Humans vs. Pandemics: A Brief History

It used to be worse. MUCH worse.

Igor Rudan
11 min readJul 18, 2020

For much of human history, there was no need to worry about a career change or life-long learning. Most people were living off agriculture and cattle breeding. They would acquire all the basic skills required for their survival early in their lives. From one generation to the next, their lives seemed quite similar. The major uncertainties were associated with what was popularly known as “the four riders of the apocalypse”: plague, war, famine, and death. Those were their four greatest fears.

Which of those four should we still fear today? Death was always an inevitable ultimate outcome, as it remains to this day. We’re doing our best to delay it, but we still have found no way of cheating it, although some are trying very hard. War is still very much with us, and it may be an even greater threat than ever before given the advanced technology of modern weapons. Famine is not worrying us nearly as much as it used to, although there are still parts of the world in which hardly anything changed over the past few centuries and which remains very much affected. There are perhaps some new riders of the apocalypse in the present day, such as road traffic accidents, terrorism, and climate change. But if we were to pick one that we should all fear more than all of the other riders combined, it should probably be the first one — the plague.

Clearly, I don’t mean it literally — as the “bubonic plague”, which is a specific infectious disease that was historically caused by Yersinia pestis and was transmitted by rats in unsanitary medieval cities. What we mean by “plague” today is an unanticipated, dramatic, rapid outbreak across many parts of the world of an entirely unknown infectious disease. This can happen when a new microbial pathogen is formed due to mutation and it gains the ability to infect our species. Since we have had no previous exposure to it so we tend to have no existing lines of defence. Such a development could still result in a massive, sudden, dramatic mortality with rapid spread throughout the human population, accompanied by global panic and mass devastation.

There have been many episodes in our history when our ancestors experienced such scares and were left decimated. One of the earliest records was left by the Ancient Greeks. In the 5th century BC, the plague of Athens, thought to be a form of typhus, claimed some 100,000 lives. But this was merely a warning of much worse times that were looming. In the 2nd and the 3rd centuries the plagues of Antonine and Cyprian — likely caused by smallpox — killed millions of people in the Roman Empire.

And it was going to get yet worse: in the 6th century, the plague of Justinian, thought to be the first bubonic plague, may have claimed up to 30 million souls, killing one- in-three people living in Europe and the Mediterranean basin. But even that wasn’t the worst that our ancestors had to endure. In the middle of the 14th century bubonic plague hit again — now remembered as the notorious “Black Death” — killing more than 70 million people worldwide, and more than one-in-three people living in Europe at the time.

The plague continued to linger in Europe through smaller outbreaks and accompanied by a scary chronic infection called leprosy. In the 17th century, bubonic plague caused panic yet again. It hit several cities in Italy before it struck London and Vienna and then reached Eastern Europe and Russia in the 18th century. Those later outbreaks claimed hundreds of thousands of lives but fell short of causing devastation on the scale that was seen in the times of the Black Death.

But something even worse than the Black Death was happening to people who were not living in the so-called “known world” at the time. Global explorations carried out by the strongest European nations and their navies did not only discover new continents but also introduced deadly infectious diseases to many indigenous populations. Whereas Europeans were genetically highly selected to resist these epidemics of deadly infections the indigenous peoples of the Americas and Australia had never been exposed to smallpox, measles, influenza, or typhus. Their contacts with the explorers from Europe caused massive mortality and the complete disappearance of some of these peoples.

In the 16th century in today’s Mexico an epidemic of an unknown disease — likely a viral hemorrhagic fever, smallpox, or both — killed 80% of the native population, ruining the civilization of Aztecs. American Indians, Incas, and Mayas fared no better in the following centuries and many now believe that the death of more than 90% of the native populations of the New World was caused by Old World diseases — above all smallpox, measles, and flu.

Smallpox also led to catastrophic mortality among the native populations of Oceania, killing between 30% and 50% of Aboriginal Australians, New Zealand Māori, Hawaiians, and the native population of the Easter Islands. But some new diseases were brought from the Americas back to Europe, too. Syphilis was introduced to Europe after Columbus’s voyages and it was more frequently fatal than it is today, becoming a major killer in Europe during the Renaissance period.

