NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
The Results of continued Study of Various Forms of Comma-
Bacilli occurring in Calcutta.
BY
BRIGADE-SURGEON LIEUTENANT-COLONEL D. D. CUNNINGHAM,
F.R.S., C.I.E.
It is now more than three years since I drew attention to the fact that
cholera in Calcutta is not invariably characterised by the presence of any
cultivable comma-bacilli in the intestinal contents, and that, even in those
cases where such organisms are present, they by no means invariably present
the characters of those described by Koch and ordinarily accepted as true
choleraic bacilli, but differ greatly in different instances both as regards their
morphological and physiological properties. The strangely implicit faith which
at that time was almost universally yielded to the finality of Koch's statements
and theories prevented these observations from producing any appreciable
impression, and even a year later, when full details were published in this
periodical regarding the subject, they were received either with entire incredu-
lity or by an attempt to force them into agreement with the requirements
of the theory. The history of the evolution and acceptance of the theory are
equally curious; the haste and confidence with which results of a few weeks'
• observations were assumed to afford sufficient grounds for the most sweeping
generalisations and the wonderfully implicit faith with which the latter were as
a rule adopted being equally phenomenal. The practical results of the theory
and its acceptation, as we now know, can hardly be regarded as very satis-
factory either for the community at large or for the judgment of its adherents,-
consisting as they have done in errors in diagnosis and failure to recognise
the presence of local epidemics of cholera until they have attained unmanage-
able proportions. Had the diagnosis of cholera in Hamburg last summer
not been delayed until 85 cases and 36 deaths had occurred because of the
belief that the disease must be accompanied by Koch's comma-bacillus, the
epidemic might never have attained the appalling magnitude which it ulti-
mately did, and had the medical profession in Berlin not been possessed by a
blind faith in the theory, we might have been spared the curious spectacle
which they furnished by their refusal to admit that any cases of disease,
however otherwise indistinguishable in symptoms and mortality they might be,
were of a truly choleraic nature, unless they conformed to Koch's dicta.
As I have had ample opportunities for continuing the study of the
subject since I last published anything regarding it, and as the results have
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been in my opinion fully confirmatory of my original views, it seems desirable
to bring them forward and compare them with the theory. As has been already
mentioned, the data obtained here were either ignored altogether or were
received by an attempt to force them as far as possible to conform to the
requirements of the theory ; the fact of the occurrence of cases, apart from the
presence of any comma-bacilli being simply ignored, and the multiplicity of
forms of comma-bacilli being regarded as explicable as the result of mere
variability and as corresponding with the existence of an indefinite number of
" atypical varieties " of one and the same species. The cases in which the
disease was present and commas absent were dismissed as not being cases of
cholera, the phenomenon being accounted for as the result of diagnostic error.
This is no doubt a very convenient method of disposing of the question, but
one which is, as we have already seen, fraught with practical danger to the
public, and, in so far as the theory itself is concerned, is a double-edged
weapon. If it once be adopted there is nothing to prevent its general applica-
tion, and it then becomes open to us to question whether the cases on which
Koch originally founded his theory were typical ones, or even cases of the
disease at all. He accepted them as true, typical cases on the ground of the
symptoms and general pathological phenomena which they presented, and if
these afford sufficient guides for diagnosis in one case, they cannot be lightly
rejected in others merely to suit the convenience of a theory. His cases were
characterised by the presence of comma-bacilli presenting certain definite
characters, but the latter are certainly not typical of the commas occurring
most frequently in Calcutta in association with the disease, If then we are
to accept the presence of Koch's commas as the real diagnostic, cholera
must be of rare occurrence in Calcutta although associated with a very
large number of cases which are indistinguishable from it in symptoms,
general pathology and mortality. We are required to believe that, due to some
inexplicable coincidence, a large number of cases of a rare disease occurred
during Koch's brief stay in Calcutta simply because it was desirable that they
should do so, or to accept a certain peculiarity which they happened to present
as of typical value, merely because he observed it. Are we to suppose
that he was endowed with supernatural powers of diagnosis, which rendered
him capable of infallibly discriminating true cases of cholera and avoiding
errors to which Indian medical men with a life-long experience of the
disease are liable ? It is all very well to regard Koch's work in connection with
cholera as typical, but, if it were typical of anything, it was of imperfect
observation and rash generalisation.
