Koch, Heinrich Hermann Robert

(b, Clausthal, Oberharz, Germany, 11 December 1843; d. Baden-Baden, Germany, 27 May 1910)

bacteriology, hygiene, tropical medicine.

Many of the basic Principles and techniques of modern bacteriology were adapted or devised by Koch, who therefore is often regarded as the chief founder of that science. His isolation of the causal agents of anthrax, tuberculosis, and cholera brought him worldwide acclaim as well as leadership of the German school of bacteriology. Directly or indirectly he influenced authorities in many countries to introduce public health legislation based on knowledge of the microbic origin of various infections, and he stimulated more enlightened popular attitudes toward hygienic and immunologic measures for controlling such diseases.

Robert was the third son of Hermann Koch, a third-generation mining official, and his wife, Mathilde Julie Henriette Biewend, daughter of an iron-mine inspector. The parents were blood relatives, Mathilde being her husband’s grandniece. They were Lutherans and natives of an old miuntain town of some 10,000 inhabitants, situated about fifty miles south of Hannover. The family tree can be traced to Hermann’s grandfather, Johann Wilhelm Koch (1730-1808), a mine foreman who married the daughter of the Clausthal town clerk. Hermann Koch began his career as a miner but broadened his horizons as a young man by visiting several European countries. His wife bore him thirteen children. Two died in infancy, leaving Robert with six brothers and two sisters younger than himself and two elder brothers. When the boy was about ten years old, his father became overseer of all local mines and acquired the title of Bergrat. Industrious, methodical, and dutiful, he encouraged in Robert a desire for travel and respect for nature’s beauties and wonders.

Management of the large household devolved upon Mathilde Koch, an industrious, thrifty, and selfless woman who promoted a harmonious, untrammeled atmosphere in which the children became self-reliant and polished each other’s manners. Particularly fond of animals and flowers, she fostered similar sentiments in Robert, her favorite child. Knowledge of plant and animal life was also stimulated by the maternal grandfather, a humorous, sensitive nature lover, and by his highly educated son, Eduard Biewend, who befriended Robert, conducted him frequently on natural history excursions, and imparted his wide interests in scientific subjects and the new art of photography. The boy avidly collected mosses and lichens, insects, and mineralized stones, identifying them with a lens. Later he dissected and mounted larger animals and prepared their skeletons.

Robert Koch taught himself to read and write before entering the local primary school in 1848. A rapid learner, he was transferred to the Clausthal Gymnasium in 1851 and headed his class four years later. Thereafter his school progress slowed, perhaps because of marked adolescent emotional turbulence, as indicated in letters collected by K. Kolle. After repeating the final grade, he graduated in 1862, with good standing in mathematics, physics, history, geography, German, and English. Despite only “satisfactory” rating in Latin, Greek, Hebrew, and French, he declared an intention to study philology; but the school principal suggested his aptitudes were for either medicine or mathematics and natural sciences. Other alternatives were apprenticeship to a shoe merchant and emigration to America. His father’s promotion to Geheimer Bergrat and improved family finances facilitated the youth’s decision to study natural sciences at Göttingen University, some fifteen miles distant, where he enrolled at Easter 1862.

After studying botany, physics, and mathematics for two semesters, Koch transferred to medicine because of a disinclination for professional teaching and the realization that natural science interests were compatible with a medical career. Several distinguished professors appreciated his unobtrusive industry and notable curiosity about vital phenomena. Many years later Koch acknowledged that his sense for scientific investigation had been awakened by the anatomist Jacob Henle, the physiologist Georg Meissner (a master of animal experimentation), and Karl Hasse, a clinician who taught him pathology and therapeutics. Especially important was his close association with Henle, whose classic essay, “Von den Miasmen und Contagien,” had appeared over twenty years before. Henle lectured only on anatomy. As Koch later emphasized, no bacteriology was taught in his student days at Göttingen; but the final section of Henle’s Handbuch der rationellen Pathologie (Brunswick, 1846-1853) reaffirms his previous convictions regarding the living nature of contagious agents. Moreover, in the early 1860’s university circles fiercely debated Louis Pasteur’s assertions about the specific fermentative properties of the lower fungi and the myth of spontaneous generation. With so promising and inquisitive a student Henle could scarcely have failed to discuss how the contagium animatum of an infective disease might be identified.

In his fifth semester Koch began a prize task set by Henle, concerning the existence and distribution of uterine nerve ganglia. He completed it during his sixth semester, while assisting Wilhelm Krause in the Pathological-Anatomical Institute. Entitled “Ueber das Vorkommen von Ganglienzellen an den Nerven des Uterus” and dedicated to his father, the report—bearing the motto “Nunquam otiosus” —won the first prize. Koch then investigated, at Meissner’s Physiological Institute, the mechanism of succinic acid development in the body and its urinary excretion. The project entailed ingestion of discomforting amounts of certain foodstuffs, such as a half-pound of butter daily for several days. Koch’s findings, entitled “Ueber das Entstehen der Bernsteinsäure im menschlichen Organismus,” appeared in 1865 in the Zeitschrift für rationelle Medizin, a journal founded by Henle. This report was accepted as his doctoral dissertation. In the final examinations at Göttingen, in January 1866, he obtained highest distinction; two months later he passed the state examination at Hannover. Upon graduating, Koch visited Berlin to attend the Charité clinics and Rudolf Virchow’s course in pathology. Finding the hospital and lectures over–crowded, he returned home after a few months and became engaged to the youngest daughter of the general superintendent of Clausthal, Emmy Adolfine Josefine Fraatz.

The next six years were very unsettled. Koch’s aspirations to become a military physician, or to see the world as a ship’s doctor, were stifled by lack of opportunities and by his fiancée’s refusal to travel abroad. In 1866 an assistantship at Hamburg General Hospital, during a cholera outbreak, familiarized him with this scourge; but since the position was unsuited to his prospective marriage, he resigned after three months. He then became assistant at an institution for retarded children in Langenhagen, a large village near Hannover where private practice was allowed, prospering sufficiently to acquire a riding horse and a large apartment and to marry Emmy Fraatz in July 1867.

Within two years Koch resigned this post because an economy drive threatened to reduce his salary. He made attempts to establish a small-town practice, mostly in the province of Posen (now Poznán, Poland). Following a brief, disappointing stay alone at Braetz, he moved with his wife to Niemegk, near Potsdam, where his only daughter, Gertrud, was born in September 1868; but the family suffered economic hardship and after ten months migrated eastward again, settling in Rakwitz. Here Koch’s quiet efficiency was recognized, his practice flourished and he became a popular figure. This idyllic interlude was interrupted by the Franco-Prussian War.

Despite severe myopia, Koch volunteered for service as a field hospital physician. He gained invaluable experience, especially while attached later to a typhoid hospital at Neufchâteau and a hospital for wounded near Orleans. Early in 1871, responding to a petition from Rakwitz citizens, he left the army and resumed practice. Shortly afterward he passed the qualifying examinations for district medical officer (Kreisphysicus) and was advised by the influential Baron von Unruhe-Bomst, an appreciative patient, to apply for a vacant position at Wollstein (now Wolsztyn, Poland). He was appointed in August 1872. For eight years the family lived happily in this lakeside town set in forested countryside. Koch became highly respected locally and started on his path to international fame.

Despite increasing professional activities, Koch found time for hobbies as well as scientific pursuits. He excavated ancient Teutonic graves in the neighborhood, developing an interest in anthropology; inquired into occupational diseases, such as lead poisoning; and intensified the studies of algae and infusoria begun at Langenhagen and Rakwitz. Because he strongly favored the parasitic over the miasmatic theory in the recurrent controversies about the etiology of infection, he extended the scale of microscopic investigations to include bacteria. The consulting area of his four-room house was divided by a curtain, and the rear part served as laboratory. Besides a good Hartnack microscope, an incubator, glass jars for mice, and sundry smaller apparatus, it contained microphotographic devices and a converted wardrobe for darkroom. At forty years of age Koch turned his attention to anthrax, then enzootic in the district.

After verifying C.-J. Davaine’s contention of ten years before, that anthrax was caused by rodlike microorganisms seen in the blood of infected sheep, Koch invented techniques for culturing them in drops of cattle blood or aqueous humor on the warm stage of his microscope, under varied conditions of moisture, temperature, and air access. He traced accurately their mode of growth and life cycle, including the phenomena of spore formation and germination, which Davaine neither observed nor suspected. Koch’s cultures developed no transitional forms or other evidence of acquired pleomorphism. Sporogenesis required adequate moisture and oxygen and temperatures above 15°C.; and whereas the bacilli were relatively short-lived, the spores withstood prolonged drying and remained infective for years. Koch showed that anthrax developed in mice only when the inoculum contained viable rods or spores of Bacillus anthracis, grown either in vitro or in infected animals. Characteristically, he sought to correlate these laboratory findings with the peculiar recurrences and seasonal incidence of anthrax, and with sound preventive measures.

Before publishing these observations, Koch sought an interview with Ferdinand Cohn, the famous botanist at Breslau (now Wroclaw, Poland), who in his pioneering Untersuchung über Bacterien (1872–1876) had stressed the fixity of bacterial species and anticipated the spore-forming properties of Bacillus anthracis. In the spring of 1876 Koch demonstrated his methods and preparations to Cohn and to the pathologist Julius Cohnheim and his assistants. After personally confirming the results, Cohn included Koch’s classic report on the etiology of anthrax in the next issue of his journal, Beiträge zur Biologie der Pflanzen. In 1877 the Beiträge contained another paper by Koch, “Verfahren zur Untersuchung, zum Conservieren und Photographieren der Bakterien.” This described techniques for dry-fixing thin films of bacterial culture on glass slides, for staining them with aniline dyes (according to information received from Carl Weigert in Breslau), and for recording their structure by microphotography. Koch used apparatus built to his own specifications, following expert advice from the physiologist Gustav Fritsch; and through extraordinary patience and ingenuity he transmuted the early inspiration from his uncle into pictures of astonishing fidelity. These clearly revealed the flagella of motile bacteria, and the morphological distinctions between harmless spirochetes in marsh water or tooth slime and those just reported by Otto Obermeier in relapsing fever.

Koch revisited Breslau in 1877 and in Cohnheim’s laboratory showed his latest findings to a group that included Paul Ehrlich and John Burdon Sanderson. He was welcomed there again in 1878; but in Berlin shortly afterward Virchow, the outstanding pathologist and quasi-miasmatist, received him ungraciously. Nevertheless, by now Koch’s self-confidence was such that in 1878 he published an aggressively critical review of Carl von Naegeli’s Die niederen Pilze in ihren Beziehungen zu den Infektionskrankheiten und der Gesundheitspflege (1877), attacking its pleomorphist doctrines. In that same year appeared Koch’s first monograph, Untersuchungen über die Aetiologie der Wundinfectionskrankheiten, an English translation of which followed in 1880.

This work reported his findings on the bacteriology of infected wounds—a problem still unsettled more than a decade after Joseph Lister introduced antisepsis. To avoid confusion from imprecise clinical terms such as “septicemia” and “pyemia” applied to human patients, Koch induced artificial infections in mice and rabbits by injecting putrid fluids. He declared that a “thoroughly satisfactory proof” of the parasitic nature of traumatic infective diseases would be forthcoming only “when the parasitic microorganisms are successfully found in all cases of the disease in question; further, when their presence is demonstrable in such numbers and distribution that all the symptoms of the disease thereby find their explanation; and finally, when for every individual traumatic infective disease, a micro-organism with well-marked morphological characters is established.” Thus he first explicitly stated the criteria implicit in Henle’s essay on contagion, which after modification became known as “Koch’s postulates.” He equipped his microscope with Ernst Abbe’s new condenser and oil-immersion system (manufactured by Carl Zeiss) so that he could detect organisms appreciably smaller than B. anthracis. Koch identified six transmissible infections, two in mice and four in rabbits, that were pathologically and bacteriologically distinctive. He deduced that human traumatic infections would prove similarly due to specitic parasites and concluded that his experiments illustrated the diversity and immutability of pathogenic bacteria. Among favorably impressed surgeons were Lister and Theodor Billroth, who thereafter strongly supported him.

Early in 1879 the Breslau medical faculty unsuccessfully petitioned the minister of public instruction (Kultus Minister) to create a professorship in hygiene for Koch in a proposed new institute. That summer, on Cohn’s urging, he was appointed city physician at Breslau; but the small salary and negligible practice made the position untenable and within three months the family was welcomed back in Wollstein. Koch’s reputation and ambitions, however, had outgrown his environment. Obligations to patients conflicted with keeping abreast of specialized literature and with conducting laboratory researches that demanded more apparatus and experimental animals than the household could accommodate. The anthrax studies required innumerable mice, in addition to guinea pigs, rabbits, frogs, dogs, a partridge, and a sparrow; and he had recently transmitted relapsing fever spirochetes to two monkeys. His wife, who had previously collected algae specimens and helped with photographic procedures, now shared with their daughter such duties as feeding animals and cleaning microscope slides: some disenchantment was understandable. In 1880, on Cohnheim’s recommendation, Koch was appointed government adviser (Regierungsrat) with the Imperial Department of Health (Kaiserlichen Reichsgesundheitsamt) in Berlin. His home henceforth was in the capital city.

The Health Department, established in 1876, occupied a former apartment house near the Charité hospital. At first Koch shared one small laboratory with his assistants, Friedrich Loeffler and George Gaffky, both army staff doctors, whose competence, industry, and loyalty eased his transition from solitary worker to team leader. Their main assignments, under the Health Department’s director, Heinrich Struck, were to develop reliable methods for isolating and cultivating pathogenic bacteria and to gather bacteriological data and establish scientific principles bearing on hygiene and public health. Koch’s disciples worked tirelessly beside him while, in Loeffler’s words, “almost daily new miracles of bacteriology displayed themselves before our astonished eyes.” As the program expanded, Ferdinand Hueppe and Bernhard Fischer were seconded from the army medical staff and chemists Georg Knorre and Bernhard Proskauer recruited. All were destined for distinguished careers, but Koch was the undisputed leader.

