DISEASE AND ITS CAUSES
W. T. COUNCILMAN, A.M., M.D., LL.D. Professor of Pathology, Harvard University
New York Henry Holt and Company London Williams and Norgate The University Press, Cambridge, U.S.A.
In this little volume the author has endeavored to portray disease as life under conditions which differ from the usual. Life embraces much that is unknown and in so far as disease is a condition of living things it too presents many problems which are insoluble with our present knowledge. Fifty years ago the extent of the unknown, and at that time insoluble questions of disease, was much greater than at present, and the problems now are in many ways different from those in the past. No attempt has been made to simplify the subject by the presentation of theories as facts.
The limitation as to space has prevented as full a consideration of the subject as would be desirable for clearness, but a fair division into the general and concrete phases of disease has been attempted. Necessarily most attention has been given to the infectious diseases and their causes. This not only because these diseases are the most important but they are also the best known and give the simplest illustrations. The space given to the infectious diseases has allowed a merely cursory description of the organic diseases and such subjects as insanity and heredity. Of the organic diseases most space has been devoted to disease of the heart. There is slight consideration of the environment and social conditions as causes of disease.
Very few authors are mentioned in the text and no bibliography is given. There is lack of literature dealing with the general aspects of disease; the book moreover is not written for physicians, and the list of investigators from whose work the knowledge of disease has been derived would be too long to cite.
It has been assumed that the reader has some familiarity with elementary anatomy and physiology, and these subjects have been considered only as much as is necessary to set the scene for the drama. I am indebted to my friend, Mr. W. R. Thayer, for patiently enduring the reading of the manuscript and for many suggestions as to phrasing.
DEFINITION OF DISEASE.—CHARACTERISTICS OF LIVING MATTER.—CELLS AS THE LIVING UNITS.—AMOEBA AS TYPE OF A UNICELLULAR ANIMAL.—THE RELATION OF LIVING MATTER TO ENVIRONMENT.—CAPACITY OF ADAPTATION TO ENVIRONMENT SHOWN BY LIVING MATTER.—INDIVIDUALITY OF LIVING MATTER.—THE CAUSES OF DISEASE EXTRINSIC.—THE RELATION OF THE HUMAN BODY TO THE ENVIRONMENT.—THE SURFACES OF THE BODY.—THE INCREASE OF SURFACE BY GLAND FORMATION.—THE REAL INTERIOR OF THE BODY REPRESENTED BY THE VARIOUS STRUCTURES PLACED BETWEEN THE SURFACES.—THE FLUIDS OF THE BODY.—THE NERVOUS SYSTEM.—THE HEART AND BLOOD-VESSELS.—THE CELLS OF THE BLOOD.—THE DUCTLESS GLANDS 9
NO SHARP LINE OF DEMARCATION BETWEEN HEALTH AND DISEASE.—THE FUNCTIONAL NUTRITIVE AND FORMATIVE ACTIVITIES OF CELLS.—DESTRUCTION AND REPAIR CONSTANT PROCESSES IN LIVING MATTER.—INJURIES TO THE BODY.—THE EFFECT OF HEAT.—THE ACTION OF POISONS.—THE LESIONS OF DISEASE.—REPAIR.—THE LAWS GOVERNING REPAIR.—RELATION OF REPAIR TO COMPLEXITY OF STRUCTURE AND AGE.—THE RESERVE FORCE OF THE BODY.—COMPENSATORY PROCESSES IN THE BODY.—OLD AGE.—THE DIMINUTION OF RESISTANCE TO THE EFFECTS OF THE ENVIRONMENT A PROMINENT FACTOR IN OLD AGE.—DEATH.—HOW BROUGHT ABOUT.—CHANGES IN THE BODY AFTER DEATH.—THE RECOGNITION OF DEATH 40
THE GROWTH OF THE BODY.—GROWTH MORE RAPID IN EMBRYONIC PERIOD.—THE COOeRDINATION AND REGULATION OF GROWTH.—TUMORS.—THE GROWTH OF TUMORS COMPARED WITH NORMAL GROWTH.—SIZE. SHAPE AND STRUCTURE OF TUMORS.—THE GROWTH CAPACITY OF TUMORS AS SHOWN BY THE INOCULATION OF TUMORS OF MICE.—BENIGN AND MALIGNANT TUMORS.—EFFECT OF INHERITANCE.—ARE TUMORS BECOMING MORE FREQUENT?—THE EFFECT PRODUCED BY A TUMOR ON THE INDIVIDUAL WHO BEARS IT.—RELATION OF TUMORS TO AGE AND SEX.—THEORIES AS TO THE CAUSE OF TUMORS.—THE PARASITIC THEORY.—THE TRAUMATIC THEORY.—THE EMBRYONIC THEORY.—THE IMPORTANCE OF THE EARLY RECOGNITION AND REMOVAL OF TUMORS 62
THE REACTIONS OF THE TISSUES OF THE BODY TO INJURIES.—INFLAMMATION.— THE CHANGES IN THE BLOOD IN THIS.—THE LMIGRATION OF THE CORPUSCLES OF THE BLOOD.—THE EVIDENT CHANGES IN THE INJURED PART AND THE MANNER IN WHICH THESE ARE PRODUCED.—HEAT REDNESS SWELLING AND PAIN.—THE PRODUCTION OF BLISTERS BY SUNBURN.—THE CHANGES IN THE CELLS OF AN INJURED PART.—THE CELLS WHICH MIGRATE FROM THE BLOOD VESSELS ACT AS PHAGOCYTES.—THE MACROPHAGES.—THE MICROPHAGES.—CHEMOTROPISM.—THE HEALING OF INFLAMMATION.—THE REMOVAL OF THE CAUSE.—CELL REPAIR AND NEW FORMATION.—NEW FORMATION OF BLOOD VESSELS.—ACUTE AND CHRONIC INFLAMMATION.—THE APPARENTLY PURPOSEFUL CHARACTER OF THE CHANGES IN INFLAMMATION 79
INFECTIOUS DISEASES.—THE HISTORICAL IMPORTANCE OF EPIDEMICS OF DISEASE.—THE LOSSES IN BATTLE CONTRASTED WITH THE LOSSES IN ARMIES PRODUCED BY INFECTIOUS DISEASES.—THE DEVELOPMENT OF KNOWLEDGE OF EPIDEMICS.—THE VIEWS OF HIPPOCRATES AND ARISTOTLE.—SPORADIC AND EPIDEMIC DISEASES.—THE THEORY OF THE EPIDEMIC CONSTITUTION.—THEORY THAT THE CONTAGIOUS MATERIAL IS LIVING.—THE DISCOVERY OF BACTERIA BY LOEWENHOECK IN 1675.—THE RELATION OF CONTAGION TO THE THEORY OF SPONTANEOUS GENERATION.—NEEDHAM AND SPALLANZANI.—THE DISCOVERY OF THE COMPOUND MICROSCOPE IN 1605.—THE PROOF THAT A LIVING ORGANISM IS THE CAUSE OF A DISEASE.—ANTHRAX.—THE DISCOVERY OF THE ANTHRAX BACILLUS IN 1851.—THE CULTIVATION OF THE BACILLUS BY KOCH.—THE MODE OF INFECTION.—THE WORK OF PASTEUR ON ANTHRAX.—THE IMPORTANCE OF THE DISEASE 97
CLASSIFICATION OF THE ORGANISMS WHICH CAUSE DISEASE.—BACTERIA SIZE SHAPE STRUCTURE CAPACITY FOR GROWTH MULTIPLICATION AND SPORE INFORMATION.—THE ARTIFICIAL CULTIVATION OF BACTERIA.—THE IMPORTANCE OF BACTERIA IN NATURE.—VARIATIONS IN BACTERIA.—SAPROPHYTIC AND PARASITIC FORMS.—PROTOZOA.—STRUCTURE MORE COMPLICATED THAN THAT OF BACTERIA.—DISTRIBUTION IN NATURE.—GROWTH AND MULTIPLICATION.—CONJUGATION AND SEXUAL REPRODUCTION.—SPORE FORMATION.—THE NECESSITY FOR A FLUID ENVIRONMENT.—THE FOOD OF PROTOZOA.—PARASITISM.—THE ULTRA MICROSCOPIC OR FILTERABLE ORGANISMS.—THE LIMITATION OF THE MICROSCOPIC.—PORCELAIN FILTERS TO SEPARATE ORGANISMS FROM A FLUID.—FOOT AND MOUTH DISEASE PRODUCED BY AN ULTRA MICROSCOPIC ORGANISM.—OTHER DISEASES SO PRODUCED.—DO NEW DISEASES APPEAR? 116
THE NATURE OF INFECTION.—THE INVASION OF THE BODY FROM ITS SURFACES.—THE PROTECTION OF THESE SURFACES.—CAN BACTERIA PASS THROUGH AN UNINJURED SURFACE?.—INFECTION FROM WOUNDS.—THE WOUNDS IN MODERN WARFARE LESS PRONE TO INFECTION.—THE RELATION OF TETANUS TO WOUNDS CAUSED BY THE TOY PISTOL.—THE PRIMARY FOCUS OR ATRIUM OF INFECTION.—THE DISSEMINATION OF BACTERIA IN THE BODY.—THE DIFFERENT DEGREES OF RESISTANCE TO BACTERIA SHOWN BY THE VARIOUS ORGANS.—MODE OF ACTION OF BACTERIA.—TOXIN PRODUCTION.—THE RESISTANCE OF THE BODY TO BACTERIA.—CONFLICT BETWEEN PARASITE AND HOST.—ON BOTH SIDES MEANS OF OFFENSE AND DEFENSE.—PHAGOCYTOSIS.—THE DESTRUCTION OF BACTERIA BY THE BLOOD.—THE TOXIC BACTERIAL DISEASES.—TOXIN AND ANTITOXIN.—IMMUNITY.— THE THEORY OF EHRLICH 135
SECONDARY TERMINAL AND MIXED INFECTIONS.—THE EXTENSION OF INFECTION IN THE INDIVIDUAL.—TUBERCULOSIS.—THE TUBERCLE BACILLUS.—FREQUENCY OF THE DISEASE.—THE PRIMARY FOCI.—THE EXTENSION OF BACILLI.—THE DISCHARGE OF BACILLI FROM THE BODY.—INFLUENCE OF THE SEAT OF DISEASE ON THE DISCHARGE OF BACILLI.—THE INTESTINAL DISEASES.—MODES OF INFECTION.—INFECTION BY SPUTUM SPRAY.—INFECTION OF WATER SUPPLIES.—EXTENSION OF INFECTION BY INSECTS.—TRYPANASOME DISEASES.—SLEEPING SICKNESS.—MALARIA.—THE PART PLAYED BY MOSQUITOES.—PARASITISM IN THE MOSQUITO.—INFECTION AS INFLUENCED BY HABITS AND CUSTOMS.—HOOKWORM DISEASE.—INTERRELATION BETWEEN HUMAN AND ANIMAL DISEASES.—PLAGUE.—PART PLAYED RATS IN TRANSMISSION.—THE PRESENT EPIDEMIC OF PLAGUE 159
