Saturday, May 5, 2012

What We Know About Cancer Gratwick Laboratory Rockefeller Institute

By Burton J. Hendrick.

What is the medical pro­fession in this country doing to stop the ravages of cancer? A short time ago Professor Ehrlich, the great German investigator, in the course of a visit to our most important cancer laboratories, made several statements which partly answer this question. As a result of recent progress in cancer research, he declared, the beginning of the end of the cancer problem is in sight. The ultimate conquest of the disease, added Ehrlich, is as certain as was the capture of Port Arthur after the Japanese had taken the first trench. It is to the cancer laboratories of the United States, he continued, that European investigators now look for the most important results. As a matter of fact, many of the dis­coveries upon which Ehrlich based his opti­mistic statements were made first on this side of the Atlantic.

The medical profession has learned more about cancer in the last six years than in the preceding six thousand. True as this statement is, however, it must not be misconstrued. No cancer "cure" has been discovered. Investi­gators have penetrated many secrets of the disease, but they have not yet restored a single human sufferer to health. From the standpoint of science, however, the discovery of new principles of eternal applicability is far more important than the discovery of specific rem­edies. Thus Pasteur's demonstration that living microbes cause contagious diseases meant more to medical science than his successful treat­ment of hydrophobia, which was merely one application of this general principle. Likewise, the cancer investigations of the last few years have revealed certain hitherto unknown princi­ples that will eventually assume great impor­tance in the practical treatment of the disease.

One in Every Eight Women Past the Age of Thirty-five Dies of Cancer

It is peculiarly appropriate that the United States should take a leading part in this work. In all probability, cancer is the worst physical scourge with which we have to deal. It annually destroys half as many lives as tuberculosis; but it is an even greater menace, because, whereas the mortality from tuber­culosis steadily decreases year by- year, that from cancer steadily increases. The actual facts even medical men themselves hesitate to discuss. How many realize, for example, that, in England, of all women who have reached the age of thirty-five years, one in every eight dies of cancer, and one in every eleven men? Yet the latest official report of the Registrar General of England coldly declares that this is the present situation. Whether the same figures apply to the United States cannot be determined with available statistics; but as living conditions and medical practice represent about the same standards in both countries, the probability is that they do.

Indeed, medical science would not be sur­prised to learn that the mortality is greater in the United States than elsewhere. We pride ourselves upon our general prosperity and enlightenment, and those seem precisely the two factors that chiefly encourage the growth of cancer. Spread out a map of the world, and mark the countries that have progressed far­thest in material well-being, in education, gov­ernment, sanitation, and other essentials of modern civilization; those are the countries that suffer most from the cancer plague. In the eastern world, not Asia or Africa, but en­lightened Europe; in the western, not Mexico, Honduras, or Panama, but the United States and Canada - these are the countries most grievously afflicted. No savage tribe is abso­lutely immune, but cancer assails most violently those peoples that have reached the highest points in civilization. And not only this, but it apparently bears heaviest upon the most sani­tary and enlightened parts of these countries. In Europe the nations that suffer most are not Russia or Hungary or Italy or Spain, but Germany, France, Sweden, Norway, and, above all, England. In London,-the greatest mor­tality is found, not in the East End, but in Hampstead, Marylebone, and Chelsea, which include the city's wealthiest parts. Similarly, in New York, the Russian Jews and Italians who so largely populate the crowded tenement sections are comparatively immune, whereas the more sanitary parts of the town are favorite breeding-places. Where diseases of known contagiousness, like tuberculosis, typhoid fever, diphtheria, and pneumonia, most abound, can­cer seems to find a less strong foothold than in other more salubrious sections; as by some mysterious and inexorable law of compensation it finds its way mainly into the homes of the prosperous and enlightened.

Cancer a Disease of Highly Developed Civilization

Thus cancer, like death itself, apparently loves a shining mark. It strikes, not so frequently at the vicious, the uncleanly, the miser­able, but at those lives that promise most to themselves and their communities. In prisons, insane asylums, and workhouses it is only ex­ceptionally found. Among men, according to experienced investigators few drunkards be­come cancerous and, among women, few prosti­tutes. Married women more frequently die from this cause than unmarried and fertile women more frequently than barren. Among animals, reptiles are practically the only species in which cancers have not been found, but it is the domesticated animals, or those living in closest association with man, that suffer most. Thus horses, cows, pigs, parrots, canary-birds, cats, mice, rats - all these have cancer; and it is the closest animal associate of man, the dog, that is the most commonly afflicted. If all the lap-dogs of Fifth Avenue and our other fashionable quarters were examined, a considerable proportion would be found to be afflicted with one or more malignant tumors.

