Pasteur, Koch and the Germ Theory of Disease
For most of recorded history the great epidemic diseases were explained by bad air, by an imbalance of the body’s humours, or by the will of God. In the space of about thirty years in the middle of the nineteenth century, that understanding was replaced by a new one: that many diseases are caused by specific living micro-organisms, that each organism produces a particular disease, and that the organisms pass from one person, animal or substance to another. This germ theory of disease was the work of many people, but two of them, the French chemist Louis Pasteur and the German physician Robert Koch, did more than any others to establish it. Pasteur showed that fermentation and putrefaction were the work of micro-organisms and that those organisms did not arise spontaneously; he went on to develop vaccines against animal diseases and against rabies. Koch showed how to isolate a single species of bacterium, grow it in pure culture and prove that it caused a particular disease, and he identified the organisms responsible for anthrax, tuberculosis and cholera. This article describes how the theory took shape, the methods on which it rested, the rivalry between its two principal figures and the changes it brought to surgery, public health and medicine.
Miasma, Contagion and the Invisible World
The idea that disease might be passed on by some living agent was not new in the nineteenth century. In 1546 the Veronese physician Girolamo Fracastoro described contagion as the transfer of tiny “seeds” of disease, seminaria, which could spread by direct contact, by contaminated objects such as clothing, or through the air. In the 1670s the Dutch draper and lens-maker Antonie van Leeuwenhoek, using single-lens microscopes of his own making, described “animalcules” in rainwater, in pepper infusions and in the scrapings from his own teeth, the first observations of bacteria and protozoa. But no one could connect these organisms with any particular disease, and the microscopes of the following century were not good enough to study them in detail.
The dominant explanation of epidemic disease in the first half of the nineteenth century was the miasma theory. On this view diseases such as cholera, typhus and malaria were caused by poisonous vapours rising from decaying organic matter, from swamps, open sewers, graveyards and overcrowded slums. The theory was not foolish. It explained why disease was worst in filthy, crowded, badly drained places, and it gave a powerful argument for sanitary reform. Edwin Chadwick’s Report on the Sanitary Condition of the Labouring Population of Great Britain in 1842 and Florence Nightingale’s work in military hospitals were both founded on miasmatic ideas, and the drains, sewers and clean water supplies they promoted did reduce disease, though not for the reasons they supposed.
Several observers in the 1840s and 1850s found evidence that did not fit. In 1847 Ignaz Semmelweis, an assistant physician at the Vienna General Hospital, noticed that the maternity ward staffed by doctors and medical students had a rate of death from puerperal fever several times higher than the ward staffed by midwives. The doctors came to the ward directly from the dissecting room. When a colleague died of an infection after being cut by a student’s scalpel during an autopsy, with symptoms like those of puerperal fever, Semmelweis concluded that “cadaverous particles” carried on the doctors’ hands were causing the disease. He required staff to wash their hands in a solution of chlorinated lime before examining patients, and the death rate on his ward fell sharply. His findings were resisted, partly because he was slow to publish them and partly because they implied that physicians were killing their patients. He left Vienna, and he died in an asylum in 1865.
In London, the physician John Snow, who was also one of the pioneers of anaesthesia with ether and chloroform, argued from the pattern of cases that cholera was spread through water contaminated with the discharges of the sick, not through the air. During the outbreak around Broad Street in Soho in 1854 he mapped the deaths and found that they clustered around one public water pump; he persuaded the local board of guardians to remove its handle. In a larger study he compared households supplied by two water companies, one of which drew its water from the Thames below the sewage outfalls and one from upstream, and found that the death rate from cholera among customers of the first was many times higher. In the same year, in Florence, the anatomist Filippo Pacini described a comma-shaped bacterium in the intestines of cholera victims. Snow and Pacini did not know of each other’s work, and neither convinced the medical establishment. The organism had been seen and the means of transmission inferred, but no one had yet shown that the one caused the disease.
What was missing was a general theory of what micro-organisms did and a set of methods for studying them. Both came first from an unexpected direction: the chemistry of wine, beer and spoiled milk.
