Dec., 1932] KOCH'S DISCOVERY OF TUBERCLE BACILLUS : SHRIKHANDE 691

KOCH'S DISCOVERY OF THE TUBERCLE BACILLUS?ITS IMPORTANCE AND SIGNIFICANCE

By Y. G. SHRIKHANDE, b.sc., m.b., b.s., t.dj). (Wales) King Edward VII Sanatorium, Bliowali, U. P.

It was just fifty years ago that Robert Koch made the epoch-making discovery of the tubercle bacillus as the cause of tuberculosis. The first announcement of this discovery was made by him in March 1882 before a meeting of the Physiological Society of Berlin and the modern era of tuberculosis may be said to begin from that date. Before this discovery tuber- culosis was believed to be due to some defect in the constitution of the individual?1 habitus

phthisicus' of Hippocrates. When Koch made the important discovery,

he believed that the bacilli causing the disease in man and animals were identical. It is rather

strange that a shrewd observer like Koch should have overlooked the difference between human and bovine tuberculosis although it was foreshadowed by Villemin as far back as 1868. Koch was also inclined to regard, at first, avian tuberculosis as identical with human and bovine

tuberculosis, but after further investigations he agreed with Maffucci who first differentiated avian bacilli from mammalian bacilli (1890). So much was the medical world carried away by Koch's opinion that no one questioned the identity between human and bovine tuberculosis. The only dissenting voice was that of Klein who claimed that Koch's work had not clearly established the identity between the two (1883). In 1898, Theobald Smith recorded the results of his investigations on human and bovine strains of tubercle bacilli and proved that the two strains were not identical. But on the

whole, no heed was paid to these discoveries" and the general belief in the identity between human and bovine bacilli remained undisturbed. The medical world was, therefore, taken by surprise when, in 190*1, Koch made the startling announcement before the British Congress of Tuberculosis that human tuberculosis was diff- erent from bovine tuberculosis and that bovine tuberculosis was not transmissible to man. The assertion that bovine tuberculosis was

not transmissible to man, naturally provoked a storm of opposition and led to an enormous

amount of experimental investigation all over

the world. The result of this investigation has been an enormous advance in our knowledge of tuberculosis. Perhaps the most important fact that has emerged from this investigation is that pulmonary tuberculosis which forms the most important type of human tuberculosis is, for all practical purposes, the outcome of the human tubercle bacillus. It is very rare indeed, for pulmonary tuberculosis to be caused by the bovine bacillus and, as Fishberg has observed, pulmonary tuberculosis caused by the bovine bacillus is a medical curiosity deserving of care- ful reporting every time it is discovered. At the. same time it has been found that Koch

underestimated the danger from the bovine bacillus being transmitted from cattle to man. Koch in overstating his case did great service to mankind in that he attracted the attention of the public authorities from a too exclusive concentration on animal sources of infection to the phthisical human being who is the chief source of infection to man.

In his original description of the bacillus, Koch had described the presence of spores, but this has since been found to be incorrect. Ex-

perimental evidence has further shown that the tubercle bacillus discovered by Koch represents but one phase in the life-history of the micro- organism which is capable of polymorphism. In 1908, Hans Much described the granular phase of the bacillus by a special method of

staining in lesions in which no acid-fast bacilli were found. He also established their specificity by inoculation experiments and considered them to be the developmental stage of the tubercle bacillus. These granules have since been called after Much's name. In 1910, Fontes described for the first time the filterable form of the bacillus and later, Haudouroy and Vaudremer described the passage of the virus through Chamberland L3 filters. Much work has since been done for and against the filterable phase of the bacillus and the result may be considered as sub judice. The above discoveries have resulted in the description of the life-cycle of the tubercle bacillus which includes a stage utterly invisible by any method, a finely granular phase, a coarsely granular phase, and finally a mature stable bacillary form. A recent development in the bacteriology of

the bacillus is the 1 dissociation' experiments carried out with it by Petroff and others. By means of cultures on suitable media, they have succeeded in isolating two kinds of 'colonies? one kind having a rough surface (' R') and the other having a smooth surface (' S ')? The ' R '

colonies contain an avirulent variety of the bacillus and the ' S ' colonies contain the virulent

variety. After the discovery of the tubercle bacillus

and its growth on artificial media, Koch attempted to make use of the bacillus and its

products in the treatment of tuberculosis. In

1890, he announced the discovery of what is called old tuberculin (T. A.) which was fol- lowed later by new tuberculin (T. R.). Since

then, an enormous variety of tuberculins has been prepared for treatment. But the use of tuberculin as a therapeutic remedy in tuber- culosis has proved a dismal failure. Tuberculin

has, however, rendered one important service; it gives valuable information about tuberculous injection which is not synonymous with tuber- culous disease. Investigations on large scales have proved that a very large majority of adults in civilized countries harbour tubercle bacilli in their bodies. In adults, a positive reaction is, however, not of much significance, but a negative reaction is very valuable as it

692 THE INDIAN MEDICAL GAZETTE [Dec., 1932

indicates virgin soil. In children, the value of the test is great. A positive reaction is of some significance in a child under 5 years, but in a child under 2 years it is of serious import owing to the risk of dissemination of the bacilli from the focus of infection. In children, the test is sometimes negative in spite of the presence of infection when sensitivity has not developed. Similarly in some adults, the test is sometimes

negative in the terminal stages of chronic tuber- culosis and also in pregnancy and parturition, and in certain acute infectious diseases like

measles, scarlet fever, enteric fever, and

influenza.

