KochTB - Robert Koch Although bacteria had been observed in...

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Unformatted text preview: Robert Koch Although bacteria had been observed in the seventeenth century, soon after the invention of the microscope, the relation between bacteria and disease was not demonstrated until relatively late in the nineteenth century. Robert Koch (1842-1910) devoted him- self to studying this relationship, and in his work he proved the specific bacterial cause for several important diseases, devised techniques of incalculable value, defined methodological prin- ciples, and trained productive investigators who brought further illumination to medical science. Koch, after an excellent preliminary education, graduated MD from Giittingen in 1866, and then, following further clinicial training in army service in the Franco-Prussian war, settled in East Prussia as a country practitioner and ‘district sumon ’. He had a successful clinical practice but he also set up his own private laboratory where, in his spare time, he carried out his researches. His first great contribution was his study on anthrax. Using mice as the experimental animal, he transmitted the disease serially, demonstrated spore formation in the bacteria and pro- perly interpreted its role, made pure cultures of the organism outside the living body (the first time this had ever been done for . a pathogenic organism) and established the bacterium as the specific cause of the disease. Even with his primitive techniques his work was so skilful that to this day it forms the basis of our knowledge of anthrax. His studies, published in 1876, attracted immediate attention and at once marked him as a brilliant investigator. When he wrote, only one other disease — relapsing fever — had been definitely traced to a specific bacterium. We can thus appreciate the giant step that Koch had taken when he established the pathogenesis of anthrax. Other steps followed quickly. In 1878 he published an important study on the infections that resulted from wounds. He showed experimentally that putrid substances, illiected into animals, produced a whole series of diseases, Robert Koch 267 shknu correlated with particular mic;::o;g::::lslé 523mm; worksdimnguismdescnbcdp?‘hogcmnalncyfltgizicalpinnovations in bacteriology, includi: staining techniques and culture methods, particularly motif: 20' if}:;:?n::r:::::rt‘l: tubercle bacillus and its: relation to tllise Sites!” tuberculosis appeared in 1:33.‘:lybe::yoil;:;: take many different forms, so varied‘t mumpuon’ sci-0m“. clinically as quite distinct diseases — e.g. comm om,“ forms, and Pott‘s disease. Were tag; 5:31.13: could you prove in maniffi‘a‘tiomfdi'stosvtrd, were they truly causal or null»: amaze how could you tell? Koch’s studies, directeilmeds ttltmahe ' s depended on new technical me . my “my thi‘e): permitted him to demonstrate the bacillus t 3.. devilfg, Ye rations and in pure culture. Hisconwptual analysis, in“ wn in}: as Koch's postulates, set up criteria flor asserting s n0 l relationship between microbial agents and mtg.“ m causa t two years Koch and his associates deinons. . and lctne‘r|i:lmc)i:uses for glanders, Asiatic cholera, diphth;i;i:sm faphoid. Other workers added further dlwahf‘. 0:30 :1 0:21 | MN. aided, the ”a" 188' ‘to Immg‘ewslfien specific agents for ‘ r o . 0f :ac:i?e::?::s disfises were being discovered, and high hopes m 3'raised for the conquest of all disease. . of minimum“ we{tom's life was by no means a succession. I dig pom- ' His studies on tuberculin led to partieu at h' phi” triumphs. h' errors are insignificant compared With is ac m" but :ceived the Nobel Prize to: Medicme In I905. merits. I382 study on tuberculosis, from which :ie preset: Thet are taken, has particular importance. Koc Imdidemity excerp ’_ ' method and new culture methods that con . . msmmnl: bacillus and he showed that tuberculosis :3“ the t‘l!:"=ttt:":tlisease' resulting from infections with. Emsetsiologic mum. And this bacillus he proved to be the Imam to the agent By identifying this agent he gave a prezifse II the different disease and deiiionStrated the similarly “(1.1m manifestations. His experimental wtoru best. analysis amplified medical science a 258 Fruitiori 21 The Etiology of Tuberculosis (1882) Excerpts from ll. Koch. "Hie Etiology of Tuberculosis', in Medan! min, vol. 2, I938, no. 3. 