In most infections there is a focus where the infectious organisms are localized; this may correspond to the point of entrance on a surface or it may be in the interior of the body, the organisms being deposited there after entrance. At this primary localization, the atrium of infection,[1] the organisms multiply and from this point further invasion takes place. Many secondary foci may be formed in the organs by distribution of the organisms, or there may be infection of the blood and fluids of the body. The injuries which are produced depend upon the nature of the infecting organisms. The most common lesion consists in the death of the tissue about the infecting organisms. In most cases the sum of the changes are so characteristic that from them the nature of the infection is easily determined, and these changes often give names to the disease; thus tuberculosis is a disease characterized by the formation of tubercles or little nodules in the body. The situation of the foci of disease is determined by many conditions, the most important being the varying resistance of the different organs of the body to the growth of bacteria. Certain organs, such as the central nervous system, the muscles, the testicles and the ovaries, have a high resistance to the growth of bacteria. The disease may be localized in certain organs because only in these do the bacteria find favorable conditions for growth. In spite of a high general resistance to infection the lesions in chronic glanders are most marked in the muscles, those of poliomyelitis in the spinal cord. There are few bacterial diseases which are localized in the blood, but many of the diseases caused by protozoa have this localization. In every infection some organisms enter the blood, which acts as a carrier and deposits them in the organs.

Bacteria cause disease by producing substances called toxines which are poisonous to the cells, and of which two sorts are distinguished. One form of toxines is produced by the bacteria as a sort of secretion, and is formed both in the body and when the bacteria are growing in cultures. Substances of this character, many of them highly poisonous, are produced both by animals and plants. They may serve the purpose both of offence and defence, as in the case of the snake venom, and in other cases they seem to benefit their producers in no way whatever, and may even be injurious to them. After the different cereals have been grown for succeeding years in the same place, growth finally diminishes not from the exhaustion of the soil, but from the accumulation in it of substances produced by the plants. Beneath certain trees, as the Norway maple, grass will not grow, and it has been shown that the tree produces substances which inhibit the growth of grass. When bacteria are grown in a culture flask, growth ceases long before the nutritive material has been consumed, from the accumulation of waste products in the fluid. The other class of toxic substances, called endotoxines, are not secretion products, but are contained in the bacterial substance and become active by the destruction and disintegration of the bacteria. They can be artificially produced by grinding up masses of bacteria, and in the body the destruction and solution of bacteria which is constantly taking place sets them free. The toxines and the endotoxines are of an albuminous nature, and act only when they come in contact with the living cells within the body. When taken into the alimentary canal they are either not absorbed or so changed by the digestive fluids as to be innocuous. Many of the ordinary food substances, even a material apparently so simple as the white of an egg, are highly injurious if they reach the tissues in an unchanged form.

By means of these substances the bacteria produce such changes in their environment within the body that this becomes adapted to their parasitic existence. In symbiosis the bacteria probably undergo changes by which they become adapted to the environment, and in parasitism the environment becomes adapted to them. In the same way man can change his immediate environment by means of clothing, artificial heating, etc., and adapt it to his needs; or by hardening his body he can adapt it to the environment. The pathogenic bacterium finds the living tissue hostile, its cells devour him, the tissue fluids destroy him, and by means of the toxines he changes the environment from that of living to dead tissue, or in other ways so alters it that it is no longer hostile. The parasite has also means of passive defence comparable to the armor of the warrior in the past. It may form a protective mantle called a capsule around itself, which serves to protect it from the action of the body fluids. Such capsule formation is a very common thing in the pathogenic organisms, and they are found only when these are growing in the body and do not appear in cultures (Fig. 17-c).

It is evident that just as the parasite has his weapons of offence and defence so has the host, otherwise there would be no recovery from infectious diseases. Although many of the infectious diseases have a high mortality, which in rare instances reaches one hundred per cent, the majority do recover. In certain cases the recovery is attended by immunity, the individual being protected to a greater or less degree from a recurrence of the same disease. The immunity is never absolute; it may last for a number of years only, and usually, if the disease be again acquired, the second attack is milder than the primary. Probably the most enduring immunity is in smallpox, although cases are known of two and even three attacks; the immunity is high in scarlet fever, measles, mumps and typhoid fever. The immunity from diphtheria is short, and in pneumonia, although there must be a temporary immunity, future susceptibility to the disease is probably increased. In certain cases the immunity is only local; the focus of disease heals because the tissue there has evolved means of protection from the parasite, but if any other part of the body be infected, the disease pursues the usual course. A boil, for example, is frequently followed by the appearance of similar boils in the vicinity due to the infection of the skin by the micrococci from the first boil, which by dressings, etc., have become spread over the surface.

The natural methods of defence of the host against the parasites have formed the main subject in the study of the infectious diseases for the last twenty years. Speculation in this territory has been rife and most of it fruitless, but by patient study of disease in man and by animal experimentation there has been gradually evolved a sum of knowledge which has been applied in many cases to the treatment of infectious diseases with immense benefit. Research was naturally turned to this subject, for it was evident that the processes by which the protection of the body was brought about must be known before there could be a really rational method of treatment directed towards the artificial induction of such processes, or hastening and strengthening those which were taking place. Previous to knowledge of the bacteria, their mode of life, their methods of infection and knowledge of the defences of the body, most of the methods of prevention and treatment of the infectious diseases was based largely on conjecture, the one brilliant exception being the discovery of vaccination by Jenner in 1798.

The host possesses the passive defences of the surfaces which have already been considered. The first theories advanced in explanation of immunity were influenced by what was known of fermentation. One, the exhaustion theory, assumed that in the course of disease substances contained in the body and necessary for the growth of the bacteria became exhausted and the bacteria died in consequence. Another, the theory of addition, assumed that in the course of the disease substances inimical to the bacteria were formed. Both these theories were inadequate and not in accord with what was known of the physiology of the body. The most general mode of defence is by phagocytosis, the property which many cells have of devouring and digesting solid substances (Fig. 16-p). Although this had been known to take place in the amoebae and other unicellular organisms, the wide extent of the process and its importance in immunity was first recognized by Metschnikoff in 1884 and the phagocytic theory of immunity advanced and defended by a brilliant series of experiments by Metschnikoff and his pupils conducted in the Pasteur Institute. Metschnikoff's first observations were made on the daphnea, a small animalcule just visible to the naked eye which lives in fresh water. The structure of the organism is simple, consisting of an external and internal surface between which there is a space, the body cavity; daphneae are transparent and can be studied under the microscope while living. Metschnikoff observed that certain of them in the aquarium gradually lost their transparency and died, and examining these he found they were attacked by a species of fungus having long, thin spores. These spores were taken into the intestine with other food; they penetrated the thin wall of the intestine, passed into the body cavity, multiplied there, and in consequence the animal died. In many cases, however, those penetrating became enclosed in cells which the body cavity contains and which correspond with the leucocytes of the blood; in these the spores were digested and destroyed. The daphneae in which this took place recovered from the infection. Here was a case in which all the stages of an infectious disease could be directly followed under the microscope, and the whole process was simple in comparison with infections in the higher animals. The pathogenic organism was known, the manner and site of invasion was clear, it was also evident that if the multiplication of the parasite was unchecked the animal died, but if the parasite was opposed by the body cells and destroyed the animal recovered. The studies were carried further into the diseases of the higher animals, and it was found the leucocytes in these played the same part as did the cells in the body cavity of the daphnea. The introduction of bacteria into certain animals was followed by their destruction within cells and no disease resulted; if this did not take place, the bacteria multiplied and produced disease. Support also was given the theory by the demonstration at about the same time that in most of the infectious diseases the leucocytes of the blood became increased in number,—that in pneumonia, for instance, instead of the usual number of eight thousand in a cubic millimeter of blood, there were often thirty thousand or even fifty thousand. At about the same time also chemotaxis, or the action of chemical substances in attracting or repelling organisms, excited attention, and all these facts together became woven into the theory. It was soon seen, however, that this theory, based as it was on observation and supported by the facts observed, was not, at least in its first crude form, capable of general application. Many animals have natural immunity to certain diseases; they do not have the disease under natural conditions, nor do they acquire the disease when the organisms causing it are artificially introduced into their tissues by inoculation. Such natural immunity seemed to be unconnected with defence by phagocytosis, for the leucocytes of the animal might or might not have phagocytic reaction to the particular organisms to which the animal was immune. It was also seen that recovery from infection in certain diseases was unconnected with phagocytosis. It had also been demonstrated, by German observers chiefly, that the serum of the blood, the colorless fluid in which the corpuscles float, was itself destructive, and that in an animal rendered immune to a special bacterium the destructive action of the serum on that organism was greatly increased. In this hostile serum the bacteria often became clumped together in masses, the bodies became swollen, broken up, and finally disintegrated. This property of the serum was described as due to a substance in the serum called alexine, which in the immune animal became greatly increased in amount. It was even denied by some that phagocytosis of living bacteria took place, and that all those included in the cells were dead, having been destroyed in the first instance by the serum. The strife became a national one between the French and Germans,—on the one side in France the phagocytic theory was defended, and in Germany, on the other, the theory of serum immunity. The mass of experimental work which poured from the laboratories of the two countries in attack and defence became so great that it could not easily be followed. It had a good influence because, without the stimulation of this national rivalry, the knowledge which gradually arose from this work would not have been so quickly acquired. It is interesting that the mode of action of the serum in destroying bacteria was demonstrated not by a German but by Bordet, a French observer and a pupil of Metschnikoff. He showed that the serum contained two distinct substances, each necessary for the destructive action. The separate action of these substances can be studied since one is thermolabile, or destroyed by heating the serum to one hundred and thirty-three degrees; the other thermostabile, or capable of withstanding a greater degree of heat. These substances are known only by their effect, they have never been separated from the serum. The thermostabile substance, or amboceptor, as it is generally called, has in itself no destructive action on the bacteria; but in some way so alters them that they can be acted on by the thermolabile substance called complement whose action is destructive. The amount of amboceptor may increase in the course of infection and its formation stimulated, the amount of complement remains unchanged. The action of the amboceptor is specific, that is, directed against a single species of bacterium only; the destructive power of the blood may be very great against a single bacterium species and have no effect on others. There seem naturally to be many different amboceptors in the blood, and the number may be very greatly increased. It has been shown as a result of the work of many investigators that the shield has two faces,—there is destruction both by cells and fluids and there is interaction by both. The amboceptors so necessary for the destructive action of the serum are produced by the body cells, particularly the leucocytes. The serum assists in pagocytosis by the action on bacteria of substances called opsonins which are contained in it, and the formation of which can be very greatly stimulated. Again, not all inclusion of bacteria within leucocytes is indicative of phagocytosis; in many cases the bacteria seem to find the best conditions for existence within the leucocytes, and these and not the bacteria are destroyed.