DISEASE CARRIERS.—THE RELATION BETWEEN SPORADIC CASES OF INFECTIOUS DISEASE AND EPIDEMICS.—SMALLPOX.—CEREBROSPINAL MENINGITIS.—POLYOMYELITIS.—VARIATION IN THE SUSCEPTIBILITY OF INDIVIDUALS.—CONDITIONS WHICH MAY INFLUENCE SUSCEPTIBILITY.—RACIAL SUSCEPTIBILITY.—INFLUENCE OF AGE AND SEX.—OCCUPATION AND ENVIRONMENT.—THE AGE PERIOD OF INFECTIOUS DISEASES 185
INHERITANCE AS A FACTOR IN DISEASE.—THE PROCESS OF CELL MULTIPLICATION.—THE SEXUAL CELLS DIFFER FROM THE OTHER CELLS OF THE BODY.—INFECTION OF THE OVUM.—INTRAUTERINE INFECTION.—THE PLACENTA AS A BARRIER TO INFECTION.—VARIATIONS AND MUTATIONS.—THE INHERITANCE OF SUSCEPTIBILITY TO DISEASE.—THE INFLUENCE OF ALCOHOLISM IN THE PARENTS ON THE DESCENDANTS.—THE HEREDITY OF NERVOUS DISEASES.—TRANSMISSION OF DISEASE BY THE FEMALE ONLY.—HEMOPHILIA.—THE INHERITANCE OF MALFORMATIONS.—THE CAUSES OF MALFORMATIONS.—MATERNAL IMPRESSIONS HAVE NO INFLUENCE.—EUGENICS 197
CHRONIC DISEASES.—DISEASE OF THE HEART AS AN EXAMPLE.—THE STRUCTURE AND FUNCTION OF THE HEART.—THE ACTION OF THE VALVES.—THE PRODUCTION OF HEART DISEASE BY INFECTION.—THE CONDITIONS PRODUCED IN THE VALVES.—THE MANNER IN WHICH DISEASE OF THE VALVES INTERFERES WITH THEIR FUNCTION,—THE COMPENSATION OF INJURY BY INCREASED ACTION OF HEART.—THE ENLARGEMENT OF THE HEART.—THE RESULT OF IMPERFECT WORK OF THE HEART.—VENOUS CONGESTION.—DROPSY.—CHRONIC DISEASE OF THE NERVOUS SYSTEM.—INSANITY.—RELATION BETWEEN INSANITY AND CRIMINALITY.—ALCOHOLISM AND SYPHILIS FREQUENT CAUSES OF INSANITY.—THE DIRECT AND INDIRECT CAUSES OF NERVOUS DISEASES.—THE RELATION BETWEEN SOCIAL LIFE AND NERVOUS DISEASES.—FUNCTIONAL AND ORGANIC DISEASE.—NEURASTHENIA 219
THE RAPID DEVELOPMENT OF MEDICINE IN THE LAST FIFTY YEARS.—THE INFLUENCE OF DARWIN.—PREVENTIVE MEDICINE.—THE DISSEMINATION OF MEDICAL KNOWLEDGE.—THE DEVELOPMENT OF CONDITIONS IN RECENT YEARS WHICH ACT AS FACTORS OF DISEASE.—FACTORY LIFE.—URBAN LIFE.—THE INCREASE OF COMMUNICATION BETWEEN PEOPLES.—THE INTRODUCTION OF PLANT PARASITES.—THE INCREASE IN ASYLUM LIFE.—INFANT MORTALITY.—WEALTH AND POVERTY AS FACTORS IN DISEASE 241
DISEASE AND ITS CAUSES
DEFINITION OF DISEASE.—CHARACTERISTICS OF LIVING MATTER.—CELLS AS THE LIVING UNITS.—AMOEBA AS TYPE OF A UNICELLULAR ANIMAL.—THE RELATION OF LIVING MATTER TO THE ENVIRONMENT.—CAPACITY OF ADAPTATION TO THE ENVIRONMENT SHOWN BY LIVING MATTER—INDIVIDUALITY OF LIVING MATTER.—THE CAUSES OF DISEASE.—EXTRINSIC.—THE RELATION OF THE HUMAN BODY TO THE ENVIRONMENT.—THE SURFACES OF THE BODY.—THE INCREASE OF SURFACE BY GLAND FORMATION.—THE REAL INTERIOR OF THE BODY REPRESENTED BY THE VARIOUS STRUCTURES PLACED BETWEEN THE SURFACES.—THE FLUIDS OF THE BODY.—THE NERVOUS SYSTEM.—THE HEART AND BLOOD-VESSELS.—THE CELLS OF THE BLOOD.—THE DUCTLESS GLANDS.
There is great difficulty, in the case of a subject so large and complex as is disease, in giving a definition which will be accurate and comprehensive. Disease may be defined as "A change produced in living things in consequence of which they are no longer in harmony with their environment." It is evident that this conception of disease is inseparable from the idea of life, since only a living thing can become diseased. In any dead body there has been a preexisting disease or injury, and, in consequence of the change produced, that particular form of activity which constitutes life has ceased. Changes such as putrefaction take place in the dead body, but they are changes which would take place in any mass similarly constituted, and are not influenced by the fact that the mass was once living. Disease may also be thought of as the negation of the normal. There is, however, in living things no definite type for the normal. An ideal normal type may be constructed by taking the average of a large number of individuals; but any single individual of the group will, to a greater or less extent, depart from it. No two individuals have been found in whom all the Bertillon measurements agree. Disease has reference to the individual; conditions which in one individual would be regarded as disease need not be so regarded in another. Comparisons between health and disease, the normal and the abnormal, must be made not between the ideal normal and abnormal, but between what constitutes the normal or usual and the abnormal in a particular individual.
The conception of disease is so inseparably associated with that of life that a brief review of the structure and properties of living things is necessary for the comprehension of the definition which has been given. Living matter is subject to the laws which govern matter, and like matter of any other sort it is composed of atoms and molecules. There is no force inherent in living matter, no vital force independent of and differing from the cosmic forces; the energy which living matter gives off is counterbalanced by the energy which it receives. It undergoes constant change, and there is constant interchange with the environment. The molecules which compose it are constantly undergoing change in their number, kind and arrangement. Atom groups as decomposition products are constantly given off from it, and in return it receives from without other atom groups with which it regenerates its substance or increases in amount. All definitions of life convey this idea of activity. Herbert Spencer says, "Life is the continuous adjustment of internal relations to external conditions." The molecules of the substances forming the living material are large, complex and unstable, and as such they constantly tend to pass from the complex to the simple, from unstable to stable equilibrium. The elementary substances which form living material are known, but it has hitherto not been found possible artificially so to combine these substances that the resulting mass will exhibit those activities which we call the phenomena of life. The distinction between living and nonliving matter is manifest only when the sum of the activities of the living matter is considered; any single phenomenon of the living may appear also in the non-living material. Probably the most distinguishing criterion of living matter is found in its individuality, which undoubtedly depends upon differences in structure, whether physical or chemical, between the different units.
Certain conditions are essential for the continued existence of living matter. It must be surrounded by a fluid or semi-fluid medium in order that there may be easy interchange with the environment. It must constantly receive from the outside a supply of energy in the form of food, and substances formed as the result of the intracellular chemical activity must be removed. In the case of many animals it seems as though the necessity of a fluid environment for living matter did not apply, for the superficial cells of the skin have no fluid around them; these cells, however, are dead, and serve merely a mechanical or protective purpose. All the living cells of the skin and all the cells beneath this have fluid around them.
Living matter occurs always in the form of small masses called "cells," which are the living units. The cells vary in form, structure and size, some being so large that they can be seen with the naked eye, while others are so small that they cannot be distinctly seen with the highest power of the microscope. The living thing or organism may be composed of a single cell or, in the case of the higher animals and plants, may be formed of great numbers of cells, those of a similar character being combined in masses to form organs such as the liver and brain.
