by Sean Martin
Robert Koch also played a pivotal role in science’s thinking about disease. Convinced that diseases were caused by germs, he formulated a set of rules that became known as Koch’s Postulates:
1. The bacterium must be present in every case of the disease.
2. The bacterium must be capable of being isolated and grown in pure culture.
3. The specific disease must occur when the culture-grown bacillus is injected or inoculated into a host.
4. The bacterium must then be recoverable from the experimentally infected hosts.
These strictures, as John Waller noted, ‘soon acquired an authority on a par with the rules Moses brought down from Mount Sinai’.335 The increased rigour demanded by Koch’s postulates meant that, while it might take time for the causative agent of a disease to become proven, such as in the case of cholera, when that agent was found, it was definitive; there could be no going back to miasmas and tainted soil. Humoural theory had at last been laid to rest. It had had a good run, dominating medical thinking since Galen’s time. What replaced it was germ theory.
In addition to Koch, the other great name of the period was the Frenchman Louis Pasteur (1822–95). The two men could be regarded as among the principal architects of germ theory, although they did not invent it. As early as the sixteenth century, Girolamo Fracastoro had proposed that diseases were caused by ‘seeds’, and the invention of the microscope in the following century suggested that the great Italian doctor was correct. Englishman Robert Hooke (1635–1703) and Dutchman Antonie van Leeuwenhoek (1632–1723) reported seeing microbes beneath their instruments, and thus virtually invented the science of microbiology. Nicolas Andry (1658–1742) and Richard Bradley (1688–1732) both believed that the small organisms seen under Hooke’s and Leeuwenhoek’s microscopes caused disease, although they had no way of proving it.
Silkworms, dead bodies, childbirth and a cattle disease all played an unlikely role in the development of germ theory in the following century. The Italian entomologist Agostino Bassi (1773–1856) discovered that muscardine, a disease that affects silkworms, was caused by a fungus (eventually dubbed Beauveria bassiana in Bassi’s honour). This was the first time a microbial organism had been shown to cause a disease. And if silkworms could be so affected, Bassi reasoned, why not humans?
In 1843, the American physician and author Oliver Wendell Holmes (1809–94) wrote an article important in the history of germ theory, in which he noted the case of a physician who had examined the body of a man who had died of gangrene of the leg, and then attended a woman giving birth. She, and six other women he had treated, all developed puerperal fever. Also known as childbed fever, it had been known to Hippocrates, and by the early nineteenth century was a frequent cause of mothers dying in childbirth, claiming 5 to 20 per cent of maternity fatalities. In some small hospitals, it was not unknown for epidemics of puerperal fever to break out, killing between 70 to 100 per cent of expectant mothers.336 Holmes believed that puerperal fever was contagious, and in the case he’d studied, it had somehow been transmitted from the dead man to the mother. Holmes argued that the chance of a woman contracting puerperal fever could be greatly reduced if doctors washed their hands thoroughly before conducting an examination. This simple solution was greeted with outrage in some quarters: Charles Meigs, an obstetrician practising in Philadelphia, countered with a typical response, exclaiming that ‘Doctors are gentlemen, and gentlemen’s hands are clean!’337
Similarly outraged gentlemen greeted the work of the Hungarian Ignaz Semmelweis (1818–65), a doctor at the Vienna maternity clinic. Puzzled by the ten per cent death rate from puerperal fever in the student wards, compared to three and a half per cent in the midwives’ ward, Semmelweis was convinced that the disease was transmitted by staff who had carried out autopsies and dissections just prior to working on the maternity wards. He advised hand-washing in a chlorine solution to sterilise the hands, whereupon the death rate fell to less than two per cent in his ward. His colleagues were outraged that Semmelweis was implying their professional practices were below par, and the ensuing row caused Semmelweis to resign and move to a hospital in Budapest. There, he wrote a book in 1861 that linked childbed fever with the autopsy room, and argued that midwives who had not worked in autopsy or dissection rooms had a much lower incidence of puerperal fever and deaths than those who had. Another furore ensued, and this time Semmelweis had a breakdown, being admitted to a mental hospital in 1865 where he contracted the skin disease erysipelas – ironically an infection caused by the same pathogens as puerperal fever – and died.338 However, Semmelweis was vindicated in 1879 by Pasteur, who, while researching sepsis in surgery (among other things), identified the bacteria (streptococci) responsible for puerperal fever, erysipelas and scarlet fever. During the 1880s and 90s, English surgeon Joseph Lister (1827–1912) would do much to improve surgical safety by sterilising equipment before use.
