Mycobacterium tuberculosis, the cause of tuberculosis, is an ancient bacterium that once thrived in primeval mud and probably afflicted humans as far back as the Neolithic era. There is documentary evidence that a disease very like it was known to the ancient Egyptians.[2] But it was in eighteenth-century Europe, as urban populations grew during the Industrial Revolution, that a highly infectious form of tuberculosis, pulmonary tuberculosis, took hold because it spread easily through coughing, sneezing and spitting. By the beginning of the nineteenth century one-quarter of all deaths in England were caused by tuberculosis and as the century progressed TB became endemic amongst the urban poor. There was no cure. People afflicted with TB turned to old wives’ remedies like cod-liver oil, pig’s pepsin, iodine and copper which, not surprisingly, provided at best minimal relief from symptoms. As tuberculosis became more entrenched and took a greater toll, it caused grave public concern.
The disease did not become known as tuberculosis until 1839 when the German physician Johann Lukas Schönlein introduced the term.[3] It was derived from the word ‘tubercle’ which seems to have originated in Sweden in the 1600s and entered the English language in 1689 when it was used by the English physician Richard Morton to describe the characteristic lesions that occur in the lungs of tuberculosis sufferers. In approximately 75 per cent of cases TB affects the lungs, the pulmonary form of the disease, where the bacterium slowly destroys lung tissue.
People can have tuberculosis for many years without knowing it. With pulmonary TB, when the infection becomes active the symptoms are a persistent dry cough, weakness, weight loss, fever and chest pains. Another form of the disease is disseminated, or miliary, TB—so called because in an X-ray the lungs resemble millet seeds. It is more common in people who have suppressed immune systems and in young children. Pulmonary TB can co-exist with extrapulmonary TB which can affect the central nervous system, the lymphatic system, the genito-urinary system, and bones and joints.
In industrialised Europe, the highly infectious pulmonary tuberculosis infected the poor in great numbers because of their impoverished living conditions. To stop the spread of the disease many were forced by public health authorities to enter sanatoriums, institutions that were more like prisons than hospitals and where there was little hope of recovery. The more affluent classes were not immune from the highly infectious disease but they could afford sanatoriums that offered excellent care and medical attention.
Despite the purported benefits of fresh air, exercise and the treatments provided in the sanatoriums, 50 per cent of patients still wasted away and were dead within five years of contracting the disease. It was the wasting that gave the disease one of its other names, ‘the consumption’, reflecting how sufferers appeared to be ‘consumed’ from within. Tuberculosis was also known as ‘the White Plague’ because sufferers appeared pale, a symptom that was associated with artistic sensitivity. It was seen as a disease that sought out the talented and creative as its victims—writers, politicians, musicians, artists and scientists. Cardinal Richelieu; Frederic Chopin; Robert Louis Stevenson; Amedeo Modigliani; Emily, Anne and Charlotte Brontë; Sir Walter Scott; Lord Byron; Simon Bolivar; Paul Gauguin; Anton Chekov; Eugene O’Neill; Jean-Jacques Rousseau; Florence Nightingale; and Alexander Graham Bell are just a few of the gifted who suffered the misery of TB.
In a perverse and paradoxical way, tuberculosis became romanticised and took on its own persona in literature, art and music. The afflicted are tragic characters in novels, operas and films. The death of Little Nell in Charles Dickens’ The Old Curiosity Shop, published in serial form during 1840 and 1841, caused genuine tears amongst readers of the tale on both sides of the Atlantic. The blood-soaked handkerchiefs and the tragic death of Margaret Gautier in Alexandre Dumas’ novel La Dame aux Camélias are legendary, and the beautiful and consumptive courtesan, Margaret, became Violetta in Verdi’s La Traviata, and Satine in the more recent film Moulin Rouge.