Increased migrations in the 19th century through trade and travel brought about a new scare: cholera. Between 1816 and 1899, the world experienced six consecutive pandemics of cholera which killed tens of millions of people from India to China, Russia, Europe, and both coasts of North America.

Unexpectedly, an old, fearsome enemy also made an unexpected return: the third pandemic of plague started in China in 1855, almost exactly 500 years after the “Black Death”. It spread to India where 10 million people died, and then throughout the rest of the world, reaching even as far as San Francisco.

Masked by those six waves of cholera and an unexpected return of the bubonic plague, another pandemic struck the world at the end of the 19th century. It was a well-known one — influenza. The Greek physician Hippocrates, the “Father of Medicine”, first described it in the 5th century BC. This time it started in Uzbekistan, became known as “the Russian flu”, spread literally everywhere, and killed 1 million people. But in a world that was buzzing with industrial development and with the building of large cities, travel, and trade, it was hardly noticed as anything more than a really bad epidemic of flu. No-one could predict, at that time, that this was an almost gentle announcement of what was to come. A period that may well be remembered as the worst seven years in the history of modern humans was just ahead.

In 1914, World War I broke out. Going back to “the four riders of the apocalypse”, this was the rider of “War” as no other before it. It claimed 17 million lives, left a further 20 million people wounded and caused massive devastation. But it got even worse. It created the perfect conditions for influenza to strike again. This time, a “Spanish flu” ripped through an exhausted, under-nourished, misplaced, and depressed human population as the war ended, killing 75 million people. This was likely the worst case of a “double blow” that we’ve experienced as a species — and it happened only some hundred years ago.

Flu pandemics keep coming back every 10–30 years as the virus keeps mutating in wild aquatic birds and waterfowl and then finds a way to jump to humans. Pigs can be infected with both human and avian strains and so can lead to mixing and new viruses. “Asian flu” pandemics in 1957 killed 2 million people, and the “Hong Kong flu” pandemics in 1968 left another 1 million people dead.

As well as bubonic plague, cholera, leprosy, and flu it is clear that the other main epidemic diseases which historically inflicted massive burdens of mortality on our ancestors were smallpox, measles, and typhus. Smallpox has surely killed well over one billion people throughout known history. It was a highly contagious disease caused by the variola virus and the first one that we managed to completely eradicate from the planet through vaccination. The eradication meant that no further human lives would be lost. Considering the cumulative lives saved since then, and the cost savings each year — now that we don’t need to protect ourselves anymore — probably means that smallpox eradication may well be our greatest global health achievement as a species.

Measles contributed to the destruction of civilizations of central and South America and caused hundreds of millions of deaths throughout human history. Typhus is sometimes called “camp fever” because it typically flares up during armed conflicts. First described during the Crusades, it remained a prominent cause of death in many other subsequent wars. Between the 16th and the 20th century, it is thought that more military personnel were killed by typhus than from military action — both while in combat and while imprisoned in detention camps.

In the 21st century, we are beginning to forget about our catastrophic collective past, and the unimaginable death toll that infectious diseases imposed on our ancestors. We are the first generations of humans who no longer fear infectious diseases. Thanks to antibiotics and vaccines, which keep us safe, the human population has increased from about 1.5 billion at the beginning of the 20th century to 7.5 billion at the beginning of the 21st century. That’s five times more humans on the planet, and mainly because we learned how to prevent and treat the most dangerous infections! But how safe are we, really?

Microbes are incredibly abundant in nature, and they have very short lifespans. They can adjust to threats, such as antibiotics, very quickly, through mutations. Massive over-use of antibiotics, not only in humans but also farmed animals, is putting us all in danger. It allows microbes to adjust to antibiotics and develop “antibiotic resistance”, leading to new future epidemics with untreatable new strains of bacteria.

In addition to antibiotic resistance, it almost defies belief that there are people who are beginning to question the value and safety of vaccines, leading to reduced coverage of population vaccination and loss of our “herd immunity” (protection of those who are unvaccinated –such as young babies too young to respond to vaccination — when vaccination levels in the population are high). There is also a theoretical concern over a phenomenon called “serotype replacement”.