As publishing medium for the Health Department’s scientific findings, Struck instituted in 1881 the Mittheilungen aus dem Kaiserlichen Gesundheitsamt. In the first article, “Zur Untersuchung von Pathogenen Organismen,” Koch extended his earlier account of bacteriological methods. He stressed the importance of avoiding contamination through use of strictly sterile techniques and advocated nutrient gelatin as a solid medium that allowed individual colonies to be selected, thus ensuring pure cultures. He also specified that newly isolated pathogens should be investigated for transferability to animals, portals of entry and localizations in the host, natural habitats, and susceptibility to harmful agents. This work, illustrated with numerous microphotographs, long remained the basic instructional manual for bacteriological laboratories. Koch then studied disinfectant substances and processes, comparing their inhibitory or destructive action on certain bacterial species, mainly anthrax bacilli and spores. His declaration in “Ueber Desinfection” that carbolic acid was inferior to mercuric spray,” and the reports, written with associates, that live steam surpassed hot air in sterilizing power revolutionized hospital operating room practices.

In 1881 Koch’s preoccupation with methodology culminated and began to yield a rich harvest. In August, while attending the International Medical Congress at London, he demonstrated his pure-culture techniques in Lister’s laboratory and there met Louis Pasteur, who magnanimously termed the methods “un grand progrès.” Upon returning to Berlin, Koch launched experiments on tuberculosis, convinced of its chronic infectious nature. In six months, working alone and without hint to colleagues, he fully verified the still-disputed claims of J.-A. Villemin, J. Cohnheim, C. J. Salomonsen, H. E. von Tappeiner, and P. C. Baumgarten that the disease was transmissible. Further, a bacillus of exacting cultural and staining properties was demonstrated and isolated from various tuberculous specimens of human and animal origin; and tuberculosis was induced by inoculating several species of animals with pure cultures of this bacterium.

Identification of the tubercle bacillus was rendered exceptionally difficult by its small size and often scanty distribution, restricted stainability (due to a waxy coat), fastidious nutritional requirements, and very slow growth in vitro. Eventually Koch found it would retain alkaline methylene blue in tissues counterstained with Bismarck brown. Inconspicuous colonial growth appeared on test-tube “slopes” of heat- coagulated cattle or sheep serum during the second week of incubation at 37°C. His resolute, singlehanded ingenuity in surmounting difficulties was matched by the thoroughness and completeness of his lecture, entitled simply “Ueber Tuberculose,” delivered before the Physiological Society in Berlin on 24 March 1882—a red-letter day in bacteriological history. Although no orator, Koch presented his evidence with such logic and conviction that the audience was too spellbound to applaud or engage in official discussion. Paul Ehrlich, who later recalled that evening as his “greatest scientific event,” developed overnight an improved method of staining tubercle bacilli, which Koch adopted. These two very different characters became firm friends. Virchow, who on pathological grounds upheld belief in the nontuberculous nature of phthisis, was absent. Inter alia, Koch’s demonstrations of tubercle bacilli in the caseous material from phthisical lungs, as well as in specimens from miliary and other forms of tuber- culosis, refuted this doctrine of duality.

Within three weeks Koch’s paper appeared in the Berliner Klinische Wochenschrift, as “Die Aetiologie der Tuberculose.” Although unsurpassed in lucidity of style and directness of statement, in thoroughness and precision of experimentation, and in stringency of requiremetns for proof, the report contains some errors. For example, the granular staining displayed by many cultures was misinterpreted as sporulation. Differences between cultures of human and cattle origin were overlooked, leading Koch to assert that bovine tuberculosis is identical with human tuberculosis and thus transmissible to man—a contention he later denied. Because of the susceptibility of experimental animals to tuberculosis he modified his criteria for establishing the causal relationship of these bacteria to the disease. He stipulated that the bacilli had to be isolated from the body and “cultivated in pure culture until freed of all adherent products of disease originating in the animal organism” and that tuberculosis must be reproduced in animals injected with the isolated bacilli. This last clause in his “postulates” presented awkward obstacles when the disease in question was not transmissible to animals. The general luster of the report nevertheless remains unblemished.

Koch’s chief findings were confirmed wherever his techniques were carefully followed—in the United States, for example, by Theobald Smith and E. L. Trudeau. The demonstration of tubercle bacilli in the sputum was soon accepted as of crucial diagnostic significance, and his co-workers began investigating such problems as the disinfection of tuberculous sputum. Koch himself continued to amass evidence for converting those who clung to the belief that tuberculosis was dyscrasic rather than infective. By 1883 he had induced the disease in over 500 animals of ten species, of which more than 200 succumbed to pure cultures of the bacillus administered by various routes, and had obtained new data on the cultural properties and modes of spread of the causal bacillus. Publication of an expanded version of “Die Aetiologie der Tuberculose” in the Mittheilungen was delayed until 1884. Meanwhile, in the Deutsche medizinische Wochenschrift, Koch deplored the “incorrect and clumsy technique” and the “altogether empty literature” of those who disputed the importance of the tubercle bacillus. In 1883 he received the title Geheimer Regierungsrat.

Koch’s propensity for aggressive criticism became conspicuous in 1881, when he attacked P. G. Grawitz, a pupil of Virchow, for espousing Naegeli’s theory of the transformation of fungi and took issue, in “Zur Aetiologie des Milzbrandes,” with Hans Buchner’s and Pasteur’s researches on anthrax. Buchner allegedly produced the disease in animals with cultures derived from the hay bacillus; but Koch exposed several sources of error, including use of unsterilized blood as nutrient medium. The dispute with Pasteur was more complex, profound, and sustained, for personal jealousy and national pride aggravated their disagreements. Koch’s indictment appeared in the Mittheilungen, supplemented by separate contributions from Gaffky and Loeffler. They disparaged much of Pasteur’s four years’ work on anthrax as plagiaristic or inaccurate and impugned the purity of his cultures. Koch disputed Pasteur’s contentions that farm animals acquired the disease through mouth abrasions caused by thistle prickles and that anthrax spores were brought to the surface by earthworms.

These attacks from Berlin, and Pasteur’s sensational demonstration at Pouilly-le-Fort that sheep could be protected against virulent anthrax cultures by vaccination with attenuated strains, were reported almost simultaneously. Pasteur was unaware of the former when he met Koch two months later in London and, amid great acclaim, addressed the Medical Congress on vaccination against chicken cholera and anthrax. In September 1882, however, before the International Congress of Hygiene and Demography at Geneva, he concluded an invited address on bacterial attenuation by repudiating the “disagreeable diatribes” of Koch and his pupils and offered to enlighten anyone who shared the opinions of his “stubborn contradictors.” Responding briefly, Koch expressed disappointment at having heard nothing new, termed the occasion inappropriate for dealing with Pasteur’s attacks, and reserved his reply for medical journals. Three months later he published an acerbic critique, whose most cogent complaint was that Pasteur offered no explicit details of his method of attenuating anthrax bacilli. Koch now conceded the feasibility of attenuation but still doubted Pasteur’s immunization claims. The latter’s eloquently scornful retort took the form of a lengthy open letter to Koch dated Christmas Day 1882. The controversy flared intermittently for another five years.

These polemics and Koch’s tuberculosis researches were interrupted by the 1883 Hygiene Exhibition in Berlin, which he helped to organize. In the Health Department’s pavilion he enjoyed demonstrating bacterial preparations to many distinguished visitors, including the crown prince. A more challenging diversion was an outbreak of cholera in the Nile delta that summer. The French government, warned by Pasteur that the epidemic could invade Europe and that the cause of cholera was probably microbial, dispatched a four-man scientific mission which reached Alexandria in mid-August. Nine days later Koch arrived, heading a German government commission that included Gaffky and Fischer. Within three weeks he had observed large numbers of tiny rods in sectioned walls of the small intestines from ten autopsied cholera cases and had isolated a gelatin-liquefying organism from the intestinal contents of about twenty cholera cadavers and patients. This organism, although unassociated with other diseases, failed to induce choleraic effects when fed to or injected into monkeys, dogs, chickens, and mice. The French team, meanwhile, suffered disappointment and tragedy. Their bouillon cultures yielded a confusing assortment of intestinal bacteria from cholera victims, whose blood, however, contained suspicious bodies. These bodies proved to be merely blood platelets, as Koch later pointed out. One month after the French mission’s arrival in Egypt the epidemic had waned; but Louis Thuillier, their youngest member, contracted fatal cholera. The German commission paid appropriate homage: Koch visited the dying man and served as pallbearer.

While awaiting governmental permission to proceed to India (where cholera persisted) to continue his investigations, Koch drew attention to the regional prevalence of amoebic dysentery and various helminthic manifestations. He also reported that “Egyptian ophthalmia” included two different disease processes, one probably gonococcal and the other due to a minute organism later known as the Koch-Weeks bacillus. His interests in sanitation and in world travel were exercised by visits to quarantine stations, a pilgrim camp, and ancient monuments.

The Egyptian findings were confirmed in Bengal. Two months after arriving at Calcutta with Gaffky and Fischer, Koch had observed the same nonsporulating, comma-shaped bacillus in seventy cholera victims. Despite inability to provoke the disease therewith in experimental animals, he asserted that it was the specific cause of cholera. His final communication from India (4 March 1884) designated village ponds, used for drinking water and all domestic purposes, as sources of localized outbreaks. He had isolated cholera bacilli from one such pond. The commission returned triumphant in May. The Kaiser awarded Koch the Order of the Crown, the Reichstag voted him 100,000 marks, and the Berlin Medical Society tendered a festive banquet in his honor at which Ernst von Bergmann lavishly praised him.

Koch’s six letter-reports to the minister during the commission’s nine months abroad were supplemented in 1887 by Gaffky’s complete account of their activities, constituting volume 3 of the Health Department’s Arbeiten. At Koch’s instigation two conferences of experts considered cholera problems at the Health Department in July 1884 and May 1885, under Virchow’s chairmanship. On the first occasion Koch detailed the properties of his comma bacillus, including its susceptibility to various disinfectants and to desiccation. Max von Pettenkofer, Germany’s senior hygienist, who believed other factors besides a microbial agent governed cholera epidemics, was invited only to the five-day second conference. Koch repudiated Pettenkofer’s hazy arguments and fallacious claims with facts and straightforward logic; and he adumbrated control measures that were adopted successfully for the German empire, although not by the International Sanitary Conference at Rome in July 1885, to which he was an official delegate.

Koch’s advisory duties became very extensive. As Health Department representative on a Reichstag commission on smallpox vaccination, he vigorously opposed antivaccinationists and initiated regulations for improving calf lymph. He reported to state and municipal authorities on problems that ranged from water supply, sewage disposal, and canal purification to testing disinfection apparatus, denaturing alcohol, and reuse of cotton wool. In addition the Health Department sponsored a training course in cholera diagnosis, and visiting doctors clamored to learn the methods that yielded so many discoveries. (Between 1882 and 1884 the bacilli of swine erysipelas, glanders, and diphtheria had been isolated by Loeffler, and the typhoid bacillus by Gaffky.) At this juncture the Minister of Public Instruction, Gustav Gossler and his adviser Friedrich Althoff decided that additional institutes of hygiene should be established in Prussia. In 1885 Koch accepted the new chair of hygiene at the University of Berlin and directorship of a prospective institute, while retaining honorary membership in the Health Department. He also received the title Geheimer Medizinalrat.

After consulting Carl Flügge, director of the Hygiene Institute at Göttingen (with whom he founded and for twenty-five years coedited the Zeitschrift für Hygiene), Koch conscientiously prepared lecture courses and organized field excursions and discussion groups for students, practitioners, and public health officials. Notable assistants and trainees of this period included Carl Fraenkel, Wilhelm Dönitz, Richard Pfeiffer, and Emil von Behring from Germany; Shibasaburo Kitasato from Japan; and William Welch and Mitchell Prudden from the United States. Late in 1886, despite oppressive teaching and administrative duties in improvised quarters, Koch informed Flügge that he had resumed experimental work “with the greatest zeal” on long-term problems. Working alone and secretively, he sought a specific remedy for tuberculosis.

On 4 August 1890, at the tenth International Medical Congress in Berlin, Koch ended a pedestrian address on bacteriological research by announcing that after testing many chemicals, he had “at last hit upon a substance which has the power of preventing the growth of tubercle bacilli,” both in vitro and in vivo. Injections of the substance into guinea pigs rendered normal animals resistant to tuberculosis and arrested the generalized disease. Hopes aroused by these incomplete experiments were enhanced in mid- November, when Koch reported excellent results in clinical trials of the agent, prepared and administered by two physicians—E. Pfuhl, his son-in-law, and A. Libbertz, of the Höchst pharmaceutical firm. Emphasizing its destructive effects upon human tuberculous tissues, Koch urged caution in treating advanced pulmonary tuberculosis but asserted that early phthisis “can be cured with certainty by this remedy.” Several distinguished clinicians, including Bergmann, also issued optimistic reports.