So far it has been shown that the best defence of the body is, as is the best defence in war, by offensive measures, as illustrated by phagocytosis and destruction by the serum. Both of these actions can be increased by their exercise just as the strength of muscular contraction can be increased by exercise, and the facility for doing everything increased by habit. Certain of the infectious diseases are, as has been said, essentially toxic in their nature, and in cultures the organisms produce poisonous substances. By the injection into the tissues of such substances the same disturbances are produced as when the bacteria are injected. Such a disease is diphtheria. In this there is only a superficial invasion of the tissues. The diphtheria bacilli are located on the surface of the tonsils or pharynx or windpipe, where, as a result of their action, the membrane so characteristic of the disease is produced. The membrane may be the cause of death when it is so extensively formed as to occlude the air passages, but the prominent symptoms of the disease, the fever, the weakness of the heart and the great prostration are due not to the presence of the membrane, but to the action of toxic substances which are formed by the bacteria growing in the superficial lesions and absorbed. Tetanus, or lockjaw, is another example of these essentially toxic diseases. The body must find some means of counteracting or destroying these injurious toxic substances. It does this by forming antagonistic substances called antitoxines, which act not by destroying the toxines, but by uniting with them, the compound substance being harmless. It has been found that the production of antitoxine can be so stimulated by the injection of toxine that the blood of the animal used for the purpose contains large amounts of antitoxine. The horse is used in this way to manufacture antitoxine, and the serum injected into a patient with diphtheria has a curative action, a greater amount being thus introduced than the patient can manufacture.



A very ingenious theory which well accords with the facts has been given by Ehrlich in explanation of the production of antitoxine and of the reaction between toxine and antitoxine (Fig. 18). This is based on the hypothesis, which is in accord with all facts and generally accepted, that the molecules which enter into the structure of any chemical substance have in each particular substance a definite arrangement, and that in a compound substance each elementary substance entering into the compound molecule has chemical affinities, most of which may be satisfied by finding a suitable mate. Ehrlich assumes that the very complex chemical substances which form the living cells have many unsatisfied chemical affinities, and that it is due to this that molecules of substances adapted for food can enter the cells and unite with them; but there must be some coincidence of molecular structure to enable the union to take place, the comparison being made of the fitting of a key into a lock. The toxines—that produced by the diphtheria bacillus being the best example—are substances whose molecular structure enables them to combine with the cells of the body, the combination being effected through certain chemical affinities belonging to the cells termed receptors. Unless the living cells have receptors which will enable the combination with the toxine to take place, no effect can be produced by the toxine and the cells are not injured. This is the case in an animal naturally immune to the action of the diphtheria bacillus or its toxines. In the case of the susceptible animal the receptors of the cells of the different organs combine with the toxine to a greater or less extent, which explains the fact that different degrees of injury are produced in the different tissues; the toxine of tetanus, or lockjaw, for example, combines by preference with the nervous tissue, that of diphtheria with the lymphatic tissue. It is known that in accordance with the general law of injury and repair, a loss in any part of the body stimulates the tissue of the same kind to new growth and the loss is thus repaired; it is assumed that the cell receptors which combine with the toxine are lost for the cell which then produces them in excess. The receptors so produced pass into the blood, where they combine with the toxine which has been absorbed; the combination is a stable one, and the toxine is thus prevented from combining with the tissue cells. The antitoxine which is formed during the disease, and the production of which in the horse can be enormously stimulated by the injection of toxine, represents merely the excess of cell receptors, and when the serum of the horse containing them is injected in a case of diphtheria the same combination takes place as in the case of receptors provided by the patient. In the case of the destruction of bacteria in the blood by the action of amboceptor and complement, the amboceptor must be able to combine with both the bacterial cell and the complement which brings about its destruction, and just as antitoxine is formed so new amboceptors may be formed.

Few hypotheses have been advanced in science which are more ingenious, in better accord with the facts, have had greater importance in enabling the student to grasp the intricacies of an obscure problem, and which have had an equal influence in stimulating research. The immunity which results from disease in accordance with this theory, is due not to conditions preventing the entrance of organisms into the body, but to greater aptitude on the part of the cells to produce these protective substances having once learned to do so. An individual need not practise for many years, having once learned them, those combinations of muscular action used in swimming; but the habit at once returns when he falls into the water.

Infectious diseases and recovery are phases of the struggle for existence between parasite and host, and illustrate the power of adaptation to environment which is so striking a characteristic of living matter.

FOOTNOTES:

[1] The comparison here is with the atrium of a Pompeiian house.



CHAPTER VIII

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.—TRYPANOSOME DISEASES.—SLEEPING SICKNESS.—MALARIA.—THE PART PLAYED BY MOSQUITOES.—PARASITISM IN THE MOSQUITO.—INFECTION AS INFLUENCED BY HABITS AND CUSTOMS.—HOOKWORM DISEASE.—INTER-RELATION BETWEEN HUMAN AND ANIMAL DISEASES.—PLAGUE.—PART PLAYED BY RATS IN TRANSMISSION.—THE PRESENT EPIDEMIC OF PLAGUE.

The infectious diseases are often complicated by secondary infections, some other organism finding opportunity for invasion in the presence of the injuries produced in the primary disease. In many diseases, such as diphtheria, scarlet fever and smallpox, death is frequently due to the secondary infection. The secondary invaders not only find local conditions favoring a successful attack, but the activity of the tissue cells on which the production of protective substances essentially depends has suffered by the primary infection, or the cells are occupied in meeting the exigencies of this. The body is in the position of a state invaded by a second power where all its forces and resources are engaged in repelling the first attack.

What are known as terminal infections occur shortly before death. No matter what the disease which causes death, in the last hours of life the body usually becomes invaded by organisms which find their opportunity in the then defenceless tissues, and the end is often hastened by this invasion.

