Here at Demystifying Science we’re all about explaining things that people have questions about - and COVID-19, this newest pandemic coronavirus sweeping across the globe is causing all kinds of confusion. Over the course of a few posts we’re going to cover the history of global pandemics, the rise of new viruses in the 20th century, a summary of the current coronavirus in context of older coronavirus outbreaks, and then look at some other epidemics - alcoholism and opiates - to get some context on the dangers of COVID-19. As these get written, I’ll come back and link them here.

What makes an epidemic a pandemic?

An epidemic is an outbreak of a communicable disease - usually something that’s bacterial or viral in nature. A pandemic is that same outbreak when it spreads and turns into a global phenomenon. Pandemic is a term that’s used to indicate urgency, that there’s a threat at the border that can be kept at bay with the right collection of responses.

There have been a few pandemics in times past - mostly of diseases we don’t see around very often. The plague (yeah, that one) swept through the world at least three times in recorded history. Cholera, too, came through at least three times. Smaller pandemics of leprosy, malaria, typhus, yellow fever mark the history of human kind. Of all the transmissible illnesses that have caused pandemics, only one has been completely eradicated from the face of the earth - smallpox.

How do we know what’s happening in an epidemic?

Our best bet is to study it, something that humans have been trying to do since before the ancient Greeks, since it seems the burden of disease is more the burden of being alive. The earliest inklings of Western epidemiology go back to an ancient Greek named Hippocrates. It’s almost impossible that he was the first person to be paying attention to disease and its spread through a population, he appears to be the only one whose writings have survived. He pointed out that there were two kinds of diseases - those that were always around, endemic diseases, and those that appeared in waves - epidemic diseases.

Endemic diseases occur regularly across populations. Epidemics occur in discrete clusters, and pandemics happen when these clusters spread out across the globe.

The study of epidemics has turned into a rigorous, highly codified study of disease, and has produced technology that can literally rid the world of a disease. One of the main driving forces for getting a handle on pandemics was the fact that the human population has periodically been wrecked by them. The first recorded pandemic was the Plague of Athens in 430BC, where something like 25% of Athen’s population died of typhoid, an infection carried by a strain of Salmonella - S. enterica. The Plague of Justinian was the first recorded instance of Yersinia pestis infection in Europe, and it killed almost half the human population over the course of 200 years. Y. pestis came back again in the 1300s, and then again in the 1800s. By the time it returned in the 1800s, it’s lethality had decreased significantly - evidence of a conserved immunity that held over time.

The Antonine Plague, in between the Plague of Athens and the Plague of Justinian, was a different beast altogether. It was smallpox, carried by Roman soldiers returning from the Near East. Variola major, the more lethal variant of smallpox, killed upwards of a quarter of those infected. There were other, smaller pandemics as well - ones in India and China that there are fewer English records on - and other pandemics of diseases we don’t spend much time thinking about today: cholera, yellow fever, measles. If you’re interested in taking a more complete tour into infectious disease, I’ll leave this here: https://en.wikipedia.org/wiki/Pandemic#Pandemics_and_notable_epidemics_throughout_history

A brief summary of the plagues that have swept through Europe and the Americas since we started recording. There are others that happened in India and Asia, but I haven’t sifted through those numbers yet and can’t evaluate them. The width of the bar… — A brief summary of the plagues that have swept through Europe and the Americas since we started recording. There are others that happened in India and Asia, but I haven’t sifted through those numbers yet and can’t evaluate them. The width of the bar tells you how long the pandemic took place for, and the grey fill tells you the case fatality rate for each infection cluster.

The takeaway from this is that we’ve been suffering the dire consequences of infectious disease for millenia, and have only recently figured out how to eradicate them completely.

What took so long?

In many ways, the sloth-like pace at which we figured out how to fight against infections had to do with record keeping, and mechanistic understanding. It’s been known that there’s a causative agent for disease since at least the Roman Empire. In 36 BC, Roman statesman Marcus Varro wrote,

“Precautions must also be taken in the neighborhood of swamps […] because there are bred certain minute creatures which cannot be seen by the eyes, which float in the air and enter the body through the mouth and nose and there cause serious diseases.”

But this was a long cry from a mechanistic understanding that could be used to prevent disease. Up until the late 1800s, the origin of disease was still up in the air. The reigning theory, popular since the middle ages, was that of miasma, a catch-all term for poison air that disturbed the humors of the body. Unbalanced humors then led to disease.

The earliest recorded instances of epidemiology can be found by the mid 1500s in both China and Europe. In China, physician Wu Youke penned his Treatise on Pestilence, while in Verona, Italy Giralomo Fracastero penned On Contagion and Contagious Disease. These documents detailed the spread of diseases and the ways that they could be treated after the infection had already occurred. It was valuable, actionable knowledge - but it did not offer a sense of how to prevent the epidemics once they had already begun.

The First Epidemiological Study

The first well-reported instance of epidemiology was in the 1800s, during the third wave of Cholera that century(1, 2, 3). It was concurrent with the third outbreak of the Plague. This 1850s plague It was the same disease that caused the Black Death in Shakespeare’s Europe. It was ravaging India and East Asia for the third time. Things were bad, and physicians in London were worried that it was going to get worse.