Pasteur and the Chemistry of Life
Louis Pasteur was born on 27 December 1822 at Dole in the Jura, the son of a tanner who had served as a sergeant in Napoleon’s army, and grew up in Arbois. He trained at the École Normale Supérieure in Paris and made his reputation in crystallography. In 1848 he showed that crystals of sodium ammonium tartrate, a salt of tartaric acid from wine sediments, came in two mirror-image forms, and that solutions of the two forms rotated polarised light in opposite directions. The discovery of molecular handedness, or chirality, led him to the observation that living things produced only one of the two forms, and to a lifelong conviction that the chemistry of life was asymmetric in ways that ordinary chemistry was not.
In 1854 Pasteur became professor of chemistry and dean of the new faculty of sciences at Lille, a centre of the sugar-beet and distilling industries. In 1856 a local manufacturer, whose son was one of Pasteur’s students, asked for help with the vats of beet juice that were going sour instead of producing alcohol. Examining the contents under the microscope, Pasteur found that the healthy vats contained round globules of yeast, while the sour ones contained much smaller rod-shaped organisms associated with the production of lactic acid. The prevailing view, championed by the German chemist Justus von Liebig, held that fermentation was a purely chemical process, a kind of decomposition set off by unstable substances, and that yeast, where present, was a product or a by-product. Pasteur argued the reverse. In a memoir on lactic fermentation in 1857 and in a long series of papers on alcoholic fermentation in the following years, he maintained that each kind of fermentation was caused by a specific living organism, that the organism fed on the sugar and produced the fermentation products as part of its life, and that a different organism produced a different product.
The practical results were immediate. In the 1860s, at the request of the Emperor Napoleon III, Pasteur studied the diseases of wine, which were costing French producers heavily in exports. He showed that the souring and other faults were caused by contaminating organisms and that they could be prevented by heating the wine gently, to between about 50 and 60 degrees Celsius, for a few minutes after fermentation was complete. The process, patented in 1865 and later applied to beer and, most importantly, to milk, became known as pasteurisation. His Études sur la bière of 1876 described the same principles for brewing, and the Carlsberg laboratory in Copenhagen, founded in 1875, applied them in developing pure strains of brewer’s yeast.
The End of Spontaneous Generation
If micro-organisms caused fermentation and putrefaction, where did they come from? The question had been argued over for two centuries. The doctrine of spontaneous generation held that living things could arise directly from non-living matter. For larger animals it had been disposed of in 1668 by Francesco Redi, who showed that maggots appeared in meat only if flies could lay eggs on it. For micro-organisms it was much harder to refute. In the eighteenth century John Needham boiled flasks of broth, sealed them and found them teeming with organisms a few days later, while Lazzaro Spallanzani, boiling his flasks for longer and sealing them by melting the glass, found that they stayed clear. Defenders of spontaneous generation replied that Spallanzani’s prolonged heating destroyed a vital force in the air or the broth that was needed for life to form.
The debate was revived in 1859 by Félix Pouchet, director of the natural history museum in Rouen, who claimed to have produced micro-organisms in sterilised hay infusions under mercury in contact with artificially produced oxygen. The French Académie des Sciences offered a prize, the Alhumbert Prize, for experiments that would settle the question. Pasteur took up the challenge. He showed by filtering air through plugs of guncotton and dissolving the cotton that the air contained large numbers of tiny bodies resembling the spores of micro-organisms. He carried sealed flasks of sterile broth to different places, opened them briefly and resealed them, and found that flasks opened in the dusty air of a city street were nearly all contaminated, while flasks opened high on the Montanvert glacier above Chamonix mostly stayed clear.
His most famous experiment used flasks whose necks he drew out in a flame into long S-shaped curves. The broth inside was boiled and left open to the air through the curved neck. Air could pass freely in and out, so no vital principle was excluded, but dust and the organisms it carried settled in the bends of the neck and did not reach the liquid. The broth remained sterile indefinitely. When the neck was broken off, or the flask tipped so that the broth touched the dust in the bend, it quickly filled with growth. Pasteur described the results in a celebrated lecture at the Sorbonne on 7 April 1864, in which he declared that spontaneous generation would never recover from the blow of that simple experiment. Some of his original swan-necked flasks are still kept at the Institut Pasteur in Paris, and their contents are said to have remained clear.