This fascination with the White Plague reflects its pervasive nature during the nineteenth century, but it was not until the 1880s when more was known about germs and infection that the very young German physician, Heinrich Hermann Robert Koch, laid the groundwork for the scientific battle against the disease. In March 1882, Robert Koch gave a lecture at the Physiological Society of Berlin to eminent doctors much more senior than himself. Showing a slide of animal tissue he pointed out the tubercle bacteria which were stained a beautiful blue.[4] These he announced were the cause of the ‘White Plague’, which at the time was responsible for one-seventh of all deaths in Europe.
It is ironic that Koch’s announcement met with the same kind of scepticism and jealousy that he and his followers meted out to Louis Pasteur; and Koch, like Pasteur, also endured the professional jealousy of many of his contemporaries. What is also ironic is that Robert Koch did much to further the work of Louis Pasteur. The discovery of the tuberculosis bacillus Mycobacterium tuberculosis established Koch as one of the founders of the science of bacteriology and he devised many of the field’s basic principles and techniques. Koch’s scientific oeuvre earned him fame in his own lifetime and won him a place in the scientific pantheon. But one of his greatest triumphs would also lead Koch to his darkest hours and a humiliating fall from grace.
KOCH’S EARLY LIFE
Born on 11 December 1843 at Clausthal in the Upper Harz Mountains, Robert Koch was the third of thirteen children born to Hermann Koch, a mining official, and Mathilde Biewend, the daughter of an iron mine inspector. Robert’s parents were astounded when they realised their son had taught himself to read from the newspapers at the age of five.[5] From this early age he displayed the methodical persistence which would be so characteristic of his professional life. Hermann Koch encouraged in Robert a fascination for the wonders of nature and also a desire for travel. He had a passion for collecting mosses and lichens and was fascinated by the anatomy of insects.
At the local high school Robert’s interest in biology strengthened and in 1862 he began studying medicine at the University of Göttingen, which was considered to be a great achievement for a boy from his social background. During his studies, Koch was exposed to a revolutionary theory that the professor of anatomy, Jacob Henle, had published in 1840. Henle hypothesised that infectious diseases were caused by living, parasitic organisms. This concept, which was later proven by Louis Pasteur, underpinned much of Koch’s research.
In 1866 Koch passed his final examinations with distinction and then passed the state medical examination in Hanover. After this he undertook studies in chemistry for six months at the Berlin Charité Hospital, the largest and oldest hospital in the city. Here Koch came under the influence of Rudolf Virchow, an influential pathologist, anthropologist and politician but from this time on Koch was never able to win the respect of the doyen of German science because of their variant views on the cause of disease.[6] Virchow proposed a cell theory of disease, believing that the presence of micro-organisms identified diseased tissue but he was convinced they were not the cause of disease.
At the age of 22 Koch, already exhibiting his peripatetic nature, took his first medical job as an intern at Hamburg General Hospital, where he saw first-hand the devastating effects of a cholera epidemic. People died in great numbers from this acute intestinal infection. In 1867 Koch became an assistant at an institution for intellectually disabled children in Langenhagen, a village near Hanover. At this time Robert Koch married Emmy Fraatz, the daughter of the Superintendant General of Clausthal, Koch’s hometown. Emmy has been described as a domineering woman who during their married life together stifled her husband’s desire to travel. But the marriage started well. After a brief sojourn in Niemegk, Emmy was happy when they settled at Rackwitz (now in Poland), where her husband established a flourishing practice.
When the Franco–Prussian War broke out in 1870, Koch volunteered for service but was rejected because of severe myopia. Perhaps it was his shortsightedness that made the microscopic world an appealing one for Rober
t Koch, one to which he would soon devote his life. On a second application to serve his country Koch was successful and was sent as a field hospital physician to France, where he worked first at a typhoid hospital at Neufchâteau and then a hospital for wounded soldiers near Orléans. Koch’s war experience gave him an understanding of typhoid and later in his career he developed public health measures for the control of both this disease and cholera. The horrors that Koch witnessed no doubt entrenched his anti-French sentiments.
After the privations of war, Robert Koch returned to Emmy and Gertrud, the couple’s only child, in the lakeside town of Wollstein, in a rural area near Berlin. While carrying out his duties as district medical officer from 1872 to 1880 Koch began his phenomenal research in a small laboratory he had built at the rear of his surgery, using a microscope that Emmy gave him for his 29th birthday. He converted a wardrobe into a darkroom and purchased microphotographic equipment that was crucial for the studies he was planning to carry out on micro-organisms.