In all probability, this prevalence of cancer in the most civilized Communities and in the most sanitary quarters is explained by the fact that it is an affliction of middle and post middle life. Among savage peoples and nations where only elementary sanitation is practiced, and the food supply is irregular, the death rate is higher, the average length of life is shorter, and infant mortality is greater. A smaller percentage of the population, in other words, reaches the can­cerous age. Thus most scientists would explain the comparative absence of cancer among pros­titutes by the brutal truth that only a small number live long enough to become subject to the disease. These considerations bring us face to face with a most startling circumstance: that nature seems to be subtly attempting to undo much of the work of modern medical science. We save yearly by diphtheria anti­toxin the lives of thousands of babies and chil­dren, only that they may grow up to become victims of cancer. We rescue many thousands of young men and women from tuberculosis, so that they may reap, as their whirlwind, an even more dreadful malady. Some economists have explained the great famines of India on the ground that modern sanitation has so de­creased the death rate that the country can­not sustain the increased population; and like­wise the increase in cancer may probably be accounted for, not by any absolute increase in virulence, but by the fact that modern medical science, in its merciful work of prolonging life, is simply providing the disease with more abundant soil.

Inasmuch as sanitation has reached a high development in this country, the likelihood is that, unless the malady is checked, it will be­come our greatest national scourge. Until 1900, however, little progress had been made. The attitude of science had been for many years one of hopeless pessimism. Modern medical progress had almost scratched the word "in­curable" from its lexicon; cancer, however, was still looked upon as one of the fundamental facts of nature, like death itself, with which we could hardly interfere. The cause of the disease had been the age-long riddle of pathological science. The greatest medical minds of the nineteenth century had attacked the problem and had retired humiliated. The endless search for the cancer parasite, the fact that forty or fifty differ­ent organisms had been described as the specific cause, had brought the whole subject more or less into disrepute.

But up to this time the investigators had not had a fair chance at the problem. In the study of cancer they had not been able to utilize the experimental method. History dis­closes the fact that nearly all great medical dis­coveries are the result of experiments on living animals. From the time when Galen cut open the arteries of a dog and found that they ac­tually contained blood, and not, as the most re­spectable schoolmen declared, simply "air," to the day when Behring evolved the diphtheria anti-toxin by experimenting upon guinea-pigs, animals have supplied the basis of nearly all real medical progress. And in the study of con­tagious diseases great advancement has been made only in those affections that can readily he transmitted to animals. We know much about typhoid fever and tuberculosis, for labo­ratory animals can be readily infected with these diseases and thus furnish the groundwork for experimentation; we know little about scarlet fever and measles - we have not even dis­covered the causative germs - because ani­mals are naturally immune to these infections. A similar condition of affairs had blocked cancer research. Nearly all animals have the disease in nature, but no method had been found of readily transmitting it to them. Several in­vestigators had even experimented upon themselves, injecting under their own skins small pieces of human cancer; in no case, however, had a malignant growth supervened. One or two investigators, especially Hanau in Germany and Moreau in France, had reported actual success in transplanting cancerous tumors from mouse to mouse; but their results had made little impression, and, by the time the new interest in the subject began, had been entirely forgotten.

Inside a Cancer Laboratory

But all this has changed. There are five American laboratories now in which animal experimentation in cancer is extensively car­ried on - the Gratwick Laboratory at Buffalo, the Medical Schools of Cornell, Harvard, and the University of Pennsylvania, and the Rocke­feller Institute in New York. White mice and white rats and a smaller number of dogs furnish the foundation for this work. The average cancer laboratory looks more like a breeder's establishment than a scientific headquarters. Upon the shelves are dozens of cages, filled with hundreds, in some cases thousands, of white mice and rats in different stages of the disease. The first sensation, on entering such a room, is naturally one of repulsion; on closer inspection, however, the situation is not as painful as the imagination at first conceives. If the animals suffer, they give few outward indications of the fact. The mice are active, playful sometimes quarrelsome - that is, they behave in every way like normal animals; they keep their coats clean and glossy, eat voraciously, and run about their cages as actively as their healthy brethren. Even mice in which good sized tumors have developed frequently give birth to young, and suckle and care for them; and in some cases, in search for society, they eat through the cages into those adjoining. Among human beings there is no physical suffering from cancer except in the latest stages, and thousands of patients do not suffer acutely even then. It is something of a relief to learn, there­fore, that practically no mice used for experi­mental purposes, and very few rats, ever reach the period when really acute pain sets in. Their tumors, for the most part, are hard nodules; if you pinch them tightly, the animal does not give the slightest indication of pain. As soon as they ulcerate - the period when, in human beings, suffering begins - the mice almost in­variably die. If they do not, they are chloro­formed, for they have then lost their usefulness for experimental purposes.

Each animal is carefully marked - a dash of purple dye on the tail, a spot of red on the back - for identification. To each is assigned a special card in an elaborate card catalogue; and upon this one can read its life history and trace the day-by-day development of its affliction.

