NationalLibraryOfScotland/medical-history-of-british-india huggingface dataset:
Me d i c a l Of f i c e r s o f t h e Ar my o f I n d i a . 9
constituents consisted of slender rods, many of them with typical comma contour,
and evidently consisting in many cases of 3 or 4 cocci included within a common
sheath.
Broth cultivations :—These failed to show any appreciable evidences of
growth, the fluid remaining perfectly limpid and devoid of any pellicle even 96
hours after inoculation. They also failed to show the faintest traces of any
purple on the addition of mineral acids, although the growths in agar-agar
media did so early and certainly.
Form β—Plate cultures on agar-agar :—The colonies in these continued
to present the same characters as those described as present in the primary
plate. Even within 24 hours they frequently became pink under the influence of
33 per cent. nitric acid, the development of the colour being, however, very
slow in occurring.
Stab-tube cultures in agar-agar :—These were almost invariably character-
ised by conspicuous evolution of large gaseous bubbles in the substance of the
medium. The surface growth is thicker and moister than that in α ,
a n d i s
further distinguished from the latter by a distinctly yellow tint and absolute
incoherence. The constituent elements have the form of rather large rods,
many of them characteristically comma-like, and either isolated, or associated
to form long, sinuous filaments, which sometimes, although rarely, show distinct
pseudo dichotomy.
Potato cultures :—The growths on these consisted of fairly thick, very
moist expansions, of an ochreous pink colour, and ordinarily frothy towards the
edges. The surface of the potato immediately around them was of a whitish
tint passing peripherally into pale neutral, and the smell was peculiar and some
- w h a t r e s e m b l e d t h a t o f s o u r s t a r c h - p a s t e . T h e c o n s t i t u e n t e l e m e n t s p r e s e n t e d
characters similar to those present in a. a. tube cultivations.
Broth-cultivations :—The liquid in these, even within 24 hours, became
densely clouded throughout, and after 48 hours was covered by an imperfect
pellicle. Up to 96 hours it gave no purple with pure sulphuric acid alone, but
within 72 hours, very decided purple with sulphuric and nitric acid.
c . Species present in the intestinal tract of a Cutlah, Catla buchanani,
Cuv. and Val ., which died during an epidemic which took place in a tank in
one of the suburbs of Calcutta in February 1896.
Two fish were sent to me by a native gentleman who was interested in the
phenomenon, One of them was dead when it reached me, the other was still
alive and, on being transferred to a fresh supply of water, remained in perfect
health until some days after, when it committed suicide by leaping out of the
vessel.
An agar-agar plate-culture was at once set from the contents of the intes
- t i n a l t r a c t o f t h e d e a d f i s h . I n t h e c o u r s e o f 2 4 h o u r s , i t y i e l d e d a v e r y
C
Medical Officers of the Army of India. 1 1
from its contents gave what was practically a pure culture of colonies of
comma-bacilli.
The colonies were of relatively small size and circular outline, of a bluish tint
under oblique illumination, and, when viewed by directly transmitted light, pale
ochre, with a central dark nucleus immediately surrounded, first by a homogene
-ous yellow zone, succeeded by a shaded zone fringed by a delicate, pale, some
- w h a t r a d i a n t m a r g i n . T h e c o n s t i t u e n t e l e m e n t s c o n s i s t e d o f s l e n d e r , p a l e , w e l l
curved, and, in many instances, distinctly beaded comma-bacilli. The colonies
failed to show any pink under the influence of 33 per cent. nitric acid.
Stab tube-cultures in agar-agar :—These were characterised by the following
features. Superficial growth occurred relatively slowly, but ultimately became of
a strong yellow colour. Interstitial growth, on the other hand, was very rapid
and diffuse, and was unattended by any gaseous evolution. The elements con
- s i s t e d o f b e a u t i f u l , t y p i c a l , h i g h l y c u r v e d c o m m a - b a c i l l i , Broth cultures :—These, within the course of 24 hours, became densely
clouded throughout and covered by a pellicle which presently assumed a
membranous character and became of considerable thickness. They struck,
bright, pure purple throughout with pure sulphuric acid within 24 hours.
