Chapter 5

To prevent scrofula it is essential not to give the food of adults to children during the first years of life; avoid exclusively solid food and prepare the same in a pappy form as much as possible. Of course a proper regulation of meal-time and a careful avoidance of overfeeding is by all means to be observed.

It is of no less importance for a successful treatment of scrofula to provide surroundings of as favorable conditions as possible.

First of all _pure air_ containing plenty of _oxygen_. Therefore the _sea-coast_ is recommended as a proper place for scrofulous children. The children ought to stay there until the signs of scrofula have disappeared and the entire nutrition has been improved. The results obtained in the sanitary stations (vacation colonies) along the sea-shore for scrofulous children have received much favorable comment.

_Mountain air_ has a similarly favorable effect especially when _salt water baths_ are used at the same time; even the plain, pure _country air_ proves beneficial to scrofulous children. _Very dry_ locations and dwellings ought to be selected. The children should remain _out of doors_ as much as possible.

Of great importance for scrofulous children, furthermore, is a suitable course in _gymnastics and rubbing-down with cold water_. To begin with the water may be 72 deg. but should gradually be reduced to the natural temperature of well water.

Just how far Koch's new method will take the place of former remedies used for scrofula can not be told at present as experiments in this direction are wanting. Nevertheless it will be possible to prevent the dangerous transition of scrofula into tuberculosis and thus save the lives of a great many persons.

Anyone who has informed himself through the foregoing as to the great number of diseases and forms of disease that are directly or indirectly connected with tuberculosis, will now be able to estimate the farreaching import of Koch's discovery. It will now be clear to him that pulmonary consumption constitutes only a part, although a great part of tuberculosis and that there are a great many diseases besides that can now be surely cured, it is hoped, with the aid of Koch's method. But this much should be remembered by everyone that this remedy also acts best and surest during the _beginning_ of a disease. We hope that no one will allow valuable time to slip unimproved; it may easily happen that it is too late for successful treatment. Everyone will be able to recognize the symptoms of diseases, which Koch has taught to cure, from the foregoing complete description, and it is better to apply the remedy once too often than miss the proper time for application.

Koch's first communications relating to the subject have just been published and will be given unabridged in the following pages. As these communications are written for physicians we will add such explanatory notes as are deemed essential for general intelligence.

THE FIRST COMMUNICATION

_Relating to a Method to Cure_

TUBERCULOSIS,

BY

Prof. R. KOCH, Berlin.

In a lecture, delivered by me several months ago, at the International Medical Congress, I referred to a remedy, which makes animal subjects impervious to the inoculation of Tubercle-bacilli, and in the case of diseased animals, checks the progress of the tuberculous disease. In the meantime experiments have been made with human subjects, about which I will report in the following.

Originally I intended to complete my investigations and especially gain sufficient experience concerning the practical application of the remedy and its production on a larger scale before I published anything concerning it. In spite of all precautions too much has already been published about it, and that distorted and exaggerated, so that I was obliged, in a way, to prevent false conceptions, to give even now a synopsis of the method as far as it has progressed at the time being. Under present circumstances it must necessarily be short and leave unanswered many important questions.

The experiments have been, and are still being made under my direction by Dr. A. Libbertz and Stabsarzt Dr. E. Pfuhl. The necessary subjects and material have been provided by Prof. Brieger from his Polyclinic, Dr. W. Levy in his Private Surgical Clinic, Geheimrath Fraentzel and Oberstabsarzt R. Koehler in the Charite-Hospital, and Geheimrath Herr v. Bergmann in the Surgical University Clinic. To all these gentlemen and their assistants I here tender my heartfelt thanks for their untiring interest which they manifested for this subject and also for the disinterested help and aid which they have offered at all times and without which it would have been impossible for me to make such progress in a few months in this difficult and responsible investigation.

As my work is far from being completed, I can not as yet make any statements relating to the origin and preparation of this remedy and reserve these for some future time.[1]

The curative is composed of a clear brown fluid, which in itself is not perishable, even without special precautionary measures. For use this fluid must be more or less diluted and these dilutions are perishable when made with distilled water; Bacterian vegetation soon develops in them and they become turbid and are no longer fit for use. To prevent this the dilutions must be sterilized through heat and be kept under cotton batting or be prepared with a 5 per cent. phenol solution which is much simpler. Through repeated heating as also through the mixture with the phenol the efficiency of the diluted solution appears to be curtailed after a time and for that reason I have always used solutions as fresh as possible.

