Columbia ®mber£ttp in tfje Citj> of Jleto gorfe COLLEGE OF PHYSICIANS AND SURGEONS Reference Library Given by •~^_2^sl*j^***-JKh Digitized by the Internet Archive in 2010 with funding from Open Knowledge Commons http://www.archive.org/details/problemofcanceroOOsavi THE PROBLEM OF GANGER OR THE PHILOSOPHY OF MALIGNANGY BY EUGENE COLEMAN SAVIDGE Member New York Academy of Medicine, New York Obstetrical Society, American Medical Association, New York State Medical Society, Society Alumni Roosevelt Hospital, and Sloane Hospital for Women; former Ass't Gynecologist, Roosevelt Hos- pital (O.P.D.); former Attending Gynecologist, St. Mark's Hospital; author of "The Philo- sophy of Radio - Activity, " "Un- classified Diseases, or The Pro- longation of Life," etc. Press of WILLIAM R. JENKINS COMPANY Sixth Avenue at 48th Street New York T^HE limited first edition of this work has not been placed on sale, but sent to those inter- ested in this subject. The publishers announce a second edition as soon .as suggestions from the laboratories and re- views enable the author to arrange it. Copyright, 1915 By Eugene Coleman Savidge All Fights Reserved PREFACE "This march of antecedents, in cancer has formed an intensely interesting chapter in my line of special study. For fifteen years I have been cautiously insinuating under the notice of the profession discussion of many minor and detached matters, that the thus printed word might b used in presenting an entirely new system of approach in medicine. This I have called "Synthetical Medicine," and have published in the Medical Record, April 7, 1906." Extract from paper read before New York Academy of Medicine Section, March 26, ipo8. April 10, 1914, The American Society for the Control of Cancer held its second meeting at the New York Academy of Medicine. Dr. Clement Cleveland presided, and the speakers were Dr. William J. Mayo, President of the American Surgical Association; Mr. Frederick C. Hoffman, Life Insurance statistical expert; Dr. Francis Car- ter Wood, Director of the George Crocker Re- search Laboratory, and Prof. J. Collins Warren, President of the Harvard Cancer Commission. 3 4 THE CANCER PROBLEM Briefly stated, the dictum of this recent and au- thoritative body stands: "Surgery will cure PRACTICALLY ALL MALIGNANCY IF ACTION IS TAKEN AT THE START; SURGERY IS THEREFORE ALWAYS FIRST,* OTHER MEASURES SECOND." May 24, 1914, The Cornell Cancer Report, referred to later in these pages, was also made be- fore the New York Academy of Medicine. October, 1914, Bainbridge published a book re- viewing fully the knowledge of the world on the subject to date. By the test that none of it was mentioned in this latest book, or in these two recent and authoritative meetings, the matter contained in this ?ketch is ori- ginal — or useless. As this MS. was practically cut from "The Phi- losophy of Radio- Activity" — as encumbering the pages of a philosophical formula, though closely related — what follows is in connection with the matter contained in that work. A DEFINITION OF CANCER By James Ewing, Professor of Pathology, Cornell Medical College, in The New York Medical Record, December 5, 1914: "Probably the best definition of the cancer process is 'atypical and destructive proliferation of epithelium.' Yet many well known forms of cancer fail to meet these re- quirements and it becomes necessary to analyze the process in much greater detail in order to admit many malignant diseases into the cancer category. This analysis requires the recognition of. at least the following criteria of a ma- lignant process: (1) Cellular overgrowth passing beyond that observed in other processes affecting the same tissue ; (2) atypical qualities of the cells, metaplasia, anaplasia; (3) loss of polarity; (4) hereterotopia ; (5) desmoplastic properties; (6) local invasive and destructive properties; (7) metastases. It will be observed that in each of these characters variations in degree are conceivable and, as a matter of fact, they are commonly observed to occur. Any one of the above attributes of cancer may be almost exclusively represented in the disease. Excessive cellular overgrowth difficult to distinguish from a physiological type chiefly characterizes some thyroid cancers. Atypical qualities of the cells are the only safe criteria of early malig- nant papilloma of the larynx. Loss of polarity is the chief 6 PROBLEM OF CANCER feature of certain large alveolar mammary carcinomas con- fined within ducts. A pronounced fibrosis about slightly altered prostatic alveoli was the most definite feature of a fatal case of prostatic cancer which I have recently studied. Local invasive and destructive properties first reveal the beginnings of some lymphosarcomas. Distant metastases are the chief evidence of malignancy in the peculiar thyroid cancers previously mentioned. Hence the diagnosis of cancer becomes a matter of judgment as to the significance of any one or all of the above features that may be com- bined in any one cancer. The disease is not always one and the same thing. On the contrary, it is a progressive proc- ess which has small and variable beginnings and unfolds more and more of its features as it advances to a fatal is- sue. It is from this point of view that the significance of precancerous lesions must be regarded. From this stand- point such lesions may be defined as pathological proc- esses which show some, but not all, of the structural fea- tures which characterize fully established cancers of the affected organ." THE PROBLEM OF CANCER; or THE PHILOSOPHY OF MALIGNANCY I Malignancy and monstrosity arise from re- inforcements AND INTERFERENCES WHICH AC- COMPANY THE SELECTIVE INVOLUTION AND EVOLU- TION OF MATTER AND LIFE. The cause of cancer and the cure of cancer, per se, probably will never be found. For cancer, together with all the other malignancies, is a series of processes, and not a well denned entity. To call epithelioma of the face, carcinoma of the stomach, and bone-marrow myeloma, the same process, or the same disease, is "not to know medicine." These processes have a common factor, malig- nancy. And malignancy is the result of molecular activities which may be studied with a hope of controlling them. But this does not mean that we may ever find a causing germ or a curative juice. It does, however, contradict our opening statement to this extent: In the conviction of the writer, a 8 THE CANCER PROBLEM profound study of the basal elements of life will show us two important things : ( 1 ) What sub-com- ponent elements are fading when malignancy is entered upon; (2) where and how we may prop this faltering sub-component, when we have learned a single process of differentiation beyond our present equipment of knowledge. Therefore, though we may never find the cause of cancer, some of its causes are already apparent. This sketch presumes, therefore, simply to point out this single missing process, and to give some hints by which the workers — more capable than the writer — may find it, if it is ever to be found. Hence it is desirable to exclude the vast bulk of knowledge gathered on the subject (as yet to scant purpose), and to focus on the single missing proc- ess which stands between us and the goal of the whole professional world. It is remarkable how quickly radium cures can- cers produced by the X-ray. If radium and the X-ray, respectively, cure some cancers and cause some cancers, it is obviously a question of dosage; a question of intra-atomic, or intra-molecular, rein- forcement and interference which we do at hap- hazard, as yet; sometimes reinforcing the right, sometimes the wrong, entity within the organism. OR THE PHILOSOPHY OF MALIGNANCY 9 If the radium cures the X-ray hurt readily, of course we have implied a different set of interfer- ences and reinforcements in the radium from those in the X-ray ; and here, precisely, is a point whereat the expert may reach an important lead. He is already able to screen off the different rays of radium and deflect them with magnets. A tabu- lated dosage of the different rays, and their wave- lengths — with a corresponding table of biological sub-components needing their application — may put humanity under lasting obligation. What, briefly and suggestively only, is the ex- cuse for adding more printing to this over-written subject? A new view for which the writer has tried to show authorities and reasons in his "The Philosophy of Radio- Activity." He will try to show, in the form of sketch and diagram: (1) The sub-components of the radio-active processes; their equilibrium; the laws of reinforce- ment and interference by which equilibrium is turned from side to side; and the resulting radio- activity, with its light and color, and "hemolyzing" differences. (2) The reinforcements and interferences in bi- ology — by selective and conjoined cytolysis, by hemolysis, by anaphylaxis, by differentiations of 10 THE CANCER PROBLEM tissue, by sex differentiations — by force of which life and evolution have proceeded. (3) The relation between the sub-components of the radial processes and the biological sub-com- ponents, by which form and mass, proportion and life, as well as monstrosity and malignancy, are controlled. (4) Thereby putting the main problems in the focus of the attention of the experts — who have already compassed marvels more than equalling the solving of these. II The Radial Forces and their Sub-Components. Again referring to elaborations in "The Phi- losophy of Radio- Activity," intra-atomic activi- ties were thus described: "Negative electrons rotate around the positive center of an atom in mutually conserving antag- onism until an appointed time brings a fractional violation of ratio, when an explosion liberates an atom of helium, and a new ratio is established for a new rhythm. The duration before the explosion probably marks the life span of an electron, or a sub-electron factor." The appointed time is accented. The mathe- matical progression is also accented. Each step down the line of transformations is by a subtrac- tion of four from the atomic weight of the pre- ceding. There is therefore a time element and a mathematical element. Biology is based on time, and connected with the solar rhythm through the gland cycle in the higher species. Monstrosity and malignancy are violations 11 12 THE CANCER PROBLEM of mass, form, time : but they have their own math- ematics and their own appointed times. Only a few of these are known. For example, Ordway claims that the transmission of cancer to other parts from the original growth occurs uniformly on the thirty-ninth day, in the Japanese mouse. The mathematics of infinitesimal fractions of duration are now well understood in the physical sciences, and they are used in daily routine to de- termine the nature of substances. No one now marvels at spectroscopic identities, some of which are based upon a velocity as high as 800 million millions of vibrations per second. For example, the alkaloids of plants have their readiest identity by means of the spectroscope. Each plant essence, of those studied, has its known lines. Each cell sub-component of each of these plants, therefore, must have a syntonism with lines in the spectrum which is invariable and as eternally con- stant as mathematics.* *The spectroscopic constancy of the alkaloid implies a similar constancy in the animal cell "essences." I do not know that any one has studied the possibility of changing the alkaloid's spectrum by the Luther Burkank method of grafts. If animal cell "essences" like the alkaloids have constant spectra, breed mixing like plant grafting should alter them. It would be easy to compare the spectra of the tissue and germinal cell "essences," respectively, of a white mother, and her half-negro child. Any cell sub-component that we may identify and influence is 21 step toward our purpose. CR THE PHILOSOPHY OF MALIGNANCY 13 If the comparatively few plants whose alkaloids are known are thus mathematically fitted to sub- components in the spectrum, there must surely be other biological identities. It may be safely as- serted that there is a syntonism between the spec- trum lines and the sub-components of each cell in organic life. The spectrum of radium — "the strong new line in the ultra-violet" — was unknown until the discovery of radium. So there is a math- ematical identity for the normal cell sub-compo- nents, and there is a mathematical identity for the sub-components of the malignant cell, and there is a difference between them which represents either a reinforcement or an interference with one or more of the sub-components. The diagrams (see page 53) which show the probable action upon a single rudimentary chromosome, in the fixing of sex, will illustrate the concept of the play of forces upon a single element in a cell — to make it benign or malignant. This is precisely what radium does, when we apply it at haphazard and "it cures some cancers and causes some cancers." And whoever fits these cell lines to the lines of the sub-components of radium will, perhaps, solve malignancy. The new concept of the atom, and the new know- ledge of intra-atomic activities, make the sub-com- ponent all important. For it is the change in the 14 THE CANCER PROBLEM sub-component which overturns equilibrium and transforms the element; in short, which gives rise to all the wonders of radio-activity. May we identify the sub-component? May we learn what determines or selects the special a-par- ticle from the revolving electrons to escape from the radio-active substance, and thus transform it? Soddy says this is dependent upon chance: ''The chance at any instant whether any atom disinte- grates or not in any particular second is fixed. It has nothing to do with any external or internal consideration we know of and in particular it is not increased by the fact that the atom has already survived any period of past time. The orientation assumed by the atom at one instant has no deter- mining influence upon the orientation about to be assumed at the next. * * * This is a funda- mental step gained, although it leaves the ultimate problem unsolved." Though we can not yet tell what influence plays upon the sub-component whose escape causes the transformation, we have yet advanced far enough to count the atoms escaping from radium. We have mastered minute entities sufficiently to be able to diagram the length of the gamma-ray, as com- pared with the X-ray, as compared with the ordi- nary light wave, as compared with the curve of the OR THE PHILOSOPHY OF MALIGNANCY 15 red blood corpuscle. We may yet measure the duration of the important sub-component, and dis- cover what cause selects it for its transforming mission, in its escape. Through what channels may help on this point come? The utmost refinements of chemical analy- sis will probably offer little aid. Color analysis, by the spectrum and fermentative tests, is yet in its infancy, though we have already gotten to the conception that color is the mathe- matical sum total of the components which go to make it. Fermentative tests — which is bacteriology call- ing to color affinities — have already been used to differentiate the isomers of a substance and show which one is capable of digestion and which one can not possibly be digested. (See page 76). Possibly the radio-active sub-components will be nosed out by similar bacteriological stainings. Until these identities are made, however, we are not entirely in the dark. From 400 million million to 800 million million vibrations per second in the color octave of the spectrum give clue to 400 mil- lion million vibratory differences which go to make up the gradations and shades. The velocity show- ing as red, when increased, shows as orange, and the yellow, and so on. Therefore, when Sudbor- 16 THE CANCER PROBLEM ough made yellow phosphorus change into red phosphorus by exposure to the Becquerel ray, evi- dently the radio-active process was an interference and not a reinforcement, and velocity was di- minished and not increased. An expert might pick out here the sub-component which met interference, and this would be a very important question of dosage; for radio-activity may diminish the veloc- ity of our organic phosphorus and denote it from yellow to red. On the other hand, when the Curies made ozone by exposing oxygen to the radio-active process, there was evidently a reinforcement and an in- crease in velocity. Ozone, though a colorless gas, when strongly cooled condenses into an indigo blue liquid which is strongly explosive. It bleaches veg- etable colors, acts rapidly on metals, instantly de- stroys rubber tubing connections, attacks organic life, and liberates iodine from the glandular tissue. We find it liberated in forming the chlorophyllian green of the plants — here a retarding of velocity from the blue, of greater velocity. May We not infer a reinforcement by radio-activity at one color extremity, and an interference by the solar-chlor- ophyllian process at the other extremity? We may work from extremities where it is not, toward the direction where it is known to be. OR THE PHILOSOPHY OF MALIGNANCY 17 The liberation of iodine from our thyroids, or the change of our phosphorus from higher placed yellow to lower placed red, is a proven radio-active result. To control the radio-active — or the solar-chlor- ophyllian — dosage, and thereby increase or dimin- ish respectively the vibratory coloring, is to con- trol the malignancy of Graves' disease, the Leu- kemias, as well as the "Cancer" malignancy. Ill The Processes of Life Dependent Upon Def- inite Mathematics Within the Cell. Biological Sub-Components. What do we know of these? We know that there are syntonic adjustments in living beings which select forces necessary for existence and ex- clude others that would imperil existence. This has been fully elaborated in the "The Philosophy of Radio- Activity/' Experiments of elementary physics disclose to us the law of wave length rein- forcement and interferences by which these selec- tions and exclusions are made. Syntonic relation is therefore the very basis of life, for it is thereby that we are protected and nourished by the identical substances which kill other life — as the oxygen which renews our blood, destroys other forms of life. We have only a few syntonic receivers. (Please remember that reference is here being made to the likeness to the receiver of wireless telegraphy, 18 OR THE PHILOSOPHY OF MALIGNANCY 19 > which must be syntonic with the sender. ) The lim- itation is with us — not in the infinity of changes about us. When our receivers, our syntonisms, are over-sped or under-sped — and they are pro- gressively under-sped in age — we lose reinforce- ments needed for our existence, or run into self- wreck, like the blindness