You are part of one of the world’s greatest endeavors: the effort to stop infectious disease.

Like other animals, infectious diseases have been with us since the dawn of our species, from herpes virus that infected our common ancestors in Africa to the Covid-19 pandemic that struck the whole world. The effort to understand these diseases has been going on for some time, too.

As far back as 400 BCE, civilisations in different parts of the world tried to work out who became ill and why. Since then, we’ve come a long way in understanding what diseases are and how they spread. And that knowledge is vital to stopping them.

But it’s not only doctors and scientists who can act on what we know. Infections involve individual people, so everything from the way you and I go about our everyday activities to the way we organise whole societies all influence how an outbreak evolves – and whether we overcome it. I’m Pardis Sabeti, a professor of genetics at Harvard University, where I study infectious diseases.

In this series, we’re going to take a deeper look at disease outbreaks, from the microbiology and genetic factors behind them to healthcare systems, social structures and people who tackle them, including you! Welcome to Crash Course Outbreak Science! [Theme Music]. The study of outbreaks is a little different from your garden variety science.

Not everything about an outbreak can be studied experimentally. Outbreaks are complex situations involving real people in their environments, so we can’t perfectly measure and control all the variables. It would also, you know, be highly unethical to release an infectious disease into a population just to study what happens – though, sadly, that hasn’t stopped people from doing just that.

Even so, it helps to be specific about what we’re talking about when using words like “epidemics” and “outbreaks”. The American Public Health Association’s Control of Communicable Diseases Manual – yes, there’s a handbook for this! – defines an epidemic as: “The occurrence, in a defined community or region, of cases of an illness (or an outbreak) with a frequency clearly in excess of normal expectancy.” In other words, an epidemic is when many more people in a group than usual develop a particular illness. We can also use the word “outbreak”, usually when the region we’re talking about is relatively small.

That might all seem straightforward, but there’s a question hidden here. What counts as a “usual” amount of illness? It turns out, it depends on the community.

For example, in the 1990s there was an outbreak of cholera in Latin America. Cholera is a bacterial disease that attacks the intestines, usually contracted from contaminated water, and nearly a million people were infected. Those kinds of numbers for cholera cases hadn’t been seen on the continent in over a century, so the sudden rise was dramatic.

But near the Ganges delta between Bangladesh and India, cases of cholera are an unfortunate and persistent fact of life because of the environment. When a disease has roughly the same incidence in a place over an extended period of time, it’s called endemic. The word endemic is derived from the ancient Greek words “en” meaning “in” and “demos” meaning “people”, like, diseases that reside in a group of people.

That’s opposed to “epidemic”, which is derived from “epi” meaning “on”, as in, diseases that act on a group of people. Similarly a pan-demic draws on the Greek word “pan” meaning “all”, as in an epidemic that spreads across borders into many countries, affecting the whole world if left unchecked. What really distinguishes an epi-demic, or outbreak, is that the number of cases of illness are much higher than they normally are within a certain community.

Which means words like “normal” and “usual” have to be taken in the context of particular groups of people, their way of life, and circumstances. It doesn’t mean that the cases of cholera were more or less important in South America than in the Ganges Delta. But it means we might approach the two situations differently.

Outbreaks are evolving situations where the disease could become more widespread. So the goal is to stop the disease spreading even further, as well as treating those who have it. It also means having organizations and systems in place that can handle the social changes an outbreak requires.

Which is a pretty tall order! What’s key to tackling those challenges is understanding the nature of an infectious disease and how people respond to them. We’ll start with the disease itself.

When it comes to diseases, different scientists have different ways of thinking about them. For example, microbiologists consider diseases in terms of their biological cause. One of the most important scientific discoveries in history is that tiny organisms that enter the human body are what’s often responsible for us contracting infectious diseases.

These are known as pathogens. The most commonly known pathogens are microorganisms like bacteria, viruses, protozoa and fungi. The science behind pathogens is pretty broad, so we’ll be looking at them in closer detail next episode!

The take-away is that microbiologists tend to characterize diseases by the pathogens that cause them. Epidemiologists meanwhile think about diseases in terms of the bigger picture, focusing on how it spreads and what its source is. Unfortunately for us, there are lots of ways pathogens can infect people.

They might be spread from person to person through contact with skin or through droplets in the air from someone’s sneezes or coughs. They might be eaten in contaminated food or injected by an insect like a mosquito. Even if the pathogens might be different, an epidemiologist would think of diseases in terms of these transmission routes.

They also consider when a community is regularly coming into contact with the same source of disease, which are called reservoirs. Sometimes, a reservoir is a group of infected people, but it could also mean a local population of animals carrying diseases like rabies. The reservoir might be soil which contains certain kinds of fungi or contaminated water.

The kind of reservoir also determines who might be at the most risk from an outbreak, as we’ll see in a moment. Finally, there are medical scientists and doctors, who tend to think of diseases by their clinical symptoms. Clinical symptoms might be familiar things like fever or difficulty breathing but also could be conditions like, say, inflammation and swelling of body parts or a whole lot of other not-so-fun things.

From a doctor's perspective, identifying diseases by their symptoms is important for treating them. It’s worth mentioning we’re going to have to be frank about the human body and some of the more icky parts when studying outbreaks. But science demands clarity!

