Germ Theory: Pasteur Vs. Koch

Germ theory is the idea that you can’t have infectious disease without some kind of disease causing pathogen, and it’s the basis behind every modern treatment from vaccines to antibiotics. And there are two big scientists who get most of the credit for advancing germ theory in the late 1800s — Louis Pasteur from France, and Robert Koch from Germany.

And before I made the videos, I knew these two guys were around at somewhat the same time, but I didn’t realize just how much their rivalry actually advanced germ theory. So today, I’m going to give you a little background on each of them, go into more detail for their first public smackdown, and how their legacies took on rivalries of their own.

But before we go any further, I know the proper German pronunciation is Koh, but it’s hard to say that sound in American English. Guys, do you want to give it a try? German listeners, I’m sorry. 

Their beef really starts in the 1870s and revolves mainly around the discovery of anthrax, but we need some character development first. 
Some quick backgroundBy the 1870s, Pasteur was already a well known scientist internationally, and the leading scientist in this new field of bacteriology. He got his start as a chemist and first got popular thanks to his discovery of a property called chirality. This is where some molecules or crystals have handedness, or mirror opposite versions of themselves. 

He also showed that the process of fermentation happens thanks to the actions of microbes, which settled a debate about whether fermentation was entirely chemical or if biology was involved. He published two big papers on the topic — one on lactic acid in 1857, and another on alcohol fermentation in 1858. 

He also did a famous experiment where he debunked a super old idea called spontaneous generation, the idea that living things can come from nonliving things. 

Part of the experiment involved taking custom-made flasks, filling them with broth, and heating them up to kill off the existing bacteria inside — this made sure he was starting the experiment with a blank slate. And since his early work on fermentation showed that microbes caused milk and beer to spoil, he got the idea that you could blast the milk, or wine or whatever with some heat, kill off the microbes, and delay spoiling. 

He published his paper on the topic in 1863 and finally, patented this process of pasteurization in 1865. 

[Max] opportunity to plug Lister episode since Lister started reading Pasteur in 1864 — around this time in the story. 

So going into the 1870s Pasteur already had a mega successful career. He’d revolutionized both food preservation and inspired Lister’s revolution in surgery. And later in the late 1860s, he helped figure out how to stop an epidemic among France’s silkworms, which helped France’s economy, since they exported quite a bit of silk.

Enter Robert Koch. He was twenty years younger than Pasteur and studied under an anatomist you might not realize you’ve heard of: Friedrich Gustav Jakob Henle. Can you three name the anatomical structure he’s known for?

Well in 1840, he also came up with a set of criteria he’d use to show that a microbe caused a disease. You had to consistently find the microbe alongside the disease, you have to isolate the microbe from living tissues, then it has to produce disease when you give it to test animals. These criteria became known as Henle’s Postulates.

So Koch graduates from school and was primed to look for germs as the cause of disease, but other than having a well respected teacher he didn’t have any big accolades before going into our next chapter which is anthrax. 
AnthraxKoch starts working out in the countryside where local livestock are getting wrecked by anthrax. 

Anthrax is a rod shaped bacteria that can turn into a little spore outside of its host, and live dormant for long periods of time. There are a bunch of different ways of getting it, like through breaks in the skin or through the GI tract. Then when they get into a body, they reactivate and turn into their pathogenic form, and can kill their host within 36 to 72 hours. LIke sometimes the first time you’d recognize your cattle had anthrax was when a couple just dropped dead.

And a few years earlier, a separate rivalry of French and German scientists found a bacteria that tended to show up in anthrax. The Germans named it Bacillus anthracis while the French scientist called it Bacteridium anthracis. And given his mentor’s postulates, if Koch found the bacillus, he could show not just an association, but a cause and effect relationship.

Sure enough, he finds B. Anthracis in a bunch of cows and sheeps that he dissects. Then he does something cool and puts the bacteria into cow eyeball fluid, which gets the bacteria to multiply. This is called a culture of bacteria. Then he took that culture and injected it into experimental mice and they developed anthrax. And that was a big deal because for the first time, someone tested the idea that a specific germ caused a specific disease, which is the central idea in germ theory. 

