, only partially true. To the single authentic cause already mentioned — namely, age — there can be added with reasonable confidence only two others.
One of these is chronic irritation, which has been shown time and time again to be closely associated with the inception of tumors. Thus there are cases of needlewomen who have developed sarcoma in a finger repeatedly pricked in sewing; of carcinoma of the skin among those who handle mineral oils, tar, pitch, soot, arsenic, and other irritants; but it is a curious fact that no cancer has yet come to light in connection with the ulcers covering the hands and arms of those whose work exposes them to salts of chromic acid. Evidently chronic irritation, like age, is only a contributing cause.
The third factor so far known is some sort of susceptibility which, it has been conjectured, may be hereditary. Experiments with animals, where breeding can be so controlled as either to eliminate or to concentrate hereditary factors, show that there is indeed an inborn tendency to develop or not to develop cancer. But how widely these results, vouched for by Tyzzer, Murray, and the Misses Slye and Lynch, can be applied to man is still an open question. Marriages are not made in deference to the wishes of the geneticist, and it seems altogether probable that any inherited tendency is kept at a low level by the random manner in which human matings take place; in any case, the insurance companies, which deal not with theories but with dollars, have seen no reason to increase their rates to those with a cancerous family history. On the other hand, it may very well be that in a few unfortunate families, like the Bonapartes, a tendency to develop cancer has been intensified to a degree surpassing that in the population at large.
Statistical inquiry has been employed for years in the attempted settlement of such questions, and, though subject to serious limitations at present, it is not without possibilities. For example, the death rate from cancer of the breast and the uterus is approximately twice as high in England as in Holland. Careful analysis of the figures permits the inference that the disparity may be genuine, and it is to be hoped that further inquiry will lead to an explanation, though at present the difference is but one more in that interminable series of riddles that confronts the student of cancer. The circumstance has been mentioned only to illustrate a situation where the statistical method may be employed with profit because reliable data are available, Unfortunately it cannot often be turned to account, as the figures relating to cancer are deceptive in the extreme. The highest death rates in Europe are recorded in the more progressive countries, and if the tables could be accepted at their face value we should have to agree that cancer is over ten times as common in Switzerland, say, as in Serbia. This it certainly is not; but medical skill and statistical accuracy are ten times as reliable in the one country as in the other.
Even under optimum conditions, such as obtain in the great hospitals of cities like Chicago, London, and Berlin, it has been shown by Wells and others that there is still an error of some thirty per cent, unavoidable at present because it is so difficult to recognize cancer when it involves the less accessible internal organs.
Records are vitiated still further by a curious reluctance on the part of surviving relatives to have cancer appear in the death certificate, so that the attending physician is persuaded to enter pneumonia or any other disease, depending on the taste and fancy of the writer. The position is exactly illustrated by the inquiry, during the exhibition of a new calculating machine, whether it would deliver the correct answer when the wrong figures were put in.
The reader will now realize why it is impossible to answer the question so often and so anxiously asked: Is cancer increasing? For, in addition to the inaccuracies just discussed, the situation is complicated again by the rescue of more people year after year from the infectious diseases, so that larger numbers survive to reach the cancer age, while, at the same time, constantly increasing skill in diagnosis discloses cancer where twenty years ago none would have been suspected.
The statistical inquiry, one of the most venerable means of research, is thus one of the least useful. Indeed, it is almost without value in comparison with the experimental method, so new as to be largely the product of the present century.
Although a few pathologists had succeeded previously in transferring cancer from one animal to another of the same species, it was the work of Jensen and Borrel in Europe and of Leo Loeb in this country that established the value of the procedure. At once it became possible to plan experiments such as could not have been carried out on patients under any consideration. Within a comparatively few years the germ hypothesis was undermined through Jensen’s observation, promptly confirmed by Bashford and Murray, that the small fragment of tumor introduced at transplantation did not infect its new host, but grew exactly as a grafted twig grows; comparisons between normal and malignant proliferation were instituted by Cramer; Russell, Haaland, Ehrlich, Apolant, Schöne, Murphy, Gaylord, Clowes, Rohdenburg, and Ewing were enabled to investigate the immunity which sometimes occurs in tumorbearing animals and to show that it differs fundamentally from the immunity characterizing the infectious diseases; Wood and Prime, as well as Mottram and Russ, took advantage of the new method to work out the necessary Xray dosage; while to the transplantable tumors of the mouse and rat, from which a veritable mine of information was obtained, Rous added a propagable sarcoma of the fowl, which proved to be of unusual interest.
In consequence of the work of these and other investigators our knowledge of cancer attained within a brief period an accuracy such as could never have followed mere observation of the disease in man. Perhaps it would be safe to say that more has been learned in the past thirty years than in the three thousand which preceded them. Yet even the most enthusiastic realized that the transplanted tumor, consisting as it does of cells that have already undergone the malignant change, could never explain the cause of cancer. There were accordingly those who continued the efforts of their predecessors to effect the appearance of a spontaneous animal tumor by applying irritants known to be active in man; but, as failure continued to be their only reward, the attempt was about to be abandoned, when success appeared from a direction entirely unsuspected. As has so often occurred before, the problem was solved through a chance observation, arising in the course of experiments quite unrelated to the point at issue.