99- 853—79. [---1 If the number of victims which a disease claims is taken as a measure of its importance, then all diseases, especially the most feared contagious diseases, plague, cholera, etc., must take a place far behind that of tuberculosis. Statistics show that one seventh of all people die of tuberculosis, and if only the pro- ductive middle aged class is considered, tuberculosis carries away a third and often more of these. [...] Attempts have been made repeatedly to investigate the nature of tuberculosis thoroughly, but up to now they have been fruit— less. The so frequently successful staining methods used for the ° demonstration of pathogenic micro-organisms have left this disease in the lurch, and the attempts made to isolate and culti- me the vinis of tuberculosis up to the present can not be regarded as successful. I...) The aim of the investigations had to be directed first toward Ilie demonstration of some sort of parasitic organism foreign to the body, which possibly could be explained as the cause of the disease. This demonstration was indeed carried out successfully by means of a certain staining method, with the aid of which characteristic bacteria, previously unknown, were found in all organs affected by tuberculosis. [There follows a technical description of the staining process] The bacteria made visible by this method show a behaviour Which, in many respects, is characteristic. They have a rod- shaped form and thus belong to the group of bacilli. They are my thin and are from a quarter to one-half of the diameter of a ml blood corpuscle in length; however, at times they attain later length, up to the full diameter of a red blood cell. [. . .l The bacilli are present in large numbers in all situations where Robert Koch 269 user... arly in origin and making rapid ' they then usually form little groupswhrch calm p33; pclosemgmlys, ther and at times are arranged In bun-mesh“ -. ' “32f lie within cells and present a picture an; 5.133;; llmeS 'Ili heaped within the cells. On the other a , us leprzbabcai‘lliare found. Particularly on the borders “Erica; in? ds of bacilli which are not rnclosed In ce Is am me. oer, crow the height of the tuberculous process ts p A's soon arite more rare, are found only in :smallgrraupihzr bac'ml belmne on the edges of tuberculous focr, [. 2.]. am. an: enllrcly a 0 r completely, yet they are rarely entirely a i may dim”? those cases in which the tuberculous process he; the“ tzd‘hlflziant cells are present in the tuberculous tissue, t arres . the bacilli lie chiefly within these structures. El. rler certain conditions, to be mentioned later, t3; :3: f s res even in the animal body; and rrrdeedo,f ovalfom birgillufzont’ains several, usually two to four spores . - at its lenslh- . which are :IiTme: through?f the bacilli in the “nous tuber- In wear "5:": l processes in man and animals the following material has cu ous been observed. a . w a were Eleven cases of miliary :ubemrm:;‘:elba(;rll;lfim ' 'l' tubercesrn , ml lafrironstrated in miliary tubercles of the They were present in abundance Ill . . . . ‘50 ' ' basrlar meningitis. A . ules of the put mater rn . ds cm ins/gala“ examined, the caser|r|usl brlonchral glan ' ' swarmsofbacrr.... . _ tanned,tn parstédznszamus bronchitis and pneumonia fetal/:3 Twelve ca ‘x cases). The presence of the bacrllr was r m f‘lrWlla‘iZntl'r: :dges of the caseous, infiltrated tissues, but they c re y bundant. [. . .] ' RI ‘fingevzfizmm tubercle of the brain, larger than a hit ' ' ou oi iant cells contained no parasites, but cacasronalnli‘gr ps :iant cell each containing one or two bacr I were the tuberculous process is e 1. Human . never lacking rn the de the lungs they could be spleen, liver and kidneys. 260 ‘Fruition Two cases of intestinal tuberculosis. In the tubercles grouped about the intestinal ulcers, the bacilli could be demonstrated especially well, and indeed, here again they were found particularly numerous in ihe most recent and smallest nodules. Three cases of recently excised scrofulous lymph nodes. In only two of these could bacilli inclosed in giant cells be demonstrated. Four cases of proliferative arthritis. In two cases bacilli were found but only in small isolated groups of giant cells. 2. In animals. Ten cases of bovine tuberculosis with calcified nodules in the lungs, several also in the peritoneum, and, in one case, on the pericardium. In all cases the bacilli were present, principally within the giant cells which were in the tissue sur- rounding the calcified masses. [. . .] Three cases in which the lungs of cattle did not contain the usual calcified nodules with uneven surfaces of the usual tuber- culosis, but on the contrary, smooth walled, round nodules filled with thick, soupy, cheesy material. Usually this form is not regarded as tuberculosis, but as bronchiectasis. However, in the vicinity of these nodules, giant cells were found and in them the tubercle bacilli. One caseous cervical lymph node of a pig contained the bacilli. In the organs of a fowl dead of tuberculosis, and, indwd, in tubercles of the bone marrow, as well as in the peculiar nodules of the intestines, liver and lungs, large numbers of bacilli were found. In three monkeys, spontaneously dead of tuberculosis, the lungs, spleen, liver, omentum, which were riddled with countless nodules, and the caseous lymph nodes, were examined and tuber- cle bacilli found in all the nodules or in their immediate vicinity. Of spontaneously ill animals, nine guinea-pigs and seven rabbits came to examination, which disclosed the bacilli everywhere in the tubercles. Beside these cases of spontaneous tuberculosis, there