He published his first anthrax paper in 1876 and published again in 1877. And it was a big hit right away. Then in 1878, Koch followed in his mentor’s footsteps and published his own postulates for disease causation. Basically, here’s how you might tell whether germ x causes disease y. 

So at this point, Koch is player on the international science stage, which got Pasteur’s attention. 

Koch mentioned in his report that the anthrax bacteria form these little spores which let them survive outside of their host, but couldn't figure out how that spore made their host sick. He just knew that when you injected the culture back into an animal, it got anthrax.

So in 1878, Pasteur’s lab basically repeated Koch’s experiments, but used a slightly different technique. From that, Pasteur reasoned that the anthrax spore morphed into the rod shaped, infectious bacillus in the body, which then caused disease. 

In an 1878 summary paper to the Academy of Sciences, Pasteur says: 

“I ask the Academy not to dismiss these curious results before I demonstrate one important theoretical conclusion. We insist on demonstrating at the start of these studies (that are opening a whole new world of knowledge) a proof that the cause of transmissible, contagious and infectious diseases resides essentially and uniquely in the presence of microorganisms”.

However, Pasteur doesn’t really acknowledge Koch’s recent work. He uses French nomenclature, Bacteridia anthracis, and doesn’t really acknowledge Koch’s recent work. That’s less to do with any personal beef they have, and more to do with national rivalries — they were coming off of the Franco Prussian war in the 1870s, which France lost.

In 1879, Pasteur and his team developed a vaccine against chicken cholera by exposing the germ to the air repeatedly. Those new, weaker cultures weren’t able to cause disease as easily as the normal bacteria, giving us the process of attenuation, which is still used today.

This was a different strategy than variolation and Jenner’s vaccination against smallpox. Chicken cholera was caused by a bacteria that they could study outside of a body. And if they could manipulate the germ, they could manipulate the course of disease. 

Pasteur started working on an anthrax vaccine next, but it behaved differently than chicken cholera. Since B. anthracis forms a spore when exposed to air, it didn’t matter how many times the Pasteur lab cultured the bacillus; they couldn’t create a weaker version. I mean, when you consider they can live dormant underground for literally decades, it’s no surprise that repeated exposure to air didn’t reduce virulence. 

So they decide to add some heat, and found that 42 to 43 celsius was just right for keeping the culture alive and replicating, but making it less virulent. 

In May 1881, Pasteur did a public experiment where he took 50 sheep and gave them all anthrax after vaccinating half of them against the disease. Sure enough, the vaccinated half all lived while the unvaccinated half all died. He got a ton of publicity for it, and stole the spotlight back from Koch. 

Koch responds by saying:
“Pasteur follows the tactic of communicating only favorable aspects of his experiments, and of ignoring even decisive unfavorable results. Such behavior may be appropriate for commercial advertising, but in science it must be totally rejected…. His behavior is simply inexplicable”.
From here, their careers split paths, but in kind of parallel tracks.Pasteur creates a rabies vaccine using a method more similar to the chicken cholera vaccine with the repeated cultures, but grown in dog and rabbit brain tissue. Rabies wasn’t affecting a ton of people, but it was an emotionally charged disease.

Koch finds the causative germ of tuberculosis and published his results in 1882, then another TB paper in 1884, which is when he updates Koch’s Postulates. In contrast to rabies, tuberculosis was a massive cause of mortality, and is still the leading cause of death from any infectious disease today.

Koch also found that Vibrio cholerae causes cholera.

In 1885, Pasteur opened the first Pasteur Institute in Paris, which was the first research center for biomedical science. It’s there where researchers start using the term microbiology instead of bacteriology. 

Koch decides he’s going to do his own research, independent of government funding, and instead fund it through applied research. Basically, a pharma company funding the research.

In 1890, comes out with tuberculin, which he touted as a TB treatment. It turned out to be ineffective, but we still use it today as the TB skin test. It was a pretty big embarrassment, but his reputation could take it. In 1891, he opened the Robert Koch Institute in Berlin with funding from the government. 

Pasteur died in 1895 but Koch, who was 20 years younger, had one more grand round in him. In 1896, he did a world tour and learns more about acquired immunity. He died in 1910
LegaciesBut even in death, their legacies have a rivalry through the institutes that they founded. 