In each cell there is a differentiated area constituting a special structure, the nucleus, which contains a peculiar material called "chromatin." The nucleus has chiefly to do with the multiplication of the cell and contains the factors which determine heredity. The mass outside of the nucleus is termed "cytoplasm," and this may be homogeneous in appearance or may contain granules. On the outside there is a more or less definite cell membrane. It is generally believed that the cell material has a semi-fluid or gelatinous consistency and is contained within an intracellular meshwork. It is an extraordinarily complex mass, whether regarded from a chemical or physical point of view. (Fig. 1.)
A simple conception of health and disease can be arrived at by the study of these conditions in a unicellular animal directly under a microscope, the animal being placed on a glass slide. For this purpose a small organism called "Amoeba" (Fig. 2), which is commonly present in freshwater ponds, may be used. This appears as a small mass, seemingly of gelatinous consistency with a clear outline, the exterior part homogeneous, the interior granular. The nucleus, which is seen with difficulty, appears as a small vesicle in the interior. Many amoebae show also in the interior a small clear space, the contractile vesicle which alternately contracts and expands, through which action the movement of the intracellular fluid is facilitated and waste products removed. The interior granules often change their position, showing that there is motion within the mass. The amoeba slowly moves along the surface of the glass by the extension of blunt processes formed from the clear outer portion which adhere to the surface and into which the interior granular mass flows. This movement does not take place by chance, but in definite directions, and may be influenced. The amoeba will move towards certain substances which may be placed in the fluid around it and away from others. In the water in which the amoebae live there are usually other organisms, particularly bacteria, on which they feed. When such a bacterium comes in contact with an amoeba, it is taken into its body by becoming enclosed in processes which the amoeba sends out. The enclosed organism then lies in a small clear space in the amoeba, surrounded by fluid which has been shown to differ in its chemical reaction from the general fluid of the interior. This clear space, which may form at any point in the body, corresponds to a stomach in a higher animal and the fluid within it to the digestive fluid or gastric juice. After a time the enclosed organism disappears, it has undergone solution and is assimilated; that is, the substances of which its body was composed have been broken up, the molecules rearranged, and a part has been converted into the substance of the amoeba. If minute insoluble substances, such as particles of carmine, are placed in the water, these may also be taken up by the amoeba; but they undergo no change, and after a time they are cast out. Under the microscope only the gross vital phenomena, motion of the mass, motion within the mass, the reception and disintegration of food particles, and the discharge of inert substances can be observed. The varied and active chemical changes which are taking place cannot be observed.
Up to the present it has been assumed that the environment of the amoeba is that to which it has become adapted and which is favorable to its existence. Under these conditions its structure conforms to the type of the species, as do also the phenomena which it exhibits, and it can assimilate food, grow and multiply. If, during the observation, a small crystal of salt be placed in the fluid, changes almost instantly take place. Motion ceases, the amoebae appear to shrink into smaller compass, and they become more granular and opaque. If they remain a sufficiently long time in this fluid, they do not regain their usual condition when placed again in fresh water. None of the phenomena which characterized the living amoebae appear: we say they are dead. After a time they begin to disintegrate, and the bacteria contained in the water and on which the amoebae fed now invade their tissue and assist in the disintegration. By varying the duration of the exposure to the salt water or the amount of salt added, a point can be reached where some, but not all, of the amoebae are destroyed. Whether few or many survive depends upon the degree of injury produced. Much the same phenomena can be produced by gradually heating the water in which the amoebae are contained. It is even possible gradually to accustom such small organisms to an environment which would destroy them if suddenly subjected to it, but in the process of adaptation many individuals will have perished.
It is evident from such an experiment that when a living organism is subject to an environment to which it has not become adapted and which is unfavorable, such alterations in its structure may be produced that it is incapable of living even when it is again returned to the conditions natural to it. Such alterations of structure or injuries are called the lesions of disease. We have seen that in certain individuals the injury was sufficient to inhibit for a time only the usual manifestations of life; these returned when the organism was removed from the unfavorable conditions, and with this or preceding it the organisms, if visibly altered, regained the usual form and structure. We may regard this as disease and recovery. In the disease there is both the injury or lesion and the derangement of vital activity dependent upon this. The cause of the disease acted on the organism from without, it was external to it. Whether the injurious external conditions act as in this case by a change in the surrounding osmotic pressure, or by the destruction of ferments within the cell, or by the introduction into the cell of substances which form stable chemical union with certain of its constituents, and thus prevent chemical processes taking place which are necessary for life, the result is the same.
The experiments with the amoebae show also two of the most striking characteristics of living matter. 1. It is adaptable. Under the influence of unusual conditions, alterations in structure and possibly in substance, may take place, in consequence of which the organisms under such external conditions may still exhibit the usual phenomena. The organism cannot adapt itself to such changes without undergoing change in structure, although there may be no evidence of such changes visible. This alteration of structure does not constitute a disease, provided the harmonious relation of the organism with the environment be not impaired. An individual without a liver should not be regarded as diseased, provided there can be such an internal adjustment that all of the vital phenomena could go on in the usual manner without the aid of this useful and frequently maligned organ. 2. It is individual. In the varying degrees of exposure to unfavorable conditions of a more serious nature some, but not all, of the organisms are destroyed; in the slight exposure, few; in the longer, many. Unfavorable conditions which will destroy all individuals of a species exposed to them must be extremely rare. There is no such individuality in non-living things. In a mass of sugar grains each grain shows just the same characteristics and reacts in exactly the same way as all the other grains of the mass. Individuality, however expressed, is due to structural variation. It is almost impossible to conceive in the enormous complexity of living things that any two individuals, whether they be single cells or whether they be formed of cell masses, can be exactly the same. It is not necessary to assume in such individual differences that there be any variation in the amount and character of the component elements, but the individuality may be due to differences in the atomic or molecular arrangements. There are two forms of tartaric-acid crystals of precisely the same chemical formula, one of which reflects polarized light to the left, and the other to the right. All the left-sided crystals and all the right-sided are, however, precisely the same. The number of possible variations in the chemical structure of a substance so complex as is protoplasm is inconceivable.
In no way is the individuality of living matter more strongly expressed than in the resistance to disease. The variation in the degree of resistance to an unfavorable environment is seen in every tale of shipwreck and exposure. In the most extensive epidemics certain individuals are spared; but here care must be exercised in interpreting the immunity, for there must be differences in the degree of exposure to the cause of the epidemic. It would not do to interpret the immunity to bullets in battle as due to any individual peculiarity, save possibly a tendency in certain individuals to remove the body from the vicinity of the bullets; in battle and in epidemics the factors of chance and of prudence enter. No other living organism is so resistant to changes in environment as is man, and to this resistance he owes his supremacy. By means of his intelligence he can change the environment. He is able to resist the action of cold by means of houses, fire and clothing; without such power of intelligent creation of the immediate environment the climatic area in which man could live would be very narrow. Just as disease can be acquired by an unfavorable environment, man can so adjust his environment to an injury that harmony will result in spite of the injury. The environment which is necessary to compensate for an injury may become very narrow. For an individual with a badly working heart more and more restriction of the free life is necessary, until finally the only environment in which life is even tolerably harmonious is between blankets and within the walls of a room.
The various conditions which may act on an organism producing the changes which are necessary for disease are manifold. Lack of resistance to injury, incapacity for adaptation, whether it be due to a congenital defect or to an acquired condition, is not in itself a disease, but the disease is produced by the action on such an individual of external conditions which may be nothing more than those to which the individuals of the species are constantly subject and which produce no harm.
[Illustration: FIG. 3.—A SECTION OF THE SKIN. 1. A hair. Notice there is a deep depression of the surface to form a small bulb from which the hair grows. 2. The superficial or horny layer of the skin; the cells here are joined to form a dense, smooth, compact layer impervious to moisture. 3. The lower layer of cells. In this layer new cells are continually being formed to supply those which as thin scales are cast off from the surface. 4. Section of a small vein. 9. Section of an artery. 8. Section of a lymphatic. The magnification is too low to show the smaller blood vessels. 5. One of the glands alongside of the hair which furnishes an oily secretion. 6. A sweat gland. 7. The fat of the skin. Notice that hair, hair glands and sweat glands are continuous with the surface and represent a downward extension of this. All the tissue below 2 and 3 is the corium from which leather is made.]
All of the causes of disease act on the body from without, and it is important to understand the relations which the body of a highly developed organism such as man has with the world external to him. This relation is effected by means of the various surfaces of the body. On the outside is the skin [Fig. 3], which surface is many times increased by the existence of glands and such appendages to the skin as the hair and nails. A gland, however complicated its structure, is nothing more than an extension of the surface into the tissue beneath [Fig. 4]. In the course of embryonic development all glands are formed by an ingrowth of the surface. The cells which line the gland surface undergo a differentiation in structure which enables them to perform certain definite functions, to take up substances from the same source of supply and transform them. The largest gland on the external surface of the body is the mammary gland [Fig. 5] in which milk is produced; there are two million small, tubular glands, the sweat glands, which produce a watery fluid which serves the purpose of cooling the body by evaporation; there are glands at the openings of the hairs which produce a fatty secretion which lubricates the hair and prevents drying, and many others.
