History of plague – Fondation Ipsen

For as long as Historians have been able to report it to us, the human species has suffered from numerous epidemics through the ages, whether during Antiquity, the Middle Ages, the Renaissance or even in our contemporary history. Each of us can attest to this today with COVID-19, which has changed our way of life in recent weeks. But when discussing the great epidemics in history, it nearly seems impossible not to think of the plague. This anthropozoonosis, a disease common to humans and animals, has wreaked havoc over the centuries and decades. It is notably caused by the bacillus Yersinia Pestis, which was discovered by Alexandre Yersin. In this episode, we will discuss the process that allowed this Swiss-born doctor to isolate this bacillus. In a second step, we will put into perspective this breakthrough so important for humanity by remembering the two largest cases of plague epidemic in history: the Plague of Justinian and the Black Death, which both ravaged Europe and other parts of the world.

Yersin, the man who struck down the plague

In June 1894, 30-year-old Alexandre Yersin disembarked in Hong Kong, then under British rule, a very active port since it was the hub of trade between the United Kingdom and China at the time. Equipped with his microscope, he is determined to try to identify and find a cure for the evil that is hitting the city. On arrival, he discovers a city which has been extremely affected and which has already been largely emptied because part of its inhabitants has been evacuated due to an epidemic of plague which started several weeks ago. In the streets, numerous corpses litter the ground, with the presence of putrid buboes on the inanimate bodies, typical of the plague. There is therefore an urgent need to take charge of these bodies, make them disappear to contain the epidemic, which is likely to spread far beyond the city. Henri Mollaret & Jacqueline Brossollet, biographers of Alexandre Yersin explain to us how the authorities present on the spot set up the care of the numerous corpses and sick: “the hastily improvised cemeteries are in fact simple graves where the corpses are thrown into lime and covered with a concrete screed. Every day, 300 British soldiers visit all the Chinese houses and take the sick to one of the hospitals.”

Alexandre Yersin was born in Switzerland and was naturalized French in 1889. A brilliant young doctor, he crossed paths with Louis Pasteur the year of his 22nd birthday. The latter then made him work within the Pasteur Institute on infectious diseases. He took part in important works, in particular on the diphtheria vaccine. Adventurer at heart, Yersin quickly chose to go into exile in the Far East, and more particularly in Indochina, then a French colony, with which he fell in love. Yersin was a brilliant scientist. Multifaceted, he devoted himself to ethnography, cartography and even astronomy in his spare time.

When he learnt that a plague epidemic was ravaging Hong Kong, he alerted the French colonial authorities of his desire to go there to understand what was going on. The authorities then gave him the mandate to go there. But as soon as he stepped on Hong-Kong, he realized that he would have to face several obstacles. Yersin did not speak English, which greatly penalized him for communicating correctly with the English authorities present on the spot. In addition, a Japanese research team, led by Prof. Kitasato, was already on the scene, and was reluctant to collaborate with the Franco-Swiss. Indeed, at the end of the 19th century, the world faced a rise in nationalism, and the scientific field was not spared. If there was to be progress, it quickly became obvious that it would not be by the collaboration of teams from different countries. In addition, it is important to note that Prof. Kitasato was not just anyone. A brilliant bacteriologist, he spent six years in Germany in the 1880s to perfect his training with the teams of the famous Robert Koch, the great rival of Louis Pasteur who had discovered the bacillus of tuberculosis in the early 1880s. This bacillus was also renamed after him: the Koch bacillus. When he landed in Hong Kong, Kitasato was already considered a prestigious scientist. During his time spent in Germany, he notably participated in the work on the creation of the serum of diphtheria and tetanus antitoxins, which allowed him to become a little celebrity in the scientific world.

But Yersin, who got wind of what the Japanese were working on, wass convinced they were on the wrong track. As convinced as he was, he needed a space to work. He then went to the Hong-Kong Hospital, where the manager of the structure only granted him a small room at the end of a corridor, while the Japanese team already had several rooms there, comfortable and equipped. The head of the hospital also did not give him access to the bodies for study, which were once again reserved for the Japanese. Faced with this situation, Yersin decided to manage things differently. By distributing tips to the right people, he finally accessed corpses. He then followed an intuition which had been trotting in his head for some time. If he and the Japanese had failed to identify the microorganism responsible for the plague, it was because they were not been looking in the right place. Would it then be possible that this microorganism is housed in the famous buboes, which are swollen and inflamed nodes?