The late Johannes Fibiger, a pathologist of Copenhagen, who was awarded the Nobel prize in medicine for his discovery, was engaged in the study of tuberculosis, and during the course of his work had occasion to autopsy three wild rats. In the stomach of each one he found a pronounced epithelial thickening which had progressed in some places to the formation of warty outgrowths, and, associated with these changes, a parasitic worm.
Neither this disorder nor the accompanying parasite had ever been described, so, in order to learn something of their nature and the conditions under which they occurred, the stomachs of over eleven hundred rats were examined, but neither was found. As attempts to transmit the disease with the affected tissues were unsuccessful, the possibility had to be considered that the parasite was not directly transferable from rat to rat, but required the intervention of another host. Now it had long been known that a certain cockroach (Periplaneta orientalis) is the intermediate host for a similar worm, and wild rats from a locality in Copenhagen that was swarming with this insect were therefore examined. Once again the search failed; and, although the rats consumed their smaller associates with relish, they remained in distressingly good health.
Not until rats from a large sugar refinery infested with a different cockroach (Periplaneta americana) were examined did success follow. Within about nine months sixty-one rats were caught in this building, in many of which the parasite and the disease that it sets up, probably as a result of some irritating secretion, were found. Furthermore, rats fed with Periplaneta americana developed the characteristic changes in the stomach, while in some of these animals the disease had progressed to actual carcinoma.
The experimental production of cancer had at last been achieved.
Questions could now be approached upon which the transplanted tumor could throw no light. Almost the first one to be investigated was the influence of age, a factor that turned out rather unexpectedly to be less decisive than had been supposed, for young rats proved as susceptible as older ones. Hence it would appear that the length of time during which the worm remains in the stomach is more important than the age of the rat when first infested, and that age is merely another way of expressing the duration of irritation.
Encouraged by these results, two Japanese pathologists, Yamagiwa and Itchikawa, determined to attempt once more the production of cancer with tar. The occurrence of carcinoma among those whose work exposes them to irritating substances was a clue that had inspired a long series of experiments, and in Germany, France, and England the problem of inciting malignant growth in animals had been on the eve of solution at any moment during the preceding three decades, though this was unsuspected at the time. The effort had failed only because an insusceptible species of animal had been unwittingly chosen or because irritation had not been continued long enough. It was the good fortune of Yamagiwa and his associate not only to select the rabbit, but to be possessed of the infinite patience necessary for applying tar week after week, month after month, without any guaranty of success.
They were rewarded, however, by the appearance of cancer in some of their animals after the lapse of about five months. The white mouse was subsequently shown to be even more sensitive than the rabbit, whereas the skin of the rat, the guinea pig, and the domestic fowl proved to be resistant. An important clue lies concealed in this diverse response to irritation, but progress is slow and difficult because the reaction is of almost incredible delicacy; thus, while the skin of the rat and the fowl is immune to tar, their connective tissues are not, for sarcoma can be elicited by subcutaneous injection of this agent.
In a third type of experimental tumor, which we owe to the work of Bullock and Curtis in this country, the same narrow specificity has been observed. Their sarcoma, produced by infesting rats with the immature stage of a tapeworm that passes its adult life in the cat, originates in the liver, but from the connective-tissue framework only, the working cells of the organ being entirely exempt; and, although the same parasite is a frequent inhabitant of the mouse liver, it never gives rise to a malignant growth in this species.
It is unnecessary to emphasize the point that these three methods of inciting tumors constitute one of the most notable advances that experimental medicine has yet seen, and no one has ventured to predict what benefits may ultimately accrue. In any case, a final solution of the question of heredity is in sight, for its settlement requires only that the response to irritation be tested in animals of known pedigree, while another task engaging the attention of many investigators is the isolation of that substance in tar which produces cancer. If this can be accomplished it may become possible to eliminate tar cancer as an industrial disease, though as tar is a mixture of several hundred ingredients, of which only about one hundred have been identified by the chemist, and as its composition varies considerably according to the coal from which it is distilled, the advance is discouragingly slow.
Still another means of attacking the problem of malignant growth is a minute investigation of the appearance and life history of the cancer cell itself. Even under the highest power of the microscope no difference has yet been discerned which would enable one to distinguish a single cancer cell from any other actively growing element, though the malignant tumor as a whole exhibits a loss of the normal architecture characterizing the organ in which it originates. As a German pathologist, more famous for his scientific than his linguistic acquirements, was in the habit of explaining to his Englishspeaking students, ‘All dose cells are in very damn disorder.’ This bizarre arrangement is so typical of malignant disease as to be the criterion upon which diagnosis is made and the scope of operation planned. The long years of observation which uncovered it and proved its significance were, therefore, well spent, even though they brought neither an understanding of how cancer originates nor any clue to a nonsurgical treatment.