The question was not quite closed. In the 1870s the English physician Henry Charlton Bastian reported growth in boiled infusions of hay and turnip, and the Irish physicist John Tyndall, working at the Royal Institution, found that some infusions needed repeated cycles of boiling and cooling to sterilise them. In 1876 the German botanist Ferdinand Cohn identified the explanation: some bacteria, including the hay bacillus, form heat-resistant spores that survive ordinary boiling and germinate later. Tyndall’s method of intermittent heating, called tyndallisation, killed the bacteria as the spores germinated between heatings. Spontaneous generation, as it was understood in the nineteenth century, did not survive these findings.
From Silkworms to the Germ Theory
The link between Pasteur’s work on fermentation and human disease was not obvious at first, and it came by way of agriculture. In 1865 the chemist Jean-Baptiste Dumas, Pasteur’s former teacher, asked him to investigate a disease of silkworms, pébrine, which had devastated the silk industry of southern France. Pasteur, who had never studied silkworms, spent five seasons at Alès in the Cévennes. With his assistants he showed that pébrine was caused by a parasite, now classified as a microsporidian, which passed from the moth to the egg, and that a second disease, flacherie, was also present. He devised a method of examining the moths under the microscope and destroying the eggs of any that were infected, which allowed the industry to recover. The work was carried out in the face of personal tragedy, since three of his five children died of typhoid fever between 1859 and 1865, and in 1868 Pasteur himself suffered a stroke that left him partly paralysed on the left side.
By the late 1860s the idea that micro-organisms might cause diseases in people was being tested in hospitals. Joseph Lister, professor of surgery at Glasgow, read Pasteur’s papers on putrefaction in 1865 and reasoned that the infections that killed a large proportion of patients after surgery, especially after compound fractures in which the broken bone pierced the skin, might be caused by organisms entering the wound from the air. Since he could not heat the wound, he looked for a chemical to kill them, and chose carbolic acid, which had been used to treat sewage at Carlisle. In August 1865 he treated the compound fracture of an eleven-year-old boy, James Greenlees, with lint soaked in carbolic acid, and the wound healed without infection. In 1867 he published a series of papers in The Lancet describing his antiseptic method, and he later introduced a carbolic spray to disinfect the air of the operating theatre. The mortality in his wards fell, and his methods were widely adopted, first in Germany and Scandinavia and more slowly in Britain. In 1874 Lister wrote to Pasteur to thank him for having demonstrated the truth of the germ theory of putrefaction, which had made his own system possible.
A Country Doctor in Wollstein
Robert Koch was born on 11 December 1843 at Clausthal in the Harz mountains, the son of a mining official, the third of thirteen children. He studied medicine at the University of Göttingen, where one of his teachers was the anatomist Jakob Henle, who had argued in 1840 that contagious diseases must be caused by living agents and had set out, in general terms, what would be needed to prove it. Koch qualified in 1866, served briefly as a volunteer surgeon in the Franco-Prussian War of 1870 and 1871, and in 1872 became district medical officer at Wollstein, a small town in the Prussian province of Posen, now Wolsztyn in Poland.
Wollstein lay in farming country where anthrax killed large numbers of sheep and cattle and sometimes the people who handled them. Rod-shaped bodies had been seen in the blood of animals dead of anthrax by Aloys Pollender, Pierre Rayer and Casimir Davaine in the 1850s and 1860s, and Davaine had shown that blood containing them could transmit the disease. But it was not clear how the disease persisted in pastures for years, or whether the rods were its cause or a consequence. In a makeshift laboratory partitioned off from his consulting room, using a microscope given to him by his wife, Emmy, Koch set out to follow the organism through its whole life. He inoculated mice with anthrax blood using slivers of wood, passed the disease from mouse to mouse through twenty generations, and found ways to grow the bacillus outside the body in drops of aqueous humour from the eyes of cattle, watching it on a warmed microscope stage. He saw that in unfavourable conditions the rods formed resistant spores, which could survive drying and lie dormant in the soil, and that the spores, introduced into a healthy animal, produced the disease again.
