Robert Koch: With System Against Disease

May 27, 2010, marked the 100th Anniversary of the death of Nobel Laureate Robert Koch. He discovered the bacillus responsible for tuberculosis and laid the ground-work for modern bacteriology and epidemic research. His true ambition, though, had been to become an explorer and world traveler like Alexander von Humboldt. Instead, he became an accomplished explorer in the world of the microscope.

In a time when the doctors were helpless against devastating diseases and held the opinion that "contaminated air" was the cause of many infectious diseases, an unknown country doctor made the great breakthrough in medical research. Robert Koch's discovery that certain diseases are caused by bacteria was the start for sweeping successes in the fight against the scourges of humanity: anthrax, tuberculosis and cholera.

Robert Koch's researches read like the ABC in a health lexicon. With anthrax, babesiosis, and cholera, he succeeded in identifying the pathogen itself or at least found their pathogenic properties. His success lay in his highly systematic way of working. It allowed him to isolate and identify individual bacteria and led him to develop specialized strategies to fight them. With his work, he laid the foundations for the teachings of hygiene and today's health system. But he had never abandoned his dream of becoming a world traveler. Whenever offered the opportunity, he didn't hesitate to combine his profession and his research with his dream of seeing the world; accordingly, he took every opportunity offered to study epidemic break-outs in the remotest corners of the world.

Robert Koch was born in 1843 into a miner's family in Clausthal in the Harz region of Germany. He went to study natural sciences at the University of Göttingen in 1862 but realized during his first year that his interests lay in a different direction and he started to study medicine instead. There, he studied under Professor for anatomy Jacob Henle.

Henle was a master in the use of the microscope which he used as part of his lectures. In 1840, he had put his reputation in jeopardy by publishing his theory that infectious diseases were caused by living parasitic organisms. He had based his theory on the find of anthrax (bacillus anthracis) in the faeces of diseased animals. The proof for the direct connection between the parasite and the disease had escaped him, though. Student Robert Koch in turn was intrigued.

Robert Koch obtained his doctorate even before his final exams. He moved to Berlin where he studied chemistry under Professor Rudolf Virchow. He then moved to Hamburg in the hope of being hired as a ship’s doctor but failed to obtain a post. Instead, he practiced in Hamburg Hospital where he was first confronted by the devastating dimensions of a cholera epidemic. Starting to investigate pathological material microscopically, his path of research was set.

The outbreak of the Franco-German war of 1870/71 made him join the military as a field doctor. The experience he gained there in wound care and in dealing with typhoid fever later proved to be invaluable assets in his research. After his return from the war, he passed his exams as a state doctor (called ‘Physical Exam’). He was then sent to rural Wollstein in the district of Poznan where he opened a private practice.

Anthrax had been decimating European livestock for centuries. In his rural practice, Robert Koch was confronted with the problem on a daily basis. Even grazing grounds that had been left lying fallow for years after an outbreak would bring the epidemic back once livestock was allowed to graze on them again. Robert Koch decided to investigate.

In his rural setting, Robert Koch was cut off from contact with scientists and far away from libraries. With limited resources, he began to conduct research in his spare time. First, he installed a makeshift laboratory in the apartment he shared with his wife and newborn daughter. Building on the works of Jacob Henle, Aloys Pollender, and Casimir Joseph Davaine on anthrax, he started to research the connection between bacteria, symptoms, and sickness. Examining blood and tissue taken from cows that had died of anthrax, he discovered millions of bacilli. He had his work cut out to prove that they were the reason for the sickness rather than an accessory to the sickness. To this end, he infected mice and guinea pigs with the bacilli to observe if they would develop any sign of sickness. They developed the typical discoloration and swelling of the spleen and soon died. Examining these corpses in turn, he found the agents in each of the dead animals.

Robert Koch was not content in taking this as proof positive that the bacilli could cause the sickness, as another unknown agent in the transferred blood could cause it just as well. For a proof positive, he would need to get organisms that had had no prior contact with blood or tissue of infected animals. He therefore started to cultivate bacteria in a nutrient made up of the aqueous excretion from the eye chambers of oxen. Repeating the process over several generations of bacteria, he went on to prove by means of more experimentally infected animals that the organisms were the cause of anthrax and not accessories.

In the course of his observations, he found that the bacilli were able to survive under inimical conditions such as lack of oxygen and that they were able to form survival structures called spores. These spores were able to lie dormant over years just to reawaken and form new anthrax bacilli. He had effectively solved the mystery of the cause of recurring loss of livestock in fields where animals had died years ago. Louis Pasteur would later build on Robert Koch’s findings to produce a vaccine.

After Robert Koch had published his research on anthrax in 1876, he used the following years to perfect his microscopic techniques. Based on the ideas of Carl Weigert, he developed a process to color the transparent bacteria. And he became the advocate of microscopic photography as a method of record and dissemination of information. With his systematic approach, microscopic evidence of breeding of organisms in pure cultures, and their transmission to laboratory animals he laid the foundation for modern bacteriology. The doors to investigating other infectious diseases had been pushed wide open.

Robert Koch was convinced that any wound infection was triggered by a specific pathogen. He therefore threw himself enthusiastically into research. In 1878, he published his findings on the aetiology of wound infections and achieved a growing reputation among experts. The newly founded Imperial Health Office became aware of him and his work and called him to Berlin. In 1880, Robert Koch took over the direction of the bacteriological department. He was finally able to continue his research under prime conditions with the most modern laboratory equipment available. 