The remedy does not act through the stomach; to effect a reliable action it must be applied subcutaneously. For our experiments we have exclusively used a syringe decided upon by myself for bacteriological purposes, which is supplied with a small india-rubber ball and which has no stamp. Such a syringe can be easily kept positively aseptic by rinsing with absolutely pure alcohol and on this we base the fact that not a single abscess has sprung from over a thousand injections.

After trying various parts of the body as places for application we selected the skin of the back between the shoulderblades and in the lumbar region, because at these places the injection was almost painless and caused the least and in most cases no local reaction.

Even at the beginning of our experiments we found that in one particularly important point the human subject was affected by the curative in a way decidedly differing from that of the animal subject generally used, the guinea pig. Therefore another confirmation of the rule for experimentors upon which hardly enough stress can be laid, not to rely upon a like effect upon the human being from the experiments on the animal without further confirmatory inquiry.

Man proved himself much more sensitive to the effects of the remedy than the guinea pig. Up to two cubic centimeters and even more of the undiluted fluid could be injected under the skin of a healthy guinea pig without causing any particularly disparaging effect. In the case of a fullgrown man on the other hand, 25 ccm. are sufficient to produce intense results. In proportion to weight of body therefore 1/1500 of the amount which has no noticeable effect on the guinea pig has a decidedly strong effect on the man.

From an injection that I have made on my upper arm I have experienced the symptoms which arise in man after an injection of 25 ccm., in short they were the following: Three or four hours after the injection a raking pain in the joints, languor, inclination to cough, oppressed breathing, which rapidly increased; in the fifth hour I experienced intense chills which lasted nearly an hour, at the same time nausea, vomiting, increase of the temperature of the body to 39.6 deg. C. After about 12 hours all these affectations ceased. The temperature sank and reached the normal height the next day. Heaviness of the limbs and languor lasted for a few more days, and for the same length of time the place of injection remained red and painful.

The lower limit of effect of the curative for a healthy man is about .01 ccm. (= 1 cubic centimeter diluted with a 100 parts) as numerous trials have shown. The majority reacted on this dose with only light pain in the joints and passing languor. With a few a slight rise in temperature set in, to 38 deg. C. or a trifle higher.

Although there is a marked difference as regards the dose of the curative (according to relative weight of body) between the animal subject and man, an evident resemblance is shown in several other qualities.

The most important of these qualities is _the specific action of this remedy on tuberculous processes of whatever kind they may be_. I will not relate the effects on the animal subject in this connection, as it would lead too far, but will at once turn to the peculiar effects on tuberculous human beings.

As we have seen, a healthy man reacts but little or not at all on .01 ccm. The same is true of diseased persons, provided they are not tuberculous. But the relations are entirely different with those afflicted with tuberculosis; a marked general and also a local reaction resulted from an injection of the same dose of the remedy (.01 ccm.)[2].

The general reaction consists of an attack of fever, which, beginning mostly with chills, raises the temperature to over 39 deg., often up to 40 deg. and even 41 deg. Other noticeable symptoms are pains in the joints, a tendency to cough, great languor, and often nausea and vomiting. Several times we observed a faint icteric coloring and in some cases the appearance on neck and breast of an exanthema resembling measles. As a rule the attack begins 4-5 hours after the injection and lasts 12-15 hours. In exceptional cases it may begin much later, but then it is not nearly so intense. The patients experience remarkably little weakness from the attack and feel relatively well as soon as it is over, generally better than they did before it came on.

The local reaction can best be observed on those patients whose tuberculose affection is plainly visible, for instance those afflicted with lupus. In them changes take place that prove the specific antitubercular action of the remedy in a most surprising way. The diseased portions of the skin in the face, etc. begin to swell and turn red even before the attack of chills set in, although the injection is made under the skin of the back, a point decidedly remote from the affected parts. The swelling and reddening increases during the fever and can attain a very marked degree so that the lupus-tissue turns reddish brown and necrotic. In the case of more sharply defined lupus centres the more swollen and dark red parts were edged by a white seam nearly a centimeter wide and this again was surrounded by a wide bright red border. The swelling of the diseased parts gradually decreases after the cession of fever and may have entirely disappeared after 2 or 3 days. A serum exudes from these lupus-centres and, drying, forms a crust on them which changes into scabs that fall off in 2-3 weeks and sometimes leave a smooth red scar after a single injection. Generally several injections are necessary to effect a complete removal of the lupose tissue, but of this I will speak further on. It is very important to note that the changes during this process are exclusively limited to the portions of the skin affected by lupus; even the faintest and smallest bits of diseased tissue go through the entire process and become visible on account of their swelling and reddening, while the actual scab-tissue in which the various stages of lupus have been completed remains unchanged.

