Okay, so the Bug Blog is usually about the clinical and scientific aspects of microbiology but this week I’m going to do something a bit different. Now I’m not someone who watches much TV; there was very little on that interested me over the Christmas period. However, I did watch a short TV hospital dramatization called Charité on Netflix which I thought was brilliant and something that anyone interested in microbiology would also enjoy. OK so it’s in German with English subtitles, but it is the best show I have watched in a long time! Let me explain.
From left to right: Robert Koch, Paul Ehrlich, Emil von Behring, Ida Lenze, Georg Tischendorf and Rudolph Virchow
Charité is in fact a real hospital; it was built in 1710, north of the city walls of Berlin, in anticipation of the threat of advancing bubonic plague from the East. In 1828 it became a university teaching hospital and today remains Europe's largest university hospital being affiliated with Humboldt and Freie Universities in Berlin.
The TV program is set in 1888 and follows the lives of a number of people associated with Charité Hospital over the coming years. OK, most of the characters in the show are fictitious, such as the heroine Ida Lenze and the aspiring Doctor Georg Tischendorf BUT what makes it truly fascinating for Microbiologists is the “real” characters that are also portrayed in the show. These include Robert Koch, Emil von Behring, Paul Ehrlich, Rudolph Virchow and Ernst von Bergmann, who all actually worked at the Charité during this time. These people were true pioneers of medicine, pathology and especially microbiology and their discoveries are uncovered during the dramatization of the era. “Historical Medical Fiction”, what a genre!
So who were these pioneers of microbiology and what did they do?
Robert Koch
All microbiologists should have heard of Robert Koch. Koch’s first major discovery was that he could isolate bacteria in pure culture using agar based media (he tried slices of potato and liquid gelatine first but these didn’t work so well). Isolating bacteria on agar allowed him to studying these bacteria in more detail, as well as inoculating them as pure cultures into animals. Koch discovered that Bacillus anthracis caused anthrax, Mycobacterium tuberculosis caused tuberculosis and Vibrio cholerae caused cholera. Imagine the sensation that this must have caused in the 1800s. Up until this time most people still believed in toxic miasmas (poisonous vapours or mists from rotting things) and the four humours (ailments of blood, phlegm, black bile and yellow bile) as the cause of most diseases, not an infectious agent too small to see with the naked eye!
The TV program is set in 1888 and follows the lives of a number of people associated with Charité Hospital over the coming years. OK, most of the characters in the show are fictitious, such as the heroine Ida Lenze and the aspiring Doctor Georg Tischendorf BUT what makes it truly fascinating for Microbiologists is the “real” characters that are also portrayed in the show. These include Robert Koch, Emil von Behring, Paul Ehrlich, Rudolph Virchow and Ernst von Bergmann, who all actually worked at the Charité during this time. These people were true pioneers of medicine, pathology and especially microbiology and their discoveries are uncovered during the dramatization of the era. “Historical Medical Fiction”, what a genre!
So who were these pioneers of microbiology and what did they do?
Robert Koch
All microbiologists should have heard of Robert Koch. Koch’s first major discovery was that he could isolate bacteria in pure culture using agar based media (he tried slices of potato and liquid gelatine first but these didn’t work so well). Isolating bacteria on agar allowed him to studying these bacteria in more detail, as well as inoculating them as pure cultures into animals. Koch discovered that Bacillus anthracis caused anthrax, Mycobacterium tuberculosis caused tuberculosis and Vibrio cholerae caused cholera. Imagine the sensation that this must have caused in the 1800s. Up until this time most people still believed in toxic miasmas (poisonous vapours or mists from rotting things) and the four humours (ailments of blood, phlegm, black bile and yellow bile) as the cause of most diseases, not an infectious agent too small to see with the naked eye!
He also proposed a system for studying the cause of disease due to bacteria which are described as Koch’s postulates. These hold true for many infections, especially bacterial. He showed that to prove a particular bacterium causes a particular infection the four postulates should be fulfilled.
1. The organism must be present in every case of the infection
2. The organism must be isolated from the host with the infection and grown in pure culture
3. A pure culture of the organism must cause the same infection when inoculated into a healthy, susceptible animal in the laboratory
4. The organism must be isolated again from the inoculated animal and must be shown to be the same organism first isolated from the original infected host
Robert Koch is widely held to be the “Father of Microbiology” and it is hard to argue with this claim; without his pioneering work on bacteria our science would not be what it is today. He was awarded the Nobel Prize in Physiology or Medicine in 1905 for his work on tuberculosis.
Emil von Behring
I suspect most of you haven’t heard of Emil von Behring and yet his discovery was one of the most dramatic of its time, so much so that he was awarded the very first Nobel Prize in Physiology or Medicine in 1901.
Emil von Behring discovered a treatment for diphtheria. At this time diphtheria was a killer that caused massive epidemics and terrified the general public. Von Behring discovered a way to make an antiserum (antibody) by injecting a horse with diphtheria and then collecting the antiserum from the horse when it had recovered from the infection (why a horse and how he knew it would survive diphtheria is not documented!)