For example, in the case of diarrhea, regardless of the pathogen or the way the patient was infected, they need to be treated with fluid replacement to keep them hydrated. So we have three ways of looking at disease: the organism behind the disease, the way it spreads, and how it affects an infected person. Which brings us to the role people play in an outbreak.

Different perspectives of disease help inform groups like healthcare providers, public health experts and the communities themselves to tackle outbreaks. To see how this all comes together, let’s look at a real life example. We’ve mentioned that cholera is endemic to the Ganges Delta, just off the coast of West Bengal in India.

Although it’s endemic in the whole region, scientists can still identify outbreaks in a given community, exceeding their expected number of cases. Let’s go to the Thought Bubble. On October 13, 2004, a healthcare facility in Kanchrapara, India, reported a cluster of cases where patients suffered from acute, watery diarrhea.

As I said, science needs clarity! A lot of those patients also were so dehydrated they were sent to the hospital — all classic signs of cholera infection. The district epidemiologist set about to confirm whether this was an outbreak.

He started by looking at the data of similar diarrhea cases from the previous months and found that the number of cases in the cluster was in fact higher than expected. To confirm that the patients definitely had cholera, he worked with the hospital to take samples, which, for clarity, were from the patients’... butts. The samples were from their butts.

Those samples were sent to a lab, where microbiologists could test them and rule out other pathogens that might be responsible too, like salmonella. Meanwhile, the epidemiologist drew a map of the cases by household. He found that most of the cases came from areas which relied on the municipal water supply.

In fact, a nearby area that used a different water supply had fewer cases. It turned out that earlier that same month, the municipal water supply had sprung a leak in its pipeline. That was a major clue.

A leak would make it possible for fluids to be sucked into the pipeline and contaminate the water. What’s more, it had been raining heavily at the time, bringing lots of sewage-contaminated water near the pipeline. Sure enough, the lab results came back positive for Vibrio cholerae, the bacteria that causes cholera, and negative for other pathogens.

At that point, it was clear there was a cholera outbreak on their hands. Thanks, Thought Bubble! A later environmental assessment with the city’s engineers found that, as suspected, the leak in the pipeline had sucked up sewage-contaminated water into the water supply.

Thankfully, by that point the leak had been repaired and water had been chlorinated. And shortly after the intervention, the number of new cholera cases had fallen rapidly! We can see how different perspectives on disease helped identify and resolve the outbreak.

The clinicians monitoring clinical symptoms helped bring the high number of diarrhea cases to light and flag up the possibility of cholera. Microbiologists confirmed this by identifying the pathogen from lab testing, while epidemiologists identified the reservoir for the disease. While outbreaks are specific to certain groups of people, the way in which they happen is often starkly similar to outbreaks all over the world.

While we’ve mentioned cholera outbreaks in Latin America and India so far, one of the most famous ones happened 150 years earlier in London, England. Though the tools at his disposal were a little different in 1854, physician John Snow used many of the same methods that the district epidemiologist in. Kanchrapara used to identify the outbreak.

Snow also used a map to trace the locations of each cholera case to find the common source of infection. Turns out, a contaminated water pipe was the culprit of that outbreak, too. Contemporary outbreak scientists still map all kinds of outbreaks, often with advanced geospatial techniques and software, including NASA earth observing research satellites.

And in both Kanchrapara and London, the reservoir also highlighted who was susceptible to certain kinds of outbreaks. It was clear that those who relied on the municipal water supply were already exposed to risks from the unfit water system, even before the outbreak. And we’ll see throughout the series, environmental conditions play a huge role in determining how often outbreaks occur and who is affected by them.

But people and practices were also at the heart of the outbreak response. In Kanchrapara, monitoring and collecting data from healthcare facilities required social practices that encouraged reporting unusual scenarios, like a cluster of symptoms. There were also organizational links between healthcare facilities and epidemiologists that made sure information was flowing in a useful way.

Transporting the samples and having laboratories equipped to analyse them required locally available technology and infrastructure. Even before the outbreak, decisions had been made to have an epidemiologist in the area and labs with the capacity to test for cholera in the first place! After the outbreak, scientists worked with hospital clinicians, city water engineers, district authorities and the chief medical officer to plan for next steps.

That included an investigation of the city pipelines for leaks so they could be fixed before the next outbreak and making sure the water was chlorinated from that point on to prevent cholera infecting the supply. Which brings us to a final point about tackling outbreaks: communication. Different groups, from patients, scientists, governments and public health workers, need to share information and collaborate during an outbreak to ensure the right steps are taken.

Throughout this series, we’ll continue to look at how the way people interact with one another and the social structures they inhabit all play a role in how outbreaks develop and how we can stop them. And hopefully, what we learn in this series will enable you to play a role too. Next time, we’ll get into the microscopic world of pathogens.

See you then! We at Crash Course and our partners Operation Outbreak and the Sabeti Lab at the Broad Institute at MIT and Harvard want to acknowledge the Indigenous people native to the land we live and work on, and their traditional and ongoing relationship with this land. We encourage you to learn about the history of the place you call home through resources like native-land.ca and by engaging with your local Indigenous and Aboriginal nations through the websites and resources they provide.

Thanks for watching this episode of Crash Course Outbreak Science, which was produced by Complexly in partnership with Operation Outbreak and the Sabeti Lab at the Broad Institute of MIT and Harvard— with generous support from the Gordon and Betty Moore Foundation. If you want to help keep Crash Course free for everyone, forever, you can join our community on Patreon.