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  • Alex Cloherty

A short microbial history: Part II

This post is a continuation of a series about how the conception of bacteria, contagious diseases, and more generally health and illness have changed over time and across the world. Last week, we zoomed way out and way back, to a variety of cultures all across time and space. This week, things will be rather less diverse. This is mainly because medical microbiology is quite a young science. Well into the 1800s, it was considered quite eccentric to maintain that disease could be caused by tiny, invisible organisms. The dominant theory at the time was "Miasma Theory", which held that infectious diseases like cholera, tuberculosis, and malaria (which literally translates to "bad air" from old Italian) were transmitted by a poisonous air. Of course, some biologists had challenged the Miasma Theory, but to say the least, their alternative ideas of disease transmission did not gain any popularity for a very long time. The Miasma Theory was painstakingly dealt its death in a three part blow, by three different scientists.

We'll begin with the story the first of these three challengers of the Miasma Theory: John Snow.

No, not that John Snow - although also one with a British accent. This John Snow was a veritable genius - he started a medical apprenticeship at age 14, and went on to be considered the Father of Epidemiology. Perhaps the most impressive quality of John Snow, though, was his talent for applied mathematics. It was by using statistical methods applied to the spread of cholera epidemics that Snow was able to deal the first, heavy blow to the Miasma Theory.

Snow seems to have first become interested in cholera early in his career, during an outbreak. In the early- to mid-1800s, cholera outbreaks were a rather regular occurence. During each successive outbreak, Snow gathered additional evidence in an attempt to piece together the reasons behind the spread of the deadly disease. Like Sherlock Holmes, Snow tried to work as logically as possible and gather plenty of evidence. He spoke to all of the cholera patients that he could, and traced how they had interacted with each other. He identified the "patient zero"s of each outbreak, and asked patients about how their symptoms progressed.

Over successive outbreaks, Snow found that all of the patients reported digestive problems as the first sign of infection. Snow reasoned that if the Miasma Theory was correct, the first signs of infection should be in the nose, throat, or lungs – the pathway of air through the body. The fact that stomach problems were a major feature of the disease made Snow believe that whatever caused cholera must have been swallowed somehow, with food or water. From there, Snow formulated a hypothesis about how the agent of disease could spread into the water supply: with the massive output of diarrhea from the patients. Most of the readers of this blog are probably lucky enough to never have experienced cholera to any degree. Before we go further, in order to understand Snow's line of reasoning it is important to appreciate the sheer volume of watery diarrhea that each cholera patient releases. Cholera victims have diarrhea to the point that death is usually due to dehydration.

After formulating his hypothesis, Snow found that in each subsequent cholera outbreak, he could link infections to a contaminated water supply. Famously, Snow hand-drew maps to connect cholera victims, and then mathematically showed that it was not due to mere chance that victims using one water pump over another, or one water supply company over another, were at the highest risk of contracting the disease. Snow's statistical work was elegant and ahead of his time – however, the Miasma Theory had such a strong hold that Snow had to resort to self-publishing pamphlets to spread his idea that cleaner water was necessary to end cholera outbreaks. Famously, during the 1853 cholera outbreak in London, Snow did manage to convince local authorities that removing the handle of the Broad Street pump, which he argued was contaminated, could end the outbreak. Indeed, the outbreak stopped after the removal of the pump handle, but this was still explained away by proponents of the Miasma Theory. When Snow died of a stroke in 1858, his theories were not widely accepted by the scientific community. The best explanation that I could find for this was that the politics of the time wouldn't permit the public to believe that they were drinking diarrhea-water.

Luckily, the illustrious Louis Pasteur was also trying to understand how diseases were transmitted, around the same time. Pasteur's work against the Miasma Theory was two-fold: he both showed the association of microbes with specific diseases, and proved that it was not air itself that could cause disease or spoilage, but rather particles carried by the air.

Pasteur was an incredibly prolific French researcher, best known for the process of pasteurization, which ensures that food and drink is not contaminated by harmful microbes. He also, however, finished the work of Ignaz Semmelweis, who we discussed last week. Semmelweis had already noted that if obstetricians washed their hands, puerperal fever and resultant death in women who had just given birth could be drastically reduced. Semmelweis died for his hypothesis, because of what seems like a ridiculous counterargument nowadays. This counterargument was well summed-up by Charles Meigs: "Doctors are gentlemen, and gentlemen's hands are clean." Pasteur proved Meigs undeniably wrong. He was able to consistently find one particular bacterium, Streptococcus pyogenes, in the blood of patients with puerperal fever. From there, Pasteur reiterated Semmelweis' theory, but with the added evidence of the disease-causing agent: doctors were infecting patients with S. pyogenes, via their not-so-clean-after-all hands. This was a point against the Miasma Theory for obvious reasons: if S. pyogenes was causing puerperal fever, then it wasn't the air.

Besides formulating the rabies and anthrax vaccines and single-handedly saving the French silk industry (from infection of silkworms by Nosema bombycis), Pasteur also performed the famous (in some circles) swan-neck flask experiment. This experiment is so simple, so elegant, yet so effective, that it can give you shivers. As is shown in the drawing to the right, all that Pasteur did was pour broth in a few flasks, and wait to see if bacteria grew in the broth. He used swan-neck flasks because bacteria would be caught in the curves of the neck, and not reach the broth – unless the flask was tipped, or its neck was broken. In this way, Pasteur showed that it was not the air itself, or the miasma, which was carrying 'disease', or spoilage. The culprits were the microbes that could float about in the air.

Remarkably, the Miasma theory was so entrenched in society at the time, that this was still not the death blow to the theory. The final blow was dealt by a third biologist, from a third country: the German Robert Koch. Based on his work with anthrax, Koch developed a scheme that would set the standard for linking the cause and effect of infectious diseases. Koch asserted that in order to show beyond a doubt that a given microbe caused a given disease, four conditions would have to be met:

  1. The organism must always be present, in every case of the disease.

  2. The organism must be isolated from a host containing the disease and grown in pure culture. This means that you have to be able to take the microbe from an infected patient or animal, and re-grow the microbe in a lab. This is the same thing that doctors still do today to test, for instance, if a patient is infected with virus or with bacteria.

  3. Samples of the organism taken from pure culture must cause the same disease when inoculated into a healthy, susceptible animal in the laboratory. This means that an animal is infected with the re-grown samples from step 2. To prove that the organism in question is causing the disease, the animal should show more or less the same symptoms as do the humans with that particular illness.

  4. The organism must be isolated from the infected animal, and then confirmed to be the same original organism first isolated from the originally diseased host. In other words, the bacteria or virus isolated from the lab-infected animal (step 3) has to be the same bacteria or virus found in steps 1 and 2.

These four conditions, known as Koch's Postulates, are still used today, with only a few revisions. When Koch proved that the bacterium Bacillus anthracis caused anthrax using this method, he finally ended the reign of the Miasma Theory and made room for its successor: the still-used Germ Theory of Disease, which asserts that many infectious diseases are caused by microbes. Koch was also politically active, which probably gave a great boost to the Germ Theory. In the 1880s, Koch was a government advisor with the German Imperial Department of Health, where he could put his theories into practice. It's not an ideal world, so good science can't always speak for itself.

Until next week - drink clean water!

- Alex

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