It is, no doubt, a characteristic feature in the majority of cases of cholera
that the intestinal contents should include large numbers of curved bacilli, but
it was only ignorance of the numerous forms of such organisms and of the
frequency with which they occur that could have led any one to assume that
Medical Officers of the Army of India.
3
they were necessarily and invariably of one species, and to neglect entirely to
notice the differences in character which they present in individual cases.
Originally, however, it was assumed that the diagnosis of any case of disease
as of truly choleraic nature might be safely and definitely founded on the
detection of comma-bacilli in the contents of the intestines, and it was not until
Lewis drew attention to the presence of such organisms in saliva and Prior
and Finkler discovered them in the dejecta of cases of what is termed in
Europe " Cholera nostras" that special stress was laid on the presence of
certain physiological details as definitely distinguishing truly choleraic bacilli
from all other similar organisms.
At this time, in order to maintain the theory, great stress was laid on
certain details in the life-history of the bacilli as of specific value, but whenever
it was pointed out that such details are not constant, for the bacilli obtained
from different cases of the disease, an immediate change of tactics was adopted,
and it was as stoutly affirmed that they were of no specific value whatever, and
that the differences were merely indicative of the existence of numerous
varieties in type of one and the same species. Now, either of these views is
logically tenable according to the opinion which its advocates may entertain as
to what it is that imparts specific value to any special characters, but it is
preposterous to attempt to maintain both of them simultaneously, merely in
order to bolster up a theory. The distinctive characters of Finkler's Comma
are either of specific value, or they are not. If they are, those of many distinct
forms of choleraic commas are equally so, and the association of the disease,
with a single species, comes to the ground ; if they are not, then the specific
relation of a distinct species to cholera ceases. It does not matter which
view is adopted, both are equally fatal to the theory, but no one is logically
entitled now to hold one and again the other merely on account of a prejudice
in favour of it.
So long as the theory appeared to require that stress should be laid on
particular characters these were regarded as of specific value, but whenever it
became inconvenient that they should be so regarded, this ceased to be the
case and their specificity was promptly denied. For a time accordingly we
were furnished with the most definite descriptions of the distinctive features
of choleraic comma-bacilli as compared with those of any similar organisms
occurring under other circumstances, but, as experience accumulated and it
became more and more certain that many very distinct forms were found in
association with the disease, one after another of their characters was affirmed
to be of no specific value, until at the present time it is hard to see what
definition of " the choleraic comma" the advocates of Koch's views could
give save that it is a bacillus occurring in the intestinal contents of most cases
of cholera, and which has formed the basis of a celebrated theory.
Whilst freely allowing that it is possible to regard all the various forms of
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the medium was neutralised with liquor potass. In these adhesiveness
absolutely disappeared, but on renewed employment of the soda medium, it
rapidly manifested itself anew. If a difficulty of this kind exists in regard to
artificial media, it is clear that it must be present in far higher degree in the
case of many natural media, such as potatoes, in which we have absolutely no
security of the presence of even approximate uniformity in the characters of any
two successive specimens. Every one must have frequently observed how.
inexplicable failures may attend attempts to transfer a growth to particular
potatoes, whilst in other cases the very same growth on transfer to tubers of
apparently precisely similar character grows rapidly and luxuriantly, so that it
is only as the result of prolonged experience that it is possible to determine
with any security that a given form is incapable of growth on potatoes gene-
rally.
We cannot be too careful in our attempts to secure approximate uniformity
in media which are to be employed in comparative experiments on the effects
of exposure to special conditions, or too carefully avoid comparing the cha-
racters of the growth of any form in one specimen of any medium—even an
artificial one—with those of another form on a distinct sample of what we
roughly term the same medium. Satisfactory comparisons can only be insti-
tuted between growths which have been developed in connection with portions
of one and the same medium in the most limited sense, that is in connection
with individual portions of one and the same sample of any artificial or natural
substratum.