There are also mixed infections in which two different organisms unite in attack, each in some way assisting in the action of the other. The best known example of this is in the highly infectious disease of swine known as hog cholera. It has been shown that in this disease two organisms are associated,—one an invisible and filterable organism, and the other a bacillus. It was first supposed that the bacillus was the specific organism; it was found in the lesions and certain, but not all, the features of the disease were produced by inoculating hogs with pure cultures. The disease so produced is not contagious, and the contagious element seems to be due to the filterable virus.

The modes of transmission of infectious diseases are of great importance and are the foundation of measures of public health. In the preceding chapter we have seen that in the infected individual the disease extends from one part of the body to another. There is a primary focus of disease from which the extension takes place, and the study of the modes of extension in the individual throws some light on the much more difficult subject of the transmission of disease from one individual to another. There are four ways by which extension in the individual may take place.

1. By continuity of tissue, an adjoining tissue or organ becoming infected by the extension of a focus of infection.

2. By means of lymphatics. Organisms easily enter these vessels which are in continuity with the tissue spaces and receive the exudate from the focus of infection. The organisms are carried to the lymph nodes, which, acting as filters, retain them and for a time prevent a further extension. The following illustrates the importance of the part the nodes may play in mechanically holding back a flood of infection. A physician examined after death the body of a person who died from infection with a very virulent micrococcus and in the course of the examination slightly scratched a finger. One of the organs of the body was removed, sent to a laboratory and received by a laboratory worker, a woman physician, who had slight abrasions and fissures in the skin of the hands from contact with irritating chemicals. In the course of a few hours the wound on the finger of the man became inflamed, intensely painful, and red lines extended up the arm in the course of the lymphatic vessels, showing that the organisms were in the lymphatics and causing inflammation in their course. The lymph nodes in the armpit into which these vessels empty became greatly inflamed, swollen, and an abscess formed in them which was opened. There was high fever, great prostration, a serious illness from which the man did not recover for several months. The woman only handled the organ which was sent to the laboratory in order to place it in a fluid for preservation. She also had a focus of infection of a finger with the same red lines on the arm, showing extension by the lymphatics; but there was no halt of the infection in the armpit, for all the lymph nodes there had been removed several years before in the course of an operation for a tumor of the breast. A general infection of the blood took place, there was very high fever, and death followed in a few days. The halt of the infection is important in allowing time for the body to make ready its means of defence. One cannot avoid comparing the lymph node with a strong fortress thrown in the path of a victorious invading army behind which the defenders may gather and which affords them time to renovate their strength.

3. By means of the blood. The blood vessels are universally distributed, the smaller vessels have thin walls easily ruptured and easily penetrated. It is probable that in every infection some organisms enter the blood which, under usual conditions, is peculiarly hostile to bacteria. These may, however, be carried by the blood to other organs and start foci of infection in these.

4. By means of continuous surfaces. The bacteria may either grow along such surfaces forming a continuous or more or less broken layer, or may be carried from place to place in the fluids which bathe them.

All these modes of extension are well shown in tuberculosis. This disease is caused by a small bacillus which does not produce spores, has no power of saphrophytic growth under natural conditions, and is easily destroyed. Moisture and darkness are favorable conditions for its existence, sunlight and dryness the reverse. There are three varieties or strains of the tubercle bacilli which infect respectively man, cattle and birds, and each class of animals shows considerable resistance to the varieties of the bacillus which are most infectious for the others.

The primary seat of the infection in man is generally in the upper part of the lung. The organisms settle on the surface here and cause multiplication of the cells and an inflammatory exudate in a small area. With the continuous growth of the bacilli in the focus, adjoining areas of the lung become affected, and there is further extension in the immediate vicinity by means of the lymphatics. Small nodules are formed and larger areas by their coalescence. Infection with tuberculosis is so common that at least three-fourths of all individuals over forty show evidences of it. The examination of two hundred and twenty-five children of the average age of five years who had died of diphtheria showed tuberculous infection in one-fifth of the cases and the frequency of infection increases with age. The defence on the part of the body is chiefly by the formation of dense masses of cicatricial tissue which walls off the affected area and in which the bacilli do not find favorable conditions for growth. This mode of defence, which is probably combined with the production of substances antagonistic to the toxines produced by the bacilli, is so efficacious that in the great majority of cases no further extension of the process takes place. In certain cases, however, the growth of the bacilli in the focus is unchecked, the tissue about them is killed and becomes converted into a soft semi-fluid material; further extension then takes place. All parts of the enormous surface of the lungs are connected by means of the system of air tubes or bronchi, and the bacilli have favorable opportunity for distribution, which is facilitated by sudden movements of the air currents in the lung produced by coughing. The defence of the body can still keep pace with the attack, and even in an advanced stage the infection can be checked in some cases permanently; in others the check is but temporary, the process of softening continues, and large cavities are produced by the destruction of the tissue. On the inner surface of these cavities there may be a rapid growth of bacilli.

From the lungs the bacilli are carried by the lymphatics to the lymph nodes at the root of the lungs, in which a similar process takes place; this, on the whole, is favorable, because further extension by this route is for a time blocked. The extension by means of surfaces continues, the abundant sputum which is formed in the lungs and which contains large numbers of bacilli, becomes the vehicle of transportation. The windpipe and larynx may become infected, the back parts of each are more closely in contact with the sputum and are the parts most generally infected. A large part of the sputum is swallowed and infection of the intestine takes place, the lesions taking the form of large ulcers. From the intestinal ulcers there is further extension by means of the lymphatics, to the large lymph nodes in the back of the abdominal cavity (Fig. 8-25); the bacilli may also pass from the ulcers into the abdominal cavity and be distributed over the surface of the peritoneum resulting in tuberculous peritonitis. When the disease has reached an advanced stage, bacilli in small numbers continually pass into the blood and are distributed by this over the body, producing small nodules in many places. In rare cases distribution by the blood is the principal method of extension, and immense numbers of small foci of disease are produced, the form of disease being known as acute miliary tuberculosis. Although the bacilli are distributed everywhere, certain organs, as the brain and muscles, are usually exempt, because in these the conditions are not favorable to further growth of the bacilli. Tuberculosis, although frequently a very acute disease, is usually one of the best types of a chronic disease and may last for many years. The chronic form is characterized by periods of slow or rapid advance when conditions arise in the body favorable for the growth of the bacilli, and periods when the disease is checked and quiescent, the defensive forces of the body having gained the upper hand. Often the intervention of some other disease so weakens the defences of the body that the bacilli again find their opportunity. Thus typhoid fever, scarlet fever and other diseases may be followed by a rapidly fatal advance of the tuberculosis, starting from some old and quiescent focus of the disease.

Tuberculosis is also one of the best examples of what is known as latent infection. In this the infectious organisms enter the body and produce primary lesions in which the organisms persist but do not extend owing to their being enclosed in a dense and resistant tissue, or to the production of a local immunity to their action. Dr. Head has recently examined the children of households in which there was open tuberculosis in some member of the household. By open tuberculosis is understood a case from which bacilli are being discharged. He found with scarcely an exception that all the children in such families showed evidences of infection. The detection of slight degrees of tuberculous infection is now made easy by certain skin reactions on inoculation of the skin with a substance derived from the tubercle bacilli. Such latent infections may never become active and in the majority of cases do not. When, however, in consequence of some intercurrent disease or conditions of malnutrition the general defences of the body become weakened extension follows. Such latent infections explain the enormous frequency of tuberculosis in prisons. Under the general prison conditions infection in the prisons probably does not take place to any extent, and the disease is as common when the prisoners are kept in individual cells as in common prisons. It is probable that in these cases the prisoners have latent tuberculosis when entering, and the disease becomes active under the moral and physical depression which prison life entails.

For the extension of infection from one individual to another the infecting organisms must in some way be transferred. The most important of the conditions influencing this are the localization of the disease and the character of the infectious organisms, particularly with regard to their resistance to the conditions met with outside of the body. The seat of disease influences the discharge of organisms; thus, if the disease involve any of the surfaces the organisms become mingled with the secretions of the surface and are discharged with these. If the seat of disease be in the lungs, the throat or the mouth, the sputum forms the medium of extension, which can take place in many ways. The sputum may become dried, forms part of the dust and the organisms enter with the inspired air. The organisms which cause most of the diseases in which the sputum becomes infectious are quickly destroyed by conditions in the open, such as the sunlight and drying; street dust does not play so prominent a part in extension as is generally supposed. Organisms find much more favorable conditions within houses. It is now generally recognized that infection with tuberculosis does not take place in the open, but in houses in which the bacilli on being discharged are not destroyed. The hands, the clothing and surroundings even with the exercise of the greatest care may become soiled with the saliva.

