Heinrich Hermann Robert Koch
- Koch's bacillus (Robert Koch)
- Koch's phenomenon (Robert Koch)
- Koch's postulates (Robert Koch)
- Koch's steam sterilization (Robert Koch)
- Koch-Weeks bacillus
Biography of Heinrich Hermann Robert Koch
Heinrich Hermann Robert Koch was one of the founders of the science of bacteriology. Many of the basic principles and techniques of modern bacteriology were adapted or devised by Koch. Among his important contributions were the discovery of the anthrax bacillus and its life-cycle, the discovery of the tubercle bacillus in 1882, and the cholera bacillus in 1883. He won the Nobel Prize for Physiology or Medicine in 1905.
A Young man's choice
Robert Koch was the third of thirteen children born to Hermann Koch, a third generation mining official, and his wife, Mathilde Julie Henriette Biewend, daughter of an iron-mine inspector. 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. As a boy, Robert avidly collected mosses and lichens, insects, and mineralized stones. Later he dissected and mounted larger animals and prepared their skeleton.
Robert Koch taught himself to read and write before entering the local primary school in 1848. A fast learner, he was transferred to the Klausthal Gymnasium in 1851 and headed his class four years later. He graduated in 1862, with good standing in mathematiccs, physics, history, geography, German and English. Despite only «satisfactory» rating in Latin, Greek, Hebrew, and French, he declared an intention to study philology in order to become a teacher, 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 the young man's decision to study natural sciences at Georgia Augusta Universität in Göttingen, some fifteen miles distant. He enrolled at Easter 1862.
Koch first studied botany, physics, and mathematics for two semesters, then transferred to medicine. Many years later he acknowledged that his sense for scientific investigation had been awakened by the anatomist and pathologist Friedrich Gustav Jacob Henle (1809-1885) and the physiologist Georg Meissner (1829-1905). Another teacher later mentioned by Koch was the clinician Ewald Hasse (1816-1902). Especially important was his close association with Henle, whose classic essay, Von den Miasmen und Contagien had appeared over twenty years before. As Koch later emphasized, no bacteriology was taught at Göttingen in his student days.
One of Koch’s projects in his fifth semester 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.
Young physician in war and peace
The next six years were unsettled. Kochs aspirations to become a military physician, or to see the world as a ships doctor, were stiffled by lack of opportunities and by his fiancées’s refusal to travel abroad. From 1866 Koch, aged twenty-two took his first medical job, an internship at Hamburg General Hospital (Allgemeines Krankenhaus), where a cholera epidemic familiarized him with this scourge. He then became assistant at an instituttion for retarded children - Idiotenanstalt - in Langenhagen, a large village near Hannover. At this time he married Emmy Fraatz, daughter of the Superintendant General of Clausthal. They had one child, a daughter.
After two years he resigned his post and tried to establish a small town practice in the province of Pozen (now Poznán, Poland). In 1868 he first lived for e brief period in Niemegk near Potsdam, and in 1869, settling in Rakewitz, Koch succeeded in establishing a flourishing practice and he became a popular figure. However, this idyllic interlude was interrupted by the Franco-Prussian War which began in July 1870.
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 Orléans.
In 1871 Koch passed the qualifying examinations for district medical officer (Kreisphysicus), and in August 1872 was appointed to a vacant position as district surgeon in Wollstein (now Wolsztyn, Poland), Kreis Bomst. For eight years the family lived happily in this lakeside town set in forested countryside.
Despite increasing profession activities, Koch found time for hobbies as well as scientific pursuits. He excavated ancient tutonic graves in the neighbourhood, developing an interest in anthropology; he inquired into occupational diseases, such as lead poisoning; and intensified studies of algae and infusoria begun at Langenhagen and Rakewitz. He also built a small laboratory – the rear part of his consulting room – separated by a curtain. His laboratory was equipped with a Hartnack microscope, a gift from his wife, now at last satisfied with her husband's position, for his twenty-ninth bithday. He also had a microtome and a homemade incubator and began his study of algae, switching later to pathogenic organisms. The laboratory also contained microphotographic devices and a converted wardrobe for darkroom. In this tiny, cluttered space, one of the most important discoveries in the whole science of healing was made.
In 1840 Gustav Jacob Henle had published the theory that infectious diseases were caused by living microscopic organisms. In 1850 the French veterinarian Pierre Rayer (1793-1867) reported that he had discovered anthrax bacillus in the blood of animals dying from anthrax and succeeded in transmitting it. Franz Antoine Pollender (1800-1879) in 1855 published the same discovery, based on observations he had made in 1849. It was no accident that the first pathogenic bacterium discovered was one of the largest discovered - Anthracis bacillus. Pollender had found bacilli in the blood of dead cattle.