In April 1876 Koch took his preparations to Breslau and demonstrated them to Ferdinand Cohn, professor of botany and one of the leading authorities on bacteria, and to the pathologist Julius Cohnheim. Cohn published Koch’s paper on the aetiology of anthrax in his journal later that year. For the first time the complete life cycle of a disease-causing bacterium had been worked out and its role in causing the disease demonstrated by experiment. Koch was still an unknown country doctor, and he went on improving his methods in Wollstein for four more years.
Methods: Stains, Plates and Pure Cultures
Koch’s most lasting contribution was methodological. Bacteria are tiny, mostly colourless and, in the material taken from a sick animal or a wound, mixed with many other organisms. To show that one particular organism caused a disease, it was necessary to see it clearly, to separate it from all the others, and to grow it in quantity without contamination.
In 1877 Koch described methods for spreading thin films of bacteria on glass slides, drying and fixing them, and staining them with the new aniline dyes produced by the German chemical industry. He was also one of the first to use photography through the microscope, arguing that a photograph was a more objective record than a drawing. In 1878 he published a study of wound infections in animals in which he distinguished several different organisms by their shapes and by the diseases they produced, and argued that each kind of bacterium was a fixed species with its own characteristic effects, against the view, held by some botanists, that bacteria could change readily from one form into another. In 1880 he was appointed to the Imperial Health Office in Berlin, where he was given a laboratory and assistants, among them Friedrich Loeffler and Georg Gaffky.
The decisive technical problem was the pure culture. In a liquid broth, different bacteria grow together and cannot be separated. Koch’s solution was to grow them on a solid surface. He first used the cut surface of a boiled potato, on which a single bacterium could multiply into a separate visible colony. He then mixed nutrient broth with gelatin, poured it onto flat glass plates and let it set, so that bacteria spread thinly across it grew into isolated colonies, each derived from a single cell, which could be picked off and transferred to fresh medium. Gelatin had drawbacks: it melted at body temperature, which was the temperature at which many disease-causing bacteria grew best, and some bacteria digested it. In 1881 Fanny Hesse, the wife of Walther Hesse, one of Koch’s assistants, suggested using agar, a seaweed extract she used in her kitchen to set fruit jellies, which she had learned of from a Dutch neighbour who had lived in Java. Agar stayed solid at body temperature and was not digested by most bacteria. In 1887 another assistant, Julius Richard Petri, introduced a pair of shallow glass dishes, one fitting over the other as a lid, which kept the plates free of airborne contamination. The agar plate in a Petri dish remains the basic tool of microbiology.
Tuberculosis and the Postulates
Tuberculosis was the greatest single cause of death in nineteenth-century Europe. It was estimated to account for about one death in seven, and much more among young adults in the crowded cities. Jean-Antoine Villemin in France had shown in 1865 that material from tuberculous lesions could transmit the disease to rabbits, so it was known to be transmissible, but the organism responsible had not been seen. It is small, grows very slowly and does not take up ordinary stains.
Koch began work on tuberculosis in August 1881. After weeks of failure he found a staining method, using methylene blue with an alkali followed by a counterstain of vesuvin, that made thin blue rods visible against a brown background in tissue from tuberculous lesions. He found the rods in material from patients and animals with many different forms of the disease, from lung tuberculosis to scrofula and bovine tuberculosis. Growing them was harder. They would not grow on the usual media, and he eventually cultured them on coagulated blood serum held at body temperature, where after about two weeks tiny dry scales appeared. He transferred the cultures repeatedly and then inoculated them into guinea pigs and other animals, which developed tuberculosis. On the evening of 24 March 1882, at a meeting of the Physiological Society in Berlin, he presented his findings in a lecture titled “Die Ätiologie der Tuberculose”, with his preparations set out on tables for inspection. The audience included most of the leading medical scientists of Berlin. Paul Ehrlich, who was present, later described it as the most important scientific experience of his life. The date is now marked as World Tuberculosis Day.
