Black Death genetic lifesaver puts immune system at risk 700 years later: Mac research

The ancient dead had a secret, and scientists at McMaster University helped unravel it nearly 700 years later.

What they found illustrates how our genetic evolutionary balance gives, and takes away, with implications for pandemics of the future.

It shows that we live today with the effects of events in deep time, of which we really had no idea," said Hendrik Poinar, an evolutionary geneticist at McMaster.

Researchers analyzed DNA from victims and survivors of the Black Death, a bacterial plague that began as a minor epidemic in Central Asia in 1346, and ultimately killed between 30 to 50 per cent of the population in Europe and parts of the Middle East and North Africa.

Poinar and an international team discovered one genetic variant (out of about 250 variants) in survivors of the Black Death that meant they were 40 to 50 times more likely to outlast the plague that snuffed out more than 50 million people.

He explained to The Spectator how this variant was found in the DNA of survivors who had two copies of a gene known as ERAP2. It performed like a set of scissors, chopping up the invading bacteria and presenting it to the immune system, basically saying: I don't know what this is, but it doesn't look good, I destroyed it, but can you use these pieces to mount an immune response?'"

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.

But the findings also reveal 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.

This is how genetic evolutionary selection" works, Poinar suggested. A variant that is a survival tool may ultimately become counter-effective, just as a genetic feature that might seem of little consequence is elevated in importance when the context changes: long necks on giraffes became critical when the best food available in arid climates was found in tall trees.

He said the hyper-effective Black Death genetic variant in humans became less important in the 20th century with improved water sanitation technology, focus on personal hygiene and, ultimately, antibiotics.

All these (sources of bacteria) disappear, and your immune system is like: Wait a minute, what's that cell - I want to attack that.' And it turns to attacking your own cells."

While it's well established that genetics play a pre-eminent role in how our immune system functions, that such an adaptation is the line between life and death in a pandemic is news.

As for applications to the COVID-19 pandemic - the virus has an average mortality rate of less than one per cent, far lower than the 50 per cent mortality of the Black Death - it would require DNA analysis of survivors and victims, to determine the role genetics played in those who died versus those who experienced minor symptoms and were young enough to pass along their genetic profiles to children - and if an evolutionary balancing countereffect may one day be discovered.

Poinar suggested that, while his team has helped to greatly advance DNA sequencing" methodologies, the symphonic cacophony" of processes framing the interaction of genes and the immune system will require artificial intelligence technology to arrive at more specific answers.

And who knows when we'll get the next big bacterial (plague)," he added. But with antibacterial resistance on the rise, it could be sooner rather than later, unfortunately."

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. Poinar is one of the authors of the paper, as is former Mac graduate student Jennifer Klunk.

The DNA for the study was drawn from skeletons in mass graves called plague pits" in England and Denmark, and the samples were studied at the McMaster Ancient DNA Centre in Hamilton.

Researchers examined DNA samples from more than 500 deceased people, focusing on a 100-year window before, during and after the Black Death, which reached London in the mid-1300s.

Poinar, whose work in the past has included sequencing the genetic blueprint of two extinct woolly mammoths, has taken part in grave extractions on-site, going back nearly 30 years to his work as a graduate student.

It's very different work, to sort of commune, in that sense, with these victims," he said. It gives you a very different perspective on mortality."

Jon Wells is a feature writer at The Spectator. jwells@thespec.com