The external surface passes into the interior of the body forming two surfaces, one of which, the intestinal canal, communicates in two places, at the mouth and anus, with the external surface; and the other, the genito-urinary surface, which communicates with the external surface at one place only. The surface of the intestinal canal is much greater in extent than the surface on the exterior, and finds enormous extensions in the lungs and in the great glands such as the liver and pancreas, which communicate with it by means of their ducts. The extent of surface within the lungs is estimated at ninety-eight square yards, which is due to the extensive infoldings of the surface [Fig 6], just as a large surface of thin cloth can, by folding, be compressed into a small space. The intestinal canal from the mouth to the anus is thirty feet long, the circumference varies greatly, but an average circumference of three inches may safely be assumed, which would give between seven and eight square feet of surface, this being many times multiplied by adding the surfaces of the glands which are connected with it. A diagram of the microscopic structure of the intestinal wall shows how little appreciation of the extent of surface the examination with the naked eye gives [Fig. 7]. By means of the intestinal canal food or substances necessary to provide the energy which the living tissue transforms are introduced. This food is liquefied and so altered by the action of the various fluids formed in the glands of the intestine and poured out on the surface, that it can pass into the interior of the body and become available for the living cells. Various food residues representing either excess of material or material incapable of digestion remain in the intestine, and after undergoing various changes, putrefactive in character, pass from the anus as feces.
By means of the lungs, which represent a part of the surface, the oxygen of the air, which is indispensable for the life of the cells, is taken into the body and carbonic acid removed. The interchange of gases is effected by the blood, which, enclosed in innumerable, small, thin-walled tubes, almost covers the surface, and comes in contact with the air within the lungs, taking from it oxygen and giving to it carbonic acid.
The genito-urinary surface is the smallest of the surfaces. In the male (Fig. 8,—27, 28, 30) this communicates with the general external surface by the small opening at the extremity of the penis, and in the female by the opening into the vagina. In its entirety it consists in a surface of wide extent, comprising in the male the urethra, a long canal which opens into the bladder, and is continuous with ducts that lead into the genital glands or testicles. The internal surface of the bladder is extended by means of two long tubes, the ureters, into the kidneys, and receives the fluid formed in these organs. In the female (Fig 9) there is a shallow external orifice which is continued into the bladder by a short canal, the urethra, the remaining urinary surface being the same as in the male; the external opening also is extended into the short, wide tube of the vagina, which is continuous with the canal of the uterus. This canal is continued on both sides into the Fallopian tubes or oviducts. There is thus in the female a more complete separation of the urinary and the genital surfaces than in the male. Practically all of the waste material of the body which results from cell activity and is passed from the cells into the fluid about them is brought by the blood to the kidneys, and removed by these from the blood, leaving the body as urine.
[Illustration: FIG. 8.—A LONGITUDINAL SECTION THROUGH THE MIDDLE OF THE BODY SHOWING THE EXTERNAL AND INTERNAL SURFACES AND THE ORGANS.
1. The skull. 2. The brain, showing the convolutions of the gray exterior in which the nerve cells are most numerous. 3. The white matter in the interior of the brain formed of nerve fibres which connect the various parts of this. 4. The small brain or cerebellum. 5. The interior of the nose. Notice the nearness of the upper part of this cavity to the brain. 6. The hard or bony palate forming the roof of the mouth. 7. The soft palate which hangs as a curtain between the mouth and the pharynx. 8. The mouth cavity. 9. The tongue. 10. The beginning of the gullet or oesophagus. 11. The larynx. 12. The windpipe or trachea. 13. The oesophagus. 14. The thyroid gland. 15. The thymus gland or sweetbread. 16. The large vein, vena cava, which conveys the blood from the brain and upper body into the heart. 17-25. Lymph nodes; 17, of the neck; 25, of the abdomen. 18. Cross section of the arch of the aorta or main artery of the body after it leaves the heart. 19. The sternum or breast bone. 20. The cavity of the heart. 21. The liver. 22. The descending aorta at the back of the abdominal cavity. 23. The pancreas. 24. The stomach. 26. Cross section of the intestines. 27. The urinary bladder. 28. The entrance into this of the ureter or canal from the kidney. 29. Cross sections of the pubic bone. 30. The canal of the urethra leading into the bladder. 31. The penis. 32. The spinal cord. 33. The bones composing the spinal column. 34. The sacrum. The space between this and No. 29 is the pelvis. 35. The coccyx or extremity of the back bone. 36. The rectum. 37. The testicles.]
Between these various surfaces is the real interior of the body, in which there are many sorts of living tissues, each, of which, in addition to maintaining itself, has some function necessary for the maintenance of the body as a whole. Many of these tissues have for their main purpose the adjustment and cooerdination of the activities of the different organs to the needs of the organism as a whole. The activity of certain of the organs is essential for the maintenance of life; without others life can exist for a time only; and others, such as the genital glands, while essential for the preservation of the life of the species, are not essential for the individual. There is a large amount of reciprocity among the tissues; in the case of paired organs the loss of one can be made good by increased activity of the remaining, and certain of the organs are so nearly alike in function that a loss can be compensated for by an increase or modification of the function of a nearly related organ. The various internal parts are connected by means of a close meshwork of interlacing fibrils, the connective tissue, support and strength being given by the various bones. Everywhere enclosing all living cells and penetrating into the densest of the tissues there is fluid. We may even consider the body between the surfaces as a bag filled with fluid into which the various cells and structures are packed.
The nervous system (Fig. 8) represents one of the most important of the enclosed organs. It serves an important function, not only in regulating and cooerdinating all functions, but by means of the special senses which are a part of it, the relations of the organism as a whole with the environment are adjusted. It consists of a large central mass, the brain and spinal cord, which is formed in the embryo by an infolding of the external surface, much in the same way that a gland is formed; but the connection with the surface is lost in further development and it becomes completely enclosed. Connected with the central nervous mass, forming really a part of it and developing from it, are the nerves, which appear as white fibrous cords and after dividing and subdividing, are as extremely fine microscopic filaments distributed to all parts of the body. By means of the nerves all impressions are conveyed to the brain and spinal cord; all impulses from this, whether conscious or unconscious, are conveyed to the muscles and other parts. The brain is the sole organ of psychical life; by means of its activity the impressions of the external world conveyed to it through the sense organs are converted into consciousness. Whatever consciousness is, and on this much has been written, it proceeds from or is associated with the activity of the brain cells just as truly as the secretion of gastric juice is due to the activity of the cells of the stomach. The activity of the nervous system is essential for extra-uterine life; life ceases by the cessation of circulation and respiration when either the whole or certain small areas of its tissue are destroyed. In intra-uterine life, with the narrow and unchanging environment of the fluid within the uterine cavity which encloses the foetus, life is compatible with the absence or rudimentary development of the nervous system. The foetus in this condition may be otherwise well developed, and it would be not a misuse of words to say that it was healthy, since it is adjusted to and in harmony with its narrow environment, but it would not be normal. The intra-uterine life of the unborn child, it must be remembered, is carried out by the transmission of energy from the mother to the foetus by means of the close relation between the maternal and foetal circulation. It is only when the free existence demands activities not necessary in intra-uterine life that existence without a central nervous system becomes impossible.
It is essential in so complicated a structure as the body that some apparatus should exist to provide for the interchange of material. The innumerable cell units of the body must have material to provide energy, and useless material which results from their activity must be removed. A household might be almost as much embarrassed by the accumulation of garbage and ashes as by the absence of food and coal. The food, which is taken into the alimentary canal and converted by the digestive fluids into material more directly adapted to the uses of cells, must be conveyed to them. A supply of oxygen is essential for the life of the cells, and the supply which is given by respiration must be carried from the lungs to every cell of the body. All this is effected by the circulation of the blood, which takes place in the system of branching closed tubes in which the blood remains (Fig. 11). Certain of these tubes, the arteries, have strong and elastic walls and serve to convey and distribute the blood to the different organs and tissues. From the ultimate branches of the arteries the blood passes into a close network of tubes, the capillaries, which in enormous numbers are distributed in the tissues and have walls so thin that they allow fluid and gaseous interchange between their contents and the fluid around them to take place. The blood from the capillaries is then collected into a series of tubes, the veins, by which it is returned to the heart. This circulation is maintained by means of a pumping organ or heart, which receives the blood from the veins and by the contraction of its powerful walls forces this into the arteries, the direction of flow being determined as in a pump, by a system of valves. The waste products of cell life pass from the cells into the fluid about them, and are in part directly returned into the blood, but for the greater part pass into it indirectly through another set of vessels, the lymphatics. These are thin-walled tubes which originate in the tissues, and in which there is a constant flow towards the heart, maintained by the constant but varying pressure of the tissue around them, the direction of flow being maintained by numerous valves. The colorless fluid within these vessels is termed "lymph." At intervals along these tubes are small structures termed the lymph nodes, which essentially are filters, and strain out from the fluid substances which might work great injury if they passed into the blood. Between the capillary vessels and the lymphatics is the tissue fluid, in which all the exchange takes place. It is constantly added to by the blood, and returns fluid to the blood and lymph; it gives material to the cells and receives material from them.
In addition to the strength and elasticity of the wall of the arteries, which enables them to resist the pressure of the blood, they have the power of varying their calibre by the contraction or expansion of their muscular walls. Many of the organs of the body function discontinuously, periods of activity alternating with comparative repose; during the period of activity a greater blood supply is demanded, and is furnished by relaxation of the muscle fibres which allows the calibre to increase, and with this the blood flow becomes greater in amount. Each part of the body regulates its supply of blood, the regulation being effected by means of nerves which control the tension of the muscle fibres. The circulation may be compared with an irrigation system in which the water supply of each particular field is regulated not by the engineer, but by an automatic device connected with the growing crop and responding to its demands.