Potato cultures :—Growth occurred rapidly and assumed the character of
very thin, ill-defined, moist, almost colourless expansions, nearly odourless or at
most of a faint, yeasty odour, and devoid of any halo of discolouration of the sur
-face of the basis around them. In the earlier stages of its development it con
- s i s t e d a l m o s t p u r e l y o f c o c c a l a n d d i p l o c o c c a l e l e m e n t s , a n d l a t e r , w h e n t h e
growth was less rapid, showed similar bodies and a certain number of others
which had assumed the characters of distinct comma-bacilli, thus once more
affording an example of the occurrence of variation in morphological characters
in association with variations in rates of growth.
C.—COMMA-BACILLI OCCURRING IN BODIES OF WATER APART FROM
THE EXISTENCE OF ANY CHOLERA IN THE VICINITY.
a. Species present in the water of a tank in the grounds of the Dalanda
Native Lunatic Asylum in Calcutta.
_The sample of water from which this species was obtained was taken in the
month of June 1896 at a time when no cases of cholera had occurred within the
Asylum for many weeks. Primary plate cultivations, as is usually the case with
those of tank-water, yielded colonies of several distinct species of schizomycete
organisms, and among these one, the elements of which were typical commas.
Plate sub-cultures of this species were characterised by possessing a faint
peculiar odour like that of herring-pickle, and similar to, but not so strong as,
C 2
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Scientific Memoirs by
that which invariably characterises tube-cultures of M. XI Within the course of
a few days the colonies acquired a distinct pink tint on adding 33 per cent. nitric
acid. Stab tube-cultures in agar-agar :—Yielded both superficial and interstitial
growth extending along the entire course of the needle-track, The surface
growth extended slowly and the track-growth was limited, but very dense. The
surface growth ultimately became thick, of a pure white colour, broke up into
'
fragments when. mixed with water, and consisted of beautiful, minute, highly
curved commas.
Broth cultures :—These became densely clouded throughout within 24 hours,
and within 48 hours were provided with a thin pellicle. Up to 96 hours they
failed, however, to show any appreciable purple with pure mineral acids.
Potato cultures :—These yielded very scanty, thin, white growths, devoid of
any appreciable halo, and consisting of rounded or oval cocci and small comma-
bacilli, either isolated or associated in vibrionic filaments and frequently distinctly
formed of a certain number of cocci included within a common, curved sheath.
b. Species derived from a sample of water which contained the scrapings
from the bottom of a reservoir for the storage of water derived from the mains o
f the ordinary municipal supply of Calcutta, and obtained at a time when there
was no cholera present among those using the reservoir-water.
This species was characterised by never yielding any interstitial growth in
stab-cultures and by consisting of rods which uniformly failed to assume
the form of commas when cultivated on agar-agar. The surface rowth in stab-
cultures was highly ropy and ultimately of pale ochreous tint.
Broth cultures :—These rapidly became lightly clouded and provided with a
thick pellicle, but gave no appreciable purple with mineral acids.
Potato cultivations :—These yielded an abundant growth of soft, ropy
consistence, with a nodulated surface, lobulated margins, and ochreous pink tint,
surrounded by a brownish halo, and consisting of very slender, long, highly
curved commas.
c. Species derived from the same source as the former,— b.
The distinctive features of this species, as compared with the previous
one, were the following:—Stab tube-cultures in agar-agar media gave abundant,
softly clouded, interstitial growth along the whole courseof the needle-track,
and superficial growth which ultimately acquired a greenish tint. The elements
consisted of very minute straight rods. Potato cultures yielded slowly develop-
ing, highly prominent patches of growth, of firm texture, nodulated surface, deep
orange tint and surrounded by a neutral halo. The elements had the form of
short, thick rods, many of typically comma form, and, not infrequently, evidently
made up of a certain number of associated cocci.