from snow, whose high- sped ultra-violet rays effect our vision. The rela- tion of this degradation of capacity to gland im- pairment is well known. We know, too, that our digestion is almost en- tirely a cytolysis depending upon reinforcement and interference. Whether the contents will "digest" the stomach or the stomach digest the contents, depends upon which way the sub-component is set — as disclosed to us by the right or left turn of polarized light. A fermentative, or bacterial, test has been necessary to reveal this to us. ( See page 22. ) And as we have seen, bacterial tests — coloni- zations — are made known to us simply and solely by color syntonisms. And color and crystal turn- ings are indexes of sub-components whose veloci- ties are increased or decreased. We know, too, that evolution upward and the retreat backward by anaphylaxis, are but expres- 20 THE CANCER PROBLEM Sions Of SELECTIVE CYTOLYSIS AND CONJOINED cytolysis — related to this power to increase or de- crease velocities in the color octave whereby it is ruled which one of two antagonistic organisms shall disappear by becoming food, and which shall increase upon such food. While cancer does not belong to bacteriology — the Harvard Commission worked this subject to a finished conclusion — yet bacteriology may furnish the cancer clue in these fermentative tests, which are the only means we have for making some dif- ferentiations. Over-sped and under-sped syntonisms — again we are referring to the likeness to the receiver of wireless telegraphy — have been traced all the way up the line of evolution. We have seen matter made from ether, and life made from matter, and sex differentiated in the cell, and the animal swerved from the vegetable cell — and the motile kingdom revert in disease to likeness to the less motile (vegetable) kingdom — all by processes which lift or lower the syntonisms. Therefore, to know the biological sub-compo- nents we must consider the animal and vegetable kingdoms, the intermediaries between them, the in- fluence which makes sex — the asexual and the sex- OR THE PHILOSOPHY OF MALIGNANCY 21 ual generations ; what adds sex and what subtracts sex — and what favors passage from the animal kingdom back to the vegetable, and thence to the mineral and inorganic. IV The Intermediaries Which Protect the Cell from Foreign Albumins. Missing Inter- , mediaries in Malignancy. In 1908 the writer published the following on this subject: "Please, therefore, let us revivify in our consciousness the absolute necessity of the ferments in making food really food to us — selecting our bread from stone for us by prac- tically the same process that Pasteur used in his laboratory years ago. "With sure selective instinct, keener than the scent of the bloodhound, as imperious as the call of an acid for its base, these our agents of assimilation and protection stand at the portal of our being, and decide: this is right deflecting, this is left deflecting: this is bread, this is stone — saying to one, 'Go ye into tissue'; and to the other, 'Get you hence!' "Let us also make vivid to ourselves this conception of the protective and curative powers contained in these newly- discovered 'ferments.' All this is in vital relation with the cancer problem." In the same paper (see page 76) attention was called to the difficulty in telling whether bone-mar- 22 OR THE PHILOSOPHY OF MALIGNANCY 23 row malignancy, or pernicious anemia, starts the well known symptom complex. The trelation of the bone marrow to the red blood corpuscle, to pernicious anemia, and to ma- lignancy is again accented. The red blood corpuscle does not reproduce it- self. It has a short life and is a terminal cell. It is the practical basis of life; iron, the most mag- netic of all the elements, is its principal compo- nent; and it is one of the few points at which animal life may touch inorganic life without other intermediary than that furnished by the "side chain" of its own molecular construction. Iron usually comes through the vegetable kingdom in- termediary; it may come directly from the inor- ganic. Why this important cell should not reproduce itself, where it is made, and the final disposition of its destroyed elements, are important biological sub-component relations with malignancy. Then, melanin has a well known relation with malignancy. It is not inconceivable that an inhar- monious color deposit in a cell may start a ma- lignant process. We have elsewhere (page 53) shown how the reinforcement, or interference, with the rudimen- tary chromosome of a germinal cell, probably de- 24 THE CANCER PROBLEM termines the sex of the offspring. If inharmonious color deposits start malignancy, it is easy to under- stand how these come to pass. Thus, the red blood corpuscle itself — though manufactured and dying a terminal cell without reproducing itself — may yet carry within itself a latent reproductive process. An adjusted synto- nism — as by the turn of a crystal from rhomboid to prism, or by the change in the cell focus — could readily fan this into activity. The process is ap- parent in the phenomenon of reproduction. A sim- ilar process might start an asexual new-cell repro- duction for the red blood corpuscle, instead of the normal death as a terminal cell. This would be as devitalizing a host in any organism as is ma- lignancy. If the X-ray reinforces a process into malig- nancy, which radium promptly cures by an inter- ference, other processes could readily substitute a scissiparity (or cell division), for a cell death; and the red blood corpuscle, when so treated, would be a malignancy when sufficiently multiplied. This is an illustration, not a theory. Yet it is a theory that from the reinforcement, or the inter- ference, of some similar sub-component process, malignancy proceeds and recedes. A tired or ex- hausted element in the "side-chain," permitting di- OR THE PHILOSOPHY OF MALIGNANCY 25 rect access from the exterior to the nucleus, would illustrate a similar defective biological sub-compo- nent. The cytolysis which selects one and rejects the other — cytolysis conjoined and cytolysis select- ive — is well understood in its relation to evolution. Hemolysis is a cytolysis of the blood cell. Diges- tion is a cytolysis. Whether the container or the contained shall melt — shall be digested — is the problem of life: and this is dependent upon so slight a difference of constitution that the spectrum and a fermentative test are necessary to tell apart two substances which only differ — as isomers — in these deeply hidden respects. The hemolysis in the blood of cancer afflicted patients has been written upon by Crile. Anaphy- laxis, or backward cytolysis from the more evolved to, the less evolved genera and species, has been elaborated by Richte, who received the Nobel prize for his work. The almost undiscoverable differ- ence in sub-components which sets the direction backwards instead of forwards — see "The Phi- losophy of Radio-Activity" — is the biological point whereat attention must be focussed. The Missing Intermediaries: The solar ray burns the grass which lacks shade and moisture. Interpose the chlorophyll at the 26 THE CANCER PROBLEM leaf's green edge, and the distilling process which is known to take place at this intermediary be- tween the solar force and the vegetable kingdom, stores what is otherwise a destruction, and makes of it force and life. In the same way, introduce the albumins by hypodermatic method into the human organism and you have anaphylactic destruction. Send the same product by the digestive tract via the inter- mediaries of digestive and other glands, and you have again force and life from what otherwise would be destructive. The intermediary makes the difference between going forward toward force and life, by melting; or backwards towards destruction, by causing the containing substance to melt — or cytolyze, or hemolyze. Therefore the intermediaries are all important in preserving these sub-components in the precise relation needed for the melting of the right sub- stance into the right substance. Before leaving this subject, elsewhere treated at length, it is accented that the time of gland fail- ure is the advent of the malignancies. Also, that the glands are the determiners of age, sex, mass and form. Harvey Cushing has done monumental work on this subject. That the glands transfer sex OR THE PHILOSOPHY OF MALIGNANCY 27 and discount, or advance age, is apparent from those well-known cases of "adrenal virilism": that is to say, organic disturbances of development, showing either precocious development of the in- fant, or the masculine aspect a woman may acquire, even after the menopause, under the influence of tumor of the supra-renal gland. (See Journ. A. M. A. June 20, 1914, page 1978.) V The Relation Between the Glands and the Sex; the Feminization of the Male by Obesity; the Belated Secretions; the Rela- tions Between Secretions, Obesity, Malig- nancy and Appetite. A Diet for Cancer Patients. Besides being probably intermediaries between the animal and the vegetable kingdoms, the glands are also directed toward modifying what is in- gested, and preparing it that it may "melt" into the body which contains it, instead of destroying the container. The difference is as slight — or as great — as the difference between one isomer of the same thing, and the opposite isomer. But this dif- ference is greater than that between bread and stone: for the isomer which is digestively unas- sailable may itself actively "digest" cells of the organism in which it is placed, and thus take on a growth therein. 28 OR THE PHILOSOPHY OF MALIGNANCY 29 The glands also preside over the sex cycle, and because so doing necessarily relate the sex cycle to the question of malignancy. The glands may be termed not only the sex, but also the age. When the thymus is absorbed at puberty the secondary sex characteristics are unlocked*. The line swerves, function diverges, vibratory changes appear; the soprano of the male becomes bass, only to revert at the end of the sex digression to the senile shrillness. So the temporarily high vibra- tory quality of the female thickens and descends as her digressive line, too, approaches the com- mon mean, where age conquers sex. The vibra- tory-conferring powers of the ductless glands are proven in castration and ovariotomy sequelae; in the female descent from high note, the male ascent from low note, the facial hirsutis of the female, the hairlessness of the male. Each malef carries a useless female rudiment, and each female carries *Steinlich (quoted by Cushing. PB., Page 276) showed the VIII International Congress of Physiologists (1911) examples of artificially produced male rats. "He had removed the ovaries from young females and implanted testes from young males into their anterior abdominal walls, with permanent change of sex characteristics, the subjects growing into normal masculine in- dividuals." As R. T. Morris (Adami, page 581) sewed another woman's ovary into a woman from whom both ovaries had been removed and pregnancy resulted later; and as Carrel has shown the via- bilty of detached parts of the organism, surgical re-arrangement of sex is by no mean^ a fantastic dream, f Adami, Prin. of Pathol. 258. 30 THE CANCER PROBLEM a useless male rudiment, in the precise manner that traces of their common origin are seen in both the animal and vegetable kingdoms. If the highest forms show the digression, it must be similarly hidden in the lowest. For the detritus of one kingdom is the nourishment of the other — the daily oxygen and carbon output of the vegetable chlorophyll, as well as the stored nitrogen, is ex- changed with the animal for the agriculturally en- riching product of animal decay. One kingdom depends upon the other: "without fauna, no flora; without flora, no fauna; without the solar ray, neither fauna nor flora," is the ancient dictum here strongly reaffirmed. We may even paraphrase it, and say "without female, no male" — and by the very inadequacy of the paraphrase find ourselves facing a subtle, yet important point: The Determination of Sex, and the Set- ting of Hereditary Type, Probably Both Lie in the Glandular Cycle. We have elsewhere described the "Contradanse" of the Chromosomes, wherein eight male chromo- somes face eight female chromosomes for a definite "rest" before fusion. What is taking place during that "rest" is the nourishment of the hungry male element. Hartog says : "It can not fuse with the female nucleus until OR THE PHILOSOPHY OF MALIGNANCY 31 it has attained a normal condition; and for this purpose it must be nourished." The sperm is taking something from the female element. The hungrier it is, the more avidity and quantity are involved. The female is adding some- thing to the male element. There is reinforcement and interference with differing result as to sex as an outcome. We see the relation is a color rela- tion. Unquestionably, sex depends upon the rein- forcement of one of the color bodies, or the inter- ference with another. Now the setting of hereditary type and the de- termination of sex, may have no closer relation with malignancy than to hint to us of a process of reinforcement or interference within the cell during the "rest" period of the "contra-danse" of the chromosomes. But this hint is very impor- tant. The Belated Secretion, Outlasting its Normal Inhibiting Antagonists: (See page 103.) "Those in whom a ferment (or glandular secretion) fails too soon, or lasts too long, have therein the basis of the pre-cancer stage. There may be special danger in the be- lated secretion, outlasting its normal inhibiting antagonists. These become the non-immune to cancer, and may grow in it the presence of a contributing cause." The author published this hint in 1910. 32 THE CANCER PROBLEM May 21, 1914, at the New York Academy of Medicine, Studies in Cancer from the General Me- morial Hospital (principally under the auspices of the Cornell laboratories), were reported. Dr. Beebe referred to the experiments made in the Cornell laboratories, wherein tadpoles fed on thy- mus protein grew very large without differentiating as frogs; but, if thyroid was then added, they be- came frogs. This seems to bear out the theory ad- vanced by the author, four years before. The Relation Between Obesity and Malig- nancy; The Relation Between Obesity and Gland- ular Secretions; The Relation Between Glandular Secre- tion and Appetite; That obesity is in dim relationship with malig- nancy, has elsewhere been cited by the author. Again reference is made to the genital hypoplasia seen in the typus femininus in males with pituitary disorder. The tenor voice of the hairless obese man is as closely associated with genital hypop- lasia, as is the exactly reverse condition in the fe- male, described by the present writer in 1904 as follows : "Even in these stolid ones of the community, however, OR THE PHILOSOPHY OF MALIGNANCY 33 may be noticed the following differences after a hysterec- tomy: a comparatively lusterless eye, a roughened voice and an increased hair growth; a flattening, or a fattening of the breast at glandular expense; an increase of fat, a devitilization, or a defeminization, or a hebetudinization, so to speak; a changing, as from the high-stepper to the cart-horse ; from the alertness of the city-bred to the hebe- tude of province, where nerve stimuli are few and slow and response thereto similar. It is a wiping out of zest, spirit, and pride of port. "These objective results are patent to the superficial ob- server. Their significance, however, is more difficult read- ing. We are helped in this reading by the almost spectac- ular restorations possible in those cases that I have called 'the self-obliterated feminine element' These cases, as elsewhere elaborated, represent the gradual stamping out in function of the selective cells of sex in women from twenty-five to forty years, who show diminished menstru- ation, loss of sensual sense and power of orgasm, with an increase of weight, roughening of skin and voice, and a growing lithemia and hebetude. As a cause, or a result, the obliteration of the feminine element in the individual al- most rivals the work of the knife in its completeness. Note that in these cases the naval orange, draught horse, lard- producing analogy and capacity are not lost. But what goes is, reproductive capacity, spirit, initiative, outlook — in other words, the 'house of the mind/ without which there can be no effective longevity. "It is only to those color-blind to the possibilities of female life, aside from reproduction, that these matters will seem unimportant. For efficient longevity is entirely a 34 THE CANCER PROBLEM class matter. There can be none of it after the time of muscular activity with those falling in my biological classi- fication." In other words, the abolition of sex throws the male over the line into the feminine type — with tenor voice, hairlessness, and genital hypoplasia; whereas, in the female, it coarsens the voice, thick- ens the skin, increases the growth of hair, but still augments the obesity as in the opposite sex. As obesity brings the typus femininus to the male we may consider the obese part of him along with the same condition in the female. We may con- sider the storage of fat, therefore, as a feminine process: as the ovum is fat filled, and when com- pared with the lean and hungry male sperm, is as "St. Peter's dome to a pin head" in size relation. The storage of fat in the female is to nourish, first the male sperm, and next the new life growing. This over-burden of nutritive femininity for nour- ishment of new life, is a dangerous magazine of stored force in the organism. If the relation of obesity to malignancy is no closer than that of being the cause of the genital hypoplasia — with its extinguishing influence on the other glands of the other cycle (the pituitary, thy- roid, mammary, adrenals, etc.) — such relation is still close enough to merit study. OR THE PHILOSOPHY OF MALIGNANCY 35 It needs no argument, in these days, to relate obesity to the glandular secretion, or to relate one glandular secretion to the entire glandular cycle. The reduction of obesity is now one of the easiest processes in medicine, and the writer has done this as routine for nearly two decades. It may need the suggestion that the appetite's quality direction depends upon the glandular se- cretions. The "longings" of pregnancy are in evi- dence when the glands are engaged in the extra work of nourishing the additional life. Others may have remarked, with the author, the great change in the direction of the appetites of patients cured of obesity. Aside from the fact that the fats cells which no longer exist, no longer clamor for food, the rest of the organism seems to have acquired entirely new food instincts. I have fre- quently taken down weight by increasing the nutri- tion; the appetite is always re-directed. It is obvious that the reawakening of sex libido in these cases also comes from restored glandular integrity.