Robert Koch: A Life in Medicine and Bacteriology
Author: Thomas D. BrockCategory: General Interest
Robert Koch's story is a stirring example of how a lone country doctor can rise above all odds to become a true scientific revolutionary. Winner of the Nobel Prize in 1905, Koch is best known today for his discoveries of the causal agents of tuberculosis, cholera, and anthrax. His vital contributions to microbiological methodology also make him the founder of the field of bacteriology and central to the establishment of the disciplines of hygiene and public health. He was also a world traveler and made numerous important research expeditions to India (where he discovered the cause of cholera), Africa, and New Guinea.
Koch's postulates, a series of guidelines for the experimental study of infectious disease, permitted Koch and his students to identify many of the causes of the most important infectious diseases of humans and animals. Even today Koch's postulates are considered whenever a new infectious disease arises.
Electronic only, 364 pages, illustrations, index.
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Chapter 1 : Introduction
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The human life span is now almost 20 years longer than it was when Koch began his work, and at least some of that increased longevity can be attributed to Koch's contributions. This chapter talks about Koch's major accomplishments. Koch's postulates provide the essential experimental basis for any study of an infectious disease, whether in human, animal, or plant. Koch's postulates also apply in the broader field of microbial ecology o f which medical microbiology is a part. The postulates thus apply to virtually any microbial process carried out in nature by a microorganism. Although these postulates were not completely new with Koch, it was Koch's experimental work that emphasized their importance. He worked out the life cycle of the anthrax bacillus, showed the importance of endospores, and related this work to effective control of the disease. This work led to the introduction of water filtration methods in large urban water supplies and resulted in major decreases in morbidity and mortality from intestinal infections. Koch was the founder of an important school of bacteriology, one of the most important schools of the late 19th and early 20th century. Koch was a strong promoter of quinine for the treatment of malaria and atoxyl for the treatment of sleeping sickness. But when one realizes that the "Koch School" was actually the forerunner of much of what is now called bacteriology or microbiology, one can truly appreciate the magnitude of his contributions.
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Chapter 2 : Koch's Early Years
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Robert Koch was born on December 11, 1843 in Clausthal, a small mining city in the Harz Mountains of Lower Saxony (Niedersachsen). Although he was much closer to his mother than to his father, of greater influence than his mother was probably his uncle, Eduard Biewend, Koch's mother's brother. Koch desired a university education and his school principal recommended that Robert study for a career in medicine or natural science, or perhaps for a career as a Gymnasium teacher. His principal apparently had some doubt about Robert's ability to apply himself, however, as he emphasized that Koch's success would depend upon his ability to concentrate his energies on a chosen field of study. Vacillating from one possibility to another, Robert strongly favored a career in natural science, since this would have permitted him to partake of research expeditions to foreign lands. Koch's main accomplishment at Gottingen was the winning of a prize of 30 ducats for carrying out a difficult anatomical study of the disposition of the nerves in the ganglia of the uterus. At the completion of this study, Koch presented his work, well illustrated with original drawings, under the title: “On the Presence of Ganglion Cells on the Nerves of the Uterus”. These youthful studies, so remote from his main opus of later years, already reveal the energy, industry, and scientific acumen with which Koch worked. In addition, he served the various clinical services in the hospital, including surgery, obstetrics, psychiatry, and pathology.
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Chapter 3 : The Young Doctor and Husband
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Koch traveled to Berlin to see the sights of the big city and to attend the lectures of Rudolf Virchow, after completing his medical studies. Virchow, the most famous German physician of his day, was to become Koch's sometime opponent 20 years later. The knowledge of the clinical picture of cholera which Koch gained in Hamburg would be of great use to him in his studies in Egypt and India 17 years later. However, the position in Hamburg did not provide a suitable income for a prospective husband, so Koch began to apply for other positions. He quickly became a popular doctor with the villagers and his medical practice flourished. As in Hamburg, he carried out microscopical studies in Langenhagen too, not only in medicine but in the whole field of natural history. According to his letters to his father, he learned more during his brief military service than he would have learned in a half year in a surgical clinic. However, his hometown of Rakwitz needed its popular doctor back, and in early 1871 he was called to return even before the war ended. At Rakwitz, Koch was received with acclamation. Despite the predominance of Polish, Koch for the first time felt that he had established a "home". But at age 28, Koch was on an important new threshold.
