How The Black Death Pandemic Shaped Our Response To Diseases Forever

The genes that once conferred protection against the Black Death are today associated with an increased susceptibility to autoimmune diseases such as Crohn's disease and rheumatoid arthritis.

The Black Death, the most fatal pandemic recorded in human history, has played a significant role in shaping how we respond to diseases. It was a bubonic plague pandemic which ravaged Europe between 1347 and 1351, claiming about 25 million lives. The pandemic also devastated North Africa. Plague is an infectious disease caused by the bacteria Yersinia pestis, usually found in small mammals and their fleas. Recently, researchers from McMaster University in Ontario, University of Chicago in Illinois, Pasteur Institute in Paris, and other organisations analysed centuries-old DNA from victims and survivors of the Black Death pandemic. 

The analysis helped them identify key genetic differences that determined who lived and who died, and how the aspects of the immune systems affecting disease response evolved over time.

The researchers analysed and identified genes that protected some people against the devastating bubonic plague pandemic that ravaged Europe, Asia and Africa nearly 700 years ago. The study describing the findings was recently published in the journal Nature.

Protective genes associated with increased susceptibility to autoimmune diseases

According to the study, the genes that once conferred protection against the Black Death are today associated with an increased susceptibility to autoimmune diseases such as Crohn's disease and rheumatoid arthritis. Crohn's disease is an inflammatory bowel disease that causes swelling of the tissues in the digestive tract. Rheumatoid arthritis is an autoimmune disease that causes pain, stiffness and swelling in the joints. 

How the study was conducted

The researchers focused on a 100-year window before, during and after the Black Death. The pandemic, which reached London in the mid-1930s, remains the greatest human mortality event in recorded history. The pandemic killed more than 50 per cent of the people in regions which, at that time, were some of the most densely populated areas of the world. 

The researchers extracted and screened more than 500 ancient DNA samples from the remains of individuals who had died before the bubonic plague, died from it, or survived the Black Death in London. These included individuals buried in the East Smithfield plague pits used for mass burials from 1348 to 1349. The researchers also took additional samples from remains buried in five other locations across Denmark. 

Four genes under selection identified

They searched for signs of genetic adaptation related to plague, and identified four genes that were under selection. All these genes are involved in the production of proteins that defend our systems from invading pathogens. 

The researchers also found that versions of those genes, called alleles, either protected or rendered one susceptible to plague. 

Which gene decided if one was protected from the disease?

They identified a gene called ERAP2. Individuals who had two identical copies of the gene survived the gene at much higher rates than those with the opposing sets of copies. This is because the 'good' copies allowed for more efficient neutralisation of Yersinia pestis by immune cells. 

In a statement released by McMaster University, Hendrik Poinar, an author on the Nature paper, said when a pandemic killing 30 to 50 per cent of the population occurs, there is bound to be a selection for protective alleles in humans. This means that people susceptible to the circulating pathogen will succumb. A slight advantage can help one survive the disease. Poinar added that the survivors who are of breeding age will pass on their genes. 

Since the Europeans living at the time of the Black Death had no recent exposure to Yersinia pestis, they were initially very vulnerable to plague. Mortality rates decreased over the following centuries as waves of the pandemic occurred again and again. 

People with the ERAP2 protective allele, or the good copy of the gene, were 40 to 50 per cent more likely to survive than those who did not, the study said. 

Luis Barreiro, an author on the paper, said the selective advantage associated with the selected loci are among the strongest ever reported in humans showing how a single pathogen can have such a strong impact on the evolution of the immune system.

Significance of the study

Over time, our immune systems have evolved to respond in different ways to pathogens. A gene that once provided protection against plague in the Middle Ages is today associated with increased susceptibility to autoimmune diseases, according to the study. 

Poinar explained that it is important to understand the dynamics that have shaped the human immune system in order to know how past pandemics, like the plague, contribute to our susceptibility to disease in modern times.

The researchers concluded that protective variants overlap with alleles that are today associated with increased susceptibility to autoimmune diseases. This provides empirical evidence for the role played by past pandemics in shaping present-day susceptibility to disease.