The reasoning by which Koch connected Mycobacterium tuberculosis with the disease became known as Koch’s postulates. In the form set out by Loeffler in 1884 in his work on diphtheria, they require that the organism be found in every case of the disease, in a distribution that explains the symptoms; that it be isolated from the diseased host and grown in pure culture; and that the pure culture, introduced into a healthy susceptible host, reproduce the disease. A fourth criterion, that the organism be recovered again from the experimentally infected host, was often added later. Koch himself never stated them as a fixed list, and he recognised that they could not always be met. Some organisms could not be grown outside the body, some caused no disease in laboratory animals, and some people carried an organism without falling ill. But as a standard of evidence the postulates turned the claim that a germ caused a disease into something that could be tested, and they set the pattern for the rapid discoveries of the next two decades.
Cholera in Egypt and India
In 1883 cholera reached Egypt, and the French and German governments each sent a scientific commission to investigate. The French commission, which included Pasteur’s colleagues Émile Roux and Louis Thuillier, failed to identify the organism, and Thuillier died of the disease in Alexandria. Koch’s commission found a curved bacillus in the intestines of victims, but the epidemic died away before he could complete the work, and he went on to Calcutta, where cholera was endemic. There, early in 1884, he isolated the comma-shaped organism, Vibrio cholerae, in pure culture, showed that it was present in the intestines of cholera patients and not of healthy people or people with other diseases, and traced it to a water tank used for bathing, washing and drinking around which cases were clustered. He could not produce the disease in animals, so the postulates were not fully satisfied, but the epidemiological evidence was strong. He returned to Berlin to a hero’s welcome. Pacini’s earlier description of the same organism was eventually recognised in 1965, when the organism’s name was formally changed to Vibrio cholerae Pacini 1854.
Not everyone was convinced. Max von Pettenkofer of Munich, the leading German authority on hygiene, held that the cholera bacterium alone was not enough to cause the disease and that local conditions of soil and groundwater were also required. In October 1892, to demonstrate the point, he drank a culture of cholera bacteria sent from Koch’s laboratory, having first neutralised his stomach acid with bicarbonate of soda. He suffered only mild diarrhoea, as did several of his assistants who repeated the experiment. The episode is usually told as an example of a scientist risking his life for a mistaken theory. It also shows that, as is now known, infection depends on the dose, the strain and the host’s immunity, and that the presence of a pathogen does not always mean disease. In the same year, a severe cholera epidemic in Hamburg, which drew its drinking water unfiltered from the Elbe, killed more than eight thousand people, while the neighbouring town of Altona, which filtered its water, was almost untouched. The contrast was a powerful argument for the bacteriologists’ view.
Vaccines and the Rivalry of the Two Schools
While Koch was developing his methods, Pasteur moved into medicine with no medical qualification. Working with Roux, Charles Chamberland and others at the École Normale, he studied chicken cholera, a bacterial disease of poultry. In 1879 he found that a culture left standing for some weeks lost its power to kill, and that chickens inoculated with the weakened culture were protected against a later dose of fresh virulent bacteria. He saw the connection with Edward Jenner‘s method of protecting against smallpox with cowpox, and in Jenner’s honour extended the term vaccination to every such procedure. The principle that a disease organism could be attenuated and then used to protect against itself was the starting point for experimental immunology.
The most public demonstration came with anthrax. In 1881, at the farm of Pouilly-le-Fort near Melun, Pasteur vaccinated twenty-four sheep, one goat and six cows with an attenuated anthrax culture and left a similar group unvaccinated. On 31 May all the animals were injected with virulent anthrax. On 2 June, in front of a crowd of farmers, veterinarians, officials and journalists, all the vaccinated sheep were alive and well, and nearly all the unvaccinated sheep were dead or dying. The trial made Pasteur a national figure. His laboratory notebooks, opened to historians only in the 1970s and studied by Gerald Geison in The Private Science of Louis Pasteur in 1995, show that the vaccine used at Pouilly-le-Fort had been attenuated with potassium dichromate by a method developed by Chamberland and Roux, closer to that of the veterinarian Jean-Joseph Toussaint than to the oxygen-attenuation method Pasteur had described in public. The discrepancy has been much discussed. It does not alter the result of the trial, but it shows that Pasteur’s public account of his methods was not always complete.
