USA > Ohio > Hancock County > Findlay > Twentieth Century History of Findlay and Hancock County, Ohio, and Representative Citizens > Part 169
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pivyeu contained the bacillus of its spores, and only under these conditions, actually inoculating frogs, mice, and rabbits with infectious material in Cohn's presence. He finally proved to Cohn that the nature and the distribution of the disease could be amply explained by the facts which he had brought to light in regard to the life history of the anthrax bacillus. This demonstration took place in the presence of a number of professors in the University of Breslau besides Cohn, notably the physiologist Leopold Auerbach, the pathologist Julius Cohnheim and his assistant Karl Weigert, and Messrs. Eidam, Lichtheim and Traube. It is said that Cohnheim was so astonished and delighted by Koch and his work that he rushed back to the Pathological Institute, called his assistants together and told them to stop their work and hasten to the Botanical Laboratory where they could see the demonstration for them- selves. He said Koch had made a startling discovery which in the simplicity and exactness of the methods employed was the more to be wondered at since he was shut off in his life from all scientific intercourse, and yet everything he had done was absolutely original and absolutely complete. " It leaves noth- ing more to be proved," said Cohnheim. " I regard it as the greatest discovery that has ever been made with bacteria, and I believe that this is not the first time that this young Robert Koch will surprise and shame us by the brilliancy of his investigations." *
The work on anthrax was published almost immediately in Cohn's Beiträge zur Biologie der Pflanzen in July, 1876. In a paper of over forty pages Koch describes with great exactness the many experiments he had conducted with the organisms of splenic fever, the methods he had employed and the con- clusions which could be drawn from his work. Not only was the sporulation of the anthrax bacillus proven and its life cycle worked out, but for the first time in the history of bacteriology a pathogenic microorganism was cultivated artificially in pure culture outside the animal body and the specific disease pro- duced. This Koch accomplished by the use of hanging drops of aqueous humor or sterile blood serum placed over hollow- ground slides. In these preparations he watched the develop- ment of the organisms for a number of generations throwing out as contaminations all those preparations which showed any- thing besides the characteristic bacillus or its spores. He made a careful study of the natural disease in cattle, sheep and horses, and produced the disease artificially in mice, guinea pigs, and rabbits by inoculation with blood or with splenic pulp from infected animals. He now produced the same disease in these animals by the use of his pure cultures grown for a number of generations outside the body. He thus settled absolutely the etiological relationship of the bacillus of anthrax to the disease and answered the arguments of those who main- tained that some virus or poison in the blood and not the or-
* Dr. W. H. Welch was working in Cohnheim's laboratory at this time and states that Cohnheim's enthusiasm over Koch's dis- covery made a profound impression upon all the men in the Pathological Institute.
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ganisms of Pollender and Davaine were the infectious agent. In addition to his production of anthrax in mice, guinea pigs and rabbits, Koch inoculated dogs and two varieties of birds, namely, partridges and sparrows and noted their resistance to infection. The same insusceptibility he found also in frogs and in his examination of the tissues of these animals, called attention to the remarkable fact that the anthrax bacilli were ingested by the white corpuscles of the blood. A similar ingestion of the organisms by blood cells he notes in material taken from the spleen of a horse dead of anthrax.
This paper is one of the great classics in bacteriology. By it the first clear light was thrown upon the dim obscurity which enveloped the world of microorganisms. By it the path was first shown along which the growth of this science was to move. It is significant that in the thirty-five years which have passed since the publication of this first paper of Koch's on an- thrax, the world-wide development of bacteriology has not thrown doubt upon the accuracy of Koch's observations, nor disproved any of the conclusions which he drew. Indeed but little of importance has been added to the facts which Koch established concerning the life history of the anthrax bacillus and the etiology of splenic fever. In November of the follow- ing year, 1877, Koch published his second paper. Here he described his method for making films of bacteria on the sur- face of coverslips, fixing them by drying or gentle heat, and his application of Weigert's use of the aniline dyes for the demonstration of bacteria in tissues, to the study of these bacterial films. In addition to the method of staining the bodies of the bacterial cells Koch also devised a method for staining the flagella on some of the motile forms. Cilia had previously been seen on bacteria, but now for the first time satisfactory proof of their existence was brought. The bulk of this paper, however, is given up to the subject of the pho- tography of bacteria, in which Koch was keenly interested be- cause of his belief that only by carefully prepared photographs could different observers compare their findings and avoid the many erroneous impressions resulting from imperfect descrip- tions of microscopic forms.
