Most people imagine themselves in a horror movie, but Sébastien Calvignac-Spencer loves dark warehouses filled with glass jars of human preparations. The French molecular virologist always hopes for unknown collections in museums and old hospitals. “A cellar where an inspired professor or devoted caretaker saved the old collection from destruction. Preferably with a yellowed index card that we can consult ”.
Because Calvignac-Spencer, a researcher at the famous Koch Institute in Berlin, is looking for fabrics. Preferably from the lungs of people who died of respiratory infections during epidemics. The devastating Spanish flu (1918-1920), for example, which caused 50 to 100 million victims, but also daily infectious diseases such as measles.
Unfortunately for him, pathologists mostly keep specimens with typical anomalies in their collections that are instructive for future doctors and surgeons. But sometimes Calvignac-Spencer finds his needle in a haystack. Two years ago, for example: the lung of a two-year-old measles victim from 1912. The preparation was kept around the corner by him in the Berliner Medizinhistorisches Museum der Charité.
The measles virus itself is no longer found there. Bacteria or viruses are irreparably damaged by the preservatives used. But there are still fragments of their hereditary material, pieces of DNA or RNA. Calvignac-Spencer’s research team was able to reconstruct the complete genome of the measles virus from which the baby died (see box). And with such an ancient genome a family tree can be established that indicates that measles has been wandering for 1500 years longer than previously thought, at least since the 6th century BC.
Spanish influence of 1918
This year, Calvignac-Spencer examined the lungs of a 17-year-old girl who died of the deadly Spanish flu virus in Munich in 1918. The virus she found appears to be nearly identical to the only two flu viruses previously found by this. pandemic. The first came from a New York victim whose lung had also been put in a mood; the other from a victim buried in Alaskan permafrost. All three viruses look a lot like an avian flu virus. While crossing the Atlantic Ocean, the Spanish flu virus did not undergo major changes at the time.
“We will never be able to describe the course of a past pandemic in such detail as is happening now with Covid-19,” Calvignac-Spencer said. AIDS is in fact the first pandemic in which the evolution of the virus, the HIV virus, has been followed. In the current corona pandemic, this is happening even faster and with greater accuracy, from the first variant in Wuhan to the new omikron variant. “But it is still not entirely clear whether it is normal for one variant to supplant the other,” says the virologist. “Evolution is an unpredictable process, but it often repeats itself. This could allow for predictions on what to expect in a pandemic ”.
Russian influence or crown?
Almost all generations have a pandemic, but fortunately not all are as serious as Covid-19. Calvignac-Spencer is now primarily looking for tissue from patients who died from Russian flu in the late nineteenth century. “That could not have been the flu but a corona epidemic. There is a coronavirus, OC43, which now only causes the common cold and which passed from bovine to human around 1890. Right during the time of the Russian flu. Finding the culprit is a challenge: a flu or a coronavirus “.
1890 is early for medical preparations. Although the oldest objects are around 300 years old, they are very rare. However, the virologist has now been able to identify an interesting preparation. “The curators are usually very helpful, but it takes time and a lot of paperwork to use such an ancient preparation. We hope to be able to start soon “.
Many infectious diseases such as plague, leprosy and tuberculosis originated about 10,000 years before Christ. People then settled in villages instead of migrating in small groups of hunter-gatherers. They grew crops and raised livestock. Viruses and bacteria therefore had a greater chance of transferring from animals to humans. And this could lead to epidemics because more people were in contact. Because when a pathogen finds no new victims, it disappears.
Going further back into the history of pandemics can be done by examining bodies buried in permafrost, mummified bodies, hollowed out skeletons, teeth and, surprisingly, ancient kidneys, stomach and gallstones or fossilized lung nodules. There, too, the genetic material may be intact enough that it can be reconstructed.
Read ancient DNA and RNA
Finding out what a virus or bacterium looked like centuries or even millennia ago primarily requires intelligent calculations through bioinformatics. The genetic material (DNA or RNA) breaks down into smaller and smaller pieces over time. The genetic code can be read from those fragments. The algorithms confuse them together again. A comparison with more recent and possibly older variants follows, in order to draw up a family tree. He can tell where or when the variants arose and also when “patient zero” must be experienced, ie when the disease has spread from animal to man. The variations found in the genome also determine how dangerous or contagious the virus or bacteria must have been. But the exact consequences of a deviated DNA or RNA fragment are still not always known.