It has been shown that in coughing and speaking very fine particles of spray are formed by the intermingling of air and saliva, which may be projected a considerable distance and remain floating in the air for some time. These particles are so fine as to be invisible; they may be inspired, and their presence in the air forms an area of indeterminate extent around the infected person within which such infection is possible. Such spray formation is also an important means of the extension of infection in the sick individual, for it is continually formed and inspired. It is in this way that the extreme prevalence of broncho-pneumonia in infants and young children is to be explained. No matter what the essential disease, an almost constant finding in young children after death is small areas of inflammation in the lungs in and around the terminations of the air tubes. The situation renders it evident that the organisms which caused the lesions entered the lung by the air tubes. The mouth of the child is unclean and harbors numbers of the same sort of organisms as those causing the lung inflammation; but in the absence of such a mode of infection as is given by spray formation it is difficult to see how the extension from the mouth to the lungs could take place. The weakened condition of the body in these cases favors the secondary infection.

If the disease be located in the intestines, as in typhoid fever and dysentery, the organisms are contained in the fecal discharges, and by means of these the infection is extended. In typhoid fever, dysentery and cholera massive infections of the populace may take place from the contamination of a water supply and the disease be extended over an entire city. One of the most striking instances of this mode of extension was in the epidemic of cholera in Hamburg in 1892. There were two sources of water supply, one of which was infected, and the cases were distributed in the city in the track of the infected supply. Many such instances have been seen in typhoid fever. Certain articles of food, particularly milk, serve as sources of infection. This is more apt to happen when the organism causing the infection grows easily outside of the body. A few such organisms entering into the milk can multiply enormously in a few hours and increase the amount of infectious material. In all these cases the sick individual remains a source of infection, for it is almost impossible to avoid some contamination of the body and the immediate surroundings with the organisms contained in the discharges.

Transmission by air plays but little part in the extension of infection. In such a disease as smallpox, where the localization is on the surface of the body, the organisms are contained in or on the thin epithelial scales which are constantly given off. These are light, and may remain floating in the air and carried by air currents just as is the pollen of plants. There seem to have been cases of smallpox where other modes of more direct transmission could be excluded and in which the organisms were carried in the air over a considerable space. All sorts of intermediate objects, both living and inanimate, such as persons, domestic animals, toys, books, money, etc., can serve as conveyors of infection.

Insects play a most important part in the transmission of disease, and in certain cases, as when a disease is localized in the blood, this is the only means of transmission. There are three ways in which the insect plays the role of conveyor.

1. The insect may play a purely passive part in that its exterior surface becomes contaminated with the discharges of the sick person, and in this way the organisms of disease may be conveyed to articles of food, etc. The ordinary house fly conveys in this way the organisms of typhoid and dysentery. Flies seek the discharges not only for food, but for the purpose of depositing their eggs, and the hairy and irregular surface of their feet facilitates contamination and conveyance. When flies eat such discharges the organisms may pass through the alimentary canal unchanged and be deposited with their feces; they also often vomit or regurgitate food, and in this way also contaminate objects. Flies very greedily devour the sputum of tuberculous patients, and the tubercle bacilli contained in this pass through them unchanged and are deposited in their feces.



2. Diseases which are localized in the blood are transmitted by biting flies. The biting apparatus becomes contaminated with the organisms contained in the blood, and these are directly inoculated into the blood of the next victim. The trypanosome diseases form the best example of this mode of transmission. The trypanosomes are widely distributed, exclusively parasitic, flagellated protozoa which live in the blood of a large number of animals and birds (Fig. 19). They may give rise to fatal diseases, but in most cases there is mutual adaptation of host and parasite and they seem to do no harm. One of the most dangerous diseases in man, the African sleeping sickness, is caused by a trypanosome, and the disease of domestic cattle in Africa, nagana, or tsetse fly disease, is also so produced. In certain regions of Africa where a biting fly, the Glossina morsitans, occurs in large numbers, it has long been known that cattle bitten by these flies sickened and died, and this prevented the settling and use of the land. In the blood of the sick cattle swarms of trypanosomes are found. The source from which the tsetse fly obtained the trypanosomes which it conveyed to the cattle was unknown until it was discovered that similar trypanosomes exist in the blood of the wild animals which inhabit the region, but these have acquired by long residence in the region immunity or adaptation to the parasite and no disease is produced. With the gradual extension of settlement of the country and the accompanying destruction of wild life the disease is diminishing. Some of the inter-relations of infections are interesting. The destruction of wild animals in South Africa which, by removing the sources of nagana, rendered the settlement of the country possible was due chiefly to the introduction of another infectious disease, rinderpest, which not only destroyed the wild animals but produced great destruction of the domestic cattle as well.

The sleeping sickness has many features of interest. In the old slavery days it was found that the negroes from the Congo region in the course of the voyage or after they were landed sometimes were affected with a peculiar disease. They were lethargic, took little notice of their surroundings, slept easily and finally passed into a condition of somnolence in which they took no food and gradually died. There was no extension of the disease and it was attributed to extreme homesickness and depression. A similar disease has been known for more than one hundred years on the west coast of Africa, and attracted a good deal of interest and curiosity on account of the peculiar lethargy which it produced and from which it has received the name of "sleeping sickness." Although apparently infectious in its native haunts, it lost the power of spreading from man upon removal to regions where it did not prevail. At first confined to a very small region on the Niger river, it gradually extended with the development of trade routes and the general increase of communications which trade brings, until it prevails in the entire Congo basin, in the British and German possessions in East Africa, and is extending north and south of these regions. The cause of the disease and its mode of conveyance was discovered in 1903. The fly Glossina palpalis which conveys the disease is a biting fly about the size of the common house fly and lives chiefly in the vicinity of water. When such a fly bites an individual who has sleeping sickness its bite can convey the disease to monkeys, on whom the transmission experiments were made. After biting the fly is infectious for a period of two days. After this it is harmless, unless it again obtains a supply of living trypanosomes. There is quite a period in which there are no symptoms of the disease, although trypanosomes are found in the blood and in the lymph nodes, and the individual is a source of infection. The peculiar lethargy which has given the disease its name does not appear until the nervous system is invaded by the parasites. It is impossible to compute accurately the numbers of deaths from this disease—in the region of Victoria Nyanza alone the estimates extend to hundreds of thousands.

3. In the third mode of insect conveyance the insect does not play a merely passive role, but becomes a part of the disease, itself undergoing infection, and a period in the life cycle of the organism takes place within it. In all these cases quite a period of time must elapse before the insect is capable of transmitting the disease; in malaria, which is the best type of such a disease, this period is ten days. Malaria is due to a small protozoan, the Plasmodium malariae, which was discovered by Lavaran, a French investigator, in 1882. The organism lives within or on the surface of the red blood corpuscles. It first appears as a very minute colorless body with active amoeboid movements, and increases in size, attacks a succession of corpuscles, and finally attains a size as large as or larger than a corpuscle. The corpuscles attacked become pale by the destruction of haemoglobin, swell up and disintegrate, the haemoglobin becoming converted into granules of black pigment inside the parasite. Having attained a definite size the organism forms a rosette and divides into a number of forms similar to the smallest seen inside the corpuscles; these small forms enter other corpuscles and the cycle again begins. This cycle of development takes place in forty-eight hours, and segmentation is always accompanied by a paroxysm of the disease shown in a chill followed by fever and sweating which is due to the effect of substances liberated by the organism at the time of segmentation. A patient may have two crops of the parasite developing independently in the blood, and the two periods of segmentation give a paroxysm for each, so that the paroxysms may appear at intervals of twenty-four hours instead of forty-eight (Fig. 20). This cycle of development may continue for an indefinite time, and there may be such a rapid increase in the parasites as to bring about the death of the individual; but with him the parasite would also perish, for there would be no way of extending the infection and providing a new crop. The disease has been transmitted by injecting the infected blood into a normal individual.