Eight years ago Dr. Leo Loeb, then of the Chicago Polyclinic and now Assistant Professor of Pathology at the University of Pennsylvania, exhibited before a medical society in Boston several white rats with large growing malignant tumors. Dr. Loeb explained that these growths had not developed naturally upon the animals, but had been transplanted to them. He had discovered a white rat with a large sarcomatous cancer on the thyroid gland, and had injected small pieces into the exhibited animals. The medical world at first refused to consider the matter seriously; in fact; Dr. Loeb had not only conclusively demonstrated the trans­plantability of cancer, but had made the first accurate observations of its method of growth. He clearly proved that a malignant tumor could be transferred from one animal of a particular species to another animal of identically the same species. Thus rat cancer, such as he originally experimented with, could be trans­ferred only to a rat. He tried it upon guinea-pigs and hens, but always failed, and he could not even make it grow upon mice. More re­markable still, this sarcoma, which found its first habitat on a white rat, would not develop upon a gray one. The only exception was furnished by a hybrid animal - a cross between a gray and white rat - upon which a trans­plantation was finally made. In later experi­ments, Dr. Loeb, as well as his successors, had similar experiences. A few years ago he came into possession of a Japanese waltzing-mouse ­- a little gray and white rodent that has the pe­culiarity of almost constant circular motion -upon which a natural cancer was growing.

All attempts to transplant this upon popular American varieties of white and gray mice failed, and Dr. Loeb had to ransack the market to find more of the Japanese breed. When he finally succeeded, he had no difficulty in making the tumor grow upon them.

No Cancer Cells Where There Have Not Been Cancer Cells Before

 More interesting still was Dr. Loeb's demon­stration of the manner in which the cancers grew. His method was to take a small section, perhaps no larger than a pin-head, and inject it under the skin. It was always at this point of inoculation that the malignant tumor ultimately appeared. Dr. Loeb soon observed that in no case had he really started a new growth. The tumor that had spontaneously developed in his first animal simply continued to grow upon the second. A microscopic examination disclosed that, when the small piece of cancer was im­planted in the new body, its central portion soon died and became putrescent, only the edges, which came into contact with the tissue of the host, remaining alive. It was always from these peripheral cells that the growth developed. Never did it start from the tissue of the new animal. The transplanted cells, that is, did not set the surrounding tissues on fire - did not infect them. No cancer cells developed where there had not been cancer cells before. Dr. Loeb had done precisely what the gardener does when he takes a plant from one garden and places it in another; he does not create a new growth, he simply finds new soil for an old one. This is exactly what happens when a human being, sick with cancer, develops secondary growths in other parts of the body. These "metas­tases," as they are called scientifically, are not independent tumors; they are caused by the fact that certain cells of the primary growth get into the blood or lymph and are lodged in other parts of the body, where they grow. This is evident from the fact that the secondary growths have all the characteristics of the first. If a cancer of the lung, for example, forms a metas­tasis in the liver, the new tumor is formed, not of liver tissue, but of lung. A piece of lung, that is, starts growing on the liver. If a cancer of the stomach metastasizes in the breast, a piece of stomach simply arises on this exterior surface.

At first blush this seemed to do away with the idea that a specific organism caused cancer, or that the disease was contagious. Apparently Dr. Loeb had at last found the cancer microbe and this turned out to be merely the cancer cell; and apparently the only way of transmitting it was the deliberate transplantation of this cell from one animal body into another of the same species. Further experiments also seemed to indicate that cancer was not contagious, at least in the commonly accepted meaning of the word. Large pieces were placed in cages full of rats, but no animals became infected. Cancer cells were mixed with their food, but the rats which devoured them in large quantities did not "catch" the disease. Dr. Loeb injected into selected animals certain fluids present in cancer growths; these frequently developed cancers, but an examination of the fluids showed, in all cases, that they contained cancer cells. He then subjected the cancerous tissue to certain chemical processes that killed the cells, but which, in all probability, would not have killed the microbes, had any been present. But he obtained no cancer grafts from any material in which the life of the cell itself had been destroyed.

These and other experiments which soon followed notably, those of Professor C. O. Jensen of Copenhagen, aroused universal in­terest in the study of cancer. Experimentalists began ransacking the world for mice and rats in which natural malignant tumors had developed. Professional dealers, tempted by large rewards, kept the closest watch upon their stock, and, up to the present time, have sent nearly one thousand such animals to the several laboratories engaged in the work. The living mouse thus becomes for cancer research what the test tube is for ordinary bacteriological work. In no field of investigation are such quantities of animals used. The Imperial Cancer Research Fund in London has had thirty thousand in six years. In three years the Buffalo Laboratory has used twenty thousand. In the same time the Rockefeller Institute has had fifteen thousand rats and mice under observation. The necessity of having so many animals explains why the experiments are practically limited to rats and mice, and are not applied to horses and cows. Not only is the initial cost lower, but the little rodents are easier to watch and care for.

Attention has been called to certain facts that seem to controvert the microbe theory; in one important respect, however, cancer growth resembles that of bacteria and disease-bearing parasites. Like disease germs, the cancer cell has unlimited power of proliferation. And, again, as with microbes, this power increases in virulence as the cells are transplanted from animal to animal. If you inject a culture of typhoid bacteria into a guinea-pig, it grows at first only with moderation. If you take this culture from this guinea-pig and inject it into another, it reproduces more rapidly; and so on from animal to animal. As long as soil - or food - is provided, there is practically no limit to growth.