He embarked on a new quest immediately. Hospitals had the problem that even routine operations would see their patients die by the score due to infections. Using his own staining technique, Robert Koch was able to demonstrate the presence of bacilli in the hospitals and, worse, on their surgical instruments. These infections occurred despite the use of carbolic acid or heat sterilization prior to operations. Robert Koch was subsequently able to prove that carbolic acid would kill life bacilli but not their spores if used as a rinse; heat sterilization suffered from the same defect. In consequence, he designed in a long series of trial and error the sterilization by super-heated steam. His subsequent publication of these results became the guidelines for bacteriology.

Robert Koch’s staining technique also allowed him to distinguish between different strains of bacteria. He was convinced that every disease had its own pathogenic organism; all he had to do was to find them, then associate them to the proper disease. This in turn would lead to an eventual cure. First, he verified that a pathogen was found in every stage of a disease in an infected host. From the diseased host, Robert Koch isolated the pathogen and then grew it in pure culture. Next, he inoculated test animals with bacteria from these cultures and observed whether they fell ill. If this was the case, he isolated the virus again from the test animal and compared it to the original under the microscope. Were they proven identical, he could say with certainty that this microorganism was the cause of illness and not its accessory. Based on Robert Koch’s research and systematic, his staff member Friedrich Loeffler formulated ‘Koch’s postulates’ for bacteriology. These postulates are still in use today, though in an adapted form.

After anthrax, tuberculosis was next on Robert Koch’s hit list. The disease killed one in seven Germans at the time. He obtained infected lung tissue from victims who had succumbed to the disease and injected it into rabbits and guinea pigs. But the bacterium itself eluded him until he had tried many different color staining methods. By that time, the infected test animals had died as well, and Robert Koch was able to prove the identical bacteria were in their blood as well. His aetiology of tuberculosis would mark the summit of his career. For his ground breaking work on tuberculosis he was awarded the Nobel Prize in 1905.

Finding the bacteria of tuberculosis was but the first step for Robert Koch. He was interested in the cure as well. Conversant with Louis Pasteur’s theory that dead bacteria vaccine should inoculate recipients against the real disease, he started testing along those lines on tuberculosis. What he came up with he called ‘Tuberculin’. It turned out to be a total failure and damaged his reputation considerably. He had kept his recipe for Tuberculin a secret as patenting of medicines at the time was not the norm. It later turned out his secrecy had a second reason as well: He didn't really know what was inside the concoction. It took Clemens von Pirquet to find a use for Robert Koch’s blunder as a reliable diagnostic method.

When Egypt succumbed to a cholera epidemic in 1883, Robert Koch was part of a German government commission travelling to Alexandria. On his way to isolate the cause for cholera, he discovered the agents for amoebic dysentery, cattle plague, bubonic plague, sleeping sickness, and bacterial conjunctivitis. By the time the epidemic subsided, he had isolated a suspect bacillus but nothing more. Taking along its pure strains he had cultivated in Alexandria he returned to Berlin.

Upon his return, Robert Koch heard of another cholera outbreak in India and embarked immediately for Calcutta. There he found the same bacteria in the victims. Although he failed in transmitting the virus to animals, he was confident that he had found the causal agent of cholera. But he needed to know how the disease was transmitted to be able to take appropriate countermeasures. After a long search, he discovered the bacteria in polluted water tanks and found out that they could be transmitted through drinking water, food, and clothing.

Robert Koch could have saved himself a lot of work on cholera by referring to the writings of Italian anatomist Filippo Pacini who had discovered the cholera pathogen in 1854. Pacini had not been taken seriously, though, as the prevailing scientific stance was that cholera was transmitted by bad miasma in the air.

Back in Berlin, Robert Koch immediately prompted periodic inspections of drinking water supplies and suggested improvements to sanitation such as water filtration. Once more systematically approaching the problem, he laid the foundation for the containment of epidemics. When in 1892 the cholera broke out in Hamburg, Robert Koch was the obvious choice to be sent to Hamburg. On his arrival, he was so appalled by the unhygienic conditions that prevailed in the slums and emigration barracks of Hamburg that he coined the phrase: "Gentlemen, I forget that I'm in Europe."

Robert Koch was then appointed head of the newly founded Institute for Hygiene of Berlin’s Friedrich Wilhelm University. When the Royal Prussian Institute for Infectious Diseases opened a few years later, Robert Koch was appointed its director. The institute would become the forerunner of the modern Robert Koch Institute. Since 1896, he had concentrated on research into tropical diseases. These included animal diseases in southern Africa, such as rinderpest, Texas fever, and coast fever. Although he didn't succeed in identifying the causative agent of rinderpest, he was able to stop the further spread of the disease by inoculating healthy animals with bile from infected animals.

His particular interest, though, was directed at diseases transmitted from animals to people such as malaria and sleeping sickness. He soon realized that there were four different forms of malaria. But how the disease was transmitted exactly escaped him at first. By the time the Briton Sir Ronald Ross published his findings on the life cycle of plasmodium parasites in anopheles mosquitoes, Robert Koch had arrived at the same conclusions. Robert Koch was successful in containing the disease with the use of quinine as a medicine.

Robert Koch retired from his directorship of the Royal Prussian Institute in 1904 but continued to research. In 1906, he returned to Central Africa to assist in the fight against sleeping sickness. David Bruce had already identified the tsetse fly as its intermediate host. Robert Koch experimented with arsenic on sick and healthy alike. The minor successes were offset by major draw-backs; the treatment soon killed more people than the disease. The news started to run before Robert Koch, and the population of whole villages tended to fade into the surroundings when Robert Koch’s helpers came near. He had more success with burning down the brush to deprive the fly of its breeding grounds.

In 1910, he suffered a heart attack while in Berlin and retired to Baden-Baden where he died in the clinic of Dr. Dengler. With Robert Koch’s background, it may hardly surprise that he had ordered his body to be cremated. His ash was taken to Berlin and he was buried in a specially erected mausoleum inside the Robert Koch Institute.

Further reading
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Prophet of The Great War