The observation of the treatment of lupus with the remedy is so instructive and must be so convincing as regards the specific nature of the remedy that every one wishing to occupy himself with the study of this remedy should if possible make his first experiments with lupus.

Less marked, but still apparent to the eye and touch are the local reactions in tuberculosis of the lymphatic glands, of the bones and joints, etc., in which case swelling and increased painfulness, and in the more superficial parts also a reddening can be observed.

The reaction in the inner organs, especially the lungs is removed from our observation unless we consider the increased coughing and expectoration of the patients after the first injection a local reaction. At the same time we must assume that these parts undergo changes directly observed in the case of lupus.

The different forms of reaction described have appeared without exception in previous trials on the dose of .01 ccm. when any form of tuberculosis prevailed in the system, and therefore I trust that I am justified in assuming, that in the future this remedy will constitute an indispensible diagnostic auxiliary. We will be enabled to diagnose in doubtful cases of phthisis even then, when it is impossible to obtain reliable information concerning the nature of the ailment, by the presence of bacilli or elastic fibres in the sputum or by a physical examination. Glandular affectations, hidden tuberculosis of the bones, doubtful tuberculosis of the skin and the like will easily and reliably prove to be such. In case of apparently completed processes of tuberculosis of the lungs or joints it will be possible to show whether the process of the disease is in reality a complete one or establish the existence of centres from which later on the disease may spread like a fire from a live coal in the ashes.

But much more important are the specific qualities of the remedy than the aids it offers for the diagnosis.

While describing the changes, that are caused by hypodermic injections of the remedy, on the parts of the skin affected by lupus, attention was called to the fact that the lupose tissue does not return to its original condition after the swelling and reddening have ceased, but is more or less destroyed and disappears. On some places, as observation teaches, the process is such, that after a single injection the diseased tissues undergo mortification and are cast off as dead matter later on. On other places it seems that a diminution or rather a kind of melting of the tissue is caused, and to effect a complete disappearance a repeated application of the remedy is necessary. As the required histological investigation is wanting, it is impossible at the present time to state with certainty how this result is brought about. Only this much is known that it is not a destruction of the tubercle bacilli, but that only the tissue containing the tubercular bacilli is affected by the application of the remedy. In this, as the visible swelling and reddening show, greater circulatory derangements are caused and with these vital changes in the _assimilation_ which result in a more or less rapid and thorough mortification of the tissue according to the manner in which the remedy is allowed to act.

To make a short repetition, the remedy therefore does not destroy the tubercle bacilli, but the tuberculous tissue; on dead tissue, for instance, gangrenous cheesy matter, necrotic bones, etc., it does not act; nor on tissue that has undergone mortification through the action of the remedy itself. Living bacilli can still linger in such dead masses of tissue, which are either cast out with the necrotic tissue, or may possibly migrate under special conditions into the adjoining living tissue.

This quality of the remedy must be particularly observed, if its full specific action is to be obtained. Therefore we must first cause the mortification of the tuberculous tissue, and then effect its removal as soon as possible, for instance, by means of a surgical operation; but where this is impossible and the excretion by the organisms themselves is necessarily slow, we must attempt by continued application of the remedy to protect the endangered living tissue from the immigration of the parasites.

As the remedy acts only on living tissue and causes mortification of tuberculous tissue, we can readily explain another exceedingly peculiar property of the remedy, namely, that it can be given in rapidly increased doses. This may apparently be explained as being based on inurement. But noting that in about three weeks the dose may be increased to 500 times the strength of the first one, it is unquestionably something more than habit, as we know of nothing analogous confirming such a rapid and farreaching adaptation to any powerful drug.

This fact can rather be explained thus: in the beginning there is an abundance of living tuberculous tissue and only a minute quantity of the effective substance is sufficient to cause a strong reaction; through each injection a certain quantity of this responsive tissue disappears, and then relatively larger doses are required to cause the same degree of reaction as before. Aside from this adaptation may assert itself within certain limits. As soon as the patient is treated with such increased doses, and that he reacts no more than one not afflicted with tuberculosis, we may assume that all the reactive tuberculous tissue is dead. It is then only necessary to continue the treatment at intervals and with gradually increased doses as long as any bacilli remain in the system, to protect the patient from a new infection.

