Allowing that intimate exposure in infancy and childhood is likely to be disastrous, there is the still more debated question as to the possible danger of intimate exposure in adult life.

Marriage is, of course, the most intimate of adult relationships, and the lack of unanimity as to the occurrence of marital contagion in tuberculosis seems to be evidence that this is, on the whole, not so very frequent. Here again there are many complicating and confusing factors. Special emphasis has been laid on the tendency of similar persons to select each other-the "assortive mating" of Karl Pearson. This, however, is flatly denied by Ward, whose numerous communications all present data in favor of frequent adult contagion. Ward thinks that people with tuberculosis are most likely to marry individuals of entirely different type.

Lawrason Brown has indicated one of the reasons for our confusion on this subject, namely the fact that many of the reports dealing with the matter are not based on the whole life history of the exposed mates, and their final mortality, but on the incidence of the disease in a short period of observation. An investigation of his own, in which this error was eliminated, covered forty thousand couples and led to the conclusion that there was an excessive incidence of tuberculosis among the marital partners of the tuberculous, but that possibly two-thirds of this was due to assortive mating. Brown himself, however, believes that adult contagion is important.

Burns has recently reported that "the histories of 229 consecutive widowed patients admitted to the Rhode Island State Sanatorium, 1905 to 1921, show that 93, or 40 per cent., lost their consorts by death from tuberculosis, a tuberculosis mortality over three times that of the married people of the community."

Crouch, at the Modern Woodmen Sanatorium in Colorado Springs, found that 58 per cent. of 233 widowed patients had lost their wives through tuberculosis. Minnig, who quotes these figures, gives 50 per cent. as his own observation.

Against these positive reports we must weigh the great body of statistics from hospitals and sanatoria, showing a lack of any excess tuberculosis morbidity and mortality among those who care for the tuberculous. Here, however, the contact is not very intimate at least it does not combine intimacy with perpetuity as marriage does.

Perhaps the various statistical researches which are now under way will illuminate this dark and disputatious corner of our ignorance. At present one feels that expert opinionwhich changes so often-is moving in the direction of more emphasis on the possible danger of very intimate and prolonged exposure to the tuberculous invalid, even in adult life, and this in spite of much erudite argument to the contrary.

It has been well said that it is easy to make laws but that it is difficult to change habits. Needless to state the anti-spitting crusade must

continue and we should suggest to people a new disgust. In the words of Dr. D. A. Stewart, "Sputum is an excretion of the human body, less repulsive than other excretions, perhaps, but not less harmful. What would be thought of us if one of the other excretions were smeared over the sidewalks as sputum is and carried on dainty slippers into otherwise clean houses?" Greater efforts must be made through education and through the visits of public health nurses in keeping children from close contact with consumptive parents or relatives. I regret to learn that in Arizona it has been necessary to reduce the number of such nurses from thirty-six to twenty. In the registration area of the United States the death rate from tuberculosis has been very greatly reduced during the past year. (United States Census shows 107,000 deaths from tuberculosis in 1920 as compared with 150,000 (?) some sixteen years ago.) There is no doubt that this reduction is in part due to the activities of state organizations, like your own, and to the efforts of the National Tuberculosis Association. We have some confirmation of this in the fact that the Metropolitan Life Insurance Company, by carrying out similar methods, has been able markedly to reduce the death rate from tuberculosis among those insured. Many attribute such results to the campaign for good living and it is exceedingly difficult to state that any one of many activities is responsible.

I have noted that the State of Arizona is not included in the Registration Area of the United States. The Department of Health of the State of Arizona has not yet been able to inaugurate a registration of vital statistics which will meet with the approval of the Federal Government.

The above-mentioned decline in the death rate from tuberculosis may, however, prove deceptive. On account of the stress of war and of the disastrous influenza epidemic of recent years, there was an acceleration in the tuberculosis death rate. We have no statistics of mortality in former war periods to be guided by.

During the siege of Paris by the Germans in the early 'seventies' the death rate from tuberculosis rapidly increased, after the siege, for a few years, a remarkable drop occurred, and it was some ten years before the figures again climbed to the pre-war tuberculosis death

rate.

From the recent war we have learned that an increased death rate from tuberculosis is closely connected with a lack of nutrition. It may well be that increased wages and the ability to buy more and better food are factors influencing tuberculosis mortality.

