THE COMPOSITION OF KOCH'S LYMPH.

WHAT PROFESSOR KOCH SAYS IT IS, AND WHAT IT CAN DO.

(By Cable to the Medical Record.)

BERLIN, January 15, 1891.

The curiosity to know the composition of the famous lymph has been gratified by the publication to-day of an article by Professor Koch on the subject. In the following, as will be seen, he reaffirms his original convictions and acknowledges the valuable assistance he has received from those who have used his fluid, and thus helped him in the accumulation of experience.

Professor Koch says: Two months ago I published the results of my experiments with the new remedy for tuberculosis, since which time many physicians who received the preparation have been enabled to become acquainted with its properties through their own experiments. So far as I have been able to review the statements published and the communications received by letter, my predictions have been fully and completely confirmed. The general consensus of opinion is that the remedy has a specific action upon tubercular tissues, and is, therefore, applicable as a very delicate and sure reagent for discovering latent and diagnosing doubtful tuberculous processes. Regarding the curative effects of the remedy, most reports agree that, despite the comparatively short duration of its application, many patients have shown more or less pronounced improvement. It has been affirmed that in not a few cases even a cure has been established. Standing quite by itself is the assertion that the remedy may not only be dangerous in cases which have advanced too far—a fact which may forthwith be conceded—but also that it actually promotes the tuberculous process, being therefore injurious.

During the past six weeks I myself have had opportunity to bring together further experiences touching the curative effects and diagnostic application of the remedy in the cases of about one hundred and fifty sufferers from tuberculosis of the most varied types in this city and in the Moabit Hospital.

I can only say that everything I have latterly seen accords with my previous observations. There has been nothing to modify in what I before reported. As long as it was only a question of proving the accuracy of my indications, it was needless for any one to know what the remedy contained or whence it was derived. On the contrary, subsequent testing would necessarily be more unbiased, the less people knew of the remedy itself. Now, after sufficient confirmatory testing, the importance of the remedy is proved, my next task is to extend my study of the remedy beyond the field where it has hitherto been applied, and if possible to apply the principle underlying the discovery to other diseases.

This task naturally demands a full knowledge of the remedy. I therefore consider that the time has arrived when the requisite indications in this direction shall be made. This is done in what follows.

Before going into the remedy itself, I deem it necessary for the better understanding of its mode of operation to state briefly the way by which I arrived at the discovery. If a healthy guinea pig be inoculated with the pure cultivation of German Kultur of tubercle bacilli, the wound caused by the inoculation mostly closes over with a sticky matter, and appears in its early days to heal. Only after ten to fourteen days a hard nodule presents itself, which, soon breaking, forms an ulcerating sore, which continues until the animal dies. Quite a different condition of things occurs when a guinea pig already suffering from tuberculosis is inoculated. An animal successfully inoculated from four to six weeks before is best adapted for this purpose. In such an animal the small indentation assumes the same sticky covering at the beginning, but no nodules form. On the contrary, on the day following, or the second day after the inoculation, the place where the lymph is injected shows a strange change. It becomes hard and assumes a darker coloring, which is not confined to the inoculation spot, but spreads to the neighboring parts until it attains a diameter of from 0.05 to 1 cm.

In a few days it becomes more and more manifest that the skin thus changed is necrotic, finally falling off, leaving a flat ulceration which usually heals rapidly and permanently without any involvement of the adjacent lymphatic glands. Thus the injected tubercular bacilli quite differently affect the skin of a healthy guinea pig from one affected with tuberculosis. This effect is not exclusively produced with living tubercular bacilli, but is also observed with the dead bacilli, the result being the same whether, as I discovered by experiments at the outset, the bacilli are killed by a somewhat prolonged application of a low temperature or boiling heat or by means of certain chemicals. This peculiar fact I followed up in all directions, and this further result was obtained—that killed pure cultivations of tubercular bacilli, after rinsing in water, might be injected in great quantities under healthy guinea pig's skin without anything occurring beyond local suppuration. Such injections belong to the simplest and surest means of producing suppurations free from living bacteria.

Tuberculous guinea pigs, on the other hand, are killed by the injection of very small quantities of such diluted cultivations. In fact, within six to forty-eight hours, according to the strength of the dose, an injection which is not sufficient to produce the death of the animal may cause extended necrosis to the skin in the vicinity of the place of injection. If the dilution is still further diluted until it is scarcely visibly clouded, the animals inoculated remain alive and a noticeable improvement in their condition soon supervenes. If the injections are continued at intervals of from one to two days, the ulcerating inoculation wound becomes smaller and finally scars over, which otherwise it never does; the size of the swollen lymphatic glands is reduced, the body becomes better nourished, and the morbid process ceases, unless it has gone too far, in which case the animal perishes from exhaustion. By this means the basis of a curative process against tuberculosis was established.