Despite the much-documented antipathy that developed between Robert Koch and Louis Pasteur there were professional synergies: independently of each other Koch and Pasteur investigated anthrax. Despite the demands of his practice and his isolation in the country away from libraries and colleagues, Koch took up his research on anthrax, a disease prevalent among farm animals, the consequences of which he had witnessed in the Wollstein district and which created significant problems for farmers in France and Germany. A number of studies had already been done on the disease. In 1850 the French veterinarian Pierre Rayer had reported discovering the anthrax bacillus in the blood of animals that were dying from the disease, and had succeeded in transmitting it. The German Franz Antoine Pollender had claimed the same discovery in a publication in 1855, reportedly based on observations he had made in 1849.
Things were already competitive when the French scientist Casimir-Joseph Davaine, who was inspired by Louis Pasteur’s work, got involved. Like many early pioneers he did not have a proper laboratory and he kept his experimental animals in a friend’s garden. Despite the privations, in 1863 Davaine proved that a healthy animal that did not have anthrax could contract the disease if it was injected with a minute amount of blood from an infected animal, blood which contained rod-like micro-organisms. Conversely, these organisms were not present in healthy animals and therefore it was highly probable that they caused anthrax.
It was at this point that Koch took up the challenge to prove scientifically that the rod-like bacillus did in fact cause anthrax. For three years, between 1873 and 1876, he spent all his spare time finding out what he could about the disease. Koch inoculated laboratory mice using slivers of wood to inject them with anthrax bacilli taken from the spleens of dead, diseased farm animals. 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 succumb. This confirmed Davaine’s work, showing that the disease could be transmitted through the blood of animals suffering from anthrax.
Not satisfied with this, Koch wanted to know whether anthrax bacilli that had never been in contact with any kind of animal could cause the disease. To solve this problem he obtained pure cultures of the bacilli by growing them on the aqueous humour of ox eyes (the fluid between the cornea and the lens). By studying, drawing and photographing these cultures, Koch recorded the multiplication of the bacilli and noted that, when conditions were unfavourable to them, especially a lack of oxygen, they produced dormant spores that could remain viable for years. Even if they had had no contact with any kind of animal, under the right conditions the spores could develop into the bacilli and cause anthrax.[7] This finding explained why this surreptitious disease could recur in pastures that had not been used for grazing for a long time and why it is an inveterate survivor.
Louis Pasteur had introduced the concept that a disease organism might be cultured outside the body but the techniques for doing this, which were essential for his groundbreaking research and for many medical advances that were to follow, were perfected by Robert Koch. The genesis of Koch’s pure-culture techniques was a discovery by Joseph Schroeter who worked with Ferdinand Cohn, the professor of botany at the University of Breslau. In 1872 Schroeter found that chromogenic, or colour-forming, bacteria would grow on what are called solid substrates such as potato, coagulated egg white, meat and bread, and that these colonies could form new colonies of the same type and colour.[8] Koch also invented the drop technique in which micro-organisms are cultured in a drop of nutrient solution on the underside of a glass slide, and so we have the stereotype of scientists dripping solutions onto slides and examining them under the lenses of their microscopes.
Koch’s anthrax experiments gave the first real proof of a relation between a particular bacillus and a particular disease. When Koch demonstrated the results of this painstaking work to Professor Cohn at the university, Cohn called a meeting of his colleagues. They were impressed. Cohn, who was the editor of a botanical journal, published Koch’s findings in 1876 and Robert Koch achieved instant fame.
As Pasteur had done Koch turned his attention to germs that specifically affected humans. He knew that infected blood contained septicaemia germs but he could not detect them under a microscope, which meant other scientists were unlikely to believe him. To prove that this specific germ causes blood poisoning Koch focused on improving his methods of fixing, staining and photographing bacteria and when it was stained with methyl violet dye he was able to see the septicaemia germ under a microscope.[9] As additional proof for the doubters Koch photographed the germs. This invaluable work on diseases caused by bacterial infections of wounds enabled Koch to provide a practical and scientific basis for the control of these infections. He published his results in 1878.