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Chapter 4 : Steps Toward Maturity: Koch in Wollstein
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Despite his increasing fortunes at Rakwitz, Koch was not content to spend his whole life as a simple country doctor. Now he received an invitation from one of his important patients, the Baron von Unruhe Bomst, to apply for the newly created position as Kreisphysikus in Wollstein. Koch applied in person, was accepted, and in April 1872 he moved to Wollstein to begin one of the most important periods of his life. When Koch arrived at Wollstein he was just a 29-year-old physician; when he left eight years later he was on his way to becoming a renowned world-class scientist. It was at Wollstein Koch carried out his pioneering researches on anthrax and the germ theory of disease. In addition to his medical practice, Koch had all the duties of the Kreisphysikus. He had responsibility for smallpox inoculations, for writing death certificates, for giving advice on general public health matters, and for overseeing the local hospital. He also worked hard at keeping up with advances in medicine, reading many medical journals and books. But not only did he find time for all these medical matters and his research, he also took an interest in archaeological explorations.
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Chapter 5 : The Lone Scientist: The Work on Anthrax
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When Robert Koch had finally built a lucrative medical practice, he started doing research. Koch's first published work on anthrax was so perfect, so detailed, so complete, that it quieted all significant objections to the germ theory of disease. In slightly more than one month, beginning on Christmas Eve, Koch had worked out the whole life cycle of the anthrax bacillus. Much work remained to be done, but the framework of future research was clear. Within weeks, Koch had worked out in great detail the biology of the anthrax bacillus. Davaine and others had shown that animals could obtain anthrax not only from other infected animals but from the soil. All of Koch's experiments were directed to discovering this suspected developmental stage of the anthrax bacillus. Koch's ability to take the giant leap from the life cycle of the anthrax bacillus to the etiology of anthrax undoubtedly depended in part upon this natural history background. The present hygienic measures against anthrax are limited to notification of the authorities, the burial of cadavers, disinfection, and quarantine of the town affected by the plague. Koch's turning point came that night when he saw spores in a slide culture and related them to the etiology of the disease. Koch moved inexorably forward, forging the bacteriological revolution that was to have such major impact on medicine and human society.
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Chapter 6 : First Recognition: Koch and Cohn
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Ferdinand Cohn was one of the first botanists in Europe to teach from living plants rather than from dried and pressed specimens. In his early years, Cohn studied algae, but by the 1860s he had turned to a study of bacteria. From careful observation of bacteria, Cohn concluded that different species of bacteria existed and that a morphological classification was possible. Cohn discussed Davaine's work on anthrax and other work that suggested that bacteria might cause contagious diseases. Realizing that Koch's work was of great medical importance, Cohn sent to the Institute of Pathology for someone to come and see Koch's cultures and observations. It was a fateful and dramatic moment, as Cohnheim was the one medical researcher who could not only appreciate the beauty of Koch's work, but could publicize Koch himself. Cohn showed that his spore-forming organism, which he named Bacillus subtilis, was resistant to boiling when spores were present, an exceedingly important discovery for the development of reproducible sterilization techniques. As Cohn's Bacillus subtilis formed spores in the manner of Koch's Bacillus anthracis, it was important to show that the disease anthrax was linked to Koch's specific organism.
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Chapter 7 : Koch's Role in the Microscope Revolution
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One of Robert Koch's main contributions was the successful adaptation of the light microscope to the study of bacteria, especially those found in diseased tissues. He was the first to use oil immersion lenses and the Abbe condenser, and he was the first to publish photomicrographs of bacteria. His research on the staining of bacteria for microscopy provided the foundation for this important topic. Much of his work was motivated by a desire to photograph bacteria through the microscope, as he realized that hand drawings were unsatisfactory for communicating the results of bacteriological investigations. His work on photomicroscopy not only forced him to improve his microscopy but also to perfect better methods of preparing specimens for microscopy. Initially, Koch used a vertical camera-microscope arrangement, as had been described by Reichardt and Sturenburg but this arrangement only permitted a magnification through the microscope of 300 X. Further magnification had to be made by enlargement of the negative, an unsatisfactory procedure. Later, Koch acquired a horizontal microscope-camera setup in which the camera, microscope, and mirror lighting arrangement were carefully aligned on an optical bench.