Both of these species afforded excellent examples of the determination of
variation in form, in relation to variation in environment.
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the ordinary view of the action of choleraic vibriones in inducing the disease, or
that which I am now inclined to hold, and according to which they act by
developing toxins in the environment under the influence of certain conditions
there, be accepted ; the fact remains, that the presence or absence of certain other
schizomycete organisms may have an influence in determining the incidence of
the disease, because they favour the continued development and multiplication
of the pathogenic organisms.
On the relation of Vibrionic Organisms to Cholera.
The continued study of the bacteriology of cholera in Calcutta has in no way
caused me to modify the views which I have, on several previous occasions, ex-
pressed in regard to the absurdity of talking of " the cholera bacillus." The
longer the question is investigated in the endemic area of the disease, as
represented by Calcutta, more and more evidence accumulates to show that the
choleraic condition is not necessarily associated with the presence or predomin-
ance of any one species of vibrio within the intestinal tract, and that any assump-
tion that such an association necessarily exists is merely founded on the fact that
Professor Koch, when in Calcutta, was either profoundly ignorant of vibrionic
schizomycetes as a group, or that, owing to his brief and limited local experience
in the locality, he accidentally encountered only a single species in connection with
the few cases of cholera which he had the opportunity of investigating. At the
same time, it must be allowed that he was the first observer who drew attention to
the undoubted fact that a very special relation does exist between the occurrence
of the disease and the predominance of vibrionic schizomycetes within the diges-
tive tract, for, although a certain number of exceptional cases do occur in which
the choleraic condition exists apart from the presence of any abnormal predomin-
ance of intestinal vibriones, there can be no question whatever that an association
of the disease with such predominance is normal. In connection with this
point, it has to be constantly borne in mind, that the fact that choleraic materials
(or cultivations immediately derived from these) contain no bodies which are
morphologically of a vibrionic character affords no sufficient ground for any
assumption of the actual absence of organisms of truly vibrionic nature in them,
for both the original materials and many successive sub-cultures derived from
them may, whilst persistently devoid of actual vibriones, contain a profusion of
potential ones. Many vibrionic organisms under certain circumstances have
the power of multiplying indefinitely in the form of cocci, diplococci and short,
straight rods, although under other conditions they are capable of assum-
ing typically vibrionic characters. This is a fact which is well known to
everyone who has practically studied the subject, and even to those who
have ever examined figures illustrative of the life history of such organisms as
Cladothrix dichotoma . This truth cannot be too clearly borne in mind in
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or as affecting the capacity of the latter for manufacturing toxic materials, or
finally, as favouring the access of pathogenic organisms or their products to
the bodies of the resident population. It appears to me to be most probable
that their most influential action is conducted in the two latter ways.
There is practically no evidence whatever to show that the vibrionic organ-
isms associated with cholera are necessarily endowed with pathogenic proper-
ties, there is abundant evidence that such organisms are normally associated
with the choleraic condition, and finally there is conclusive evidence that the
physiological properties of such organisms may vary conspicuously under
different circumstances. The mere presence of local conditions favouring the
growth of choleraic vibriones need not necessarily imply a coincident prevalence
of the disease, because mere multiplication does not necessitate the presence of
the pathogenic property ; but it may imply a coincident prevalence of the disease
where not only multiplication, but also the manufacture of special toxic pro-
ducts by the multiplying organisms occurs. The evidence which is at present
available certainly does not tend to show that the normal intestinal tract
provides a favourable environment for the manufacture of any toxic materials
by vibrionic organisms capable of giving rise to the choleraic condition, or one
which is favourable to the multiplication of the latter. On the other hand, the
choleraic intestinal tract does provide an exceptionally favourable environment
for vibrionic organisms, but there is no proof that the latter, on escaping from
it, have any necessary choleragenic property. Guided by such considerations,
von Pettenkofer was led to assume that the contents of the choleraic intestinal
tract contained elements of the nature of germs, which, so long as they retained
this character, were innocuous, and which were only a source of danger because,
after issuing from the site of their original development, they were capable
of acquiring pathogenic properties as the result of processes of maturation
which could only be carried out under certain conditions of environment. The
evidence which led him to frame such a theory has certainly only gained
additional strength with the advance of our knowledge in regard to the epi-
demiological phenomena which are presented by the disease, and there is now
only one point in which it seems to me that his doctrine may with advantage be
modified.
