How the Black Death still affects our health today

By Mark Waghorn via SWNS

Diabetes, arthritis and multiple sclerosis can be traced back to the Black Death, according to new research.

The plague that ravaged Middle Age Europe fueled genes that make people vulnerable to autoimmune diseases.

It shaped human evolution by influencing responses against pathogens. Pandemics may continue to do so in the future - with implications for Covid-19.

Natural selection occurred at pace in survivors - leaving their descendants at increased risk, say scientists.

Co-author Professor Hendrik Poinar, of McMaster University in Ontario, explained: "When a pandemic of this nature - killing 30 to 50 percent of the population - occurs, there is bound to be selection for protective alleles (mutations) in humans, which is to say people susceptible to the circulating pathogen will succumb.

"Even a slight advantage means the difference between surviving or passing. Of course, those survivors who are of breeding age will pass on their genes."

The findings are based on 516 ancient DNA samples extracted from the teeth of individuals who died before, during or soon after outbreaks in London and Denmark.

A century-long "window" enabled the international team to identify genetic differences that dictated who survived the virus.

Some were from the remains of corpses dumped in a mass grave in East Smithfield outside the City.

Historical records and radiocarbon dating revealed they all died between 1348 and 1349.

Analysis showed those with a protective variant known as ERAP2 were around 40 to 50 percent more likely to survive.

Co-author Professor Luis Barreiro, of Chicago University, said: "The selective advantage associated with the selected lociare (gene) among the strongest ever reported in humans showing how a single pathogen can have such a strong impact to the evolution of the immune system."

Over time our immune systems have evolved to respond in different ways to pathogens.

It is a delicate balancing act. Some variants increase the risk of autoimmune diseases like rheumatoid arthritis.

It may not have mattered during the Black Death as the urgency made the trade-off inevitable.

So what had once been a protective gene against plague in the Middle Ages is today associated with increased susceptibility to illness.

Autoimmune disease happens when the body's natural defense system can't tell the difference between your own and foreign cells.

The body mistakenly attacks itself. There are more than 80 types that affect a wide range of organs.

The Black Death is the most deadly pandemic recorded in human history, claiming up to 200 million lives between 1346 and 1353.

It was caused by the bacterium Yersinia pestis carried by fleas and spread across Europe, the Middle East and northern Africa - killing up to half the population.

It suggests little to prior immunological adaptation to the bug. In subsequent bubonic plague outbreaks over the next 400 years, mortality rates decreased.

This could have been as a result of changing cultural practices, pathogen evolution - or human genetic resistance.

The researchers found evidence for positive selection of mutations in immune-related genes during and after the Black Death.

They identified 245 variants that were "highly differentiated" when comparing pre and post-Black Death samples from London - four of which were replicated in the Danish cohort.

These were selected for at a speed and intensity never observed before in human
genomes.

Individuals who carried some or all probably had immune defenses that responded efficiently to Y. pestis, and, as a result, had much better odds of surviving infections.

Barreiro said: "They are associated with protection from Y. pestis and overlap with mutations associated with increased susceptibility to autoimmune diseases.

"It highlights the role past pandemics may have had in shaping present-day disease risk."

The Black Death remains the single greatest human mortality event in recorded history, wiping out communities in some of the most densely populated areas.

Those with two identical copies of ERAP2 survived the pandemic at a much higher rate than peers with the opposing set. They neutralized Y. pestisby immune cells.

Europeans living at the time were initially very vulnerable because they had had no recent exposure to Yersinia pestis.

As waves of the pandemic occurred again and again over the following centuries, mortality rates decreased.

Poinar added: "Understanding the dynamics that have shaped the human immune system is key to understanding how past pandemics, like the plague, contribute to our susceptibility to disease in modern times."

The study, published in the journal Nature, is the result of seven years of work that took an unprecedented look at the immune genes of victims of the Black Death.