[Illustration: FIG. 20.—PART OF THE CYCLE OF DEVELOPMENT OF THE ORGANISM OF MALARIA, a-g, Cycle of forty-eight hour development, the period of chill coinciding with the appearance of f and g in the blood. The organisms g, which result from segmentation, attack other corpuscles and a new cycle begins. h, The male form or microgametocyte, with the protruding and actively moving spermatozoa, one of which is shown free. i and j are the macrogametes or female forms. k shows one of these in the act of being fertilized by the entering spermatozooen. The differentiation into male and female forms takes place in the blood, the further development of the sexual cycle within the mosquito.]

If a mosquito of the species anopheles bites the affected person, it obtains a large amount of blood which contains many parasites. Within the mosquito the parasite undergoes a further development into male and female sexual forms, which may also form in the blood, termed respectively microgametocyte and macrogamete. From the microgametocyte small flagellate bodies, the male sexual elements microgametes or spermatozoa, develop and fertilize the macrogametes; after fertilization this develops into a large body, the ooecyst which is attached to the wall of the stomach of the mosquito. Within the ooecyst, innumerable small bodies, the sporozoites, develop, make their way into the salivary glands and are injected into the individual who becomes the prey of the mosquito, and again the cycle of development begins. The presence of the parasite within the mosquito does not constitute a disease. So far as can be determined, life goes on in the usual way, and its duration in the insect is not shortened.

The nature of the parasite which produces yellow fever is unknown, for it belongs to the filterable viruses; the infectious material, however, has been shown by inoculation to exist in the blood, and the disease is transmitted by a mosquito of another species, the stegomyia. The development cycle within this takes a period of twelve days, which time must elapse after the mosquito has bitten before it can transmit the disease. Here again the mutual interdependence of knowledge is shown. Nothing could have seemed less useful than the study of mosquitoes, the differentiation of the different species, their mode of life, etc., and yet without this knowledge discoveries so beneficial and of such far-reaching importance to the whole human race as that of the cause and mode of transmission of malaria and yellow fever would have been impossible; for it could easily have been shown that the ordinary culex mosquito played no role. The role which insects may play in the transmission of disease was first shown by Theobald Smith in this country, in the transmission by a tick of the disease of cattle known as Texas fever. The infecting organism pyrosoma bigenimum is a tiny pear-shaped parasite of the red corpuscles. Smith's investigations on the disease, published in 1893, is one of the classics in medicine, and one of the few examples of an investigation which has not been changed or added to by further work.

One of the most interesting methods of extension of infection, showing on what small circumstances infection may depend, is seen in the case of the hookworm disease, which causes such devastation in the Southern States. The organism which produces the disease, the Uncinaria, belongs to the more highly developed parasites, and is a small round worm one-third of an inch long. The worms which inhabit the intestines have a sharp biting mouth by which they fasten themselves to the mucous membrane and devour the blood. The most prominent symptom of the disease is anaemia, or loss of blood, due not only to the direct eating of the parasite, but to bleeding from the small wounds caused by its bite. Large numbers of eggs are produced by the parasite which are passed out with the feces, which becomes the only infectious material. In a city provided with water-closets and a system of sewerage there would be no means of extension of infection. The eggs in the feces in conditions of warmth and moisture develop into small crawling larvae which can penetrate the skin, producing inflammation of this, known in the region as the ground itch. The larvae enter the circulation and are carried to the lungs, where they perforate the capillaries and reach the inner surface; from this they pass along the windpipe, and then by way of the gullet and stomach reach their habitat, the small intestine. Unfortunately, the habits and poverty of the people in every way facilitate the extension of the infection. There is no proper disposal of the feces, few of the houses have even a privy attached to them, and the feces are distributed in the vicinity of the houses. This leads to contamination of the soil over wide areas. Most of the inhabitants of the country go barefoot the greater part of the year, and this gives ready means of contact with the larvae which crawl over the surface of the ground. The disease is necessarily associated with poverty and ignorance, the amount of blood is reduced to a low point, and industry, energy and ambition fall with the blood reduction; the schools are few and inefficient; the children are backward, for no child can learn whose brain cells receive but a small proportion of the necessary oxygen; and a general condition of apathy and hopelessness prevails in the effected communities. The control of the disease depends upon the disinfection of the feces, or at least their disposal in some hygienic method, the wearing of shoes, and the better education of the people, all of which conditions seem almost hopeless of attainment. The infection is also extended by means of the negroes who harbor the parasite, but who have acquired a high degree of immunity to its effects and whose hygienic habits are even worse than those of the whites. The organism was probably imported with the negroes from Africa and is one of the legacies of slavery.

The diseases of animals are in many ways closely linked with those of man. In the case of the larger parasites, such as the tapeworms and the trichina, there is a direct interchange of disease with animals, certain phases of the life cycle of the organisms are passed in man and others in various of the domestic animals. A small inconspicuous tapeworm inhabits the intestine of dogs and seems to produce no ill effects. The eggs are passed from the dog, taken into man, and result in the formation of large cystic tumors which not infrequently cause death. Where the companionship between dog and man is very close, as in Iceland, the cases are numerous.

Most of the diseases in animals caused by bacteria and protozoa are not transmitted to man, but there is a conspicuous exception. Plague is now recognized as essentially an animal disease affecting rats and other small rodents, and from these the disease from time to time makes excursions to the human family with dire results. The greatest epidemics of which we have any knowledge are of plague. In the time of Justinian, 542 B.C., a great epidemic of plague extended over what was then regarded as the inhabited earth. This pandemic lasted for fifty years, the disease disappeared and appeared again in many places and caused frightful destruction of life. Cities were depopulated, the land in many places reverted to a wilderness, and the works of man disappeared. The actual mortality cannot be known, but has been estimated at fifty millions. Plague played a large part in the epidemics of the Middle Ages. An epidemic started in 1346 and had as great an extension as the Justinian plague, destroying a fourth of the inhabitants of the places attacked; and during the fifteenth and sixteenth and seventeenth centuries the disease repeatedly raised its head, producing smaller and greater epidemics, the best known of which, from the wonderful description of De Foe, is that of London in 1665, and called the Black Death. Little was heard of the disease in the nineteenth century, although its existence in Asia was known. In 1894 it appeared in Hong Kong, extended to Canton, thence to India, Japan, San Francisco, Mexico, and, in fact, few parts of the tropics or temperate regions of the earth have been free from it. Mortality has varied greatly, being greatest in China and in India; in the last the estimate since 1900 is seven million five hundred thousand deaths. The disease is caused by a small bacillus discovered in 1894 which forms no spores and is easily destroyed by sunlight, but in the dark is capable of living with undiminished virulence for an indefinite time. The disease in man appears in two forms, the most common known as bubonic plague, from the great enlargement of the lymph nodes, those of the groin being most frequently affected. The more fatal form is known as pneumonic plague, and in this the lungs are the seat of the disease.

In the old descriptions of the disease it was frequently mentioned that large numbers of dead rats were found when it was prevalent, and the most striking fact of the recent investigations is the demonstration that the infection in man is due to transference of the bacillus from infected rats. There are endemic foci of the disease where it exists in animals, the present epidemic having started from such a focus in Northern China, in which region the Tarabagan, a small fur-bearing animal of the squirrel species, was infected. Rats are easily infected, the close social habits of the animal, the vermin which they harbor, and the habits of devouring their dead fellows favor the extension of infection. The disease extends from the rat to man chiefly by means of the fleas which contain the bacilli, and in cases of pneumonic plague from man to man by means of sputum infection. The disease once established in animals tends to remain, the virus being kept alive by transmission from animal to animal, and the persistence of the infection is favored by mild and chronic cases.



CHAPTER IX

DISEASE CARRIERS.—THE RELATION BETWEEN SPORADIC CASES OF INFECTIOUS DISEASE AND EPIDEMICS.—SMALLPOX.—CEREBRO-SPINAL MENINGITIS.—POLIOMYELITIS.—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.

