tain uniformity of experimental conditions. Finally, in any series of animals one will find animals of high, low, and intermediate degrees of resistance, and the proportions of these three classes of animals is remarkably constant being approximately 1:1:3 respectively, and the proportions appear to remain constant independent of any other known factor.

Facts such as these indicate very clearly that the ability to combat a syphilitic infection is an inherent constitutional trait. It is, however, not a property with a fixed value but may increase or decrease with age and with changes in the physical condition of the animal, and is in all cases subject to periodic increase or decrease in response to certain external influences such as are represented by changes in climate or in meterorological conditions.

Going still further, it has been possible to correlate resistance or susceptibility to syphilitic infection with anatomical and physiological states of the animal organism. This applies especially to the endocrine mechanism and the associated system of lymphoid tissues. In animals, this group of organs and tissues undergoes a striking series of changes as a result of syphilitic infection, and the changes that occur bear a definite relation to the course of the disease and to the eventual development and maintenance of the state of latency or immunity. Moreover, it has been found that operative removal of a part or the whole of such an organ as the thyroid will produce a profound alteration in the character and efficiency of the response of such animals to syphilitic infection.4

In like manner, the spontaneous variations in resistance that occur at different seasons of the year or from year to year can also be correlated with changes in the animal organism. For example, the mass relations of different organs are subject to periodic variations which correspond roughly with seasonal changes, but while these changes tend to follow the same general course from year to year the exact time of their occurrence and the extent of the change are also subject to variation. Neither the cause nor the purpose of these changes in the animal organism is definitely known, but they correspond in time and character, on the one hand, with changes in animal resistance, and on the other, with changes in certain meteorological conditions such as sunlight. By comparing these three conditions it is possible, therefore, to establish a correlation between meteorological influences, animal organization, and resistance to disease."

Apparently we are not dealing with a specific effect, except in so far as the conditions referred to may affect some part or the whole of a particular mechanism that is concerned in combating one disease more than another. are, however, dealing with a mechan

We

These statements concerning constitutional resistance of experimental animals are based upon a long series of observations and experiments which are still in progress and for the most part unpublished. The reader is referred to the following preliminary reports: Brown, Wade H., and Pearce, Louise: Proc. Soc. Exper. Biol. and Med., 1923, xx, 472. Brown, W. H., Pearce, L., and Van Allen, C. M.: Seasonal changes in organ weights and their relation to meteoro

logical conditions, Proc. Soc. Exper. Biol.

and Med., 1924, xxi, 373.

ism that is concerned with processes of growth and development, and one that is of vital importance in the maintenance of health.

When we speak, therefore, of the necessity for avoiding the use of therapeutic measures that interfere with the patient's own efforts to control his infection or of the possibility of employing measures that will aid such activities, we have something concrete on which to base such statements. Moreover, since practically all of the drugs that are used in the treatment of syphilis at the present time, arsenicals and mercurials as well as iodides, have a profound effect on the system of organs referred to, it is almost impossible to avoid influencing the resistance of the patient in one way or another. Hence it is essential that we recognize this fact and that we make proper provision for the study of effects of this kind in order that we may make the best possible use of our opportunities, experimentally and clinically.

The idea of drawing a distinction between methods of treatment that are applicable to the treatment of early syphilitic infections and those that are adapted to the treatment of advanced infections together with the idea of conserving the resources of the patient is by no means new, but the wisdom of such a policy cannot be emphasized too strongly. In placing

so much stress on this aspect of the treatment of syphilis it is not our intention to minimize the importance of parasiticidal agents. Drugs of this class have a definite purpose to serve. The "therapeia magna sterilizans" of Ehrlich is an ideal to be attained, but the point has not been reached. where we can afford to neglect other features of drug action. Meantime, if we are to progress, we must realize that success is not apt to be achieved by an effort to reduce the problem of human therapy to the level of the simplest order of laboratory experimentation. In effect, this is what has been done on the assumption that all that we need know in order to make a correct estimate of the probable value of a given drug was its so-called therapeutic index. This we know to be an erroneous assumption, and the hope for future progress in the treatment of syphilis lies in an effort to correct this error by elevating our experimental work to a plane as closely approximating that of human conditions as is possible, with a view to obtaining more exact knowledge of all of those qualities of action that may be of advantage or disadvantage in the treatment of syphilis.

This means a broadening out of clinical and experimental investigations based upon an exact knowledge. of the biology and pathology of syphilitic infections.

B

as

EFORE the war but very little recognition was given, by the average practitioner at least, to the subject of neurocirculatory asthenia. All of us were meeting with these cases, and for the greater part we were classing them neurasthenics, as hyperthyroids, or as hysterical persons. It was only when large groups were gathered together, and when we were able, as it were, to view the condition in bulk, that we were brought to a realization of the importance of the condition and to estimate adequately its very frequent occurrence. Even now many text books entirely ignore the subject, or describe it in such a brief and inadequate fashion that the student conceives no proper appreciation of its importance until he is brought into actual contact with the cases in his hospital or private practice.