It is not hard to find examples of the origin of conspicuous alterations in
the characters of choleraic comma-bacilli in connection with alterations in the
nature of their environment. When cultivated in agar-agar-beef-juice all the
forms with which I am acquainted save one normally show rapid growth through-
out the substance of the medium so long as this is neutralised or only feebly
alkaline, but purely superficial growth where it is acid or strongly alkaline. In
certain cases, too, this change in habit is accompanied by conspicuous
alteration in form of the constituent elements of the growth. For example, when
the form described as species γ in my former paper on this subject is grown in
non-neutralised specimens of the medium, the elements no longer retain the
elongated, slender form which characterises them in neutralised specimens,
but are so much shortened and relatively thickened that they come closely
to resemble those which species β presents, whether in neutralised or non-
neutralised media. Even more striking results in many cases attend the
transfer of a growth from an agar-agar or common gelatine medium to potatoes.
In certain cases the alteration in form is so great that it would be quite impossi-
ble to recognise the essential identity of the growths in the two media from
any mere consideration of the morphological characters of their constituent
elements. The degree of alteration in form attending the transfer is in many
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in addition of even more persistent functional change. The common agar-agar
growths, like those of almost all other choleraic comma-bacilli, when transferred
to' bouillon, give rise to changes in it which lead to the 'development of the so
called cholera-purple on the addition of acids. But it is quite exceptional to
find the growths on potatoes retaining this property, and even those which
have been developed on renewed transfer to agar-agar media, and which
have even for' a considerable time resumed a typical comma-form may remain
devoid of it for an indefinite period, and when they do regain it only do so
gradually and by insensible degrees.
The same bacillus affords examples of farther modifications, for in some
cases transfer from potatoes to agar-agar media fails to give rise to, any
interstitial growth throughout the latter, no development occurring along the.
course of the needle track in' stable-cultures although abundant growth takes
place over the surface. In such cases there is little or no tendency to imme-
diate resumption of the typical comma-form, even in plate-cultures, and the
growth at the same time on retransfer to potatoes is at once vigorous and cer-
tain, whereas in cases where the typical form and the capacity for interstitial
growth are regained in the agar-agar this is not nearly so constantly the case.
Why such differences should present themselves remains meantime a mystery.
There is absolutely nothing in either the macroscopic or microscopic features
in the potato-growths which distinguishes specimens at once regaining the
typical form and possessing the capacity for interstitial growth in agar-agar
from those which do not do so. In many cases a growth which for a time does
not regain the typical form or show interstitial growth on transfer will at a later
period become capable of doing both without otherwise showing any appreciable
change of character, and a growth on one potato devoid of such capacities
will give rise to a growth on another which possesses them in the highest
degree.
The influence of the environment in determining modification does not
only appear in connection with cases of transfer from one medium to another
of different nature, for in many instances quite as conspicuous changes are
gradually produced in connection with prolonged exposure to the influence of
media of uniform character. Prolonged cultivation in agar-agar media has
thus in many cases very greatly modified the capacity for liquefying gelatine
which the various forms of bacilli originally possessed. The modification of
property has in some cases led to a great increase, and in others to
as conspicuous a decrease in liquefying power, or has produced conspicuous
differences in the details of the process of liquefaction. The same holds
good in regard to capacity for growth on potatoes. In most cases prolonged
cultivation in agar-agar media has greatly decreased or apparently entirely
abolished' the capacity, but in one form at all events a precisely opposite effect
has been produced. The degree of modification which has attended prolonged
Medical Officers of the Army of India.
cultivation in agar-agar media differs greatly in the case of different forms.
Some have retained their original characters almost unaltered, whilst others
have become very greatly altered both morphologically and physiologically.
The nature, too, of the modification differs in different cases, for whilst in some
forms the morphological characters have remained uniform and the physiological
ones have become greatly altered, in others exactly the reverse has been the
case.