In one of his many correspondences during these events, Alexandre Yersin said: “we open one of the coffins, I remove a little whitewash to discover the crural region, the bubo is very clean, I remove it in less time than a minute and I go up to my laboratory. I quickly make a preparation and put it under the microscope. At first glance, I recognize a veritable mash of microbes, all similar. These are small, stocky sticks, with rounded ends, and fairly poorly colored.’’ By quickly preparing his sample, Yersin did not make the same mistake as the Japanese. He cultivated his preparation at room temperature, while the Japanese grew their samples at a temperature of 37°C. Thus, it is very likely that Yersin’s lack of means gave him, very ironically, an advantage over the Japanese. And it makes sense though! If the bacteria was in the buboes, it was because it was trying to flee the temperature of the body!

An Italian priest then helped Yersin to hastily build a cabin made of straw and bamboo, so that the scientist could work quietly. He also alerted the head of the hospital of his discovery, and the latter then finally gave him access to the corpses. Eager to find a cure quickly, he began testing. Yersin inoculated the plague bacillus to mice and other animals. The mice died in 24 hours, and the other animals took three to six days to succumb. But what was very important was that all the animals had plague buboes. The doubts were then dispelled and the work to create a serum continued. Week after week, the Institut Pasteur was kept informed, and Yersin even sent samples to Paris.

In the spring of 1895, Yersin returned to Paris for a while to work with his colleagues at the Institut Pasteur. But he returned very quickly to Indochina, the summer of that same year. In 1896, he developed a serum to treat men and women, which he tested on a Chinese seminarian affected by the plague. And there, the success was total. On the strength of this incredible advance, he went to Bombay in 1897 where an epidemic of plague broke out, and where his serum, even if it was still perfectible, saved a large number of lives. On site, he worked in collaboration with Paul-Louis Simond, also a Doctor at the Institut Pasteur. Because even if the plague bacillus had been formally identified by Yersin, a big question still remained unanswered. How is this disease transmitted from rat to man? When examining the patients, Simond found very small blisters, almost invisible to the naked eye, characteristic of insect bites. There was no longer any doubt that the culprit who had been designated for centuries in the transmission of this scourge to humans, who were rats, was found innocent. The real culprit turned out to be the rat flea. A year after the Bombay events, a new plague epidemic surfaced in Karachi. This time, thanks to his experiences, Simond succeeded in proving his hypothesis, and declared: “That day, June 2, 1898, I felt an inexpressible emotion at the thought that I had just violated a secret which anguished humanity since the appearance of the plague in the world. ”

At the time when Simond confirmed his theory, the first vaccine against bubonic plague had already been developed by Waldemar Haffkin, a bacteriologist born in Imperial Russia, in Odessa (present-day Ukraine). Haffkin had also been mandated by the authorities of his country to study the plague epidemic which raged in Bombay in 1896 and 1897. He was therefore there at the same time as Simond and Yersin. In particular, he tested the vaccine there on his own person. Once the results were published, a test phase was launched on prisoners from a prison south of Bombay. Of course, the prisoners were volunteers, and they survived, while seven inmates from the control group, who were not treated, died.

Of course, the work of Yersin, Simond and Haffkine does not mean that the plague was completely eradicated at the end of the 19th century. Many plague epidemics would rage in the 20th century. But from this remarkable work, plague epidemics were better controlled, and patients could, if treated in time, be managed effectively. This is a turning point in the history of mankind because, as we will see, the plague had claimed countless victims over the centuries and millennia.

Indeed, over the centuries, mankind has long attributed the name “plague” to various epidemics, such as in Athens in 430 BCE. Although opinions differ, consensus has been reached among historians and scientists to describe the epidemic as not being a plague. The most likely candidates are typhoid fever or hemorrhagic pox. Still, almost a third of the Athenian population was decimated, representing around 80,000 people.

It is also possible to cite the “Antonine plague,” which spread from 165 to 170. Today considered as an epidemic of smallpox, it is estimated that it cost the lives of nearly 5 million people in the Roman Empire, which at the time represented 10% of its total population. Many historians also agree that this epidemic was one of the causes of the decline of the Empire, which found it very difficult to recover, both demographically and economically.

Plague of Justinian

The plague has therefore been known for a long time. The Roman Emperor Titus died of it in the year 81. But the first great epidemic of plague is undoubtedly the “plague of Justinian.” Why this name? Well, because this terrible epidemic appeared during the reign of the Eastern Roman Emperor Justinian, who lived from 482 to 565. At the time, thanks to the conquests of the Emperor and his generals, the Roman Empire of the Orient or Byzantine Empire is at its peak. The vast majority of the Mediterranean coast had indeed been reconquered. According to the Historian Procopius of Caesarea, contemporary of the epidemic, the plague may have originated in Egypt, at Peluse in 541. It then spread to Alexandria, before following the trade route leading to the capital Constantinople, thus passing through Palestine, Syria and Anatolia.