In Austria, as a result of the war, not only was there a very great increase in deaths from tuberculosis, but it was found that malnutrition among the children was leading to rachitic changes in 90 per cent. Von Pirquet, to whom we owe one of the epoch-making discoveries in tuberculosis-that of the skin tuberculin testdeveloped a simple scientific system of nutri

tion which was applied to feeding on a large scale and which was utilized by the Hoover Relief.

The percentage of nutrition (pelidisi), the physical examination (sacratama), and a nutritional unit (nem) have already been applied to some 1,200 children in San Francisco schools. The highest degree of malnutrition was found in a school in a very poor quarter, and curiously the next highest was found in a school in the wealthy district. One-half the children of the series showed a mild degree of malnutrition. School physicians and nurses in this country have for some time been encountering similar conditions, although possibly not so scientifically studied, and the extra supplies of food and vitamines to under-nourished children will no doubt aid in decreasing the death rate in the coming generation of adults.

You will all be interested to learn some of the achievements of the Framingham, Mass., demonstration of the last four years. The demonstration was started by the National Association and the Metropolitan Life Insurance Company to ascertain if it was possible to banish tuberculosis from an average city.

The introduction of physicians into the factories of this town, the opening of dispensaries, the use of visiting nurses, and the examination of almost every one of the 18,000 inhabitants, together with all known anti-tuberculosis methods, have revealed interesting data and results. Among other developments, it was found in Framingham that—

1. One per cent. of the inhabitants had active tuberculosis.

2. Another 1 per cent. had inactive pulmonary tuberculosis.

3. That the death rate from this disease was reduced from 120 per 100,000 living inhabitants to 80.

4. That before the demonstration started, 13 cases of tuberculosis were reported to the Board of Health each year, whereas now 43 were discovered early each year.

From the above figures we may safely estimate that there are some 2,000,000 consumptives in the United States. The eyes of the world are focussed on this practical demonstration and similar results can be obtained in any community that has the will to make a similar effort.

In spite of the importation of so many consumptives, Arizona has a native death rate of only 80 per 100,000, yet this is none too low considering the lack of congestion. The re.port of the Committee of the National Tuberculosis Association on your migratory con- . sumption problem shows indeed what a burden you carry in caring for the indigent consumptives of other states. The report indicates that over 80 per cent. of these unfortunates have come here on the advice of physicians. Every effort is being made to enlighten such physicians, and a resolution passed the House of Delegates of the American Medical Association at the annual meeting in Boston last June devoted to this question.

The Arizona State Board of Health has been most generous in contributing to the tuberculosis campaign, and your sale of Christmas Seals places you among the first ten states in the per capita raised. Yet still more funds are necessary, as in any conflict, to ensure the success of your endeavors to rid Arizona of tuberculosis.

The decline of the death rate in most parts of the world led the London Lancet recently to state that tuberculosis was a moribund disease. It is certainly too early to make such a claim. Tuberculosis has been stated to be the product of an incomplete civilization. We must remember most thoroughly that the campaign against this dreaded disease results in general betterment of the race and a decline in the morbidity and mortality of many other diseases.

I have noted that the people who give most generously to this campaign are those who themselves have suffered directly or indirectly from the disease. It would seem that those who have not suffered should be the most generous in gratitude for having escaped such disaster!

At the recent meeting in London of the International Union Against Tuberculosis two important topics were discussed:

1. The spread of tuberculosis in the civilized world.

2. The better education of physicians in tuberculosis.

Professor Calmette, of Paris, basing his work on that of Cotton and Schroeder, of the U. S. Bureau of Animal Industry in cattle investigations, claimed that all closed cases of tuberculosis, in fact, all infected human beings were "carriers" of this disease and could infect others. Fortunately such possible infection would probably be with small doses and would rarely prove the danger that open cases of consumptives prove to be. May I emphasize once more that the danger of an open case is great for children, but need be little feared by an adult.

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When we carefully analyze what we know regarding tuberculosis and what we do know, we are amazed to find how much more we have to learn about this plague. It was therefore most gratifying to me, that during my term as president of the National Tuberculosis Association, a start was made to help competent investigators to increase our knowl edge. Already a sum of $10,000 has been set aside, and this is being distributed to investigators belonging to the Universities, whose work has been judged by a competent committee as worthy of assistance. Five per cent. of the money raised in the Seal Sale in each State goes towards the upkeep of the National Association, and I am sure each contributor will be proud to know that in addition to supporting the many activities of this organization, such as the medical service, the field service, the publicity service, the Modern Health: Crusade and other services, the purchaser of Christmas Seals is now aiding in increasing

between infections will be of some importance in shaping the later development of disease.