First up was diphtheria —  a team of Koch’s students finds the diphtheria toxin, and one of them Emil Von Behring, starts working on a weakened antitoxin to create a vaccine. One of Pasteur’s close assistants and collaborators, Emile Roux, came up with a different serum therapy, using horses’ blood to produce it. 

Next, syphilis. Paul Ehrlich was a student and collaborator with Koch. After his time at the Koch Institute, he did a bunch of work with dyes which led him to salvarsan, which is one of the first effective antibiotics, albeit a narrow-use one. But syphilis was a big problem at the time, and antibiotics would become a much bigger deal.

Then, there was plague: One of the scientists who worked with Roux on diphtheria at the Pasteur Institute was a guy named Alexandre Yersin, who you might know as the namesake of Yersinia pestis, which he identified after leaving the Pasteur Institute. 

Then we go back to Tuberculosis. While Koch tried to cure tuberculosis with his failed tuberculin treatment, it was two french scientists at the Pasteur Institute who spent the early twentieth century creating a more effective anti-tuberculosis vaccine, called the BCG, which stands for bacille Calmette Guerin. 

From there, the Pasteur Institute expands globally (including one in NYC) and works on epidemic typhus and typhoid. The RKI unfortunately was used for scientific research during WWII, which meant Nazis.

References:
1- germ theory, in medicine, the theory that certain diseases are caused by the invasion of the body by microorganisms https://www.britannica.com/science/germ-theory
2-germ theory: the doctrine that infectious diseases are caused by the presence and activity of microorganisms, such as bacteria, viruses, or fungi, in body tissues. https://dictionary.apa.org/germ-theory
3- His studies on the optical activity and crystallography of these molecules allowed Pasteur to identify their molecular dissymmetry and their mirror-image nature. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027159/ 
4-  Among them, Louis Pasteur is certainly the father of molecular chirality (the so-called molecular dissymmetry) https://onlinelibrary.wiley.com/doi/full/10.1002/chir.23349
5- Demonstration of the experiment he used to show chirality at the molecular level. https://youtu.be/ZejAu_uPxMs?t=227
6- The fact that fermentation is part of the action of a living entity had been hypothesized since Antoine van Leeuwenhoek (1623-1723) observed yeast under a microscope in 1680. The link between these cells and the fermentation process was described in 1787 by Adamo Fabroni https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9027159/
7- In 1856, Pasteur was able to observe the microbes responsible for alcoholic fermentation under a microscope, as a professor of science in the University of Lille. https://en.m.wikipedia.org/wiki/Fermentation_theory
8- Pasteur began his research in the topic by repeating and confirming works of Theodor Schwann, who demonstrated a decade earlier that yeast were alive. https://en.wikipedia.org/wiki/Louis_Pasteur
9- Well, what he did was to discover that the fermentation was caused instead by living microorganisms, bacteria that he identified through the microscope. Now, this was a high-profile investigation in the 1860s, for the simple reason that the production of wine and beer involved two of France’s major economic activities. https://oyc.yale.edu/history/hist-234/lecture-14
10- Thus, he accumulated observations consistent with his hypothesis that lactic fermentation occurs in the presence of living organisms. https://www.frontiersin.org/articles/10.3389/fimmu.2012.00068/full
11-But in 1857, Pasteur proved that a microscopic plant caused the souring of milk (lactic acid fermentation). Pasteur was able to prove that living cells, the yeast, were responsible for forming alcohol from sugar, and that contaminating microorganisms found in ordinary air could turn the fermentations sour. https://lemelson.mit.edu/resources/louis-pasteur
12- Primary source! https://ssaal.univ-lille.fr/wp-content/uploads/2014/07/Sol_2007_p8-15_lactique1.pdf
13- Spontaneous generation or abiogenesis, the idea that living things could arise from inanimate objects, dates back to Aristotle in the fourth century BC…. Organisms such as flies and worms were “observed” to come from lifeless objects such as meat or decaying matter https://www.jstor.org/stable/4451121
14- …he incorporated the use of the now famous swan necked flasks in his experimental research. Swan-necked flasks permitted him to boil the broth and allow “natural air” to enter; however, these flasks prevented airborne microbes from reaching the broth, and thus the broth remained free of microbial growth https://www.jstor.org/stable/4451121
