The Plague — Alles bleibt anders

A tiny virus can turn all our lives upside down – as we have recently learnt. Without, it seems, much of a warning we find ourselves in the midst of a pandemic, dealing with concepts like seasonal waves, R values, herd immunity, excess mortality. Such concepts are sad reminders of the “new normal”. But how new is it really? How long have pandemics been with us? And how did people in earlier times cope?
These are questions that we in the CRC 1266 have been thinking about. We know that infectious disease has been a constant presence in the history of humanity, and we have all heard of the “black death”, the deadliest pandemic of the Middle Ages. Yet the bacterium that caused it, Yersinia pestis, has been around for at least 5,300 years.

A Stone Age plague in northern Europe

The scene is Latvia, approximately 5,300 years ago. A group of hunter-gathers has set up camp on the banks of the river Salaca, near Lake Burtnieks, where they will spend the season fishing and gathering molluscs. The furs, flesh, bones and teeth of wild animals such as beavers are precious everyday commodities. But processing them can be dangerous: whether from being bitten by a beaver or while cutting up its corpse, a young man is infected with Yersinia pestis, a rodent disease. He dies and is buried according to the traditions of his time.

The river Salaca today — a good place to live even 5,300 years ago.
Well-preserved Neolithic skeletons from Riņņukalns.
A child’s skeleton has also remained intact throughout the millennia.
The river Salaca today — a good place to live even 5,300 years ago.

The Riņņukalns excavation site, thousands of years later

Researchers dig up his skeleton, scan his bones and teeth for traces of DNA and pathogens — and find Yersinia pestis. This is truly a surprising discovery, confirming that the bubonic plague has indeed been with us since the Stone Age.

But the remains of his companions show no such traces. The search continues, with hundreds of skeletons from sites across Europe — including ones dating from more recent prehistoric eras — being tested for traces of plague bacteria. Yet such traces continue to be a rarity. Was there no Stone Age plague pandemic after all?

The black death — the medieval plague

Fast forward to the Middle Ages: settlements of all kinds are densely populated, with people living at close quarters with each other and their animals in towns and villages alike. While global trade is thriving, basic hygiene leaves much to be desired. People are often sick, and Yersinia pestis has been on the march for centuries. It first struck in Late Antiquity, with the Justinian plague killing an estimated twenty to thirty per cent of the population of Europe and northern Asia between 541 and 770 CE. A second wave, deadlier still, struck Europe in the fourteenth century, killing nearly one third of the European population.

The social and economic consequences were devastating, with barely a household spared severe illness and death. So many people died in so short a time that mass burials were resorted to — and seldom in consecrated ground, something of immense importance to contemporaries. The causes of the disease were unknown at the time; explanations included divine punishment and contaminated air.

Such protective measures as closing ports and cities or imposing quarantine (from the Italian quaranta giorni, "forty days") had some success in containing the spread of the plague, but could never be comprehensively enforced. Local or regional outbreaks were to continue for several hundred years.

A medieval mass burial in Lübeck, c.1350—1370.
The plague was not the only widespread disease: traces of the bacteria causing typhoid were identified in several of these skeletons, whereas Yersinia pestis remains to be confirmed.
Unlike the Neolithic, the Middle Ages have left written accounts of plague epidemics.
A medieval mass burial in Lübeck, c.1350—1370.

Although the resemblance is striking, this illustration from the Toggenburg Bible probably depicts the symptoms of smallpox rather than those of the plague.

Excursion

Ancient and unwelcome companions: the bacteria and viruses that have been following humans around for millennia
The plague is not the only infectious disease with a long history. We know that pathogens known today, such as the hepatitis B virus and parvovirus B19 (Primate erythroparvovirus), a form of ringworm, are "as old as the Stone Age". The bacteria Heliobacter pylori and Salomoella enterica also caused stomach aches and diarrhoea for Stone Age people.
Leprosy (Mycobacterium leprae) and tuberculosis (Mycobacterium tuberculosis) developed from early strains of the pathogen and became established several millennia later. High infection rates of both diseases are only documented in the Middle Ages, for tuberculosis even later (also known as "consumption"). Today, it is the infectious disease with the most deaths in the world.
The viruses of smallpox (Orthopox variolae), the trigger for the invention of modern vaccination in the 19th century, and measles (MeV) are also older than their epidemic times. So we know many pathogens of the present from the distant past, but probably only a fraction of those that actually circulated among humans and animals at the time.
These virus and bacteria species, which are unknown to us, had different characteristics, just as they do today. They were not infectious or deadly to the same extent, were constantly changing and thus held very different pandemic potential for the populations of the time.

Has the plague always been “the plague”?

We know of only a few cases of Yersinia pestis in the millennia between the Neolithic and the Justinian plague in Late Antiquity (541—770 CE). How is this possible?

As a zoonotic disease, the plague chiefly affects rodents — not humans. Yet after two thousand years of coexistence between rodents and Yersinia pestis, the bacterium made a decisive evolutionary leap — quite literally. A gene known as YMT made the flea the principal agent of transmission from animals to humans. Yet this seems initially not to have been much of a threat. However, over the following 2,500 years human lifestyles developed in a manner conducive to the spread of the disease. As rats, fleas and humans came to live together at ever closer quarters, the risk of infection rapidly grew, and the Justinian plague was the first major outbreak we know of.