The portal of entry of the germ, the place where it enters the body, will mean much in relation to what will take place later. Swallowed germs will set up a different type of infection than inhaled germs, and infection originating beneath the skin or from germs put into a vein will take a still different course in each instance.

If, therefore, we should find that animal tistues react regularly in uniform manner to tubercle bacilli, we have demonstrated with scientific surety that virulence and dosage of bacilli and their place of entering the body are contributory causative factors in making for variability of the results of infection.

The place of man and tubercle bacilli in the world at large makes for great variation of environmental conditions as these affect the three contributory causes mentioned above. The virulence of bacilli, available for human infection, will be influenced markedly by the media of infection in which they exist and by physical and chemical forces to which these media are subjected. There is an essential difference of virulence for man between human and bovine bacilli-between those germs commonly present in sputum and those in milk; and exposure to light, heat, drying, pulverization, etc., and the time between elimination from the diseased person or animal and reception by a second person, will do something toward altering virulence. The bacilli of droplets, dust, milk and crude sputum cannot always be of the same virulence at the time they are taken into the body. All environmental factors which modify tubercle bacilli enter, therefore, into the category of the causative factors of tuberculosis.

As for the matter of dosage, the possibilities are beyond computation. These must occur in every single degree-from bacilli so few they are just enough to initiate lesion (perhaps a single bacillus will do this) to countless numbers. The effect is bound to vary tremendously from a miroscopic and transient outcropping of several cells to many germs taken into lymphatics and on past lymph nodes to many remote parts of the body. A human being may presumably take into his mouth the minutest droplet expelled by a consumptive who expectorates a few bacilli; or he may drink a pint of milk which contains countless numbers of germs.

The exact point of entry and first lodgment of germs in the body must be of no little moment in influencing the subsequent course of infection. Inhaled bacilli surely penetrate mucous membranes at any point between throat and the terminal air cells of the lungs, and swallowed bacilli anywhere between the lips and gullet, and in the large and small intestine. Infection arising in tonsil or in neck node will begin a very different career from that which starts in lung or its nodes, or that in intestine and its lymphatics.

That branch of descriptive medicine which treats of the causes of disease is called etiology.

It has come to comprehend every observed and presumptive factor which may have some weight in influencing the occurrence and development of disease. Variations of particular diseases have been noticed to occur according to race, sex, age, occupation, family, physical constitution, climate, etc. On occasion factors such as these play a predominant part in the etiology of certain diseases: the lead poisoning of printers, the hemophilia (bleeders' disease) of males, and not a few organic nervous diseases are cases in point. From earliest times etiological factors of these types have been associated with phthisis or tuberculosis. And it may be well to discuss briefly in this place those factors which presumably depend upon differences of bodily constitution, established by inheritance.

The best known of these is that of familial or inherited disposition to tuberculosis. It is probably the oldest idea of the etiological relationships of the disease. Phthisis has a habit of recurring again and again in many families, especially among young adults, and frequently after years have elapsed since any known familial contact with tuberculosis has existed. This repeated occurrence of consumption in families is so outstanding a feature of the affection that before its infectious nature was satisfactorily proved, it was perhaps the best medical opinion that the disease was always implanted in soil made peculiarly susceptible to it by an inherited constitutional fault or vice.

After tuberculosis was universally accepted as originating through infection, the point of view swung to the opposite extreme. For years it has been dinned into us that familial predisposition plays no part whatever in the development of tuberculosis, and that a higher incidence of the affection in certain families is to be attributed to the greater opportunities for infection which exist in families with consumptive numbers. In other words, more tuberculosis in "tuberculous" families is a matter of larger and more frequently repeated dosage of bacilli than usually obtains.

The latter explanation is certainly true in part. Infants and young children of tuberculous parentage do more frequently contract tuberculosis and die of it than do those of nontuberculous antecedents: and, even with economic factors given their proper weight, more than usual infection would suffice to explain this circumstance. But it is not so clear why, on this basis alone, we meet with so many young men and women who are the children of parents, years dead of tuberculosis or recovered from it, and who first manifest signs of the disease as they go from adolescence into adult life. We now know, indeed, that tuberculous infection may remain dormant for years -for a lifetime. But why is it aroused to activity in an unusual proportion of instances in "tuberculous" families?