Koch’s name was now on all lips: doctors and patients made pilgrimages to Berlin, filling hospitals, clinics, and hotels, clamoring for his “lymph.” He received the honorary freedom of Clausthal, Wollstein, and Berlin; awards from foreign rulers and societies; Pasteur’s congratulations; and the Grand Cross of the Red Eagle from the Kaiser. Minister of Public Instruction Gossler informed the Prussian legislature that Koch disclosed to him in October his discovery of a specific against tuberculosis, which he wished to investigate outside the state service. Although he had relinquished direction of the Hygiene Institute, the government intended to build hospital facilities near the Charité and to provide an adjacent bacteriological research institute which Koch would direct. Meanwhile, in the Moabit municipal hospital, 150 beds were reserved for specific treatment of tuberculous paupers under Ehrlich’s supervision. Gossler discounted rumors of exorbitant charges for injections and undertook to safeguard the remedy’s manufacture; to discourage imitations, he had persuaded Koch to postpone revealing its nature.

The government’s plan to monopolize production of Koch’s fluid was viewed unfavorably at home and abroad. Moreover, despite Ehrlich’s good results from small dosages in early phthisis, and Lister’s endorsement after visiting Berlin, mounting evidence of the drug’s toxicity—particularly Virchow’s postmortem demonstrations of intense local inflammatory reactions in treated cases—intensified demands for revelation of its nature. In January 1891, Koch published the long-awaited formula in “Fortsetzung der Mittheilungen über ein Heilmittel gegen Tuberkulose”;but the report proved anticlimactic. His definition, “a glycerine extract of pure cultures of tubercle bacilli,” lacked essential details and was somewhat misleading. Besides, although his paper correctly described the contrasting responses of normal and previously exposed guinea pigs to injections of tubercle bacilli (subsequently termed “Koch’s phenomenon”), which he claimed instigated his discovery, he attempted to explain the agent’s curative action in terms of its necrotizing rather than its allergenic properties.

Widespread doubts now arose about the remedy. Its merits were debated at length in the Berlin Medical Society, and some centers banned its use. Koch’s projected hospital and research institute seemed in jeopardy. Disturbed by these developments and also by increasing marital infelicity, he journeyed to Egypt to recover equanimity. (He had become infatuated with Hedwig Freiburg, a comely minor actress some thirty years his junior. A consequent divorce and remarriage in 1893 provoked more censure than sympathy, but the childless union lasted and was happy.) Koch stayed away from Berlin until his buildings were assured. Gossler resigned as Minister in March, having misguidedly pressed Koch to announce his discovery and having recently boasted that it was unique for a secret remedy to be “accepted by the entire world on the strength of one man’s name.” Despite the domestic scandal and professional skepticism temporarily clouding Koch’s reputation, the government felt honor-bound to support him. Althoff secured funds for converting a three-story edifice (the “Triangle”) into the Institute for Infectious Diseases, and he persuaded the city of Berlin to complete a multipavilion barrack hospital (later known as “Koch’s sheds”) accommodating over 100 patients. In the legislature Virchow protested without avail the hasty approveal fo Koch’s 20,000-mark salary as overall director and of a budget equaling the total research funds for all scientific departments at Berlin University.

In October 1891, shortly after occupying the new quarters, Koch reported certain chemical characteristics of “tuberculin.” Previous allusions to complicated methods of preparation had been misleading, for now crude tuberculin was revealed as a filtrate of tubercle bacilli grown for six to eight weeks in a glycerol-containing medium (described by E. Nocard and E. Roux in 1887) evaporated to one-tenth volume. Koch chided fellow bacteriologists for neigher following nor developing his method but did not mention the unsuccessful attempts of several French workers, and of Trudeau and others in th United States, to immuuize animals with derivatives of tubercle bacilli. Hueppe bitterly criticized his former chief for graver errors than those he had condemned unjustly in Pasteur. When others disputed Koch’s findings, Bergmann sought his autopsy records on the experimentally protected animals. These were unavailable: autopsies had not been performed.

Still undaunted, Koch and such followers as L. Brieger, F. Neufeld, and J. Petruschky endeavored to improve tuberculin’s safety and efficacy and to determine its optimal dosage. In “Ueber neue Tuberkulinpräparate” (1897), describing three new forms of tuberculin, Koch asserted that “nothing better of this kind can be produced.” Eventually the specific diagnostic value of the hypersensitive response of tuberculous patients and cattle to tuberculin injections helped to restore the prestige lost through excessive confidence in the agent’s curative powers. Koch realized that these local reactions were of different significance from the antitoxic immunity of tetanus and diphtheria, and from the specific bacteriolytic phenomenon involving V. cholerae, observed in his institute by Behring and Kitasato (1890) and by Pfeiffer (1894), respectively; but the “allergy” concept, which illuminated the connection between immune mechanisms and tuberculin hypersensitivity, was first proposed in 1906 by C. von Pirquet.

Others now working with Koch included P. Ehrlich, H. Kossel, B. Proskauer, and A. von Wasserman. Ehrlich, allowed to choose his field of work, conducted brilliant studies on active and passive immunity and was an indispensable help to Behring in producing potent antitoxins. Visitors flocked to the Institute, some attracted by the sudden fame of Behring, who, on leaving the Institute in 1894, began exploring aggressively the antitoxin treatment of tuberculosis. Unable to produce a serum effective in cattle, he developed a bewildering succession of vaccines for “Jennerization” against bovine tuberculosis. Koch, whose prime lifelong quest was tuberculosis control, considered Behring an interloper and resented this challenge to his superstar status. Their worsening relationship culminated in 1898-1899 when the Höchst Farbwerke and Behring obtained patents for two different extracts of tubercle bacilli, despite Koch’s formal opposition.

Cholera reached Hamburg in August 1892. Within ten weeks 18,000 cases occurred, including about 8,200 fatalities. Koch responded to the city’s pleas and, in collaboration with Gaffky and W. P. Dunbar, stressed early bacteriological detection and isolation of ambulant cases, disinfection of patients’ excreta, and scrupulous sanitation of water supplies. Pettenkofer disparaged these measures; and to dramatize his conviction that comma bacilli alone could not induce cholera, swallowed some freshly isolated culture. Rudolf Emmerich and a few other disciples followed his example. Two developed a choleraic syndrome; but since no experimenter died and he himself suffered only mild diarrhea, Pettenkofer claimed his theory was verified. In three subsequent papers (1893) Koch reported on the bacteriological diagnosis of cholera, the control of sand filtration of water, and the waterborne origins of the Hamburg and related Prussian epidemics. His views won widespread support, while Pettenkofer’s adherents dwindled. Berlin’s water supplies had been tested regularly at the Hygiene Institute since 1885. During and after these outbreaks, Koch’s new Institute examined countless fecal, sewage, and water samples. The undertaking verified the existence of cholera carriers and of nonpathogenic vibrios resembling V. cholerae which could be differentiated through Pfeiffer’s bacteriolytic reaction.

Koch’s tireless leadership in the cholera emergency brought him increased public responsibilities. He established stations in the Institute for Pasteurian treatment of rabies and for diphtheria antitoxin assay. The communicable diseases control law promulgated in 1900 incorporated his recommendations of the early 1890’s. Following his leprosy survey in Memel in 1896, the disease became notifiable in Prussia and a leprosarium was established. Then the Cape Colony government engaged him to investigate rinderpest, ravaging cattle north of the Orange River. His thirst for foreign travel revived, and his microbiological interests were redirected. Arriving at Kimberley in December 1896, accompanied by his wife and staff surgeon Paul Kohlstock, Koch assembled a menagerie of experimental animals and with in four months found that the infective agent was nonbacterial, transmissible by infected blood, and unattenuated by passage through animals. He achieved active immunization by inoculating susceptible cattle with a mixture of blood serum from recovered animals and virulent rinderpest-infected blood. Inoculation with bile from cattle freshly dead of the disease was even more protective. These procedures, outlined in succinct reports, were implemented by Kohlstock and veterinary officer G. Turner and further developed by W. Kolle (from the Institute), who replaced Koch after his departure for India to head a German government plague commission made up os his disciples Gaffky, Pfeiffer, G. Sticker, and A. Dieudonné.

By May 1897, when Koch reached Bombay, bubonic plague was epidemic in upper India; and other European governments had sent scientific missions. Under Gaffky’s direction the German commission had confirmed the etiologic role of the plague bacillus (discovered in 1894 by A. Yersin and by kitasato) and had launched epidemiological inquiries. Koch organized laboratory tests of Yersin’s serum and W. Haffkine’s vaccine against plague. He designated rats as plague source and urged reoriented control measures, but (overlooking the flea as vector) he presumed the reservoir to be maintained by cannibalism. Visiting the North-West Frontier Province, he and Gaffky recognized a local disease as endemic plague.

Koch left India for Dar-es-Salaam when invited to German East Africa to curb rinderpest. Instead he found two protozoan diseases—surra, a trypanosomiasis affecting horses, and Texas cattle fever, identified as a piroplasmosis by Theobald Smith. He began to study malaria and blackwater fever—soon attributing the latter to quinine intoxication—and detected an endemic plague focus at Kisiba on Lake Victoria. Returning to Berlin in May 1898, after eighteen months’ absence, Koch delivered to the German Colonial Society an address entitled “Aertzliche Beobachtungen in den Tropen.” He described four types of malaria, favored the mosquito-borne theory, compared immunity in malaria and Texas fever, and asserted that he had “pioneered new routes and set new goals in malaria research.” The various accomplishments were recounted in Reise-Berichtüber Rinderpest, Bubonenpest in Indien und Afrika… (1898).

Koch recommended to the government that further malaria studies would foster colonial development and improve military hygiene. He proposed another visit to Italy, followed by an extensive tropical expedition. That autumn, working with Pfeiffer and Kossel in the Lombardy plains, the Campagna di Roma, and other Italian malarial districts, he confirmed Ronald Ross’s discovery of the avian malaria parasite ’s life cycle. The main expedition started in April 1899, halted in Tuscany (where Koch and P. Frosch correlated mosquito activities and the incidence of estivoautumnal fever), and proceeded to Java. Although quinine had abated the disease there, Koch noted the high susceptibility of young children, particularly Europeans, and the apparent immunity of native adults in endemic areas. Orangutans and gibbons resisted experimental human malaria He found no mosquito-free localities harboring malaria and averred “no mosquitoes, no endemic malaria.”

In German New Guinea, where his wife became ill and was sent home, the disease was prevalent. Because mosquito eradication seemed hopeless, Koch evolved a control policy based on destruction of the parasite within its exclusive host. This entailed microscopic blood examinations of the population concerned, with systematic quininization of all parasite carriers until they were symptomless and relapse-free, and had negative blood films. The regimen, subsequently adopted throughout the German empire, was intrinsically handicapped by the imperfect specificity and potential toxicity of quinine; but it was successful when drug supplies and trained physicians were freely available and the population disciplined. The owner and 300 inhabitants of the Istrian islet of Brioni erected a monument to Koch for liberating them from malaria. In 1901 the Kaiser Wilhelm Academy acknowledged the value of his discoveries to military hygiene by electing him to its senate, with the rank of major general.

Koch returned to Berlin in October 1900, having spent only nine months there in four years. Pfeiffer’s loyalty as acting director could not compensate for these prolonged absences. The Institute’s transfer to planned larger quarters in north Berlin, adjoining the Rudolf Virchow Hospital, needed supervision. Indignous public health problems demanded attention. In July 1901, Koch presented to the first British Tuberculosis Congress in London an address entitled “The Fight Against Tuberculosis.” He specified sputum as main source of infection in man but cited cattle experiments (conducted with W. Schütz) that indicated human bacilli could not infect cattle. The converse possibility was so negligible that he deemed countermeasures inadvisable. Lord Lister, who chaired the meeting, disputed this “doctrine of the immunity of man to bovine tubercle.” Koch’s assertion caused consternation in Britain. Two royal commissions had declared ingestion of tuberculous matter in food to be dangerous, and milk from cows with tuberculous udders had recently been banned for human consumption. Yet in October 1902, at the International Congress on Tuberculosis in Berlin, Koch reaffirmed this position—in stark contrast with the etiological opinion he had expressed twenty years before.

Typhoid fever was prevalent in Prussia. From endemic foci serious waterborne epidemics arose, such as that involving 2,000 cases at Beuthen, Silesia, in 1887. A similar outbreak occurred in 1901 at Gelsenkirchen, in the Ruhr. Koch was requested to report on this and subsequent outbreaks in the Trier vicinity. Besides emphasizing sanitary water supplies and sewage disposal, he stressed the importance of contact infections. Key control measures were early detection and isolation of cases and “bacillary carriers,” disinfection of their excreta, and bacteriological investigation of their surroundings. This program required several new redgional laboratories, bacteriologically trained health officers, and special efforts at the Institute by W. von Drigalski and H. Conradi to improve culture media and techniques. Koch’s broad experience, thoroughness, and zealous leadership halted the epidemics and the typhoid morbidity fell.

Early in 1903 Koch and his wife departed for Bulawayo, Southern Rhodesia, accompanied by F. Neufeld and F. W. Kleine. He had been invited to investigate “Rhodesian redwater,” another cattle epizootic, a tick-borne piroplasmosis resembling Texas fever. Since he had noted the same blood parasite in East African coastal cattle, Koch termed the disease African coast fever. After painstaking field and laboratory research he recommended control measures that included immunization by repeated injections of parasite-infected blood. Similar studies on “horse-sickness” (pferdesterbe) failed to disclose a causal bacterium or protozoon, for—like rinderpest—this is a viral disease; but he could induce protection by alternately injecting serum from recovered horses and infected blood.

As his sixtieth birthday approached, Koch proposed to retire from state service. The authorities offered generous working privileges at the Institute, with appointment as consulting hygienist. On his return to Berlin in June 1904, disciples and admirers presented a Festschrift, with contributions from over forty pupils, and a marble bust. In voicing appreciation, tinged with bitterness at increasing competition and “passionate opposition,” Koch undertook to serve science as long as sterngth permitted. With Gffky, his favorite disciple and successor, he maintained an unblemished relationship to the end. Retirement was sweetened with an annual honorarium of 10,000 marks, besides the statutory pension. The Kaiser awarded him the Order of Wilhelm.