Relations between Pasteur and Koch were poor from the beginning, coloured by national feeling after the Franco-Prussian War. Pasteur had returned an honorary degree to the University of Bonn in protest at the German bombardment of Paris in 1871. Koch and Loeffler criticised Pasteur’s anthrax work sharply in 1881, arguing that his cultures were impure and his methods unreliable, and at the International Congress of Hygiene in Geneva in 1882 the two men clashed in public, with the exchange made worse by a mistranslation of Koch’s phrase “recueil allemand”, a German collection of papers, as “orgueil allemand”, German arrogance. The rivalry divided two schools with different strengths. The German school excelled in isolating and identifying organisms; the French school in attenuating them and in the study of immunity.
Pasteur’s last great piece of work was on rabies. The organism responsible could not be seen with the microscopes of the day, because it is a virus, much smaller than any bacterium, and it could not be grown in culture. Pasteur and Roux passed it through the brains and spinal cords of rabbits and attenuated it by drying the spinal cords in sterile flasks for different periods. Dogs given a series of injections of progressively less attenuated cord material became resistant to rabies. On 6 July 1885 a nine-year-old Alsatian boy, Joseph Meister, who had been badly bitten by a rabid dog two days earlier, was brought to Pasteur’s laboratory. Since rabies has a long incubation period, there was time to build up immunity before symptoms appeared. Because Pasteur was not a physician, the injections were given by the physicians Alfred Vulpian and Jacques-Joseph Grancher. Over eleven days Meister received thirteen injections of increasingly virulent material. He did not develop rabies. In October a second patient, the shepherd boy Jean-Baptiste Jupille, was treated successfully, and within a year more than two thousand people had received the treatment. Public subscription raised the funds to found the Institut Pasteur in Paris, which opened in November 1888. Meister later worked there as a caretaker.
Koch’s attempt at a cure for tuberculosis was less fortunate. In August 1890, at the International Medical Congress in Berlin, he announced that he had found a substance that halted the growth of tubercle bacilli in guinea pigs. Under pressure from the Prussian government, which was eager for a national triumph, he released the remedy, later named tuberculin, a glycerine extract of the bacilli, before he had tested it properly or disclosed its composition. Thousands of patients travelled to Berlin to receive it. It did not cure tuberculosis, and in some patients it caused severe reactions and death. The affair damaged Koch’s reputation, though tuberculin later proved valuable as a diagnostic test, since people previously infected with the organism react to it in the skin. In 1891 the Prussian state founded an Institute for Infectious Diseases for him in Berlin, now the Robert Koch Institute.
The Bacteriological Era
Using Koch’s methods, his pupils and others identified the causes of a long list of diseases within two decades. Albert Neisser identified the gonococcus in 1879. Carl Eberth described the typhoid bacillus in 1880 and Gaffky grew it in 1884. Loeffler and Edwin Klebs identified the diphtheria bacillus in 1883 and 1884, and Arthur Nicolaier described the tetanus bacillus in 1884, which Shibasaburo Kitasato, working in Koch’s laboratory, grew in pure culture in 1889. Theodor Escherich described the common colon bacterium now named after him in 1885, Anton Weichselbaum the meningococcus in 1887, and Alexandre Yersin and Kitasato the plague bacillus in Hong Kong in 1894. In 1890 Emil von Behring and Kitasato showed that the blood serum of animals immunised against diphtheria or tetanus contained antitoxins that could protect other animals, and diphtheria antitoxin, produced commercially from horses, was in use by 1894. Behring received the first Nobel Prize in Physiology or Medicine in 1901.