The blood consists of a fluid, the blood plasma, in which numerous cells are contained. The most numerous of these are small cup-shaped cells which contain a substance called haemoglobin, to which the red color of the blood is due. There are five million of these cells in a cubic millimeter (a millimeter is .03937 of an inch), giving a total number for the average adult of twenty-five trillion. The surface area of all these, each being one thirty-three hundredth of an inch in diameter, is about thirty-three hundred square yards. The haemoglobin which they contain combines in the lungs with the oxygen in the inspired air, and they give up this indispensable substance to the cells everywhere in the body. There are also eight thousand leucocytes or colorless cells in a cubic millimeter of blood, this giving a total number of four billion in the average adult, and these vary in character and in relative numbers (Fig. 12). The most numerous of these are round and slightly larger than the red cells; they have a nucleus of peculiar shape and contain granules of a definite character. These cells serve an important part in infectious diseases in devouring and destroying parasites. They have power of active independent motion and somewhat resemble certain of the free living unicellular organisms. The blood plasma, when taken from the vessels, clots or passes from a fluid into a gelatinous or semi-solid condition, which is due to the formation within it of a network of fine threads termed fibrin. It is by means of the clotting of the blood that the escape of blood from ruptured vessels is arrested.
Several of the organs of the body, in addition to the formation of secretions which are discharged on the surfaces by means of their ducts, produce also substances which pass directly into the blood or lymph, and have an influence in stimulating or otherwise regulating the activity of other organs. There are also certain organs of glandular structure which are called the ductless glands; these are not connected with the surface and all their secretion passes into the blood. It is a part of recent knowledge that the substances produced in these glands are of great importance for the body, some of them even essential for the maintenance of life. In front of the neck is such an organ, the thyroid gland (Fig. 8, 14). Imperfect development or absence of this organ, or an inactive condition of it, produces in the child arrested growth and deficient mental development known as cretinism, and in the adult the same condition gives rise to mental deterioration, swelling of the skin, due to a greater content of water, and loss of hair. This deficiency in the production of thyroid secretion can be made good and the symptoms removed by feeding the patient with similar glands removed from animals. The very complex disease known as exophthalmic goitre, and shown by irregular and rapid action of the heart, protruding eyeballs and a variety of mental symptoms, is also associated with this gland, and occasioned not by a deficiency but by an excess or perversion of its secretion.
Adjoining the thyroid there are four small glands, the parathyroids, each about the size of a split pea. The removal of these glands in animals produces a condition resembling acute poisoning accompanied by spasmodic contraction of the muscles. A small glandular organ at the base of the brain, the pituitary body, produces a secretion, one of the most marked properties of which is a control of growth, particularly that of the bones. Most cases of giantism, combined as they are with imperfect mentality, are due to disease of this gland. There are glands near the kidney which regulate the pressure of the blood in the arteries by causing contraction of their muscular walls. The sexual characteristics in the male and female are due to an internal secretion produced by the respective sexual glands which affects growth, body development and mentality.
So is the body constituted. A series of surfaces, all connected, of enormous size, which enclose a large number of organs and tissues, the activities of which differ, but all are cooerdinated to serve the purposes of the organism as a whole. We should think of the body not as an assemblage of more or less independent entities, but as a single organism in which all parts are firmly knit together both in structure and in function, as are the components of a single cell.
FOOTNOTES:  They do, however, take place, since within comparatively few years whole species have completely disappeared; for example, the great auk and the passenger pigeon. In these cases it is not known what part disease played in the destruction.
 A tissue represents an aggregate of similar cells with the intercellular substances in relation with these as connective tissue, muscular tissue, etc. Where such cell aggregates are localized and where the cells are arranged in structures having definite form and size and performing a definite function, it is customary to designate such structures as organs, as the brain, liver, etc.
NO SHARP LINE OF DEMARKATION BETWEEN HEALTH AND DISEASE.—THE FUNCTIONAL NUTRITIVE AND FORMATIVE ACTIVITIES OF CELLS.—DESTRUCTION AND REPAIR CONSTANT PROCESSES IN LIVING MATTER.—INJURIES TO THE BODY.—THE EFFECT OF HEAT.—THE ACTION OF POISONS.—THE LESIONS OF DISEASE.—REPAIR.—THE LAWS GOVERNING REPAIR.—RELATION OF REPAIR TO COMPLEXITY OF STRUCTURE AND AGE.—THE RESERVE FORCE OF THE BODY.— COMPENSATORY PROCESSES IN THE BODY.—OLD AGE.—THE DIMINUTION OF RESISTANCE TO THE EFFECT OF THE ENVIRONMENT A PROMINENT FACTOR IN OLD AGE.—DEATH.—HOW BROUGHT ABOUT.—CHANGES IN THE BODY AFTER DEATH.— THE RECOGNITION OF DEATH.
There is no sharp line separating health from disease; changes in the tissues of the same nature, or closely akin to those which are found in disease, are constantly occurring in a state of health. The importance of parasites in causing disease has led to the conception of disease as almost synonymous with parasitism; but it must be remembered that the presence of parasites living at the expense of the body is perfectly consistent with a state of health. Degeneration, decay and parasitism only become disease factors when the conditions produced by them interfere with the life which is the normal or usual for the individual concerned.
All the changes which take place in the cells are of great importance in conditions of both health and disease, for life consists in cooerdinated cell activity. The activities of the cells can be divided into those which are nutritive, those which are functional and those which are formative. In the functional activity the cell gives off energy, this loss being made good by the receipt of new energy in the form of nutritive material with which the cell renews itself. In certain cells an exact balance seems to be maintained, but in those cells whose activity is periodic function takes place at the expense of the cell substance, the loss being restored by nutrition during the period of repose. This is shown particularly well in the case of the nerve cells (Fig. 13). Both the functional and nutritive activity can be greatly stimulated, but they must balance; otherwise the condition is that of disease.
The formative activity of cells is also essential to the normal state. Destruction of cells is constantly taking place in the body, and more rapidly in certain tissues than in others. Dried and dead cells are constantly and in great numbers thrown off from the surface of the skin: such epidermic appendages as the hair and nails grow and are removed, millions of cells are represented in the beard which is daily removed. Cells are constantly being destroyed on the intestinal surface and in the glands. There is an enormous destruction of the blood cells constantly taking place, certain essential pigments, as that of the bile, being formed from the haemoglobin which the red blood corpuscles contain and which becomes available on their destruction. All such loss of cells must be made good by the formation of new ones and, as in the case of the nutritive and functional activity, the loss and renewal must balance. The formative activity of cells is of great importance, for it is by means of this that wounds heal and diseases are recovered from. This constant destruction and renewal of the body is well known, and it is no doubt this which has given rise to the belief, widely held, that the body renews itself in seven years and that the changes impressed upon it by vaccination endure for this period only. The truth is that the destruction and renewal of most tissues in the body takes place in a much shorter interval, and, as we shall see, this has nothing to do with the changes concerned in vaccination. All these activities of the cells vary in different individuals, in different parts and at different ages.
The lesions or injuries of the body which form so prominent a part of disease vary in kind, degree and situation, depending upon the character of the injurious agent, the duration of its action and the character of the tissue affected. The most obvious injuries are those produced by violence. By a cut, blood vessels are severed, the relations of tissues disturbed, and at the gaping edges of the wound the tissue usually protected by the skin is exposed to the air, resulting in destruction of the cells contained in a thin layer of the surface. The discoloration and swelling of the skin following a blow is due to rupture of vessels and escape of blood and fluid, and further injury may result from the interruption of the circulation.
By the application of heat the tissue may be charred and the albumen of the blood and tissue fluids coagulated. Living cells are very susceptible to the action of heat, a temperature of 130 degrees being the thermal death point, and even lower temperatures are fatal when their action is prolonged. The action of the heat may produce definite coagulation of the fluid within the cells in the same way that the white of an egg is coagulated. Certain of the albumens of the body coagulate at a much lower temperature than the white of the egg (as the myosin, one of the albumens of the muscle which coagulates at 115 deg. F., egg white coagulating at 158 deg. F.), and in addition to such coagulation or without it the ferments within the cell and to the action of which cellular activity is due may be destroyed.
In diseases due to parasites, the parasite produces a change in the tissue in its immediate vicinity often so great as to result in the death of the cells. The most general direct cause of lesions is toxic or poisonous substances, either introduced from without or formed in the body. In the case of the parasitic diseases the mere presence of the parasite in the body produces little or no harm, the injury being caused by poisons which it produces, and which act both locally in the vicinity of the parasite and at a distance, being absorbed and entering the blood stream. How certain of the poisonous substances act is easy to see. Strong caustics act by coagulating the albumen, or by the withdrawal of water from the cell. Other poisons act by forming stable chemical compounds with certain of the cell constituents and thereby preventing the usual chemical processes from taking place. Death from the inhalation of illuminating gas is due to the carbon monoxide contained in this, forming a firm chemical union with the haemoglobin of the red corpuscles so that the function of these as oxygen carriers is stopped.
In order that most poisons may act, it is essential that they enter into the cell, and they cannot do this unless they are able to combine chemically with certain of the cell constituents. To this is due the selective action of many poisons. Morphine, for example, acts chiefly on the cells of the brain; strychnine acts on the cells of the spinal cord which excite motion and thus causes the characteristic muscular spasm. The poisonous substances produced by bacteria, as in the case of diphtheria, act on certain of the organs only. Different animal species owe their immunity to certain poisons to their cells being so constituted that a poison cannot gain entrance into them; pigeons, for example, cannot be poisoned by morphia. Individual variations play an important part also; thus, shellfish are poisonous for certain individuals and not so for others. Owing to the variability of living structures a substance may be poisonous at one time and not at another, as the following example shows. A man, very fond of crab meat, was once violently poisoned after eating crabs, being at that time seemingly in his usual state of health, and no illness resulted in others who had partaken of the same crabs. Two months later a hearty meal of crabs produced no ill result. There are also individuals so constituted that so simple a food as the egg is for them an active poison.