From what has been already mentioned in regard to the action of vari-
ations in external conditions in giving rise to modifications in the characters
of the various forms of choleraic comma-bacilli, it may have been remarked that
the results have differed in different instances. This, however, does not in
itself constitute 'satisfactory evidence of the existence of specific differences
between variable organisms obtained from distinct sources and which may have
been antecedently exposed to unlike conditions. The point which has to be
specially considered in connection with the question of specificity is, how far
has continued exposure to the influence of like conditions given rise to any
general assimilation of characters in the organisms which have been subjected
to its influence. The most satisfactory method of dealing with this question
in the present instance will be to institute a detailed comparison of the principal
features which originally distinguished the various choleraic bacilli from one
another with those which they now present after prolonged cultivation under
uniform common conditions. A continued series of agar-agar beef-juice cultures
has been carried out for each form from the date of its original discovery up to
the present time, and, although, as all the forms were not simultaneously
obtained, all of them have not been subject to the influence of a common
environment for the same length of time, they have all, at all events, been subject
to its action for a period of many months' duration, so that any,inherent tendency
towards a general assimilation in their characters ought clearly to have manifested
itself in greater or less degree. The series of cultivations have throughout
been conducted in such a fashion as to secure as far as possible that all the
organisms experimented with shall actually have been exposed to like conditions.
In starting new cultures all the forms under observation have been transplanted
simultaneously and into tubes containing portions of the same sample of the
nutrient medium, and subsequent to inoculation all the individual tubes of one
date have been exposed to identical external conditions. None of the choleraic
bacilli, which I propose specially to consider here, have been for less than a
year in continued cultivation, and certain of them have been so for three years
and a half.
In my previous paper on this subject the characters on which I laid most
weight as affording evidence of the existence of various distinct species of
choleraic comma-bacilli were the morphological peculiarities of the constituent
elements, and the general characters of the growths occurring .in common
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initial morbid symptoms lies in the environment, and not within the bodies of the
sick. If the manufacture of the poison took place within the bodies of the sick,
there could be no sufficient reason why a change of site should produce any
appreciable effect on the prevalence of the disease. But practical experience
has demonstrated unequivocally that it does produce such an effect in such high
degree in many instances that an immediate arrest is put upon any further ex-
tension of the disease—a few cases possibly manifesting themselves immediately
after transit, but none occurring which can be fairly credited to the new locality,
whilst premature return to the primary one is followed by renewed prevalence.
In a certain number of instances, no doubt, no appreciable benefit follows change
of locality, and the disease continues to prevail in the new site, but this is no
evidence against the influence of local conditions, as it is, of course, impossible
invariably to secure that in changing localities an immediate transit to one
presenting unfavourable conditions for the local development of the specific
cause of the disease should be secured. The general good result following transit
are inexplicable on the theory that the essential site of manufacture of the
specific poison lies within the bodies of the sick; the occasional absence of
appreciable benefit is no evidence whatever against the overweening influence
of local conditions.
The cases which speak most strongly in favour of the belief in the local and
not personal, manufacture of the specific cause of cholera—in favour of its deve-
lopment in the environment, and not in the bodies of the sick—are, however, not
so much those in which repeated importation of the disease is followed by no
result whatever, or those in which change of locality is attended by disappear-
ance of disease as those in which a certain amount of diffusion follows importa-
tion, but is confined solely to those who have come into direct or indirect relation
to the imported cases. Professor von Pettenkofer long ago drew attention to
the significance of such cases. Among other instances he records a striking
case which occurred during the course of the epidemic in South Germany in
18 54.* In the year 18 54 an individual arrived in Munich, where a violent
epidemic of cholera was prevalent, from Stuttgart, a locality which had always
previously enjoyed an exemption from the disease. After a brief stay in Munich
during which he became affected by diarrhœa, he returned to Stuttgart, was
attacked by cholera and died. A few days later a person who had attended him
during his illness in Stuttgart, a woman in a neighbouring village who had washed
his clothes there and her husband, who had never left the village, were affected
by the disease, but with this the diffusion ceased, and no more cases of cholera
occurred.