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Chapter 8 : Studies on Wound Infections: the Later Wollstein Years
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Throughout the period after Robert Koch's initial success with anthrax, his self-confidence increased enormously. All his spare time was now occupied with research, and he continued to show new and innovative approaches. Koch also used some o f the spleen o f the dead mouse to inoculate rabbits, which died 24 hours after inoculation. Considering Koch's later detractors, and the tremendous criticisms that he suffered, we can see here, in a nutshell, the essence of Koch's personality. Koch's work on anthrax was strongly based on the idea that a given disease was caused by a single organism. Microscopy o f wound infections was carried out by the German Edwin Klebs independently of Davaine. Building on the animal work of Davaine and the microscopic work of Klebs, Koch carried out extensive investigations at Wollstein and developed the theory that each septic condition was due to a different organism. Koch studied a wide variety of traumatic infective diseases, including tissue gangrene in mice, spreading abscess in rabbits, pyemia in rabbits, septicemia in rabbits, and erysipelas in rabbits. But the connection of Koch's work on sepsis to humans was lacking. Certainly Koch would have worked with humans if he had been in a medical center, but isolated in Wollstein, he lacked the necessary clinical material.
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Chapter 9 : On to Berlin
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It had become increasingly apparent to Koch that it would be impossible to satisfy his scientific aspirations in Wollstein. By July 1880 Koch was in Berlin, beginning an exciting new position. The letter of nomination included the names of distinguished professors of the medical faculty, as well as the Dean and the Rector of the University. After much worry about whether this was the right move, Koch agreed to take this position and moved with his family to Breslau in July 1879. In July 1880, Koch moved to Berlin, the head of a newly established laboratory for bacteriological research. When the German states were brought together by Otto von Bismarck in 1871 as the German Empire, Berlin became its capital. This was to become Robert Koch's first laboratory in Berlin. However, the position Struck had engineered at this time was primarily honorary, and Koch would still have had to practice medicine in Berlin to make ends meet. For the rest of his life, Struck took great pride in telling everyone that it was he, Struck, who had discovered Koch and brought him to Berlin.
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Chapter 10 : Koch at the Crossroads: From Lone Doctor to Group Leader
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This chapter talks about Robert Koch and his first assistants, Georg Gaffky and Friedrich Loeffler, both of whom were to become major figures in bacteriology. Loeffler had been transferred from the General Headquarters of the Army to the Gesundheitsamt a year earlier, and had worked as an assistant in the hygiene and chemistry laboratories during that time. He is best known for his discovery of the causal agent of diphtheria, Corynebocterium diphtheriae, and for his proof that the causal agent of foot-and-mouth disease was filterable, the first animal virus to be so characterized. In a short time, Koch was surrounded by an enthusiastic group o f dedicated workers. Thus, his position at the Amt brought him not only more space and time for research than he had at Wollstein, but interaction with intelligent colleagues. Koch matured rapidly in this new milieu, moving readily from lone scientist in Wollstein to group leader in Berlin. Koch also had a paper on anthrax which was partly an attack on Pasteur.
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Chapter 11 : Simple Gifts: The Plate Technique
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Perhaps Koch's greatest contribution to the development of bacteriology and microbiology as independent sciences was his introduction of a pure culture technique using solid or semi-solid media—soon known throughout the world as "Koch's plate technique" (Plattenverfahren). The basis of the plate technique is the development of isolated colonies on solid or semi-solid surfaces. Koch began the section on pure cultures with this solidly based statement: "The pure culture is the foundation for all research on infectious diseases." In his paper, Koch then turned to an explanation of the rationale for the plate technique that he had developed. Koch's work described in this paper was an amazing tour de force, one rarely duplicated in the scientific world. Koch realized immediately that the plate technique had many uses besides its value for the isolation of pure cultures. One final extension of the plate technique should be mentioned here: the development by Richard J. Petri of a special plate for agar or gelatin culture. The far-reaching implications of the Koch plate technique are obvious to all bacteriologists. When we contemplate this miracle now, we might wonder why the plate technique had not been thought of earlier. Certainly one o f the major reasons was that earlier workers lacked the will to develop new techniques. As long as one had doubts about the germ theory o f disease, there was little motivation for thinking up new techniques.