The work on anthrax was accepted everywhere in Germany, but met with much opposition in France at the hands of the physiologist Paul Bert. Bert maintained that every disease must be caused by a virus of the nature of an organized ferment whose activity was inhibited by oxygen. Since the anthrax bacillus could develop in the presence of oxygen, it could not be the virus which produced the disease. Bert's opposition to Koch's conclusions led the great Pasteur into the study of anthrax and into the field of infectious diseases, where as he himself said at the time "he had thus far been a stranger." Pasteur confirmed all of Koch's observations and completely overwhelmed Bert with the force of his arguments.
The study of anthrax, however, started Pasteur upon the study of other infectious conditions and in the course of his experiments he found an organism which was the cause of a `wania in animals, to which he gave the name vibrion The septicemia produced by the vibrion septique
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was entirely different from the septicemia produced t. t. ganism of splenic fever. As a result of Pasteur's v : anthrax and on the septicemia due to his vibrion west mind was again turned to the relation between ferme: and disease and we find him on April 30, 1878, in collay :. with Joubert and Chamberland advocating publicly doctrine of the dependence of disease upon the p.s. microorganisms within the body. Even before : however, Koch had been putting this theory to a prat studying with great minuteness the various efecte re produced in animals by inoculation with all sorts < material. The results obtained by Koch were also ;. in 1878 in a paper entitled, Untersuchungen über ologie der Wundinfektionskrankheiten, which consit: third of his important publications. In this paper Ke. forward clearly the exact state of knowledge on the : of surgical infections ; he explains the difficulties whiet. :. be overcome in working out their etiology and describe sults which others before him had achieved. He the: that he determined to study especially analogous con .- animals resulting from the subcutaneous introductie terial from various sources. He tells how he succeede! : ficially producing conditions which were strictly compa- surgical wound infections and how these infections ze were always due to microorganisms. He reports six (" kinds of infection so produced, pictures the organa: ciated with each, describes in detail the appearances !: gans and tissues of the infected animals. He notes ! that certain species are susceptible to one kind of micro ism, other species to other kinds, points out that tx . body itself is the very best medium in which to cks cultures and that the pure cultures so obtained car : alive by the continuous inoculation of fresh anima greater proof that infectious material consists of : kinds of living microorganisms capable of indenti :: plication could be asked, except the cultivation of t= isms in pure culture outside the animal body ani : duction of the lesions by the organisms themse'. proof had already been furnished by Koch for anc'. eral improvements in bacteriological technique wert : scribed by Koch in this paper, the most important adoption of the oil-immersion lens of Stephensen - Abbe condenser for the study of microscopic forms.