Although the name of neurocirculatory asthenia is by no means generally accepted, it probably is that term which most satisfactorily describes the condition. The complex has been perfectly recognized for a great many years, and one of the earliest and best descriptions is by a famous Philadelphian, Da Costa, then an acting assistant surgeon,

'Read before the Medical Section, Philadelphia College of Medicine, March 24,

1924.

I believe, in the Union Army. The medical volumes of the Surgeon General's History of the War of the Rebellion frequently refer to the condition and while the comment is made that it has been largely brought to the fore by conditions of military life, it is fully recognized that the syndrome is but a tendency or condition very frequent in civil life which is, perhaps, brought to full attention under military conditions.

Perhaps the complex is best known in civil life under the title of the "irritable heart" and this was the name suggested by Da Costa, who with Weir Mitchell, referred to it as the "irritable heart of the soldier."

Every one of us, no matter what specialty we practice, meets with these cases, and this is the reason that I bring it before you for discussion tonight. It is no more to be grouped as a military disease or condition than red hair or hernia, pes planus, myopia or chronic otitis media, all of which conditions become dominantly apparent under universal mobilization of any sort.

The British seem to prefer the term of effort syndrome, since they found it chiefly apparent in their young soldiers who had been abruptly plunged with very little physical preparation into the stress of modern warfare. We found it more frequent in our recruits who had never seen

anything approaching actual war conditions, aside from the tremendous emotional state which always sweeps over a country during such public calamities. The explanation of the British standpoint as compared to ours, for you will find a most striking and essential divergence in the two descriptions of the one condition, lies essentially in this fact. The British recruit of this tendency, broke because he had been submitted to war stress without a primary careful elimination of these men by an examination, or at least not one so critical as that to which we submitted our men. Our cases for the greater part were eliminated from the combatant forces before they reached France. I did see among our own men, in France, many cases of effort syndrome precisely such as the British describe, but only because a certain percentage of these defectives had escaped elimination through insufficient examination and were sent with our combatant units. These of our cases were precisely like those of the British, French and Italians. This explanation will, I think, suffice to make clear the very wide apparent divergence between. our descriptions of the complex and those of the British, notably.

The syndrome has always become dominant in conditions of great emotional disturbance, during revivals, business depressions, war and the like. It exists at all times, but those who suffer from it most strikingly manifest the evidences of the condition only under emotional stress, for the syndrome as a whole is definitely allied to emotional instability.

The physical appearance of these cases is quite characteristic. In most cases it is almost conclusively diagnostic. As to the figure, there are two types. In the one the patient is tall and slender, likely to be slightly stooped in posture. The thorax is narrow, long and rounded in form. The extremities are long, slender and more of the female type in general configuration. Muscle development rarely becomes prominent. The hands and feet are usually long and slender, and they are practically always cyanosed, cold and sweating. The capillary return in them is almost always delayed and a postural cyanosis is present.

The other type, which is by far the less frequent, is of a coarse build. The trunk is flat, almost to the point of thinness, the chest is broad, fixed, and little respiratory alternation take place. The figure is squat and the skin coarse.

As a rule the skin of the first and predominant type is very smooth and soft. The deposit of adipose is rarely large, though occasionally one sees cases of the squat type who become quite fat. Dermographia is very marked and alternate flushing and pallor of the skin are strikingly manifest, especially under emotional stresses. The hair is thin, soft and likely to be curly. Its distribution in males is more like the normal to the female, and in the female more like that in the typical male. The beard is sparse and often entirely wanting.

The external genitals are usually small, frequently defective in some way, and the testes are often unde

scended. The occurrence of inguinal hernia is common. The scrotum is small, rarely pendulous. In the females the pelvis is often poorly developed, and it reverts to the neutral form. The breasts are almost always poorly developed, and in pregnancy they are usually unable to maintain lactation in any sufficient degree. Hypoplasia and malformation of the uterus and ovaries are common.

The thyroid gland is nearly always prominent, the neck notably long and thin. The facial expression is mobile, sensitive, and the eyes usually prominent, though not necessarily exophthalmic. The lines of the face are rarely deep, or the expression

sinister.

AGE

The condition is chiefly apparent during the most emotional ages. It is a disease of early puberty. It is seen rarely and only in a much modified and reduced type in old age. During adult life it is much less frequent than in the teens and early twenties. We may represent its occurrence as to age with a rapid crescendo beginning with the early manifestations of puberty and a prolonged diminuendo as age advances.

SEX

As to the occurrence-rate determined by sex, I am somewhat in doubt. My observations during the war, the only time when I had ample opportunity to carefully study the condition in its daily manifestations has, of course, strongly influenced my impressions as to its chief occurrence being among young men,

The condition shows also very definite racial or national influences. Statistics collected by Dr. Goddard at Camp Upton showed that of these cases among the men of the 77th Division, by far the most frequent appeared among the Hebrews, notably among the Russian Hebrews. Next in occurrence came the Italians, then the Irish, the American, the British, Scotch, German, and last of all in point of frequency of occurrence was the Negro. From an entire brigade of negro troops mobilized largely from this territory, though augmented by several contingents from the south-west, but one case