* *Vide Cushing's case shown in photograph to 1913 London Congress, of a girl of six who looked sixteen and had puberty at two. (The photographs shown by Cushing in "The Pituitary Body" disclose the typus femininus, and the accompanying genital hypo- plasia.) Napoleon, whose later tendency to globularity and resemblance to a woman, showed glandular disorder, is now considered as having had a bruised stalk of the pituitary body. (Vide discus- sion 1913 London Congress.) 36 THE CANCER PROBLEM The Carbohydrate Tolerance; The Carbohydrates and Malignancy; The Sugar Content of the Blood in Ma- lignancy; The relation of the carbohydrates to obesity is well known. The increased assimilative limit for carbohydrates is so well known an accompaniment of glandular disorder and obesity, that definite routine has been established for its determination. What are the other symptoms of under-glandular tone? Cushing says: Hypo-adrenalism gives : Hypopituitarism gives : asthenia, pigmentation, low blood pressure. sub-normal temperature, dry skin, loss of hair, slowed pulse, lowered blood pressure, asthenia, increased assimilative limit for carbohydrates. Cushing's rule to determine the carbohydrate tol- erance is: "In the lack of a definite symptomatic tell-tale of the degree of hypophyseal insufficiency, we have had recourse to the carbohydrate toler- OR THE PHILOSOPHY OF MALIGNANCY 37 ance as a measure of the deficit, and so far as our experience has gone this furnishes us with the only rational estimate of the requisite dosage of a given preparation." That there should be a mathematical point at which there is a "'turn-over" of sugar taken by mouth into the urine, which mathematical point may be varied by gland feeding — very conclusively ties the glands up to a control over what may enter the body, and what must be rejected. Glandular inactivity means that this turn-over point is set high; glandular feeding and freshen- ing, mean that this turn-over point is set lower, and the dangerous matter is turned into the sewer and not stored in the tissues. See page 22 pub- lished by the author in 1908 on this subject. The Cornell report of May 21, 1914 (Doctors S. R. Benedict and R. C. Lewis), established the fact of the sugar content of the blood in malignancy, and the fact that it increases up until death. Obesity is in dim relationship with ma- lignancy. The sugar content of the blood in obes- ity, which has now a routine method for its de- termination; and THE TURN-OVER POINT OF TOLER- ANCE, which is also a mathematical point (variable at our will), are now able to throw a distinct ray of lisrht into this dimness. 38 THE CANCER PROBLEM Latent diabetes is now a discoverable, removable antecedent to the following "malignancies" : arterio- sclerosis, contracted kidney, cerebral hemorrhage, cataract, eczema, ferunculosis, and gangrene. (We are conscious of naming the symptoms of the un- derlying "malignancies," as the best means of point- ing to the malignancies themselves. See "Unclas- sified Diseases," by the author.) A color response — the Fehling reaction — is what the suboxids give to the right call, and we are able to follow with our mathematics at this point the result of diet upon the sub-components within the cell! "Bang's method for determining abnormal proportions of sugar in the blood has proved simple and reliable, and Bornstein commends it highly. Three drops of blood are soaked up into a piece of blotting paper, 16 by 28 mm. When dry, 5 c.c. of a boiling solution of potassium chlorid is poured over it. (136 c.c. of a concentrated solution of potassium chlorid; 64 c.c. distilled water, and 0.15 c.c. of 25 per cent, hydrochloric acid.) This coagulates the albu- min in the blood, while the sugar diffuses in the fluid and the Fehling reaction is applied after half an hour. If this does not precipitate any suboxids, then the sugar content of the blood is normal (below 0.15 per cent.). A precipitate means hyperglycemia. With four drops of blood a reac- tion is obtained with a sugar content of only 0.12 per cent., which is the lowest limit of normal range." (Berliner Klin- ische Wochenschrift, May 18, 1914: N. Roth.) OR THE PHILOSOPHY OF MALIGNANCY 39 But equally as significant is the communication of Dr. S. P. Beebe at the same meeting. By with- holding carbohydrates from 26 planted* rats and feeding normal diet to 26 other similarly planted rats, the results were as given in the following table : Special Diet Control 26 rats planted; 26 rats planted; 100% takes; 100% takes 2 died; 24 died; 4 accidents, cause un- 2 regressed, known ; 20 regressed. The superficial cancer cures reported at the same meeting by Dr. A. F. Holding, who projected photo- graphs on the screen, were principally in obese patients, whose physiognomies, after cure, re- minded the present writer of the awakened apa- thies frequently seen in his cured obesity cases. There are cancers in the thin, of course. And loss of weight is an early symptom of malignancy. But *The planting was done with the Buffalo sarcoma. Dr. Beebe quoted Mendell's experiments, on the use of lard and butter as fats. Incomplete proteid diet will stunt animals ; they live but do not grow. Add complete proteins, and they resume growth. It is similar with the cancer cell. Butter, for example, will "recover" a receding cancer which was losing its virulence under the lard diet. 40 THE CANCER PROBLEM many malignancies have been overweight at the start.* The butter-lard protein tests, if not simply- remarkable coincidences, give us a formula to ex- press the application of a dietary sub-component to a biological sub-component, with a resulting ma- lignancy. Butter-proteins minus lard-proteins leave a pro- tein group which recovers receding malignancy; which is needed to keep malignancy from receding. In "Arteriosclerosis," Dr. Louis Faugeres Bishop speaks of the advantages of the few protein diet, instead of a restricted diet of many proteins. In other words, he holds that allowing sufficient quan- tity of a small group is better than allowing a re- stricted quantity of a mixed group. Robin and Gautier (Robin, Tuberculosis, 136) point out an interesting relation between the sub- component of diet and the sub-component of cell life: "The ashes of bread are acid. To saturate the bases con- tained in 100 grms. of bread, 0/232 grm. of phosphoric acid ♦"There is no heredity in cancer, but there has been a tendency to over-weight in insured who have died of cancer — though thin men also suffer." — Mr. Frederick C. Hoffman, Chairman Board of Statistics Prudential Life Insurance Co. Obviously an active thyroid means no over-weight, hence good guardianship against malignancy. An abnormally active thyroid, on the other hand, is no longer a good guardian ; it is itself malig- mancy of another sort, — (i. e., Graves' Disease, Leukemia, etc.) OR THE PHILOSOPHY OF MALIGNANCY 41 would be sufficient. Well, these ashes themselves contain 0.470 grm. The difference (0.238 grm.) has therefore tc be borrowed from the organism for saturation and elimina- tion. Hence the importance of not giving too large a quan- tity of bread. . . . and of ordering in its stead po- tatoes, the ashes of which are alkaline and rich in mag- nesia." The obese are notoriously great bread eaters, and are thereby demineralizing their blood, which is already both relatively and actually less in quan- tity than that of persons of normal weight. When we recall that iron, the most magnetic of the elements, is the chief color bearer of the blood, and that the malignant cell — as we shall see later — is a decolorized cell, to a certain definite extent, we again obtain view of the dim relationship be- tween obesity and malignancy. There may be assumed, therefore, proven rela- tion between sex, gland, obesity, carbohydrates. There is also a proven mathematical point where- at cell acceptance becomes cell rejection, and we may change this rejection point at will by measuring the amount of glucose or levulose taken in, and adding proper dosage of glandular substance. 42 THE CANCER PROBLEM It is very important to discover if this is by crys- tal turn, or simply by an elective sensitivity of cer- tain cells to dextro or sinistro rotary light. (See page 76). It seems the guard point at the thresh- old of malignancy. Both complete protein feeding, and the presence of carbohydrates in the diet — that is, normal diet — allow the growth of the can- cer cell. Restricting the carbohydrates causes planted tumors tc regress. Restricting the pro- teins — giving the incomplete protein — seems also to bring about a retarding of the cancer cell growth. But complete starvation, as occurs in some py- loric conditions, does not cure the patients. Logic would point to an incomplete protein, with restricted carbohydrates, as the diet for malig- nancy. This may be a lead in a direction promising hope. Hens will not lay without proteins. The relation of protein to the reproductive glands is as close as the relation of the reproductive glands to malignancy. The nitrogen turn-over point as surely ex- ists, and is probably as surely controllable as is the carbohydrate turn-over point; only we have not found it yet. There are some recent suggestions relating 1 to it. Schamberg (quoted by Bulkley, Med. Record, Oct. 24, 1914), has studied the strong tendencies of psoriasic patients to store nitrogen. OR THE PHILOSOPHY OF MALIGNANCY 43 If obesity be a disease characterized by a high car- bohydrate turn-over point, psoriasis may be said to be a disease characterized by a high nitrogen turn- over point. The present writer, following Bulkley, has frequently controlled the perverted and active proliferation of epithelial cells by restricting pro- teins and enforcing Bulkley's rice-butter diet. Here is again a direct dietary control of a cellular subcomponent. We get sure clinical answer, but have as yet no laboratory mathematics — as we have with carbohydrates. (See J. Walter Vaughan, "Protein Split Products," Journ. A. M. A., Oct. 10, 1914, page 1258.) The supply of potash for fertilizers being de- rived almost exclusive from Germany, the pres- ent war has accented to the whole public how a lacking element of soil diet alters a subcomponent in a vegetable cell. Bulkley quotes Ross with ap- proval, that there is a similar failure in the pot- ash elements in patients who are subject to cancer. No one would yet be justified in postponing sur- gery for dietary delay. But after surgery, recur- rences may be avoided by careful study of these two turn-over points. Post-surgical cancer cases, there- fore, strongly need medical supervision. As the diabetic craves sweets, as the lithemic craves meat, we may follow the craving as a symp- 44 THE CANCER PROBLEM torn of a hidden high turn-over point, and find an element which has sure relation with cell subcom- ponents. There is a new lead on this subject. The secret power in the pituitary body to cause extrusion of the contents of the womb is now established. Tak- ing the extrusive power of the pituitary as the standard, oxy toxic powers of other tissues have been studied, and even the cells of the lining of the intestines are seen to contain an extrusive secretion, with mathematical relation to the power of the standard of extrusion. Now, if the proteins affect this extrusive power — and this is a subject suggested to the experts — we have another relation, mathematically fixed, be- tween diet and sub-components within the cell. We already know how to alter the rejection point for carbohydrates ; and there will probably be discovered the mathematics of extrusive power in the cells of each tissue. Perhaps this will be found in definite relation with the incontinent nucleus of the malignant cell, referred to in the next section. VI The Incontinent Nucleus; the Loss of Nu- clear Color in Sex Decline and in Fatigue; the Control of Overgrowths. The new hair growths of the climacteric — the dechromatized hairs — grow twice as rapidly as the remaining fully colored hairs. This would imply that there is something in the coloring matter, which retards some growth. Fatigue takes color from the nucleus of each brain, liver, adrenal and thyroid cell — as shown by the photographs taken by Crile in his experiments on this subject. Reversion to asexual generation, as in the algues, reduces the color in the nuclei to exactly one-half. Sexual generation, at each alternate generation in those genera and species which still preserve both methods, doubles the color at the nuclear center. We may count the chromo- somes. 45 46 THE CANCER PROBLEM From this it would seem that fatigue, and the loss of sex quality, both divide the central nuclear color. From which, logic may advance a further step and say that fatigue and loss of sex quality remove a control process governing the growth of certain cells — notably the decolorized hairs, and possibly the malignant cell, which is also a cell minus part of its central nuclear color. Color loss implies fatigue and loss of sex quality — and also a loss of a quality which holds in check "weed cell" growth. This may be illustrated from another angle. Large persons, the "pituitary tall," are notoriously undervitalized and deficient in sex powers. The diminutives — the "thyroid small" — are as notoriously virile and active sexually. There- fore, either the capacity, or the employment of the capacity, checks a cell growth which unchecked would yield the giant. There is, therefore, presump- tively a check in the glands of the sexual cycle as potent as that in the thymus gland — which latter prevents the development of all secondary sexual characteristics until its absorption. ( See page 32. ) Why are the breasts which are unable to suckle child more prone to cancer? (Bainbridge, 104.) The glandular cycle is a co-related system, each part being as related to the secondary sexual char- acteristics as to each other part. OR THE PHILOSOPHY OF MALIGNANCY 47 Therefore there is glandular control of mass and form, and growth and overgrowth, and the frontier integrity of the differentiated tissues. The incontinent nucleus, whose chromatin escapes into the cytoplasm, is characteristic of the malignant cell. This is analogous with the involuntary pas- sage of urine and feces; or dilated pupils, or invol- untary sex dreams, in the individual. It is a true incontinence due to the removal of some central control. The sub-component defect of control which al- lows this nuclear incontinence is very important; it should be found. Perhaps the remarkable bodies observable in the cancer cells are what result from the efforts of na- ture to repair the color losses entailed by the incon- tinent nucleus. Many observers hold that these bodies, seen with fair frequency — sometimes in great abundance — are sporozoa. Gaylord thinks these bodies present both animal and vegetable char- acteristics. The general opinion now is that they are modified cell and nuclear products. But the processes of life elsewhere would be reversed in the cell if nature made no effort to repair the leakage of the chromatin in malignancy. The present writer refers to a possibility presented on page 49. Perhaps the X-ray and the y-ray may only stim- 48 THE CANCER PROBLEM ulate the control of this leakage of chromatin from the nucleus. Or a direct stimulation to color pro- duction may ensue. For Meirowsky has seen pig- ment in cells, after subjecting the skin to Finsen light, collecting more abundantly on the side near the source of light. This pigment in cells sends out processes which assume the characteristic chromatophose type. The solar ray draws out pigment in great abund- ance. In blood demineralized — and we have seen how easily this may be done — there is a loss of color. And the loss of color implies not only a loss of inhibition of weed cell growth, but exposure of a partially uncurtained normal cell to the solar ray, whose draft of pigment toward itself is doubt- less similar to that proven in response to the Finsen ray. How readily could this arrangement of pigment in cells stir to activity the latent third type of asexual reproduction — in a terminal cell like the red blood corpuscle, for example — and give us the whole phenomenon of malignancy ! To uncurtain a blood cell and expose it to unwonted light, needs only a crystal turn, or a change in the cell focus. Arnold Knapp says that age may be told with almost math- ematical precision from the change in the eye focus. The present writer believes that each cell has a cor- OR THE PHILOSOPHY OF MALIGNANCY 49 responding change of focus advancing with age; and that age is a relative matter depending upon glandular integrity.* *Gowers believes that the whitening of the hair is due to nerve center traumatism, and that there is a compensating effort made to increase pigmentation in the vicinity of its loss ; that there is a close relation between the plus and minus in the pigmentary process. "A remarkable illustration : one of my cases a man with traumatic miningeal hemorrhage over the left hemisphere. As a result of this, during the three days he lived after the injury, the right opposite half of the hair of his head and of his brown moustache and beard became white. The change was watched during life and carefully noted after death. . . Disordered innervation changed the secretion at the roots of the hairs. . . . We noticed another thing after death : The very gray, almost white, right half of the beard was separated from the brown left half by a narrow verticle line, or narrow zone, in the middle line, IN WHICH THE HAIR HAD BECOME ALMOST BLACK. Apparently, where the disordered influence ceased ... a change in the pigmentary processes occurred of an opposite character." (Clinical Lectures by Sir William Gowers, M.D., F.R.S., 1914, P. 153.) VII The Glands and Pigmentation. The Heredi- tary Pigments. The X-Ray and Radium and Sterility. The Glands and Cancer Houses. Pigmentation, a deposit of melanin granules, is in direct relation with disorder of the adrenals, or the thyroid in Graves' disease, or in pregnancy when the glands are occupied with the new life. When the pigmentation of the skin shows at the time the hair whitens, the glands are failing, and meat as food becomes dangerous — as it is in age; in Graves' disease ; as it sometimes throws the pig- mented pregnant woman into elampsia. The inter- mediary is missing, and it is as though the proteins were injected under the skin and got into the or- ganism without preparation. (It must be remem- bered that what is in the alimentary canal is not 50 OR THE PHILOSOPHY OF MALIGNANCY 51 yet in the organism.) That meat is positive poison to a patient with Graves' disease is, unfortunately, too frequently proven by the disobedience of faith- less patients, who long for meat as eagerly as the diabetic craves sweets. Gland failure, proteid poisoning, hair whitening and loss, skin pigmentation — are all at the time of cancer incidence, and we cannot shut our eyes to the close inter-relations. Pigmentation, which may be potential malig- nancy, is either a specialized function (a reinforce- ment) ; or, from imperfect metabolism (an inter- ference). As it is the interaction between the nuclear and cell body which gives rise to the secretions ; as glands govern secretions; as malignancy shows an altered distribution of nuclear matter — chromatin being dis" charged into the cytoplasm — "preserving the habit of growth, but having lost the potentiality for dif- ferentiating" — it is on best pathological authority that this intimate relation is claimed. See Adami, 724, 776, 925, P. of P.