It remains to be learnt in the future whether this conception and the deductions based thereon are correct. For the present I have directed the manner of application of the remedy on this basis, which in our experiments resulted as follows:

To begin again with the simplest case, namely lupus, we injected the full dose of .01 ccm. in nearly all such patients to begin with, and allowed the reaction to take its full course, after 1-2 weeks we again injected .01 ccm. and so forth until the reaction became less and less and finally ceased. In the case of two patients with facial lupus three respectively four injections in this manner resulted in a clean, smooth scar in place of the affected parts; the remaining patients of this kind have also improved in a measure proportioned to the time of treatment. All the patients have suffered from their afflictions for years and have been treated by various methods without success.

Tuberculosis of the glands, bones and joints has been treated in a very similar manner, as in these cases larger doses were applied at longer intervals. The result was the same as with lupus, a rapid cure in the lighter and milder cases and a slowly progressing improvement in the severer ones.

With the majority of our patients, those suffering from pulmonary consumption, the conditions are somewhat different, patients with decided pulmonary tuberculosis are very much more responsive to this remedy, than those afflicted with surgical tubercles. We were forced to reduce the quantity of the first dose of .01 ccm. as prepared for the phthisicist, and we found that as a rule he reacted strongly on a dose of .002 and even .001 ccm., but that the quantity could be rapidly increased from this low initial dose to that which could be easily tolerated by the other patients. We generally proceeded in such a manner that the patient at first received an injection of .001 ccm. and if a rise in the temperature set in this dose was repeated once daily until the reaction ceased. Only then the dose was increased to .002 ccm. and applied till the reactions failed to appear. And so forth, always increasing the dose only .001 or at the most .002 up to .01 ccm. and higher. This mild procedure seemed to me imperative, especially with such patient as were in a weak and feeble condition. Proceeding in the manner just described we can easily attain the application of very light doses with but slight attacks of fever and hardly perceptible to the patient. Some of the stronger consumptives were treated with larger doses from the beginning, partly with a forced increase in the dosing when it seemed as though the favorable result was obtained in a correspondingly shorter time. The action of the remedy on the phthisicist generally seemed to be such that cough and expectoration increased somewhat after the first injection, then gradually diminished and in favorable cases disappeared entirely; the sputum lost its purulent nature and became slimy. The number of bacilli as a rule did not decrease until the sputum had attained a phlegmy appearance (only such patients were selected for these experiments in whose expectorations bacilli were contained). They entirely disappeared temporarily, but were again met with from time to time until the expectoration had completely stopped. At the same time the night-sweats left off, and the patients improved in appearance and gained in weight. All patients treated in the first stages of phthisis were freed from all symptoms of disease in the course of 4-6 weeks so that they could be considered as cured. Even patients with cavities not too large were considerably improved and nearly healed. But in the case of such consumptives, whose lungs contained many and large cavities no objective improvement could be marked, although the expectoration diminished and they appeared to feel much better. I am inclined to assume on the basis of these experiences, that the _earliest stages of phthisis can with certainty be cured by this remedy_.[3] This may also hold good in cases that are not too far advanced.

In exceptional cases only will pulmonary consumptives, with large cavities, derive continued benefits through the application of the remedy, when other complications exist, for instance, the penetration of other supurative micro-organisms, irremovable pathological changes in other organs, etc. Even such patients were in most cases temporarily improved. It must follow that even in them the original process of the disease, tuberculosis, is influenced in the same manner by this remedy as in other patients, but that it is impossible to remove the gangrenous masses of tissue and also the secondary supurative processes. Naturally we are led to think that perhaps in some of these severe cases cures may be effected by means of a combination of this healing process together with surgical aid (after the manner of operating empyema) or some other curative means. I would not advise anyone however, to apply this remedy without discrimination in every case of tuberculosis. The simplest mode of application will certainly be required in treating the first stages of phthisis and simple surgical affections, but in all other forms of tuberculosis medical science should draw on all its resources and individualize carefully to supplement and sustain the action of the remedy. In many cases I have had the decided impression that the attendance to and nursing of the patient was of no little influence on the curative process, and therefore I would prefer the application of the remedy in suitably adapted institutions, where a close observation of the patient and the adequate attention to them is possible, to the ambulant or home treatment. No estimate can at present be made as to the extent in which a profitable combination can be made between this new method to cure and those modes of treatment that have thus far been considered beneficial, the application of mountain climate, the free air treatment, specific nourishment, etc.; but I trust, that these remedial factors will be of considerable use in conjunction with the new method in many cases, especially the severe and neglected as also in the convalescent stages.[4]