Not all diseases fitted the bacterial model. In 1892 the Russian botanist Dmitri Ivanovsky found that the agent of tobacco mosaic disease passed through the porcelain filters developed by Chamberland, which held back all bacteria, and in 1898 the Dutch microbiologist Martinus Beijerinck concluded that it was a new kind of infectious agent, which he called a contagious living fluid. In the same year Loeffler and Paul Frosch showed that foot-and-mouth disease was caused by a similarly filterable agent. These viruses could not be seen or cultured with nineteenth-century methods, and they did not satisfy Koch’s postulates in their original form. The search for them, and for the agents of diseases such as influenza, poliomyelitis and later AIDS, required new techniques. The history of the discovery of HIV in the 1980s shows the same questions that occupied Koch, about how to prove that a particular organism causes a particular disease, being argued with molecular tools.
Koch received the Nobel Prize in Physiology or Medicine in 1905 for his investigations and discoveries in relation to tuberculosis. In his later years he worked on sleeping sickness in East Africa, on malaria and on plague, and he emphasised the role of healthy human carriers in spreading diseases such as typhoid. He died of a heart attack at Baden-Baden on 27 May 1910. Pasteur had died at Marnes-la-Coquette, near Paris, on 28 September 1895, and was buried in a crypt within the Institut Pasteur.
What the Germ Theory Changed
The germ theory gave medicine, for the first time, a specific explanation of the causes of many of the commonest and most lethal diseases. Once it was known that tuberculosis, cholera and typhoid were caused by particular organisms spread in particular ways, it became possible to interrupt their transmission deliberately. Water filtration and later chlorination, the pasteurisation of milk, the inspection of meat, the isolation of infectious patients, the disinfection of rooms and the testing of carriers all followed. Surgery was transformed, first by Lister’s antiseptic methods and then by aseptic surgery, in which instruments, dressings, gowns and gloves were sterilised by steam before an operation so that organisms never reached the wound. Combined with anaesthesia, asepsis made it possible to open the abdomen, the chest and the skull with a reasonable chance of survival.
The theory also made possible the search for drugs that would kill bacteria inside the body without harming the patient. Paul Ehrlich, who had sat in the audience at Koch’s tuberculosis lecture, introduced the arsenic compound Salvarsan against syphilis in 1910. Gerhard Domagk’s sulphonamide drugs followed in the 1930s, and the discovery of penicillin by Alexander Fleming in 1928, and its development as a drug by Howard Florey, Ernst Chain and their colleagues at Oxford in the early 1940s, opened the era of antibiotics. Each of these steps rested on the agar plates and pure cultures that Koch’s laboratory had developed in the early 1880s, and on Pasteur’s demonstration that micro-organisms are living things with their own needs, which can be studied, weakened and killed.
References
- Germ theory of disease - Grokipedia, from Fracastoro and Leeuwenhoek to Pasteur, Koch and the bacteriological era
- Louis Pasteur - Grokipedia, molecular chirality, fermentation, spontaneous generation, vaccines and rabies
- History of the Institut Pasteur - Institut Pasteur, Paris
- Robert Koch - Grokipedia, anthrax, bacteriological methods, tuberculosis, cholera and tuberculin
- Robert Koch: Facts - NobelPrize.org, the Nobel Prize in Physiology or Medicine 1905
- Robert Koch: The Current State of the Struggle against Tuberculosis, Nobel Lecture - NobelPrize.org, 12 December 1905
- Koch’s postulates - Grokipedia, Henle, Koch, Loeffler and the limits of the criteria
- Spontaneous generation - Grokipedia, Redi, Needham, Spallanzani, Pouchet, Pasteur and Tyndall
- Ignaz Semmelweis - Grokipedia, puerperal fever at the Vienna General Hospital
- John Snow - Grokipedia, the Broad Street outbreak and the water companies study of 1854
- Joseph Lister - Grokipedia, carbolic acid and antiseptic surgery
- Pasteurization - Grokipedia, wine, beer and milk
- Petri dish - Grokipedia, solid media, agar and Julius Richard Petri
- Tuberculosis: fact sheet - World Health Organization, Geneva