Around this time, anthrax entered the story of germ theory. Anthrax has a long history. It has been speculated that the fifth and sixth Plagues of Egypt in the Book of Exodus could have been anthrax (see Chapter 2), while Virgil graphically records a virulent animal plague in The Georgics (III) that humans were also susceptible to. Anthrax is a disease that affects primarily cattle, sheep and goats. Humans can become infected through contact with animals or animal products, although they can’t spread it from one person to another. There are three forms of human anthrax, and they are all at the ghastly end of the scale. The gastrointestinal form is caused by eating contaminated meat, when it attacks the intestines, causing severe diarrhoea and vomiting; the cutaneous form is contracted through cuts or lesions in the skin, and can cause malignant pustules and vivid rashes; or the disease can take hold via the airways, when it settles in the lungs, and causes pneumonia-like symptoms and collapse of the lungs. This pulmonary form is the most lethal, with mortality rates around 80 per cent. Even the mildest form of anthrax, the cutaneous, claims around 20 per cent of those infected. The gastrointestinal form is somewhere between the two. Its effects on animal victims are equally severe.
The causative agent, Bacillus anthracis, was discovered by the French physician Casimir-Joseph Davaine in 1863, although Davaine could not prove at the time that the rod-shaped bacillus was definitely the cause of the disease. Davaine also couldn’t provide a solution for one of the key mysteries of anthrax – the puzzle of how a herd of cattle or flock of sheep could be healthy one day, but dead the next. Robert Koch agreed with Davaine that the rod-shaped bacillus was the cause of anthrax, and set about proving it.
In the early 1870s, Koch was living in the small Polish town of Wolsztyn (then part of Germany), which was at the time plagued with anthrax. Koch decided that if the elongated corpuscles Davaine had seen were indeed the cause of anthrax, then they must be able to survive outside of an animal’s body for long periods of time. Experimenting by injecting infected blood into ox eyes, Koch surmised that the spores produced by the bacillus lie in grass and soil until ingested by an animal. Once in the animal’s system, the bacillus is able to feed, grow and replicate itself, killing the animal in the process. Koch injected some of the spores into mice, which quickly developed anthrax and died. He then injected other mice with a different spore-producing microbe, and the second batch of mice remained healthy. Koch was convinced that the elongated bacillus caused anthrax. Now he had to prove germ theory to everyone else.
Koch demonstrated his findings to leading bacteriologist Ferdinand Cohn at the University of Breslau. Cohn was convinced, and word soon spread. Koch published his findings, but still had critics, who pointed out that he had not been able to isolate the anthrax bacillus from the blood. A chance, however slender, remained that the disease was caused by a mysterious something else in the blood. In 1876, Louis Pasteur managed to grow Bacillus anthracis in a culture of urine, which was then injected into guinea pigs. No blood was used in this experiment; the animals developed anthrax and died. (The use of guinea pigs in these and other pioneer
ing experiments is the origin of the term ‘guinea pig’ to mean any experimental subject.)
Now all that was needed to prove that a germ caused anthrax was a vaccine, and that is what Pasteur was able to demonstrate in 1881. In May, 25 sheep were given two shots of Pasteur’s vaccine, 25 were not. On 31 May, all 50 animals in the experiment were injected with a virulent strain of anthrax. On 2 June, it was found that all 25 of the control group were dead or dying, while all but one of the vaccinated group were healthy. (The vaccine used on the day had been developed by one of Pasteur’s team, Charles Chamberland. Pasteur took all the glory, and made further refinements to his colleague’s vaccine. The vaccine had really been a team effort, but Pasteur, ever the showman, is the one who is remembered.) As Bassi had wondered about infection, so too did Pasteur (who kept a portrait of the Italian in his office). If germs caused anthrax, then surely the same must hold true for other diseases? Perhaps all?
