(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.
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