In 1891, Koch discovered a peculiar pheno- menon which has since been associated with his name. He found that when tubercle bacilli are injected into an already-infected guinea-pig, it reacted quite differently from when they were injected into a healthy animal. While in the

healthy animal apparently nothing abnormal was noticed, in the infected animal the inocula- tion was followed by severe clinical symptoms and ulceration at the point of inoculation. The

phenomenon of Koch, as this reaction to rein- fection is called, forms the basis of all tubercu- lous processes that take place in the diseased

body. The term '

allergy ' was coined by Von

Pirquet to define the state of a body infected with the bacillus and means

' altered reaction '. The allergic phenomena are, as a rule, inflam- matory and are, without doubt, manifestations of immunity and tend to localise or ward off the disease by causing destruction or fixation of the bacilli.

Ever since the discovery of the tubercle bacil- lus, many attempts have been made to produce prophylactic immunisation against tuberculosis. Many methods have been recommended for the purpose but the important ones are vaccination with (1) virulent living tubercle bacilli, (2) virulent dead bacilli, (3) pseudo-tubercle bacilli, and (4) living avirulent tubercle bacilli. It was found that virulent living organisms were too dangerous for the purpose and the results with dead bacilli were not satisfactory, while the pseudo-tubercle bacilli conferred no protec- tion against tuberculosis; for the last purpose Friedmann's turtle-bacillus vaccine was tried. It was thought that a lasting immunity could be obtained by the use of living but avirulent tubercle bacilli. With this idea, Calmette and his co-workers in France have produced a vac- cine, now well-known as B. C. G. According to Calmette, the bacillus was originally of viru- lent bovine origin but after repeated cultivation on glycerine-potato-ox-bile medium for a

number of years it has lost its virulence. Cal- mette claims that' B. C. G. differs from ordinary preparations containing tubercle bacilli only by its almost total lack of virulence. It possesses definite antigenic properties and consequently produces anti-bodies and in culture media forms tuberculin. But B. C. G. is perfectly harmless for all animal species susceptible to tubercu-

losisCalmette believes that most of the

infection in children takes place by the digestive root and for this reason and also because of its

simplicity he advises the administration of

B. C. G. by mouth within the first ten days of life. But experiments by others have shown

that B. C. G. given by mouth does not produce a positive Von Pirquet reaction, though when given subcutaneously it does so.

Petroff has carried out ' dissociation' experi-

ments with B. C. G. and has been able to isolate ' S ' colonies from it. He therefore claims that

while Calmette has been able to eliminate

gradually most of the ' S ' colonies, allowing the

' R' to predominate, the virulent ' S ' colonies have not been completely eliminated and though present in small numbers they may, under favourable conditions, increase in number to such an extent that reversibility of virulence will take place. In Petroff's opinion, therefore, the use of B. C. G. as a prophylactic measure is fraught with danger.

Calmette has produced a very large number of figures to substantiate the value of B. C. G. but his statistics have been subjected to very severe criticism by Greenwood. The trend of

the medical opinion at the Conference of the

International Union against Tuberculosis held

in Oslo (Norway) in 1930 seemed to be in

favour of Calmette. In the opinion of the

conference B. C. G. produced temporary im- munity against mild infection.

Such, in short, has been the advancement in our knowledge of the tubercle bacillus since the time of its discovery by Robert Koch. All this would not have been possible without this great gift which Koch gave to medical science? the discovery of the tubercle bacillus. As Koch

?truly said, the gold was lying on the surface when he began, but later was to be mined only with hard labour. Much has been accom-

plished; much remains to be done by concerted effort to discover the peeper mysteries of tuberculosis. His discovery only has made it

possible for us to appreciate that tuberculosis is caused by infection by the tubercle bacillus brought about chiefly by inhalation and inges- tion. The former is the more important route in pulmonary infection with the human bacillus and the latter in man is the route taken by the bovine bacillus. By carefully-controlled and

compulsory pasteurisation of milk, all practical risk of bovine infection could be eliminated. The most potent source of pulmonary infection is germ-laden sputum. It should be our duty, therefore, to urge on the public the importance of sputum precautions and on the authorities concerned of the importance of pasteurisation of milk.

References Baldwin, E. R., Petroff, S. A., and Gardner, L. V.

(1927). Tuberculosis: Bacteriology, Pathology and Laboratory Diagnosis. London: Bailliere, Tindall and Cox.

Burrell, L. S. T. (1931). Recent Advances in Pulmonary Tubercidosis. London: J. and A. Churchill. Calmette, A. (1932). Brit. Joum. Tuberculosis. July.

{Continued at foot of opposite page)

(Continued from previous page) Cobbett, L. (1917). The Causes of Tuberculosis.

Cambridge: Cambridge University Press. Fishberg, M. (1932). Pulmonary Tuberculosis.

London: Henry Kimpton. Greenwood, M. (1928). Brit. Med. Journ., Vol. I, p. 793. Petroff, S. A., and Branch, A. (1928). Amer. Journ.

Pub. Health, Vol. XVIII, p. 843.