Yersinia pestis

As the pathogen changes, so do the symptoms

We do not know how sick the man from Riņņukalns really was. Bacterial infection with Yersinia pestis may have caused sepsis, leading rapidly to death.

The bubonic plague commonly associated with the Middle Ages takes its name from the buboes, swellings resulting from inflammation of the lymph nodes. They are typical of transmission by flea bites and hence are unlikely to have occurred in the Stone Age.

Excursion

Old DNA from archaeological material: tiny remains, huge discoveries
It’s something of a little miracle: minute remnants of molecular matter from organisms — humans, animals, plants, viruses and bacteria — can last for thousands of years. We analyse their organic material (i.e. parts of the cells), which contains fragments of DNA, their genetic code. In human and animal remains, such material can usually be found in teeth and bones.
Remnants of pathogens can often be found in the well-protected inside of teeth, in the root canal. A particularly valuable material for biological analysis is tartar, a mineralised biofilm. It is a breeding ground not only for pathogens but also for the “good” bacteria that make up the oral microbiome on which a healthy oral cavity depends. Tartar may also retain traces of food or its component elements.
Something similar is true of ancient birch tar, which served early humans both as an adhesive and a form of chewing gum. Finds of the substance thus often contain genetic material. Organic material may also survive as food crusts on ceramic vessels or in fossilised excrement. With the range of materials they contain — from body tissue to the contents of their stomachs to their clothing — mummies are a particularly rich source of potential DNA finds.
As a rule, even the oldest sample can still contain valuable genetic material. Whether it does so is due in large part to the environmental influences to which it was exposed over the course of the millennia. Of particular importance is the interplay of ventilation, moisture, temperature, soil composition and the activity of microorganisms.
Much work goes into obtaining a DNA sequence from an archaeological sample. The sample must be mechanically prepared and the DNA biochemically isolated in a cleanroom. This DNA must then be tested to verify that it is “authentic”, i.e. old, before going on to quality checks, further amplifications, sequencing and the analysis of genetic codes.
This process can take months for a single sample. A final fun fact — this makes aDNA (ancient DNA) research the most data-intensive branch of bioarchaeology.

It takes humans to make pandemics

More than four thousand years separate the first known cases of Yersinia pestis in the Stone Age from the black death of the middle ages. Yet whether they lived as groups of hunter-gatherers, as agriculturalists or in urban centres, human beings have always provided an ideal breeding ground for infectious diseases. Yersinia pestis stuck around, grew increasingly virulent and ultimately claimed the lives of more than twenty-five million people. Even today, there are approximately three thousand cases of bubonic plague each year, resulting in five hundred deaths.

It seems that, even in the Stone Age, death by plague or other infectious disease had a profound impact on individuals and communities. Yet deadly pandemics seem to be a more recent phenomenon, one belonging to the history of modern humans. Today, we are able to identify bacteria and viruses under the microscope, subject them to genetic analysis and understand their workings. We can draw up courses of treatment and strategies for combatting epidemics and pandemics. Science has given us far more effective tools against pandemics than we have ever had before.

Skeletons — and skulls in particular — are the primary repositories for information concerning infectious diseases and pandemics in the past.

Excavation

Large areas, small holes: different excavation depths must be defined during fieldwork.
Exposing human bones is delicate work and best done with a brush.
Removing soil substrate from the pelvic area of a skeleton — we hope it contains some interesting bacteria!
Patience is an essential requirement — as when pumping a night’s rainfall from the excavation pit.
Whatever is dug up must be recorded. Modern technology, including this drone, makes it much easier to record the position of finds.
Large areas, small holes: different excavation depths must be defined during fieldwork.

Zoonotic diseases today

Climate change and infectious disease — a deadly duo?

The consequences of human intervention in the environment are not yet fully understood. What is certain is that they are far-reaching; what is less certain is that it will all end well.

Climate change has reached crisis point, causing environmental disasters. We hear of these catastrophes in the news and can see change playing out before our own eyes — sometimes experiencing it in our own bodies. Amid altered ecosystems and precarious conditions of life, infectious diseases — already the second-most frequent cause of death — are set to pose an even greater threat in the future.

As humans claim more of the natural environment for themselves, new zoonotic diseases emerge, and as host animals move into more exotic surroundings, the risk of infection increases.

At the present, this can be observed in the case of tick-borne encephalitis and Lyme disease (Lyme borreliosis). The vector for both is the tick, which thrives in long summers and mild winters. The same is true of the tiger mosquito, which carries the Zika, Chikungunya, West Nile and Dengue viruses.

Sars-Cov-2 was the first zoonotic pathogen to be systematically analysed, giving valuable insights into epidemiology and evolution.

Our research into the basic mechanisms of zoonotic diseases are still in their early stages. This makes the perspective offered by the past — by ancient DNA — all the more valuable for the perspective on the future.

Ben Krause-Kyora is a molecular biologist researching pathogens and their influence on human life over the past ten thousand years at the Institute of Clinical Molecular Biology (IKMB), Kiel University. He takes a particular interest in the first settled farmers, whose novel way of life bought them into close and lasting proximity with domesticated animals, remaking the environment and exposing them to new pathogens in the process. Over the millennia, the impact of the resulting pathogens and the pandemics they caused has changed the human genome and left traces in its present form.

Text, images and content by Katharina Fuchs
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