Koch's growing reputation prevented his longer Wollstein and the impression which his experiments c: sonality had made on Ferdinand Cohn and the ccx: Breslau led them to procure a place for him there es arzt or Municipal Physician. In the summer of !5. moved his family to Breslau and took up the work !" position. The strenuous life of a city practitist." little to Koch's liking, the salary of the new position ". below that required for himself and his family at. too he found that his scientific work was interfered any rate after three months sojourn in Breslau ben: steps to Wollstein where his old place was still =z. Google
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futle community. About this time Finkelnberg, one of members of the Gesundheitsamt in Berlin, resigned to t a professorship and Koch, largely through the instru- ility of Cohnheim, was selected as his successor. He I his family to Berlin and from this time on devoted him- ‹clusively to laboratory work. At the time he entered the dheitsamt bacteriological investigation, which had pre- y been carried out there with some zeal, was largely oned. With characteristic energy Koch gathered about If a number of assistants and students and with their improved and applied the methods and technique which eviously had devised. At the end of the first year the zations were published in the Mittheilungen aus dem lichen Gesundheitsamte for 1881. In this volume g other articles were three papers by Koch alone, one by and Wolfhügel and one by Koch, Gaffky and Loeffler, ntributions of the greatest importance to the now rapidly ping science of bacteriology. Many of the methods for zation and disinfection which are now in vogue were d at this time and many great improvements in bacterio- I technique were introduced. In the first paper in this le Koch described what we must regard as his greatest zement, his poured-plate method for the isolation of or- ms in pure culture. Up to this time no method had ever devised for obtaining pure cultures of organisms from tres. We know that Koch had pure cultures of the ax bacillus, for in this work he first obtained the organ- from the blood of an infected animal, using the greatest ations to prevent contamination, and employing carefully zed instruments, sterilized slides and coverslips. In on he actually watched the development of the bacteria the microscope, casting aside as worthless any prepara- which showed extraneous organisms and controlling his by constantly producing the disease by inoculation. We also that he recognized the value of the animal body as a m in which to obtain pure cultures of bacteria and in rk on wound infections showed how one organism would p exclusively in one animal, another organism in another. vas entirely a different matter, however, from obtaining cultures from mixtures. No scheme had yet been hit no apparatus had been invented by means of which this be accomplished. Attempts to solve the problem had ountless and the difficulty of solving it is apparent when recalled that such skillful investigators as Hallier, Lister, Naegeli, Salamonson and Buchner had all de- apparatus and methods for this purpose, but had failed t with success. Koch in order to obtain pure cultures use of nutrient gelatin. This material had previously employed in the cultivation of microorganisms, but i solutions so dilute as not to harden and furnish the ansparent medium Koch desired for the study of his B. Koch now used the gelatin in such proportions as to solid coagulum when cooled, and added to this gelatin
substances ittesbaly 101 treff nutrition. ilf his previous work Koch had observed that if a slice of potato was sterilized by cooking and kept under aseptic precautions in closed and ster- ilized vessels, no growth of any sort or description appeared upon the cut surface. If a similar slice of potato was exposed to the air for a few minutes and then put in a warm chamber, after a few days its surface was covered by colonies of various colors, which when examined microscopically were found to be made up each of its own kind of microorganism. Acting upon this idea Koch spread his newly devised gelatin upon the surface of sterile glass slides or dishes and inoculated the sur- face by drawing over it a platinum wire which after steriliza- tion had been immersed in the mixture of bacteria to be studied. He now found that isolated colonies developed along the line of these streaks and that these colonies were each composed of but one kind of microorganism. He next further improved this method by inoculating the melted gelatin di- rectly, shaking it well to get a separation of the individual cells and pouring this over the surface of a sterilized glass dish. This method of making streak cultures and of pouring plates gave pure cultures and solved the problem which had been attempted by so many of his predecessors, the problem which the scientific world recognized had to be solved before the science of bacteriology could advance very far beyond the place where it had rested for so many years.
Simple as the poured-plate method appears to us at the present time and clear as are the various steps taken by Koch in the solution of the difficulty, it still remains to us the only practical procedure for obtaining pure cultures of micro- organisms, the slight modifications which it has undergone in the quarter of a century since its discovery relating largely to the composition of the medium which is employed. For us in America it is interesting to note that the only real improve- ment over Koch's poured-plate method came from the hands of an American investigator, Professor Barbour, who has de- vised an ingenious apparatus by means of which he can obtain cultures from isolated bacterial cells. From the difficulty of using this method, however, it can have but a limited applica- tion in bacteriology.
The end of the year 1881 may be said to mark the close of the inventive or constructive period in Koch's life. In the decade from 1872, when he returned from the Franco-Prussian war, to the year 1882 the science of bacteriology had changed from a chaos of conflicting views and observations to a well ordered system. The methods for fixing and staining bacteria so as to make their microscopic study possible had been devised, their cilia had been stained, the oil-immersion lens and the Abbe condenser had been utilized, a method of separating sin- gle species from mixtures had been found, the pathogenic bacteria had been cultivated in pure culture, the etiology of infections had been cleared up, the germ theory of disease had become a proven doctrine. For most of this advance in knowledge Koch was himself responsible.