One of the first to observe organisms in the blood of persons sufferingfrom certain diseases was the French general practitioner and parasitologist Casimir-Joseph Davaine (1812-1882). Inspired by the work of the French microbiologist Louis Pasteur (1822-1895), Davaine in 1863 showed that it was highly probable that, because the sheep did not become diseased in the absence of these rodlike bodies, anthrax was due to to the presence of such organisms in the blood. The natural history of the disease was, nevertheless, far from complete. Davaine did not even have a laboratory, he kept his experimental animals in a friend’s garden. He succeeded in demonstrating that injection of 1 millionth of a drop of infected blood caused anthrax in a cow.
It was a this point that Koch began. At that time anthrax had plagued the animals throughout the farms in Wollstein district. Koch, although he had no scientific equipment and was cut off entirely from libraries and contact with other scientific workers, embarked, in a study of this disease.
He inoculated mice, by means of home-made slivers of wood, with anthrax bacilli taken from the spleens of farm animals that had died of anthrax, and found that these mice were all killed by the bacilli, whereas mice inoculated at the same time with blood from the spleens of healthy animals did not suffer from the disease.
He cultivated the anthrax organisms in suitable media on microscopic slides, demonstrated their growth into long filaments, and discovered the formation within them of oval, translucent bodies - dormant spores. Koch found that the dried spores could remain viable for years, even under exposed conditions. This finding explained the recurrence of the disease in pastures long unused for grazing, for the spores could, under the right conditions, develop into the rod-shaped bacilli that cause
This confirmed the work of others who had shown that the disease could be transmitted by means of the blood of animals suffering from anthrax. Koch had gone farther and after plenty of experiments, he demonstrated the complete life cycle of an organism. His anthrax experiments gave the first real proof of a relation between a bacillus and a particular disease. Between 1873 and 1876 he investigated anthrax and developed techniques to view, grow, and stain organisms, and then photographed them.
The botanist who helped this village doctor, Robert Koch
Before publishing his observations on the anthrax life cycle, Koch sought an interviw with Ferdiand Cohn (1828-1898), 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 famous pathologist Julius Cohnheim (1839-1884) and his assistants. Julius Cohnheim was deeply impressed by Koch’s presentation:. «It leaves nothing more to be proved,» he said. «I regard it as the greatest discovery ever made with bacteria and I believe that this is not the last time that this young Robert Koch will surprise and shape us by the brilliance of his investigations.» Cohn was also very much impressed and generously helped to prepare the engraving for Koch’s epochal paper, which he also published in his journal Beiträge zur Buologie der Pflanzen.
In 1872 one of Cohn’spupils, the physician and mycologist Joseph Schroeter (1837-1894), had found that chromogenic (colour-forming) bacteria would grow on such solid substrates as potato, coagulated egg white, meat, and bread and that these colonies wer capable of forming new colonies of the same colour, consisting of organisms of the same type. This was the starting point of Koch’s pure-culture techniques, which he worked out a few years later. That a disease organism might be cultured outside the body was a concept introduced by Louis Pasteur, but the pure-culture techniques for doing so were perfected by Koch, whose precise and ingenious experiments demonstrated the complete life cycle of an important organism. His anthrax work afforded for the first time convincing proof of the definite causal relation of a particular bacillus to a particular disease.
The great bacteriologist
In 1877 Koch published an important paper on the investigation, preservation, and photography of bacteria. His work was illustrated by superb photomicrographs. In this paper he described his method of preparing thin layers og bacteria on glass slides and fixing them by gentle heat. Koch also invented the apparatus and the procedure for the very useful drop technique, whereby microorganisms could be cultured in a drop of nutrient solution on the underside of a glass slide.
Koch revisited Breslau in 1877 and in Cohnheim’s laboratory showed his latest findings to a group that included Paul Ehrlich (1854-1915) and the English physician John Burdon Sanderson (1828-1906). He was welcomed there again in 1878.
To gain support for his work, Koch decided to approach Rudolf Virchow, the celebrated chief pathologist at the Berlin Charité Hospital, distinguished for his cell theory and pathologic studies of disease. Koch knew that a benediction from Virchow could make his career. But the extremely busy and peppery Virchow had also been known to ruin careers. A former student, anxious to finish his examination, once caught Virchow, dressed in tails, about to rush off to a session of the Berlin City Council. The candidate was invited to join the famous man in his coach, where Virchow proceeded to quiz him. After a ride along Unter den Linden, they reached the Brandenburg Gate. Here Virchow served the student an abrupt notice: "Please get out, you failed."
