The Black Death is thought to have killed about 50 million Europeans by the mid 1300s, according to estimates based on historical records and accounts. More recent research on agricultural activity at the time – which would have plummeted amid so many deaths – has suggested that the toll may not have been so dramatic everywhere, with some regions being devastated by the disease and others barely touched. Over the centuries, however, plague is estimated to have killed at least 200 million people.
Because plague outbreaks were so catastrophic, researchers have long wondered whether they left some permanent imprint on the human immune system. In particular, one theory suggests that the Black Death could have been widespread enough in the 14th Century to have created a form of natural selection. The idea was that some of the individuals who survived it were able to pass on any genetic quirks that helped them do so to future generations.
“The Black Death put a huge pressure on the human population in Europe,” says Norman. “It was persistent and damaging, and anybody with the slightest advantage in that situation through their genetics would have been more likely to survive.”
But until relatively recently, gathering any kind of data to answer this question was next to impossible. Sequencing DNA from the skeletons of ancient plague victims found in mass burial sites is notoriously challenging, with scientists often having to work with the tiniest fragments of DNA, many of which are highly contaminated.
“It’s quite common to find that the majority of the DNA is actually from the soil or bacteria which have invaded the skeleton after the person died,” says Swedish geneticist Pontus Skogland, who leads the ancient genomics laboratory at London’s Francis Crick Institute.
Experts have discovered, however, one piece of the skeleton where intact human DNA can still be reliably found. Called the bony labyrinth, it lies within the inner ear and is one of the densest parts of the human body. “It’s the most successful place to extract DNA from,” says Norman. “It’s a very, very tiny bone which is still protected in skull specimens. Without wanting to get too grisly, you have to really drill into the skull to get that bit of bone, while something like the leg bone is extremely porous and bacteria get in there much more easily.”
Over the last three years this has helped yield new insights into who survived past plague outbreaks and why.
Regulating immunity
The human leukocyte antigen (HLA) system consists of a group of genes that encode proteins on the surface of our cells, which play an important role in co-ordinating the immune response. A recent study has shown that some people who were asymptomatic to Covid-19 benefitted from a genetic lottery which meant they had certain HLA variants that acted as a form of natural protection against the virus.
“The role of HLA genes is to identify foreign invasion in the body and direct the immune system to seek out cells infected with pathogen proteins and destroy them,” says Norman. “Relatively rare variants of these genes can help some people survive a pandemic, and if Covid fatalities had been a lot higher, the human population would have been left with a much higher frequency of these variants.”