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Chapter 12 : Sterilization, Disinfection, and other Techniques
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One of the main missions of the Imperial Health Office was public health, and Robert Koch and his associates set to work enthusiastically to place various public health practices on a rational basis. Among the most important tasks was the development of methods for sterilization and disinfection. An important consideration in this discussion is the distinction between sterilization, which involves the complete killing of both spores and vegetative cells, and disinfection, in which vegetative cells are killed but spores are not necessarily all killed. Koch’s studies provided the groundwork for subsequent research on chemical disinfection. Koch’s work on chemical sterilization was important not only because it led to the discovery of new and more effective antiseptics and disinfectants, but because it provided a precise and reproducible method for studying the whole disinfection process. The practical application of heat sterilization to bacteriological technique was worked out by Robert Koch and his associates at the Imperial Health Office. The procedures for the experiments with heat could be simpler than those for chemical disinfection, since the agent did not have to be removed after treatment. After cooling, the cultures were transferred to suitable media and their viabilities determined by incubation.
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Chapter 13 : The London Meeting: Koch, Lister, and Pasteur
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In the summer of 1881, Robert Koch went as a delegate of the German government to London to attend the Seventh International Medical Congress. In London for the first time, Koch found himself surrounded by many interested workers who were following Lister's lead. Lister not only mentioned Koch in the speech he gave to the Pathology Section of the meeting, but also arranged for Koch's demonstration to be set up in Lister's own laboratory at King's College. Also present at the London Congress was Louis Pasteur, now at the height of his powers. At the London meeting, Pasteur was received everywhere with acclaim. He reported details of his fowl cholera studies, studies that were to lead him on the road to the major work of the last quarter of his life— the use of attenuation in the development of vaccines against infectious disease. Only a few days after he returned from his London triumph, Koch began his work on tuberculosis, work that was to make his name known, not only throughout the scientific world, but to the general public as well.
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Chapter 14 : World Fame: The Discovery of the Tubercle Bacillus
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Less than two weeks after Robert Koch returned from his triumphant success in London, he began his research on the etiology of tuberculosis. At the time Koch began his work, one-seventh of all reported deaths of human beings were ascribed to tuberculosis, and if one considered only the productive middle-age groups, one-third of the deaths were due to this dread disease. Tuberculosis had been recognized as a specific disease entity since antiquity. Although tuberculosis of the lungs does not seem to have been common in Egypt, pulmonary tuberculosis (also called phthisis) was well recognized by the Greeks, and extensive descriptions can be found in the writings of Hippocrates and others. Another major form of tuberculosis was subsequently recognized, miliary tuberculosis, in which the lesions are tiny nodules disseminated throughout the body. Koch's aim, from the beginning, was the demonstration of a parasite as the causal agent of tuberculosis. To this end, he employed all of the methods that he had so carefully developed over the previous six years: microscopy, staining of tissues, pure culture isolation, animal inoculation. As is now well known, Mycobacterium tuberculosis, the tubercle bacillus, is very difficult to stain with conventional bacteriological stains because of its extremely waxy nature. The properties of the tubercle bacillus make it extremely difficult to work with, and it is remarkable that Koch achieved such quick success in his experiments.
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Chapter 15 : The World Traveler: To Egypt and India in Search of Cholera
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Robert Koch was about to embark on a new venture. Cholera had broken out in Egypt and threatened to move into Europe again—it had been absent since the Hamburg epidemic of 1866. One of the most dreaded diseases of humans, cholera must not be allowed to enter Europe. His work on tuberculosis, begun only two years earlier, was set aside, and he would not return to further work on this disease until 1890 when he began his controversial work on tuberculin. The mysterious appearance and disappearance of cholera was completely unexplained, but the fear of cholera was widespread and when a new epidemic spread from India to Asia Minor and Egypt in 1883, great concern was expressed in many European countries. Extensive animal inoculation studies were carried out, using monkeys, dogs, cats, chickens, and mice, looking for a suitable animal model. In all cases in which the typical clinical symptoms of cholera were present, a characteristic bacterium was found in the tissue of the intestine. Today, more than 100 years after its etiology was explained by Robert Koch, cholera remains an important public health problem.