Although the battle against tuberculosis remained his prime concern, Koch spent most of the next three years in equatorial Africa. Early in 1905 he arrived at Dar-es-Salaam. On this expedition he investigated the life cycles of the piroplasmas of Coast and Texas fevers, and of sleeping sickness trypanosomes in Glossina (tsetse flies). He also showed African relapsing fever to be a spirochetosis transmitted by Ornithodoros moubata, a tick infesting caravan routes and native huts. Monkeys exposed to infected tick progeny hatched in isolation acquired the disease, indicating transovarian passage of spirochetes in the arachnid. Similar findings made independently in the Belgian Congo by J. E. Dutton and J. L. Todd had prior publication. Koch returned to Berlin the following October. Three months later, in Stockholm, he received the 1905 Nobel Prize for physiology or medicine for his work on tuberculosis. His lecture on current control measures against this disease scarcely mentioned tuberculin but reasserted that bovine bacilli were harmless to man.

In April 1906, Koch led the German Sleeping Sickness Commission, comprising M. Beck, F. W. Kleine, O. Panse, and R. Kudicke, to East Africa After visiting regional stations, Koch sent his wife home from Entebbe, to spare her the hardships and dangers of the Sesse Islands, Uganda—an area of rampant trypanosomiasis in northwestern Lake Victoria, where the expedition established straw hut head quarters and patients’ camp. They studied indefatigably all aspects of the disease, from symptomatology to laboratory diagnosis and prevention. Therapeutic trials of atoxyl indicated large doses were effectively trypanocidal; but of 1,633 patients treated, 23 became permanently blind from optic atrophy. Koch proposed some drastic alternatives, such as eliminating tsetse fly harborages through clearance of undergrowth and tree-cutting on the littoral, and exterminating crocodiles, on whose blood Glossina palpalis fed. In November 1907 he and Beck returned to Berlin: the others continued investigations.

Many honors were now bestowed on Koch. To previous awards, such as the 1901 Harben Medal and foreign membership in the Paris Academy of Sciences (he succeeded Virchow in 1902), were added in 1906 the Prussian order Pour le Mérite and—following his latest tropical exploits—the title Wirklicher Geheimer Rat with the predicate Excellenz. Early in 1908, Berlin physicians attended a festive evening to witness his receiving the first Robert Koch Medal—starting a series intended to commemorate the greatest living physicians. Proposals for a Robert Koch Foundation to combat tuberculosis won official approval, and over a million marks quickly accumulated. The Kaiser contributed 100,000 and Andrew Carnegie 500,000 marks.

Koch and his wife now embarked upon a journey planned as a restful world tour. In April the New York German Medical Society feted him at a sumptuous banquet, where he was eulogized by W. H. Welch, his best-known American disciple, and by Carnegie. After visiting his brothers and other relatives in Chicago and St. Louis, Koch traveled via Honolulu to Japan, to be welcomed with solemn honors by Kitasato, presented to the mikado, and escorted like a demigod around the country. This idyll was disrupted by instructions to lead Germany’s delegates to the Sixth International Congress on Tuberculosis at Washington, D.C., at the end of September. Koch gave an address entitled “The Relationship Between Human and Cattle Tuberculosis.” After belatedly acknowledging that Theobald Smith (who was present) had first drawn attention to differences between human and bovine tubercle bacilli, he again defended his entrenched position, somewhat equivocally. He disputed some key findings on the potential dangers of the bovine bacillus to man, documented in the very thorough report of the royal commission (1904) appointed after the 1901 London Congress. An informal conference to resolve these issues was held in camera a few days later under the chairmanship of Hermann Biggs, whose antituberculosis program for New York City had been praised by Koch. However, the latter’s intransigence frustrated this attempt by leading international experts to reach common ground with him.

The remainder of Koch’s life was devted to tuberculosis control. He worked daily at the Institute, supervising production and clinical trials of new tuberculins. In 1910 earlier intimations of cardiac trouble became insistent. On April 9, three nights after lecturing on the epidemiology of tuberculosis before the Berlin Academy of Sciences, he suffered a severe anginal attack. He failed to recuperate and died peacefully in his chair at a sanatorium. His ashes were deposited in a mausoleum at the Institute, which the Kaiser ordered named after Robert Koch; a shrine was dedicated to him in Japan; and Metchni–koff brought from the Pasteur Institute a plaque of gilded laurel and palm.

The former Kreisphysicus of Wollstein was ranked by Ehrlich among “the few princes of medical science”; and Theobald Smith—not given to loose praise—called him “the master of us all in bacteriology”. Such tributes were evoked by a remarkable combination of qualities—extraordinarily methodical technique, dogged perseverance in verifying theories and fearless logic in applying findings, and tireless industry. “Nicht locker lassen” (don”t let up) was a favorite exhortation to himself and associates. These characteristics emerged at a crucial time, as Koch modestly admitted in New York in 1908: “I have worked as hard as I could and have fulfilled my duty and obligations. If the success really was greater than is usually the case, the reason for it is ... that in my wanderings through the medical field I came upon regions where gold was still lying by the wayside”. Considering how much territory he prospected, the true gold was seldom confused with base metals.

Koch was thoroughly German, a senior civil servant and government consultant, and accustomed to assistants with military background. His consequent hierarchical concepts and attitudes partly account for such faults attributed to him as pugnacity, arrogance, failure to acknowledge borrowed ideas or to give credit where due, and reluctance to admit mistakes. He was also accused of self–interest, particularly in connection with his sojourns abroad. These doubtless satisfied his yearnings for travel, furnished escape from social disapproval in the capital, and offered fieldwork opportunities in beguiling environments where his wide knowledge of botany and zoology could be fully exercised. Never–theless, he wore himself out in the imperial service, helping to elucidate intricate medical and veterinary mysteries in a period of national rivalries so intense that his verdict was necessary to stimulate government action on public health issues.

Koch was liable to be suspicious and aloof with strangers; but to friends and colleagues he was kind and considerate, and with his daughter he remained on affectionate terms. In congenial company he reminisced entertainingly, revealing the wide scope of his secondary interests. These ranged from the arts to astronomy and mathematics; from anthropology, ethnology, and geography to the dilemmas of missionaries on furlough. He was a great admirer of Goethe and addicted to chess. Although unattracted by didactic lecturing, on special occasions he enjoyed the role of praeceptor mundi. An unfortunate tendency to use the pen as sword and cudgel sometimes marred the lucidity and persuasiveness of his earlier writings.

Koch expressed his career’s basic motivation in his first paper on tuberculosis: “I have undertaken my investigations in the interests of public health and I hope the greatest benefits will accrue therefrom”. Less impersonal compassion was displayed in his determination to maintain contacts with patients and in his continuing quests for specific remedies—diphtheria antitoxin, tuberculin, quinine, and atoxyl. In disclosing the causes of disease and expounding the means of prevention, Robert Koch at his best was unexcelled. The Faustian weaknesses and perplexities he carried do not diminish the lasting benefits that his aspirations bestowed upon mankind.

BIBLIOGRAPHY

I. Original Works. The only ed. of Koch’s collected works is Gesammelte Werke von Robert Koch, 2 vols. in 3 pts. J. Schwalbe, ed., in association with G. Gaffky and E. Pfuhl (Leipzig, 1912), containing repros. of 99 of his published monographs and scientific papers, as well as 92 previously unpublished reports to national, state, and municipal authorities. Vol. I includes his early classic reports on anthrax, wound infections, disinfection, and methods of isolating bacteria, and 18 papers on tuberculosis that appeared between 1882 and 1910. Vol. II, pt. 1, contains 9 publications on cholera and 30 on tropical diseases, chiefly malaria and sleeping sickness. Among the reports to governments in vol. II, pt. 2, 53 deal with zoonoses, acute infectious diseases (including cholera and typhoid fever), and tropical diseases; 8 with tuberculosis; 5 with vaccination regulations and procedures; 14 with sewage disposal and water supplies; and 12 with miscel– laneous topics, ranging from the denaturing of alcohol to smoke nuisances. The entire text is German, except for two short articles in English. A few additional addresses and reports first appeared in English, and several others were translated and republished in English journals and texts. Some of his best–known articles were also translated into French, Italian, and other languages. A detailed bibliography of 80 items in Medical Classics,2 (1937-1938), 720- 731, has many minor inaccuracies and lacks several publications reproduced in Gesammelte Werke but includes some unimportant works omitted from the latter. Appended to the obituary by W. W. Ford (see below) is a list of 61 of Koch’s chief publications.

Monographs by Koch include Untersuchungen über die Aetiologe der Wundinfectionskrankheiten (Leipzig, 1878), trans, by W. W. Cheyne as Investigations Into the Etiology of Traumatic Infective Diseases (London, 1880); Die Cholera auf ihren neuesten Standpunkte (Berlin, 1886); Bericht über die im hygienischen Laboratorium der Universität Berlin ausgeführten Untersuchungen des Berliner Leitungs–wassers in der Zeit vom 1.Juni 1885 bis I. April 1886 (Berlin, 1887); Die Bekämpfung der Infektiomkrankheiten, insbesondere der Kriegsseuchen (Berlin, 1888); Reise–Berichte über Renderpets, Bubonenpest in Indien und Afrika, Tsetse–oder Surrakrankheit, Texasfieber, tropische Malaria, Schwarzwassserfieber (Berlin, 1898); Interim Report on Rhodesian Redwater or African Coast Fever (Salisbury, 1903); and Bericht über die Tätigkeit der deutschen Expedition zur Erforschung der Schlafkrankheit im Jahre 1906/07 nach Ostafrika entsandten Kommission (Berlin, 1909), written with M. Beck and F. Kleine, which also appeared in Arbeiten aus dem Kaiserlichen Gesundheitsamt, 31 (1911), 1-320.

Among his more important and characteristic early works are “Ueber das Vorkommen von Ganglienzellen an den Nerven des Uterus”, prize dissertation, Medical Faculty (Göttingen, 1865); “Ueber das Entstehen der Bernsteinsäure im menschlichen Organismus”, in Zeitschrift für rationelle Medizin, 3rd ser., 24 (1865), 264-274, published while he was still a medical student; “Die Aetiologie der Milzbrand–Krankhiet, begründet auf die Entwicklungsgeschichte des Bacillus Anthracis”, in Beitage zur Biologie der Pflanzen,2 (1876), 277-311, repro. in Karl Sudhoff’s Klassiker der Medizin, no. 9 (1910), trans. as “The Etiology of Anthrax, Based on the Ontogeny of the Anthrax Bacillus” in Medical Classics,2 (1937-1938), 787-820, and abstr. as “The Etiology of Anthrax, Based on the Life History of Bacillus Anthracis,” in Milestones in Microbiology, T. Brock, ed. (Englewood Cliffs, N.J., 1961), pp. 89-95; and “Entgegnung auf den von Dr. Grawitz in der Berliner medizinischen Gesellschaft gehaltenen Vortrag iiber die Anpassungstheorie der Schimmelpilze,” in Berliner Klinische Wochenschrift,18 (1881), 769-774.

Koch’s fundamental contributions to bacteriological techniques are in “Verfahren zur Untersuchung, zum Conservieren und Photographieren der Bakterien,” in Beiträge zur Biologie der Pflanzen,2 (1877), 399-434, trans. and abstr. as “Methods for Studying, Preserving, and Photographing Bacteria” in Microbilogy: Historical Contributions from 1776 to 1908, R. N. Doetsch, Jr., ed, (New Brunswick, N.J., 1960), pp.67-73; Zur Untersuchung von pathogenen Organismen,” in Mittheilungen aus dem Kaiserlichen Gesundheitsamt,1 (1881), 1-48, trans by V. Horsley as “On the Investigation of Pathogenic Organisms,”in Microparasites in Disease. Selected Essays, W. W. Cheyne, ed. (London, 1886), pp.3-64, and abstr. by T. Brock as “Methods for the Study of Pathogenic Organisms,” in Milestones in Microbiology, pp. 101-108; “Ueber die niuen Untersuchungsmethoden zum Nachweis der Mikro–organismen in Boden, Luft and Wasser,” in Aerztliches Vereinblatt für Deutschland, no.237 (1883), 244-250, trans.by R. N. Doetsch, Jr., in Microbiology: Historical Contributions from 1776 to 1908, pp. 122-131.

With associates Koch published a series of papers on disinfection, including “Ueber Desinfection,” in Mittheilungen aus dem Kaiserlichen Gesundheitsamt,1 (1881), 234-282; “Untersuchungen über die Desinfection mit heisser Luft.” ibid., 301-321, written with G. Wolffhügel; and “Versuche uber die Vermerthbarkeit heisser Wasserdämpfe zu Desinfectinszwecken,” ibid., 322-340, written with G. Gaffky and F. Loeffler. These were trans. and abstr. by B. A. Whitelegge in Microparasites in Disease. Selected Essays, as “On Disinfection,” pp.493-518, “Disinfection by Hot Air,” pp.519-525, and “Disinfection by Steam.” pp.526-533.

Koch’s dispute with pasteur over anthrax is covered in “Zur Aetiologie des Milzbrandes,” in Mitthelilungen aus dem Kaiserlichen Gesundheitsamt,1 (1881), 49-79; Ueber die Milzbrandimpfung. Eine Entgegnung auf den von Pasteur in Genf gehaltenen Vortrag (Leipzig, 1882); “Experimentelle Studien über die künstlliche Abschwachung der Milzbrand–bazillen undMilzbrandinfection durch Fütterung,” in Mittheilungen aus dem Kaiserlichen Gesundheitsamt,2 (1884), 147-181, written with G. Gaffky and F. Loeffler; and “Ueber die Pasteurschen Milzbrandimpfungen,” in Deutsche medizinische Wochenschrift,13 (1887), 722.

