Black Death 700 Years Ago Puts Immune System at Risk Today

The devastation of the plague pandemic left such an incredible genetic imprint on the human race that it’s still impacting our health nearly 700 years later.

Up to half of the people died when the Black Death swept through Europe in the mid-1300s.

A pioneering study analyzing the DNA of centuries-old skeletons saw mutations that helped people survive the plague.

But those same mutations are linked to auto-immune diseases affecting people even today.

Modern researches show that, genetically, the virus Y. pestis has barely changed and is almost identical to its Middle Ages cousin. However, its infection profile in the modern world seems to have changed significantly.

The Black Death was a bubonic plague pandemic occurring in Western Eurasia and North Africa from 1346 to 1353. It is the deadliest pandemic ever recorded in human history, causing the deaths of 75–200 million people, peaking in Europe from 1347 to 1351.

Even earlier many researchers suspected that an event of such enormity must have shaped human evolution in some way.

Based on this hypothesis, they analyzed DNA taken from the teeth of 206 ancient skeletons and were able to precisely date the human remains before, during, or after the Black Death.

The analysis included bones from the East Smithfield plague pits which were used for mass burials in London with more samples coming from Denmark.

Mutations in a gene called ERAP2 that lead to survival now cause auto-immune disease

The standout finding, published in the journal Nature, surrounded mutations in a gene called ERAP2.

If you had the right mutations you were 40% more likely to survive the plague.

The results from the study, which also involved researchers from the University of Chicago and the Pasteur Institute in France, were published in the science journal “Nature” on Wednesday, Oct. 19.

“That’s huge, it’s a huge effect, it’s a surprise to find something like that in the human genome,” Professor Luis Barreiro, from the University of Chicago told BBC.

The gene’s job is to make the proteins that dice up intruding microbes and show the fragments to the immune system, priming it more effectively to recognize and neutralize the invisible enemy.

The gene comes in different versions – those that work well and those that do nothing – and you get a copy from each parent.

So the lucky ones, who were most likely to survive, inherited a high-functioning version from their parents.

In turn, survivors with this adaptation who were young enough to have children passed along the genetic trait to future generations, ultimately helping to eradicate the plague.

The young survivors had children and so passed those helpful mutations on so they suddenly became much more common.

“It’s huge we see a 10% shift over two to three generations, it’s the strongest selection event in humans to date,” evolutionary geneticist Professor Hendrik Poinar, from McMaster University, told me.

The results were confirmed in modern-day experiments using the plague bacterium – Yersinia pestis. Samples of blood from people with the helpful mutations were more able to resist the infection than those without.

“It’s like watching the Black Death unfold in a petri-dish – that’s eye-opening,” said Prof Poinar.

Even today those plague-resisting mutations are more common than they were before the Black Death.

But the findings also demonstrate an evolutionary twist — those who carry this plague-slaying genetic trait today are more susceptible to autoimmune diseases like Crohn’s disease and rheumatoid arthritis when the immune system mistakenly kills healthy cells.

Other historic forces on our DNA have a legacy we feel. Around 1-4% of modern human DNA comes from our ancestors sleeping with Neanderthals and this inheritance affects our ability to respond to diseases including Covid.

“So those scars from the past still impact our susceptibility to disease today, in a quite remarkable way,” said Prof Barreiro.

Prof Barreiro said the 40% survival advantage was the “strongest selective fitness effect ever estimated in humans”. It seemingly dwarfs the benefit of HIV-resistance mutations or those that help digest milk – although he warns direct comparisons are tricky.

The Covid pandemic will not leave a similar legacy though.

Evolution works through your ability to reproduce and pass on your genes. Covid largely kills the elderly who have already passed the point of having children.

It was the plague’s ability to kill across the age spectrum and in such great numbers that meant it had such a lasting impact.