Once this antiserum had been purified it was injected into patients with diphtheria leading to a dramatic improvement in the condition and their eventual recovery. Amazingly over 100 years later, we still use antiserum to treat diphtheria in the same way that von Behring did,… just without the horse. We also use antibodies to prevent or treat a number of other infections such as Varicella Zoster (Chicken Pox), Hepatitis B and recently with Ebola.
Von Behring’s story is not without controversy though, as many believe he cheated our next pioneer Paul Ehrlich, who worked with von Behring, out of recognition and financial reward by taking all of the credit for the discovery of diphtheria antiserum all for himself, as well as a lucrative contract with a pharmaceutical company to produce the antiserum as a drug.
Paul Ehrlich
Not only did Paul Ehrlich work on antiserums with von Behring but in 1907 he also discovered arsphenamine, the first antimicrobial. Arsphenamine, or its trade name Salvarsan, was the first effective treatment for gonorrhoea. Ehrlich was also the first to use the term “chemotherapeutic” to describe a drug.
Ehrlich was in fact an all-round clever chap. He made significant discoveries in the field of haematology, immunology, microbiology as well as antimicrobials. He invented various ways of staining bacteria and tissue cells to allow them to be studied in more detail, discovering various nucleated blood cells along the way (immature blood cells containing a nucleus, which are normally only present in foetus or new-borns therefore can indicate pathology or bone marrow disorders in adults).
In the field of immunology Ehrlich also worked out the concept of inherited immunity whereby the new-born baby acquires immunity from its mother. He also proposed that there were interactions between antibodies and antigens and hence paved the way for further work to be done in this area.
However, Ehrlich spent much of his time trying to find a single magic bullet that could kill all disease causing bacteria. Ehrlich based this theory on the observation that the compound methylene blue (which is often still used as a counter stain in the Ziehl-Neelsen stain for mycobacteria) would kill bacteria. The problem with methylene blue was that it was toxic to humans as well. He never found his magic bullet, but he made a lot of other discoveries along the way. Paul Ehrlich was awarded the Nobel Prize in Physiology or Medicine in 1908 for his work in immunology rather than microbiology, but I personally think both areas of his work were worthy of the prize.
Rudolph Virchow
Virchow is known as the “Father of Modern Pathology”. He was also a strong influence in the field of public health, being credited as one of the main forces that eventually saw the move away from the four humours to a more scientific way of studying medicine.
Virchow did a lot of work in the field of cell biology and discovered the abnormal blood cells causing a haematological cancer which he called “leukämie” which later changed to leukaemia. He also worked out that an enlarged left supraclavicular lymph node is an early sign of gastric cancer (and occasionally lung cancer) and we still examine for “Virchow’s node” when we see patients today.
We can also thank Virchow for discovering the process of clot formation and for the terms “thrombosis” and “embolism”.
In microbiology he worked out that many infections were transmitted from animals to humans and he used the term “zoonoses” to describe them. He also realised that parasites in particular were good at doing this and he called these intestinal worms “helminths”.
These are only a small number of the contributions to medicine that Rudolph Virchow made, which is why I find it baffling that he was never awarded the Nobel Prize in Physiology or Medicine. Maybe it was because none of his discoveries were considered ground-breaking enough, or maybe it was down to politics at which Virchow was a key player but may not have been popular! Whatever the reason he made a large number of worthy contributions.
Ernst von Bergmann
Although Von Bergman plays only a minor role in the TV show, he did make one big contribution to the field of microbiology. He is consider a pioneer of aseptic surgery in that he was the first surgeon to insist on heat sterilising his surgical instruments thereby significantly reducing the rate of post-operative infections.
If you have ever had an operation then the instruments used on you are likely to also have been heat sterilised, and for that you have Von Bergman to thank. He also didn’t win the Nobel Prize in Physiology or Medicine!
So there we have it. Five big names in the history of medicine all taking part in a TV show set in the Charité Hospital, Berlin, from 1888. The show is so believable because the set design and costumes are amazing. The choice of actors to play the historical medical figures is especially inspired too. If you watch the show and then look at photographs of the real people you will be hard pressed to tell the real men from the actors. Not only do they look the part, they also act the part brilliantly.
So I take my hat off to all those involved in Charité. It is brilliant and “Ich empfehle Ihnen dringend, es auszuprobieren” or [I strongly recommend you try it]. I personally cannot wait until the second series this year… who knows what will happen next?! There is 130 years of Historical Medical Fiction to be told, there must be another series!
1. The organism must be present in every case of the infection
2. The organism must be isolated from the host with the infection and grown in pure culture
3. A pure culture of the organism must cause the same infection when inoculated into a healthy, susceptible animal in the laboratory
4. The organism must be isolated again from the inoculated animal and must be shown to be the same organism first isolated from the original infected host
Robert Koch is widely held to be the “Father of Microbiology” and it is hard to argue with this claim; without his pioneering work on bacteria our science would not be what it is today. He was awarded the Nobel Prize in Physiology or Medicine in 1905 for his work on tuberculosis.