His pioneer report,“Die Aetiologie der Tuberculose,” in Berliner klinische Wochenschrift,19 (1882), 221-230, trans. by B. Pinner and M. Pinner, appears as “The Aetiology of Tuberculosis,” with foreword by A. K. Krause, in American Review of Tuberculosis,25 (1932), 285-323, and as a pamphlet published by the National Tuberculosis Association (New York, 1932). Another version of this report appears in Medical Classics,2 (1937-1938), 853-880, trans. by W. de Rouville. There followed “Kritische Besprechung der gegen die Bedeutung der Tuberkelbazillen gerichteten Publicationen.” in Deutsche medizinische Wochenschrift,9 (1883), 137-141; and “Die Aetiologie der Tuberkulose,” in Mittheilungen aus dem Kaiserlichen Gesundheitsamt,2 (1884), 1-88, trans. by S. Boyd as “The Etiology of Tuberculosis,” in Microparasites in Disease, pp. 67-201, and abstr. in H. A. Lechevalier and M. Solotorovsky, Three Centuries of Microbiology (New York, 1965), pp. 69-79.

His chief earlier works on cholera are “Cholera–Berichte aus Egypten und Indien,” in Deutsche Vierteljahrsschrift für öffentliche Gesundheitspflege,16 (1884), 493-515; “Confernz zur Erorterung der Cholerafrage am 26. Juli 1884,” in Berliner Klinische Wochenschrift,21 (1884), 478-483, 493-503; (trans. by G. L. Laycock in Microparasites in Disease. Selected Essays, pp.327-369), followed by discussion, pp. 509-521; “Ueber die Cholerabakterien,” in Deutsche mediiznische Wochenschrift,10 (1884), 725-728; “Conferenz zur Erörterug der Cholerafrage. (Zweites Jahr),” ibid., 11 (1885), 1-60, of which Koch’s opening address, pp.1-8, at the Second Conference on Cholera, appears in part trans. by G. L. Laycock in microparasites in Disease, pp.370-384, and also trans. in full as “Further Researches on Cholera,” in British Medical Journal (1886), 1, 6-8, 62-66.

Koch’s first paper on tuberculin was “Ueber bakteriologische Forschung,” in Verhandlungen des X. internationalen medizinische Kongresses, I (Berlin, 1890), 35-47, trans. as “An Address on Bacterological Research,” in British Medical Journal (1890), 2 380-383. Three other papers—“Weitere Mittheilungen uber ein Heilmittel gegen Tuber – kulose,” in Deutsche medizinische Wochenschrift16 (1890) 1029-1032; “Fortsetzung der Mittheilungen uber ein Heil– mittel gegen Tuberkulose,” ibid.,17 (1891), 101; and “Weitere Mittheilungen über das Tuberkulin,” ibid., 1189-1192—are repro.in Sudhoff’s Klassiker der Medizin, no. 19 (Leikpzig, 1912), and are also abstr. and trans. as “A Further Communication on a Remedy for Tuberculosis,” in British Medical Journal (1890), 2 1193-1195; (1891), 1 , 125-127; and (1891), 2 966-968. For comments on some of the issues involved see “Correspondence From Berlin,” in British Medical Journal (1890), 2 1197-1198, 1327- 1328; (1891), 1, 1096-1097; and editorial, ibid. (1891), 2, 954-955. His last report in this field was “Ueber neue Tuberkulinpräparate,” in Deutsche medizinische Wochenschrift,23 (1897), 209-213.

The later reports on cholera, following the Hamburg epidemic of 1892, include “Ueber den augenblicklichen Stand der bakteriologischen Choleradiagnose,” in Zeitschrift für Hygiene und Infektionskrankheiten,14 (1893), 319-338: “Wasserfiltration und Cholera,” ibid., 393-426; and “Die Cholera in Deutschland während des Winters 1892 bis 1893,” ibid.,15 (1893), 89-165. These appear tran., respectively, in Practitioner,51 (1893) 466-476; ibid., 146-160. 218-240; and Lancet (1893), 2, 828-830, 891. The three reports wre repub. in book form as Professor Koch on Cholera, trans. by G. Duncan (Edinburgh, 1894).

Koch’s views on the innocuousness of bovine tuberculosis to man began with “The Fight Against Tuberculosis in the Light of Experience Gained in the Successful Combat of other Infectious Diseases,” in British Medical Journal (1901), 2, 189-193, and with slightly modified title in Journal of State Medicine,9 (1901), 441-457. The German version appeared later as “Die Bekämpfung der Tuber– kulose unter Berücksichtigung der Erfahrungen, welche bei der erfolgreichen Bekämpfung anderer Infektions–Krankheiten gemacht sind,” in Deutsche Mediznische Wochenschrift,27 (1901), 549-554. His opinions were reiterated in “Uebertragbarkeit der Rindertuberkulose auf den Menschen,” ibid.,28 (1902), 857-862, trans. as “The Transference of Bovine Tuberculosis to Man,” in British Medical Journal (1902), 2, 1885-1889; and again in “The Relations of Human and Bovine tuberculosis, to Man,” in Journal of the American medical Association, 51 (1908), 1256-1258, with discussion pp.1258-1260, followed by “Confernce in Camera on Human and Bovine tuberculosis,” pp. 1262-1268; and in “Das Verhältnis zwischen menschenund Rindertuberkulose,” in Berliner klinische Wochenchrift,45 (1908), 2001-2003, with discussion pp.2003-2006.

Koch’s continuing interest in tuberculosis is further exemplified by “Ueber die Agglutination der Tuberkel– bazillen und über die Verwerthung dieser Agglutinaion.” in Deutsche medizinische Wochenschrift,27 (1901), 829-834; “Ueber die Immunisierung von Rindern gegen Tuberkulose,” in Zeitschrift fur Hygiene und Infektions Krankheiten,51 (1905), 300-327, written with W. Schütz, F. Neufeld, and H. Miessner; “Ueber den derzeitigen Stand der Tuberkulosebekämpfung,” Nobel prize address;, 12 Dec. 1905, in Deutsche mediznische Wochenschrift,32 (1906), 89-92, trans as “How the Fight Against Tuberculosis Now Stands,” in Lancet (1906), 1, 1449-1451; “Ueber therapeutische Verwndug von Tuberkulinl” in medizinische Woche,7 (1906), 493-496; “Zur medikamentösen Behandlung der Lungentuberkulose;” in Therapeutische Rundschau, 3 (1909), 101-103; and “Epidemiologie der tuberkulose,” in Zeitschrift fur Hygiene und Infektionkrankheiten,67 (1910), 1-18, trans. in Smithosnian Instituion Annual report for 1910, no.2049 (1911), 659-674.

The investigations of rinderpest in South Africa were reported in English to the Secretary for Agriculture, in Cape of Good Hope Agricultural Journal,10 (1897), 94-96, 96-101, 216-219, 220-221, 413-418, 418-419; as “Researches Into the Cause of Cattle Plague,” in British Medical Journal (1897) 1 1245-1246, trans of two letters to the editor; and as “Berichte des Prof. Dr. Koch uber seine in Kimberley gemachten Versuche bezüglich Bekämpfug der rinderpest,” in Centralblatt für Bakteriologie, Abt.1, 21 (1897), 526-537.

Reports on malaria included “Berchte des Geheimen Medicinalrathes Professor Dr. R. Kock über die Ergebnisse seiner Forschungen inDeutsch–Ostafrika,” in Arbeiten aus dem Kaiserlichen Gesundheitsnmt,14 (1898)—“Die Malaria,”292-304, “Das Schwarzwasserfieber,” 304-308; “Ergebnisse der wissenschaftlichen Expedition des Geheimen Medicinalrathes Professor Dr. Koch nach Italien zur Erforschung der Malaria,” in Deutsche mediznische Wochenschrift,25 (1899), 69-70. The findings of the 1899- 1900 expedition to the Dutch East Indies and New Guinea appeared in six articles, followed by a summary, in Deutsche medizinische Wochenschrift, the first being “Erste Bericht über die Thätigkeit der Malaria– expedition. Aufenthalt in Grosseto von 25. April bis 1. August 1899,” ibid25 (1899), 601-604. The final report appears as” Zusammenfassende Darstellung der Ergebnisse der Malariaexpedition,” Ibid., 781-783, 801-805. Other papers on malaria problems are “Ueber die Entwicklung der Malariaparasiten,” in Zeitschrift für Hygiene und Infektionskrankheiten,32 (1899), 1-24; “Die Bekämpfung der Malaria,” 43 (1903), 1-4; and “Address on Malaria to the Congress at Eastbourne,” in Journal of state Medcine,9 (1901), 613-625.

Koch’s extensive activities in tropical medicine are further illustrated by “Ein Versuch zur Immunisierung von Rindern gegen tsetsekrankheit (Surra),” in Deutsches Kolonialblatt, 12 (1901), 1-4; “Framboesia tropica und Tinea imbricata,”in Archiv fur Dermatologie und Syhilis,59 (1902), 3-8, “On Rhodesian Redwater or African Coast Fever,” aseries of four reports, of which the first two were published separately in Salisbury (1903) and the third in Bulawayo (1903), and also in Journal of Comparative Pathology and Therapeutics, 16 (1903), 273-280, 280-284, 390-398, and 17 (1904), 175-181. The first three reports, trans. by R. Hollandt, appear as “Ueber das Rhodesische Rotwasser oder “Afrikanische Küstenfieber,” in Archiv für wissenschaftliche und praktische Tierheilkunde, 30 (1904), 281- 319; and the foruth is included in English as “Fourth Report on African Coast Fever”, in Gesammelte Werke, II, pt, 2, 787-798. Also noteworthy are “Ueber die Trypanosomenkrankheiten”, in Deutsche medizinische Wochenschrift, 30 (1904), 1705-1711, trans. as “Remarks on Trypanosome Diseases”, in British Medical Journal (1904), 2 , 1445-1449; “Untersuchungen uber Schutimpfungen gegen Horse–Sickness (Pferdesterbe),” in Deutsches Kolonialblatt, 15 (1904), 420-424, 459-463; “vorlaufige Mittheilungen uber die Ergebnisse einer Forschungsreise nach Ostafrika”, ibid., 31 (1905), 1865-1869, trans. by P. Falcke as “Preliminary Statement on the Results of a Voyage of Investigation to East Africa”, in Journal of Tropical Medicine, 9 (1906), 43-45, 75-76, 104-105, 137- 138; “Beiträge zur Entwicklungsgeschichichte der Piroplasmen”, in Zeitschrift fur Hygiene und Ifektionskrankheiten, 54 (1906), 1-9; “Ueber afrikanischen Rekurrens”, in Berliner klinische Wochenschrift, 43 (1906), 185-194, trans. by H. T. Brooks as “African Recurrent Fever”, in Post Graduate (New York), 21 (1906), 770-789; and “ueper den bisherigen Verlauf der deutschen Expedition zur Erforschung der Schlafkrankheit im Ostafrika”, in Deutsche medizinische Wochenscrift,, 32 (1906), 1-8.

Miscellaneous publications that further illustrate the scope of Koch’s versatility include “Versuche über die Desinfection des Kiel–oder Bilgeraumes von Schiffen”, in Arbeiten aus dem Kaiserlichen Gesundheitsamt, 1 (1886), 199-221; “Beobachtungen uber Erysipel–Impfungen am Menschen”, in Zeitschrift fur Hygiene und Infektionskrankhiten, 23 (1896), 477-489, written with J. Petruschky; “Die Lepra“Erkrankungen im Kreise Memel”, in Klinisches Jahrbuch, 6 (1897), 239-253; “Ueber die Verbritung der Bubonenpest”, in Deutsche medizinische Wochenschrift, 24 (1898), 437-439; “Typhusepidemie in Gelsenkirchen. Berlin, 21. Oktober 1901”, in Gesammelte Werke, II, pt.2, 910-915; and “Berchte uber die Wertbestimmung des pariser Pesterums”, in Klinisches Jahrbuch, 9 (1902), 643-704, written with E.von Behring, R. Pfeiffer, W. Kolle, and E. Martini.

Koch’s personal scientific library of just over 300 vols. was bequeathed to the Robert Koch Institute in Berlin, where it has been kept intact. His ashes, an bust, and a memorial tablet citing his accomplishments are in a mausoleum at the Institute. In an adjacent small museum are personal memorabilia, including a few handwritten letters and photographs, a diary kept during his journey to South Africa, and a map depicting his various travel routes. there are also sample vials of tuberculin labeled by him, some early laboratory apparatus, and other relics. A collection made by H. B. Jacobs of about 60 handwritten letters from Koch to Carl Flügge, dating from 1879 to 1907, is in the Welch Library, Institute of the History of Medicine, Johns Hopkins University, Baltimore.

II. Secondary Literature.Obituraries in German include P. Ehrllich, “Robert Koch, 1843-1910”., in Frankfurter Zeittung (Erstes Morgenblatt), 54 , no. 150 (2 June 1910), 1-3, trans. by S.klein in Chicago Medical Recorder, 32 (1910), 443-450; and “Robert Kock †”, in Zeischrift für Immunitätsforschung, 6 (1910), preface; C. Fraenkel, “Robert Koch”, in Münchener medizinische Wochenschrift, 57 (1910), 1345-1349; G. Gaffky, “Gedächnisrede auf Robert Koch”, in Deutsche mediziniche Wochenschrift, 36 (1910), 2321-2324; M. Kircner, & Robert koch”, in Zeitschrift für Tuberkulose, 16 (1910), 105-114; and R. Pfeiffer, “Robert Koch †”, in Berliner Klinische Wochenschrift, 47 (1910), 1045-1048.