The lesions produced by the action of injurious conditions are usually so distinctive in situation and character that by the examination of the body after death the cause of death can be ascertained. The lesions of diseases may be very obvious to the naked eye, or in other cases only the most careful microscopic examination can detect even the presence of alterations. In the case of poisons the capacity of the cell for adaptation to unusual conditions is of great importance. It is probable that certain changes take place within the cells, owing to which the function can be continued in spite of the unusual conditions which the presence of the poison brings about. It is in this way that the habitual use of such poisons as morphine, alcohol and tobacco, to speak only of those best known, is tolerated. The cell life can become so accustomed to the presence of poisons that the cell activities may suffer in their absence.
Repair of the injuries which the body receives is effected in a variety of ways. We do not know how intracellular repair takes place, but most probably the cells get rid of the injured areas either by ejecting them, or chemical changes are produced in the altered cell substance breaking up and recombining the molecules. When single cells are destroyed, the loss is made good by new formation of cells, the cell loss stimulating the formative activity of the cells in the vicinity. The body maintains a cell and tissue equilibrium, and a loss is in most cases repaired. The blood fluid lost in a haemorrhage is quickly restored by a withdrawal of the fluid from the tissues into the blood, but the cells lost are restored by new formation of cells in the blood-forming organs. The blood cells are all formed in bone marrow and in the lymph nodes, and not from the cells which circulate in the blood, and the stimulus to new cell formation which the loss of blood brings about affects this remote tissue.
In general, repair takes place most easily in tissues of a simple character, and where there is the least differentiation of cell structure for the purposes of function. A high degree of function in which the cell produces material of a complex character necessitates a complex chemical apparatus to carry this out, and a complicated mechanism is formed less easily than a simple one. In certain tissues the cells have become so highly differentiated that all formative activity is lost. Such is the case in the nerve cells of the brain and spinal cord, a loss in which tissue is never repaired by the formation of new cells; and in the muscles the same is true. The least differentiation is seen in those cells which serve the purpose of mechanical protection only, as the cells of the skin, and in these the formative activity is very great. Not only must the usual loss be supplied, but we are all conscious of slight injuries of the surface which are quickly repaired.
Repair, other things being equal, takes place more easily in the young than in the old. New formation of cells goes on with great rapidity in intra-uterine life, the child, beginning its existence as a single cell one two hundred and fiftieth of an inch in diameter, attains in nine months a weight of seven pounds. The only similar rapidity of cell formation is seen in certain tumors; although the body may add a greater amount of weight and in a shorter time, by deposit of fat, this in but slight measure represents a new formation of tissue, but is merely a storage of food material in cells. The remarkable repair and even the new formation of entire parts of the body in the tadpole will not take place in the completely developed frog.
Repair will also take place the more readily the less complicated is the architectural structure of the part affected. When a series of tissues variously and closely related to one another enter into the structure of an organ, there may be new formation of cells; but when the loss involves more than this, the complicated architectural structure will not be completely replaced. A brick which has been knocked out of a building can be easily replaced, but the renewal of an area of the wall is more difficult. In the kidney, for example, the destruction of single cells is quickly made good by new cell formation, but the loss of an area of tissue is never restored. In the liver, on the other hand, which is of much simpler construction, large areas of tissue can be newly formed. For the formation of new cells in a part there must be a sufficient amount of formative material; then the circulation of the blood becomes more active, more blood being brought to the part by dilatation of the vessels supplying it.
Repair after a loss can be perfect or imperfect. The tissue lost can be restored so perfectly that no trace of an injury remains; but when the loss has been extensive, and in a tissue of complex structure, complete restoration does not take place and a less perfect tissue is formed which is called a scar. Examination of the skin in almost anyone will show some such scars which have resulted from wounds. They are also found in the internal organs of the body as the result of injuries which have healed. The scar represents a very imperfect repair. In the skin, for example, the scar tissue never contains such complicated apparatus as hair and sweat glands; the white area is composed of an imperfectly vascularized fibrous tissue which is covered with a modified epidermis. The scar is less resistant than the normal tissue, injury takes place more easily in it and heals with more difficulty.
Loss brought about by the injuries of disease can be compensated for, even when the healing is imperfect, by increased function of similar tissue in the body. There always seems to be in the body under the usual conditions a reserve force, no tissue being worked to its full capacity. Meltzer has compared the reserve force of the body to the factor of safety in mechanical construction. A bridge is constructed to sustain the weight of the usual traffic, but is in addition given strength to meet unusual and unforeseen demands. The stomach provides secretion to meet the usual demands of digestion, but can take care of an unusual amount of food. The work of the heart may be doubled by severe exertions, and it meets this demand by increased force and rapidity of contraction; and the same is true of the muscles attached to the skeleton. The constant exercise of this reserve force breaks down the adjustment. If the weight of the traffic over the bridge be constantly all that it can carry, there quickly comes a time when some slight and unforeseen increase of weight brings disaster. The conditions in the body are rather better than in the case of the bridge, because with the increased demand for activity the heart, for example, becomes larger and stronger, and reserve force rises with the load to be carried, but the ratio of reserve force is diminished.
This discussion of injury and repair leads to the question of old age. Old age, as such, should not be discussed in a book on disease, for it is not a disease; it is just as natural to grow old and to die as it is to be born. Disease, however, differs in many respects in the old as compared with the young and renders some discussion of the condition necessary. Changes are constantly taking place in the body with the advance of years, and in the embryo with the advance of days. In every period of life in the child, in the adult, in the middle-aged and in the old we meet with conditions which were not present at earlier periods. There is no definite period at which the changes which we are accustomed to regard as those of old age begin. This is true of both the external appearances of age and the internal changes. One individual may be fully as old, as far as is indicated by the changes of age, at fifty as another at eighty.
With advancing age certain organs of the body atrophy; they become diminished in size, and the microscopic examination shows absence or diminished numbers of the cells which are peculiar to them. The most striking example of this is seen in the sexual glands of females, and, to a less degree, in those of the male. There is a small mass or glandular tissue at the root of the neck, the thymus, which gradually grows from birth and reaches its greatest size at the age of fifteen, when it begins slowly to atrophy and almost disappears at the age of forty. This is the gland which in the calf is known as the sweetbread and is a delicious and valued article of food. The tonsils, which in the child may be so large as to interfere with breathing and swallowing, have almost disappeared in the adult; and there are other such examples.
In age atrophy is a prominent change. It is seen in the loss of the teeth, in the whitening and loss of the hair, in the thinning of the skin so that it more easily wrinkles, in the thinning and weakening of the muscles so that there is not only diminished force of muscular contraction, but weakening of the muscles of support. The back curves from the action of gravity, the strength of the support of the muscles at the back not counteracting the pull of the weight of the abdominal viscera in front. The bones become more porous and more brittle.
The effect of atrophy is also seen in the diminution of all functions, and in loss of weight in individual organs. That the brain shares in the general atrophy is evident both anatomically and in function. Mental activity is more sluggish, impressions are received with more difficulty, their accuracy may be impaired by accompanying changes in the sense organs, and the concepts formed from the impressions may differ from the usual. The slowness of mental action and the diminution in the range of mental activity excited by impressions, and the slowness of expression, may give a false idea of the value of the judgment expressed. The expression changes, the face becomes more impassive because the facial muscles no longer reflect the constant and ever changing impressions which the youthful sense organs convey to a youthful and active brain. That the young should ape the old, should seek to acquire the gravity of demeanor, to restrain the quick impulse, is not of advantage. Loss of weight of the body as a whole is not so apparent, there being a tendency to fat formation owing to the non-use of fat or fat-forming material which is taken into the body. One of the most evident alterations is a general diminution in the fluid of the tissues, to which is chiefly due the lack of plumpness, the wrinkles of age. The facial appearance of age is given to an infant when, in consequence of a long-continued diarrhoea, the tissues become drained of fluid. Every market-man knows that an old animal is not so available for food, the tissues are tougher, more fibrous, not so easily disintegrated by chewing. This is due to a relative increase in the connective tissue which binds all parts together and is represented in the white fibres of meat.
Senile atrophy is complex in its causes and modes of production. The atrophy affects different organs in different degree and shows great variation in situation, in degree and in progress. Atrophic changes of the blood vessels are of great importance, for this affects the circulation on which the nutrition of all tissues depends. While there is undoubted progressive wear of all tissues, this becomes most evident in the case of the blood vessels of the body. It is rare that arteries which can be regarded as in all respects normal are found in individuals over forty, and these changes progress rapidly with advancing age. So striking and constant are these vascular changes that they seem almost in themselves sufficient to explain the senile changes, and this has been frequently expressed in the remark that age is determined not by years, but by the condition of the arteries. Comparative studies show the falsity of this view, for animals which are but little or not at all subject to arterial disease show senile changes of much the same character as those found in man.
There is another condition which must be considered in a study of causes of age. In the ordinary course of life slight injuries are constantly being received and more or less perfectly repaired. An infection which may but slightly affect the ordinary well-being of the individual may produce a considerable damage. Excess or deficiency or improper food, occasional or continued use of alcohol and other poisons may lead to very definite lesions. Repair after injury is rarely perfect, the repaired tissue is more susceptible to injury, and with advancing age there is constant diminution in the ease and perfection of repair. The effect of the sum of all these changes becomes operative: a vicious circle is established in which injury becomes progressively easier to acquire and repair constantly less perfect. There is some adjustment, however, in that the range of activities is diminished, the environment becomes narrower and the organism adapts its life to that environment which makes the least demands upon it.