Cancer Cell the Anarchist of the Body

Cancer cells behave in practically the same way, and it is only in its marvelous reproductive capacity that cancer tissue materially differs from normal tissue. Under the microscope the cancer cell and the normal cell appear as virtu­ally the same thing. In our imagination we associate cancer with everything disgusting and horrible; looked at through the microscope, however, it is really very beautiful. It assumes millions of delicate, intricate forms, resembling hoar-frost in its fine network, its crystalline and constantly varying tracery. This tissue becomes a menace only because it has the power of persistent and unlimited growth. General body cells reproduce themselves only slightly: normal tissue is constantly wearing out, and new cells grow to take its place; the body cells, that is, reproduce only for regenerative purposes. One's thumb, for example, reaches a certain size and then stops; the tissue cells that compose it multiply only to replace wear and tear. If the cells did continuously proliferate, in a few years our thumbs would become several feet long; if all the body cells grew uninterrupt­edly we should all develop into frightful Brob­dingnagians. But a subtle influence, called by scientists the power of organization, super­vises this growth, keeps each member in check, and makes it develop symmetrically in accord­ance with the requirements of the body and the external world. But this power of organization has no influence upon the cancer cell. It is the anarchist of the body; it defies all laws, acknow­ledges no responsibilities - simply starts off on an absolutely aimless course of its own, and grows and grows and grows. It is normal tissue gone wild - running amuck. In clumsy fashion it reproduces the form, and sometimes the func­tions of the particular part of the body on which it starts. A cancer of the breast in women secretes a rudimentary case in; a cancer of the stomach has traces of the gastric juices; a cancer of the pancreas has vestiges of trypsin - the digestive fluid which the normal pancreas pro­vides; a cancer of the skin, like the skin itself, tends to hornify. So far as science can dis­cover, this cancer tissue in itself contains no death dealing properties. It simply grows and grows, digs down into surrounding tissue and frequently involves and destroys a bodily organ, such as the stomach or liver, which is indispensable to human life. In the large majority of cases, the unequal pressure upon the growing mass causes part of the cancer tissue to die, ulceration sets in, and the wound, like any other exposed wound, becomes infected with blood-poisoning bacteria. Cancer victims die, that is, not from any destructive toxin inherent in the cancer growth itself, but usually from toxemia.

Cancer Tissue Apparently Immortal

How tremendous is this capacity for growth the recent experiments on animals have for the first time made clear. In the early attempts there were only a small proportion of "takes." Thus, the first experimenters failed because they used only one or two, or, at most, a dozen animals. But one of the important facts learned is that, in the first transplantations, only a few animals, even of the same species, are susceptible to these grafts. Sometimes only one mouse in a hundred can be inoculated. At the Imperial Cancer Institute in London, a primary tumor has been transplanted nearly four hundred times without being made to grow on a single mouse. But after a naturally growing cancer has been transferred from the first animal into the second, it can be trans­planted much more readily into the third. Clinical observations long ago established the fact that any irritating interference with a cancer almost always stimulates its growth. In his earliest experiments Dr. Loeb found that, by merely drawing a silk thread through a dormant or slowly developing tumor, he could transform it into a rapidly growing one. Cutting with a knife produced the same effect. This accounts for the commonly observed fact that, when extirpated cancers in human beings recur, they increase in size much more rapidly than the original growth.

In 1902 Professor C. O. Jensen of Copen­hagen came into possession of a white mouse afflicted with a cancer on the mammary gland. He transplanted this into hundreds of other animals and sent them to all parts of the world - to Berlin, Frankfort, Paris, Rome, Tokyo, London, New York, Boston, Phila­delphia, and Buffalo. This tumor, which has been transplanted into hundreds of thousands of mice, has developed a most amazing viru­lence. It has been steadily growing for six years, and has already reached its one hun­dredth generation. Apparently nothing can stop it; from present indications it may be growing thousands of years hence. As long as it regularly receives soil and nourishment ­that is, animals to grow upon - it is immortal. Several tons have already accumulated. When we consider that two hundred mice can be inoculated from a piece no bigger than the tip of one's finger, and that each of these two hundred can in turn be used to inoculate two hundred more, its possibilities of growth are seen to be measurable only by the infinite. A single in­oculation, if transplanted as many times and into as many animals as possible, in a short time would consume, in its growth, all the earth's nitrogen. In a single year, according to an ingenious mathematical computation, it would attain a bulk eight hundred and ninety times larger than the sun and fill a space that it would take light one hundred and five years to trav­erse. And the amazing thing is that the un­countable cells that would make up this mass would all be lineal descendants of the cancer cells first found upon the little Copenhagen mouse. The scientist who today places under the microscope a Jensen tumor from any of the numerous laboratories in which they are growing, will find the structure of the cells to be identically the same. In all these transplantations they have not once taken on the character of the tissues of the animal in which they have grown, but have maintained their own individuality.