In framing any theory in regard to the causation of cholera, we have
to take the following facts into account, to which the evidence at present
available unequivocally leads :—
1. The artificial introduction of large numbers of choleraic comma-
bacilli into the digestive tract is only very rarely followed by the
development of the choleraic condition.
2. Where such artificial administration has been carried out, the contents
of the intestinal tract may abound in comma-bacilli and all
choleraic symptoms may be absent.
Medical Officers of the Army of India.
21
3. At periods when cholera is prevalent, comma-bacilli may be present
in the intestinal contents of perfectly healthy individuals.
4. The choleraic condition may be present in individuals whose intes-
tinal contents are seemingly entirely devoid of comma-bacilli.
5. In cases of cholera, in connection with which comma-bacilli are pre-
sent in the dejecta, there is no necessary direct relation between
the numbers of the latter and the severity of the symptoms.
6. The artificial administration of distinct species of vibrionic organisms
may lead to the development of the choleraic condition.
7. The physiological properties of vibrionic and other schizomycete
organisms may unequivocally vary very greatly under different
circumstances, in connection with growth in different environments,
and consequently the nature of the products to which they give
rise must also vary greatly.
8. There is a great mass of evidence to show that the result of the
introduction of cases of cholera into any locality is not necessarily
followed by any diffusion of the disease within the latter—that is,
that local predisposition comes in as an essential factor in deter-
mining the result of importation of cases of cholera, and that
choleraic excreta in themselves have very little power in giving
rise to local occurrence of the disease.
9. The normal association of the choleraic condition with the prevalence
of vibrionic organisms within the digestive tract is difficult to
account for, unless such organisms are in some way causally
related to the morbid condition which they accompany.
1 0 . B u t v i b r i o n e s , p r e s e n t i n g a l l t h e c h a r a c t e r i s t i c f e a t u r e s o f c h o l e r a i c
ones, may be present in large numbers in sources of water-supply,
and yet the disease may be entirely absent from the population
employing the latter.
1 1 . T h e d e v e l o p m e n t o f t h e c h o l e r a i c c o n d i t i o n i n s o m e c a s e s i s o f a n
explosively sudden character, and in others follows a gradual and
progressive course.
Influenced by considerations of this nature, Buchner and Metchnikoff
have come to the conclusion that choleraic comma-bacilli, although essentially
acting as the immediate cause of the development of the choleraic condition,
can only do so when acting in co-operation with the presence of certain other
adjuvant organisms, or with the absence of certain inimical ones within the
intestine, the result, in either case, being to secure the persistent life and
multiplication of the choleraic vibriones within the digestive tract, and the elabo-
ration there of the specific toxins which induce the choleraic state. According
to this view, the only action of the environment is to secure certain
peculiarities in the nature of the intestinal flora, favouring the multiplication and
Medical Officers of the Army of India. 23
large doses of the toxin, and also that it would imply that in every case an
attack of cholera should be of a sudden, explosive character, whereas in many
instances this is not so, the development of characteristic choleraic symptoms
only supervening on a given period of systemic disturbance. Neither of these
phenomena appear, however, to constitute conclusive objections. About two
and a half grains of powerful, dried cobra-venom probably amount to a fatal dose
for any average human subject, and it by no means necessarily follows that with
this we have reached the maximum of lethality of an organic poison. Dried
venom, moreover, does not consist of the specific toxin alone, so that the amount
of the latter constituting a lethal dose must be very considerably less, and, in
any case, it cannot be affirmed that maximum of toxicity for organic poisons
has been reached by the active principle of cobra-venom,— 1/50 grain aconitia will
kill a dog. Moreover, we find that it is not necessary that a lethal dose of cobra-
venom should be administered at once, in order to give rise to fatal effects ; but
that, where fractional doses are administered at intervals, they act cumulatively,
and that all that is necessary in order to induce a fatal result is that a lethal
amount of the toxin should enter the system within a given period. It remains
uncertain how far the subdivision of the lethal dose can be carried, and how far
the intervals between the administration of fractional quantities can be extended
without interfering with the development of fatal intoxication, but the fact that
the venom has a cumulative action even where the individual doses enter the
system at 24 hours intervals,* is not open to question. It does not, therefore,
appear to be in any way inconceivable, that the development of the choleraic
condition may be dependent on the entrance of an elaborated toxin, rather than
on that of its elaborating factors, into the system. The hypothesis that this is
actually the case would appear to afford the means of accounting for the actual
epidemiological phenomena quite as readily, and certainly much more
simply, than any other theory will.