Koch did no better. He arrived in Berlin on an unbearably hot day. Virchow was in a bad temper, though even in the best of humors he was highly skeptical of bacteriologic claims. As Koch waited in suspense, the pathologist turned over a few pages of the anthrax manuscript, then muttered, "The whole thing seems highly improbable."
However, Koch was now a man of self-confidence. He spent the evening in a music hall before returning to his laboratory in Wollstein, and in 1878 he published an aggressively critical review of Carl von Naegeli’s Die niederen Pilze in ihren Beziehungen zu den Infektionskrankheiten und die Gesundhaitspflege (1877), attacking its pleomorphic doctrines.
In 1878 Koch also published his first monograph, Untersuchungen über die Aetiologie der Wundinfektionskrankheiten. In this book he summarized his experiments on the aetiology of wound infection, each due to a specific microorganism. He then transferred these infections by inoculating through several kinds of animals, reproducing the original six types. In this study, he also observed differences in pathogenicity for different species of hosts and demonstrated that the animal body is an excellent appartus for the cultivation of bacteria. Koch now had 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 Bacillus anthracis.
In the summer of 1879, at Cohn’s urging, Koch was appointed city physician at Breslau; but the small salary and negligible practice made the practice untenable and within three months the family was welcomed back in Wollstein. Koch’s reputationa 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 requires innumerable mice, in addition to guinea pigs, rabbits, frogs, 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 cleaninc microscope slides; some disenchantment was understandable.
Research on tuberculosis
Koch, now recognized as a scientific investigator of the first rank, on Cohnheims’s recommendation, obtained a position in Berlin in the Imperial department of Health - the Kaiserliches Gesundheitsamt – as ordentlicher Mitglied des Reichs-Gesundheitsamtes – in 1880. 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 August Johannes Loeffler (1852-1915) and Georg Theodor August Gaffky (1850-1918), both army staff doctors, whose competence, industry, and loyalty eased his transition from solitary worker to team leader.
Their main assignment, under the Health Department’s director, Heinrich Struck (1825-1902), was 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 astnished eyes.»
The elegant simplicity of Koch's methods is best illustrated by his procedure for separating a mixture of micro-organisms into its component parts. Taking a drop of the mixture, Koch would smear it on a sterile slice of boiled potato, where each individual bacterium would proceed to grow into a small, pure colony. Before the invention of this method, pure cultures could be obtained only if a single bacterium could be isolated from a hanging drop of mixture, an uncertain task at best.
Another of Koch's remarkable innovations was the use of agar jelly as a solid culture medium. This medium, still in use today, is advantageous because any nutrients required to grow the organism in question may be mixed with the jelly before it solidifies. The source of Koch's inspiration for both the potato and the jelly was the same: Emmy's kitchen.
As the program expanded, Ferdinand Hueppe (1852-1938) and Bernhard Fischer (1852-1915) were seconded from the army medical staff and chemists Georg von Knorre (1859-1910) and Bernhard Proskauer (1851-1915) 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.
A haughty man in London
In 1881 Koch was invited to address the Seventh International Medical Congress in London. With a magic lantern and his photographic slides he demonstrated his technique for obtaining pure cultures on solid media. Louis Pasteur and Joseph Lister (1827-1912) were among the members of the audience, and the gentle, friendly Lister decided to introduce Pasteur to Koch.
This was not a simple task. The mutual antagonism between the Germans and the French was so deep that Lister could not have both to dinner at his home on the same day. And there was no more rabid anti-German than Pasteur, who wrote during the Franco-Prussian War, "I want to see France resisting to the last man and the last defense work. I want to see the War prolonged into the depths of winter, so that, with the elements rallying to our side, all those vandals confronting us shall perish of cold and hunger and disease. All my work, to my dying day, will bear as an inscription, ‘Hatred towards Prussia! Revenge! Revenge!’”
Somehow, Lister managed to get the two scientists together. Pasteur gritted his teeth, took Koch's hand, and mumbled with suppressed jealousy, "That's great progress, Monsieur." These were the last civil words that the Frenchman ever spoke to his German colleague. Pasteur by this time had repeated and embellished Koch's anthrax work, and in addition had developed an effective anthrax vaccine. Koch's haughty response: Pasteur really hadn't accomplished what he claimed and had added nothing new.
