DR. KOCH'S BERLIN LECTURE ON CHOLERA AND THE COMMA BACILLUS.

An important conference upon cholera was held in Berlin, at the

Imperial Board of Health, on the evening of July 26. There were present

Drs. Von Bergman, Coler, Eulenberg, B. Frankel, Gaffky, Hirsch, Koch,

Leyden, S. Neumann, Pistor, Schubert, Skrezcka, Struck, Virchow, and

Wollfhugel. The conference had been called at the instance of the

Berlin Medical Society, whose President, Professor Virchow, explained

that it was thought advisable Dr. Koch should in the first instance

give a demonstration of his work before a smaller body than the whole

Society, so that the proceedings might be fully reported in the medical

press. He mentioned that Herr Director Lucanus and President Sydow

had expressed their regret at being unable to be present, as well as

many others, including Drs. Von Lauer, Von Frerichs, Mehlhausen, and

Kersandt. Dr. Koch first showed various specimens of the bacilli and

their method of preparation (see _Berliner Klinische Wochenschrift_,

August 4). This resembles that for the tubercle bacillus, viz.,

drying on a cover glass and staining with fuchsin or methyl-olin.

Koch then gave a history of his work while in Egypt and India. His

post-mortem examinations led him to believe that the intestines were

the nidus of the disease. At first his microscopical examinations were

unsatisfactory, but finally he got fresh dejecta and acute cases, and

then discovered the comma bacillus.

This, he said, is smaller than the tubercle bacillus, being only about

half or at most two-thirds the size of the latter, but much more plump,

thicker, and slightly curved. As a rule, the curve is no more than that

of a comma (,), but sometimes it assumes a semicircular shape, and he

has seen it forming a double curve like an S; these two variations from

the normal being suggestive of the junction of two individual bacilli.

In cultures there always appears a remarkably free development of

comma-shaped bacilli.

These bacilli often grow out to form long threads, not in the manner

of anthrax bacilli, nor with a simple undulating form, but assuming

the shape of delicate long spirals--a corkscrew shape--reminding one

very forcibly of the spirochæte of relapsing fever. Indeed, it would be

difficult to distinguish the two if placed side by side. On account of

this developmental change, he doubted if the cholera organism should

be ranked with bacilli; it is rather a transitional form between the

bacillus and the spirillum. Possibly it is true spirillum, portions

of which appear in the comma shape, much as in other spirilla, _e.

g._, spirilla undula, which do not always form complete spirals, but

consist only of more or less curved rods. The comma bacilli thrive

well in meat infusion, growing in it with great rapidity. By examining

microscopically a drop of this broth culture the bacilli are seen in

active movement, swarming at the margins of the drop, interspersed with

the spiral threads, which are also apparently mobile. They grow also

in other fluids, _e. g._, very abundantly in milk, without coagulating

it or changing its appearance. Also in blood serum they grow very

richly. Another good nutrient medium is gelatine, wherein the comma

bacilli form colonies of a perfectly characteristic kind, different

from those of any other form of bacteria. The colony when very young

appears as a pale and small spot, not completely spherical as other

bacterial colonies in gelatine are wont to be, but with a more or less

irregular, protruding, or jagged contour. It also very soon takes on

a somewhat granular appearance. As the colony increases the granular

character becomes more marked, until it seems to be made up of highly

refractile granules, like a mass of particles of glass. In its further

growth the gelatine is liquefied in the vicinity of the colony, which

at the same time sinks down deeper into the gelatine mass, and makes a

small thread-like excavation in the gelatine, in the center of which

the colony appears as a small white point. This again is peculiar;

it is never seen, at least so marked, with any other bacterium. And

a similar appearance is produced when gelatine is inoculated with a

pure culture of this bacillus, the gelatine liquefying at the seat of

inoculation, and the small colony continually enlarging; but above it

there occurs the excavated spot, like a bubble of air floating over

the bacillary colony. It gives the impression that the bacillus growth

not only liquefies the gelatine, but causes a rapid evaporation of the

fluid so formed. Many bacteria also have the power of so liquefying

gelatine with which they are inoculated, but never do they produce such

an excavation with the bladder like cavity on the surface. Another

peculiarity was the slowness with which the gelatine liquefied, and

the narrow limits of this liquefaction in the case of a gelatine disk.

Cultures of the comma bacillus were also made in agar-agar jelly, which

is not liquefied by them. On potato these bacilli grow like those of

glanders, forming a grayish-brown layer on the surface. The comma

bacilli thrive best at temperatures between 30° and 40° C., but they

are not very sensitive to low temperatures, their growth not being

prevented until 17° or 16° C. is reached. In this respect they agree

with anthrax bacilli. Koch made an experiment to ascertain whether

a very low temperature not merely checked development, but killed

them, and subjected the comma bacilli to a temperature of -10° C.