This can occur when there are various strains (or “serotypes”) of specific bacteria, which are competing against each other in nature. If we use a vaccine to prevent infections with the most prevalent strains, then those strains will struggle to survive and may soon be replaced by some other strains. Those new strains are presently not included in the life-saving vaccines and may start causing more disease. Clearly, our apparent safety from infections is heavily dependent on antibiotics and vaccines. We should continue to invest heavily in improving the existing ones and adding new ones and to ensure that safety standards in their production and use are kept very high.

A growing major concern is our recently-acquired ability to manipulate the genetic codes of bacteria and viruses. Understanding what makes them contagious and lethal could theoretically lead to the development of genetically engineered strains that could wipe out our entire species. Historically, there are examples of the use of anthrax, smallpox, plague and cholera as weapons in biological warfare. We can only hope that no such idea would be considered in modern times. Our current level of technology could already lead to artificially designed and genetically manipulated strains that could eventually cause far more deaths than any weapons.

Even though we may be feeling safer from infections in the 21st century, we’ve already witnessed quite a few scares in the first 15 years of this century alone. Firstly, in 2002, more than 750 deaths resulted from SARS — severe acute respiratory syndrome — a new, atypical, pneumonia caused by a coronavirus. Rapid response from health authorities helped to stop widespread spread but the disease has not been eradicated and it could yet re-emerge and become a pandemic.

Then, in 2009, a flu pandemic broke out. It caused a major scare because its antigenic signature — H1N1 — was the same as that of the Spanish flu pandemic in 1918. Luckily, this new strain of H1N1 resulted from reassortment of bird, swine and human flu viruses, which led to a common popular term for this pandemic — “swine flu”. It caused about 15,000 deaths globally. In 2012, outbreaks of MERS — Middle East Respiratory Syndrome — were reported in more than 20 countries, and they were again caused by a newly emerged variant of coronavirus. MERS caused more than 400 deaths in those countries and it remains a threat.

A year later, in 2013, we were reminded again of the dangers posed to us all by viral hemorrhagic fevers — all of which are both deadly and highly contagious, with the theoretical potential to become pandemics. In this case, an Ebola virus epidemic devastated the very poor countries of Guinea, Liberia, and Sierra Leone in West Africa. About half of all affected cases died and more than 10,000 deaths were confirmed. The World Health Organization was heavily criticized for a slow and disorganized response to this epidemic in a number of subsequent reports and analyses, while non-governmental agencies, such as Medecines Sans Frontiers (MSF) and Doctors Without Borders, were praised for their role in drawing attention and responding to the epidemic.

Finally, the most recent alarm in this century was raised in 2015, with an outbreak of Zika virus which affected more than 10 countries in the Americas. The virus, spread by mosquitoes, causes Zika fever — a minor illness that causes fever and a rash. But early in 2016, the World Health Organization raised concerns over mounting evidence that Zika infections of pregnant women could cause birth defects and microcephaly in particular.

Whenever a new epidemic strikes, this is an opportunity to use public attention to generate political support to improve health information systems and build infrastructure in those fragile health systems. This investment could prevent future outbreaks, or help to deal with them much better while improving conditions to protect the safety of health workers. But health information systems are weak in most poor countries where these threats are looming large. The communication between scientists and doctors in the field, those who have the mandate to process their messages and present them to the public, and the media have typically been suboptimal. There have been examples where too much hype was raised over the issues that weren’t nearly dramatic, while in others not enough concern was raised when it needed to be.

With all the investments today that go into weapons production, the cosmetics industry, entertainment, sports, infrastructure projects, and sports competitions, the world should really find resources to also build a reliable and functioning health information systems and laboratory infrastructure. This would enable us to collect reliable information quickly in order to raise the alarm and also to spread information in a collaborative way to the scientific community and communicate it responsibly to the public.

It is remarkable how much effort is being invested in building other resources for humanity, and how under-prepared we all are for something that could make all those efforts entirely irrelevant. This COVID-19 pandemic is a good example. We were simply running our luck for a very long time, but now we have an opportunity to become the masters of our own fate, at least when it comes to the threat from new epidemics. It’s really one of the most obvious choices for us all. We should really seize this opportunity before we live to regret that we didn’t.

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Image credit: Kuma Kum,



Igor Rudan

Director, Centre for Global Health at the University of Edinburgh, UK; President, International Society of Global Health; Editor, Journal of Global Health;