Certainly Koch could have afforded to be more charitable, for he had long since finished with anthrax. In strictest secrecy, not telling even some of his closest friends, he had begun work on an even more formidable disease, tuberculosis. His celebrated studies of this fierce epidemic illness were to bring him both fame and a certain measure of disgrace.
Discovery of the tubercle bacillus
Although it was known that tuberculosis was due to an infective agent, the organism had not yet been isolated and identified. So Koch set to work. His first tuberculous tissue was from the body of a powerful thirty-six-year-old laborer. This man had been in perfect health until three weeks before his death, when he developed a cough, chest pains, and severe emaciation. Four days after entering the hospital he was dead, his body riddled with yellowish tubercles.
Koch ground up the tuberculous material between two heated knives and injected it into the eyes of rabbits and under the skins of guinea pigs. While waiting for infection to appear, he smeared the laborer's infected tissue on glass slides and peered at it through his microscope.
For days he observed nothing. The tubercle bacillus is extremely tiny, approximately a third the size of the anthrax bacillus, and is difficult to see because it congregates in small numbers. For this reason, other microscopists had failed to find it. But after hours of soaking in various dyes, the bacteria finally were persuaded to take up sufficient color to stand out from their surroundings. Among the diseased lung cells, Koch could see them: tiny blue-colored rods.
In the meantime, the infected animals began to die one by one. Koch pinned them down, soaked their hair with bichloride of mercury disinfectant, and cut them open. Inside were yellowish tubercles identical to those in the body of the laborer. Microscopic examination revealed the same tiny blue-colored rods.
Now certain that he had identified the tubercle bacillus, Koch went to hospitals everywhere in Berlin to obtain infected tissue from the bodies of patients who had died of tuberculosis. He injected this tissue into guinea pigs, rabbits, three dogs, thirteen cats, ten chickens, and twelve pigeons, as well as white mice, field mice, rats, and two marmots. Only when animal or man developed the disease could Koch find the blue-stained rods; never could the bacteria be found in healthy animals.
Yet the most difficult part of the study still remained: the organism had to be grown in pure culture and then used to produce the infection. Koch began by inoculating his regular solid media with diseased tissue. Nothing grew out. Then, reasoning that the bacillus must be a very fastidious one, he prepared a blood serum agar from heat sterilized animal blood, which he inoculated with tissue from the lung of a diseased guinea pig.
One day passed. Two days passed. Still nothing appeared, though every other microbe he had worked with grew into large colonies within this period of time. Long after other investigators probably would have thrown the cultures away and started over, Koch waited with infinite patience, repeatedly inspecting the material in his incubator. Finally, on the morning of the fifteenth day, he was able to see through his pocket lens tiny glistening colonies on the surface of the agar. After making serial cultures with these organisms to exclude any residual animal matter, he was able to infect and kill guinea pigs with the bacteria.
After six months working alone without a hint to colleagues, Koch had succeeded in isolating the organism on a succession of media. Its aetiologic role was now established. On March 24, 1882, Koch announced before the Physiological Society of Berlin in one of its small reading rooms that he had isolated and grown the tubercle bacillus, which he believed to be the cause of all forms of tuberculosis. After Koch finished speaking, a long hush fell over the distinguished audience crowded into the room. Virchow, the doyen of German science, was there; he left without saying a word. Another young scientist present. Paul Ehrlich, who later recalled that evening as his «greatest scientific event,» developed overnight an improved method of staining tubercle bacilli, which Koch adopted. The next day the discovery was front-page news throughout the world.
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, the resport contains some errors. The general luster of the report, however, nevertheless remains unblemished.
One man not delighted by this string of sudden triumphs was Louis Pasteur. He met Koch again at the International Congress of Hygiene in Geneva in 1882, and the antagonism between the two was intense. After Koch asserted that Pasteur had contributed nothing new to science, Pasteur furiously demanded a face-to-face confrontation, a debate. When Koch refused, Pasteur spent Christmas Day 1882 writing a biting letter to his German adversary. Thus the two most prominent bacteriologists had shown themselves to be small, petty, jealous men.
Koch’s chief findings were confirmed wherever his techniques were carefully followed – in the United States, for example, by Theobald Smith (1859-1934) and Edward Livingston Trudeau (1848-1915). The demonstration of tubercle bacilli in the sputum was soon accepted as of crucial diagnostic significance.
Paul Clemens von Baumgarten (1848-1928) described the tubercle becillus in 1882, the same year as Koch - and independent of him. Based on numerous experimental investigations, Baumgarten refuted Ilya Ilich Mechnikov’s (Elie Metchnikoff, 1845-1916) theory of phagocytes, and he established that neither Robert Koch’s new or old method had any curative effect on tubercles inoculated into in rabbits or guinea pigs. Baumgarten's textbook of pathological mucology is the first attempt to develop the pathogenesis of infectious diseases and pathologival histology based on the modern doctrine of pathogenous microorganisms.