In the minds of some investigators, this power of endless growth strongly supports the theory that cancer is of parasitic origin. What gives cancer this inexhaustible vitality and this increasing virulence? Only life itself, they believe, could furnish such a stimulus; only in bacteria and parasitic organisms is anything found comparable with it. It is hardly worthwhile to treat in detail this vexed question. That cancer is contagious in the sense in which contagion is generally understood - that is, something readily transmissible through a micro­organism from individual to individual - no­body at present believes; that, however, a microorganism may be present, and, in some obscure, complex, roundabout fashion, may find its way from the sick to the well, many leading authorities, such as Borrel, of the Pasteur Institute, and Dr. Harvey R. Gaylord, of the Gratwick Laboratory at Buffalo, think en­tirely probable.

The Question of Heredity in Cancer

Results recently obtained in experimental breeding, however, indicate that cancer is hereditary - at least in mice. In the whole perplexing subject there has probably been no more controversial topic than this. Families in which cancer seems abnormally prevalent are familiar facts of every-day life. Several of these apparently cancerous families, the most notable being the Bonaparte’s, have figured in history. Napoleon himself died of cancer of the stomach, as did his father, his brother Lucien, and his sisters Caroline and Pauline. Among human beings, however, cancer is so common that any large family is almost certain to have its victims. On the other hand, the fact that when cancer is common in a family it almost always takes the same shape in all sufferers - the cancerous Bonaparte’s, for ex­ample, all dying of cancer of the stomach ­supports the popular idea that heredity is an important factor. Recent experiments at the Harvard Medical School, conducted by Dr. D. E. Tyzzer, tend to substantiate this impression.

Dr. Tyzzer found a female mouse with, a large growing tumor and mated her with a normal healthy mouse. In a short time this couple had one hundred descendants, all of which were kept under close observation. It takes about five months for a mouse to reach maturity ­reach the period, that is, when it becomes sus­ceptible to cancer. Mortality among the young animals is high, and of this brood, one hundred strong, thirty-five died of common mice in­fections before attaining mature age. Of the sixty-five that reached the cancerous period, twenty - developed natural tumors; of which they ultimately died. One in every three, in other words, fell victims to the mother's dis­ease. According to Dr. Bashford, of the British Cancer Institute, one out of every twenty-five hundred mice naturally develops cancer. Un­questionably the disease is far more common than this; but the frightful mortality among Dr. Tyzzer's one hundred mice can be explained only on the grounds of heredity. That the de­scendants of this cancerous parent inherited the disease outright, that the cancer cell or possibly a cancer parasite was directly transmitted from mother to offspring, does not necessarily follow. The tuberculous children of tuberculous parents inherit, not the disease, but a constitution es­pecially adaptable to it, and so these cancerous mice probably derive from their parent an in­creased susceptibility.

It was at the Buffalo Laboratory, under the direction of Dr. Gaylord and Dr. G. A. Clowes, that one of the most important modern dis­coveries concerning cancer was made. Because they believed that cancer was a contagious dis­ease, Drs. Gaylord and Clowes were led to in­vestigate the question of immunity.

Does Nature Ever Cure Cancer?

Medical science has now established one funda­mental fact: that, in practically all bacterial infections, the employment of drugs, as direct curatives, is virtually useless. No factor, ex­trinsic to the body itself, ever cured a human being of typhoid fever, diphtheria, tuberculosis, or any other bacterial disease. The really curative agency is this great physical power called immunity. This may be defined as the resistance manifested by the normal body to any extrinsic forces that seek to destroy it. The animal organism is not passive in the face of these attacks; when assailed it rouses itself and brings against the invader powerful though hitherto quiescent forces. For every body that assails it from without, it produces an anti-body within; for every toxin evolved by the invading bacteria, it produces its anti-toxin. Though these forces in some shape always exist within us, it is only when the specific disease appears that they manifest themselves in useful form. Thus, when the diphtheria toxin assails us, the body in turn manufactures its diphtheria anti­toxin to destroy it. If the patient recovers, these anti-toxins remain in the blood indefinitely - which explains why, when once we have rid ourselves of a specific contagious disease we seldom contract it again. Now, medical science, in its attempts to cure these infections, aims merely to assist nature herself - to repeat artificially nature's process. In many cases of diphtheria the afflicted body produces sufficient anti-toxins to destroy the disease, but in a large number of cases it fails, and death results. In order to assist nature in her work, the physician reinforces these anti-toxins with enormous quantities manufactured outside, usually in the body of a horse which has recovered from the disease, and whose blood therefore contains these properties. The modern method, that is, is to find out how nature herself cures the dis­ease and then attempt to do the same thing artificially.

