How the Black Death Still Affects the Human Immune System

The Black Death, the world’s most devastating disease outbreak, killed half the population of medieval Europe in the space of seven years during the 14th century, changing the course of human history.

But what about the survivors of what remains the biggest fatality event on record? One new research published in the journal Nature suggests that it was more than luck that determined who lived and who died at that time.

Secular DNA analysis of victims and survivors of the Black Death identified key genetic differences that helped people survive the plague, according to a study by the universities of Chicago and Ontario in the United States.

These genetic differences continue to shape the human immune system to this day, with genes that once provided protection against the plague are now linked to greater vulnerability to autoimmune diseases such as Crohn’s disease and rheumatoid arthritis, the study says.

“We are descendants of those who survived past pandemics […] and understanding the evolutionary mechanisms that have contributed to our survival is not only important from a scientific point of view, but can also inform the genetic mechanisms and determinants of current disease susceptibility,” said study co-author Luis Barreiro, professor of genetic medicine at the University of Chicago.

Plague tomb samples

The seven-year study involved extracting DNA isolated from three different groups of skeletal remains unearthed in London and Denmark: plague victims, those who died before the Black Death, and those who died between 10 and 100 years after the plague broke out. .

More than 300 samples came from London, a city really hit by the plague, including from individuals buried in East Smithfield tombs used for mass burials at the height of the outbreak between 1348-1349. Another 198 samples were taken from human remains buried at five sites in Denmark.

DNA was extracted from the dentin in the individuals’ tooth roots, and the researchers were also able to check for the presence of Yersinia pestis, the bacterium that causes plague. They then looked for signs of genetic adaptation to the disease.

“It’s a long process, but in the end you have the sequence of these genes for these people from before, during and after the plague and you can ask: did the genes that one population carried looked different than the ones that another population carried,” said co-author Hendrik Poinar, professor of anthropology at McMaster University in Hamilton, Ontario.

The team identified a variant of one gene in particular, known as ERAP2, that appeared to have a strong association with the plague. Before the Black Death, the ERAP2 variant considered protective against the plague was found in 40% of individuals included in the London study.

After the Black Death, it was found in 50% of individuals. In Denmark, the percentage disparity was more pronounced – it changed from about 45% of samples buried before the plague to 70% of those buried afterwards.

The team still doesn’t know exactly why this variant conferred protection, but their laboratory experiments on cultured cells indicated that, in people with the ERAP2 variant, an immune cell known as a macrophage provoked a very different response to Yersinia pestis, Barreiro explained.

Macrophages from individuals with the variant were better able to kill the bacteria in laboratory experiments than macrophages from individuals who did not have it.

“We don’t know if this still protects against plague, as the number of cases in current populations is very low, but we speculate that it should,” he said. The variant is also likely to be beneficial against other pathogens – although this was not part of the research.

price of immunity

The downside of the variant is that it has been linked to an increased susceptibility to autoimmune disorders such as Crohn’s disease, where the immune system becomes overactive.

“This suggests that populations that survived the Black Death paid a price, which is to have an immune system that increases our susceptibility to react against ourselves,” said Barreiro.

He said the Covid-19 outbreak was unlikely to shape our immune systems in a similar way — largely because the disease predominantly kills people past reproductive age, meaning genes that confer protection are unlikely to be passed on to the mother. next generation.

This change in human genetic makeup that occurs over a matter of decades is also a rare example of rapid natural selection, said David Enard, a professor in the department of ecology and evolutionary biology at the University of Arizona who was not involved in the research.

“The narrow time window from which the samples were collected and the large number of samples analyzed are important points of the study,” he said in a commentary published alongside the study, “allowing the authors to accurately date natural selection.” .

“Although evolutionary biologists have already wondered about the possibility of natural selection during the Black Death, proper investigation was not possible without this precise dating of many samples.”