Human immunity is still being affected by the Black Death.

Half of medieval Europe's population perished in the Black Plague, the world's largest and most catastrophic plague epidemic, over seven years in the 14th century, changing the trajectory of human history.

What about the survival of what is still the single largest documented loss event? According to a recent study, which was published on Wednesday in the journal Nature, more than just chance affected who lives and who died.

A study that was accepted for publication in Nature identified important genetic variations that enabled people to survive the plague through analysis of centuries-old Genetic material from both Black Death victims and survivors.

According to the findings, these genetic variations still influence how human immune systems function today. Genes that originally gave protection against the plague are now associated with a higher susceptibility to autoimmune illnesses including Crohn's and rheumatoid arthritis.

According to study co-author and University of Chicago professor of genetic medicine Luis Barreiro, "We are the descendants of those that survived past pandemics... and understanding the evolutionary mechanisms that contributed to our survival is not only important from a scientific standpoint but can also inform on the mechanisms and genetic determinants of present-day susceptibility to disease."

Specimens from plague pits

The seven-year investigation comprised the extraction of DNA from skeletal remains discovered in London and Denmark belonging to three distinct populations: plague victims, those who perished before the Black Death, and people who perished between 10 and 100 years after the outbreak.

In addition to samples from those interred in the East Smithfield plague pits, which were utilized for mass interments during the peak of the epidemic in 1348–1349, more than 300 samples originated from London, a city that was particularly badly struck by the plague. 198 further samples were obtained from human remains interred in five different places around Denmark.

The group identified a gene mutation called ERAP 2 that looked to have a high correlation with the plague. In the London trial, 40% of the participants had the ERAP2 variation that was discovered to be protective against the plague.

Following the Black Death, it was 50%. In Denmark, the percentile difference was more pronounced; it increased from around 45% of samples interred prior to the epidemic to 70% interred following it.

The researchers are still unsure of the precise mechanism by which this variant offered protection, but laboratory tests on grown cells showed that individuals with the ERAP 2 variant had a substantially different immunological response to Yersinia pestis from those without the variant, according to Barreiro. In lab tests, macrophages from people who had the mutation killed the germs more effectively than macrophages from those who didn't have it.

Because there are so few occurrences of the plague in modern communities, we do not know if it still offers protection, but we surmised that it may. The variation probably also protects against other infections, albeit this wasn't included in the study.

The cost of immunity

The disadvantage of the variety is that it has been connected to a higher vulnerability to autoimmune illnesses, where the immune system becomes hyperactive, including Crohn's disease.

This implies that populations that survived the Black Death paid a price, and that price is to have an immune system that makes us more likely to retaliate against ourselves.

He asserted that it was unlikely that the COVID-19 outbreak would have a similar impact on our immune system, in large part because the disease primarily affects people after they reach reproductive age, making it unlikely that genes conferring protection would be passed down to the following generation.

According to David Enard, a professor in the department of ecology and evolutionary biology at the University of Arizona who was not involved in the research, this alteration in the genetic composition of humans that has a place in a couple of decades is also a rare example of quick natural selection.

The study's selling features, according to him, are the limited time range from which samples were collected and the sheer volume of samples that were examined, which allowed the investigators to precisely date natural selection.

The notion of natural selection occurring during the Black Death has previously intrigued evolutionary scientists, but a thorough analysis was impossible without this accurate date of several samples.