Less than a year later, on 24 March 1882 in Berlin, Koch delivered his paper ‘On the Aetiology of Tuberculosis’, in which he demonstrated that he had isolated the tuberculosis bacillus. Koch’s audience were stunned. The immunologist Paul Ehrlich recorded that ‘All those present were deeply moved and that evening has remained my greatest experience in science.’339 Koch explained how he had followed the lead of the French doctor Jean-Antoine Villemin who, in 1865, had been almost alone in claiming that tuberculosis was contagious, capable of being passed from humans to rabbits. Probably due to the fact that TB is only mildly contagious, many scientists were unable to replicate Villemin’s results. Worse, there was no sign of the TB germ.
As John Waller notes, one of the problems in proving that a microbe was the cause of tuberculosis was that it was very difficult to make the TB bacillus stand out in a culture. Koch began using industrial dyes, first methyline blue and then ‘washing’ it with another dye called vesuvin, which isolated the ‘elongated, wiry but incredibly small germ’ that ‘seemed to be present in all cases of TB’.340 Another problem had been the slow rate at which the TB bacteria replicate themselves. Although most bacteria can replicate within 24 hours, thus providing the scientist with a ‘healthy’ culture overnight, Koch had to wait two weeks for the TB bacillus to produce a colony. (The disease can also have a very long incubation period, making it impossible to tell when a person will actually start to become sick.) Once he had his colony, Koch injected the bacillus into healthy guinea pigs, which developed tuberculosis.
Koch’s discovery was a major step forward for advocates of germ theory, and the new discipline of bacteriology. As John Waller notes, ‘Everywhere, from the hospital ward to the parlour room and the public house, the danger of the invisible germ began to capture the public’s attention.’341 Germs quickly became the nineteenth century equivalent of mediaeval demons, who were thought to lurk everywhere. But unlike demons, germs could be seen under the microscope.
Pasteur, Koch and their respective teams, together with other scientists around the world, spent the last two decades of the nineteenth century on a crusade. Both men set up research facilities that continue to exist today, the Pasteur Institute in Paris and the Robert Koch Institute in Berlin. Germs were conclusively proven to be the cause of disease in case after case: in addition to cholera and tuberculosis, rabies, puerperal fever, undulant fever, diphtheria, leprosy and tetanus – among others – were shown to be caused by microbes. Vaccines were developed for many. Epilepsy was revealed to be a neurological disease, even if its mysteries still went unfathomed. The historian and explorer William Winwood Reade rhapsodised that ‘Disease will be extirpated; the causes of decay will be removed; immortality will be invented.’342 Although such hubris now seems woefully premature, we can’t hold Reade’s optimism against him. This was, after all, an age giddy with invention; Victorians and Edwardians thought that they would invent everything, cure everything, conquer all.
The Third Plague Pandemic
Both Koch and Pasteur can claim indirect credit for the victory over one of the most feared diseases in history – plague. The Third Pandemic of plague began in the Yunnan province of China in 1855 and would have probably remained contained there were it not for a rebellion by the Hui – indigenous Chinese who practised Islam – and other Muslim ethnic groups. This uprising, known as the Dungan Revolt, began in 1862 and lasted for fifteen years. The waves of refugees that the conflict generated took the plague with them, often heading towards more densely populated regions of China and resulting in the pandemic reaching ports such as Shanghai and Canton, where there was a catastrophic outbreak in 1894, which killed 60,000 people in a matter of weeks.
It was while the plague was raging in Hong Kong in the summer of 1894, killing an estimated 100,000 people – 75 per cent of the population – in just two months, that a young Franco-Swiss bacteriologist named Alexandre Yersin (1863–1943), who had studied under Pasteur in Paris, began to examine plague victims in search of the cause of the disease. He had little money or equipment, and worked in a hut he built himself in the grounds of the city’s Alice Memorial Hospital. Made to feel unwelcome by the British head of the hospital, Yersin was virtually persona non grata and had to acquire cadavers through bribery.
