It may be safely said that no disease which has afflicted mankind has received as much attention as Cancer, or concerning which there has been as much diligent search to find out its nature and cause. Tuberculosis, which seemed at one time to threaten even the existence of the race, has sunk into relative significance, as we have learned its true nature and conquered some of the causes of its ravages, and reduced its mortality very largely. Syphilis, under various names, forms, and aspects, was formerly much more of a menace than now, and in earlier years caused veritable epidemics, but is now well understood and controlled. Leprosy is less of a terror than in earlier times, since it has been definitely shown not to be contagious. Smallpox no longer rages, and yellow fever, and the plague, and hook worm disease have been hunted down by scientific study and the application of proper sanitary and medical measures. And so on in regard to many of the ills which afflict mankind.
But cancer has held its own and has even increased in frequency, with rapid strides and bounds in some localities, until now it looms large as a national[1] or even universal scourge; it has been estimated to cause the death of half a million persons yearly among the civilized people of the earth, and untold misery and suffering to many times this number. And all this is still going on in spite of the earnest, faithful, and intelligent labors of innumerable research workers, the sacrifice of countless animal lives, and the expenditure of vast sums of money; and the end, as far as relates to its prevention and cure, seems almost as far away as ever, for many surgeons, in past and present times, have acknowledged their inability to cope with the disease.
Much, however, has already been established by scientific research, and still more earnest thought, observation, and endeavor should be given to seeking most diligently for the cause of the disease, in the laboratory as well as in practice; for there must be some cause of cancer, and also some reason for its steady increase.
But it is never to be forgotten that, as Pope says, “the proper study of mankind is man,” and clinical observation, with laboratory research, on cancer as it appears in the human being, must be the ultimate base upon which all true advance in the knowledge of the nature, treatment, and prevention of the malady can ever rest. To effect this we must study the human being in all relations of life, must know the constitution and class of subjects in which the disease is most apt to manifest itself, understand the chemico-physiologic actions going on in the system, before and during the existence of the disease, and by a process of synthesis and deduction understand what is wrong and endeavor to correct it.
All this is indeed a great undertaking, and can only be accomplished by great effort on the part of many careful and skilled observers. But I want, in these lectures, to give you an outline of my own thought and study for many years, and, if possible, to let you see as I do the lines along which investigation should be directed. It is hoped, therefore, that this and the following lectures will throw some light on the connection of cancer with diet and mode of life, and some suggestions as to its prevention and cure.
Parasitism has been excluded: for while at different times many observers have reported various organisms which were thought to be the cause of malignant growths, none of these have been definitely confirmed by others, in spite of earnest endeavor; and all experimental and clinical evidence is against a parasitic etiology of cancer. It is therefore seen how improper it is to speak any longer of “the germ of cancer,” for, as is now widely acknowledged, there is no such germ, it is an ignis fatuus which has been chased in vain.
The contagiousness of cancer has also been excluded, certainly in the sense in which this term is applied to other affections. For while in some animals inoculation experiments have resulted in the transmission of certain tumors, little has been determined except that such tumor material when transplanted can, in some unknown manner, multiply its cells indefinitely and form a focus of malignant disease, with disastrous effects on adjoining tissue. The same occurs in metastasis in cancer patients. But this does not at all explain the true basic nature of cancer, nor its development in those who have had no connection with other patients so afflicted. On the other hand the instances of suggested or supposed human transmission of cancer from one individual to another are so remarkably few, and so exceedingly doubtful, that a recent author, Janeway, states that “no well-authenticated cases of the transfer of a malignant tumor from one human being to another exist.” It has been found impossible to inoculate human cancer into rats, mice, and apes, nor can animal tumors be inoculated into animals of a different species.
Heredity has been advanced as a cause, but statistics fail to verify this in any degree whatever. While certain instances have been brought forward in which heredity seemed evident, the study of large numbers of those afflicted with cancer, in connection with others free from the disease, has shown almost the same proportion of antecedents with cancer in both classes of persons; although some recent evidence seems to show that there is some tendency in different families for different organs. Experimental studies have, it is true, seemed to demonstrate that tumors occur apparently along hereditary lines in some animals in regard to certain organs; but in these instances it is to be remembered that the animals were kept in captivity, and all fed alike, conditions which have been found to cause the development of malignant disease in wild animals when confined in Zoölogical Gardens.