Obituaries in English include W. W. Ford, “The Life and Work of Robert Koch”, in Bulletin of the Johns Hopkins Hospital, 22 (1911), 415-425; S. A. Knopf, “Robert Koch (December 11, 1843-May 27, 1910). The Father of the Modern Science of Tuberculosis”, ibid., 425-428; C. J. Martin, “Robert Koch, M. D”., in British Medical Journal (1910), 1 1386-1388; and “Robert Koch, 1843-1910-, in Proceedings of the Royal Society, 83 (1910), xviii–xxiv; G. S. Woodhead, “Robert Koch”, in Journal of Pathology and Bacteriology, 15 (1911), 108-114; J. A. Wyeth “Memorial Address on Doctor Robert Koch”, in Medical Record, 79 (1911), 95-97; and the following unsigned tributes: “Robert Koch, M.D”., in British Medical Journal (1910), 1 , 1383-1386; “Professor Robert Koch”, in Lancet (1910), 1 , 1583-1588; and -Robert Koch and His Achievements”, in Journal of the American Medical Association, 54 (1910), 1872-1876.

Other references in German to Koch’s life and work are R. Bassenge, M. Beck, L. Brieger, et al., Festschrift Zum sechzigsten Geburtstage von Robert Koch (Jena, 1903), containing contributions from former colleagues and pupils; P. Boerner, “R. Koch’s Polemik gegen Buchner und Pasteur”, in Deutsche medizinische Wochenschrift, 8 (1882), 40-41; L. Brieger and F. Kraus, “Krankheitsgeschichte Robert Kochs,” ibid., 58 (1932), 508-509; W.von Drigalski, “Planmässige Seuchenbekämpfung nach Robert Koch, mit besonderer Berüksichtigung der Typhus Bekämpfung”, ibid., 503-505; and “Robert Koch und die Entwicklung der kommunalen Gesundheitspflege”, in Medizinische Welt, 6 (1932), 348-350; P. Ehrlich, “Erinnerung aus der Zeit der ätiologische Tuberculoseforschung Rober Kochs”, in Deutsche medizinische wochenscrift, 39 (1913), 2444-2446; J. Fibiger and C. O Jensen, “Untersuchungen uber die Beziehungen zwischen der Tuberkulose und den Tuberkelbacillen des Menschen und der Tuberkulsoe und den Tuberkelbacillen des rindes”, in Berliner Klinische Wochenschrift, 45 (1908), 1977-1980, 2026-2031; I. Fischer, “Robert Koch”, in Biographisches Lexikon der hervorragenden Arzte der letzten funfzig Jahre, I (Berlin–Vienna, 1932), 784-786; G. Gaffky, “Dem Andenken Robert Kochs”, in Deutsche medizinische Wochenschrift, 42 (1916), 653-655; S. Guttmann, ed., Robert Koch’s Heilmittel gegen die Tuberculose (Berlin–Leipzig, 1890); L. Haendel, “Robert Koch und das Reichsgesundheitsamt”, in Medizinische Welt, 6 (1932), 351–353; R. Harms, Robert Koch, Arzt und Forscher. Ein biographische Roman (Hamburg, 1966); B. Heymann, “Zur Fünfzig-Jahr-Feier der Entdeckung des Tuberkelbacillus,” in Klinische Wochenschrift, 12 (1932), 489–490; and Robert Koch (Leipzig, 1932), covering the period to 1882; F. Hueppe, “R. Koch’s Mittheilungen über Tuberkulin,” in Berliner klinische Wochenschrift, 28 (1891), 1121–1122; G. Jaeckel, Die Charité, 2nd ed. (Bayreuth, 1965), pp. 276– 296; J. Kathe, Robert Koch und sein Werk (Berlin, 1961); M. Kirchner, “Robert Koch,” in Meister der Heilkunde, M. Neuberger, ed., V. (Vienna–Berllin, 1924), 7–84; K. Kisskalt, “Robert Kochs Gedächtnis. Die Entdeckung des Tuberkelbazillus,” in Münchener medizinische Wochenschrift, 79 (1932), 497–501; and “Die ersten Beurteilungen Robert Kochs durch die Schule Pettenkofers,” in Archiv für Hygiene uond Bakteriologie, 112 (1934), 167–180; F. K. Kleinie, “Ein Tagebuch von Robert Koch Während seiner deutsch-ostafrikanischen Schlafkrankheitsexpedition i. J. 1906/07,” in Deutsche medizinische Wochenschrift, 50 (1924), 21–24, 55–56, 88–89 121–122, 152–153, 184– 185, 216–217, 248–249,; and “Der Anteil R. Kochs an der Erforschung tropischer Seuchen,” ibid., 58 (1932), 505–508; K. Kolle, ed., Robert Koch Briefe an Wilhelm Kolle (Stuttgart, 1959); W. Kolle, “Zur Erinnerung an Robert Koch. Gedenkrede, gehalten zur 70. Wiederkehr seines Geburtstags am 11. Dezember 1913,” in Medizinische Klinik, 9 (1913), 2137–2138, 2159-2161; “Robert Koch und das Spezifizitätsproblem,” in Deutsche medizinische Wochenschrift, 39 (1913), 2446–2448; and “Robert Koch,” in Zentralblatt für Bakteriologie, 127 (1932), 3–10; H. Kossel, “Zeitliche und örtliche Disposition obeio IOnfekotions-krankheiten im Lichte experimenteller Forschuong,” in Deutsche medizinische Wochenschrift, 39 (1913), 2448– 2450; W. Leibbrand, “Robert Koch, 1843–1910,” in Die grossen Deutschen, IV (Berliin, 1957), 93–102; F. Loeffler, “Zur Immunitätsfrage,” in Mittheilungen aus dem Kaiserliche Gesundheitsamt, 1 (1881), 137–187; and “Zum 25Jährigen Gedenktage der Entdeckung des Tuberkelbacillus,” in Deutsche medizinische Wochenschrift, 33 (1907), 449–451, 489–495; R. Maresch, N. Jagié and F. Hamburger, “Zum 24. März 1882,” in Wiener klinische Wochenschrift, 45 (1932), 417–422; P. Martell, “Roobert Koch,” in Zeitschirift für ärztliche Fortbildung, 32 (1935), 332–335; M. Miyajima, “Robert Koch in Japan,” in Deustsche medizinische Wochenschrift, 58 (1932), 509–511; B. Möllers, Dr. med. Robert Koch: Persönlichkeit und Lebenswerk, 1843–1910 (Hannover, 1950); R. Paltauf, “Robert Koch,” in Wiiener klinische Wochenschrift, 16 (1903), 1377–1381; E. Pfuhl, “Privatbriefe von Robert Koch,” in Deutsche medizinische Wochenschrift, 37 (1911), 1399–1400, 1443– 1444, 1483–185, 1524–1526; and “Robert Kochs Entwicklung zum bahnbrechenden Forscher,” ibid., 38 (1912), 1101–1102, 1148–1150, 1195–1197; L. Roudolf, “Bemerkungen zu den Forschuongsreisen Robert Kochs mit besonderer Berücksichtigung Afrikas,” ibid., 87 (1962), 1680– 1686; and “Die wissenschaftliche Bibliothek Robert Kochs,” in Zentralblatt für Bakteriologie, I. Referate, 175 (1960), 447–472; F. Sauerbruch, “Robert Koch,” in Zeitschrift für Tuberkulose, 64 (1932), 7–9; J. Schwalbe, “Robert Koch zum Gedächtnis,” in Deutsche medizinische Wochenschrift, 39 (1913), 2441; and “Die Enthüllung des Robert Koch Denkmals,” ibid., 42 (1916), 704-705; G. Seiffert, “Die Tuberkulose als übertragbare Krankheit und ihre Bekämpfung vor Robert Koch,” in Münchener medizinische wochenschrift, 79 (1932), 501-506; H. Unger, Robert Koch, Roman eines grossen Lebens (Berlin-Vienna, 1936); W. von Waldeyer-Harz, Lebensermnnerungen (Bonn, 1921), pp. 283-285; F. A. Weber, “Robert Koch und die Bekaämpfung der Tuberkulose. Zur Erinnerung an die Entdeckung des Tuberkelbazillus vor 50 Jahren,” in Zeitschrift für Tuberkulose, 64 (1932), 399-415; K. Wezel, Robert Koch (Berlin, 1912); and H. Zeiss and R. Bieling, Behring, Gestalt und Werk (Berlin, 1940).

English and French references to Koch’s life and work include E. R. Baldwin, “A Call Upon Robert Koch in His Laboratory in 1902,” in Journal of the Outdoor Life, 16 (1919), 302-303; E.von Bergmann, “Demonstration of Cases Treated by Koch’s Anti-Tubercular Liquid,” in Lancet (1890), 2 1120-1122; (1891), 1 , 50-51; L. Brown, “Robert Koch,” in Bulletin of the New York Academy of Medicine, 8 (1932), 549-584; and “Robert Koch (1843- 1910). An American Tribute,” in Annals of Medical History, n.s. 7 (1935), 99-112, 292-304, 385-401; editorial, “Koch’s Work Upon Tuberculosis, and the Present Condition of the Question,” in Science, 4 (1884), 59-61; editorial, “The Debate on Koch’s Remedy at the Berlin Medical Society,” in Lancet (1891), 1 215-217, 271-272, 328-330, 389, 450-452, 506-507, 567-568, 630-631; H. C. Ernst, “Robert Koch (1843-1910),” in Proceedings of the American Academy of Arts and Sciences, 53 (1918), 825-827; S. Flexner and J. T. Flexner, William Henry Welch and The Heroic Age of American Medicine (New York, 1941), pp. 146-149; A. P. Hitchens and M. C. Leikund, “The Introduction of Agar–Agar Into Bacteriogy,” in Journal of Bacteriology, 37 (1939), 485-493; T. James, “Professor Robert Koch in South Africa,” in South African Medical Journal, 44 (1970), 621-624; L. S. King, “Dr. Koch’s Postulates,” in Journal of the History of Medicine and Allied Sciences, 7 (1952), 350-361; A. K. Krause, “Essays on Tuberculosis. IV. The Tubercle Bacillus,” in Journal of the Outdoor Life, 15 (1918), 129-137, and “XVI. The First Experiments in Resistance. The Discovery of Tuberculin: Trudeau and Koch,” ibid., 16 (1919), 129-132, 150-152; E. Lagrange, Robert Koch: Sa vie et son oeuvre (Tours, 1938); H. R. M. Landis, “The Reception of Koch’s Discovery in the United States,” in Annals of Medical History, n.s. 4 (1932), 531-537; Sir Joseph Lister, “Koch’s Treatment of Tuberculosis,” in Lancet (1890), 2 1257-1260; E. Metchnikoff, The Founders of Modern Medicine: Pasteur, Koch. Lister, D. Berger, trans. (New York, 1939), pp. 60-75, 112-124; G. H. F. Nuttall, “Biographical Notes Bearing on Koch, Ehrlich, Behring and Loeffler, With Their Portraits and Letters From Three of Them,” in Parasitology, 16 (1924), 214- 238—“Robert Koch, 1843-1910,” pp. 214-223; L. Pasteur, “De l’atténuation des virus,” in Revue scientifique, 2nd ser., 4 (1882), 353-361, Written with C. Chamberland, E. Roux, and L. Thuillier; and “La vaccination charbonneuse. Réponse à un mémoire de M. Koch,” ibid., 5 (1883), 74-84; Sir Robert Philip,” Koch’s Discovery of the Tubercle Bacillus, Some of Its Implications and Results,” in British Medical Journal (1932), 2, 1-5; J. Plesch, Janos, the Story of a Doctor, E. Fitzgerald, trans. (London, 1947), pp. 50-51; V. Robinson, “Robert Koch,” in Pathfinders in Medicine (New York, 1929), pp. 714-746; T. Smith, “Koch’s views on the Stability of Species Among Bacteria,” in Annals of Medical History, n.s. 4 (1932), 524-530; D. A. Stewart, “The Robert Koch Anniversary—the Man and His Work,” in Canadian Medical Association Journal, 26 (1932), 475-478; E. L. Trudeau, “An Experimental Study of Preventive Inoculation in Tuberculosis,” in Medical Record, 38 (1890), 565-568;” Some Personal Reminiscences of Robert Koch’s Two Greatest Achievements in Tuberculosis,” in Journal of the Outdoor Life,7 (1910), 189-192; and An Autobiography (Philadelphia-New York, 1916), pp. 212-216; R. Virchow, “On the Action of Koch’s Remedy Upon Internal Organs in Tuberculosis,” in Lancet (1891), 1 , 130-132; M. E. M. Walker, “Robert Koch, M.D., F.R.S., 1843-1910),” i Annals of Medical History, n.s. 4 (1932), 509-523; W. Welch, “Tribute to Robert Koch,” in Journal of the Outdoor Life, 5 (1908), 165-167; and C. -E. A. Winslow, The Life of Hermann Biggs (Philadelphia, 1929), pp. 54-56, 176-180, 216-220.