It’s in this context that one London Physician, John Snow, did the first modern epidemiological study. He lived in a time of ambiguity about what, exactly, makes us sick. But he was a good record keeper, and figured that seeing the epidemic clearly drawn out might help him and other London physicians figure out what was going on. He made a map of the cases in a London neighborhood, and found that they clustered around a single pump on Broad Street. He convinces Parish authorities to remove the handle of the pump, and the epidemic slows. His reasoning is further supported by the cessation of cholera in other locales that were switched to cleaner sources of water.

Industrial London in the background, wreathed in a thick smog. In the foreground, a skeleton rows a wooden boat through water filled with floating animal carcasses.

His study demonstrated for the first time that that outbreaks can, in fact, be controlled through record-keeping and an understanding of how the disease spreads. Cholera in the 1850s was not yet understood to be communicable through contaminated water, and two utility companies were providing their customers with contaminated water from the Thames. After Snow’s demonstration of the infection being transmitted through the water supply, the city was able to turn the tide on the outbreak and insist that utilities provided better filtration to their customers. Eventually, when the river got to be sufficiently disgusting that the smell couldn’t be ignored, London even built a sewer to keep human waste from running directly into the river.

Cross section of the Thames, showing the new sewage lines running underneath the embankment of the river. This didn’t stop Londoners from polluting the river with sewage - it just ensured that the pollution that happened was downstream of where they… — Cross section of the Thames, showing the new sewage lines running underneath the embankment of the river. This didn’t stop Londoners from polluting the river with sewage - it just ensured that the pollution that happened was downstream of where they were taking most of their drinking water. Sewage practices through history are a different entry altogether..

Functional Treatment

One of the greatest pandemics of recorded history was the New World pandemic, brought on by a lethal combination - a previously unexposed Native population, and colonists that were silent carriers of diseases that were no longer as lethal in the old world. Over the course of 300 years following first contact, something like 95% of the Native population of the Americas perished from measles, smallpox, and influenza. What’s hard to wrap your mind around is that, as early as the 1500s, there was already a technology that could have prevented the widespread fatalities seen among the Natives of the Americas.

Variolation was the practice of preventing the spread of disease through controlled exposure. It’s a more lethal prototype to immunization, and appears in the historical record as early as the 1500s. Chinese physicians were able to produce immunity to smallpox through controlled exposure - a pustule sliced off a sick patient was placed into a cut made on the limb of a healthy person. Yikes! The death rate for something like this was only about 2%, which was much more favorable than then 30-40% death rate from getting infected by Variola major, the deadlier of the two smallpox viruses.

A systemic improvement on variolation came along in the late 1700s. A British physician named Edward Jenner was aware of anecdotal evidence of milkmaid resistance to smallpox. He, and others, surmised that this was because of their exposure to the cowpox virus. He confirmed this hunch in way unethical enough to take your breath away - he used his gardener’s child. He variolated the child directly with cowpox, waited for him to recover from the procedure, and then exposed the child to smallpox. The young boy didn’t get sick, and Jenner declared his new process a vaccine against smallpox.

You would be forgiven for thinking that it isn’t an enormous change from the variolation practiced in China, India, and West Africa. There’s a small but important improvement in vaccines vs variolation. The cowpox pustule caused an infection that was neither transmissible nor deadly. Instead of a 2% fatality rate seen with variolation, the Jenner smallpox vaccine had almost non-existent mortality rates. Another benefit? The cowpox virus, unlike smallpox, couldn’t be communicated from person to person.

Variolation on the left, vaccination on the right. Cowpox produced a much smaller reaction, and the pustule formed couldn’t infect anyone else. Variolation with smallpox, on the other hand, led to a more severe outbreak and the possibility of commun… — Variolation on the left, vaccination on the right. Cowpox produced a much smaller reaction, and the pustule formed couldn’t infect anyone else. Variolation with smallpox, on the other hand, led to a more severe outbreak and the possibility of community-derived infections.

This small step, an incremental improvement on a practice that had been taking place for at least 200 years, was a turning point. Despite not having a true theory for what caused disease in the first place, physicians were convinced that this was an effective method for preventing smallpox infection. They applied it to their own patients, and the incidence of smallpox began to decrease. Eventually, the smallpox vaccine was distributed on an industrialized scale. A disease that killed more than 500 million people from 1800-1900 was considered “eradicated” from the world by 1980. Vaccines, until the Wakefield study in the 1990s, were unquestionably heralded as victories over diseases that had been culling the very young and the very weak for centuries.

Finding and Fighting Germs

Even greater improvements to our ability to study and control During the close of the 19th century, there were a couple of experiments that accelerated the adoption of epidemiology as a viable discipline. The Germ Theory of disease, which states that contagious disease has a causative agent that can be identified through microscopic or molecular techniques, has only been around since the 1890s - only about 130 years ago. Before this, miasma theory of poisoned air and spontaneous generation were the predominant theories for why sickness occurred.

As vaccines were developed for the infectious diseases that plagued humankind for most of our history, the landscape of sickness changed. Instead of seeing the same problems appear over and over again, new diseases were appearing, opportunistic viruses jumping the species barrier from wildlife into humans.

In the next segment, we’ll spend some time talking about the pandemics of the last century - the Spanish Flu, the HIV epidemic. We’ll talk about where they come from, and ways in which they’re different from previous pandemics.