We have seen that insects serve as carriers of disease in two ways: in one, by becoming contaminated with organisms they serve as passive carriers, and in the other they undergo infection and form a link in the disease. The more recent investigations of modes of transmission of infectious diseases have shown that man, in addition to serving while sick as a source of infection, may serve as a passive carrier in two ways. For infection to take place not only must the pathogenic organism be present, but it must be able to overcome the passive and active defences of the body and produce injury. Pathogenic organisms may find conditions favorable for growth on the surfaces of the body, and may live there, but be unable to produce infection, and the individual who simply harbors the organisms can transmit them to others. Such an individual may be a greater source of infection than one with the disease, because there is no suspicion of danger. The organisms which thus grow on the surfaces have in some cases been shown to be of diminished virulence, but in others have full pathogenic power. Such passive carriers of infection have been found for a number of diseases, as cerebro-spinal meningitis, diphtheria, poliomyelitis and cholera. In all these cases the organisms are most frequently found in those individuals who have been exposed to infection as members of a family in which there have been cases of disease. The other sort of carrier has had and overcome the disease, but mutual relations have been established with the organism which continues to live in the body cavity. Diphtheria bacilli usually linger in the throat after convalescence is established, and until they have disappeared the individual is more dangerous than one actually sick with the disease. Health officers have recognized this in continuing the quarantine against the disease until the organism disappears. In typhoid fever bacilli may remain in the body for a long time and be continually discharged, as in the well-known case of "typhoid Mary."[1]

Single cases of certain infectious diseases may appear in a community year after year, and at intervals the cases become so numerous that the disease is said to be epidemic. Such a disease is smallpox. This is a highly infectious disease, towards which all mankind is susceptible. Complete protection against the disease can be conferred by Jenner's discovery of vaccination. The disease becomes modified when transferred to cattle, producing what is known as cowpox, in which vesicles similar to those of smallpox appear on the skin. The inoculation of man with the contents of such a vesicle produces a mild form of disease known as vaccinia, which protects the individual from smallpox. This protection is fully as adequate as that produced by an attack of smallpox, and we are warranted in saying that if thorough vaccination, or the inoculation with vaccinia, were carried out smallpox would disappear. There are great difficulties in the way of carrying out effective vaccination of the whole population, which are accentuated by the active opposition of people who are ignorant and wilfully remain so. There exists in every state a number of people unprotected by vaccination, and among these single cases of smallpox appear. The unprotected individuals gradually increase in number, forming an inflammable material awaiting the spark or infection which produces a conflagration in the one case and an epidemic in the other.

Cerebro-spinal meningitis is another example of a disease which exists in sporadic and epidemic form. This disease is caused by a small micrococcus, the organisms joined in pairs. The seat of the disease is in the meninges or membranes around the brain and spinal cord. The micrococci enter the body from the throat and nose, and either pass directly from here into the meninges, or they enter into the blood and are carried by this into the meninges. The organisms are easily destroyed and cannot long survive the conditions outside the body, so that for infection to take place the transmission must be very direct. Carriers who have the organisms in the throat, but who do not have the disease, are the principal agents in dissemination. The mortality is high, and even in recovery permanent damage is often done to the brain or to the organs of special sense. Sporadic cases constantly occur in small numbers, and it is difficult or impossible to trace any connection between these cases. At varying intervals, often twenty years intervening, an epidemic appears which sometimes remains local in a city or state, sometimes extends to adjoining cities or states, and may even extend over a very large area. In the epidemics the mortality is much higher than in the sporadic cases. The same explanation given for smallpox cannot apply here, for there is not a similar accumulation of susceptible material. We know there is a great deal of variation in the virulence of the different pathogenic organisms, and the virulence can be artificially increased and diminished. In epidemics of meningitis the virulence of the organisms is increased, as is shown by the greater mortality. It is highly probable that such epidemics are due to changes which arise in the organisms from causes we do not know and which increase their capacity for harm. It is possible that such a change would convert a carrier into a case of disease, the organism acquiring greater powers of invasion. Such a strain of organisms arising in one place and producing an epidemic could be transported to another locality and exert the same action, or similar changes in the organisms could arise simultaneously in a number of places. Analogies to such conditions are given in plants. In certain plants it has been shown that from unknown causes there appears a tendency to the production of variations. A very beautiful herbaceous peony known as "Bridesmaid" after having grown for a number of years in single form, in one year wherever grown suddenly became double. The peculiar thing with the lower unicellular organisms is that the changes which so arise do not tend to become permanent, the organism reverts to its usual character, the disease to its sporadic type.

A very fatal form of poliomyelitis has for a number of years prevailed in Sweden. In the United States there have been continually a number of single cases of the disease, and it is not impossible that a more pathogenic strain of the organism has developed in Sweden and has been imported into this country, giving rise to the much greater extension of the disease in a number of places.

The most cursory study of the infectious diseases shows that there is great variation in the susceptibility of individuals. Even in the most severe epidemics all are not equally affected, some escape the infection, others have the disease lightly, others severely, some die. Chance enters into this, but plays a small part, for the same varying individual susceptibility is shown experimentally. If a given number of animals of the same species, age and weight, even those from the same litter, be inoculated with a given number of bacteria shown to be pathogenic for that species, the results differ. If the dose be necessarily fatal, death will take place at intervals; if a dose smaller than the fatal be used, some animals will die, others will recover. The defences of the organism being centred in the activity of the living tissue, any condition which depresses cell activity may have an effect in increasing susceptibility to infection. Animals which ordinarily are not susceptible to infection with a certain organism may be made so by prolonged hunger, or fatigue, by the influence of narcotics, by reduction of the body temperature, by loss of blood. In man prolonged fatigue, cold, the use of alcohol to excess and even psychic depression increases susceptibility. It has been shown that such conditions are accompanied by a diminution in the power of the blood to destroy bacteria.

There is variation in the susceptibility to infection in the different races of man. If a race be confined to one habitat with close intercourse between the people, such a race may acquire a high degree of immunity to local diseases by a gradual weeding out of the individuals who are most susceptible. A degree of comparative harmony may be gradually established between host and parasite, as is the case in wild animals. These have few diseases, the weak die, the resistant breed; they harbor, it is true, large numbers of parasites, but there is mutual adjustment between parasite and host. Diseases in animals greatly increase under the artificial conditions of domestication. Certain highly specialized breeds of cattle, as the Alderneys, are much more susceptible to tuberculosis than the less specialized. The high development of the variation which consists in a marked ability to produce milk fat is probably combined with other qualities, shown in diminished resistance to disease, and under natural conditions the variation would not have persisted. The introduction of a new disease into an isolated people has often been attended with dire consequences. It is much the same thing with the introduction of disease of plants. In Europe the brown-tail moth and the gypsy moth produce continuously a certain amount of damage to the trees, but their parasitic enemies have developed with them and check their increase. These pests were brought to this country in which there were no conditions retarding their increase and have produced great damage.

It is very difficult to estimate the degree of racial susceptibility. The negro race seems to be more susceptible to certain diseases, such as tuberculosis and smallpox, less so to others, as yellow fever, malaria and uncinariasis. What are apparently differences in susceptibility may be explained by racial customs. A statistical inquiry into death in India from poisonous snakes might be interpreted as showing a marked resistance on the part of the white to the action of the venom, but it is merely a question of the boots of the whites and the naked feet and legs of the natives. The relatively greater frequency of smallpox in the blacks is due to the greater difficulties in carrying out vaccination measures among them and the greater opportunity for infection which results from their less hygienic life. It has always been noted that when plague prevails in Oriental cities, the natives are more frequently attacked than are Europeans. This does not depend upon differences in susceptibility, but on the better hygienic conditions of the whites which prevent the close relation to rats and vermin by which infection is extended. There would be but little extension of the hookworm disease in a community where shoes were worn and the habits were cleanly.

It is by no means improbable that the formation of the habits of civilization was influenced by infection. Most of these habits, such as personal cleanliness, the avoidance of close contact, the demand for individual utensils for eating and drinking, are all of distinct advantage in opposing infection. Certain habits, on the other hand, such as kissing, which probably represents the extension of a habit of sexual origin, are disadvantageous and infection is often transmitted in this way. In syphilitic infection the mouth forms one of the most common localizations of the disease and may contain the causal organisms in great numbers. This, the spirochaeta pallida, is an organism of great virulence, and man is the most susceptible animal. The disease, like gonorrhoea, is essentially a sexual disease, the primary location is in the sexual organs, and it is transmitted chiefly by sexual contact. Of all the infectious diseases, it is the one most frequently transmitted to the unborn child; in certain cases the disease is transmitted, in others the developing foetus may be so injured by the toxic products of the disease that various imperfections of development result, as is shown in deformities, or in conditions which render the entire organism or individual organs, particularly the nervous system, more susceptible to injury. Following the primary localization of the acquired form of the disease, there is usually secondary localization in the mucous membrane of the mouth, and the disease may be transmitted by kissing or by the use of contaminated utensils. The habit of indiscriminate kissing is one which might with great benefit be given up.

