This Disease is Deadlier Than The Plague
Hello, Steve here. Today I am moving over as the voice of Kurzgesagt for something really special. Our dearest friend John Green would like to tell you a story that's very close to his heart. So, let's hear it from him directly.
Hey, John!
Hey, Steve. Thanks so much! Let's dive right in: The white death has haunted humanity like no other disease following us for thousands, maybe millions of years. It was there when we tamed fire, invented culture, and ventured out of Africa to conquer the world. In 1815 it caused one in four deaths in Britain. In the last 200 years, it killed a billion people, way more than all wars and natural disasters combined. Even today, it’s the infectious disease with the highest kill count.
But… do you even know what we are talking about? We’re talking about Mycobacterium tuberculosis, which causes tuberculosis or TB – our original arch enemy. Right now, one in four humans alive are infected with the bacterium – you may be one of them. So how is it possible that we never hear about TB? Well, the White Death is the perfect human predator: very infectious but very quiet most of the time, careful not to murder recklessly. Perfectly adapted to your immune system and just physically incredibly hard to kill.
What exactly makes it so powerful?
The Perfect Human Predator
Usually, the bacterium enters your body through the airways and sets up home in the lungs, a giant living cave system, defended by billions of macrophages, powerful guard cells that hunt and kill intruders. The TB bug is quickly attacked and devoured alive. Unfortunately, this is its plan. The white death is the worst kind of parasite – an immune system parasite. Macrophages grab their victims, trap them inside a phagosome, and flood it with acid that rips them to pieces. But TB evolved a thick, waxy coat that makes it completely immune to those acids. Worse, it captures and modifies the macrophage to be a perfect host. Like a tiny vampire, the parasite slowly consumes the cell.
TB then replicates extremely slowly. Other microbes that make you sick multiply up to 60 times faster, exploding their numbers before the immune system can eradicate them. But the white death is so well adapted to you; it has already won by being here. No need to rush things. When its host cell is sucked dry and dies, the bacteria infect new macrophages. Although these bacteria are stealthy, the decaying corpses they leave behind do activate a proper immune response – your body knows something is up and mobilizes its forces.
But once again, this is part of the plan. Macrophages and many other immune cells try to kill the bacteria, but that thick cell wall makes them a formidable fortress and resistant to many attacks. And it infects its attackers in the process. So when your cells can’t kill them, they do the next best thing: keep the parasites from escaping. A granuloma is formed, a sort of white blob. In the center is a core of infected and dead macrophages – a pleasant home and food for the bacterium.
Other immune cells surround this sphere of death to contain it – creating a safe space where TB can sit for years. Worse, it is perfectly protected from medication and releases chemicals that make it hard for your heavy immune weapons to be activated. This is the stalemate version of tuberculosis. The infection is sleeping and the bacteria are doing their thing. This is going on right now in up to two billion people! But in one in ten of them, the disease will become active.
Active tuberculosis is an emergency. But again, a slow one. If your immune system can’t contain the infection anymore, granulomas burst. Suddenly your lungs are filled with macrophage corpses and fresh bacteria. Your immune system panics and overreacts. Hordes of soldiers leave your blood and rush to the infected areas. They order inflammation, and fluids flood into your lungs. But unfortunately, your lungs are not made to be a battlefield. In their panic, your immune cells don’t care – they’re running around with flamethrowers, trying to purge the infection but causing terrible damage.
As fluids and dead tissue amass, it becomes difficult to breathe and you begin coughing hard, sometimes even coughing up blood. And again, this is part of the plan because now you spread millions of bacteria catching rides in tiny droplets. You burn a high fever and lose weight as your body is severely stressed. You turn into a ghost version of yourself. Even if you are treated, this phase can last weeks to months and is very serious. Insufficiently treated, TB will, over months, years, or even decades, slowly overtake your body. Especially for children or those already weakened, this can be too much and the disease wins the war.
The bacterium spreads to other organs, lung function breaks down, and the patient dies. 1.3 million people died this way in 2023 alone.
The Worst Kind of Problem
Tuberculosis is the worst kind of problem: a slow one. Instead of killing millions quickly like Covid, scaring a panicked humanity into frantic action, TB is a smoldering fire. Killing too slowly for our short attention span. The symptoms are often mild for many months, so you don’t feel in danger. Tuberculosis doesn’t want to kill you; of course, it wants to stay alive and spread. And to do this, it exploits human behavior: the people you are most likely to infect are your family and friends, coworkers or neighbors, the people you spend a lot of time with.
When Covid brought the world to a halt, the average patient infected 2-3 people. An active TB patient infects 5-15 people in a year. Most people catch it via breathing in tiny droplets from a cough or sneeze. This is especially common in crowded, poorly ventilated housing or workplaces. Which is why TB exploded during the Industrial Revolution. And indeed, wherever we see new unplanned and overcrowded urbanization, from Lagos to St. Petersburg, we tend to see a rise of the White Death alongside it.
Today, most cases of active tuberculosis – the version that spreads the disease further – can be cured with a four-month regimen of four different antibiotics. But if that’s the case… how is this still the deadliest infectious disease on earth? Between 1940 and 1965, humans developed several drugs to fight TB, finally making it curable. It was a true achievement of human ingenuity. But we didn’t do a great job of distributing the cure. While tuberculosis is almost extinct in much of Europe, the US, and the Middle East, it is still a very real threat in most of the world. TB kills people primarily in Africa, South America, and Asia.
In 2022, two-thirds of all TB cases were in just six countries: India, China, Indonesia, the Philippines, Pakistan, and Nigeria. Almost half of all tuberculosis deaths happened in Southeast Asia. But as it is a slow problem like climate change, it was ignored instead of fought aggressively, which enabled more and more strains of TB to develop antibiotic resistance.
Which is a problem because we kinda stopped making new drugs. In the first twenty-five years of the antibiotic era, we developed eight different classes of drugs to treat TB. And then, in the 47 years between 1965 and 2012, we developed none. Developing new drugs is extremely expensive and there was no concentrated effort to eradicate TB, and there simply wasn’t enough profit incentive. There is a vaccine, but it’s over 100 years old and not particularly effective.
But beginning in 2012, we did finally develop two new classes of drugs that treat TB, and we may finally be at an inflection point again, as better vaccines are on the horizon. Companies that made Covid tests also developed a quick test for TB. So, we now have a real opportunity to push this disease back until it dies forever. But only if we get enough people to know about TB – like you do now – and to care about it.
A century ago in the United States, there were almost as many hospital beds for TB patients as for treating all other illnesses and injuries combined. The White Death was a leading cause of death in the US and then one day it just wasn’t anymore. And we can do this again. 4,000 people died of tuberculosis yesterday, and we simply don’t have to accept a world where so many of us still die of a disease we know how to cure.
The White Death has been with us for millions of years. It is time to continue our journey without it. If you want to learn more about tuberculosis and the folks working to fight it through clinical trials and care delivery and also learn how you can help, check out the organization Partners in Health at pih.org/programs/tuberculosis. We’ve put a link in the description for you.
Also, if this wasn’t enough TB for you, there’s a Crash Course Lecture on the history and presence of TB. We’ll include a link to that as well.
Steve, I'll see you on Fri....no! This isn't Vlogbrothers...soon. I'll see you soon, Steve.