Travelling in Cholera
In 1883 Koch’s tuberculosis researches, as well as his polemics with Pasteur and others, were interrupted by the 1883 Hygiene Exhibition in Berlin, which he helped to organize. In the Health Department’s pavillion 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 was warned by Louis Pasteur that the epidemic could invade Europe and that the cause of cholerea was probably microbial. Pasteur, fully occupied in Paris trying to cure rabies, sent a four man scientific mission, including his two assistants, Emile Roux and Louis Thuillier. They reached Alexandria in mid-August.
Nine days later Koch arrived, heading a German government commission that included Gaffky and Bernhard Fischer (1852-1915), as well as microscopes and experimental animals. He soon had reason to suspect a particular comma-shaped bacillus as the specific cause of cholera, but suddenly the epidemic began to wane. While the two French scientists relaxed and cooled themselves with swims in the sea, Koch and Gaffky sweated and dripped over their microscopes as they examined the last infected material.
Nevertheless, he discovered the cause of amoebic dysentery and the bacilli of two varieties of Egyptian conjunctivitis, an agent now known as Koch-Week bacillus. Koch’s interests in sanitation and in world travel were exercised by visits to quarantine stations, a pilgrim camp, and ancient monuments. The German commission was thus successful after all.
The French team, however, suffered disappointment and tragedy. Their bouillion cultures yelded a confusing assortment of intestinal bacteria from cholerea victims, whose blood, however, contained suspicious bodies. These bodies proved to be merely blood platelets, as Koch later pointed out.
At three A.M. on September 15 a messenger awakened Koch with the news that Louis Thuillier, the youngest member of the French mission, was seriously ill with cholera. Koch hurried to the bed where the twenty-seven-year-old Frenchman lay dying. "Have we found the cholera bacillus?" Thuillier asked. As Roux had requested, Koch lied and answered yes. Within a few hours, Thuillier was dead. Koch was one of the pallbearers and laid wreaths on the coffin.
Now the epidemic was over. Koch rushed back to Berlin with specimens containing the organism he had identified, a little vibrating bacterium, or vibrio, shaped like a comma. But to be certain that this vibrio was indeed the right bug, Koch went to India to study the regions where the disease had been endemic for so long. In Bengal his Egyptian findings were confirmed.
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, and that it was transmitted via drinking water, food, and clothing. This same germ was not to be found in the feces of any healthy individuals, nor was it present in any animal. The cholera vibrio, Koch found, could be easily grown on beef broth agar. Though drying quickly killed it, the organism readily infected healthy persons handling the soiled linen of cholera victims. And the germ could often be found in the dirty water tanks around the native huts. Only in this highly polluted water or in the human intestine could the vibrio survive. His final communication from India, dated March 4, 1884, designated village ponds used for drinking water and all domestic purposes, as sources of local 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 with Star, 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:
"Homer describes a peculiar virtue in Ajax, that he, when he was driven back by his opponents, turned around like a fly and attacked them from another side, continuously, stubbornly, and forcefully. Those are the virtues we see in our heroes, and which have been demonstrated so many times by our clebrated friend Koch. Where his experiments often failed at the first attempt, in staining, lighting, drying and isolation, in sterilizing and in pure cultures, he never gave up, but only made a new attempt, from a new angle, until the formidable opponent cracked and had to give up its secret."
Koch’s six letter-reports to the minister during the commissions nine months abroad were supplemented in 1887 by Gaffky’s complete account of their activities, constituting volume 3 of the Health Department’s Arbeiten aus dem Kaiserlichen Gesundheitsamte. 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. In 1885 he was appointed professor ordinarius of hygiene and bacteriology at the University of Berlin.
Privy medical counsellor
During the years 1882-1884 the bacilli of swine erysipelas, glanders, and diphteria had been isolated by Loeffler, and the typhoid bacillus by Gaffky. At this juncture the Minister of Public Instruction, Gustav Gossler (1838-1902) and his advisor Friedrich Althoff (1839-1908) 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 - privy medical counsellor.
Koch’s notable assistants and trainees in this period included Carl Fraenkel (1861-1915), Wilhelm Dönitz (1838-1912), Richard Friedrich Johannes Pfeiffer (1858-1945), and Emil Adolf von Behring (1854-1913) from Germany, Shibasaburo Kitasato (1856-1931) from Japan; and William Henry Welch (1850-1934) and Theophil Mitchell Prudden (1849-1924) from the United States.