It was in the middle of spring 542 that the epidemic broke out in the capital, and it wreaked havoc! On this subject, Procopius, in his History of the Wars, told us: “Most of the victims contracted the disease without knowing it. They carried it away in that way. All of a sudden, they were feverish […]. The body did not change color, its temperature was not particularly high, as in the case of a feverish attack and no inflammation appeared. The fever was so little pronounced from its onset until the evening that no one, neither the patient nor the doctor examining it, feared the slightest danger. It was natural, therefore, that none of those who had contracted the disease expected to die from it. But on the same day, in some cases, in others the next day, in others still a few days later, a bubonic blister formed”. Procopius also told us that the affected body parts were the armpits, the side of the ears, the lower part of the abdomen, and the thighs. At the time, medicine had no way of fighting this epidemic, which lasted for four months in the capital. Caregivers still tried to treat the sick by referring to the famous Theory of Humors, but it quickly became clear that these practices were not effective. The population then turned to less traditional and belief-based treatments, which prove to be just as ineffective. At its initial stage, the epidemic did not cause many deaths. But, as Procopius points out, it was only a mirage and it would quickly mow down an incredible number of people. “Soon there were five thousand deaths every day, then ten thousand, and more.” In order to cope with this number of corpses and to reduce the risk of other serious health problems, people organized themselves as best they could. They then witnessed terrible scenes. At first, the dead were buried normally, but the lack of space pushed families to place their dead in already existing graves. An illegal practice, this act was often done in secret, then in front of everyone’s eyes by forcing the passage. The disorder then settled little by little. Faced with this uncontrollable situation, the authorities then decided to dig pits in front of the city walls, in order to deposit the corpses there. But Procopius tells us that even these pits were not enough to accommodate all the dead. Drastic measures were then taken. The inhabitants started by piling up the corpses in buildings, before throwing them into the sea.

But these times of crisis sometimes have the merit of bringing people together. Thus, our Historian tells us that “those who had been members of factions renounced their mutual enmities and attended the funeral together.” This did not mean, however, that the people of Constantinople remained carefree in the face of the epidemic and went about their business as if nothing had happened. At the height of the crisis, the streets were deserted. Residents stayed at home, isolated themselves, to protect themselves or to care for their loved ones. The workshops were stopped. There was no activity whatsoever, and access to food became very difficult. The specter of another scourge was therefore added to the epidemic: famine. This Plague of Justinian would therefore have a considerable impact on the economy of the empire.

Even if Procopius’s stories were above all testimonies of what he himself saw and experienced, we now know that this epidemic did spread widely in Europe, in particular because of two factors. First, the Byzantine trade was already very organized, and the trade routes widely followed, which favored the spread of the disease. Second, the military power of the Empire and its presence on almost the entire Mediterranean coast involved regular troop movements, which also favored the spread. In the end, even if the epidemic episode in Constantinople only lasted four months, the disease gradually spread, arising many times across Europe for two centuries, until 750 AD, date of the last epidemic episode. It affected most European countries, and it is estimated that it made nearly half the European population sick, and killed between 25 and 30%, at least 25 million people. In Constantinople, it decimated between 20 and 30% of the population in four months.

In 2014, a study published in the famous journal The Lancet confirmed that this epidemic was indeed an epidemic of bubonic plague. While working on a medieval cemetery identified as dating from the Justinian plague period, many traces of Yersinia pestis were found by researchers. And this Yersinia pestis was also the cause of the largest plague epidemic in history: the famous “Black Death.”