* *"Van Leyden has extracted from the normal liver of animals a preparation of ferments which applied to tumors is said to have caused their disappearance." Adami, page 780. Altered distribution of nuclear matter • Farmer, Moore and Walker, Bashford have withdrawn their views regarding "the ring form of chromosomes such as are seen in process of nuclear reduction of the oocyte and the spermacyte." 52 THE CANCER PROBLEM Pigments, iron and sulphur free, are like the dark- ening of certain proteins — as the browning of a cut apple — and are "of the nature of members of the aromatic series of derivatives of the protein mole- cule." Black substances are transmitted by heredity. The placing of this hereditary pigment in the germi- nal cells to set the hereditary type, if not the sex itself, will illustrate the asexual pigmentation which goes on in the tissue cells at the time the reproduc- tive cycle wanes and when all such pigmentations may be potential malignancies. Since the time of the "cell rest" theory of Cohnheim, it has been im- possible to turn the mind from the reproductive view of cancer. The glands and the germinal pigment de- termining SEX, SUGGEST AN UNDER-PIGMENTATION CAUSING AN ASEXUAL CELL PRODUCTION WHICH IS MALIGNANCY. As early as 1908 the present writer published the view that there were radial influences within the glands which had relation with malignancy. The 1913 Medical Congress at London gave first public recognition to a similar purport. The radial focussing upon the rudimentary color body in the germinal cell to determine sex is dia- grammed as per figure on page 53. THE LATEST ESTIMATE OF THE NUMBER Or CHROMOSOMES IN THE HUMAN TISSUE CELL IS NOW 24 INSTEAD OF IS chr. A B The Contra-dance ok the Chromosomes. "This is the bright color line about which has centered most of humanity's love, ethics, religion and law, — The "quadrille" or "contra-dance" of the Chromosomes, in their mitotic field before fusion. This diagram, after Wilson, Morgan, Hartog, Adami, shows the supposed "contra-dance" of the Chromosomes in the human nucleus while "resting" before fusion. Human tissue cells are sup- posed to contain 16 chromosomes, and human germinal cells would then contain eight chromosomes for each sex. "A" shows eight for eight from each sex, from which even combination in the lower forms of life a male invariably results. "B" shows the rudimentary, or missing, — formerly called the Accessory — chromosome, from which odd number presentation in lower forms, a female invariably results. As the "resting" period before fusion is said to be passed in "nourishing" the hungry male element up to the tune or color required for fusion, it is to be seen that equilibrium, ratio, re- inforcement and interference influences which determine sex, may focus upon this rudimentary, or missing, chromosome. OR THE PHILOSOPHY OF MALIGNANCY 53 Zoologists tell us there were originally three gen- ders in lower life forms : "A given species may consist of three different types of individuals, male, female and indifferent, each multiplying its own line. Complicated alternations of generations oc- cur, asexual and sexual. It is interesting to note sexual forms produce more resistant forms capable of braving adverse conditions or violent changes." (E. A. Minchin Prof. Protzoology, London University, Ency. Brit. XXII, 487.) Therefore, if radial action upon a cell center may influence male and female, with equal facility it may influence the third (now outgrown and abandoned type for the human ) ; i. e., the asexual type of cell reproduction. This is the precise type of the malig- nant cell. The subtle influences which go to determine sex may thus be considered.* *Mothers of sons have been compared with mothers of daugh- ters as biologically different. The rise and fall of male ca pacity and prestige — in mixed families — have been scanned for a relation to the sex secret of their offspring, born under the re- spective curves of prestige or eclipse. Statistics have been culled from the sex of offsprings of divorced couples. The excess of male births in time of national (not individual) disaster — such as war, famine, pestilence, earthquake — has been cited. Heloise has been called the type of son-mother; Delilah, the type of daughter mother to Sampson. Anti-feminists have cited "conjugal sabottage" as cause as well as result of the nearly two million excess female over males in the population of England, and have stated that the inequality may only be starting, because 54 THE CANCER PROBLEM The glands, the sex cycle, sterility, the x-ray and radium. Here again we have surely related sub-compo- nents, biological and radio-active. The sterility of vegetables and animals induced by X-ray and radio-activity, is too well known to need citation. Even the trypanosomes are influ- enced by these rays. The X-ray treatment of fibroid tumors, inducing sterility from three months to permanency, has now a growing list for study in the literature. The sterilization of water by the ultra-violet rays aspires to remove typhoid from large encampments in the future. The quick response of enlarged gland in the leukemias to the X-ray is another familiar relation. And the frequent involvement of the glands by leukemic disorders after double ovariotomy, is an- other study-deserving connection. This is espe- of the increasing feministic rebellion. The queen bee is probably made to differ from the female "workers" among the bees by a similar radial reinforcement, or interference, process. This is as interesting as offensive, if true ; but the virilism of the _ male-determining element may depend even more upon its intrinsic vitality than upon any reinforcement, or interference, re- ceived from the female during the "rest" period of the contra- danse of the chromosomes. This has relation to the subject as illustrating what may be done to divert germinal cells from one sex to the other; with possibility of reversion to the asexual form of cell reproduction, as found in cocidea and zorozoa. OR THE PHILOSOPHY OF MALIGNANCY 55 cially significant, since the "malignancy" of the leu- kemias and pernicious anemias is almost as severe, though not as speedy, as the other malignancies. The glands and cancer houses : While cancer is not hereditary nor yet contagious, the so called "cancer houses" (which have sheltered more than one case of cancer) should not be ascribed to coincidence or chance. By so doing we fail to trace the source of cancer cause. When we recall that the maximum cancer death rate is in Switzerland — where thyroid troubles are rife; where the water supply may be traced to a melted snow source; where the ultra-violet ray re- lation of snow is also seen in the known snow blind- ness from its ultra-violet rays; we must reach a conclusion that topographical influences have re- lation with gland disorders — if not with malignancy production. The water supply, a chimney condition of imper- fect coal combustion, certain magnetic influences — all should be considered. If a steamer's engine can demagnetize a watch, the radium in surface rocks is as capable of sub-component interference or re- inforcement. So with coal and pitch in the mines. W. Hanna Thomson ("Graves' Disease," page 111) says: "St. Leger relates that youths in certain townships in S- 56 THE CANCER PROBLEM France, in order to escape military service, drank copiously from a well, noted for causing goitre. Their thyroid glands enlarged, and by this means they escaped military duty. Lombroso relates a similar case in Lombardy where men made themselves goitrous in 15 days." There is at present under investigation a town in Wisconsin where men and women and even horses, dogs and cats are commonly goitrous. The rays surely interfere with a process neces- sary for growth; or reinforce a control process which retards growth. And each "cancer house" should start very serious investigations in all the possible lines, according to its location. We are not unmindful of Bashford's dictum that there are no cancer houses, or cancer cages. This agrees with our theory in the case of 200,000 planted mice. It agrees with our theory in the case of any number of human cancer cases gathered together in one institution. But we register a possible dissent with regard to what are called coincidences of several cancers to a house, occurring spontaneously. The geological aspect of cancer needs research. The radium found in the rocks of the Simplon tun- nel by Prof. Joly may have direct bearing on the goitrous and cancerous high curves of the Alps re- gion. OR THE PHILOSOPHY OF MALIGNANCY 57 Pathologists may be as reluctant to accept the new factor of radio-activity as are the astrono- mers. VIII Giant-Cell Malignancy Easy to Cure. Ray Wave Ratioto-Cell-Curve. Sizes of the Varied Ray Waves. As giant-cell malignancy is readily cured by the ray-therapy, there may be importance in the ratio of ray wave length to the cell curve. That it does not form metastasis may or may not be because of its cell size. If small round-cell malignancy could be trans- planted with giant-cell malignancy — for which we have, apparently, well fitting curable ray~— the con- quest of malignancy would be at hand. The ultra-violet light wave very accurately cor- responds with the curve of the red blood corpuscle. The X-ray wave is 1/10,000 of the length of this. The y ray is 1/100 of the length of the X-ray, or 1/1,000,000 of the length of the ultra-violet wave ray.* ♦Dr. Chas. Parson,, Columbia College, March 31, 1914. (Chief Chemist, Department of Interior.) 58 OR THE PHILOSOPHY OF MALIGNANCY 59 The "pin head to St. Peter's dome" contrast has been used to illustrate the disparity between the spermatozoon and the ovum — a far less variant ra- tio — which allows the invasion of a huge cell by an infinitely smaller provoker of growth. Size relation in biology for such stimulation may be as important as velocity is in radio-activity to overcome the friction line, and acquire the property of inter penetrability. There is an analogy between the spermatozoon which enters a relatively gigantic cell and rein- forces elements which start a growth — and the ray wave of one-to-a-million curve relation, which also enters a cell and reinforces certain color bodies and also starts a growth. This is all the more significant when we reflect that the difference between the growth started by the first and second entrant is precisely that which we find between the sexual and the asexual gene- rations of the algues in their alternate generations — an unvarying mathematical difference in color bodies. But there is a further tremendous difference in the subsequent issue — the normal process is one of differentiation, with definite laws of mass and form. The second is a lawless combination of monstrosity 60 THE CANCER PROBLEM and malignancy because something which should limit and differentiate is not there. As Prof. Adami has pointed out (page 776), "the properties of oldest acquirement are the last to be lost." Undifferentiated growth — the growth of cells of the same kind — was the oldest property. Sex life brought the differentiation; we then had cells of many kinds instead of cells of one kind. Cancer cells thus have lost the latest property ac- quired — differentiation, which seems to have been sex-conferred. This is why we say it is as if malig- nancy were all maleness, or all femaleness > respec- tively, dissolved from the tissue cells. Our confused conception of what happens at a cell nucleus is being cleared up. Leibig said, "The enzymes owe their power of producing fermenta- tion to the motions of certain atoms or groups of atoms." We now penetrate the atom, and discuss the sub-components, and the influences that work upon sub-components. The radio-active power to delay or arrest fer- mentation entirely, probably depends upon an inter- ference, and not a reinforcement. And the work is wrought upon a sub-component of the atom — in philosophical terms, "by detaching fractions of du- ration from fractions of space." Malignancy, then, seems to be a state wherein is OR THE PHILOSOPHY OF MALIGNANCY 61 only one half of the normal color at nucleolar cen- ters. Please remember, too, that the new theory of colors is that they are the mathematical sums of their components. Therefore, malignancy when cured by radio-ac- tivity is cured because radio-activity has rein- forced its color. It is caused by radio-activity when radio-activity interferes with its color — as it does when changing yellow phosphorus to red phospho- rus. If this be true, the problem is to isolate the sub- component which reinforces from that which inter- feres. The profession has had a very definite "lead" in the direction of color, already. The Eosin Selenium combination — a red powder soluble in warm water, whose composition is not yet made public — has been used to prevent normal cells from absorbing metals in chemo-therapeutical experiments. Sodium sele- nate and tellurate are salts whose metal is reduced by living cells and deposited near the nucleus as a black or red residue. Perhaps when we can put the color into the cell with radio-activity instead of chemistry, we will have solved the problem. Perhaps a harmless color bearing bacterium (analogous with the use of the Bulgarian bacillus in the colon), may be found 62 THE CANCER PROBLEM which will do this work. Bacteriology, therefore, may mark out the sub-components, and further, put sufficient color into the cell centers. But biology may be needed to overcome the half -quantum cells and substitute a growth wherein the continent cell nucleus contains the normal number of cell bodies. If a freshly removed tubal gestation were trans- planted into a malignancy so as to continue growth doubtless some surprises would await the experi- menter. The transplant of sound organs from accidental sources, was referred to by the present writer in a paper read before the New York Obstetrical Society in 1910, as follows: "The Imperial Cancer Research Fund in seven years has studied 200,000 mice. It has sixty different species of cancer growing. It is still growing the identical cancers which have been transplanted through four successive gen- erations of mice. It fires the imagination to see proved a relatively immortal living entity, nourished by a great- grandsire's blood, transplanted and retransplanted, and still promising a continuous life. I quote: " 'Seven years ago no one conceived it possible that por- tions of the mammalian organism could be kept growing for a period four times the life of the whole animal/ "Could this same process succeed in an antithetical be- nign sense, no sound organ — from adrenal to brain — would ever be interred with our accidental dead, but instead transplanted upon the living defective." OR THE PHILOSOPHY OF MALIGNANCY 63 Since we know that glandular feeding will change the mathematics involved in the amount of glucose or levulose ingested — by altering the rejection point; since we also know that increasing the ve- locity of a sub-component may release the iodine from our thyroids; since we may measure the dif- ference between 500 million million vibrations per second and 400 million million vibrations per second — as shown by the colors of yellow phosphorous and red phosphorus respectively, when demoted in ve- locity — since it is routine surgery to make similar vibratory changes in castrations and ovariotomies — we feel justified in tying the gland cycle firmly to the question of malignancy. This includes the malignancy of the mind, that of the leukemias, and that of Graves' disease, as well as the more rapid malignancies popularly called cancer. IX The Locks and the Keys Which Need Fit- ting and Tagging. A Relation of Size, or Space, as Well as Velocity, Involved in the Ray Wave-Lengths. Scientists have presumed to figure upon the dis- tances between the electrons which make up an atom, and to give this a relation to the diameter of the electron itself. This distance is probably one hundred million times the diameter of the electron. In The Philosophy of Radio-Activity the au- thor has contended that as definite a reason and law exist for the measure of the short orbit as for the time and distance involved in the Earth's journey- around the sun. By the same warrant it is contended that there is a law under the ratio of ray-wave length to cell curve. If the giant-cell sarcoma melts like wax un- der radium, there is a ratio in this case measurably differing from that obtaining in the small round- cell malignancy. 64 OR THE PHILOSOPHY OF MALIGNANCY 65 If rays of one ratio-to-cell-curve, cause a cancer which rays of a vastly different ratio-to-cell-curve speedily cure : there is a definite problem in mathe- matics for the experts to solve. In "The Philosophy of Radio-Activity" the writer has also tried to establish the identity of "the thing which changes," under all the qualities and indwelling all the conditions. Is there any doubt that the X-ray, taken from the ordinary street current, is other than the ultra-violet light wave altered in its proportions ? Probably, the y-ray is simply the light-ray-wave, re-subdivided to the extreme of smallness. If so, we are dealing only with "the thing which changes" ; and it is a question of quality — of mathematics, of dosage, of ratio-to-cell-curve — in using solar energy to cause and to cure malignancy. Therefore, in the baldest form of diagram we place in opposition the fragments of the missing whole. Whoever fits the parts together reads the secret : THE RADIAL SUB-COMPONENTS (a) The Solar Ray, whose ultra-violet wave length fits the blood corpuscles curve ; (b) The X-ray, made from the ordinary street current, 1/10,000 the wave length of the first. 