From this time on the work of Koch and his pupils was
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largely the application of the methods already perfected to the study of other conditions and the next few years were rife with epoch-making discoveries in the field of infectious diseases. As he himself said, when once the right method was found, the solutions of the problem came to their hands as easily as ripe apples fell from the trees. It was the method which was es- sential. It was the method which Koch had looked for. It was the method which he had found.
In 1882 Koch worked out the etiology of tuberculosis by his discovery of the tubercle bacillus. To do this he devised a new method of staining by means of which he could differen- tiate between the organisms always present in tuberculous lesions, and those accidentially found there, finally succeeding in cultivating the organisms he had stained on solidified blood serum, and proving their relation to the disease by inoculation experiments. The preliminary report of this work appeared in 1882 in the Berliner klinische Wochenschrift, the full account of the many experiments being published in 1884 in the second volume of Mittheilungen aus dem kaiserlichen Gesundheits- amtc. The main points in the life history of the tubercle bacillus, its relation to tuberculosis and the methods which should logically be adopted to prevent the spread of this dis- ease were presented with great clarity and not only are these publications of Koch's models for future generations of scientists, but the practical importance of the knowledge fur- nished the world by Koch at this time can hardly be over- estimated. In reading these papers it is interesting to note that in his early work Koch held certain ideas which could not later be substantiated. Thus he believed that the small highly refractile bodies seen in the tubercle bacillus were spores, a point of view not subsequently confirmed. He also taught that tuberculosis of man and of animals was identical and due to the same bacillus, and that the bovine disease was a source of great danger to the human race, and was to be treated like other diseases of animals transmissible to man. As is well known this opinion was greatly modified by Koch himself in his later work.
In this communication Koch seems for the first time to have clearly formulated in print the laws which go by the name of "Koch's postulates," although he evidently made use of these postulates in verbal communications before this period. In & later address entitled Ueber bakteriologische Forschung which Koch delivered before the International Medical Con- gress in Berlin in 1890, we find the fullest and most satisfac- tory exposition of these laws. According to these postulates a parasite to be regarded as the cause of a disease must fulfill certain conditions. First, it must be found in every case of the disease, and under conditions which explain the pathologi- cal changes and the clinical symptoms. Secondly, it must not be found as an accidental and harmless parasite in other dis- eases. Thirdly, after isolation from the body and cultivation in pure culture, it must have the ability to produce the disease. When these conditions are fulfilled then no other relation be- tween the parasite and the disease can be imagined than that site is the cause of the disease.
In 1883 Koch was made the head of the German (iz Commission and went first to Egypt and then to Indir . a painstaking investigation of Asiatic cholera, both in pri- and in the post mortem room, he not only established :.: new points concerning the pathology of the infectie, isolated the cholera vibrio and brought forth convincing p. of its etiological relationship. Of especial importance : the public health standpoint was his cultivation of the r: from drinking water and from articles of food. The posr. of contact infection in this disease was not overlooked by E. and some of his earliest work demonstrated the presence c. living vibrios on the clothing of patients. On Koch'sr. from India he was given a donation of 100,000 mark: :: State and Kaiser Wilhelm I bestowed upon him the Orie the Crown, second class.
In 1885 Koch left the Gesundheitsamt and became Pris of Hygiene and Bacteriology in the University of Be': chair with this title being made for him. Both a: Gesundheitsamt, and later at the University his labers:" were crowded with men from all over the world an' learn the new methods and technique. England, Ac: France and Italy were well represented but German phys . flocked to him especially, many of them to take the cocT- Cholera Diagnosis which he offered at the Gesundhe's this being required by the Government of the official te. men who were stationed on the frontier. In the list de: ents who worked with Koch or took the courses ofe .. his laboratory are many of the foremost investigators c .: present day, included among the number being Gaffky, Lo Hueppe, Wolfhügel, Esmarck, Behring, Flügge, P. Gärtner, Fisher, Wassermann, Froboenius, Kolik. . Fraenkel, Hesse, Weiss and Kossel in Germany: Prudden, Abbott, Vaughan, Novy, Biggs, Laplace, An. Ernst and Shakespeare in this country. But three !: these last named, however, actually worked under Koa. self, Dr. Welch and Dr. Prudden and later Dr. Ernst, : Hygenic Laboratory of the University.