There is definite relation between age and the infectious diseases. In general, susceptibility is increased in the young; young animals can be successfully inoculated with diseases to which the adults of the species are immune, and certain human diseases, such as scarlet fever, measles and whooping cough, seem to be the prerogatives of the child. It must be remembered, however, that one attack of these diseases confers a strong and lasting immunity and children represent a raw material unprotected by previous disease. Where measles has been introduced into an island population for the first time, all ages seem equally susceptible. All ages are equally susceptible to smallpox, and yet in the general prevalence of the disease in the prevaccination period it was almost confined to children, the adults being protected by a previous attack. The habits and environment at different ages have an influence on the opportunities for infection. There is comparatively little opportunity for infection during the first year, in which period the infant is nursed and has a narrow environment within which infection is easily controlled. With increasing years the opportunities for infection increase. When the child begins to move and crawl on hands and knees the hands become contaminated, and the habit of putting objects handled into the mouth makes infection by this route possible. Food also becomes more varied, milk forms an important part of the diet, and we are now appreciating the possibilities of raw milk in conveying infection. With the enlarging environment, with the school age bringing greater contact of the child with others, there come greater opportunities for infection which are partly offset by the increase in cleanliness. The dangers of infection in the school period are now greatly lessened by medical inspection and care of the school children. In the small epidemic of smallpox which prevailed in Boston from 1881 to 1883, there was a sharp decline in the incidence of the disease in children as soon as the school age was reached, this being due to the demand of vaccination as a condition for entrance into the schools. Many of the infectious diseases are much milder in children than in adults. This is the case in typhoid fever, malaria and yellow fever. The comparative immunity of the natives to yellow fever in regions where this prevails seems to be due to their having acquired the disease in infancy in so mild a form that it was not recognized as such.

The infectious diseases are preeminently the diseases of the first third of life. After the age of forty man represents a select material. He has acquired immunity to many infections by having experienced them. Habits of life have become fixed and there is a general adjustment to environment. The only infectious disease which shows no abatement in its incidence is pneumonia, and the mortality in this increases with age. Between thirty-five and fifty-five man stands on a tolerably firm foundation regarding health; after this the age atrophies begin, the effects of previous damage begin to be apparent, and the tumor incidence increases.

FOOTNOTE: [1] This was the case of a woman, by occupation a cook, whose numerous exchanges of service were accompanied by the appearance of cases of typhoid fever in the families. This became so marked that an examination was made and she was found to be a typhoid carrier and as such constantly discharging typhoid bacilli. She is now isolated.



CHAPTER X

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.—INTRA-UTERINE 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.

The question of inheritance of disease is closely associated with the study of infection, and the general subject of heredity in its bearing on disease can be considered here. By heredity is understood the transference of similar characteristics from one generation of organisms to another. The formation of the sexual cells is a much more complex process than that of the formation of single differentiated cells, for the properties of all the cells of the body are represented in the sexual cells, to the union of which the heredity transmission of the qualities of the parents is due. In the nucleus of all the cells in the body there is a material called chromatin, which in the process of cell division forms a convoluted thread; this afterwards divides into a number of loops called chromosomes, the number of which are constant for each animal species. In cell division these loops divide longitudinally, one-half of each going to the two new cells which result from the division; each new cell has one-half of all the chromatin contained in the old and also one-half of the cytoplasm or the cell material outside of the nucleus. The process of sexual fertilization consists in the union of the male and female sex cells and an equal blending of the chromatin contained in each (Fig. 22). In the process of formation of the sexual cells a diminution of the number of chromosomes contained in them takes place, but this is preceded by such an intimate intermingling of the chromatin that the sexual cells contain part of all the chromosomes of the undifferentiated cells from which they were formed. The new cell which is formed by the union of the male and female sexual cells and which constitutes a new organism, contains the number of chromosomes characteristic of the species and parts of all the chromatin of the undifferentiated cells of male and female ancestors. As a result of this the most complicated mechanism in nature, it is evident that in a strict sense there can be no heredity of a disease because heredity in the mammal is solely a matter of the chromosomes and these could not convey a parasite. The new organism can, however, quickly become diseased and, by the transference of disease to it and by either parent, there is the appearance of hereditary transmission of disease, though in reality it is not such. The ovum itself can become the site of infection; this, which was first discovered by Pasteur in the eggs of silkworms, takes place not infrequently in the infection of insects with protozoa. In Texas fever the ticks which transmit the disease, after filling with the infected blood, drop off and lay eggs which contain the parasites, and the disease is propagated by the young ticks in whom the parasites have multiplied. The same thing is true in regard to the African relapsing or tick fever, which is also transferred by a tick. In the white diarrhoea of chickens the eggs become infected before they are laid and the young chick is infected before it emerges from the shell. It is highly improbable, and there is no certain evidence for it, that the extremely small amount of material contributed by the male can become infected and bring infection to the new organism. In the cases in which disease of the male parent is transferred to the offspring, it is either by an infection of the female by the male, with transference of the infection from her to the developing organism, or with the male sexual cells there may be a transference to the female of the infectious material and the new organism may be directly infected. No other disease in man is so easily and directly transferred from either parent to offspring as is syphilis, and the disease is extremely malignant for the foetus, usually causing death before the normal period of intra-uterine development is reached.



The mother gives the protection of a narrow and unchanging environment and food to the new organism which develops within the uterus, and there is always a membranous separation between them. Disease of the mother may affect the foetus in a number of ways. In most cases the membrane of separation is an efficient guard preventing pathogenic organisms reaching the foetus from the mother. In certain cases, however, the guard can be passed. In smallpox, not infrequently, the disease extends from the mother to the foetus, and the child may die of the infection or be born at term with the scars resulting from the disease upon it. Syphilis in the mother in an active stage is practically always extended to the foetus. We have said that in an infectious disease substances of an injurious character are produced by bacteria, and such substances being in solution in the blood of the infected mother can pass through the membranous barrier and may destroy the foetus although the mother recovers from the infection.



Living matter is always individual, and this individuality is expressed in slight structural variations from the type of the species as shown in an average of measurements, and also in slight variations in function or the reactions which living tissue shows towards the conditions acting upon it. The anatomical variations are more striking because they can be demonstrated by weight and measure, but the functional variations are equally numerous. Thus, no two brains react in exactly the same way to the impressions received by the sense organs; there are differences in muscular action, differences in digestion; these variations in function are due to variations in the structure of living material which are too minute for our comparatively coarse methods of detection. In the enormous complexity of living matter it is impossible that there should not be minute differences in molecular arrangement and to this such functional variations may be due. Chemistry gives us a number of examples of variations in the reaction of substances which with the same composition differ in the molecular arrangement. Even in so simple a mechanism as a watch there are slight differences in structure which gives to each watch certain individual characteristics, but the type as an instrument constructed for recording time remains. In the fusion of the chromosomes of the male and female sexual cells, to which the hereditary transmission of the ancestral qualities to the new offspring is due, there are differences in the qualities of each, for the individuality of the parents is expressed in the germ cells, and the varying way in which these may fuse gives to the new cell qualities of its own in addition to qualities which come from each ancestor, and from remote ancestors through these. The qualities with which the new organism starts are those which it has received from its ancestors plus its individuality. The fact that the sexual cells are formed from the early formed cells of the new organism which represent all of the qualities of the fertilized ovum or primordial cell, renders it unlikely that the new offspring will contain qualities which the parents have acquired. The question of the inheritance of characteristics which the parents have acquired as the result of the action of environment upon them is one which is still actively investigated by the students of heredity, but the weight of evidence is opposed to this belief.

In the new organism the type of the species is preserved and the variations from the mean to which individuality is due are slight. We are accustomed to regard as variations somewhat greater departures from the species type than is represented in individuality, but there is no sharp dividing line between them.