In the minds of those who believed that cancer was contagious, the question naturally arose. Do the laws of immunity apply to it? When the cancer cell began its destructive work, did the human body lie supine and helpless, or did it attempt to throw it off? If so, did it ever succeed? In human cases, natural re­coveries from cancer were hardly known; this did not necessarily imply that the body mani­fested no resistance to it. Thirty years ago, tuberculosis was regarded as hopelessly in­curable; now we know that its cause is a specific microorganism; that the body manu­factures a natural resistance against it; and that, if attacked properly at the right time, it can be cured. In other words, nature herself can cure tuberculosis; when human ingenuity dis­covers the mechanism that it uses, and evolves some way of applying it artificially, this afflic­tion will cease to be a universal terror.

The question now arose with cancer. Does nature herself ever cure this malady? If so, do the general principles of immunity apply to it? If we recover from it once, can we ever have it again? If nature does resist it, will it be possible to discover and apply the principles according to which nature works?

Some Mice Can be Inoculated with Cancers, Others Not: Why?

In the early part of 1904, Dr. Gaylord, re­turning from a professional visit to Europe, brought back to this country two of Professor Jensen's cancerous mice. Both died on the train between New York and Buffalo, but, from the cancer of one of them, several hundred mice were ultimately inoculated. At this time the tumor possessed high virulence, and, of every one hundred animals in which it was trans­planted, sixty fell ill with the disease. Hitherto cancer investigators had all recorded the fact that a variable proportion of inoculated mice failed to develop tumors, but had attached no particular importance to it. When investigating the question of immunity, however, this initial circumstance might signify much. Here the experimenter injects one hundred mice of prac­tically the same size, age, and breed with iden­tically the same cancer cells; sixty contract the disease and forty do not. Why do these forty escape? Manifestly there must be an explana­tion; and this explanation must be found inside the animals themselves, inasmuch as the ex­trinsic conditions of the experiment were iden­tically the same in the one hundred cases. Did the forty mice that went through the experiment unharmed develop a natural resistance that destroyed the cancer cells and prevented their growth? Only experiment could show; mean­while it was sufficient to observe that precisely the same thing happened in diseases in which the laws of immunity appeared. If you in­jected  pure cultures of diphtheria germs into a hundred children, a large proportion would take the disease, while a few would escape. The immunity of the latter, that is, would be so powerful that the disease, even in its first stages, could make no headway.

In two years the Buffalo Laboratory inocu­lated 1,600 mice with the Jensen strain of tumor, and, of these, 1,250 proved absolutely resistant. The remaining 350 animals, in which cancers developed, were kept under the closest observa­tion. For this purpose, the Buffalo experi­menters evolved an ingenious method of keeping records. For each animal, in addition to elab­orate statistics, a separate chart was made. This represented a series of outline figures of a mouse, and upon these, at different intervals were drawn in silhouette pictures giving the shape and exact size of the growing tumor. Thus, after a few months, by glancing at these drawings, one saw precisely how the growth developed.

These records soon disclosed a momentous fact. While most of the cancers kept increasing in size until the animal died, a few clearly stopped growing, and others began to retrogress, in many cases diminishing to the vanishing-point. An inspection of the animals more graphically emphasized the same fact. In some the cancers grew as large as a hazelnut or an almond, and then slowly began to grow smaller. When they disappeared, they left absolutely no trace, not even a scar, and there was no recurrence. The skin and hair above the spot where this malignant tumor had been became white, glossy, and indistinguishable from the remaining surface. In the course of two years' observation it developed that about twenty per cent of all mouse cancers ultimately disappeared. In a few cases these were fairly large; in most instances they were quite small, perhaps an eighth of an inch in diameter. In other words, the smaller the tumor, the greater chance it had to become absorbed.

Cancer, in Principle, Is Not an Incurable Disease

What did this mean? Simply this: that can­cer was a curable disease; the destructive cells did not necessarily mean death. Clearly nature herself knew how to rid the animal body of this malignant growth. The presence of the cancer cell started into life certain forces that arose in all their might and threw off the incubus. These simple experiments for all time took human cancer out of the class of incurable dis­eases. Precisely how nature accomplished this work is not known now, may indeed never be known; the method may be too complex for the human mind to grasp: but, in principle, the disease can be mastered.

And now investigators began to recall certain incidents that had for years spasmodically figured in medical literature, but which had never received serious consideration. These were the stories of so-called "spontaneous cures" of cancer in human beings. Now and then for the last two hundred years practitioners have arisen in their local medical societies and entertained their colleagues with marvelous tales. A patient had fallen ill of malignant cancer; the growth had rapidly progressed; it had been cut out, and recurred; it had been ex­tirpated again, and again it had come back, and the patient at last had been hopelessly re­turned to his friends to die. A few months had passed, and lo! the cancer had entirely dis­appeared. The patient had become healthy and busy about his daily tasks. Learned medical societies usually howled down these picturesque anecdotes; the physician who countenanced them was discredited and sometimes absolutely disgraced. Dr. Gaylord's mice, however, proved that many of these stories were unquestionably true. Ask Dr. James Ewing of Cornell, Pro­fessor Ehrlich, Dr. E. H. Bashford, or any of the leading cancer experts, this question: "Do human beings ever spontaneously, recover from cancer?" and the answer is always a quiet "Yes. Dr. Gaylord, has ransacked medical literature for specific instances; and, amid a mass of more or less uncertain matter, has found fourteen cases concerning which there cannot be the slightest scientific doubt. Unquestion­ably there are thousands that are not recorded, and many more of which the medical profes­sion, and even the patients themselves, know nothing.