In former years malaria was believed to have an influence in the production of cancer, and some investigators have thought to trace the prevalence of the disease to telluric influences, showing a preponderance of cases along certain water courses, or in certain streets or houses; but no definite proof of such connection has ever been established, and this theory is dismissed by the best authorities. Syphilis, in its latent effects, has also been claimed as an element in the causation of cancer, and undoubtedly the disease may develop, in suitable persons, upon old syphilitic lesions, especially about the mouth, anus, and genital region: but no one well informed in regard to cancer would regard syphilis as the real cause of the disease. All these and other etiological propositions are no longer considered to be tenable, and the very multiplicity of suggested causes shows that we are yet very far from the true etiology of cancer.
Age undoubtedly has a powerful influence in the development of cancer, the vast majority of cases occurring after the age of forty or fifty. But, again, this does not at all explain the true nature of the disease, for only a certain proportion of elderly people are so afflicted, and malignant tumors have been observed in those of all ages, and even in young children. The degeneration of tissue belonging to advancing years undoubtedly renders it more susceptible to malignant disease, but this does not explain why one person is affected and not another, nor why the tissues in one locality or another take on this morbid action.
More recent scientific study has attempted to show that cancer originates from what are called “embryonic rests,” or pre-natal, wrongly placed, tissue elements, which at some time or other take on morbid action and develop into what we know as the various forms of cancer. Williams says, “From a biological standpoint tumor formation must be regarded as a phenomenon of the same order as reproduction in general: that is to say, as a special form of overgrowth of the individual.” But here again it is necessary to determine what causes them at certain times and in certain places to thus proliferate and form new tissue, which then becomes malignant and may proceed to destroy all contiguous tissues, and even to cause death.
Traumatism has been claimed by many as the cause which determines the activity of the misplaced cells, and starts them on their disastrous or rampant course: the various percentages of the cases in which it was believed that traumatism started up the malignant process has varied greatly with different observers, even up to 50 per cent, or more. But it is far from proven that this is always the case, nor does local injury in any way explain the persistency with which malignant disease, when once started, pursues its destructive and even fatal career; nor can traumatism account for the great tendency to recurrence constantly observed, either in the former site or at some distant focus, through the agency of the lymphatic or vascular system. For of multitudinous traumatisms, even in cancer subjects, how few ever develop into malignant disease!
It would seem, therefore, that for the development of the local manifestation of cancer (the tumor or new growth) three elements are requisite, namely: 1. A predisposition or suitable blood condition. 2. A local stimulation or irritation of the part affected, upon, 3. The site of an “embryonic rest.”
On the basis of the embryonic theory surgeons have of late most earnestly advocated the very early and complete removal of malignant lesions, including those of suspected malignancy, and even also the removal of many innocent lesions which are observed occasionally to lead to cancerous formation; and unless a better plan can be determined this cannot be urged too strongly in proper cases.
But while early operation has improved surgical statistics, it has not contributed to our real knowledge of the basic cause of cancer, nor has it taught us why those lesions or “embryonic rests” will remain quiescent for years, or prove harmless in some individuals, while in others they become most formidable agents of destruction. For it is now recognized that these wrongly placed tissue elements are very common anatomical or histological accidents, indeed it is claimed that they occur and exist in every individual: and the removal of isolated “embryonic rests” which have developed into cancer, does not by any means prevent the transformation of other similarly misplaced cells into malignant disease, as the frequent recurrence of cancer after operation demonstrates.
The same is true of the many and various forms of treatment other than surgical excision, such as deep acting caustics, and even the X-ray and radium, which like surgery, only remove the focus of possible systemic infection, and do not affect the basic cause of the complaint: this latter is being shown more and more, by scientific investigation and observation, to be associated with metabolic or chemico-physiological changes in the system, and evidence is accumulating that it is dependent upon them.
All this leads thoughtful persons to inquire if there is not some deeper, fundamental cause lying back of the trouble, which should be reached and rectified by medical skill and acumen, something to do with the life or diet of a person which renders the tissues liable to take on malignant disease. So that a recent surgical writer on cancer states that “all study, whether clinical, pathological, or experimental, points to the fact that there is some underlying, hidden cause which leads to that aberration in the action of tissue cells which we call cancer,” ... a cause “residing in only the cells themselves or in some abnormal chemical constitution of the plasma bathing the cells, or in both of these possibilities acting together.”
Occupation has been questioned, but with most unsatisfactory results, for in some statistics which have been gathered cancer has been observed in those following all possible pursuits: and while laborers stood first on the list, clergymen stood fourth, while carters, threshers, and guides, who would be exposed to local injury, were at the bottom of a long list. It has been found, however, to be more frequent in trades or occupations in which the individual is most subject to the habitual abuse of alcoholics, as in bartenders, printers, etc.