In contrast, a Japanese team that arrived days before Yersin had been extended every courtesy, being given a room in the hospital in which to work, and all the equipment they needed. The Japanese effort was led by Aoyama Tanemichi (1859–1917) and Shibasaburo Kitasato (1853–1931), a former student of Koch’s in Berlin, who had also worked on antitoxins for tetanus, diphtheria and anthrax. Within a fortnight of arrival, Tanemichi and two other members of the team had contracted plague (one fatally). Undeterred by the loss of half his team to the disease they were studying, Kitasato continued working, and on 14 June, he announced that he had found the bacillus that caused plague. Within days, Yersin emerged from his hut to announce the same news. It was yet another controversy. Kitasato had made the discovery first, but Yersin’s was the better science. The plague bacillus, Pasteurella pestis, was eventually renamed Yersinia pestis in his honour. Yersin noted that Hong Kong seemed to have more than its fair share of dead rats, and four years later the French bacteriologist Paul-Louis Simond (1858–1947), another Pasteur Institute alumnus, discovered that plague was a rodent disease, and that their fleas, X. cheopis, were the main plague vector.
The next major triumph over plague took place in Bombay, where the pandemic claimed 19,000 lives in the space of the six months from August 1896 to February 1897. In the midst of this runaway death toll, Waldemar Haffkine – like Yersin and Simond, a student of Pasteur – was called in to offer what assistance he could in containing the disease. Working in the unlikely setting of a makeshift laboratory set up in a corridor in the city’s Grant Medical College, Haffkine spent three months of round-the-clock work trying to find a vaccine against plague. It was a strenuous and difficult task; two of his assistants walked out on him, while a third had a nervous breakdown. On 10 January 1897, Haffkine felt that the vaccine was ready and tested it on himself. He then asked for volunteers from a local jail: all those who had been inoculated survived, while the control group, who had not had the vaccine, lost seven members to the plague.
Despite these scientific breakthroughs, the Third Pandemic proved impossible to stop. As with the Black Death, the disease spread along trade routes. International shipping unwittingly helped to spread the disease more rapidly around the globe, and it struck with particular virulence in India, Australasia, North Africa, South Africa and South America. Hawaii suffered a severe outbreak in late 1899, and the Board of Health decided on the drastic action of burning down Honolulu’s Chinatown in a last-ditch effort to stop the disease spreading further. San Francisco was affected in 1900–1904, and again in 1907–1909, the second outbreak being exacerbated by insanitary conditions following the earthquake of 1906. Probably travelling over land, the pandemic also reached Russia, which experienced the last major European outbreak of plague during the last two decades of
the nineteenth century. It continued to add to the sufferings of the Russian people, however, well into the 1920s, by which time the country had experienced revolution and was wracked by civil war.
Western Europe looked on aghast as the pandemic seemed to get ever nearer, and medical authorities met in Vienna in 1897 to draw up contingency plans in case the disease travelled any further west. It did, coming in with the ships, but remained contained in ports such as Glasgow, Liverpool, Cardiff and Hamburg where there were only a handful of deaths, mainly among port workers. Sporadic outbreaks continued worldwide for years. The last significant outbreak occurred in Peru and Argentina in 1945. The World Health Organization did not declare the Third Pandemic officially over until 1959, although some researchers believe it has yet to run its course completely.
The White Man’s Burden
Disease could still surprise. In January 1875, the Fiji islands were subjected to an epidemic of measles. In Europe, this was a usually harmless childhood disease. But in six months in the Fiji islands, around one quarter of the islands’ population of 135,000 died. The same disaster had happened in Hawaii in 1853, just as the Maori in New Zealand were succumbing to measles, smallpox, whooping cough and flu. Between 1840 and 1860, Maori numbers fell from over 100,000 to 40,000.’343 The Australian Aborigines likewise fell victim to smallpox, cholera, typhus and flu, followed by tuberculosis and leprosy, ending their forty thousand year isolation from the world’s diseases.