Perhaps Most of Us, at Some Time, Have Had Cancers

The mice experiments show that most re­coveries take place when the cancers are very small. Upon all of us little cancers may have appeared and then vanished without our know­ledge. Especially would this be the case if they attacked the internal organs, as they constantly do. Autopsies show, by the presence of little atrophied nodules, that nearly all human beings at some time have had tuberculosis and, in many cases, have recovered; perhaps likewise we have nearly all of us had cancer. In the case of cancer, autopsies would not disclose this, were it a fact, for, when the cancers disappear, they leave almost no trace.

If You Have Cancer Once, and Get Well, You Will Not Have It Again

Thus nature, in cancer as in diphtheria, starts forces that sometimes rid the body of the disease. And Dr. Gaylord and Dr. Clowes showed that the parallel extended further; in cancer, also, these new resisting forces remained in the animal and protected it against a second attack. If you have cancer once, and recover from it, you will almost never have it again! In other words, the great principle of immunity applies to this affliction as much as to measles, smallpox, and other contagious diseases. The animals in the Buffalo Laboratory that had spontaneously recovered were used for these further experiments, thirty mice that had spon­taneously recovered being inoculated again. In these no tumors deyeloped. Ten were inoculated a third time and still were adamant to the can­cer cell. Recent experiments, while not weaken­ing the general principle, have shown that immunity in cancer is not quite so constant as this. It is now found that a very small proportion of spontaneously recovered mice can be inocu­lated again; but that practically all that survive this second inoculation are proof against a third. Even in contagious diseases the immu­nity principle does not always work, instances not being uncommon in which one person may have the same disease twice in the same year.

This Buffalo demonstration of cancer immu­nity was so revolutionary that the medical world did not readily accept it. Dr. E. H. Bashford, the English expert, officially published his disbelief in the accuracy of the observations, and ex­plained in detail how Dr. Gaylord had made the mistake. The so-called regressing cancers, he said, were not cancers at all; they were merely little ulcerous swellings caused by the needle with which the inoculations had been made. In a few months, however, practically all the cancer laboratories in the world - in­cluding that of Dr. Bashford - had repeated the Buffalo experiments and confirmed them.

Immunity in Cancer Not the Same as in Bacterial Diseases

Clearly there was immunity in cancer; but was it of the same nature as that which exists in bacterial diseases? In these latter infections the molecules that destroy the destructive bacteria and their poisons exist in the serum, or the liquid part of the blood. Medical science cures diphtheria, dysentery, spinal meningitis, and sometimes tetanus by injecting the serum of an animal that has recovered from the dis­ease. The action of this serum is constant and well understood. It degenerates the bacteria in the diseased body, sometimes destroys them outright, and prepares them for final exter­mination within the white blood corpuscles. Does the serum of the recovered cancer patient have a similar effect upon the cancer cells? In order to answer this question, Dr. Gaylord in­jected the serum of spontaneously recovered mice into animals with large growing cancers. The first cases promised well, but subsequent experiments, in this country and in Europe, have not yielded similarly encouraging results. The leading investigators do not now believe that these immune properties are present in the serum. The immune serum does not act upon the cancer cell as does the immune serum in a bacterial disease; that is, it does not destroy the cancer cell or have much appreciable influence upon its growth.

No, natural protection and normal resistance against cancer exists, but it is different from anything known. The most trifling circum­stances frequently inhibit the growth of the cancer cell. How transplanted tumors grow only in animals of the same species, and how a transplantation cannot be made from a white rat to a gray rat, and vice versa, has already been described. Moreover, in many cases cancers can be transplanted from one mouse only to another mouse of the same color and species and living in the same locality. Thus it has been found that Berlin white mice will take tumors that have grown on other Berlin white mice, but that Christiania white mice will not. These and other facts make it clear that, while a definite immunity has been established, it is something more delicate, more subtle, more illusive than anything hitherto known.

To the lay mind, the demonstration of im­munity in cancer would seem an added indication that the disease must be contagious. According to the scientist, however, this does not necessarily follow. The point involves too many technicalities for discussion in this place; it is well known, however, that immunity re­actions exist toward other extrinsic forces than microbic infections.

Animals Can be Vaccinated Against Cancer

When the law according to which this immu­nity works is discovered the solution of the cancer problem will be finally in hand. Mean­while, though the things learned so far are of the utmost importance, they cannot yet be put to practical use. Thus Ehrlich has demon­strated, as a principle, that animals, and prob­ably human beings, can be vaccinated against cancer. He inoculates a mouse with a weak strain, a new tumor grows, and in the majority of cases it retrogresses. The mouse is then proof against inoculation with more malignant strains. The difficulty, however, is that, in order to secure protection, an original tumor must de­velop, and, in a small proportion of cases, this does not regress, but becomes malignant and kills the animal. If we used this system of vaccina­tion with men and women, therefore, we should kill a considerable percentage of all those treated.