15- Pasteur's research also showed that the growth of microorganisms was responsible for spoiling beverages, such as beer, wine and milk. With this established, he invented a process in which liquids such as milk were heated to a temperature between 60 and 100 °C. https://en.wikipedia.org/wiki/Louis_Pasteur
16- He developed a protocol to fight the diseases, heating the wine to between 55°C and 60°C, a temperature at which it does not deteriorate and its bouquet is preserved. This method is now known worldwide as pasteurization. https://www.pasteur.fr/en/institut-pasteur/history/middle-years-1862-1877 
17- Pasteur and Claude Bernard completed tests on blood and urine on 20 April 1862.[67] Pasteur patented the process, to fight the "diseases" of wine, in 1865.[66] The method became known as pasteurization, and was soon applied to beer and milk. https://en.wikipedia.org/wiki/Louis_Pasteur
18- In 1864, while working at Glasgow University as Professor of Surgery, Lister was introduced to Pasteur’s germ theory of disease, and he decided to apply it to the problem of surgical infections.
19-During this time, which spanned the Franco-Prussian war of 1870, the end of the Second Empire and the start of the Third Republic, Pasteur became the equivalent of a “rock star,” essentially a household word and the epitome of a scientist, as well as a national hero. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3342039/
20-Pasteur had already discovered molecular chirality, investigated fermentation, refuted spontaneous generation, inspired Lister's introduction of antisepsis to surgery, introduced pasteurization to France's wine industry, answered the silkworm diseases blighting France's silkworm industry https://en.m.wikipedia.org/wiki/Koch%E2%80%93Pasteur_rivalry
21-  Let us begin with Robert Koch himself, who was born December 11, 1843, the son of a mining engineer. Koch studied medicine at the University of Göttingen, where he was influenced by Jacob Henle, the professor of anatomy who had published in 1840 on the possible relationship of microorganisms to disease and who name is often linked with Koch’s in discussions of the postulates https://www.jstor.org/stable/23331663
22-  In 1840, Jakob Henle enunciated the concepts of causation in a book which has been translated into English by Dr. George Rosen (1). Henle was then 31 years old and just starting his duties as professor of anatomy in Zurich https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2595276/pdf/yjbm00143-0072.pdf
23- If the inoculated person or animal did not die and therefore no autopsy could be performed, one could not always determine with certainty whether the disease produced in the second instance was the same as that in the original case https://www-jstor-org.harker.idm.oclc.org/stable/pdf/24618980.pdf?refreqid=fastly-default%3A77514f395d9aa05ef04e45dfd348e059&ab_segments=0%2Fbasic_search_gsv2%2Fcontrol&origin=&initiator=search-results&acceptTC=1
24- The organism must be found constantly in association with the disease, and in the living tissues; it must be isolated; it must then be tested by experiments, including animal inoculation. https://www.jstor.org/stable/43428369
25- In his spare time, Robert Koch began researching into anthrax: around Wollstein, the disease regularly claimed the lives of both animals and humans – but the cause was completely unknown. https://www.rki.de/EN/Content/Institute/History/rk_node_en.html 
26- A large, gram-positive, rod (bacillus), Bacillus anthracis is the causative agent of anthrax (Greek for “coal”), named for the black lesions of cutaneous anthrax. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6860146/
27- The first form is due to a microbe called Bacteridium anthracis
28- In doing so, Robert Koch was the first to prove that a microorganism was the cause of an infectious disease. https://www.rki.de/EN/Content/Institute/History/rk_node_en.html
29-Two years later, in 1878, Koch published two papers on wound infections. He utilized similar absence arguments as the basis for proving bacterial etiology. In the second paper, Koch laid out for the first time his specific criteria for establishing causation — the first statement of his postulates. https://www.jstor.org/stable/23331663
30-Koch had transformed bacteriology by introducing the technique of pure culture, whereby he established the microbial cause of the disease anthrax (1876) https://en.m.wikipedia.org/wiki/Koch%E2%80%93Pasteur_rivalry