The hypothesis is, that choleraic vibriones are organisms which have the
property of elaborating certain toxic products when developed under certain con-
ditions, but that the latter are not provided by the interior of the digestive tract
and are only provided by the external environment under certain circumstances.
Similarly, Hemp when cultivated under certain conditions yields an abundance of
toxic resin, when grown under different conditions it fails to do so to any appre-
ciable extent. The principal data of laboratory work and epidemiological
experience which have to be explained have been already enumerated on pp.
20 and 21 , and it now remains to ascertain how such an hypothesis as the
above will satisfactorily account for them.
1. The choleraic condition is sometimes developed explosively and
suddenly, sometimes gradually and progessively.
* Vide Kanthack.
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Scientific Memoirs by
This is a phenomenon which certainly presents great difficulties to the
theory of local manufacture of the toxin within the interior of the digestive
tract, but none whatever to that which is here advocated. Sudden explosive
cases are unequivocally very hard to explain as the result of intraintestinal
manufacture of a toxin, but are readily explicable as the result of the sudden
-ingestion of lethal doses of an elaborated one, and, granting the possibility of
cumulative action, there is equally little difficulty in explaining the occurrence
of cases in which the choleraic condition is only gradually developed. The
hypothesis accounts satisfactorily both for the sudden and the progressive estab-
lishment of the condition, and also for the impossibility of drawing any sharp
line of demarcation between cholera and choleraic diarrhœa.
2. The artificial introduction of large quantities of choleraic vibriones
into the interior of the digestive tract is only very rarely followed
by the development of the choleraic condition.
This is a phenomenon which hardly calls for any discussion, for, if it be
allowed that the choleraic vibriones have only the capacity for the manufacture
of their specific toxin under the influence of certain external conditions,—con-
ditions which are not present within the digestive tract, there can be no reason
to expect that their introduction into the latter, even in very large numbers, will
necessarily lead to any toxic effect. The ingestion of yeast or other alcohol-
ogenic fungi, apart from their products does not lead to alcoholic intoxication.
The administration of the specific products will do so, but that of the factors
alone will not.
3. At periods at which cholera is prevalent, choleraic vibriones may occur
in the intestinal contents of perfectly healthy individuals.
This is a phenomenon which can be readily accounted for, seeing that
the prevalence of the disease necessarily implies corresponding prevalence
of the factors of the specific toxin, and consequently the possibility of the
occasional access of the former apart from the latter to the intestinal tract.
3a. The artificial introduction of choleraic vibriones into the digestive
tract may be followed by evidences of the persistent vitality
and multiplication of the former in the intestinal contents, without
any coincident evolution of choleraic symptoms. This, of course
is simply to be regarded as indicating that the contents of the
intestinal tract may, under other abnormal conditions than those
originating in connection with the establishment of the choleraic
state, occasionally constitute a favourable nidus for the growth of
organisms of such a nature without allowing them to manufacture
certain specific products.
4. But the choleraic condition is normally associated with the presence of
choleraic vibriones within the intestinal tract, because, as a rule,