Besides the 60th birthday Festschrift, various medical journals honored Koch’s work through commemorative numbers or special contributions. To celebrate the 70th anniversary of his birth, several papers on tuberculosis, by W. Kolle, H. Kossel, F. Loeffler, and others, appeared in the Deutsche medizinische Wochenschrift, 39 (1913), 2442-2466. To mark the 50th anniversary of the discovery of the tubercle bacillus many journals issued memorial numbers, including the Deutsche medizinische Wochenschrift, 58 (1932), 475-511, with contributions by W. Bulloch, W. von Drigalski, F. K. Kleine, and others; Medizinische Klinik,28 (1932), 387-424, with contributions by P. Uhlenhuth, L. Aschoff, T. Burgsch, and others; Medizinische Welt, 6 (1932), 325-364, with contributions by O. Lenz, R. Otto, R. Pfeiffer, and others; and Zeitschrift für Tuberkulose, 64 (1932), 1-126, 476-499, with 17 contributions. Some articles from these anniversary publications are cited above.

Claude E. Dolman

Koch, Robert (1843-1910)

German physician

Robert Koch pioneered principles and techniques in studying bacteria and discovered the specific agents that cause tuberculosis , cholera, and anthrax . For this he is often regarded as a founder of microbiology and public health , aiding legislation and changing prevailing attitudes about hygiene to prevent the spread of various infectious diseases. For his work on tuberculosis, he was awarded the Nobel Prize in 1905.

Robert Heinrich Hermann Koch was born in a small town near Klausthal, Hanover, Germany, to Hermann Koch, an administrator in the local mines, and Mathilde Julie Henriette Biewend, a daughter of a mine inspector. The Kochs had thirteen children, two of whom died in infancy. Robert was the third son. Both parents were industrious and ambitious. Robert's father rose in the ranks of the mining industry, becoming the overseer of all the local mines. His mother passed her love of nature on to Robert who, at an early age, collected various plants and insects.

Before starting primary school in 1848, Robert taught himself to read and write. At the top of his class during his early school years, he had to repeat his final year. Nevertheless, he graduated in 1862 with good marks in the sciences and mathematics. A university education became available to Robert when his father was once again promoted and the family's finances improved. Robert decided to study natural sciences at Göttingen University, close to his home.

After two semesters, Koch transferred his field of study to medicine. He had dreams of becoming a physician on a ship. His father had traveled widely in Europe and passed a desire for travel on to his son. Although bacteriology was not taught then at the University, Koch would later credit his interest in that field to Jacob Henle, an anatomist who had published a theory of contagion in 1840. Many ideas about contagious diseases, particularly those of chemist and microbiologist Louis Pasteur , who was challenging the prevailing myth of spontaneous generation, were still being debated in universities in the 1860s.

During Koch's fifth semester at medical school, Henle recruited him to participate in a research project on the structure of uterine nerves. The resulting essay won first prize. It was dedicated to his father and bore the Latin motto, Nunquam Otiosus,, meaning never idle. During his sixth semester, he assisted Georg Meissner at the Physiological Institute. There he studied the secretion of succinic acid in animals fed only on fat. Koch decided to experiment on himself, eating a half-pound of butter each day. After five days, however, he was so sick that he limited his study to animals. The findings of this study eventually became Koch's dissertation. In January 1866, he finished the final exams for medical school and graduated with highest distinction.

After finishing medical school, Koch held various positions; he worked as an assistant at a hospital in Hamburg, where he became familiar with cholera, and also as an assistant at a hospital for developmentally delayed children. In addition, he made several attempts to establish a private practice. In July, 1867, he married Emmy Adolfine Josephine Fraatz, a daughter of an official in his hometown. Their only child, a daughter, was born in 1868. Koch finally succeeded in establishing a practice in the small town of Rakwitz where he settled with his family.

Shortly after moving to Rakwitz, the Franco-Prussian War broke out and Koch volunteered as a field hospital physician. In 1871, the citizens of Rakwitz petitioned Koch to return to their town. He responded, leaving the army to resume his practice, but he didn't stay long. He soon took the exams to qualify for district medical officer and in August 1872 was appointed to a vacant position at Wollstein, a small town near the Polish border.

It was here that Koch's ambitions were finally able to flourish. Though he continued to see patients, Koch converted part of his office into a laboratory. He obtained a microscope and observed, at close range, the diseases his patients confronted him with.

One such disease was anthrax, which is spread from animals to humans through contaminated wool, by eating uncooked meat, or by breathing in airborne spores emanating from contaminated products. Koch examined under the microscope the blood of infected sheep and saw specific microorganisms that confirmed a thesis put forth ten years earlier by biologist C. J. Davaine that anthrax was caused by a bacillus. Koch attempted to culture (grow) these bacilli in cattle blood so he could observe their life cycle, including their formation into spores and their germination. Koch performed scrupulous research both in the laboratory and in animals before showing his work to Ferdinand Cohn, a botanist at the University of Breslau. Cohn was impressed with the work and replicated the findings in his own laboratory. He published Koch's paper in 1876.

In 1877, Koch published another paper that elucidated the techniques he had used to isolate Bacillus anthracis. He had dry-fixed bacterial cultures onto glass slides, then stained the cultures with dyes to better observe them, and photographed them through the microscope.

It was only a matter of time that Koch's research eclipsed his practice. In 1880, he accepted an appointment as a government advisor with the Imperial Department of Health in Berlin. His task was to develop methods of isolating and cultivating disease-producing bacteria and to formulate strategies for preventing their spread. In 1881 he published a report advocating the importance of pure cultures in isolating disease-causing organisms and describing in detail how to obtain them. The methods and theory espoused in this paper are still considered fundamental to the field of modern bacteriology. Four basic criteria, now known as Koch's postulates , are essential for an organism to be identified as pathogenic, or capable of causing disease. First, the organism must be found in the tissues of animals with the disease and not in disease-free animals. Second, the organism must be isolated from the diseased animal and grown in a pure culture outside the body, or in vitro. Third, the cultured organism must be able to be transferred to a healthy animal, which will subsequently show signs of infection. And fourth, the organisms must be able to be isolated from the infected animal.

While in Berlin, Koch became interested in tuberculosis, which he was convinced was infectious, and, therefore, caused by a bacterium. Several scientists had made similar claims but none had been verified. Many other scientists persisted in believing that tuberculosis was an inherited disease. In six months, Koch succeeded in isolating a bacillus from tissues of humans and animals infected with tuberculosis. In 1882, he published a paper declaring that this bacillus met his four conditions—that is, it was isolated from diseased animals, it was grown in a pure culture, it was transferred to a healthy animal who then developed the disease, and it was isolated from the animal infected by the cultured organism. When he presented his findings before the Physiological Society in Berlin on March 24, he held the audience spellbound, so logical and thorough was his delivery of this important finding. This day has come to be known as the day modern bacteriology was born.

In 1883, Koch's work on tuberculosis was interrupted by the Hygiene Exhibition in Berlin, which, as part of his duties with the health department, he helped organize. Later that year, he finally realized his dreams of travel when he was invited to head a delegation to Egypt where an outbreak of cholera had occurred. Louis Pasteur had hypothesized that cholera was caused by a microorganism; within three weeks, Koch had identified a comma-shaped organism in the intestines of people who had died of cholera. However, when testing this organism against his four postulates, he found that the disease did not spread when injected into other animals. Undeterred, Koch proceeded to India where cholera was also a growing problem. There, he succeeded in finding the same organism in the intestines of the victims of cholera, and although he was still unable to induce the disease in experimental animals, he did identify the bacillus when he examined, under the microscope, water from the ponds used for drinking water. He remained convinced that this bacillus was the cause of cholera and that the key to prevention lay in improving hygiene and sanitation.

Koch returned to Germany and from 1885–1890 was administrator and professor at Berlin University. He was highly praised for his work, though some high-ranking scientists and doctors continued to disagree with his conclusions. Koch was an adept researcher, able to support each claim with his exacting methodology. In 1890, however, Koch faltered from his usual perfectionism and announced at the International Medical Congress in Berlin that he had found an inoculum that could prevent tuberculosis. He called this agent tuberculin. People flocked to Berlin in hopes of a cure and Koch was persuaded to keep the exact formulation of tuberculin a secret, in order to discourage imitations. Although optimistic reports had come out of the clinical trials Koch had set up, it soon became clear from autopsies that tuberculin was causing severe inflammation in many patients. In January 1891, under pressure from other scientists, Koch finally published the nature of the substance, but it was an uncharacteristically vague and misleading report which came under immediate criticism from his peers.

Koch left Berlin for a time after this incident to recover from the professional setback, although the German government continued to support him throughout this time. An Institute for Infectious Diseases was established and Koch was named director. With a team of researchers, he continued his work with tuberculin, attempting to determine the ideal dose at which the agent could be the safest and most effective. The discovery that tuberculin was a valuable diagnostic tool (causing a reaction in those infected but none in those not infected), rather than a cure, helped restore Koch's reputation. In 1892, there was a cholera outbreak in Hamburg. Thousands of people died. Koch advocated strict sanitary conditions and isolation of those found to be infected with the bacillus. Germany's senior hygienist, Max von Pettenkofer, was unconvinced that the bacillus alone could cause cholera. He doubted Koch's ideas, going so far as to drink a freshly isolated culture. Several of his colleagues joined him in this demonstration. Two developed symptoms of cholera, Pettenkofer suffered from diarrhea, but no one died; Pettenkofer felt vindicated in his opposition to Koch. Nevertheless, Koch focused much of his energy on testing the water supply of Hamburg and Berlin and perfecting techniques for filtering drinking water to prevent the spread of the bacillus.

In the following years, he gave the directorship of the Institute over to one of his students so he could travel again. He went to India, New Guinea, Africa, and Italy, where he studied diseases such as the plague, malaria , rabies , and various unexplained fevers. In 1905, after returning to Berlin from Africa, he was awarded the Nobel Prize for physiology and medicine for his work on tuberculosis. Subsequently, many other honors were awarded him recognizing not only his work on tuberculosis, but his more recent research on tropical diseases, including the Prussian Order Pour le Merits in 1906 and the Robert Koch medal in 1908. The Robert Koch Medal was established to honor the greatest living physicians, and the Robert Koch Foundation, established with generous grants from the German government and from the American philanthropist, Andrew Carnegie, was founded to work toward the eradication of tuberculosis.

Meanwhile, Koch settled back into the Institute where he supervised clinical trials and production of new tuberculins. He attempted to answer, once and for all, the question of whether tuberculosis in cattle was the same disease as it was in humans. Between 1882 and 1901 he had changed his mind on this question, coming to accept that bovine tuberculosis was not a danger to humans, as he had previously thought. He presented his arguments at conferences in the United States and Britain during a time when many governments were attempting large-scale efforts to minimize the transmission of tuberculosis through limiting meat and milk.

Koch did not live to see this question answered. On April 9, 1910, three days after lecturing on tuberculosis at the Berlin Academy of Sciences, he suffered a heart attack from which he never fully recovered. He died at Baden Baden the next month at the age of 67. He was honored after death by the naming of the Institute after him. In the first paper he wrote on tuberculosis, he stated his lifelong goal, which he clearly achieved: "I have undertaken my investigations in the interests of public health and I hope the greatest benefits will accrue therefrom."

See also Bacteria and bacterial infection; History of microbiology; History of public health; Koch's postulates; Laboratory techniques in microbiology

KOCH, ROBERT

KOCH, ROBERT (1843–1910), German bacteriologist.

Heinrich Hermann Robert Koch was one of the founding fathers of medical bacteriology, a discipline that established the association of bacteria with disease. He identified a number of bacterial pathogens, devised or improved essential laboratory technologies within the field, reflected on the methodology of establishing bacterial etiologies of infectious diseases, and developed a number of practical applications.

education and early career

Koch was born 11 December 1843 into the family of a senior mining official in Clausthal, a northern German town. Six of his eight brothers emigrated from Germany, but Koch—who dreamed of emigration himself—stayed and attended the nearby University of Göttingen in 1862. What remained from his youthful dreams was a passion for travel that played an important role in the later stages of his career. Koch initially studied natural sciences, but decided on medicine in 1863 and turned out to be a gifted student. Even though Friedrich Gustav Jacob Henle (1809–1885), who had written an influential treatise on infectious diseases and their causation in 1840, was one of his teachers, it is unlikely that Koch received any inspiration for his future career during his years in Göttingen.

In 1866 he left the university, married Emmy Fraatz, and tried to establish himself as a general practitioner. After several failed attempts to find a position that satisfied his financial needs, Koch finally settled in 1872 as district physician in Pomeranian Wollstein (today Wolstyn, Poland). It seems that he started to work as a bacteriologist in 1873; the chosen object of study was anthrax, a common veterinary disease that was well researched. That this condition could be transmitted by rodshaped structures found in the blood of infected animals was widely assumed. Koch based his experiments on the microbiology of Ferdinand Julius Cohn (1828–1898), a botanist from Breslau (today Wrocław, Poland), and was able to identify these structures as Bacillus anthracis. He established its full life cycle and demonstrated its pathogenicity in animal experiments.

It is not surprising that Koch then turned to Cohn. The latter gave him an enthusiastic welcome and published Koch's paper in a journal that he edited. He also freed him intellectually from the solitude of his countryside practice and brought him into contact with the Breslau pathologist Julius Friedrich Cohnheim (1839–1884) and Carl Weigert (1845–1904), his prosector (one who performs dissections for anatomic demonstration). This opened contacts into the medical world and enabled Koch to complete his education as a medical researcher by learning up-to-date methods of experimental pathology such as the use of the microtome or staining preparations with aniline dyes.

It was on this basis that Koch from 1877 made his own contributions to methodology and technology, most notably the microphotography of bacteria. This improved technology was then tried on the pièce de résistance of pathology of the time, the etiology of septic infections, on which Koch published in 1878. He showed himself to be an ingenious animal experimenter who succeeded in taking the study of human infectious diseases away from the sickbed and into the laboratory. It was also in this context that Koch for the first time made systematic arguments about how to establish bacterial etiologies. These later became known as Koch's postulates and included the three steps of isolation, cultivation, and inoculation. However, methodology differed widely over the years, and the phrase Koch's postulates was coined by others.