Very much wider departures from the species type are known as mutations. Such variations and mutations, like individuality, may be expressed in qualities which can be weighed and measured, or in function, and all these can be inherited; certain of them known as dominant characteristics more readily than others, which are known as recessive. If these variations from the type are advantageous, they may be preserved and become the property of the species, and it is in this way that the characteristics of the different races have arisen. Certain of the variations are unfavorable to the race. The varying predisposition to infection which undoubtedly exists and may be inherited represents such a variation. Tuberculosis is an instance of this; for, while the cause of the disease is the tubercle bacillus, there is enormous difference in the resistance of the body to its action in different individuals. The disease is to a considerable extent one of families, but while this is true the degree of the influence exerted by heredity can be greatly overestimated. The disease is so common that in tracing the ancestry of tuberculous patients it is rare to find the disease not represented in the ancestors. A further difficulty is that the environment is also inherited. The child of a tuberculous parent has much better opportunity to acquire the infection than a child without such an environment [page 167]. Other diseases than the infectious seem to be inherited, of which gout is an example. In gout there is an unusual action of the cells of the body which leads to the formation and the retention in the body of substances which are injurious. Here it is not the disease which is inherited, but the variation in structure to which the unusual and injurious action of the cells is due.

While tuberculosis and gout represent instances in which, although the disease itself is not inherited yet the presence of the disease in the ascendants so affects the germinal material that the offspring is more susceptible to these particular diseases, much more common are the cases in which disease in the parents produces a defective offspring, the defect consisting in a general loss of resistance manifested in a variety of ways, but not necessarily repeating the diseased condition of the parent. In these cases the disease in the parents affects all the cells of the body including the germinal cells, and the defective qualities in the germ cells will affect the cells of the offspring which are derived from these. There is a tendency in these cases to the repetition in the offspring of the disease of the parents, because the particular form of the parental disease may have been due to or influenced by variation of structure. One of the best examples of affection of the offspring by diseased conditions of the parents produced by a toxic agent which directly or indirectly affects all the cells of the body is afforded by alcohol when used in excess. Since drunkenness has become a medical rather than a moral question, a great deal of reliable data has accumulated in regard to it as a factor in the heredity of disease. Grotjahn gives the following examples: Six families were investigated in which there were thirty-one children. In all these families the father and grandfather on the father's side were chronic alcoholics, and in certain of the families drunkenness prevailed in the more remote ancestors. The following was the fate of the children: eight died shortly after birth of general weakness, seven died of convulsions in the first month, three were malformed, three were idiotic, three were feeble-minded, three were dwarfs, three were epileptics, two were normal. In a second group of three families there were twenty children. The fathers were drunkards, but their immediate ancestors were free: four children died of general weakness, three of convulsions in the first month, two were feeble-minded, one was a dwarf, one was an epileptic, seven were normal. In a family in which both father and mother and their ancestors were drunkards there were six children: three died of convulsions within six months, one was an idiot, one a dwarf, and one an epileptic. For comparison there were taken from the same station in life ten families in which there was no drunkenness: three children died from general weakness, three from intestinal troubles, two of nervous affection, two were feeble-minded, two were malformed, fifty were normal. Legrain has studied on a larger scale the descendants of two hundred and fifteen families of drunkards in which there were eight hundred and nineteen children. One hundred and forty-five of these were insane, sixty-two were criminals, and one hundred and ninety-seven drunkards. Of course all this cannot be attributed to alcohol alone. There is first to be considered a probable variation in the nervous system which is expressed in the alcoholic habit; second, the environment consisting in poverty, bad associates, etc., which the alcoholic habit brings; third, the alcohol alone. That defective inheritance so frequently takes the form of alcoholism is largely due to the environment. There has never been the opportunity to study on a large scale the effect of the complete deprivation of alcohol from a people living in the environment of modern civilization. There is a possibility, and even probability, that the defective nervous organization which predisposes to alcoholism would seek satisfaction in the use of some other sedative drug. So complex are all the interrelations of the social system that it would be possible to regard alcohol as an agent useful in removing the defective, were it not for its long-enduring action and its effects on the descendants, procreation not being affected by its use.

Diseases of the nervous system are particularly apt to affect the offspring, and often the inherited condition repeats that of the parents. This is due to the fact that most of the nervous diseases depend both upon intrinsic factors which consist in some defective condition of the nervous system representing a variation, and extrinsic factors due to environment or occupation which make the basal condition operative. The definite relation between alcoholism and insanity is due to alcohol acting not as an intrinsic but an extrinsic factor, bringing into effectiveness the hereditary weakness of the nervous system. The influence of heredity in producing insanity is variously estimated at from twenty-six per cent to sixty per cent of all cases. This great difference in the estimation of the hereditary influence is due to the personal equation of the statistician, and the care with which other factors are eliminated. In the more severe form of the hereditary degeneration the same pathological conditions are repeated in the descendants. In certain cases the severity of the condition increases from generation to generation. According to Morel there may be merely what is recognized as a nervous temperament often associated with moral depravity and various excesses in the first generation; in the second, severe neuroses, a tendency to apoplexy and alcoholism; in the third, psychic disturbances, suicidal tendencies and intellectual incapacity; and in the fourth, congenital idiocy, malformations and arrests of development. There are some very definite data with regard to inheritance in the nervous disease known as epilepsy. The essential condition in this consists in attacks of unconsciousness, usually accompanied by a discharge of nerve force shown in convulsions, the attack being often preceded by peculiar sensations of some sort known as the aura. In the most marked forms of the affection heredity plays but little part, owing to the early supervention of imbecility and helplessness, and it is a greater factor in the better classes of society than in the proletariat. In the better classes, owing to the greater care of the cases and the avoidance of exciting causes of the attacks, the disease is better controlled and rarely advances to the extent that it does among the poor. The association of epilepsy and alcoholism is especially dangerous, for a slight amount of alcohol may greatly accentuate the disease. In five hundred and thirty-five children in whose parentage there were sixty-two male and seventy-four female epileptics, twenty-two were born dead, one hundred and ninety-five died from convulsions in infancy, twenty-seven died in infancy from other causes, seventy-eight were epileptics, eleven were insane, thirty-nine were paralyzed, forty-five were hysterical, six had St. Vitus's dance, one hundred and five were ordinarily healthy. That variations in the nervous system which produce more or less unusual mental peculiarities and which do not take the form of nervous disease are inherited, the most superficial consideration shows. A child in its mental characteristics is said to take after one or the other of its parents, certain habits and mental traits are the same, often even the handwriting of a child resembles that of a parent.

In certain cases the inheritance is transmitted by the female alone. This is the case in the haemophilia, the unfortunate subjects of which are known as bleeders. There is in this a marked tendency to haemorrhage which depends upon an alteration in the character of the blood which prevents clotting. This, the natural means of stopping bleeding from small wounds, being in abeyance, fatal haemorrhage may result from pulling a tooth or from an insignificant wound. There is a seeming injustice in the inheritance, for the females do not suffer from the disease although they transmit it, while the males who have the disease cannot even create additional sympathy by transmitting it.

The most obvious inheritance is seen in the case of malformations. These represent wide departures from the type of the species as represented in the form. There is no hard and fast line separating the slight departures from the normal type known as variations and mutations, from the malformations. Certain of the malformations known as monstrosities hardly represent the human type. These are the cases in which the foetus is represented in a formless mass of tissue, or there is absence of development of important parts such as the nervous system or there is more or less extensive duplication of the body. There has always been a great deal of popular interest attached to the malformations owing to the part which maternal impressions are supposed to play in their production. In this, some striking impression made on the pregnant woman is supposed to affect in a definite way the structure of the child. The cases, for instance, in which a woman sees an accident involving a wound or a loss of an arm and the child at birth shows a malformation involving the same part. There is no association between maternal impressions and malformations, although there have been many striking coincidences. All malformations arise during the first six weeks of pregnancy known as the embryonic period, in which the development of the form of the child is taking place, and during which time there is little consciousness of pregnancy. Maternal impressions are usually received at a later period, when the form of the child is complete and it is merely growing. It must be remembered also that there is neither nervous nor vascular connection between the child in the uterus and the mother, the child being from the period of conception an independent entity to which the mother gives nutriment merely. Of course, as has been said, the mother may transmit to the child substances which are injurious, and in certain cases parasites may pass from the mother to the foetus. The same types of malformations which occur in man are also seen in birds, and it would require a more vigorous imagination than is usual to believe that a brooding hen could transmit an impression to an egg and that a headless chick could result from witnessing the sacrifice of an associate. The idea of the importance of maternal impressions in influencing the character of the offspring is a very old one, a well-known instance being the sharp practice of Jacob's using peeled wands to influence the color of his cattle. In regard to coincidences the great number of cases in which strong impressions made on the mind of the pregnant mother without result on the offspring are forgotten. The belief has been productive of great anxiety and even unhappiness during a period which is necessarily a trying one, and should be dismissed as being both theoretically impossible and unsupported by fact.