Dogs Can be Cured of Cancer

Though we cannot cure cancer in human beings, we can cure it in dogs. Among these animals a particular cancerous growth, known technically as a lymphosarcoma is a virtual scourge. It is especially prevalent among high-bred animals, aristocratic bulldogs, pet span­iels and the like, though also frequent among common breeds. Though not infectious in the technical sense, it has a certain analogy to infectious disease, which fact has led Dr. Bashford, the English expert, to deny that it is a cancer at all. All the leading Ger­man, French, and American investigators to­tally disagree with him; microscopic exam­ination, as well as its method of growth and transplantation, clearly demonstrates its can­cerous nature. Dr. James Ewing, Professor of Pathology at Cornell University, has studied this tumor thoroughly, and definitely proved that it is a cancer. It was at the Loomis Laboratory, through experiments conducted by Dr. S. P. Beebe and Dr. George W. Crile, of Cleveland, that its curability was demonstrated.

At these experiments nine dogs in succession were cured of malignant growths and restored to normal health. The experimenters accom­plished this result simply by transfusing into the diseased animals the blood of other dogs that were demonstrated to be immune to this type of cancer. They inoculated a consider­able number of dogs; in some the tumor de­veloped and in others it failed to do so. The latter were therefore regarded as resistant to the disease. After the growth had gained marked headway and the patients manifested nearly all the symptoms of cancer in its last stages, practically all the blood in their bodies was drained off. In its place was transfused the blood of animals which had proved resistant to inoculation. In nine out of ten cases the sick dogs got well; their tumors entirely dis­appeared, their condition became normal, and their own blood could then be used to affect similar cures. These experiments seem to in­dicate that, while the immune properties in cancer are not found in the serum when it is separated from the blood, they may be found when the whole body of the blood is used. An­other explanation is that the blood of the dis­eased animal contained nourishment especially adaptable to the cancer cell, and that when this was withdrawn the cancer cell was virtually deprived of its food. On the other hand, the blood of the second animal furnished no nour­ishment to the cancer, as evidenced by the fact that, after the inoculation of the growth, it failed to develop. When this blood therefore, was transfused into the body of the diseased dog it supplied wholesome nourishment to his normal tissues, but absolutely none to the cancer cells, which consequently atrophied and disappeared.

For dogs afflicted with this particular tumor science has thus discovered that great medical desideratum - an actual cure for cancer. In the course of the writer's visit to the Buffalo Laboratory, a large, fine, valuable English bulldog was brought in fearfully afflicted with this disease; the treatment was at once begun, and in a few weeks he will unquestionably be sent back entirely well. Whether dogs suffer­ing from other forms of malignant tumor can he similarly cured is not- known, inasmuch as this lymphosarcoma is the only type with which they can be inoculated. It is impossible to repeat the experiment on mice, because their veins and arteries are so small and delicate that blood transfusions cannot be made. With human beings the reproduction of the con­ditions of the experiment is absolutely im­possible. We should be compelled to bring together two individuals, one suffering from a particular type of cancer and one who had spontaneously recovered from identically the same affliction. For practical purposes it would be impossible to accomplish this, and the ex­periments, therefore, outside of their practical importance in restoring suffering dogs to health, are interesting chiefly for the new light which they shed upon the general problem, and for the additional demonstration that cancer, in itself, is not incurable.

All the facts described above, indeed, have placed the question upon an entirely new foot­ing. Medical science is now on tiptoe in the face of this problem. Everything is expecta­tion. The important facts already learned have only stimulated the desire for more. After finding out so many things, it is not likely that experimental science has reached its limit. No new fact about cancer would now surprise the medical world. No one has yet succeeded in assimilating all these new facts, in placing them in their proper sequence and wringing from them the great generalization that will yield the secret. But then, the experimental science of cancer is really less than ten years old. This malady is by no means so mysterious to the present generation as were the common contagious diseases to our grandfathers. It was not until that wonderful genius, Louis Pasteur, brushed away the superstitions and absurdities of three thousand years and showed the cause of these infections, that modern medical science and modern sanitation began. That some similarly penetrating mind - perhaps it is at work even now in some obscure pathological laboratory - will penetrate the meaning of all the recently discovered facts is the general expectation. The age-long pessimism has disappeared. Sci­entists now know that, in the usual sense of the term, cancer is not contagious. They know that heredity plays an important part in its development. Above everything else, they know what ten years ago they would hardly have dared to imagine: That cancer is not neces­sarily an incurable disease; that animals and human beings have it and spontaneously get well. They know that nature has her own method of curing it, that the great principles of immunity are applicable to it, and that under­lying all these facts is some broad general law which, when unearthed, will bring relief to hundreds of thousands of sufferers.

Originally published in McClure’s Magazine in July of 1909.

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