Against the practical application of such dilutions of dead tubercle bacilli there presented itself the fact that the tubercle bacilli are not absorbed at the inoculation points, nor do they disappear in another way, but for a long time remain unchanged, and engender greater or smaller suppurative foci. Anything, therefore, intended to exercise a healing effect on the tuberculous process must be a soluble substance which would be liberated to a certain extent by the fluids of the body floating around the tubercle bacilli, and be transferred in a fairly rapid manner to the juices of the body; while the substance producing suppuration apparently remains behind in the tubercular bacilli, or dissolves but very slowly. The only important point was, therefore, to induce outside the body the process going on inside, if possible, and to extract from the tubercular bacilli alone the curative substance. This demanded time and toil, until I finally succeeded, with the aid of a forty to fifty per cent. solution of glycerine, in obtaining an effective substance from the tubercular bacilli. With the fluid so obtained I made further experiments on animals, and finally on human beings. These fluids were given to other physicians to enable them to repeat the experiments.

The remedy which is used in the new treatment consists of a glycerine extract, derived from the pure cultivation of tubercle bacilli. Into the simple extract there naturally passes from the tubercular bacilli, besides the effective substance, all the other matter soluble in fifty per cent. glycerine.

Consequently, it contains a certain quantity of mineral salts, coloring substances, and other unknown extractive matters. Some of these substances can be removed from it tolerably easily. The effective substance is insoluble in absolute alcohol. It can be precipitated by it, though not, indeed, in a pure condition, but still combined with the other extractive matter. It is likewise insoluble in alcohol. The coloring matter may also be removed, rendering it possible to obtain from the extract a colorless, dry substance containing the effective principle in a much more concentrated form than the original glycerine solution. For application in practice this purification of the glycerine extract offers no advantage, because the substances so eliminated are unessential for the human organism. The process of purification would make the cost of the remedy unnecessarily high.

Regarding the constitution of the more effective substances, only surmises may for the present be expressed. It appears to me to be derivative from albuminous bodies, having a close affinity to them. It does not belong to the group of so-called toxalbumins, because it bears high temperatures, and in the dialyzer goes easily and quickly through the membrane. The proportion of the substance in the extract to all appearance is very small. It is estimated at fractions of one per cent., which, if correct, we should have to do with a matter whose effects upon organisms attacked with tuberculosis go far beyond what is known to us of the strongest drugs.

Regarding the manner in which the specific action of the remedy on tuberculous tissue is to be represented, various hypotheses may naturally be put forward. Without wishing to affirm that my view affords the best explanation, I represent the process myself in the following manner:

The tubercle bacilli produced when growing in living tissues, the same as in artificial cultivations, contain substances which variously and notably unfavorably influence living elements in their vicinity. Among these is a substance which in a certain degree of concentration kills or so alters living protoplasm that it passes into a condition that Weigert describes as coagulation necrosis. In tissue thus become necrotic the bacillus finds such unfavorable conditions of nourishment that it can grow no more and sometimes dies.

This explains the remarkable phenomenon that in organs newly attacked with tuberculosis, for instance in guinea pigs' spleen and liver, which then are covered with gray nodules, numbers of bacilli are found, whereas they are rare or wholly absent when the enormously enlarged spleen consists almost entirely of whitish substance in a condition of coagulation necrosis, such as is often found in cases of natural death in tuberculous guinea pigs. The single bacillus cannot, therefore, induce necrosis at a great distance, for as soon as necrosis attains a certain extension the growth of the bacillus subsides, and therewith the production of the necrotizing substance. A kind of reciprocal compensation thus occurs, causing the vegetation of isolated bacilli to remain so extraordinarily restricted, as, for instance, in lupus and scrofulous glands.

In such cases the necrosis generally extends only to a part of the cells, which then, with further growth, assume the peculiar form of riesen zelle, or giant cells. Thus, in this interpretation, follow first the explanation Weigert gives of the production of giant cells.

If now one increased artificially in the vicinity of the bacillus the amount of necrotizing substance in the tissue, the necrosis would spread a greater distance. The conditions of nourishment for the bacillus would thereby become more unfavorable than usual.

In the first place the tissue which had become necrotic over a large extent would decay and detach itself, and where such were possible would carry off the inclosed bacilli and eject them outwardly, so far disturbing their vegetation that they would much more speedily be killed than under ordinary circumstances.

It is just in looking at such changes that the effect of the remedy appears to consist. It contains a certain quantity of necrotizing substance, a correspondingly large dose of which injures certain tissue elements even in a healthy person, and perhaps the white blood corpuscles or adjacent cells, thereby producing fever and a complication of symptoms, whereas with tuberculous patients a much smaller quantity suffices to induce at certain places, namely, where tubercle bacilli are vegetating and have already impregnated the adjacent region with the same necrotizing matter, more or less extensive necrosis of the cells, with the phenomena in the whole organism which result from and are connected with it.

For the present, at least, it is impossible to explain the specific influence which the remedy, in accurately defined doses, exercises upon tuberculous tissue, and the possibility of increasing the doses with such remarkable rapidity, and the remedial effects which have unquestionably been produced under not too favorable circumstances.

Of the consumptive patients whom he described as temporarily cured, two have been returned to the Moabit Hospital for further observation.

No bacilli have appeared in their sputum for the past three months, and their phthisical symptoms have gradually and completely disappeared.