If family predisposition plays no part whatever, we can think of only one possible explanation of this obscure feature of the infection. In the bodies of human beings there re

side quiescent infections (tuberculous) of every variety, extent and degree. It would be conceivable that those persons who were unusually exposed in childhood, as the offspring of tuberculous parents would be, and who nevertheless failed to develop manifest tuberculosis then, would, in general, carry into adult life more extensive and more lasting quiescent infections, which, in a greater number of instances, would be more open to activation than in the rest of the population.

We cannot believe that the question of familial predisposition is settled; nor will it be until we obtain decisive information from controlled experimentation on animals. Scattered impressions which one gets from the observation of diseases in general lead one to presuppose that inborn variation of reaction to tubercle bacilli--and, as a consequence-inborn predisposition or resistance is a biological necessity. It is impossible to believe that the native response of all animals of a species or of a race can be alike. But whether "tuberculous" families will be shown to possess an unusual susceptibility is another question. There are those who maintain that if the members of families which have suffered tuberculosis for generations inherit anything, it must be an increased specific resistance to tubercle bacilli-a phase of etiology which will be touched upon when we take up immunity as a modifying factor of tuberculous infection.

We shall learn the truth about inherited predisposition some day; and it is encouraging that Lewis, of the Phipps Institute, has begun an experimental study of this important subject. His work has not progressed far, but he has observed effects which indicate to him that some stocks or families of guinea pigs are natively less resistant to infection than are others. If his further study should establish this as a fact, it would be a next step to discover whether over-susceptibility can be wiped out or fortified by cross-mating.

Among the factors which most writers would associate with variations in the course of tuberculous infection is that of the age of the recipient of tubercle bacilli. Observers practically agree that manifest tuberculosis is peculiarly and extraordinarily fatal to human beings during the first two years of life, comparatively benign from then until about twelve to fifteen years, again increasingly fatal until about thirty or thirty-five and after this once more less malignant. As concerns the infant, the usual explanation is that tuberculosis is so florid in it because its resistance is slight, and its resistance is slight because infants have not been immunized by previous contact (infection) with the germs.

Until we prove the truth of this proposition we must accept it with great reserve. It is incontestable that a huge proportion of tuberculous babies die. But, if the 20 per cent. which several students have shown to be the proportion of clinic children which is infected with tubercle bacilli is a fair average of infection for babies which are brought to dis

pensaries, then most infected babies do not develop manifest tuberculosis; for assuredly the number of dispensary babies ill with tuberculosis is not 20 per cent. or anything near it.

In the case of babies we must not forget to take into account the factors of high dosage and repeated infection with high dosage. As a general thing, it is quite probably true that when babies are in contact with tubercle bacilli, exposure is more likely to be extreme and unremitting for prolongd periods than for older persons. A baby lives in a relatively fixed and uniform environment. If a parent or familial associate is consumptive it will be in closer physical contact with it than will older children. If it is unfortunate enough to be fed with tuberculous milk it receives a diet which is entirely or almost entirely contaminated with the germs of disease, while an older child will use such milk as only part, perhaps a small part, of its diet: the character of intestinal contents in the two cases will certainly be very different as regards exposure to tubercle bacilli. We would expect babies in tuberculous surroundings to receive much larger numbers of tubercle bacilli than the same class of older children; and we must give this opportunity for greater dosage its proper weight in accounting for the unusual malignancy of tuberculosis in infants.

I do not doubt that the lymphatic paths of infants are more open to the widespread dissemination of tubercle bacilli than are those of older children. Indeed, the greater frequency of lymph node tuberculosis in children after three years of age suggests that such is the case; and I incline to the supposition that automatic differences of this nature are really the basis of apparent differences of resistance to infection: I have never had presented to me the evidence that would convince me that the tissues of infants are inherently less immune than those of older children.

The above considerations are set down to clear the ground and prepare the way for a discussion of what the writer considers the best substantiated factors in causing tuberculosis to take on its variegated hue, namley, factors of environment. As they come to light in the world, most cases of manifest tuberculosis do not develop uninterruptedly and progressively from the intake of relatively large numbers of bacilli. Infection is established in most of us at varying ages, but in over half of us before we emerge from childhood. Immunity is laid down with tubercle. Tubercle and immunity fluctuate, up and down; and there is good reason to believe that often both die out in many of us. Reinfection perhaps occurs-on old soil and on new. Manifest disease results from old quiescent infection and from reinfection. Whatever halts infection and whatever whips it into renewed life; or whatever allows reinfection to take hold and initiate a new cycle, with or without disease, is a causative factor of tuberculosis; and it is these which will receive attention in the next part of this Essay.