66 THE RADIAL SUB-COMPONENTS (c) The y-RAY, 1/100 of the wave length of the last; one million times smaller than the ultra-violet ray wave — "the pin- head to St. Peter's dome" at the cell border. Thus, the solar energy, as "the thing which changes," in different qualities and sizes touches the curve of the cell circumference. THE BIOLOGICAL SUB-COMPONENTS a) The Chlorophyll, storing the solar energy in the vegetable kingdom ; b) The Ozone, forming at the leaf-edge in the process; c) The Nitrogen, passing through the vegetable Intermediary to — d) The Animal Frame, made up of protein sub- stances, in contra-distinction with e) The Animal Force Reservoir, consisting of stored carbohydrates. f ) The Glands, comprising sex differentiation, color, reduction of chromosomes from tissue cell to germinal cell number; their invalidity involving loss of col- or, abnormal pigmentation, loss of re- sistance, loss of border-line integrity, resembling a demotion to asexual reproduction, without the differentiat- ing counter-process. THE RADIAL SUB-COMPONENTS 67 (g) The First Acquired and the Last Yielded Being the process of growth without differentiation. The last acquired was sex and its accompanying differ- entiation ; hence this is the first to go. The application of some of the radial to some of the biological factors reinforces (or interferes) and cures cancer. The application of some others of the radial to certain biological, interferes (or reinforces) and causes cancer. Whoever picks the needed sub-component from the first group and applies it properly to the falter- ing (or overspeeding) sub-component of the second group, will save 200 lives a day in the United States alone. FINIS. NOTES Some partially supporting views from institutional and duly recognized pathological authority, will be found in the following excerpts from Professor James Ewing's pa- per on "Precancerous Diseases and Precancerous Lesions/' from the New York Medical Record, December 5, 1914. SOLAR LIGHT: "Senile and presenile degeneration of the skin takes the form of keratosis, and is seen in the seaman's skin, and other disorders leading to multiple cancer. It affects ex- posed regions subjected to repeated irritation of sunlight, heat and cold." (See page 48.) GALLSTONES FAVOR CANCER : (THE RELATION IS CLOSE BETWEEN OBESITY AND GALL- STONES.) "The most notable example of carcinoma following chron- ic inflammation is probably that observed in the gall-bladder from cholelithiasis. The disease form 5 or 6 per cent, of all carcinomas (Kaufmann), and is four or five times as frequent in women as in men. Gallstones were present in 69 per cent, of Musser's 100 cases ; 70 per cent, in Fut terer's ; 85 per cent, in Zenker's ; 91 per cent, in Cour- voisier's; 95 per cent, in Siegert's, and 100 per cent, in Janowski's. (See page 37.) 69 70 NOTES THE INTEGRITY OF TISSUE FRONTIERS OF VI- TAL IMPORTANCE: "The cervical erosion is the most definite established lesion known to precede cervical carcinoma." (See page 66.) COAL TAR DYES ASSOCIATED WITH PITCH AND SOOT AS CANCER CAUSE "Specific vesical irritants as observed in analin workers are especially effective in producing vesical carcinomas, chiefly at the ureteral orifices (Rehn, Leichtenstern). A frgh proportion (50%) of these tumors are malignant (Ley- bert)." (See page 55.) PROTEIN DIET: "In fish, the functional overactivity and hypertrophy of the thyroid observed in crowded ponds where the animals are fed on protein diet leads in a small proportion of cases to malignant overgrowth, which is a specific form of can- cer. This condition has been produced under experimental conditions and fully traced by Gaylord." (See page 42.) The foreman of a well-known trout hatch- ery expressed to the writer the layman's conviction that thyroid cancer in Adirondack trout is due to the high per- centage of iron in the water, disclaiming any cancer in his own trout from the chopped meat diet.) THE ELUSIVE BIRTH MOMENT OF THE CANCER PROCESS : "Ribbert states that no one has ever seen the beginnings of a mammary cancer. Moreover, when a cancer does de- velop in chronic mastitis, it very soon overgrows and oblit- erates the original lesion. There is often a perceptible gap between the atypical proliferation and the smallest estab- NOTES 71 lished carcinomas. Hence comes the impression that when carcinoma is grafted on mastitis a wholly new disease is added." (See page 59.) GRAVES' DISEASE: "There is reason to believe that thyroid cancer of young girls and possibly at later ages sometimes arises under paral- lel conditions (to the thyroid cancer in fish, quoted above). Few cases of thyroid carcinoma develop in subjects with entirely normal thyroid history, but many follow goiter, intersitial thyroiditis and Graves' Disease. (See page 50.) "... On the other hand, extreme grades of some- what atypical cellular hyperplasia with giant cells and ill- formed alveoli, are observed in the wholly benign goiter of Graves' Disease." THE CANCER PROBLEM.* By EUGENE COLEMAN SAVIDGE, M.D.. NEW TORE. "It must be confessed that in spite of the time, brains, energy, and money which have been expended during the past few years in the attempt to solve the problem of can- cer in almost all parts of the civilized world, little or no apparent progress has been made." — Editorial, Medical Record, June 29, 1907. The present writer is as orthodox as any mem- ber of this society regarding the prompt operation for surely recognized malignant disease. He is not alone, however, in asking whether life is really prolonged by surgery in some cases, notably in malignant diseases of the uterus. Nevertheless, the majority of the profession at present, for the lack of better resource, advise prompt operation. But, because such provisional attitude is apt to grow in- to a habit during the years when we are losing our plasticity, is just why we should keep additionally alert to other possibilities, — while not wavering in the best we have. When your Chairman drafted me for this paper it was my intention to present you the sifting from a wide range of reading. I have not found time to do this; instead, I shall try to ask some questions *Read at a meeting of the Section on Obstetrics and Gynecology of the New York Academy of Medicine, March 26, 1908. 74 THE CANCER PROBLEM which will bring out your experience in the dis- cussion. This society will probably agree as follows re- garding the state popularly known as cancer. (The subdivisions will litter and obscure our discussion) : i. The quotation heading this paper has ac- curately stated our present relation to the problem of cancer. 2. That researches as to cancer cause based on bacteriological transmission — to go into detail — have yielded no result. Therefore nothing can be expected from either antiseptic or antitoxin treat- ment. 3. That even if the theory of wandering cell from embryonal life were capable of proof, such proof would give us nothing of value in treatment. We could never penetrate fetal life and anchor the displaced or wandering cell. 4. That though surgery has done thoroughly clean work, at least in uterine cases, it has been followed with prompt recurrence and speedy death. If this society does so agree it must necessarily hold that our present resource, while the best we have, is unsatisfactory ; and that our position, while not abandoning our best and time-honored resource, is one of "hopeful expectation." Notwithstanding the foregoing statements, the writer believes there are signs of promise important enough to merit studied consideration. We have an indication of the cancer cause. We have a sane hope, confirmatory of this indication, regarding the successful treatment of cancer. This indication, which becomes more conclusive the more we study it, lies in the physical variation in the isomeric qual- ity of the most primitive elements entering into the THE PHILOSOPHY OF MALIGNANCY 75 composition of protoplasm. (The isomers, let us refresh our minds, are "substances having the same centesimal composition, but whose molecules have essentially different structure and chemical prop- erties.") The trail of our search, therefore, leads directly to the subtle mystery why elemental carbon exists as coal and as diamond ; or why certain substances are, under varying conditions, dextrorotary and levorotary — diverting the rays in one quality to the right, in another, to the left — when submitted to polarized light. The hope of successful cure lies in the restora- tion, or the preservation, of certain ferments the secretions containing which seem to be altered, or abolished, long before the human organism reaches the state of cancer. As the ptyalin of the saliva, for example, mysteriously changes starch into dex- trin and sugar in a manner similar to the mysterious transformation of the isomers from right to left rotary quality, and vice versa, from one side of the polariscope to the other, this application of fer- ments to changed isomeric quality is an exact dove- tailing between theory of cause and hope of cure. It may be added that it is not based upon so simple a procedure as the application of trypsin to the local manifestation of cancer. The writer doubts if the cancer problem will ever be solved by the ap- plication of a juice to a spot; or even the hypo- dermatic application of a ferment to the organism. Without entering too deeply upon the great work on fermentation by Pasteur — beginning about i860, passing through the crucible of indifference if not ridicule, but now fully entered into the warp and woof of medical knowledge — let us consider in out- line its connection with cancer. 76 THE CANCER PROBLEM OR Pasteur discovered the dimorphism of the double tartrate crystal. One isomer in solution is dextro- rotary in the spectroscope; the other is levorotary. That is, one of these varieties of the same thing turns the polarized light to the right, the other turns it to the left. As a laboratory test, to sep- arate these two diverging forms of + he same thing, they were subjected to certain fermentative tests. The yeast plant ferment was found to act on the left isomer, while the ferment of the mold acted upon the right solution. Please stick a pin in this fact; it has a vital bearing on what follows. The left-hand isomer, susceptible to the yeast ferment, is indifferent to the mold ferment; and the right- hand isomer, susceptible to the mold, is unacted upon by the yeast plant. Another important point accented by Pasteur was the difference between the same thing — to use an apparent Hibernianism — according to its derivation. The difference between laboratory pro- ducts and the same substances derived from organic compounds was this: the natural organic products rotate the polarized light either to the right or left according to quality. — but always one way, to the exclusion of the other isomer. Or, as Duclaux, quoted by Beard, says: "Nature alone knows how to manufacture one isomer without making the other." So much for the "asymmetry of the carbon atom and the nitrogen pentavalent atom," — to quote the resonant technique. Now, Beard, building upon Pasteur's work, or independently of it, has discov- ered an analogous asymmetry in the organic as well as in the inorganic world. In certain fish and amphibians, he has found the existence of "two THE PHILOSOPHY OF MALIGNANCY 77 distinct and separate nervous systems in their life history, — the transient nervous system functioning for a time, then suddenly begins to fade away in slow degeneration." _ This analogy in the organic world may be simply significant; it may not mean that cosmic laws act on the elemental compounds of the ganglionic pro- toplasm sufficiently to divert the rotatory quality; as, for example, the irritation of a nerve center has produced glycosuria. On the other hand, it may mean more. As the embryological development of the human individual passes from the simple cell all the way up the line, distinctly through the fish- life analogy (remember, surgery is sometimes nec- essary to close the branchial clefts remaining open after birth, as evidence of the time in the evolution of the fetus when it had gills like a fish) — so might it be within the same range of possibility that there is a similar asymmetry of the nervous system in fetal life as that found in certain fish by Beard. But this would prove too much for the present writer's exposition; it would throw part of the causation back into fetal life, and except as ex- plaining fetal or adolescent cancers, would help us no more for practical curative purposes than the wandering cell theory of Conheim. I prefer to cite it as an analogy, that it may not disturb the bright- er hope. This asymmetry both in the organic and the in- organic compounds, like that of the two nervous systems, in the words of Beard, "is based upon the fundamental verity of the asymmetry of the carbon atom." Now, if the carbon atom were symmetrical, and carbon existed only as diamond, we would freeze to death in winter. So with our food stuff. If 78 THE CANCER PROBLEM OR the carbon atom should suddenly become symmet- rical, existing only in its left-hand isomer while our digestive ferments attack only the right-hand iso- mer, or vice versa, we would likewise starve to death. With warehouses full of levoalbumins, levocarbohydrates, famine would still stalk the land, because our digestive ferments could no more change them into assimilable substance than they now can the granite of the mountains. Further, and of transcending importance to life, — for without the fact there would be no life, — this very powerlessness of our digestive ferments to act upon the levoalbumins of the human body is perhaps the basal reason why the human stomach does not digest its own walls. Otherwise, like the anaconda engaged in swallowing his own tail, at the conclusion of each complete digestive act the individual would disappear in a cloud of his own dust and vapor. Isomeric integrity may be the life principle; it is certainly the life principle which prevents self- digestion, as any stomach in condition would digest another stomach if put therein, — as we eat tripe, for example. In fact, this is Herbert Spencer's theory of nerve force: that "in nervous action the disturbance transmitted is a wave of isomeric change." In other words, our molecules vibrate from right to left, or the reverse, to produce nerve action. Should they stay wrongly right, or wrong- ly left, or stop altogether, it is not hard to presume disaster. To assail isomeric integrity, therefore, may be to entail sectional death; and cancer undoubtedly is this. The importance of the ferments of the body, — called here digestive, and including the opsonins THE PHILOSOPHY OF MALIGNANCY 79 of the blood, — is becoming daily clearer to the pro- fession. They are the elements of assimilation, the agents of protection. Yet daily we have to ex- plain to the laity that, when the secretions are locked up by fever, — when the ferments are not be- ing secreted, — putting food requiring digestion in- to the alimentary canal is just like hiding meat particles between the teeth. There being no fer- ments to prepare it for assimilation, it carries with itself and gathers from about it, elements for its own decay. It is a toxin instead of a nutrition. Plus secretion it is friend; minus secretion, it is foe and poison. But recently even further importance has been shown in the ferments. The opsonins in the blood are still acquaintances almost too new for men out- side of laboratories to discuss. Yet we are suffi- ciently established in our knowledge to say that certain ferments in the blood make the germ pal- atable to the phagocyte, thereby assisting these lat- ter to digest specific infections in the blood. We can talk about the opsonic index in furunculosis, in tuberculosis, in syphilis; we can almost definitely state that for each infection an opsonin ferment exists in the blood, which when in condition pro- tects the organism by making that specific germ pal- atable to the blood scavengers — thereby assisting in the destruction of the infection. We even pretend to say that when the opsonic index for tuberculosis is below normal the patient has tuberculosis, even though no bacilus may yet be found. We are even injecting our products into the blood to irritate or stimulate the opsonins for the specific malady we wish to conquer. I am able at this point to report a perfectly well authenticated opsonin cure of malignant tertiary 80 THE CANCER PROBLEM OR syphilis of the most extreme type. A miner, af- flicted with ignored syphilis, untreated until its ma- lignancy crippled him, was stricken with smallpox. His employer, one of my own patients, himself having had smallpox, charitably nursed this double leper through the scourge. Recovery from small- pox left him permanently cured of his tertiary syph- ilis. The explanation then was that the smallpox germ had killed the great pox germ. The explana- tion is now simpler. The stimulation of the op- sonins by the acute infection brought a collateral stimulation of the opsonins of syphilis, and this ferment caused the cure of the man of a disease in- curable in him at that time by drugs. Whether this was an accidental collateral stimulation of op- sonins, or a direct stimulation, we do not know. But suppose we had always available a less objection- able but equally swift and efficient method, would not humanity greatly profit? Please, therefore, let us revivify in our con- sciousness the absolute necessity of the ferments in making food really food to us, — selecting our bread from stone for us by practically the same process that Pasteur used in his laboratory years ago. With sure selective instinct, keener than the scent of the bloodhound, as imperious as the call of an acid for its base, these our agents of assimilation and protection stand at the portal of our being, and decide : this is right deflecting, this is left deflecting ; this is bread, this is stone — saying to one, "Go ye into tissue" ; and to the other, "Get you hence !" Let us also make vivid to ourselves this concep- tion of the protective and curative powers con- tained in these newly-discovered ferments in our blood. All this is in vital relation with the cancer problem. THE PHILOSOPHY OF MALIGNANCY 81 In a paper read before the New York Obstetri- cal Society in 1903, the present writer said: "Wo- men have lacerations, retained secundines, ectopics, fibroids, and cancers. And we operate on them brilliantly, with this or that technique, on whose minor details we spend much time in discussion. But in all these things — / am not sure that I will except even the malignant troubles — we get behind the outward symptom and arrive at first causes when we 'get them together' in