They were then completely frozen, but yet retained vitality, growing

in gelatine afterward. Other experiments, by excluding air from the

gelatine cultures, or placing them under an exhausted bell-jar, or in

an atmosphere of carbonic acid, went to prove that they required air

and oxygen for their growth; but the deprivation did not kill them,

since on removing them from these conditions they again began to grow.

The growth of these bacilli is exceptionally rapid, quickly attaining

its height, and after a brief stationary period as quickly terminating.

The dying bacilli lose their shape, sometimes appearing shriveled,

sometimes swollen, and then staining very slightly or not at all. The

special features of their vegetation are best seen when substances

which also contain other forms of bacteria are taken, _e. g._, the

intestinal contents or choleraic evacuations mixed with moistened earth

or linen and kept damp.

A most important statement was that the comma bacillus seems to be

killed by the bacteria of putrefaction, and consequently agents that

destroy the latter organisms without the former may really do injury,

by removing from the cholera bacillus an impediment to its growth.

As for destructive agents to the bacillus, he found it killed by

solutions in the following proportions: oil of peppermint, 1 in 2,000;

sulphate of copper, 1 in 2,500 (a remedy much employed, but how much

would really be needed merely to hinder the growth of the bacilli in

the intestine!); quinine, 1 in 5,000; and sublimate, 1 in 100,000.

In contrast with the foregoing measure for preventing the growth of

these bacilli is the striking fact that they are readily killed by

drying. This fact is proved by merely drying a small drop of material

containing the bacilli on a cover glass, and then placing this over

some of the fluid on a glass slide. With anthrax bacilli vitality is

retained for nearly a week; whereas, the comma bacillus appears to be

killed in a very short time.

Dr. Koch having found and cultivated the comma bacillus and ascertained

its distinctive character, next proceeded to investigate its relation

to cholera. In all there were now about one hundred cases of cholera

in which the bacillus had been found, while it was never found in

connection with other diseases. Three different views, said the

speaker, as to its relation to the cholera process are tenable:

1. That the disease favors the growth of these bacilli by affording

them a suitable soil. If so, it would mean that the bacillus in

question is most widely diffused, since it has been found in such

different regions as Egypt, India, and France; whereas the contrary is

the case, for the bacilli do not occur in other diseases, nor in the

healthy, nor apart from human beings in localities most favorable to

bacterial life. They only appear with the cholera.

2. It might be said that cholera produces conditions leading to a

change in form and properties of the numerous intestinal bacteria,

a pure hypothesis; the only instance of such a conversion refers to

a change of physiological and pathogenic action, and not of form.

Anthrax bacilli under certain conditions lose their pathogenic power,

but undergo no change in shape; and that is an instance of a loss of

pathogenic properties, while there is no analogy to support the view of

the harmless intestinal bacteria becoming the deadly cholera bacilli.

The more bacterial morphology is studied, the more certain it is that

bacteria are constant in their form; moreover, the comma bacillus

retains its special characters unchanged through many generations of

culture.

3. Lastly, there is the view that the cholera process and the comma

bacilli are intimately related, and there is no other conceivable

relation but that the bacilli precede the disease and excite it. "For

my own part," said Dr. Koch, "the matter is proved that the comma

bacilli are the cause of cholera."

Dr. Koch then described his attempts to inoculate lower animals with

the bacillus, and explained the cause of his failure in the natural

immunity of the animals against the disease.

In advocating the local Indian origin of the disease he said: That the

virus can be reproduced and multiplied outside the body is apparent,

since the bacillus can be cultivated artificially, and its growth is

not affected by comparatively low temperatures. Probably it does not

grow in streams and rivers, where, owing to the current, a sufficient

concentration of nutrient substance does not occur; but in stagnant

water and at the mouths of drains, etc., vegetable and animal refuse

may accumulate and afford the necessary nutriment. Thus is explained

the propagation of cholera by the subsoil water, and the increase of

epidemics with the sinking of its level, which lessens the flow and

diminishes the amount of surface water. Admitting the dependence of

cholera upon this micro-organism it is impossible to conceive the

disease having an autochthonous origin in any particular place; for a

bacillus must obey the laws of vegetable life, and have an antecedent;

and since the comma bacillus does not belong to the widely diffused

micro-organisms, it must have a limited habitat. Therefore, the

occurrence of cholera on the delta of the Nile does not depend on its

resemblance to the delta of the Ganges; but the disease must have

been imported there as it is into Europe. It was once thought that an

outbreak in Poland had a local origin until it was discovered to have

been introduced from Russia. Again, about ten years ago, there was a

sudden outbreak at Hamar (Syria), thought to be an instance of local

origin, but erroneously, as shown by a statement of Lortet, who told

Koch, when at Lyons, that the epidemic had been introduced into Hamar,

where he was at the time, by Turkish soldiers from Djeddah. All great

epidemics of cholera began in South Bengal, where the conditions for

the development and growth of the bacillus are most perfect.--_Med.

Record._

Scientific American Supplement, No. 467, December 13, 1884 · 第 38 / 76 题