Tuberculin - the great man's great disappointment
After the discovery of the cholera bacillus, Koch's meteoric rise appeared to have halted. For six years he was able to produce nothing that matched the caliber of his early work. Increasingly, he became more nervous, secretive, and suspicious. However, resuming his studies of tuberculosis, working alone and secretively, he sought a specific remedy for tuberculosis. He investigated what effect an injection of dead bacilli would have on a person who subsequently received a dose of living ones. He concluded that the local reaction produced might prove the means by which the disease could not only be diagnosed but, in the early stages, perhaps even cured. In his studies, he used the active agent as a sterile liquid produced from cultures of the bacillus.
On August 4, 1890, at the tenth International Medical Kongress in Berlin, Koch ended a pedestrian address on bacteriological reasearch by annpuncing that after testing many chemicals, he had «At last hit upon a substance which has the power of preventing the growth of the tubercle bacilli,» both in vitro and in vivo. Injections of the substance into guinea pigs renderd normal animals resistant to tuberculosis and arrested the generalized disease and, in November, Koch reported excellent results in clinical trials of the agent, prepared and administered by two physicians - Eduard Pfuhl (1852-1917) his son-in-law, and Arnold Libbertz, who from May 1892 supervised the production of tuberculin at the Hoechst AG.
Koch’s name was now on all lips; doctor’s and patients made pilgrimages to Berlin, filling hospitals, clinics, and hotels, clamoring for his «lymph.» He received the honorary freedom of Klausthal, Wollstein, and Berlin; awards from foreign rulers and societies; Pasteur’s congratulations; and the Grand Cross of the Red Eagle from the Kaiser. However, Koch’s liquid, the tuberculin, proved disappointing as a curative agent, and, consequently, its importance as a means of detecting a present or past tubercular state was not immediately recognized.
In January 1891 Rudolf Virchow, always skeptical of Koch's discoveries, published the results of autopsies on twenty-one consumptives treated with tuberculin. All of the bodies had been riddled with miliary tuberculosis, the most advanced and dreaded form of the disease, worse than the pathologist had ever seen before. The uproar produced by this report forced Koch to reveal the exact nature of tuberculin.
To produce his wonder drug, Koch had grown tubercle bacilli on a glycerin broth for several weeks, then killed the bacteria with heat and filtered off the nutritive medium. This simple method had been employed earlier by Emile Roux to isolate diphtheria toxin, but why Koch believed that his filtrate would cure tuberculosis is unknown.
In fact, a valuable medical tool did emerge from the tuberculin disaster, though it was obscured by the terrible outcry at the time. Koch noted that tuberculin injected into the skin of tuberculous patients produced a reddish allergic reaction at the spot within forty-eight hours. This reaction, the Koch phenomenon, allows doctors today to determine whether an individual has been infected with tubercle bacilli, even before symptoms develop.
But discovery of the tuberculin skin test was of little immediate consolation. Koch had too many deaths on his conscience. The secrecy surrounding tuberculin, established to protect priority, was seen by detractors as Koch's way of assuring a fortune from the discovery, and they may have been right.
Koch's marriage had been unhappy Twenty years of marriage to the domineering Emmy had not improved the relationship, and at the age of forty-five the bespectacled, bearded, balding Koch began looking around. One day, while he was sitting in an artist's studio for an official portrait, his glance fell upon a finished canvas, the portrait of a seventeen-year-old girl, a beauty. Inquiry revealed that she was the illegitimate daughter of a Berlin workman. She played bit parts at the Schiller Theater in Berlin and was also the artist's student. A meeting was arranged; soon the girl, Hedwig Freiburg, was Koch's mistress and the center of his life.
In 1893 he divorced his wife to marry Hedwig Freiburg. The divorce and remarriage provoked more censure than sympathy, but the childless union lasted and was happy. Rumours were even circulated that he had sold his patent on tuberculin to Boehringwerke AG in Marburg and allowed it to be tried in patients, before it had been properly proved, in order to have sufficient money to support his second wife. A tablet which had been placed on the walls of his home in by his fellow citizens of Clasuthal was torn down.
Despite this domestic scandal and professional scepticism 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 Königlich Preußisches Institut für Infektionskrankheiten – the Institute for Infectious Diseases – and he persuaded the city of Berlin to complete a multipavillion barrack hospital – later known as «Koch’s sheds» – accommodating over 100 patients, in Berlin-Wedding. In the legislature Rudolf Virchow protested without avail the hasty approval of a budget equaling the total research funds for all scientific departments at Berlin University. In 1912, on the the thirtieth anniversary of the discovery of the tubercle bacillus, the Königlich Preußisches Institut für Infektionskrankheiten became the Robert Koch Institut.