the tubular system, as we clinch our fist, or contract our body when expecting a blow. We thus symbolize the great passion of the universe — the movement from cir- cumference to center — 'the love of a ton of lead for the center of the earth.' " This reference to the malignant troubles was more than literary fervor. I had long pondered over the fact that cancer was locally but an ex- aggeration of normal cell tissue, as seen by the microscope. As the isomers may be defined as "the difference between the same thing," so cancer may be called an isomer of normal tissue. Then, certain distinctly noted antecedents of cancer had. forced themselves upon my attention in my opening professional days, when abundant clinical material was at hand. In most of the can- cers I saw, the appearance of the patient suggested the diagnosis. Is this not a common experience with others? The local examination usually only confirms what we knew before we make it. When, then, did the pallor, the significant loss of weight, the distinctive physiognomy — the cancer family re- semblance—begin with relation to the malignancy? This was my first self-questioning. The diminution, or absence of the free hydro- chloric acid in the gastric juice in cancer of the 82 THE CANCER PROBLEM OR stomach was the next insistent point. Did this ap- pear before the cancer? Had it any relation to the cancer cause? Or was it the result of malignancy, and why? What caused the marked increase in saliva no- ticeable in cancer patients? The saliva has its fer- ment. Was this increase simply more water poured out in the struggle of the organism to bring up its supply of ptyalin? — just as we have more urine in advanced Bright's, in the effort of the or- ganism to get out in this way the diminishing pro- portion of solid constituents. Or was it an actual increase in ferment production in the saliva? And did it precede cancer; or did cancer precede it? What, too, had the thryoid gland to do with it? Why was the thyroid altered in cancer, and did the change precede the malignancy or come with it? We all know what subtle influence the thyroid gland, when given by mouth, has on the organism — how obesity melts away and the individual disap- pears fractionally from the landscape. Perhaps, like the fleeing obesity, it is the malignancy that is kept on the run by a vigilant thyroid in healthy in- dividuals. Perhaps, in whole or in part, it is the slowly changing thyroid which allows the installa- tion of the malignancy in the others : who knows ? Has this change in the thyroid any connection with the significant loss of weight? If we can ac- complish this result with thyroid taken from an animal and administered by mouth, could not the thyroid within the individual by perversion cause this undue reduction in weight? If we saw in a patient with suspected malignancy a slowly gaining weight would we not give it a second consideration? Graves' disease with its glandular — and hence ferment — relations, has always seemed to me to be THE PHILOSOPHY OF MALIGNANCY 83 a preparatory stage of cancer — the cure either averting the cancer, or the severity of the prepara- tory stage killing the patient before the culmina- tion is reached. Just as the spleen is charged with certain ob- scure relations to pernicious anemia and leucocy- themia — as grave as cancer — so may the spleen, pancreas, as well as the ductless and intestinal glands, be said to bear an equal relation to the ma- lignancy of cancer. Indeed, noting the frequency of sarcomatous growths in the bone marrow in pernicious anemia, who can say whether a given case may not have been first a bone-marrow cancer, or even a blood- cell cancer before it becan e pernicious anemia ? If this is not the order, the reverse order is equal- ly convincing. For if pernicious anemia prepared for cancer, this proves a step in the march toward cancer — for the arrest of which there is certainly hope. I have elsewhere cited a significant seeming re- lation between ferment secretion and another dis- ease, — presenting an analogy with the present dis- cussion. If adrenalin released into the blood causes the arterial tension observable long before the en- suing Bright's disease is shown in the urine, may there not be a relation between this release of ad- renalin and the suppressing of the selective action of the ovaries, as seen in patients after double ovariotomy? Testicular inactivity, in presenil- ity of the other sex, has also seemed to show the same relation to arterial tension long before urinal- ysis shows a reason in the kidney. Let us, therefore, not lose the vivid realization that all these glandular activities have to do with the ferments upon whose integrity depends our life. 84 THE CANCER PROBLEM OR It is a sane hope that such glands, showing incip- ient failure, can be restored to full integrity. That we do know a force that will cure some cancers and cause some cancers I believe will be denied by 'no man in the profession. This is one thing known. A second thing known is the action of this force upon the ferments. We have thus two known links in the chain. With the mighty uplifting of the veil during the last decade few more important hidden things have been revealed than ^r-ray and radium. The exact re- lation of these two rays to each other, to the sun, and to polarized light, we do not know. May we call these occult powers of light, cosmic, telluric, or radial? This much at least we know: the sun, the .r-ray, and the radium ray — this occult radical force — both cure and cause diseases, and each acts significantly upon the ferments. The solar action upon fermentation is embodied in the proverbs of all the languages : "Where the sun comes the doctor shuns ; mold is found on the shady side, etc." But this, like many of our other half-truth complacencies, will need readjust- ment. Briefly, this "radial" force can cause disease: Blonds can not live in the tropics ; they lack a cur- tain of pigment to shield their blood cells. Qui- nine has been found to have opalescent qualities which rob the Plasmodium of light required for its existence. Hence, this quinine-bestowed curtain to the blood cell containing the Plasmodium, explains backwards and forwards why quinine is good and sunlight bad for malaria. (Remembering what has already been said about pernicious anemia, why may not this anemia with its blood cells uncurtained THE PHILOSOPHY OF MALIGNANCY 85 by hemoglobin allow too great a radial action from the sun upon the protective epsonic ferments, and if only by their destruction and no more direct action, aid in the mysterious change in isomeric quality?) Recall the burns caused by the x-ray; the inhibiting action on the procreative glands, etc. In the Annals of Surgery, November, 1907, is a thorough study of the increasing list of ;r-ray car- cinomata. See also Osier's "Modern Medicine," Vol. I, pages 63 and 64, for data regarding gan- grene and cancer from ^r-rays, as well as injuries following exposure to radium. With equal brevity let us look at the side of cures from the occult radial forces. There are ap- parently more cures than hurts. In the Berliner Minis che Wochenschrift, April 1, 1907, Widmer reports the cure of a carcinoma by repeated exposure to the direct rays of the sun. Radiotherapy has been employed with success in pernicious anemia by Grego of Geneva. (I ask again, how can we know it was not marrow can- cer?) The ^r-rays have also been used with suc- cess in similar conditions by Beaujard of Paris. (Semaine Medical, Nov. 17, 1907, page 202.) Dr. Robert Abbe, in the Medical Record of Oc- tober 12, 1907, presents an extended paper on the subject of cures by radium and its influence on an- imal and bacterial life. For example, dry seed ex- posed to radium has its growth retarded after planting, according to the time of exposure. In animal life, meal worms are repressed in their life history cycle by radium, while their brothers and sisters, "unradiumized," complete several cycles as beetles, eggs, meal worms, etc. So likewise is bac- terial life checked or destroyed. This radial action — of sun and ray and ray — is 86 THE CANCER PROBLEM OR probably in the direction of a cure when it acts re- pressively on the noxious bacterial (or ferment) life. It is probably acting in the direction of hurt when it destroys our assimilative and protective ferments. Our conception does not require that it act di- rectly as a changer of isomeric quality — though it probably can do this as easily as the sun draws pigment — for it is easy to see how it reaches the same result indirectly when it destroys the ferments which would otherwise digest the noxious isomer. Proven beyond all cavil, however, is the existence of this occult force which brings both hurt and cure. We know that it acts on the ferments; we know that ferments destroy one isomer and allow the other to remain untouched; we know then that it thus acts at least once removed on isomers. We know what the force does, pro and con ; but we have not yet succeeded in bridling it so that it will always act pro and never con. This may be our next success when we have learned its rela- tion to isomeric integrity. But that one known force can thus act pro and con presupposes that other forces may so act. This march of antecedents, in cancer has formed an intensely interesting chapter in my line of special study. For fifteen years I have been cautiously insinuating under the notice of the profession dis- cussion of many minor and detached matters, that the thus printed word might be used in presenting an entirely new system of approach in medicine. This I have called "Synthetical Medicine," and have published in the Medical Record, April 7, 1906. Synthetical Medicine, the science of the unclassi- fied, "assumes to recognize and postpone that even- tual trouble, be it in heart, liver, kidney, or blood- THE PHILOSOPHY OF MALIGNANCY 87 vessel, which a grouping and study of present con- ditions will often show years before it takes place in its text-book form; ... it asks, what trouble in addition to the text-book classification, has the patient ?" The profession has not understood this, nor con- sidered it very important, nor shown much interest ; but I cite it here to show the formed mental habit which brought this march of antecedents in can- cer under my notice. The extent of my debt in this special subject of cancer to the suggestions of Beard and Bell is ap- parent. But the conception herein differs widely from that held by either. If the asymmetry of the carbon atom causes one form of the same thing to assume a right rotary quality and another form a left rotary to the polar- ized light; if one of these quailties is assimilable under our digestive ferments, is acted upon by our protective ferments, and the other is not; if the cell proliferation of cancer is simply an exaggera- tion of normal cell proliferation, — either of oppo- site isomeric quality, hence insusceptible to our ferments ; or of the same quality, and undisciplined by our ferments because impaired — then, whatever deflects our protoplasm from one isomer to its op- posite, or impairs the quality of our protective fer- ments, may be said to be the cause of cancer, long before its local manifestation. And whatever de- flects this malign isomer to its benign opposite, or whatever restores the integrity of the failing fer- ments, — long before the local manifestation — may be said to be the cure for cancer. If the radial forces — the sun and ray and ray- even if not acting directly upon the carbon atom in our protoplasm, act repressively on our protective 88 THE CANCER PROBLEM OR ferments, thereby allowing the wrong isomer to flourish into exaggerated cell life like the rank foliage of the tropics, then the "radial" forces may be said to cause such a cancer. If pigment absorption, hair graying, hemoglobin disappearance, allow the radial forces to attack the cancer opsonin among the thus uncurtained blood- cells, then here is a more remote cause of cancer. Conversely, if we can shield our protective fer- ments from the destructive radial forces, and at the same time expose our noxious elements there- to, the radial forces may be said to cure such can- cers. If a perverted thyroid, withdrawn from its mys- terious guardianship against wrong isomers, leaves them to flourish like weeds in the absence of the gardener, while the recreant gland disrobes the skeleton of flesh, then perverted thyroid is another cause of cancer. And conversely, the restoration of such a thyroid is the cure for cancer so produced. But whether one item, or all, whatever restores glandular activity, replaces the disturbed ferment protection, restores the isomeric integrity, — that item, or aggregate of items, thereby cures the can- cer. The incipient cause, the study of the march of antecedents, the application of the cures, all lie in the domain of Synthetical Medicine. The use of trypsin for the cure of developed cancer as Beard says, "fits like a key in the lock" with the theory outlined above. Beard's idea is not its local application, but the overwhelming the sys- tem with it hypodermically. Many careful men are trying this and I believe a fair view of their conclu- sion is that trypsin does not cure the cancer. That trypsin may fail even in most developed THE PHILOSOPHY OF MALIGNANCY 89 cases would not nullify the importance of its testi- mony if it succeeds in any. Fof if it has any power over the local manifestation of cancer — aside from a certain digestive action such as pineapple juice might have on thickened mucus in the throat, — it proves that the excessive cell proliferation by be- ing susceptible to the ferment, contains a carbon atom of that isomeric quality acted upon by that ferment — and not of the opposite quality. This is as sure a test as our test for albumin and sugar. Here, then, is light; here is differentiation; here is invitation along a new line of research. For while medical humanity may prefer a sign, a specific, a single "distinctly defined" process of application, we must not hope always to have given us such a definite entity as we received in the anti- toxin for diphtheria, for example. It is doubtful whether we shall ever be able to apply a juice to a spot, merely, and cure a cancer. Nor can we hope to secure a single injectable curative juice. How simple this would be for the man who had the juice! The very theory of the complex causes of cancer is against this hope. But if we can increase the opsonin ferments, stimulate a phagocytosis, and thus make a man's blood corpuscles eat up his own cancer; or if we can stop the change in the thy- roid, the alteration of the saliva, the gastric, pan- creatic, and intestinal juices, the ominous loss of weight, the ghastly robbery of the hemoglobin cur- tain for the cells of the blood, there may still be ad- ditional help from the injectable juice, or from the local juice at the local spot. But the source is more important than the local manifestation. This conception of making an element in a man's blood eat up his own disease, though hardly born to the medical profession, probably points the line 90 THE CANCER PROBLEM OR of our future march. But to use this new possi- bility we must see things earlier than we are wont under our present methods, which teach us to see only the accomplished fact and blind us to the widely scattered preliminary stages. It is only when these are finally focused that they realize our textbook descriptions. For example, though all medical men may not agree, I firmly believe that the more skilful among us can foretell the advent of tuberculosis long be- fore the bacillus gives any sign of its presence. A rougher, cruder diagnostician, who must have his hectic, cavity, and bacillus, before he can see the tuberculosis, naturally is limited to short range pro- cedure. He is more of a prognostician than a di- agnostician. He can foresee death more clearly than cure. His resources are climate, overfeeding, and creosote, — frequently helpful; but far removed from what might have been done had the earlier picture been seen — the falling opsonic index, the wasting muscles, the depleted vitality, the unfair nutritive division, — the bulk of the nutrition going to the brightly burning nervous system, with the lower forms of tissue slowly starving, as the sap- pers and miners prepare the soil for the seed. We should infer the harvest when we see the plow. This is Synthetical Medicine. If cancer, therefore, is the climax of a synthet- ical progression, finally showing itself locally, we may be able to avert it when so understood and so attacked. Perhaps this has been done. I would not dare report seriously to this Acad- emy what I honestly hal f -believe : that these begin- ning changes have been seen and have been pur- posefully attacked, and the cancer has been averted. But this is a fair report: Patients with all the pre- THE PHILOSOPHY OF MALIGNANCY 91 liminaries have been restored to health. But of course there is no proof that cancer (uterine, is the special reference), would ever have culminated. But this, too, is a fair report: If any man here- after sees a patient with these detailed preliminar- ies of cancer state — long before the patient has the disease classified in our text-books — and does not purposefully wipe offending item after item off the slate, such a man is not protecting his patient as he should. To accentuate the relation of the general condi- tion to cancer, let me continue from the quotation begun at the head of this paper: "There are five distinct groups of malignant tu- mors, and Mr. Sutton draws attention to the fact that in dealing with these tumors, the position is such that we are unable to point to any absolute histological indication of malignancy, and that clin- ical and histological characters must be considered together. Microscopic examination, even when conducted by the most expert microscopist, can not determine with precise certainty whether a tumor is malignant or not. 