We see, then, that thus far no satisfactory cause has been established for the occurrence of cancer, much less for the steady and great increase of the disease of late years. And as far as can be learned, no measures are recognized, or at least generally adopted, to prevent its occurrence or recurrence; although, as already stated, modern surgery has seemed to improve the statistics in regard to its mortality in certain forms or locations, and the X-ray and radium have certainly also been able to remove, perhaps temporarily, some of the products of the disease.
We come then to the question, what is the real nature of cancer? Alas, all scientific, experimental, and clinical investigations have failed to solve the problem, except that all “evidence points to the conclusion that cancer is to be considered as a pathological disturbance of the normal cell life,” from some unknown cause. A curious suggestion has been made by Schmidt, who found that of 241 cases of cancer of the chylopoietic system, 180 had never had any infectious disease of childhood, and 99 went through life without any infection of any kind; the figures point to the existence of a cancer diathesis—one which is resistent to germs.
It would carry us too far from the practical side of our subject, even if we were at all able, to present or analyze the vast number of contributions which have been made to the pathological histology of cancer, and the changes which take place in the transformation of normal cells into those of malignant character: the amount of microscopic work which has been done along this line can hardly be imagined, and the literature relating to it is enormous.
Ewing, accepting the definition that the cancer process is “atypical and destructive proliferation of epithelium,” quotes Ribert as saying that “no one has ever seen the beginnings of mammary cancer”: but he does not bring us much nearer to the solution of the cancer problem than we were before. Bainbridge rejects all possibility of a blood condition, and finds the only solution of it in the early removal of everything which is thought to lead to cancer, even the simplest benign new formations, but Ewing states that “in some cases carcinoma has developed after excision of wholly benign fibro-adenoma”: and the immense number of cases of recurrent cancer after operations shows that we must look further than surgery if we wish to stay the progress of this formidable disease.
It would be useless to attempt to present the many theories which have been advanced relating to cellular metaplasia, or even to detail all the more or less accepted views in regard to the manner in which normal cells change and degenerate into those of malignant character: but some of the principal facts may be of service in understanding somewhat of the mode of development of malignant tissue from that which has been normal.
The statement of Virchow, “Omnis cellula e cellula,” that is, “where a cell arises there a cell must have previously existed, just as an animal can spring only from an animal and a plant from a plant,” forms the basis of all study on the genesis of cancer and all tumor formation; karyokinesis, or indirect nuclear or cell division, is at the bottom of all growth, both normal and malignant, and the two classes of growth differ only in their methods and activity. In healthy tissues cell proliferation and destruction proceed in an orderly manner, forming homologous structures, as when the hair and nails are constantly produced from newly formed cells at the root, and the result of this new growth is removed mechanically when the hair and nails are cut from time to time, or the hairs fall out. In the case of the skin the epidermal layers are pushed forward and finally exfoliated as useless epithelial débris.
With the cells composing other, or internal structures, however, the process is different. For here each normal cell reproduces others of homologous structure, and the different parts of the system are thus kept in active service through anabolism, by means of which new cells are formed with renewed vitality, and the older, or effete cells are removed by catabolism; the elements of which they are composed are thus split up into their component parts, and carried off by the blood or lymph stream, and are then either discharged as effete substances or reutilized in the system, along physiological lines. Wakefield has pretty clearly shown that the developing cancer cell is the product of sub-catabolism, or a sub-oxygenation, induced by hyperacidity or oxidase deficiency in the surrounding medium of the blood plasma.
A great deal of thought, study, and speculation have been given in regard to the behavior of the cells themselves, and strong arguments are adduced for a local cell pathology, that is, regarding the cells as “autonomous beings, possessed of morphological and physiological independence.” But on the other hand we must recognize some restraining influence which continually causes the great mass of cells to reproduce those of homologous structure, in an orderly manner, and only very rarely some of them to break loose and form tumors, which may then become malignant and even destroy life. How this restraining influence is modified or withdrawn is, of course, a part of the problem of cancer. Those who maintain their autogenous character lay great stress upon the polarity of cells, and the relation of the centrosome to the nucleus, indicating a change in the polar axis in cells about to be cancer-genetic, as does Ewing in his recent classical study of pre-cancerous lesions. But whatever changes are observed microscopically we must recognize that the cells themselves must be influenced ultimately by that mysterious force which we call life, which ends with its extinction from the body as a whole, and which is ultimately related to nerve action. We must also recognize that the cells everywhere depend for their life and activity upon the plasma in which they are bathed and from whence they draw their sustenance; and this plasma is renewed day by day from the food and drink taken.
Students of cancer are more and more recognizing and acknowledging that “all these phenomena, apparently so different, are merely protean manifestations of one common process which underlies and is the cause of them all, to wit, cell growth and proliferation. The particular outcome of the process in any given case is due to the influence of the conditions of nutrition—understanding by this term the whole of the material changes wrought in the organism through its relation with the surrounding world. This being so it is easy to understand how, under favorable conditions, certain cells may take on independent action, growing and multiplying without regard to the requirements of adjacent tissues and of the organism as a whole.”