was pro- vided for me a not inconsiderable number of animals which were infected by means of inoculation with various tuberculous sub— stances; [. . J. The number of animals infected in this way amounts to I72 guinea-pigs, 32 rabbits and 5 cats. The demon- station of the bacilli in the majority of these cases had to be Ruben Koch. 261 rum, limited to examination of the tubercles of the lungs which were always present in large numbers. In these the bacilli were not absent a single time; [. . .1. It is striking that in spite of the regularity of the occurrence or“ the tubercle bacilli, no one up to the present has seen them. Yet this can be explained by the fact that the bacilli are extraordinarily tiny structures and for the most part are so scant in number, especially when their presence is limited to the interior of the giant cells, that without special staining methods they must escape the most careful observer. Even though they are present in large numbers, they are mixed with finely granular detritis and obscured by it in such a way that their recognition is extremely diflicult. Moreover, there are several accounts of micro-organisms having been found in tissues showing the changes of tuberculosis. Thus Schilller mentions in his paper on scrofulous and tuberculous joint diseases that he has found micrococci constantly. Doubtless we are concerned here, just as in the case of Klebs, who found extremely tiny motile granules in tubercles, with something other than the tubercle bacilli which I observed, and which are non-motile and rod shaped. [He gives other examples.) On the basis of my numerous observations I state it to be proved that the bacteria designated by me as the tubercle bacilli are present in allcases of tuberculous disease of man and animals. and that they may be dilferentiated from all other micro- c properties. It does not necessarily organisms by t heir characteristi follow from this coincidence of the tuberculous disease and the bacilli that the two phenomena have an original association. although no small amount of probability is or progressing, and that they disappear disease comes to a standstill. In order to prove that tubercul by the invasion of the bacilli an growth and proliferation of the latter, lated from the body and cultivated in pu of all adherent products of disease origina organism; and, finally, through transf animals, the same clinical picture of 262 letion given to this theory by the fact the bacilli are found chiefly where the process is beginning in those places where the osis is a parasitic disease caused d primarily influenced by the the bacilli had to be iso- re culture until devoid ting from the animal er of the isolated bacilli to tuberculosis as is obtained empirically by the injection r material had to be Produced? naturally developed tuberculous [aidescribes the technique of culture.) ' cultures resulting from the . growth of tubercl ' ' firzmirpear to the naked eye in the second week after inorfulzrgfll us [es y not until after the tenth day, as very tiny points and d ’ :2“; [£08.] If only a.very few bacilli were present in the materigl from :he 2 then it rs hardly ever possible to free the bacilli a...“ messsue and bring them into direct contact with the the bits off tum. In .thrscase they develop their colonies within 1 . ‘ lIlssne and rfthts rs transparent enough — if, for example I :lr‘ritfisglrlia mom which have been taken from scrofulous glands — . . , porn s may be seen within 't ' strikes it. [. . .] The markedl 1 when the hub! . y slow growth whi ' ’ ingubat? gnaw", the peculiarly dfyh 23mm fill: 1 ion 0 t bacillary colonies occur ' . in no othe mum bacteria, so that confusion of the cultures of 25:13:; rwrt those of other bacteria is impossible; and after only a small amount of practice no ‘ ' . . ‘hms Is easier to accidental contamination of the cultu detect at once than I. . .] Among hundreds of recently bought ' ' gurnea- r ' mg: can; to autopsy in the course of other 3:33.? wlmis alwa on a single tuberculous one. Spontaneous tuber: mm of thgmxdéznr‘s'ohged instances and never before the been in the same room with 30:21::ng is” the animals had mmzls spontaneously ill of tuberculosis, I fgrnzumzsnzhia': Morenmd ,. wrthout exception, to be uncommonly large and focus Maw? In“; pus and usually in the lungs also a large caseous “In“ true caar'ta fvanoecl necrosis in the centre, so that several mm The dig; ormatron had taken place exactly as in human ”a m- behj dopment of tubercles in the abdominal viscera acts in m In that in the lungs. [. . .] Inoculation tuberculosis m mil“zi'rtrrely drfierent manner. The site of inoculation in lymph s was In the belly in the vicinity of the inguinal early mnodesi ("These swelled first of all and thereby gave an “Minn a rble sign as to the success of the inoculation The rs ran a much more rapid course than the spontaneous Robert Koch 263 luwzsu tuberculosis, because to begin with, a larger amount of infectious material was taken into the body; and on section of