Intensive study of the life history of the cancer cell has been even more disappointing, for no useful difference has so far been disclosed between its activities and those of the body cells on their lawful occasions. When the diet of a tumor-bearing animal is restricted, even to the danger point, the cancer cell continues to grow; vitamin deficiency does not affect it; severe acidosis kills the host before the guest succumbs; high fever does more harm to the bearer than to the tumor; and so on.
It is this very similarity between the cancer cell and its normal prototype that delays the discovery of a specific cure. Obviously this must be some agent which will destroy the tumor without inflicting on the rest of the body, during the fray, the traditional fate of the innocent bystander. But in addition it must be able to exert its effect after subcutaneous or intravenous injection, as antitoxin does in diphtheria, for cancer so often involves a remote organ that a remedy which had to be introduced directly into the growth would be hardly worth the trouble of preparing.
The feature that makes cancer so difficult to cure by surgery, once the disease has become well established, is the way in which its cells wander out, one by one, invading the circumjacent tissues so diffusely that the margin of the growth is as hard to define as the edge of a drop of water on a tablecloth. The surgeon is expected to remove all the tumor, yet he cannot precisely delimit it; if he cuts too widely he may harm some indispensable structure, yet if he does not go far enough cancer cells will be left behind to continue their growth and give rise to a recurrence which only too often cannot by any possibility be extirpated. Frequently his operation has to be a compromise, therefore, unless the tumor affects a part which can be removed in its entirety. Even then his effort may be vain, for during their invasion the cancer cells must ultimately reach a blood vessel and pass through its walls into the circulation, to be instantly disseminated throughout the body. If this has occurred before operation, what possible chance of recovery can there be?
But, in spite of the difficulties arrayed against him, the surgeon has even now a record of many brilliant cures, and the proportion of early cases coming to him for help is steadily rising, thanks to the educational programme of the American Society for the Control of Cancer, which for years has been pressing on the public the necessity for early diagnosis and immediate operation.
In a few fortunate cases surgical intervention will not be necessary, for certain types of malignant disease yield to the X-ray or to radium. It should never be forgotten, however, that possession of the necessary apparatus is no guaranty of skill or, unhappily, even of common honesty.
‘Soothing, balmy oils’ do no good, save to the pocketbooks of those who advertise them, and ‘electrical treatment’ is often a fraud of the basest kind. Apart from the X-ray, electricity is being used, certainly, by qualified men, but the method lends itself so easily to exploitation that the patient should be sure he is not in the hands of a charlatan before consenting to undertake it. An excellent rule in all cases of doubt is this: Beware of those who promise to cure.
The injection of lead, introduced a few years ago by Blair Bell, of Liverpool, has been followed by some miraculous recoveries, though it has failed much more often than it has succeeded, and is not without danger even in skilled hands. Attempts are under way to prepare a less poisonous form of lead, but it is probable that the treatment will remain in the experimental stage for years to come. In the meantime it will be instructive for the reader to recall the manner in which it was introduced. It came from a surgeon of recognized standing whose experiments were conducted in a hospital of the highest repute; it was reported in the medical journals in a series of communications describing the method of preparation and scrupulously recording failures as well as cures; it was employed only with patients who were far beyond any help from surgery; and, finally, it was administered without charge more often than not.
Now let this dignified procedure be contrasted with the way of the quack. His ‘cure’ is a secret remedy that either has been in the family for years or has been obtained from an Indian chief, though it is hard to see why either of these sources should commend it to anyone over ten years of age; it is advertised in newspapers which are still not ashamed to admit such material to their columns; it is sold at an exorbitant price; and it is implied, if not explicitly stated, that only the jealousy of the medical profession withholds this priceless boon from humanity.
It passes understanding that anyone old enough to have cancer could believe such rubbish, yet there are hundreds of unfortunates throughout the country, their savings in the pocket of a quack, their disease in a hopelessly advanced stage, appealing for help which cannot now be given.
One of the duties of an institution devoted to cancer research is the investigation of such ‘cures’ as are not too preposterous, and it is within the knowledge of the writer that not a single one of all those that have been tested has proved of the slightest value. At the worst they have been equivalent to a barefaced robbery; at the best, the product of an ignorant enthusiast; and it cannot be too strongly emphasized that no drug, serum, vaccine, or other preparation is known that will select and destroy the cancer cell without detriment to the normal tissues surrounding it.
What are the chances that such a remedy ever will be discovered? Good, I think, remembering what man has already accomplished. Flung into this world naked and homeless, he has learned to build shelters and to subdue fire to his wishes; to ride first the wave and then the air; to weigh the stars and measure the atom. Much more essential to his comfort than these last, the infectious diseases arc within his control and could be banished to-morrow, for the knowledge is there. Only ignorance and superstition stand in the way.
It is impossible to remain unmoved by these achievements, and I must confess to an optimism as incurable as the last stages of cancer itself.