The German Official Memoir regarding the European epidemic of 1892
records the occurrence of similar phenomena at Koblenz. On the 29th of August
* " Über Cholera auf Schiffen and den Zweck der Quarantanen,"—Von Max v. Pettenkofer.
Medical Officers of the Army of India.
57
caused by the products of independent factors whose activity is called into play
by the primary choleraic condition, immunity from the action of these products
would limit the morbid effects in any case to those directly due to that of the
primary poison, and with this there is every reason to believe that a great
reduction in the mortality of the disease would occur. Whilst, therefore, there
are no grounds for believing that M. Haffkine's treatment can have any effect in
reducing the prevalence of cholera, it remains possible that it may affect its
mortality.
1 Y
PLATE I.α.
CHOLERAIC COMMA-BACILLI.
TUBE CULTIVATIONS IN 10% NELSON'S PHOTOGRAPHIC GELATINE, 5 DAYS GROWTH-TEMPERATURE OF PERIOD 58° O TO 65°7 F.
Fiģ.l. a, Species α ; b, Species β.
Fiģ. 3. a. Speciesζ ;
b . S p e c i e sЄ
.
Fiģ. 2. a, Species
γ ;
Ъ . S p e c i e sθ
.
Fiģ. 4. a. Species
η; b , S p e c i e s
< i l l e g i b l e > .
Reproduced full-scale from photographs by Col. J.Waterhouse.
Photo-etchinģ.
Survey of India Offices, Calcutta, December 1893.
PLATE I.b .
CHOLERAIC COMMA-BACILLI &c.
TUBE CULTIVATIONS IN IO% NELSON'S PHOTOGRAPHIC GELATINE, 5 DAYS GROWTH TEMPERATURE OF PERIOD 58° 0 TO 65°7 F.
Fig. 5. a, Species κ : b, Species λ.
Fig 6. a, Species μ : b. Species ν.
Fig. 7. a, Species ξ : b. Species O=Crofton–Hall comma.
Re p r o d u c e d f u l l - s c a l e f r o m p h o t o g r a p h s b y Co l . J . Wa t e r h o u s e .
Photo-etchinģ.
Survey of India Offices, Calcutta, November 1893.
Reg No. 454, San Comr, I.—Sept. 93.—350.
Litho., S. I. O.,
Calcutta.
PLATE II a.
GELATINE TUBE-CULTURES OF CHOLERAIC COMMA-BACILLI
—
Series 1.
Heinrich's "gold label" gelatine; 10%; 72 hours,
Dec. 1890.
2.
" " " "
"
Dec. 1891.
" 3 .
Nelson's "photographic" gelatine; "
7 days,
Jan. 1892.
" 4 .
Heinrich's "gold label" gelatine;
"
8 days,
Dec. 1892.
" 5 .
" " " "
9 days,
Dec. 1892.
" 6 & 7 . * Nelson's "photographic” gelatine; "
48 hours: 6 days, Nov. 1892.
" 8 .
" " " "
6 days,
Jan. 1893.
PLATE IIb.
GELATINE TUBE-CULTURES OF CHOLERAIC COMMA-BACILLI
—
Series 1.
Heinrich's "gold label" gelatine; 10%; 72 hours,
Dec. 1890.
"
2.
" " " "
"
Dec. 1891.
" 3.
Nelson's "photographic" gelatine; „
7 days,
Jan. 1892.
" 4.
Heinrich's "gold label" gelatine;
„
8 days,
Dec. 1892.
" 5.
" " " "
9 days,
Dec. 1892.
" 6&7.* Nelson's "photographic" gelatine; "
48 hours: 6 days, Nov. 1892.
" 8
" " " "
6 days.
Jan. 1893.
* The Same cultures at different dates.
Litho.,S.I.O,calcutta.
R e g . N o . 4 5 4 , S a n . C o m r . I . — S e p t . 9 3 — 3 5 0 .
L i t h o . , S . I . O . , C a l c u t t a .