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Chapter 16 : The Pasteur/Koch Controversy
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Throughout most of Koch's career, his relationships with Pasteur were very poor. The reasons for this are complex and difficult to unravel; however, it is clear that the Pasteur-Koch controversy not only influenced the lives of these two outstanding scientists, but also had implications for the development of the microbial sciences. The reasons for this are complex and difficult to unravel; however, it is clear that the Pasteur-Koch controversy not only influenced the lives of these two outstanding scientists, but also had implications for the development of the microbial sciences. Indeed, even the name for the discipline is linked to the controversy: the Pasteur school preferred "microbiology" whereas the Koch school preferred "bacteriology". Evidence for the Pasteur-Koch controversy can be found in the scientific writings of these two savants and in their correspondence. The whole controversy has been masterfully outlined by Mollaret in 1983 and this paper is summarized briefly here. As discussed, Pasteur and Koch first met at London in 1881 at the International Congress of Medicine. Most of Koch's attacks on Pasteur were gratuitous, and can only be explained as the young upstart resenting being ignored by the grand master. Koch's co-workers, Loeffler and Gaffky, were even less polite in their articles published in the same volume of the Mitteilungen. The basis of the controversy between Koch's group and Pasteur was over the validity of Pasteur's method of attentuation.
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Chapter 17 : The Berlin Professor
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Robert Koch's triumph with cholera confirmed to the world that his earlier success with tuberculosis had not been an accident. He soon became one of the most illustrious lights in German science, and his methods and accomplishments attracted visitors from all over the world. Koch's postulates are essentially a series of steps or procedures that should be followed in order to prove that a specific microorganism is the causal agent of a specific infectious disease. As emphasized by Carter, Koch used different criteria for establishing causality over the course of his research, and it was not until 1884 that he published the postulates in the form we use today. A key requirement of the postulates which can often not be fulfilled is that for animal inoculation studies. Koch himself was certainly aware of the difficulties this sometimes presented. The difficulty of developing an adequate animal model to fulfill Koch's postulates is one that has plagued medical researchers ever since Koch's first work. The background of the founding of the Institute of Hygiene is interesting, since it provides insight into how the whole discipline of public health became established.
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Chapter 18 : At the Center of a Storm: Koch's Work on Tuberculin
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Up to now, bacteriology had given strong insights into the nature of infectious disease but had led to no remedies. In fact, many physicians criticized the "new bacteriology" because it had not led to any successful cures. But now bacteriology had found not only a cure, but a cure for the greatest scourge of humankind. Tuberculosis in Robert Koch's time was quite different from the disease we have today. In addition to the chronic lung infections we know, many cases of tuberculosis were rampant generalized infections of the body (miliary tuberculosis) or ugly, disfiguring skin infections, mainly around the nose and ears (lupus). Additionally, tuberculosis did not respect social or economic status, affecting rich and poor alike. Activated T cells, derived from the thymus, play a helper role in antibody formation, but also play a direct role in the destruction of cancer cells. Another important role of activated T cells is their involvement in a type of allergic response called delayed-type hypersensitivity. It is in this latter process that Koch's tuberculin played a role. Many of the symptoms of tuberculosis are a result of the delayed hypersensitivity reaction that is brought about by infection with the tubercle bacillus. What Koch found was that an extract of a pure culture of the tubercle bacillus, when injected under the skin of the guinea pig, brings about a remarkable response if the animal is infected.