The history of the plague is rewritten
Thanks to such research, for example, the history book of the plague has been rewritten in recent years. One pioneer is the German paleogenetics professor Johannes Krause (Max Plank Institute, Leipzig), who is fascinated by the most infamous pandemic in European history: the Black Death (1347-1351). Within five years, nearly all Europeans were infected with the plague bacterium and it is estimated that half died from it.
Krause’s research team first demonstrated two years ago that the Black Death was actually caused by the plague bacteria: Yersinia plague. Krause found 99 percent of the bacterial genes in the tooth roots of medieval skulls from a special plague cemetery in London. It is surprising that subsequent bacterial variants of that medieval epidemic, which Krause’s group has meanwhile also found, have changes that likely made the disease milder. An evolution similar to the one we are seeing now with Covid-19.
The London plague bacterium of 1348 appears to be a precursor to many modern variants. The plague has not yet been eradicated. This also does not work, because the bacterium has a natural reservoir: it lives in rodents such as marmots and rats, especially in Central Asia. Around 2,500 people around the world are still infected each year. It usually ends well now; over 95 percent survive on antibiotics. The last real plague epidemic, the Hong Kong epidemic, dates back to the second half of the nineteenth century and hitchhiked around the world via ship rats.
De oorsprong: Tian Shan
Krause was recently cleared to examine skeletons from the Tian Shan mountainous region of Kyrgyzstan in St. Petersburg. These were interesting because the original tombstones mention a great death in 1338, eight years before the plague bacteria caused a massacre in Europe. And it is known from historical writings that the disease came “from the east”.
Even now Krause has actually found the DNA of the plague bacterium, a variant that is genetically exact as the precursor to all strains that later passed into the world. So seven centuries later, one of the very first victims of the Black Death and the origin of the epidemic was found, the “Wuhan” of that time. In Tian Shan, the bacteria jumped onto a mountain dweller, most likely via a flea. And this did not happen in the 11th century, as previously believed, but just eight years before the Black Death struck Europe.
It wasn’t the first time that bacteria jumped and caused a pandemic. The oldest genome of a plague bacterium that has been recovered dates back to the Stone Age, from a skeleton of no less than 5,000 years that was found near the Black Sea. However, this bacterium turns out to be a variant of a side branch. now extinct from the genealogical tree of the plague bacterium.
An incredible change
It is surprising that the original bacterium does not have the genes that guarantee flea survival. Because it was those fleas that caused the infection during the Black Death. If fleas are infected with more modern plague bacteria via a mouse, it blocks their entry into the stomach. If the flea bites, the blood it wants to suck can’t get in, and it spits it back into its victim with the bacteria and all. And since the flea stays hungry, it keeps biting until it dies after a few days. The oldest plague bacterium discovered to know this evil trick dates back to 3800 BC Krause: “There must have been a startling change in the evolution of plague bacteria between four and five thousand years ago.”
With all those historical variants of the plague, Krause can sketch a distribution pattern from the Stone Age. That picture bears a great resemblance to the migratory models developed by historians. The disease traveled with humans, which makes sense. But Krause wonders if it could not be the other way around: did people in prehistoric times flee from epidemics? Were pandemics an important reason for population movements?
Surprising discoveries
Genetic research on ancient viruses and bacteria in mummies, skeletons, pathological preparations or permafrost bodies can rewrite history. Some exhibits:
• Tuberculosis did not come from Africa with modern humans, Homo sapiens, about twenty centuries ago, but it arose between two and eight thousand years ago. And tuberculosis did not result from bovine tuberculosis; that disease is younger.
• Hepatitis B is older than previously thought, at least 7,000 years. The virus evolves very slowly.
Smallpox was not the cause of major deaths in central Mexico in the sixteenth century. Researchers found salmonella and paratyphoid fever and severe drought occurred.
• The Iceman Ötzi (5300 years old, found in the Alps), suffered from a stomach ulcer caused by an Asian variant of the bacterium. Helicobacter pyloria predecessor of the current European variant which is a mix of tribes from Africa and Asia.
• The bacteria of leprosy, Mycobacterium leprae, little evolved in the last thousand years. The fact that leprosy has disappeared from much of the world is due to better hygiene and medical care, not because the current bacteria are milder than in the Middle Ages.
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The virus is hiding in the beast
Coronavirus is a zoonosis, it jumped from an animal, presumably a bat. This is not the first time this has happened, e definitely not the last.