In 1880 Koch took up an academic position. With Cohnheim's help he became head of the imperial health offices bacteriological laboratory and moved to Berlin. The following years were his most productive. He published on laboratory technique in "Zur Untersuchung pathogener Mikroorganismen" ("On the Study of Pathogenic Organisms"), which described his own method of producing mass pure cultures and other important work such as methods for sterilization. In the same period Koch increased the cohesiveness of his group by launching an attack on the French bacteriologist Louis Pasteur (1822–1895).

World fame came in two steps. First, on 24 March 1882 Koch presented the tubercle bacillus Mycobacterium tuberculosis as the pathogen of that condition. Even though Koch was by no means the first to advocate the idea of tuberculosis as an infectious disease, it was his bacillus that firmly established the connection of the various clinical forms of that disease and paved the way to an easy and plausible understanding of its etiology. His identification of the Vibrio cholera as the pathogen of cholera in 1884 was much less satisfying on the scientific side—it did not fulfill the standards of the postulates, and the bacterium as such had been known for decades. However, because part of the research was carried out during an expedition to Egypt and India and because the work itself represented sharp competition with a French group, it raised enormous public interest and shaped Koch's image as a crusader against plagues.

crises

The years after 1885 brought a series of crises to Koch's life and work. After a failed attempt to found and head an imperial institute for bacteriology, Koch was promoted to a professorship at Berlin University in 1885. However, this appointment had been forced on the university by the state administration and was met with stiff resistance from inside the faculty of medicine. Koch had little experience and liking for professorial obligations. Moreover, Koch had problems with his research strategies. While his early successes had largely depended on microbe hunting, it was clear that this could hardly be prolonged. Furthermore, the popular embodiment of diseases as bacteria had raised hopes of specific therapies. These hopes had remained unfulfilled, while—to make things worse—Koch's rival Pasteur had achieved a public triumph with his rabies vaccine in 1885.

Koch attempted to find a way out of this crisis by developing a remedy for tuberculosis, which became known as tuberculin. When tuberculin became available in late 1890, it produced an unprecedented euphoria, even though its composition was kept secret. Public pressure led Koch to publish a description of tuberculin, which turned out to be an extract of tuberculosis pure cultures dissolved in glycerine. It turned out that his secrecy had blocked from view his fantastic commercial plans and the fact that his views on the medicine's therapeutic qualities were highly speculative. Separation from his wife and an affair with the seventeen-year-old student of fine arts Hedwig Freiberg, who later became his second wife, damaged his reputation further, and in early summer 1891 Koch found himself in public disgrace.

Still, Prussian government officials had used the short-lived euphoria following the release of tuberculin to get a parliament decision to found a new institute for research on infectious diseases. In 1891 Koch was appointed director of what today is the Robert-Koch-Institute in Berlin, but he had to accept harsh conditions: he effectively lost the right to hold patents since he had to assign all rights to his future inventions to the Prussian state in advance.

Koch's reputation was restored by the 1892 cholera epidemic that hit Hamburg, where the municipal sanitary administration had produced a disaster. A team of hygienists headed by Koch was sent in by the imperial government to combat the epidemic. On the scientific side the cholera epidemic was a turning point for Koch, who now abandoned the rather simple models of infection that he had employed so far. Epidemiology became important for him; he began to take note of phenomena such as aclinical or subclinical infections, and a few years later put forward the concept of healthy carriers (individuals who carried a disease without showing any symptoms of it themselves), which greatly influenced infectiology and epidemiology.

Beginning in the mid 1890s, Koch focused on tropical infections of humans and animals. Such research enabled him to combine his interest in epidemiology with his lifelong passion for travel and to relaunch his old interest in etiology in research on vector borne tropical diseases. Long periods of absence from Berlin followed, during which the directorship of his institute was effectively left to others. Koch frequently worked for the British colonial office on cattle diseases, and his research on human diseases centered on the two paradigmatic diseases of tropical medicine, malaria and sleeping sickness. In the first case he focused on the developmental cycle of the pathogen, Plasmodium falciparum. In the latter case his work took a more therapeutic direction. This culminated in a large expedition from 1906 to 1907, which occurred after his early retirement in 1904. Because Koch failed to openly reveal the poor efficacy and severe side effects of atoxyl in treating sleeping sickness, this medicine became the basis of a large eradication campaign in the German colonies.

Koch received numerous honors, such as the the Nobel prize in 1905 as well as Prussia's most prestigious medal, awarded the following year. Koch died on 27 May 1910 during a stay at the south German spa of Baden-Baden.

See alsoCholera; Disease; Pasteur, Louis; Public Health; Tuberculosis.

bibliography

Primary Sources

Essays of Robert Koch. Translated by K. Codell Carter. New York, 1987.

Gesammelte Werke von Robert Koch. 2 vols. Edited by Julius Schwalbe. Leipzig, Germany, 1912.

Secondary Sources

Brock, Thomas D. Robert Koch: A Life in Medicine and Bacteriology. Madison, Wis., 1988.

Gradmann, Christoph. Krankheit im Labor: Robert Koch und die medizinische Bakteriologie. Göttingen, Germany, 2005.

Christoph Gradmann

Heinrich Hermann Robert Koch

The German physician and bacteriologist Heinrich Hermann Robert Koch (1843-1910) devised many bacteriological techniques and established the bacterial causes of a number of infectious diseases.

Robert Koch was born at Clausthal, Hanover, on Dec. 11, 1843, the third of a family of 13. He enrolled in medical classes at the University of Göttingen in 1862, and in 1866 he passed the qualifying examinations. He spent some time in clinical study in Berlin but did not wish to engage in general practice. When the Franco-Prussian War broke out in 1870, he was accepted for service in the army.

In 1872 Koch was appointed district medical officer at Wollstein. That year he began his bacteriological research with a microscope his wife gave him. Following the publication of some of his early findings, Koch was appointed to the Imperial Health Office at Berlin in 1880. In 1885 he became professor of hygiene at the University of Berlin and director of the newly founded Institute of Hygiene at the university. In 1891 the Institute for Infectious Diseases was founded for him, and he acted as director until 1904.

Foundations of Bacteriology

One of the first diseases Koch studied was anthrax, an ancient and highly fatal cattle disease. While the bacillus associated with anthrax had been identified by C. J. Davaine in 1868, no significant advances had been made in the prevention or treatment of this disease. In addition, it had been noted that cattle became infected not only from other cattle but from grazing in fields where infected cattle had been kept years before. This observation seemed to discredit the bacillus as a causative agent.

Koch, attracted by the frequency of occurrence and the unusual behavior of anthrax, set out to solve the problem. He arrived at several valid conclusions: under certain conditions the anthrax bacillus forms spores which are viable but which remain dormant for several years, thus explaining the mystery of the infected fields; the integrity of the bacillus is maintained even though the infection passes through several generations of mice; and the cattle are usually inoculated with the bacillus by eating fodder soiled with the numerous organisms in excreta of infected animals.

In arriving at these conclusions, Koch acted on certain principles that are often referred to as "Koch's postulates": to prove that an organism is the specific cause of any disease, it must be present invariably in all cases; it must be isolated in pure culture; and when a susceptible host is inoculated with a live culture, the disease must be reproduced. Koch for the first time irrefutably proved the manner in which anthrax arises and is transmitted. Thus the foundations of medical bacteriology were laid, and rational principles of hygiene and epidemiology in man and animals were established.

Studies of Tuberculosis

In 1881 Koch announced his discovery of the tubercle bacillus. He isolated the organisms from tubercular lesions and grew them successfully in pure cultures. This was a remarkable achievement at that time, for the bacillus is fastidious in its food requirements and grows very slowly. However, Koch experienced several disappointments with his studies of tuberculosis. Having found that tuberculosis in cattle was produced by an organism which differed from that of the human variety in both cultural characteristics and virulence, he formed the opinion that human tuberculosis was not transmitted to cattle, and bovine tuberculosis could not be transmitted to man. This was completely disproved by the British Royal Commission on Tuberculosis in 1911. Koch's other disappointment was associated with tuberculin, a protein component extracted from a killed culture of tubercle bacilli. It has proved a valuable diagnostic tool, as Koch suggested, but it has no effect as a curative agent, although Koch originally offered it to the public as a treatment.

Another major discovery which revolutionized bacteriology was Koch's use of culture media which could be rendered solid, for example, blood serum by heating, meat broth by adding gelatin or agar, a product derived from seaweed. The advantage of growing bacteria on solid media is that isolated colonies are obtained which often have a characteristic appearance, thereby enabling one to select pure cultures easily. Thus it can be readily understood how within some 10 years a whole series of specific pathogens— including the causal agents of cholera, typhoid fever, and diphtheria; common pyogenic bacteria which cause suppuration in wounds; and varieties of intestinal flora—were isolated by Koch and others.

Almost every medical bacteriologist of the next generation was trained by Koch. His help was constantly in demand by the governments of his and other countries with microbiological problems, human or veterinary. He was always a hygienist who never forgot the essential importance of clean air, food, water, and soil in protecting populations from infective diseases. As a pure bacteriologist, he remained unequaled. His techniques are the basis of all modern bacteriological methods. In 1905 he received the Nobel Prize. He died in Baden-Baden on May 27, 1910.

Further Reading

There are two studies of Koch in German: Karl Wezel, Robert Koch (1912), and Bruno Heymann, Robert Koch (1932). In English, he is treated at length in Paul de Kruif, Microbe Hunters (1926), and lago Galdston, Progress in Medicine: A Critical Review of the Last Hundred Years (1940). □

Koch, Heinrich Hermann Robert

Heinrich Hermann Robert Koch's (1843-1910) research helped prove French researcher Louis Pasteur's (1822-1895) theory that germs, or small microorganisms, caused diseases. Koch also worked diligently to find the causes of diseases such as cholera (a severe intestinal disease) and tuberculosis (an infectious disease of the lungs).

Early Life

One of thirteen children born to a mining engineer and his wife, Koch spent his youth in the Harz Mountains in Clausthal, Germany. During Koch's adolescent years, his father insisted he learn the shoemaker's trade. When money became available for an academic career, however, Koch entered the University of Gottingen as a student of medicine and natural science at the age of 19. He graduated in 1866.

After service as a surgeon in the Franco-Prussian War (1870-1871), Koch started a practice as a country doctor in Wollstein, what is now Wolsztyn, Poland. At this time he also began his microscopic studies of bacteria. One of Koch's most important developments was a technique to use gelatin on glass slides to produce a transparent background for examining microorganisms. Koch's techniques are still used in the study of diseases.

Koch Studies Anthrax

One of Koch's early projects was to discover the cause of anthrax, a deadly disease of cattle and sheep. For years, farmers had been confused about outbreaks of anthrax in fields where infected cattle had been removed years earlier. After isolating strains of the anthrax bacillus, Koch showed that, under certain conditions, the bacilli formed spores (a tiny reproductive body) that could remain dormant Inactive) for several years. These spores remained in infected fields and could develop into the disease-causing anthrax bacillus if conditions were right.

By the late nineteenth century, researchers such as Pasteur had put forth the germ theory of disease, but no one had been able to prove that a single identifiable microorganism was responsible for a given disease. Koch's publication of his work with the anthrax bacillus helped prove that Pasteur was right.

Koch and Cholera

In 1883 Koch turned his attention to cholera, a very infectious disease that causes often fatal cases of diarrhea. In intense competition with Pasteur (who had taken a team to Egypt), Koch also took a group of German scientists to Egypt in an attempt to win the race to isolate the causative (responsible) agent. But the epidemic in Egypt ended before Koch's research was completed. He subsequently went to India, where he was able to isolate the comma-shaped bacillus responsible for cholera, Vibrio cholerae, from samples of drinking water, food, and clothing.

The Four Postulates

Koch became famous for his discoveries in the field of bacteriology. In 1885 he was named director of the new Institute of Hygiene in Berlin, Germany. Five years later, Koch published the "Four Postulates" ("four rules") on which modern bacteriological studies have been built. The postulates are:

• The organism must be present in every case of the disease.
• The organism must be cultivated in a pure culture.
• The organism must produce the disease in a susceptible animal upon inoculation.
• The organism must produce the same disease when healthy animals are inoculated.

Tuberculosis Studies Causes Controversy

Koch also contributed to the study of tuberculosis, a disease which attacks the lungs and slowly destroys them. In 1882 he was able to isolate Mycobacterium tuberculosis, the tiny bacillus that causes tuberculosis. It was Koch's search for a cure for tuberculosis, however, that would cause him temporary shame in the eyes of his fellow researchers. He thought he had found the cure, and in 1890, under pressure from the German government, he announced that he had "at last hit upon a substance that has the power of preventing the growth of the tubercle bacillus not only in the test-tube, but in the body of an animal."

Thousands of tubercular patients rushed to Berlin for tuberculin treatment. Those inoculated (injected with the vaccine) eventually died of miliary tuberculosis, considered the worst form of the disease. Koch, who had always conducted his research in secrecy, was forced to reveal the method he used to obtained tuberculin. In his search for a cure, he had cultured tubercle bacilli, heat-killed them, and filtered off the liquid. He had hoped to develop an effective vaccine from this method. But rather than discovering the cure for tuberculosis, Koch actually had discovered the substance that is now used to diagnosis the disease.

Despite the disappointment with his tuberculosis error, Koch received the 1905 Nobel Prize for medicine for his work with tuberculosis. He died in 1910, before he or any of his German colleagues could find a cure for tuberculosis. But his achievement in proving the germ theory of disease was critical to the development of vaccines and cures for many diseases.

[See also Inoculation ]