31- He discovered the dormant stage of the pathogen, anthrax spores, and thus unraveled the previously unexplained chain of infection and the bacterium’s strong resistance to environmental factors.
32-  He was the first to succeed in changing the thread-like microscopical corpuscles identified by others into identifiable long filaments (chains of rods) and then into beads consisting of minute grains, the spores…. Of course, as a result of Koch’s experiments, now we know that the ability of the microbe to sporulate enables it to withstand harsh temperatures and conditions that occur during the winter months. https://www.frontiersin.org/articles/10.3389/fimmu.2012.00068/full#h4
33-He repeated the same process used by Koch: successive dilution--essentially taking a few drops from a flask in which he grew anthrax, diluting it in a new flask, over and over, until there was no doubt that every other potentially contagious element had disappeared then injecting the pure culture into host animals, who reliably contracted the disease. Miracle Cure p26
34- The endospores discovered by Koch were the reason that seemingly dead bacteria remained carriers of disease: Anthrax cells weren't killed by oxygen, but simply became dormant inside the walls of a spore. The groundbreaking understanding of anthrax- a combination of Koch's spores and Pasteur's dilutions- was the first to link the German physician with the French chemist. It would not be the last.” Miracle Cure p26
35- Two years after Koch’s publication proving the microbial nature of anthrax, Pasteur presented a Summary to the Sessions of the Academy of Sciences (Pasteur et al., 1878). According to Pasteur: https://www.frontiersin.org/articles/10.3389/fimmu.2012.00068/full#h4
36- https://www.frontiersin.org/articles/10.3389/fimmu.2012.00068/full#h4
37-  Original French version (no mention of Koch)  https://gallica.bnf.fr/ark:/12148/bpt6k15133278
38- English translation of certain sections. He uses the French Bacteridia https://sourcebooks.fordham.edu/mod/1878pasteur-germ.asp
39- https://en.wikipedia.org/wiki/Franco-Prussian_War
40- Pasteur reasoned that exposure to oxygen had caused the loss of virulence. He found that sealed bacterial cultures maintained their virulence, whereas those exposed to air for differing periods of time before inoculation showed a predictable decline in virulence. He named this progressive loss of virulence ‘attenuation’, a term still in use today. https://www.nature.com/articles/d42859-020-00008-5
41- Pasteur, along with Charles Chamberland and Emile Roux, went on to develop a live attenuated vaccine for anthrax. Unlike cultures of the chicken cholera bacterium, Bacillus anthracis cultures exposed to air readily formed spores that remained highly virulent irrespective of culture duration https://www.nature.com/articles/d42859-020-00008-5
42-  However, Pasteur discovered that anthrax cultures would grow readily at a temperature of 42–43 °C but were then unable to form spores. These non-sporulating cultures could be maintained at 42–43 °C for 4–6 weeks but exhibited a marked decline in virulence over this period when inoculated into animals.  https://www.nature.com/articles/d42859-020-00008-5
43- Miracle Cure p27/28
44-Concomitantly with the work on cholera, Koch investigated the etiology of tuberculosis. IN 1882, he announced the discovery of a bacillus as the cause of the White Plague https://www.jstor.org/stable/23331663 
45- TB is the leading infectious disease killer in the world, claiming 1.5 million lives each year. https://www.cdc.gov/globalhealth/newsroom/topics/tb/index.html#
46- 1895 Louis Pasteur died in Villeneuve-l’Étang on September 28. https://www.pasteur.fr/en/institut-pasteur/history
47- From 1896 onwards, Robert Koch spent several months each year on expeditions to investigate tropical diseases – his second wife Hedwig Freiberg nearly always accompanied him. https://www.rki.de/EN/Content/Institute/History/rk_node_en.html
48-  At the beginning of April 1910, Robert Koch suffered a massive heart attack in Berlin. He died during a subsequent stay at a sanatorium in Baden-Baden on 27 Mai 1910. https://www.rki.de/EN/Content/Institute/History/rk_node_en.html
49-  Not long after the institute's inauguration, Roux, now less occupied in the fight against rabies, resumed in a new lab and with the help of a new colleague, Yersin, his experiments on diphtheria. https://en.wikipedia.org/wiki/Pasteur_Institute

Patrick Kelly @PatKellyTeaches

Special Guest Episode.  Notes above including research and references are the excellent work of Patrick Kelly.