Among those now working with Robert Koch were Paul Ehrlich, Hermann Kossel (1864-925), Bernhard Proskauer, and August Paul von Wassermann (1866-1925). Ehrlich was indispensable in helping Emil von Behring to produce potent antitoxins. The relationship between Behring, of rising fame, and Robert Koch, soon soured. 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. Emil von Behring in 1901 was the first recipient of the Nobel Prize for Physiology or Medicine.
Cholera, leprosy, rinderpest, and bubonic plague
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 Georg Gaffky and William Philip Dunbar (1863-1922), stressed early bacteriological detection and isolation of ambulant cases,disinfection of patient’s excreta, and scrupulous sanitation of water supplies.
At that time not all scientists were convinced that cholera was caused by the vibrio. One asked Koch to send over a vial of cholera bacilli, then publicly swallowed the contents, remarkably without ill effect. The controversy continued to rage until 1892, when the outbreak in Hamburg settled the matter.
Hamburg, an old free city, had remained self-governing within the German Reich and drew its water from the Elbe without special treatment. Just adjacent was the Prussian town of Altona, where the imperial government had installed a water purification plant. When cholera broke out in Hamburg, it ran down one side of the street dividing the two cities, sparing Altona completely. No more graphic demonstration of the importance of the water supply could have been intentionally devised, and the miasmatists were silenced completely.
In 1896 Koch undertook a leprosy survey in Memel. The disease had become notifiable in Prussia and a leprosarium was established. Then, the same year, the Cape Colony government in South Africa engaged Koch 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 (1861-1901), Koch assembled a menagerie of experimental animals and within 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 micture of blood serum from recovered animals and virulent rinderpest-infected blood. Inoculation with bile from cattle freshly dead from the disease proved even more protective.
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 aetiologic role of the plague bacillus Yersionia pestis - discovered in 1894 by Aleaxandre Yersin (1863-1943) and by Kitasato and had launched epidemiologival inquiries. Koch organized laboratory tests of Yersin’s serum and Waldemar Mordecai Wolfe Haffkine’s (1860-1930) 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. Visiitng 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 (Deutsch Ostafrika – Tanganyika, now the mainland part of Tanzania) to curb rinderpest. Instead he found two protozoan diseases – surra, a trypanosomasis affecting horses, and Texas cattle fever, identified as a prisoplasmosis by Theobald Smith. He began to study malaria and Blackwater fever – soon attributing the latter to quinine intoxication - and detected an endemic plague focus as 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 coals in malaria research.» The various accomplishments were recounted in Reise-Bericht über Rinderpest, Bubonenpest in Indien und Afrika . . . (1898). The spread of malaria was still a mystery; Koch had nearly satisfied himself that it was transmitted by mosquitoes when the british bacteriologist Ronald Ross (1857-1932) published his findings pointing to the same conclusion.
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 Richard Friedrich Johannes Pfeiffer (1858-1945) and Hermann Kossel (1864-1925) in the Lombardy plains, the Campagna di Roma, and other Italian malarial districts, he confirmed Ronald Ross’ discovery of the avian malaria parasite’s life cycle.
When the expedition reached German New Guinea, his wife became ill and was sent home. Here the malaria 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 succesful 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 discovery to military hygiene by electing him to its senate, with the rank of major general.
Back in Germany
Koch returned to Berlin in October 1900, having spent only nine months there in four years. Richard Pfeiffer’s loyalty as acting director could not compensate for these prolonged abseces. The Institute’s transfer to planned larger quarters in north Berlin, adjoining the Rudolf Virchow Hospital, needed supervision. Indigenous health probelms also demanded attention.
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 investigations of their surroundings. Koch’s broad experience, throurghness, and zealous leadership halted the epidemics and the typhoid morbidity fell.
African coast fever
Early in 1903 Koch and his wife departed for Bulawayo, Southern Rhodesia, accompanied by Fred Neufeld (1869-1945) and Friedrich Karl Kleine (1869-1951). 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.
A sort of retirement
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 appreaciation, tinged with bitterness at increasing competition and «passionate opposition,» Koch undertook to serve science as long as strength permitted. With Gaffky, 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.