Whether there is, entirely apart from all conditions affecting nutrition and the effect of injuries which disturb the usual cell activities, an actual senescence of the cells of the body is uncertain. In the presence of the many factors which influence the obvious diminution of cell activity in the old, it is impossible to say whether the loss of cell activity is intrinsic or extrinsic. The life of the plant cell seems to be immortal; it does not grow old. Trees die owing to accidents or because the tree acquires in the course of its growth a mass of tissue in which there is little or no life, and which becomes the prey of parasites. The growing tissue of a tree is comprised in a thin layer below the bark, and the life of this may seemingly be indefinitely prolonged by placing it in a situation in which it escapes the action of accidental injuries and decay, as by grafting on young trees. Where the nature of the dead wood is such that it is immune from parasites and decay, as in the case of the Sequoias, life seems to be indefinitely prolonged. The growing branches of one of these trees, whose age has been estimated with seeming accuracy at six thousand years, are just as fresh and the tree produces its flowers and fruit in the same degree as a youthful brother of one thousand years. Nor does old age supervene in the unicellular organisms. An amoeba assimilates, grows and multiplies just as long as the environment is favorable.
Old age in itself is seldom a cause of death. In rare cases in the very old a condition is found in which no change is present to which death can be attributed, all organs seem to share alike in the senescence. Death is usually due to some of the accidents of life, a slight infection to which the less resistant body succumbs, or to the rupture of a weakened blood vessel in the brain, or to more advanced decay in some organ whose function is indispensable. The causes and conditions of age have been a fertile source for speculation. Many of the hypotheses have been interesting, that of Metschnikoff, for example, who finds as a dominating influence in causing senescence the absorption of toxic substances formed in the large intestine by certain bacteria. He further finds that the cells of the body which have phagocytic powers turn their activity against cells and tissues which have become weakened. There may be absorption of injurious substances from the intestines which the body in a vigorous condition is able to destroy or to counteract their influence, and these may be more operative in the weaker condition of the body in the old. Phagocytes will remove cells which are dead and often cells which are superfluous in a part, but there is no evidence that this is ever other than a conservative process. Since it is impossible to single out any one condition to which old age is due, the hypothesis of Metschnikoff should have no more regard given it than the many other hypotheses which have been presented.
Death of the body as a whole takes place from the cessation of the action of the central nervous system or of the respiratory system or of the circulation. There are other organs of the body, such as the intestine, kidney, liver, whose function is essential for life, but death does not take place immediately on the cessation of their function. The functions of the heart, the brain and the lungs are intimately associated. Oxygen is indispensable for the life of the tissues, and its supply is dependent upon the integrity of the three organs mentioned, which have been called the tripos of life. Respiration is brought about by the stimulation of certain nerve cells in the brain, the most effective stimulus to these cells being a diminution of oxygen in the blood supplying them. These cells send out impulses to the muscles concerned in inspiration, the chest expands, and air is taken into the lungs. Respiration is then a more complicated process than is the action of the heart, for its contraction, which causes the blood to circulate, is not immediately dependent upon extrinsic influences. Death is usually more immediately due to failure of respiration than to failure of circulation, for the heart often continues beating for a time after respiration has ceased. Thus, in cases of drowning and suffocation, by means of artificial respiration in which air is passively taken into and expelled from the lungs, giving oxygen to the blood, the heart may continue to beat and the circulation continue for hours after all evident signs of life and all sensation has ceased.
By this general death is meant the death of the organism as a whole, but all parts of the body do not die at the same time. The muscles and nerves may react, the heart may be kept beating, and organs of the body when removed and supplied with blood will continue to function. Certain tissues die early, and the first to succumb to the lack of oxygenated blood are the nerve cells of the brain. If respiration and circulation have ceased for as short a time as twelve minutes, life ceases in certain of these cells and cannot be restored. This is again an example of the greater vulnerability of the more highly differentiated structure in which all other forms of cell activity are subordinated to function. There are, however, pretty well authenticated cases of resuscitation after immersion in water for a longer period than twelve minutes, but these cases have not been carefully timed, and time under such conditions may seem longer than it actually is; and there is, moreover, the possibility of a slight gaseous interchange between the blood and the water in the lungs, as in the case of the fish which uses the water for an oxygen supply as the mammal does the air. There are also examples of apparent death or trances which have lasted longer, and the cases of fakirs who have been buried for prolonged periods and again restored to life. In these conditions, however, all the activities of the body are reduced to the utmost, and respiration and circulation, so feeble as to be imperceptible to ordinary observation, suffice to keep the cells living.
With the cessation of life the body is subject to the unmodified action of its physical environment. There is no further production of heat and the body takes the temperature of the surroundings. The only exceptions are rare cases in which such active chemical changes take place in the dead body that heat is generated by chemical action. At a varying interval after death, usually within twelve hours, there is a general contraction and hardening of the muscles due to chemical changes, probably of the nature of coagulation, in them. This begins in the muscles of the head, extends to the extremities, and usually disappears in twenty-four hours. It is always most intense and most rapid in its onset when death is preceded by active muscular exertion. There have been cases of instantaneous death in battle where the body has remained in the position it held at the moment of death, this being due to the instantaneous onset of muscular rigidity. The blood remains fluid for a time after death and settles in the more dependent parts of the body, producing bluish red mottled discolorations. Later the blood coagulates in the vessels. The body loses moisture by evaporation. Drying of the surface takes place where the epidermis is thin, as over the transparent part of the eye and over areas deprived of epidermis. Decomposition and putrefaction of the body due to bacterial action takes place. The bacteria ever present in the alimentary canal make their way from this into the dead tissue. Certain of these bacteria produce gas which accumulates in the tissues and the body often swells enormously. A greenish discoloration appears, which is due to the union of the products of decomposition with the iron in the blood; this is more prominent over the abdomen and appears in lines along the course of the veins. The rapidity with which decomposition takes place varies, and is dependent upon many factors, such as the surrounding temperature, the nutrition of the body at the time of death, the cause of death. It is usually not difficult to recognize that a body is dead. In certain cases, however, the heart's action may be so feeble that no pulse is felt at the wrist, and the current of the expired air may not move a feather held to the nostril or cloud the surface of a mirror by the precipitation of moisture upon it. This condition, combined with unconsciousness and paralysis of all the voluntary muscles, may very closely simulate death. The only absolute evidence of death is given by such changes as loss of body heat, rigor mortis or stiffening of the muscles, coagulation of the blood and decomposition.
THE GROWTH OF THE BODY.—GROWTH MORE RAPID IN EMBRYONIC PERIOD.—THE COOeRDINATION AND REGULATION OF GROWTH.—TUMORS.—THE GROWTH OF TUMORS COMPARED WITH NORMAL GROWTH.—SIZE, SHAPE AND STRUCTURE OF TUMORS.— THE GROWTH CAPACITY OF TUMORS AS SHOWN BY THE INOCULATION OF TUMORS OF MICE.—BENIGN AND MALIGNANT TUMORS.—EFFECT OF INHERITANCE.—ARE TUMORS BECOMING MORE FREQUENT?—THE EFFECT PRODUCED BY A TUMOR ON THE INDIVIDUAL WHO BEARS IT.—RELATION OF TUMORS TO AGE AND SEX.—THEORIES AS TO THE CAUSE OF TUMORS.—THE PARASITIC THEORY.—THE TRAUMATIC THEORY.—THE EMBRYONIC THEORY.—THE IMPORTANCE OF THE EARLY RECOGNITION AND REMOVAL OF TUMORS.
The power of growth is possessed by every living thing, but growth is not limited to the living. Crystals also will grow, and the rapidity and character of growth and the maximum size of the crystal depends upon the character of the substance which forms the crystal. From the single cell or ovum formed by the union of the male and female sexual cells, growth is continuous until a size corresponding to the type of the species is attained. From this time onward growth is limited to the degree necessary to supply the constant loss of material which the body undergoes. The rapidity of the growth of the body and of its component parts differs at different ages, and becomes progressively less active from its beginning in the ovum until the adult type of the species is attained. As determined by the volume, the embryo increases more than ten thousand times in size during the first month of intra-uterine life. At birth the average weight is six and a half pounds; at the end of the first year eighteen and a half pounds, a gain of twelve pounds; at the end of the second year twenty-three pounds, a gain of four and a half pounds. The growth is cooerdinated, the size of the single organs bearing a definite ratio, which varies within slight limits, to the size of the body, a large individual having organs of corresponding size. Knowing that the capacity of growth is one of the inherent properties of living matter, it is much easier to understand the continuance of growth than its cessation. It is impossible to avoid the conclusion that there is some internal mechanism of the body which controls and regulates growth. In the first chapter reference was made to organs producing substances which pass directly into the circulation; these substances act by control of the activities of other parts, stimulating or depressing or altering their function. Two of these glands, the thymus, lying in front, where the neck joins the body and which attains its greatest size at puberty, and the pituitary body, placed beneath the brain but forming no part of it, have been shown by recent investigations to have a very definite relation to growth, especially the growth of the skeleton. The growth energy chiefly resides in the skeleton, and if the growing animal has a diet sufficient only to maintain the body weight, the skeleton will continue to grow at the expense of the other tissues, literally living upon the rest of the body. Disease of the glands mentioned leading to an increase or diminution or alteration of their function may not only inhibit or unduly increase the growth of the skeleton, but may also interfere with the sexual development which accompanies the skeleton growth.