'The true character of such tu- mors can only be determined by careful observa- tion of the patient.' " Dr. Robert A. Murray, before the New York Obstetrical Society, November 12, 1907, quoted au- thorities on this same fact. Many cases of fibroids show precisely the same microscopy as cancer. Prof. James Ewing, at the last meeting of this section, February 6, 1908, quoted authorities who characterize chorioepithelioma as varying so much in significance that at one extremity it is criminal to operate because it is so benign as to recover sometimes spontaneously; while at the other ex- tremity it is criminal to operate because it is so 92 THE CANCER PROBLEM OR malignant that the end is hastened by operation. These facts are vitally significant. The same mi- croscopic slide, therefore, which, plus history of un- impaired general condition, would bring a benign verdict, becomes cancer when pinned to the his- tory of cachexia. The cachexia is the cancer, therefore. For a broken down and infected fibroid, like an infected leg, is only a surgical problem of infection and suppuration, or of gangrene from compression — it has no relation to the general problem of impaired ferments, isomeric integrity, plus a local malignancy. "An ounce of prevention is worth a pound of cure," and "keeping in good condition," as a basis of this theory is as fatuous a conception as would be futile the efforts of the man lazily adopting it. On the contrary, it implies direct, purposeful attack upon a start toward a definite and fatal end; it is by no means a good-natured, tolerant, passive state of ordinary hygiene. Human limitation implies that we rarely see or hear the obscure upon which we have not had our attention concentrated. Our experience, as em- bodied in the answers to the following questions, may therefore be no experience at all, unless we have specially directed our attention to the points involved. I respectfully solicit the wisdom of the profession upon the following points : i. Who have seen cancer develop in patients that have been under observation, say a year before the cancer became unmistakable? 2. What has been the relation observed between the cancer and the cachexia? What observations have been made of the various secretions? When did the glands begin to fail; when did the weight loss beein? etc. THE PHILOSOPHY OF MALIGNANCY 93 3. This question is preceded with an avowal that no desire exists to discredit surgical methods. Re- stricting the question to uterine cases, what is the honest conviction of those with the experience re- garding the quick and possibly more virulent return of the malignancy after operation? (Perhaps those who operate most frequently are the least qualified to sayhow long life might have lasted without an operation, as they do not know this side. The ex- cellence of their equipment in one direction is the measure of their limitation in the other.) Yet the strictest estimate is necessary on this point, for if there is anything in the new trend, surgery may be the worst thing to do to a cancer. Like the po- tato which would grow but one plant as a whole, subdivided grows a plant for each eye — like cell segmentation, like sowing parts each capable of re- producing the whole — cutting may be simply spread- ing elsewhere the local manifestation. Quite on the other hand, if it be true that the only nonrecurrences of cancer after surgery are found with those who were operated upon before the advent of cachexia, then the new trend all the more imperatively demands even prompter surgery. Starting, therefore, with the frank admission that nothing as yet has been accomplished; still clinging to our best procedure of surgery, is there not rea- son to consider this sequence with scientific open- ness of mind? A certain known, but not understood, "radial" force can act upon products containing the asym- metrical carbon atom to change their isomeric qual- ity as shown by polarized light. That one force can so act presupposes that other forces may so act. The natural ferments contained in the secretions of the body, digestive and protective, "digest" one 94 THE CANCER PROBLEM series of isomers and leave the opposite series un- touched. Therefore, the action of this occult "radial" force — this assailing of isomeric integrity, — can change protoplasm from digestibility to in- digestibility to the natural ferments, and vice versa. The local cancer product consists presumably of changed isomers allowed to grow instead of being "digested." This is made all the more probable by the disappearance of the opsonic ferments in the blood in all such diseases as have been subjected to controlled observation; and, specifically in cancer, by the gradual suppression of the enumerated fer- ments. These ferments — presumably — begin to modify long before transition from the preliminary to the final state called cancer. Therefore, even if there be no change in isomeric quality, the secre- tion suppression would explain the growth of the cancer weed cells that effective ferments would have removed. If there be no flaw in these significances, the cure for cancer as well as its prevention, lies in the realm of Synthetical Medicine, to which the atten- tion of the profession is again respectfully directed. If the foregoing seems as radical as some of my earlier papers, I beg that you will pardon this al- most unpardonable reminder: Ten years ago before this Academy, alone in the profession so far as I know, I had the temerity to say regarding overzealous abdominal operations al- most precisely what Dr. Boldt, at our last section meeting, outlined to you in reviewing "the recent advances in gynecology." The adverse reception first given this presenta- tion, and the cordial welcome greeting it ten years later, are alike matters of record, — both gratifying and instructive. [Reprinted from the American Journal of Obstetrics and Diseases of Women and Children, Vol. LXII, No. 2, 1910.] WHAT MAY WE NOW TELL THE COMMUN- ITY REGARDING CANCER?* BY EUGENE COLEMAN SAVIDGE, M. D., New York. It is estimated that 80,000 unsuspecting people in this country, apparently well at this moment, will be afflicted with incurable cancer in six months. These are Crile's figures. It would be important to these to establish that there is a recognizable pre-cancer stage. Has cancer an antecedent stage in which it may be prevented or cured? What special conditions favor the development of cancer? These are vital questions. In "The Cancer Problem," published two years ago {Medical Record, May 2, 1908), the present writer gave reasons for belief in a pre-cancer stage; pointed to the relation between glandular activity, ferment integrity, and cancer; dwelt upon the possibility of making the organism cure its own cancer; and announced a half -conviction that this had been done. Exactly one month later Crile published hi9 * Read before the New York Obstetrical Society, April 12, 1910. 96 THE CANCER PROBLEM OR memorable paper, under identical title, likewise announcing belief in a pre-cancer stage, and giving the result of his study of the blood of cancer subjects. September 4, 1909, Dr. E. F. Bashford, Director of the Imperial Cancer Research Fund, published his report of that body. And February 26, 1910, Hodenpyle published his intensely significant account of a patient who did cure herself of her inoperable and apparently fatal cancers, and whose ascitic fluid has had an arresting or modifying effect on other cancers, now being studied. Therefore there may, indeed, be an antecedent stage to cancer. Cancer may depend vitally upon condition. Cancer may have been cured by the organism growing it, in other cases than that re- ported by Hodenpyle. But while debating the unknown we can point out certain known avenues of cancer approach, many of which can be blocked. The time limit will permit only a bare deduction, and a quotation to prove it — principally from Director Bashford's report, cited above. The Imperial Cancer Research Fund in seven years has studied 200,000 mice. It has sixty differ- ent species of cancer growing. It is still growing the identical cancers which have been transplanted through four successive generations of mice. It fires the imagination to see proved a relatively im- THE PHILOSOPHY OF MALIGNANCY 97 mortal living entity, nourished by a great-grand- sire's blood, transplanted and retransplanted, and still promising a continuous life. I quote: "Seven years ago no one conceived it possible that portions of the mammalian organism could be kept growing for a period four times the life of the whole animal." Could this same process succeed in an antitheti- cal benign sense, no sound organ — from adrenal to brain — would ever be interred with our acci- dental dead, but instead transplanted upon the living defective. Authority. — -Capable men, studying sufficiently ample material, with scientific method of recorded observation and honest intent in collating and re- porting, bring us as near final authority as human intelligence can get in an evolving question. Such is the source of my quotation for deduction. IDENTITY OF HUMAN CANCER WITH TRANSPLANTED CANCER EN MICE. Director Bashford says: "The experimental production, at will, of the lesions of carcinoma and sarcoma, has to-day be- come a mere matter of laboratory routine. . . . With the lapse of time the material accumulated has made the demonstration of the anatomical lesions and clinical features more and more perfect, and to-day it lacks nothing in completeness." CANCER IS A DISEASE OF AGE. "The age incidence of cancer reveals a law ap- 98 THE CANCER PROBLEM OR plicable to all vertebrates. Statistically, cancer is a function of age; and when considered biologically, a function of senescence." CANCER CANNOT BE INOCULATED UPON THE AGED. The seeming contradiction in the following is very important. It may disclose the whole secret of the pre-cancer stage: " Old mice are less suited for transplanting than young. . . . "Old mice cured themselves in four weeks. . . . There is more rapid growth in the human subject when developing in the young. " Senescence is not necessary for cancer's contin- uous growth. "Old age itself renders mice absolutely resistant to the inoculation of cancer. "The growth is frequently terminated by the immunity which the tumors induce against them- selves." THE RELATION OF CONDITION TO CANCER. Age brings complete imunity to inoculation. The fact is simply cited here with reference to condition and cancer. The seeming contradiction will be treated later. Age brings complete immunity; complete im- munity is a condition; and how to get that con- dition under control is the problem for the expert. THE INTERMEDIATE STAGES OF CONDITION. But what of these intermediate stages of condi- tion when the battle wages across the frontier of THE PHILOSOPHY OF MALIGNANCY 99 immunity and back again into susceptibility? I quote from source cited: "Propagable tumors inoculated into mice with spontaneous tumors caused the spontaneous tumors to outstrip the inoculated tumor." This certainly shows the relation of changed condition. Again: "Repeated transplantations aided the process (in the new mice) with yet no progress taking place in the mouse yielding the mother tumor." Some soil is therefore more inviting than other soil for the same cancer. Again: " As yet we have not got much beyond denning that the cancer cell has many of the properties of rapidly growing tissue, without containing any- thing extraneous, and without secreting anything directly deleterious to the organism." The present writer will later cite a distinct minus quality in the cancer cell. Continuing : "There is no evidence of toxic products (from propagated tumors) injurious to the hosts; on the contrary, there is a compensatory enhanced vitality on their part. ... In the end compensation breaks down, and finally the tumor lives at the expense of the host. . . . The host becomes an assimilative and excretory apparatus for the tumor." COMPENSATORY ENHANCED VITALITY IN CANCER. This observation is very important. The very superficial sense of well-being — like the exaltation of the initial fever — is not only one of the phases 100 THE CANCER PROBLEM OR of the pre-cancer condition, but also a proof that the organism is fighting and checking the cancer up to a certain point. THE CACHEXIA AND THE CANCER. The cachexia is the recognizable symbol of van- ished immunity, abandoned resistance, and the arrival of the hopeless malignancy. Unfortunately this is usually the condition in which the surgeon gets his cancer patient. Continuing : "In 1905 we described the cycle alterations in the energy and growth of Jensen's tumor. Since then we have been able to confirm these observa- tions on every one of the sixty propagable tumors growing in the laboratory. ... In the human subject there are corresponding fluctuations in the growth of cancer. In one part of the tumor the growth is proceeding rapidly, in another part slowly. . . . Further, secondary nodules of growth are known to disappear while others are growing, and occasionally primary growths have disap- peared." A REMEDIAL STRUGGLE IN EVERY CANCER HOST. Every case has its remedial struggle. Dr. Hodenpyle's cancer patient had in her organism sufficient power of remedial struggle to cure her own cancer. Condition — of unknown quality, but yet condition — prevailed against cancer. Cancer usually prevails against condition. The problem of the expert is to discover the quality and defect of such condition. THE PHILOSOPHY OF MALIGNANCY 101 CANCER CANNOT BE CAUGHT; IT MUST BE GROWN. Is cancer infectious or contagious? Director Bashford says: " Cancer is ubiquitous, yet there are most strik- ing limitations to its conveyance from one indi- vidual to another. Continued growth takes place after inoculation into animals of the same species only. . . . Inoculation is only successful by im- plantation of living cells, but experiments show that this risk (that is, the risk of a surgeon acquir- ing it while operating) is negligible, if it exists at all in nature." This would imply no danger to man from eating a lower animal afflicted with cancer — as for example trout, particularly cancer-ridden among fish — but would indicate that a cannibal as host might acquire the cancer of his banquet. If cancers of lower animals have no danger to man, we yet know that sheep thyroid and hog pepsin act beneficently in the human subject. Has man only a susceptibility to their benign products? Does nature make an exception wherein only "good health is catching?" CANCER IS NOT HEREDITARY BUT ACQUIRED OR GROWN. The report says : " The question of the hereditary transmission of cancer has not been settled either one way or the other for man. The short duration of the mouse's life . . . makes it the ideal animal for the study of heredity. . . . No indication of any inborn 102 THE CANCER PROBLEM OR When and how did this disassociation begin? PROGRESSIVE, PROPORTIONATE ALTERATION OF CELL POISE. There is a known time when distinct changes take place in cell activities, and especially in the internal secretions which — as all know — govern blood pressure, and through blood pressure control function. These alterations, beginning about the time of maturity — like the turn of the leaf in autumn — are normally proportionate and in adjusted relation. Flexor and extensor muscles, vasoconstrictor and vasodilator secretions, etc., increase and atrophy in like proportion and at appointed time. They are progressively immune to cancer in whom these changes so proceed. In the abnormal non-immune few who get cancer, these processes go on irregularly, out of proper timing with respect to compensatory antagonisms. For example, a vasodilator internal secretion failing earlier than normal would leave behind a relatively more forceful vasoconstrictor antagonism — and vice versa — than if the rhythm and proportion had been proper. Childhood, as a further example — with its mar- velous activity of cell reproduction — is yet immune from sex-cell growth until the thymus goes. But at any time after that, until age bestows immunity, we may bring at will the "flashes" of the meno- THE PHILOSOPHY OF MALIGNANCY 103 — extending to some complete immunity; to others a (rare) self -cure; but to the majority of the afflicted a rhythmic attempt at self -cure, with final defeat. It bears no relation to kind of diet; it is not hereditary; it is not contagious or infectious. Cancer must be grown, and its cell is differentiated according to the tissue from which it arises. From this known we pass to what, though unsettled, has sufficiently crystallized to give us practical aid. A PROGRESSIVE IMMUNITY TO CANCER COMES WITH NORMAL AGE. If the aged cannot be inoculated at all; if the less aged rapidly cure themselves of transplanted cancers; and if — as in the human subject — the younger the host the more virulent the cancer — then logic forces a conclusion. Some change in the organism makes cancer progressively harder to inoculate. And yet facts also show that cancer is a disease of age. How explain? The explanation is found in the conception of a pre-cancer stage. The minority, non-immune, who acquire spon- taneous cancer in age, do so because they have become disassociated from that force which confers the progressive immunity upon the majority. These non-immune could also be inoculated in age — with the effect of hastening the spontaneous cancer, already cited. 10-i THE CANCER PROBLEM OR disposition playing a part in determining either a local or constitutional liability to the disease, or even so much as an enhanced suitability for inocula- tion, has been shown. . . . Therefore it would appear that the disease ... is always acquired. . . . Other facts are even more emphatically opposed to the idea (of heredity)." THE KIND OF DIET BEARS NO RELATION TO CANCER. " Exceptional opportunities are afforded in India for the study of the incidence of cancer in vege- tarians and flesh-eaters, since the diet is strictly ordained by the customs of the different native castes. In India the disease occurs irrespective of vegetarian or meat diet, just as it occurs in the herbivorous and carnivorous mammals." Nutritive excess or deficiency is not contemplated in the above quotation. THE DIFFERENTIATION IN THE CANCER CELL. Cancer cells differ according to the kind of tissue from which they are derived. The report says: " Cancer cells are specialized. No single species is an exact duplicate of the others. They still possess characters of less obvious kind." Cancer cells are therefore obviously derived from many kinds of tissue. RESUME OF AUTHORITATIVE STATEMENTS. Mouse cancer is analogous with human cancer. Cancer is a disease of age. Cancer cannot be in- oculated upon the aged. Condition is vital in cancer THE PHILOSOPHY OF MALIGNANCY 105 pause — as by double ovariotomy. But age confers an immunity to this vasodilator disturbance which yet may be said to be a disturbance of age. The internal secretions which cause it — the younger the subject, the stronger the disturbance — have been progressively, mutually, proportionately ad- justed. To the remotest individual cell there is an adjusted cell poise, entirely lacking at the crucial periods — as at puberty; as at maturity; when the boy's unstable voice, the girl's helpless blush, the matron's vasodilator hot-flashes — paint the story in broadest relief. Those in whom a "ferment" fails too soon, or lasts too long, have therein the basis of the pre- cancer stage. There may be special danger in the belated secretion, outlasting its normal inhibiting antagonists. These become the non-immune to cancer, and may grow it in the presence of a con- tributing cause. SPECIAL IRRITATIONS AND CANCER. Those in the first group, immune to cancer, un- dergo without danger the identical irritations which produce cancer in the non-immune few. Irritations unquestionably produce cancer, but only in the presence of another cancer element. Without the cancer element they produce no cancer. Irritations are therefore only a half-cause of cancer. 