Emil von Behring
I suspect most of you haven’t heard of Emil von Behring and yet his discovery was one of the most dramatic of its time, so much so that he was awarded the very first Nobel Prize in Physiology or Medicine in 1901.
Emil von Behring discovered a treatment for diphtheria. At this time diphtheria was a killer that caused massive epidemics and terrified the general public. Von Behring discovered a way to make an antiserum (antibody) by injecting a horse with diphtheria and then collecting the antiserum from the horse when it had recovered from the infection (why a horse and how he knew it would survive diphtheria is not documented!)
Once this antiserum had been purified it was injected into patients with diphtheria leading to a dramatic improvement in the condition and their eventual recovery. Amazingly over 100 years later, we still use antiserum to treat diphtheria in the same way that von Behring did,… just without the horse. We also use antibodies to prevent or treat a number of other infections such as Varicella Zoster (Chicken Pox), Hepatitis B and recently with Ebola.
Von Behring’s story is not without controversy though, as many believe he cheated our next pioneer Paul Ehrlich, who worked with von Behring, out of recognition and financial reward by taking all of the credit for the discovery of diphtheria antiserum all for himself, as well as a lucrative contract with a pharmaceutical company to produce the antiserum as a drug.
Paul Ehrlich
Not only did Paul Ehrlich work on antiserums with von Behring but in 1907 he also discovered arsphenamine, the first antimicrobial. Arsphenamine, or its trade name Salvarsan, was the first effective treatment for gonorrhoea. Ehrlich was also the first to use the term “chemotherapeutic” to describe a drug.
Ehrlich was in fact an all-round clever chap. He made significant discoveries in the field of haematology, immunology, microbiology as well as antimicrobials. He invented various ways of staining bacteria and tissue cells to allow them to be studied in more detail, discovering various nucleated blood cells along the way (immature blood cells containing a nucleus, which are normally only present in foetus or new-borns therefore can indicate pathology or bone marrow disorders in adults).
In the field of immunology Ehrlich also worked out the concept of inherited immunity whereby the new-born baby acquires immunity from its mother. He also proposed that there were interactions between antibodies and antigens and hence paved the way for further work to be done in this area.
However, Ehrlich spent much of his time trying to find a single magic bullet that could kill all disease causing bacteria. Ehrlich based this theory on the observation that the compound methylene blue (which is often still used as a counter stain in the Ziehl-Neelsen stain for mycobacteria) would kill bacteria. The problem with methylene blue was that it was toxic to humans as well. He never found his magic bullet, but he made a lot of other discoveries along the way. Paul Ehrlich was awarded the Nobel Prize in Physiology or Medicine in 1908 for his work in immunology rather than microbiology, but I personally think both areas of his work were worthy of the prize.
Rudolph Virchow
Virchow is known as the “Father of Modern Pathology”. He was also a strong influence in the field of public health, being credited as one of the main forces that eventually saw the move away from the four humours to a more scientific way of studying medicine.
Virchow did a lot of work in the field of cell biology and discovered the abnormal blood cells causing a haematological cancer which he called “leukämie” which later changed to leukaemia. He also worked out that an enlarged left supraclavicular lymph node is an early sign of gastric cancer (and occasionally lung cancer) and we still examine for “Virchow’s node” when we see patients today.
We can also thank Virchow for discovering the process of clot formation and for the terms “thrombosis” and “embolism”.
In microbiology he worked out that many infections were transmitted from animals to humans and he used the term “zoonoses” to describe them. He also realised that parasites in particular were good at doing this and he called these intestinal worms “helminths”.
These are only a small number of the contributions to medicine that Rudolph Virchow made, which is why I find it baffling that he was never awarded the Nobel Prize in Physiology or Medicine. Maybe it was because none of his discoveries were considered ground-breaking enough, or maybe it was down to politics at which Virchow was a key player but may not have been popular! Whatever the reason he made a large number of worthy contributions.
Ernst von Bergmann
Although Von Bergman plays only a minor role in the TV show, he did make one big contribution to the field of microbiology. He is consider a pioneer of aseptic surgery in that he was the first surgeon to insist on heat sterilising his surgical instruments thereby significantly reducing the rate of post-operative infections.
If you have ever had an operation then the instruments used on you are likely to also have been heat sterilised, and for that you have Von Bergman to thank. He also didn’t win the Nobel Prize in Physiology or Medicine!
So there we have it. Five big names in the history of medicine all taking part in a TV show set in the Charité Hospital, Berlin, from 1888. The show is so believable because the set design and costumes are amazing. The choice of actors to play the historical medical figures is especially inspired too. If you watch the show and then look at photographs of the real people you will be hard pressed to tell the real men from the actors. Not only do they look the part, they also act the part brilliantly.
So I take my hat off to all those involved in Charité. It is brilliant and “Ich empfehle Ihnen dringend, es auszuprobieren” or [I strongly recommend you try it]. I personally cannot wait until the second series this year… who knows what will happen next?! There is 130 years of Historical Medical Fiction to be told, there must be another series!
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