There seems to be some reason to support the view advocated by Williams, that tumor formation and growth are but forms of agamogenesis, or non-sexual reproduction of cells, distinctly related to the decline in growth of the body in general. Hence while the forces of growth, development, and reproduction are in greatest activity the tendency to this disease is relatively small: but when growth declines and nutrition is relatively low the cells undergo gemmation, owing to perverted nutriment, and thus hyperplasia and not inflammation is the starting point of every neoplasm.
Experimental work has time and again demonstrated that cell growth, either good or bad, is modified in no uncertain way by the character of the nutrition furnished. Cancer has repeatedly been observed to disappear spontaneously, as such cases are on record by careful and competent medical men: in certain of these instances it has occurred in connection with a radical change in the mode of life and diet, but in the majority of instances there is no record of the special cause of its disappearance. The lesson to be learned from this is that there are conditions of the system which are antagonistic to the abnormal proliferation of cell tissue, even when it has begun to take place, as we must believe that there are other conditions of the system which favor such diseased action of aberrant cells.
An interesting confirmation of this is attributed to Ehrlich, but I cannot find the original reference. He “has shown that mice living upon a rice diet cannot be inoculated with cancer, while mice living on a meat diet can be readily inoculated, cancerous tumors developing quickly and continuing to grow until the animal dies. Ehrlich also found that when mice with cancerous tumors, the result of inoculation, were placed upon a rice diet, the tumors ceased to grow, and in many cases degenerated and disappeared.” Valuable corroboration of this has been given by Sweet, Corson, White, and Saxon. They made a series of experiments in regard to the “influence of certain diets upon the growth of experimental tumors,” all with the same results. Of fifty white mice, 25 fed on glutenin and gliadin, and 25 on normal diet, 23 of the 25 on normal diet acquired tumors, against only 4 in the 25 on the glutenin and gliadin. This was repeated on 50 males, with the result of 18 in 25 against 3 in 25: and in a third series, of 50 females, the figures were 15 in 25 against 7 in 25. Thus, they found that 75 per cent. of 75 mice developed experimentally inoculated tumors when under normal diet, while only 19 per cent. of other 75 mice developed such tumors when under a diet of glutenin and gliadin, that is, vegetable proteins; moreover, the tumors in the latter were in 30 days hardly larger than those in the former in 10 days. Rous has recently shown that large growths of certain transplanted rat and mouse tumors are checked in their development by underfeeding the host on a special diet.
The chemistry of cancer has been studied in most varied directions, and the literature relating thereto is very voluminous and can be hardly more than alluded to here. It is unfortunate, however, that most of the researches have been made in connection with patients who have advanced cancer, and very commonly with the disease affecting internal organs, which of itself interferes very greatly with their function, and so causes many of the perturbations of metabolism observed. What is needed are researches in regard to the metabolism of patients before the development of the disease, or in its earlier stages, before it has exerted its injurious effects on the system, in order to learn of the causes which lead up to and induce the wrong action of the cellular elements, whose invasion and malignant action subsequently become so serious.
It is quite impossible in these lectures to enter at all fully upon the various bio-chemical studies which have been carried on in regard to cancer, but brief mention will be shortly made of some of the salient points. Not only has the structure of carcinomatous tissue been examined chemically, but the blood and urine have been submitted to most painstaking investigation, and metabolism in general has been studied in almost all possible directions, in the search for the cause of cancer; and yet, as Beebe says, “no phase of metabolism has been described in cancer which does not have a counterpart in non-cancerous conditions.” But, as previously mentioned, all these observations and studies have been largely made upon advanced cancer cases, when the system has already felt the unsettling and depressing effect of what is probably an injurious secretion from the deranged and actively proliferating cells of the cancerous mass. In a later lecture we will consider some of these matters in so far as they have relation to the dietetic and medical treatment of cancer.
The essence of our study thus far has been, that in every instance what is called malignant disease is but an aberrant action of originally normal body cells. That, as normal cells find their nutriment in the circulating plasma, so some pathological change in this latter causes them to take on abnormal action, and they no longer develop homologous cells, capable of forming normal tissue, but heterologous elements which have a natural tendency to disintegrate or break down, and exert a destructive influence on adjoining cells of any kind; and in this process they secrete a hormone which is prejudicial to the system and tends to destroy life. In later lectures we shall endeavor to understand this more perfectly, and consider some of the elements in life which tend towards the production and arrest of cancer.