The illness caused the eruption of a sort of boil, the size of a lentil, on the thigh or arm, which so infected and invaded the body that the victims violently coughed up blood, and after three days’ incessant vomiting, for which there was no remedy, they died… . Not just one person in a house died, but the whole household, down to the cats and the livestock, followed their master to death.— Michele da Piazza, 1347 BCE
The above lines were written by Michele da Piazza way back in 1347 CE (Walløe, 2019). He was indeed talking about the Black Death, a mysterious infection that killed millions of people across the world in the 14th century. In fact, the infection occurred as three separate pandemics, the worst being the second one, which occurred between 1347 and 1352 CE. As Michele points out, it was known to cause strange boils on peoples’ bodies and is said to have wiped out close to one-third of Europe’s population. Those were desperate times. Not knowing the cause for the infection, people burnt everything from their clothes to their cats, thinking these might contain the infectious agent (Glatter and Finkelman, 2020).
Interestingly, as deadly as this infection was, there were several people who managed to survive it. They were considered the lucky few. However, research now shows that surviving the Black Death may have come with a price tag (Klunk et al., 2022).
.](/static/87bc602a61fee909a7e59072990282a2/c08c5/Yersinia_pestis_bacteria.jpg "A high resolution microscopy image of the bacteria that causes bubonic plague - *Yersinia pestis* (purple). Credit: [Wikimedia](https://commons.wikimedia.org/wiki/File:Yersinia_pestis_Bacteria.jpg).")
A high resolution microscopy image of the bacteria that causes bubonic plague - Yersinia pestis (purple). Credit: Wikimedia.
Studies show that Black Death was caused by an infection called plague, and the bacteria responsible for this was Yersinia pestis. The bacteria were transmitted by fleas (similar to malaria, transmitted by mosquitoes), present in the bodies of rats. In fact, the Black Death is said to have spread from Central Asia to Europe through ships which were infested with flea carrying rats.
.](/static/c1ed4053de03e1322582d82a756444e8/589fa/Plague_buboes.jpg "A patient with a large swollen lymph node - a typical symptom of bubonic plague. Credit: [Wikimedia](https://commons.wikimedia.org/wiki/File:Plague_-buboes.jpg).")
A patient with a large swollen lymph node - a typical symptom of bubonic plague. Credit: Wikimedia.
Plague manifested itself in different clinical forms, the most common among them was the bubonic plague. Bubonic plague spread through flea bites. On being bitten by a flea, the bacteria entered the body and reproduced in the lymph nodes of the host. These caused painful swellings in the lymph nodes, some enlarging to the size of an egg. Patients also suffered from high fever and terrible pains in the limbs and abdomen. Many infected individuals, if untreated, died within one week of the infection.
.](/static/f4acb53e167e787ebe2579d0f005861c/9cb74/Acral_gangrene_due_to_plague.jpg "Right hand of a plague patient displaying gangrene. Gangrene is one of the symptoms of plague. Credit: [Wikimedia](https://commons.wikimedia.org/wiki/File:Acral_gangrene_due_to_plague.jpg).")
Right hand of a plague patient displaying gangrene. Gangrene is one of the symptoms of plague. Credit: Wikimedia.
Another rarer clinical form was called septicemic plague. This caused gangrenes of the hands, ears and nose. This is possibly why the infection was called the Black Death.
Although a rare disease now, we still see plague outbreaks in some parts of the world, with Madagascar, Congo and Peru being the most plague endemic countries (Glatter and Finkelman, 2020).
Our DNA contains a fixed number of genes. Every gene is responsible for a specific function. Interestingly, each gene can exist in alternative forms called alleles. These alternative gene forms are, in part, responsible for the variation in physical traits we see from person to person. Natural selection ensures that the fittest forms of the genes are passed down from one generation to the next.
A group of scientists in a recent research published in Nature were interested to see if the Black Death caused specific gene forms to get positively selected. In other words, were there specific gene forms that helped resist the infection and were hence passed down to the generations to come?
To understand this, they obtained ancient DNA extracts from individuals who died before, during and after the Black Death from regions of London and Denmark. From these DNA samples, they then analysed hundreds of genes which specifically played a role in immune function.
To their surprise, they found some compelling results with a specific immune function related gene called ERAP2. The gene is known to exist in two alternative forms. They found that individuals with one specific form of this gene were 40% more likely to survive the Black Death than the ones who had the other form. They also found that individuals with this gene form showed a unique immune response to the Yersinia pestis bacteria. This might have made them immune to the otherwise deadly infection.
However, what is more interesting and unfortunate at the same time is that studies also show that individuals with this very ERAP2 gene form that helped survive the Black Death, also have an increased risk of developing an immune disorder called Crohn’s disease. Crohn’s disease is an immune disorder that causes chronic inflammation of the digestive tract. It is estimated that millions of people across the world suffer from the disease (Ananthakrishnan et al., 2020).
Additionally, they also found a few other gene forms that gave a selective advantage in surviving the Black Death, and saw that these were also associated with serious immune disorders like Rheumatoid Arthritis and Systemic Lupus Erythematosus (SLE).
It is indeed interesting to note that gene forms that seemed like an advantage at a certain point of time, came with a high cost for the generations to come.
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