In 1901 Koch reported work done on the pathogenicity of the human tubercle bacillus for domestic animals. He believed that infection of human beings by bovine tuberculosis is so rare that it is not necessary to take any measures against it. This conclusion was rejected by commissions of inquiry in Europe and America in an extensive and important work that was stimulated by Koch’s theory, even though it proved to be partly wrong. But, in most cases, the successful measures of prophylaxis were those firmly laid down by Koch.
Dream of horses
Early in 1905 Koch again arrived in 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. Koch returned to Berlin the following October. The months later, in Stockholm, he received the 1905 Nobel Price for phyrsiology or medicine for his work on tuberculosis.
In April 1906, Koch led the German Sleeping Sickness Commission, comprising the Regierungsrat (Government advisor) professor M. Beck, Friedrich Kleine, O. Panse, and Robert Kudicke (1876-1961), to East Africa, After visiting regional stations, Koch sent his wife home from Entebbe to spare her the hardships and dangers of Sesse Islands, Uganda - an area of rampant trypanosomiasis in northwestern Lake Victoria, where the expedition established straw hut headquarters and patient’s 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 ill from optic atrophy. Koch proposed some drastic alternatives, such as eliminating tstse fly harborages through clearance of undergrowth and tre-cutting on the littoral, and exterminating crocodiles, on whose blood Glossina palpalis fed.
Once during this research trip, Koch shook awake his assistant, Friedrich Kleine, at five A.M. for help dissecting an infected horse that had just died. Kleine, completely exhausted by Koch's demands, answered that he was too tired and had dreamed of horses all night long. "How can you hope to make any progress," the astonished Koch asked, "if you don't dream about horses?" In November 1907 he and Bech returned to Berlin; the others continued investigations.
A man of many honours
Many honours were nor 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 (Wilhelm II, 1859-1941) contributed 100.000 mark and Andrew Carnegie (1835-1919) 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 a sumptuous banquet, where he was eulogized by William Henry Welch (1850-1934), his best-known American disciple, and by Andrew Carnegie. After visiting his brothers and other relatives in Chicago and St. Louis, Koch traveled via Honolulu to Japan, to be welcomed with solemn honours by Shibasaburo Kitasato (1852-1931), presented to the mikado, and escorted like a demigod around the country.
The remainder of Koch’s life was devoted 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 peacfullt 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 Metchnikoff brought from the Pasteur Institute a plaque of guilded 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.» In New York in 1908 Koch said: «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 thorugh the medical field I came upon regions where gold was still lying by the wayside.»
Koch was thoroughly German, a senior civil servant and government consultant, and accustomed to assistants with military background. His consequent hierarchical concepts and attituded 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.
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 unfortinate tendency to use the pen as a sword and cudgel sometimes marred the lucidity and persuasiveness of his earlier writings.
Koch expresses his career’s basic motivation in his first paper on tuberculosis: «I have undertaken my investigations in the interest of public health and I hope the greatest benefits will accrue teherefrom.» Less impersonal compassion was displayed in his determination to maintain contacts with patients and in his continuing quest for specific remedies - diphteria antitoxin, tuberculin, quinine, and atoxyl. In disclosing the causes of disease and expounding the means of prevention, Robert Koch at his best was unexcelled. Tha Faustian weaknesses and perplexities he carried do not diminish the lasting benefits that his aspirations bestowed upon mankind.
Koch's personal scientific library of just over 300 volumes was bequeathed to the Robert Koch Institute in Berlin, where it has been kept intact.
- “Wenn die Reichen sich abwenden von der Not der Armen, triumphieren die Mikroben.”
Der Spiegel 43/1998
«It is certainly a one-sided opinion - even thoughe generally adopted at the moment - that all infectious agents which are still unknown must be bacteria. Why should not other microoganisms just as well be able to exist as parasites in the body of animals?»
Zur Untersuchung von pathologischen Organismen. 1881.
Translated by Max Samter.
«If we are continuellay guided in this enterprise by the spirit of genuine preventive medical science; if we utilise the experience gained in conflict with other pestilences, and aim, with clear recognition of the purpose and resolute avoidance of wrong roads, at striking the evil at its roots, then the battle against tuberculosis cannot fail to have a victorious issue.»
The fight against tuberculosis.
"Drop everything and go at once to Koch. This man has made a splendid discovery, which is all the more astonishing because Koch has had no scientific connections and has worked entirely on his own initiative and has produced something absolutely complete. There is nothing more to be done. I consider this the greatest discovery in the field of bacteriology and believe that Koch will again astonish and shame us with still further discoveries."
Kohn to his students in Breslau when Koch demonstrated his discovery of the anthrax bacillus.