The Black Death

The “Black Death” is undoubtedly the greatest scourge in the history of the Western world. We know today that it was a bubonic plague, to which was added the pneumonic plague, which is the most virulent form of plague. It began in Europe in October 1347 in Messina, Sicily. On this date, Genoese ships indeed entered the port, and it was very logically supposed that these ships arrived with many riches from the east. But, inside these ships, one quickly realized that there were a large number of sick people. The symptoms were terrible, and many patients seemed already dead. The smell was pestilential. In Messina, the port authorities quickly understood that the plague took part of the journey. Two weeks earlier, these merchants were in Caffa, Crimea, a hub for trade with the Orient, making it a strategic point that strongly attracted lust. In 1347, it was surrounded by a Mongol army which was soon struck by an epidemic which decimated the Mongol army itself. Forced to lift the siege, the Mongols then had the fatal idea, out of revenge, to catapult purulent corpses in the city. This is how the plague was declared inside the city. Faced with the rapid spread of this evil, several merchants therefore decided to leave, but this decision would only facilitate the spread of the evil. They soon realized during the trip that several people had been affected by the epidemic. Many of these merchants would not only go to Messina but would stop at Constantinople, Venice or Marseille. On the Messina side, the decision was made to force the return of the boats to the sea before it was too late, but unfortunately, the damage was done. The plague was already spreading in the city, and, like in Caffa, many residents decided to leave, not suspecting that they would also spread the scourge. Many regions were soon affected. In addition, there was the spread through trade. The plague thus reached the south of England in June 1348. It went up to Scotland and then reached Ireland. It also continued its progression through the Baltic and affected the Scandinavian countries and Poland, before closing the circle and reaching Russia and Crimea, from where it had all started. The cities, because of their very large population, facilitated the spread of the disease and were very strongly affected. Barbara Tuchman, famous American Historian, gave us details on the spread and the consequences of this scourge in her book A distant mirror. The 14th century, a century of calamity: “In overcrowded Avignon, it was guaranteed that 400 people would die every day. 7,000 empty houses had been closed, and a single cemetery had received 11,000 bodies in six weeks. Once all the cemeteries were filled, the bodies were thrown into the Rhône, until mass graves were dug.” The example of Avignon is not trivial since at that time, the city was the place of residence of the Pope and was therefore one of the centers of the Christian world, with all the population movements that this implied. In 1348, Florence, Bremen, Paris, Brussels, London were affected. The plague had spread across the continent. In some places there were so many dead that the population didn’t know what to do with them. There was no longer a single living soul in certain villages.

Medicine at the time was powerless in front of the epidemic. It must be admitted that it was not much more advanced than during the Plague of Justinian. Indeed, caregivers still referred to ancient practices from the Theory of Humours. Doctors tried to treat the sick with bleeding, purging, and directly burned the buboes. But all of these practices prove to be ineffective. Quarantines were then put in place by the authorities, but the plague continued to spread, and gave the impression of having no limits. However, some doctors of the time were of good advice. This is particularly the case of Pierre de Damouzy, who taught at the Faculty of Medicine in Paris and who was, during the epidemic, Canon of Reims. To his local population, he advised: “above all, stay at home“! But habits were hardskinned. The population of the Middle Ages was very pious and would soon be convinced that the plague came from a divine anger. In Rouen, for example, measures were taken to calm this divine anger. The authorities of the cities ordered the population to stop gambling, using swear words, and consuming alcohol. Long processions and group prayers were held that gathered large crowds, which, unfortunately, would create a very fertile ground for propagation. Groups of flagellants also formed. They passed from village to village, reciting incantations before flogging themselves to the blood using whips, the ends of the straps of which were reinforced with metal. These groups were particularly active in Picardy and Champagne. For some, the wrath of God was also a pretext for finding scapegoats. Many lepers were found guilty and massacred across Europe. The various Jewish communities in the continent were also targeted. In January 1349 in Basel, hundreds of people of the Jewish faith were assembled, locked up and then burned alive in a building. In Strasbourg, between 1,000 and 2,000 Jews were massacred and burned, accused by the population of spreading the evil.

From the years 1351-1352, the plague wave finally died down. In less than five years, it had ravaged the whole of Europe, killing between 1/3 and half of its population. It is estimated that it killed nearly 50 million people. But it did not stop there. As with the Plague of Justinian, evil re-emerged many times until the end of the 14th century. Other large epidemics of plague appeared, fortunately without making as many victims, as for example in London in 1665 where it all the same cost the life to approximately 80 000 people, or in Marseilles, in 1720 where it is estimated that it killed between 80,000 and 120,000 people, half of its population.

In his fable The animals sicks of the plague, Jean de la Fontaine told us: “ They died not all, but all were sick.” In its days, and for most of the time before it, yersinia pestis killed between 60 and 80% of the sick. Thanks to Yersin’s incredible journey, the destructive capacity of this anthropozoonosis has been greatly reduced. However, it has not disappeared and continues to declare itself regularly around the world. Today, the World Health Organization tells us that “if diagnosed early, bubonic plague can be successfully treated with antibiotics.” In these particular times, it is useful for us to look at what has happened in the course of history. The great epidemics have, over the centuries, wreaked havoc and the scientific progress of the last 150 years now protect us largely against this type of epidemics. However, as we have seen with the Justinian Plague and the Black Death, we must be wary of these diseases for which we have not yet found a cure, regardless of their mortality rate. At the time, good reflexes were not known, the means of communication were primitive. The population did not know that the gatherings favored the spread of epidemics, did not know the barrier gestures, did not have the same hygienic conditions etc. Today, we all have access to the information we need to protect ourselves and our loved ones. If in doubt, trust the recommendations available on many platforms, such as that of the French government, namely https://www.gouvernement.fr/info-coronavirus. We have no excuse and must use lessons from the past. If you have the capacity to do so, as Pierre de Damouzy said a little less than 700 years ago: “above all, stay at home“!

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