106 THE CANCER PROBLEM OR THE BASAL HALF-CAUSE OF CANCER. This lies as deep as the concept of the intra- atomic corpuscle, which, growing out of our recent study of radium, has revolutionized modern physics. For example : "Cancer of the abdominal skin is unknown in Europe, but occurs with extraordinary frequency in Kasmir, where natives wear next to the skin an oven containing burning charcoal." This hot oven is the half-cause of this special cancer, restricted to Kasmir; but not the whole cause, for only a few who wear the oven get the cancer. What is the other cancer element? Likewise, chewing betel-nut in Ceylon and India brings a great frequency of cancer of the inside of the mouth almost exclusively in these regions. But the majority chew with impunity; another element must obtain with the few who acquire cancer therefrom. A hundred sewing women may each prick a finger the same number of times, but irritation brings cancer only to the non-immune few. So with all the locomotive drivers, and all the smokers of cigarette or short-stem clay pipe; the identical irritation will bring the actinic or radiant cancer — on shin-bone or tongue, respectively — only to the few non-immune. And it is the same all through the list of irritations from which cancer may be developed. THE PHILOSOPHY OF MALIGNANCY 107 THE CANCER ELEMENT ALONE AND NO SPECIFIC IRRITATION. It would be important to prove that specific irri- tations have to be added to the basal cancer ele- ment to make cancer. For we surely could avoid the specific irritations. It may be — let us hope not — that life's exigencies would always furnish sufficient wear and tear to develop the basal element of cancer. The basal half-cause may thus be really the whole cause. WHAT IS THE BASAL CANCER ELEMENT? If we can once agree that age is a condition and not a date — that one can die of acute old age in childhood, as in thymic death — there need be no exceptions to the dogma that cancer is in relation to senescence. The known interrelations between the internal secretions of the body, and the variation between their times of appearance and fading, makes this an easy conception. For what is our youth if it be not the integrity of our glandular activities with their "ferments?" A man may be no older than his arteries, but behind the tubular works of the body are the protecting internal secretions. We are trustees of our thymus for the brief watch of our childhood, and in a few decades we surrender our thyroid. Life is a progressive, pro- portionate adjustment of cell poise to changing 108 THE CANCER PROBLEM OR conditions of internal secretions — as thymus and thyroid, sex glands and suprarenals, lessen and finally withdraw their special secretions. As a gland upon a platter our youth is automatically passed onward at each measurement of time, and each period prints itself beyond the effacing power of cosmetic. Puberty and the climacteric — and then the skin takes the pigment the hair ought to have. An illness may put a man to bed young, and shortly release him irrevocably old. Of another we predicate, regardless of dates, " He has his color- ing yet; his glands are working; his 'ferments' are still with him." One has failed in adjustment; the other is ad- vancing in proper proportions. FUNCTIONS OF THE INDIVIDUAL CELL AND THE SPECIAL CELL FERMENT. If the cell has not five senses, it has five func- tions. It must (a) assimilate and excrete to nourish itself; (b) it must reproduce itself; (c) it must per- form special selective function according to its class of tissue; (d) it must help to keep the frontier of its own tissue class inviolate; (e) and it must make its general contribution to the whole organism. Besides secreting its own bile, or tears, or adre- nalin — according to kind — each must make a gen- eral vital contribution to the whole. The aggre- gate vitality is the sum of the units. THE PHILOSOPHY OF MALIGNANCY 109 For this purpose each cell has a store of albumen and a special cell ferment, and in this latter lies all the distinctive quality of the cell. And the provable law governing the better known internal secretions presumptively governs the special dis- tinctive secretion of the individual cell. Therefore altered cell poise, as the basal cause of cancer, probably means disproportionate change in its own ferment secretion as well as the changes in those internal secretions whose cycles are better known, and provable. THE BORDER-LINE BETWEEN SPECIAL TISSUES. One of the duties of a cell is to guard the fron- tier line of its own special tissue. The lip must not extend over the face; the uterine mucous mem- brane must not proliferate over the vaginal cervix. The connective tissue must not extend into the pulp; the cataract must not invade the eye; nor the hardening process creep into the artery. The excrescence grows out over the surround- ing tissue as much from failure of repelling power as from overcharge of energy in the growth. Improper timing and disproportionate atrophy of one tissue puts it at a disadvantage when facing contiguous tissue— or its antagonistic inhibiting relation. A.nd tissue frontiers — between pulp and con- nective tissue, between gland and capsule, between fiber and sheath — are the almost exclusive seats of cancer. 110 THE CANCER PROBLEM OR A DISCERNIBLE MINUS IN THE CANCER CELL. There is only space here to cite the role of the chromosomes in cell life — especially cell reproduc- tion. Likewise, only simple mention can be made of the difference in thermic and actinic color re- lation, respectively, as shown by stainability, pre- sented by the cell representing sex from the female and the cell representing sex from the male. For example, the ovum cell differs from the sperm cell, not only in the quality of its color relation — one being thermal and the other chemic — but in that the male cell has exactly one less chromosome than the female cell. Search for the lost chromosome, therefore, may solve the problem of sex deter- mination. Now the cancer cell instead of being just one chromosome minus — as the male cell is less than the female — contains just half the number of chromosomes shown by the normal cell. Do the lost chromosomes bear any relation to the problem? This minus is visible and accords with the logic of the cancer situation. RELATION OF THE FERMENTS TO CANCER. Two years ago the writer drew attention to the relation between thyroid and cancer. Director Bashford says on this subject: "The trout is peculiary liable under certain con- ditions, to a general hyperplasia of the thyroid. THE PHILOSOPHY OF MALIGNANCY 111 We have records of 2000 cases, in many of which true carcinomata have supervened, as shown on the slide." At the same time the present writer outlined how isomeric attractions and repulsions are related to blood pressure and quality and the internal secretions. This is, presumptively, the process in the individual cell, viz.: "Pasteur discovered the dimorphism of the double tartrate crystal. One isomer in solution is dextrorotatory in the spectroscope; the other is levorotatory. That is, one of these varieties of the same thing turns the polarized light to the right, the other turns it to the left. As a laboratory test, to separate these two diverging forms of the same thing, they were subjected to certain fermentative tests. The yeast plant ferment was found to act on the left isomer, while the ferment of the mold acted upon the right solution. Please stick a pin in this fact; it has a vital bearing on what follows. The left-hand isomer, susceptible to the yeast ferment, is indifferent to the mold ferment; and the right- hand isomer, susceptible to the mold, is unacted upon by the yeast plant. Now, if the carbon atom were symmetrical, and carbon existed only as diamond, we would freeze to death in winter. So with our food stuff. If the carbon atom should suddenly become symmetrical, existing only in its left-hand isomer while our digestive ferments attack only the right-hand isomer, or -vice versa, we would likewise starve to death. With warehouses full of levo-albumins, levo-carbohydrates, famine would still stalk the land, because our digestive ferments could no more 112 THE CANCER PROBLEM OR change them into assimilable substance than they now can the granite of the mountains. Further, and of transcending importance to life — for without the fact there would be no life — this very powerlessness of our digestive ferments to act upon the levo-albumins of the human body is per- haps the basal reason why the human stomach does not digest its own walls." Coalescing capacity with this, and coalescing in- capacity with the other, isomer of the protoplasm atom is probably the basis of intracell action and the tissue frontier guards. THE FERMENTS AND BLOOD PRESSURE; BLOOD PRESSURE AND FUNCTION. More easily proved is this relation. All the functions — cerebration, salivation, digestion, etc. — start and stop with the rise and fall of blood pressure. Will-power may determine it to a cer- tain extent, but the real regulators of blood press- ure are the glands that secrete the stuff — respect- ively vasoconstrictor, vasodilator. Leaving aside the hemolytic action of the great glands like the spleen — whose blood dissolving power, when in disorder, quickly blanches the organism, as in Graves' disease, leukemia, pernicious anemia, and kindred diseases which seem pre- cancer steps — let us see what is known of the re- lation between the internal secretions and blood pressure. THE PHILOSOPHY OF MALIGNANCY 113 THE INTERNAL SECRETIONS. The following is abstracted from " Internal Secre- tions,"* by Professor Oliver T. Osborne, of Yale: "The pituitary body secretes vasoconstrictor stuff. ... It seems probable that in every case of gigantism the pituitary body hypersecretes. . . . The thyroid secretes vasodilator stuff. . . . The thyroid secretion has been shown to exert pro- found influence on the secretion of the pancreas. . . . It should be emphasized that disturbances of the interrelations between the ductless glands, whether by disturbed secretion of one or more of them, . . . may sufficiently disturb the pancreatic secretion to cause glycosuria, and yet no apparent disease of the pancreas be found on autopsy. "The suprarenals secrete vasoconstrictor stuff. ... A proper amount seems necessary to the normal development and health of the red blood corpuscles. ... A preparation of ovaries con- tains a vasodilator substance. . . . When both ovaries are removed . . . various symptoms occur which are evidently distinctly due to the removal of the ovarian internal secretion. . . . Cancer of the breast may cease to grow after a double ovariotomy; this before the menopause. . . . Os- teomalacia has been arrested by the removal of the ovaries; hence this may be due to disturbed ovarian secretion, perhaps an oversecretion. . . . Ovarian substance has been administered in Graves' disease with some apparent success. . . . "There is a secretion from the testicles which is necessary for the normal development and health of the male. . . . Castration before puberty cause9 jien and animals to grow taller than normal, and * Jour. A. M. A., February 26, 1910. 114 THE CANCER PROBLEM OR to grow fat. ... If there is thyroid insufficiency the testicles do not develop properly, and if the testicles are removed the thyroid remains small. The testicle contains vasodilator stuff. " The parotid shows an unexplained relation to the sexual glands — there is the ever frequent oc- currence of the infection of mumps causing the peculiar metastasis to the testicles and ovaries. "The thyroid is most fully developed and active from the age of puberty to the age of forty-five. From that time its secretion is decreased until the gland atrophies in old age. Sexual excitement increases thyroid secretion, and when there is hyosecretion of the thyroid sexual desire is lost." Note the antagonisms: Vasoconstrictor inhibits vasodilator. Hypersecretion of pituitary body grows a giant, whereas an excess of thyroid secre- tion checks development of the epiphyses and makes the dwarf. The relation between the vasodilator glands is very close, and they begin fading about the same time. The vasoconstrictor stuff from adrenals and pituitary body apparently outlasts the vasodilator supply. Not to reduce humanity to a sweetbread, we may yet say that pleasure, joy, blandness, youth, are vasodilator stuff; while anxiety, fear, acidity, acerbity, and age are vasoconstrictor stuff. THE CONSTRICTOR QUALITY OF CONNECTIVE TISSUE. The "pulp" of cell or organ — like the pulp of an orange — is its distinctive dynamic part, whereas THE PHILOSOPHY OF MALIGNANCY 115 the connective tissue is the frame-work holding the motor in working position. An exact harmonizing of the picture of vasocon- strictor overcoming vasodilator is shown in the hardening processes of age. The connective tissue constricts the elastic pulp tissues of the arteries, of the brain, of the heart, the liver, the kidney — just as by metaplasia true bone tissue is formed in the choroid of the eye which has lost its function. The acids bite off the enamel of the teeth, extend the womb out over the vaginal cervix, extend the erosion from the vagina, in senile vaginitis, out over the vulva. What is this, also, but failure of contiguous ter- ritory to guard its frontier? A disproportionate, premature or late, action of one set of secretion accents the quality of its inhibiting antagonizing secretion. We may therefore discover that cancer is a question of internal secretion dosage. THE QUESTION OF DOSAGE AND THE PRE- CANCER STATE. Remembering that " the x-ray will cure some cancers and will cause some cancers," remember- ing that internal secretion excess or defect can grow a giant or dwarf; remembering also that elec- tricity will stimulate a muscle and, contradictorily, under proper dosage, will likewise induce general anesthesia, — we can better realize the importance of dosage. As fat cells and connective-tissue cells have 116 THE CANCER PROBLEM OR neither the selective ferment nor function of "pulp" cells, their substitution for "pulp" cells of course reduces the production of the selected in- ternal secretions. Just as the obese are absolutely as well as relatively deficient in blood quantity, so must the change to the non-selective cell result in absolute lessening of ferment production. If we can increase the pulp cells by use — as we can muscle cells, for example — does this not of necessity increase the supply of special cell ferment to go therewith? And might not an extra supply of cell ferment — could we separate it and give it as we daily give the larger gland substances — act protectively against the connective tissue invasion, as thyroid substance acts against obesity? Does the ascitic fluid used by Hodenpyle — from his self -cured patient — contain any of the extruded special cell ferment? I ask the hematologists: Is the blood from which is deducted the vasodilator stuff of the thyroid and sex glands and the vasoconstrictor stuff (>,, he adrenals the same as the blood from which no such deduction is being made — because of failing or failed glands? Is not the retention of these unlifted secretions in the blood as abnormal as the retention of urea in renal insufficiency? Probably the secret of the precancer stage lies in the relation between altered cell poise and this in- ternal secretion timing and dosage. Practical Deductions. — If cancer cannot be THE PHILOSOPHY OF MALIGNANCY 117 caught, cannot be inherited, but must be grown, and if its growth depends upon precancer condition plus a specific irritation, we have help for the community. A purposeful scrutiny by one who knows the rhythm of the inevitable readjustments in cell poise may allow corrections of internal secretion timing and dosage. As glands regulate internal secretion, and as internal secretions govern blood pressure and quality, and as these later determine function and longevity — herein is the field of pre- cancer work. Glands have been awakened from torpor; more "ferments" have remoistened the dry channels; more pulp has been regrown be- tween the constricting frame-work tissue. A dose of aconite, even — vasodilator — has sometimes soft- ened a pulse and poured out through the kidneys a large increase of urea, as though releasing the kidney "pulp" from constriction to action. These results are all the more striking where one set of glands falls under or outruns the ordained pro- portion and progression in senescence. While the general wear and tear of life is still beyond our reach, the specific irritations which are the half -causes of cancer can surely be controlled. Give the sewing woman knowledge and a thimble. Lengthen the knowledge and short-stem clay pipe of the smoker. Teach the locomotive driver to shield his shins as the x-ray operator screens his ferments from the deadly ray. The betel-nut need 118 THE CANCER PROBLEM not be chewed, and the hot oven on the abdomen may be insulated if it must be carried hot. CUT QUICKLY OR NOT AT ALL IN CANCER. Prompt surgery may remove chronic irritations, ulcers, irritated moles, benign tumors — all of which Crile calls "potential cancers." But surgery should be early, and should not wait until cachexia shows. It is because of the precancer condition that local heat, electricity, local juices and late surgery will all frequently fail. Though one local spot be removed, another will grow, the basal cause remaining the same. Thus purposeful scrutiny, effective treatment, and prompt surgery enable us to control abso- lutely the special irritant half-causes of cancer. The unsuspecting eighty thousand — probably a million in the world — marked for hopeless cancer in six months should know this. I hazard the belief that many could be saved if they knew it and acted upon the knowledge. And as to the basal half-cause of cancer, this much can now be positively stated from our new knowledge of the reparative processes of the organ- ism: Every cancer patient at the start furnishes a partial cure of his own cancer. What can we add to make it a whole cure? It is one of the maxims of synthetical medicine that An incurable thing may sometimes be cured by curing all the other curable things in sight.