We live in unprecedented times. At the inception of 2020, who knew that we would exist in a world where our actions are defined by the risk of catching Covid 19? Consumed by the uprooting of our lives, it is easy to forget that this is not the first pandemic to bedevil the human race, nor will it be the last. In part I of this series on pandemics, I will discuss The Plague. 

Bubonic plague

In Shakespeare’s Romeo and Juliet, the character of Mercutio comes off worse in a fight and curses his opponents with a “plague on both your houses!” as he is dying. The disease that Mercutio refers to is the bubonic plague, commonly attributed to the 14th century Black Death and two other plague pandemics: The plague of Justinian in 541 AD and the Third plague pandemic in the mid 19th century. The bubonic plague is caused by a bacterium calledYersinia pestis, which usually lives on fleas, that in turn are primarily hosted by rats. As Y. pestis multiplies, it blocks the flea’s digestive tract, which makes it very infectious and very hungry. As the flea is feeding, it infects its rat host with Y. pestis, which eventually kills the rat. Now without a host to feed on and starving, the flea goes looking for another host. If this happens to be a human in close proximity, which was often the case on crowded rat- infested ships, that unfortunate person gets bubonic plague. 

What really caused the Black Death? 

We’ve been told for over two centuries that Black Death was the bubonic plague. What if it wasn’t? Scientists started questioning the narrative when they compared the spread of the Black Death in the late 14th century to the third plague pandemic. Here’s the evidence they presented. 

  1. The disease spread too rapidly for it to be a rat and flea borne disease. The Black Death spread across Northern Europe in the middle of a harsh winter (conditions unfavourable for flea and rat survival). The rate of spread was 4 km per day, much faster than a rat can move. In contrast, the 19th century plague in India took 6 months to move 100 meters. The disease was also identified in towns hundreds of kilometres away from each other, without any reported intermediary infections. 
  2. The disease was violent for too long. The Black Death ravaged Europe for 300 years. In fact, France would have annual outbreaks and some of these spawned European epidemics. Typically, infected fleas kill their rodent hosts, resulting in cycling of rodent populations. This does not allow the disease to establish itself as there cannot exist a stable, disease resistant rodent population. 
  3. The mortality rate was too high. The Black Death had a mortality rate of nearly 100%. This was 10 times higher than the reported mortality of modern bubonic plague. In fact, humans can be infected with Y. pestis without falling ill and there are milder forms of the bacteria that do not kill. 
  4. The Black Death was directly infectious. Mandatory social distancing (4 meters) was imposed during the Black Death. It was found to be extremely beneficial, indicating that disease transmission was propagated by human to human contact. This is in direct contrast to what we know about the bubonic plague requiring intermediary flea carriers.
  5. Development of disease resistant mutations in humans. There is a specific genetic mutation (CCR5-∆32) that is enriched in European populations. Research suggests that this CCR5 deletion appeared roughly 2000 years ago, and its frequency increased to present levels due to positive selection by several plague epidemics/ pandemics, including the Black Death. Basically, this mutation protected people from dying of the plague, so survivors passed it on to their progeny, hence amplifying the mutation in the human population. The CCR5 protein is actually used by the HIV virus to access human cells. Hence, people with this mutation that deletes CCR5 are protected from HIV. However, there is no evidence to suggest that this protein is also used by Y. pestis to gain cell access. 

Based on these anecdotal evidences, scientists came up with an alternate hypothesis: Perhaps the Black Death was caused by a virus. More specifically, a haemorrhagic virus like Ebola, due to the similarities in symptoms between the two diseases. It should be noted that this theory is backed up by circumstantial evidence and not hard, irrefutable data. 

A virus? Really? 

Fierce critics of this theory have offered up compelling counterarguments in support of the widely accepted bubonic plague explanation. 

  1. Rats and fleas were not the carriers. Although Y. pestis is typically transmitted by fleas that live on rats, perhaps this was not the primary transport mechanism during the Black Death. Scientists identified human body lice that can transmit Y. pestis from sick to healthy rabbits. Replace rabbits with humans and this could explain how the disease could spread in a cold climate. Similarly, plague does not exclusively require rats to propagate. Potentially, an animal that is not as severely affected as rats and humans could have developed resistance and sustained the disease for a long time. There were also no records of a spike in rat deaths around this time, lending credence to the idea that they were not the only animal carrier. 
  2. Fleas may have spread the disease earlier than thought. There are several flea species that can become infectious before multiplying bacteria block off their stomachs and starve them. Hence, an infectious flea can jump from human- human, thereby spreading the infection in the absence of rats. Personal hygiene was not high during the 14th century and humans infested with fleas/ lice were not uncommon. This might explain why social distancing seemed to help curb the spread of Black Death. 
  3. Pneumonic, not bubonic plague. Another form of plague that is also caused by Y. pestis is pneumonic plague. It infects the lungs and can spread from person to person via droplets. In the absence of antibiotics in the 14th century, this plague would’ve had a 100% fatality rate. This could explain the human- human transmission and rapidity of the spread. 
  4. DNA analysis of plague victims. Scientists went digging in the burial sites of plague victims to isolate DNA from the causative pathogen. Early results were conflicting as 700-year-old DNA can be quite degraded, making it difficult to interpret results. Scientists tweaked their methods and identified a circular DNA called a plasmid, that is unique to bacteria. Sequencing this plasmid DNA revealed that it was a match to plasmid DNA found in modern versions of Y. pestis. Further sequencing of the nuclear DNA revealed changes to the sequence in ancient Y. pestis compared to its modern relative. Another genetic analysis identified two previously unknown strains of Y. pestis in victims of the Black Death. These data support the presence of a different strain of Y. pestis in Black Death victims. Essentially the same pathogen, but it appeared to have caused a very different disease. It is possible that these ancient strains are no longer present, or perhaps they mutated into the less virulent strain that caused the modern plague pandemic in the 19th century. 

My inexpert opinion

I should stress that I am not an expert and this section is purely speculative. With the available evidence, I am inclined to agree with the majority that the Black Death was the bubonic plague, albeit caused by a different bacterial strain. However, I do think there are unanswered questions. In my mind, the biggest question is why there was an increase in frequency of the CCR5 deletion. There is some data that implies this could be due to small pox (another viral disease) and not the bubonic plague as originally thought. The small pox virus family is known to access immune cells using proteins similar to CCR5 and has been around more consistently than the plague. This could silence some sceptics, but the true impact of small pox on positive gene selection needs to be better evaluated. There is clearly hard DNA data indicating that bubonic plague was the Black Death. However, it should be noted that acquiring and analysing ancient DNA is not without flaws. Due to DNA degradation and myriad contaminants, extracting the right DNA is a Herculean task that can have a high error rate. Although the plasmid DNA data presented in support of bubonic plague is compelling, the ‘different strain’ theory is incomplete without full genome analysis of the ancient bacteria. Personally, I don’t think the virus theory should be entirely discounted until it is comprehensively disproved. If there really is an unknown, devastating virus out there that can re-emerge at any time, we should do our best to establish its existence (or lack thereof). After all, we do not want to end up with another COVID-19 situation, do we? 

Published by The Very Curious Biochemist

I am a protein biochemist by training, with a keen interest in new and fascinating science. I am passionate about communicating and discussing science and life as a scientist. As I belong to the rare species that actually enjoys writing, I thought I'd start this blog. I'm currently a postdoctoral scientist, so this really offers me an excellent distraction from the rigours of research. I hope you lovely visitors enjoy the material on offer!


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