The difficulties which arise in an endeavor to comprehend normal growth are greater when the growth of tumors is considered. A tumor is a mass of newly formed tissue which in structure, in growth, and the relations which it forms with adjoining tissues departs to a greater or less degree from the type of the tissue to which it is related in structure or from which it originates. It is an independent structure which, like a parasite, grows at the expense of the body, contributing nothing to it, and its capacity for growth is unlimited. A tumor cannot be considered as an organ, its activities not being coordinated with those of the body. A part of the body it certainly is, but in the household economy it is to be considered as a wild and lawless guest, not influenced by or conforming with the regulations of the household. The rapidity of growth varies; certain tumors for years increase but little in size, while others may be seen to increase from day to day. The growth is often intermittent, periods of great activity of growth alternating with periods of quiescence. The nutrition and growth of a tumor is only slightly influenced by the condition of nutrition of the bearer. Its cells have a greater avidity for food than have those of the body, and, like the growing bones of an insufficiently fed animal, growth in some cases seems to take place at the expense of the body, the normal cells not obtaining sufficient nutriment to repair their waste.
A tumor may be of any size: so small as to be invisible to the naked eye, or its weight may exceed that of the individual who bears it. The limitations to its growth are extrinsic and not intrinsic. There is no distinct color. Certain tumors have color which depends upon the presence of a dark brown or black pigment within the cells. Haemorrhages within them are not infrequent, and they may be colored by the blood or by pigments formed from it. Usually they have a gray color modified by their varying vascularity, or the cut surface may be mottled due to areas of cell degeneration. The consistency varies; some tumors are so soft that they can be pressed through a sieve, others are of stony hardness. There is no distinct shape, this being influenced by the nature of the tumor, the manner of growth and situation. When the tumor grows on or near a surface, it may project from this and be attached by a narrow band only; in the interior of the body it may be irregular in outline, round or lobular, the shape being influenced by many factors. Tumors like the tissues of the normal body are nourished by the blood and contain blood vessels often in great numbers.
A tumor arises by the cells of a part of the body beginning to grow and taking on the characteristics of a tumor. Its growth is independent, the cells of the adjoining tissue taking no part in it. The tissue in the vicinity of the tumor is partly pushed aside by the mass, or the tumor grows into it and the tissue disappears as the tumor advances. The destruction of the surrounding tissue is brought about partly by the pressure which the tumor exerts, partly by the compression of the blood vessels or the blood supply of the organs is diverted to the tumor.
The characteristics of a tumor are due to the cells which it contains (Fig 14). These often become separated from the main mass and are carried by the blood into other parts of the body, where they grow and form tumors similar in character to the parent tumor. In the extraordinary capacity for growth possessed by tumor cells, they resemble vegetable rather than animal cells. There is no limit to the growth of a tumor save by the death of the individual who bears it, thus cutting off the supply of nutrition. The cells of tumors peculiar to man show a narrow range of adaptation. They will grow only in the body of the individual to whom the tumor belongs, and die when grafted on another individual. In the case of tumors which arise in animals, pieces of the tumor when grafted on another animal of the same species will grow, and in this way the growth capacity of the tumor cells has been estimated. Thus, by transplanting a small section of a mouse tumor into other mice, the small transplanted fragments will in two weeks grow to the size of filberts, and each of these will furnish material to engraft upon ten mice. These new tumors are similar in character to the original tumor, and really represent parts of it in the same way that all the Baldwin apples in the world are parts of the original tree which was found in Baldwinville many years ago, and as all the Concord grape vines are really parts of the original vine. It has been estimated that if all the growth capacity of this mouse tumor were availed of by the successive inoculation of other mice, a mass of tumor several times the diameter of the sun would grow in two years. The condition of the individual seems to exert no influence upon the growth of the tumor. Growth may be as rapid when the bearer is in a condition of extreme emaciation as it is when the bearer is well nourished and robust.
Those tumors which grow rapidly and invade and destroy the surrounding tissue are called malignant tumors or cancers, but in a strict sense no tumor can be regarded as benign, for none can serve a useful purpose. A tumor after a period of slow growth can begin to grow rapidly. Tumors may arise in any part of the body, but there are certain places of preference particularly for the more malignant tumors. These are places where the cells naturally have a marked power of growth, and especially where growth is intermittent as in the uterus and mammary gland.
Little is known in regard to the influence of inheritance on the formation of tumors. Study of the tumors of mice show a slightly greater susceptibility to tumor formation in the progeny of mice who have developed tumors. Studies of human families seem to show that heredity has a slight influence, but in the frequency of tumors such statistical evidence is of little value. The question of inheritance has much bearing on the origin of tumors. If the tumor is accidental and due entirely to extraneous causes, inheritance is not probable; but if there is some predisposition to tumor formation in certain individuals due to some peculiarity, then inheritance may exert an influence.
The question as to whether tumors are an increasing cause of disease is equally difficult of solution. The mortality statistics, if taken at their face value, show an enormous increase in frequency; but there are many factors which must be considered and which render the decision difficult and doubtful. Tumors are largely a prerogative of age, and the increased duration of life which preventive medicine has brought about brings more people into the age when tumors are more common. Owing to the greater skill in the diagnosis of tumors, especially those of the internal organs, they are now recognized more frequently and more deaths are correctly ascribed to them. Deaths from tumors were formerly often purposely concealed and attributed to some other cause.
No age is immune to tumors. They may be present at birth or develop shortly afterwards. The age from five to twenty years is the most free from them, that from forty-five to sixty-five the most susceptible, particularly to the more malignant forms.
A tumor is a local disease. The growing tissue of the tumor is the disease, and it is evident that if the entire tumor were removed the disease would be cured. This is the end sought by surgical interference, but notwithstanding seemingly thorough removal, the tumor often reappears after an interval of months or years. There are many conditions which may render the complete removal of a tumor difficult or impossible. It is often impossible to ascertain just how far the tumor cells have invaded the neighboring structures; the situation of the tumor may be such that an extended removal would injure organs which are essential for life, or at the time of removal the tumor cells may have been conveyed elsewhere by the blood or lymphatic vessels.
Successful removal depends mainly upon the length of time the tumor has been growing. At an early stage even the most malignant tumor may be successfully removed. It is evident from this how disastrous may be the neglect of proper surgical treatment of a tumor. The time may be very short between the first evidence of the presence of a tumor and the development of a condition which would render complete removal impossible.
The effect of a tumor upon its bearer depends upon its character and situation. Pain is very commonly present, and is due to the pressure which the growing tumor exerts upon the sensory nerves. Pain may, however, not be present or appear only at the last. A condition of malnutrition and emaciation often results due to the passage into the blood of injurious substances formed in the tumor, or to the destruction of important organs by the growing tumor. The growth of a tumor in the intestine may obstruct or close the canal and thus interfere with nutrition.
The cause or causes of tumors are unknown. We know that the tumor represents essentially an abnormal growth, and that this growth is due to new formation of cells. In certain cases the tumor repeats the structure of the organ or tissue in which it originates, in others it departs widely from this; always, however, its structure resembles structures found in the body at some period of life. The tumor cells, like all other cells of the body, grow by means of the nutriment which the body supplies; they have no intrinsic sources of energy. The great problem is what starts the cells to grow and why the growth differs from that of normal tissue, why it is not regulated and cooerdinated as are other forms of growth. When a small piece of the skin, for instance, is cut out growth as rapid as that in tumors takes place in the adjoining cells, but it ceases when the loss is restored. The same is true when a piece of the liver is removed.
Various hypotheses have been formed to explain the tumor, all of them of interest, and they have had great importance in that the attempt to prove or disprove the hypothesis by continued observation and experiment along definite lines has produced new knowledge. The various theories as to cause may be divided into three heads.
The parasitic theory. This supposes that a living parasite invades the body, and by its presence excites the cells of certain tissues to grow in tumor form. It is known that active growth of the cells of the body can be excited in a number of ways, by chemical substances such as certain of the coal tar products, and that it often takes place under the influence of bacteria. It is further known that parasites can produce tumor-like growths in plants. The large, rough excrescences on the oaks are produced by a fly which lays its eggs in or beneath the bark, and the larva which develops from the egg secretes a substance which causes the cells about it to multiply, and a huge mass is formed which serves the developing insect for both food and protection. Large tumor-like masses are formed on the roots and stalk of cabbages as the result of the invasion of the cells by a minute organism: the tumors of olive trees are due to a bacterium; the peculiar growths on cedar trees, the so-called "witches' brooms," are produced by a fungus, and there are many other such examples. These have many analogies with tumors in animals. Under the stimulus of the parasite the cells seem to have unlimited growth capacity and a greater nutritive avidity than have the normal plant cells; the character of the mass produced differs as does the tumor, to a greater or less extent, from the normal growth; on the cedar, for instance, the "witches' broom" consists of a thick mass of foliage with small stems less green than the usual foliage, the leaves wider and not so closely applied to the stems. The entire plant suffers in its nutrition and a condition resembling tumor cachexia is produced, and there are no fundamental differences between the plant and animal tumors. Support has also been given to the parasitic theory by the discovery within tumor cells of bodies which were supposed to be a peculiar sort of parasite. If the truth of the parasitic theory could be proved, there would be justifiable expectation that the tumor disease might be controlled as are many of the parasitic diseases, but the hypothesis awaits the demonstration of its correctness. Despite the study of tumors which is being actively pursued in many places and by the most skilled investigators, no parasites have been found in animal tumors; the objects previously described as parasites have been found not to be such. It is difficult to bring in accord with the parasitic theory the great variation in tumor structure, the relation of certain tumors, as the malignant tumors of the breast and uterus, with the age of the bearer, the congenital tumors which develop in intra-uterine life, and there are many other conditions which oppose the theory.