In the summer of 1879, Koch was appointed to the position of city physician at Breslau but found the salary inadequate, perhaps for Emmy more than himself, and after three months returned to Wollstein. As Koch’s reputation and ambition grew, his patients took second place to his research and marital harmony was jeopardised as he spent more time closeted in his laboratory experimenting and reading research papers, and as an increasing number of menial tasks were delegated to his wife and daughter. More scientific apparatus was needed and the Koch household had to accommodate and feed the growing number of animals required for experimentation: innumerable mice, guinea pigs, rabbits, frogs, assorted birds and two monkeys.
By 1879 Robert Koch had perfected methods which made it easy to obtain and identify pathogenic bacteria in pure culture, free from other organisms. As a result Koch laid down the conditions that needed to be fulfilled in order to prove that particular bacteria cause particular diseases. Modifications that he made to these rules in 1882 resulted in what have become known as ‘Koch’s Postulates’.[10] The four postulates have since made it possible to accurately identify the causes of countless microbial diseases. They are: that the microbe or organism must be discoverable in every case of the disease; that once recovered from the body the microbe or organism must be grown in pure cultures for several generations; that the disease can be reproduced in experimental animals (i.e. a non-diseased susceptible ‘host’) through pure culture; and that the microbe or organism can be recovered from the inoculated animal or host that was experimentally infected, and then be recultured.
Robert Koch’s circumstances changed in 1880 when he was appointed to the Imperial Health Bureau in Berlin. Initially given only a small room, Koch was soon provided with a laboratory where he worked with his assistants, Friedrich Loeffler and Georg Gaffky. In Berlin Koch refined the bacteriological methods he had used in his cramped home lab in Wollstein. He perfected the technique of growing pure cultures of germs using a mix of potatoes and gelatine on a specially designed flat dish that was invented by another of his colleagues, Julius Petri. We may not know of Julius but we are certainly familiar with his dish, which is still in common use today. Koch’s techniques opened new horizons for future scientific discove
ries.
For various reasons, some of which were purely economic, governments in many countries in the nineteenth century were becoming increasingly involved in the control of hygiene and public health and advances in science were providing the means to do this. Koch’s reputation as a leading scientist was growing rapidly and in 1881, he and his team of researchers, under the health department’s director Heinrich Struck, were assigned to develop reliable methods for isolating and cultivating pathogenic bacteria and to gather bacteriological data and establish scientific principles which could be applied to hygiene and public health. Koch’s disciples worked tirelessly beside him and, according to Friedrich Loeffler, ‘almost daily new miracles of bacteriology displayed themselves’; one of these was the discovery of the tuberculosis bacillus.
DEFEATING DISEASE—A GLOBAL PURSUIT
When Robert Koch was invited to address the seventh International Medical Congress in London in 1881, to demonstrate his technique for obtaining pure cultures on solid media, he was already working on tuberculosis, a great threat to public health. It was at this conference that Joseph Lister introduced Louis Pasteur to Robert Koch and the animosity between the French and German scientists began. Some critics say that when Pasteur congratulated Koch on his work in Lister’s rooms, he did so with suppressed jealousy. Koch may also have been peeved because Pasteur had surpassed his anthrax work and developed a vaccine. This may have been the motivation for Koch’s arrogance when he publicly announced that Pasteur had added nothing new to anthrax research, after which the two men never again spoke civilly to each other.
Abandoning anthrax, the new driving force behind Koch’s research was to prove conclusively that tuberculosis was caused by an infective agent. This meant finding a way to identify and isolate the specific micro-organism. Koch began by taking tuberculous tissue from the body of a young man who in the space of three weeks had gone from being fit and well to having developed a cough and severe chest pains. Four days after being admitted to hospital he died, his emaciated body riddled with yellowish tubercles.
Smallpox, Syphilis and Salvation Page 9