these animals, the sp!een and liver showed far more changes of tuberculosis than did the lungs. Thus it is not at all difficult to differentiate spontaneous tuberculosis from inoculation tuberculosis in labora- tory animals. [...] The results were uniform throughout. In all animals which were inoculated with fresh material containing tubercle bacilli the tiny injection wound was almost always cmsted over on the following day. It remained unchanged for about eight days, then a nodule formed which either enlarged without breaking down or, as was the usual case, developed into a flat dry ulcer. Within two weeks the inguinal nodes on the side of the inoculation wound, at times also the axillary nodes, were enlarged to pea size. From then on the animals quickly became emaciated, and died after four to six weeks, or were killed in order to avoid any combination with a later developing spontaneous tuberculosis. In the organs of all these animals, and chiefly in the spleen and liver, the characteristic, well-known tuberculous changes of guinea-pigs were found. That, indeed, the infection of the guinea-‘ pigs in this series of experiments resulted only from the injected material is demonstrated by the fact that, in other series of experiments with inoculation of a scrofulous gland, and fungous material from a joint in which no tubercle bacilli could be found. and after injections of pulmonary tubercles (monkey), which had been dried for two months and with some which had been kept in alcohol for a month, not a single one of the animals inoculated became ill, while those injected with material containing bacilli showed marked tuberculosis in four weeks without exception. From such guinea-pigs as had been infected by inoculation with tubercles'from the lungs of monkeys, with miliary tubercles from the brain and lungs of humans, with caseous material from phthisical lungs and with nodes from the lungs and peritoneum of tuberculous cattle, cultures of tubercle bacilli were obtained in the manner previously described. As a result, it was found that. just as the clinical picture which the various substances enum- ated produced in the guinea-pigs never varied, so the cultures 0‘ bacilli obtained did not difl‘er from one another in the slightest 264 Fruition degree. In all, fifteen such pure cultures of tubercle bacilli _ were obtained and of these four were from guinea-pigs which mmifegeted Iwith tuberculosis from monkeys fm-r mi"- u re . . -,_, n.-. humans. u osrs and seven With tuberculous material from However in order to exclude an ' ' . , y possible objection th change in the nature of the bacilli, possibly a bringing abouilo: similarity between previously dissimilar organisms, was caused by the inoculation of the tuberculous material into the guinea- 3::flflnf attemhpet was made to cultivate the tubercle bacilli y romt 'seased aim”. spontaneously di organs of humans and 'l‘hisbteaxperiment succeeded many times and pure cultures rue o ined from two human lungs with miliary tuberculosis rom another. With caseous pneumonia, twice from the contents, of small caVIties of phthisical lungs, once from caseous mesenteric ng‘des and tWIce from freshly extirpated scrofulous nodes in :nditmttwice f;om thleelungs of cattle with bovine tuberculosis imes rom t lungs of guinea-pigs spontaneo ' . usl ll :if tuberculosis. Moreover, these cultures were entime sim’iliir "irrwangher, just as were those obtained by the roundabout o inoculating guinea-pigs, so that the unity of identity of the bacilli ' ' be doubted. present in the various tuberculous processes can not I. . .1 Thus, up to this point my investigations have est ' , ablis m; trmnce of characteristic bacilli is regularly boundhijpl “banal osrs and that these bacilli can be obtained from to In: ous organs and isolated in pure culture. It now remained ba' .wer the weighty question as to whether the isolated cilli if again introduced into the body are able to rod the pathological processes of tuberculosis: P m “:irfrder to exclude any error from the solution of this question, mm in ies the crux'of the whole investigation of the tubercle and 1Agataif.‘iariltierr"reign.ts, as varied as possible, were set up the point in qmuonat in detail because of the significance of First experiments with sim ' ' , . ple inoculation of the ' ' ' the manner previously described were set up. mm. m Robert Koch 285 Experiment I Of six newly bought guinea-pigs which were kept in the same cage, four were inoculated on the abdomen with cultures of bacilli obtained from human lungs with miliary tuberculosis and cultivated for 54 days through five changes of culture material. Two animals remained uninjected. After l4 days the inguinal nodes of the inoculated animals swelled, the sites of injection ulcerated and the animals became emaciated. After 32 days one of the animals inoculated died. After 35 days the remainder of the animals were killed. The injected animals, the one which had died as wel...
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