It is significant that the etiology of many if net t . jority of the infectious diseases which we now unders .? ". solved by Koch or his pupils. Thus to Koch himself to> credit anthrax, tuberculosis, cholera, infectious conjun: to daffky. typhoid fever; to Loeffler, diphtheria and gle :. to Pfeiffer, influenza ; to Kitasato, tetanus, symptama. thrax, and bubonic plague in part. In many other is. the methods which Koch devised, when adopted by !: lowers all over the world, have brought solution te pr .. of the greatest importance in medicine and surgery.
It is interesting to us at Johns Hopkins that D: came directly from his studies in Berlin, where he w :.: sonal student of Koch at the University and took Ko. course in bacteriology, to Baltimore when the par." laboratory of the Johns Hopkins Hospital was Apeli brought with him cultures of a number of mierc. and at once gave courses in bacteriology similar to fix in Berlin. Our laboratory is thus one of the fr: Google
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1+ wwwyou, auu w Dr. weich more than ny one else American medicine is indebted for the introduc- of the Koch methods.
the establishment of the Saranac laboratory for the study uberculosis by Dr. Trudeau may also be regarded as the et ouicome of Koch's first paper on tuberculosis published 882.
1890 Koch described the preparation of tuberculin which immediately heralded about the world as the great specific tuberculosis. Its failure to become this specific is the one on Koch's reputation. As Trudeau so clearly points out, h in his first investigation on this remedy departs for the · time in his life from the rigid methods which he pre- isly and subsequently applied to all his work. Careful nination of Koch's original publication on tuberculin es little doubt that Koch was himself thoroughly convinced it was a great healing remedy for early cases of tuber- sis of the lung. Why it was that he did not demand of self the rigid proof for his statements which he knew others Id at once demand of him will always remain a mystery. what other man of science can it be said, however, that ing a life-activity of forty years but one of the many im- ant conclusions which he drew from his work could not be equently confirmed ?
n 1891 Koch became Director of the Institut für Infec- skrankheiten in Berlin which was built under his special ction. Here he remained as Director till 1904 when he relieved at his own request, his place being taken by his ner pupil Gaffky. From 1904 till his death he was Ehren- jlied or Honorary member of the Institute and continued e his active investigations. The Institute, like the Hy- ic Laboratory of the University and the Gesundheitsamt, 's turn became the Mecca for native and foreign students, h gathered about himself a number of the foremost inves- ors in Germany who attracted to themselves men from ous parts of the world. Wassermann, one of the ablest of i's assistants, has been especially friendly to Americans a number of Johns Hopkins graduates have worked with thus coming indirectly under Koch's influence. Among 's in this country who worked in the Institute may be ioned : Strong, Ford, Cole, Moss, Jobbling and Mitchel. iring the period when Koch served as Director of the In- te he was constantly engaged in the study of the infectious ses and was especially concerned with the problem of de- g the proper measures to limit their spread. The pro- 'es adopted at the time of the great cholera epidemic in burg in 1892 were largely the result of his discoveries. following year he made further important contributions r knowledge of this disease and pointed out how clearly of the great epidemics could be traced to polluted water, ating water filtration as the best means of preventing its I by this path .*
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infectious diseases and in his earliest publication calls attention to the possibility that protozoa as well as bacteria may be the cause of disease in man. In 1896 at the behest of the English Government he went to South Africa and Cape Colony to study rinderpest. He devised a method of preventive inoculation to control this disease and spent some time there in the study of protozoan parasites. Upon his return to Berlin he published the results of his investigations upon Texas fever, tropical malaria, black-water fever, surra, and also upon rinderpest and bubonic plague. He was particularly interested in the study of malaria and spent some time in Italy in 1898 investi- gating the disease in that country.
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