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Chapter 19 : Consolidation and Transition
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Koch's discovery provided the basis for the field of cellular immunology and Behring and Kitasato's for that of humoral immunology. It is amazing to consider that both these discoveries were made in nearby laboratories in the same building on Klosterstrasse. Lister alluded to this work in the report on his visit to Koch's laboratory in the fall of 1890. Although this work was all done in Koch's institute, much of it was privately financed by Behring himself, including the purchase of the animals needed for the in vivo experiments. This work was so clear and convincing that it became the basis for regulations prepared by a government commission in which Koch participated. These regulations required the bacteriological examination of all public water supplies in Germany which used surface water, and prescribed exactly how the filters should be evaluated. It is of interest that Koch had wanted to leave work on hygiene to return to infectious disease, but he was barely established in his new institute before he was involved in one of the most important hygiene issues of the day. This work was done by Koch's assistants Fred Neufeld and August von Wassermann in goats, donkeys, and cattle, testing for the success of the immunization by subsequently injecting virulent tubercle bacilli. The details of this work are of little current scientific interest, but resulted in strained relationships between Behring and Koch for the rest of Koch's life.
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Chapter 20 : Africa Years: Robert Koch's Research in Tropical Medicine
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By 1890 the bacterial etiologies of many important infectious diseases had been determined, following the methods and procedures which Robert Koch had developed. Koch's name is well known in the annals of tropical diseases. He made many important contributions to the study of malaria, sleeping sickness, and numerous viral diseases of veterinary interest. The only organisms ever named for Koch were protozoa: a trypanosome that was thought to be the cause of Rhodesian red water disease of cattle, Theileria kochi (the name was later changed), and an amoeba that was thought to be the cause of simian malaria, Haemamoeba kochi. Koch developed methods for the control of several important cattle diseases in Africa, and his services were widely sought by African governments. Doing bacteriology in a primitive field setting is always a challenge. Although Koch had previous experience with primitive conditions when studying cholera in India, the facilities in Calcutta were actually palatial compared to what could be obtained in South Africa. In 1897, the same year that Koch was in Africa and India, Ronald Ross was carrying out his epochal work on malaria in Calcutta, proving that the parasite is transmitted by the mosquito. This work was to have far reaching consequences for the control of malaria.
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Chapter 21 : The World Tour: Koch in America and Japan
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This chapter talks about Koch’s trip to America and Japan. A celebration was held in honor o f the 25th anniversary of the announcement o f Koch's discovery of the tubercle bacillus. This inspired the establishment o f the Robert Koch Foundation for the Conquest o f Tuberculosis. A commission of noted German health officers and doctors was established, and a goal was set to collect a large sum of money. An international fund-raising drive was initiated, the prospectus noting how appropriate it was that the fund was to be named in honor of Robert Koch, "one of the greatest researchers of all times." Robert Koch’s goal in the United States was primarily to visit his brothers who had left Germany years earlier and settled in the Midwest, and then continue across the country to San Francisco, where he could get a steamer to Japan. After Japan, his original intention was to return home to Europe by way of China, thus having travelled completely around the world. Koch was naturally interested in the manner of operation of the New York City Department of Health. He had told the New York Times reporter, perhaps tactlessly, that his main scientific interest was Japan rather than the United States. Koch's influence in America was virtually eliminated, as the U.S. medical and public health establishment proceeded to solidify their agenda for the control of infectious disease. One of the bulwarks of this agenda was the universal pasteurization of milk.
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Chapter 22 : An Assessment of Koch and His Work
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Robert Koch was one of the most influential and dedicated medical researchers of the nineteenth century. It can almost be said that Koch created the field of bacteriology. Koch's influence on medical microbiology can be most effectively demonstrated by reference to the table which summarizes the fruits of Koch's concepts and methods. It is still inconceivable that it took Koch only nine months to detect, isolate, and characterize the tubercle bacillus. The slow-growing tubercle bacillus presented numerous experimental difficulties, which Koch overcame in masterful fashion. The two discoveries, the tubercle bacillus and the comma bacillus, coming so quickly one after the other, established Koch's reputation for all time. A Koch myth developed: the great Koch could do no wrong. Advances in food and water bacteriology were built on the foundations which Koch laid. Koch postulated: The suspected pathogen must he constantly present when the disease is present can only be fulfilled by means of microscopic pathology. It was left to others, much later, to explain the Koch phenomenon (as it was called) and assess its significance for infection and immunity. Koch's story can be an inspiration to all who are fascinated by the interplay of science and medicine. In Koch's day, bacteriology was just such an off-beat field. It has been said that science continually opens up new fields to view. Many new fields, whatever they may be, await the coming generations of Robert Kochs!
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