Humanity's worst-case scenario — stay up all night with me on this one…

"Measles is no big deal," she said to me. I'd been arguing with a "crunchy mom" type on the train from Washington to Philadelphia. She was convinced that two dead children in Texas and one dead adult in New Mexico (all three unvaccinated) were no big deal. Why? The current Secretary of Health and Human Services had told her so. "You get it and become immune for life."

"Sure," I said as I rolled my eyes. "A one in twenty chance of hospitalization, a one in one thousand chance of encephalitis, one in one thousand of death, and one in one thousand of a deadly encephalitis years later. Sounds safe."

"Safer than the vaccine," she sneered.

"So what would it take to 'scare' you into getting vaccinated?" I asked. She had earlier claimed she was not vaccinated against anything and went through COVID-19 without ever testing positive. Probable but unlikely.

"It would take something being a threat to all of humanity, not just the obese people who don't eat healthy and eat all that processed food."

Challenge accepted. Let's see what kind of pathogen would threaten all of humanity. What would end all of us once and for all…

A High R-Naught

The R-naught or basic reproduction number is the average number of people infected by one case of a communicable disease. Measles is the most infectious virus known, with an R-naught of 18. That is, one case of measles will produce 18 additional cases, on average.

This number is not static. If one kid with measles stands in a room filled with 100 vaccinated kids, maybe one of the vaccinated will get measles. I write "maybe" because the vaccine effectiveness of two doses is 99%, and even that additional 1% might mount enough of a response not to get fully sick and only get modified measles. But put that kid with measles in a big gym with 100 unvaccinated kids for a whole day? You're going to end up with more than 18 additional cases.

Of course, if you put into place a quick response, you'll end up with a decreased number of secondary cases and, thus, a lowered R-naught. This is where the idea of quarantines comes into play. We quarantine people who have been exposed but are not showing signs or symptoms of the disease. And we leave them in quarantine until enough time has passed from their exposure and they have no symptoms (or test negative), thus making it unlikely they've been infected.

Once someone shows signs and symptoms, we place them in isolation. They stay in isolation until their symptoms resolve, and we know they're no longer contagious. This is important, and you'll see why in a little bit.

So the perfect killing infectious agent, the one to end all of us, will have to best measles in its infectiousness.

By Any Means Available

This killer would have to have more than one way of being transmitted from host to host. (Why "host" and not "person"? You'll see further down in the story.) We're talking airborne transmission, especially across long distances. Measles is (again) a perfect virus for this because it can float in the air for up to two hours after someone coughs/sneezes/breathes it out.

But what if our theoretical global killer could also be spread through food or water? That would add to the possible sources of exposure and make containment that much harder. Not only would we have to worry about even a few people on a train or at a grocery store exhaling the virus somehow. We would also have to worry about sick people preparing food at restaurants or fast food places.

And what if our killer virus managed to get into the blood supply because there wasn't any test to detect it in the blood? Or into the water supply like cholera? The more transmission routes, the harder it would be for the "Wender" (World Ender) virus to be contained.

A Matter of Time

A few years ago, a video game named Plague Inc. was released on the iOS (Apple) platform. The objective of the game is to infect the entire world with a pathogen. You could choose your pathogen's characteristics, like its genetics or how fast it could be transmitted. But one characteristic allowed me to win every time: The contagious (infectious) period. This is the time when you can pass the virus to others. (The incubation period is the time from exposure to symptoms.)

A pathogen that is contagious before the host has symptoms spreads easily. With influenza, you are contagious about 24 hours before you have symptoms, and you stay contagious for about a week after your symptoms appear (even if you're feeling better). This means you don't know you're sick, so you still go to work on the train or bus. You still travel on a plane. You still visit Grandma at the old folk's home.

While you may have a prodrome with measles, a time when you're not at one hundred percent, you have been spreading the virus four days before the rash appears. Chickenpox? Two days before the rash appears. Smallpox, on the other hand, is not contagious until you develop the rash. By then, everyone who could see the rash (well-known in its time) would know to stay away from you.

Knowing this, I would engineer my pathogen in Plague Inc. to be communicable before any symptoms appeared. I would also make it so the disease spreads easily from person to person by air, food/water, and blood. Finally, I would make it so it was highly deadly once symptoms started, preventing the victims from being appropriately treated.

So imagine a virus that infects you without making you sick for a week while it multiplies many times inside you. Then you're contagious for days before you have any kind of symptoms. You feel perfectly well and go about your daily life, unknowingly infecting others. Then, once this long incubation period ended, you became sick and died in a matter of hours.

That would make it almost impossible to contain "Wender."

Death and Disability Everywhere

Then there's the matter of who is most affected by our deadly little friend. In 2009, the H1N1 influenza strain affected younger people the most, though it wasn't very fatal to the whole population. However, pregnant women and others with compromised immune systems were at high risk of complications and death from it. It killed about 284,000 people around the world at a time when the global population was 6.9 billion.

COVID-19 left children alone, for the most part. Children still died from it, and it was a leading cause of death in children. Compared to other age groups, however, children were far less likely to get it and die. It killed 20 to 30 million people out of a global population of about 8 billion.

And back in 1918, the influenza virus killed young people easily with an overreaction of the immune system (a "cytokine storm") while not doing the same to other populations. This was perhaps because younger people had stronger immune responses or because they were the ones most likely to get exposed as they were redeploying from World War I. It killed about 50 million people in a global population of about 1.8 billion people.

In our nightmare scenario, Wender infects and kills indiscriminately. Everyone is at high risk of dying from it, regardless of age, sex, weight, ethnicity, wealth, etc. No one can escape it through any natural means or by protections granted to them by their status (or access to care). It has a 50% case fatality rate. Half of all who get it die in a matter of days.

And those who are not killed are left with a severe and lifelong disability, like we're seeing with "Long COVID" or sometimes with SSPE (subacute sclerosing panencephalitis, a form of brain inflammation) from measles.

Welcomed in All Species

I used "host" up there because our World Ender is not exclusive to humans. As with so many infectious diseases, Wender comes at us from animals. And not just one species of animal. To make it a true menace to humanity, the virus travels long distances in birds, comes into communities in domesticated animals, and taints our food supply through chickens, pigs, cattle, and fish.

This also makes it difficult to contain. After all, you can reasonably quarantine or isolate people. We're big and dumb compared to many animals' scurrying and escaping abilities. Just go outside and try to catch a sparrow or run after a herd of deer. Sure, you can shoot at them, but the Emu War in Australia clearly shows that nature will find a way to outsmart us.

Zigs and Zags the Immune System

Do you know why we don't have a vaccine against HIV yet? The virus has adapted to evade the human immune system in two ways. First, it infects cells in the immune system itself. Hence, "immunodeficiency" is seen in advanced cases. Second, when the virus breaks off the host cell through a process called "budding," it takes some of its outer layer with it. When the host immune cells come along, they don't "see" HIV; they see a cell just like them.

On the other hand, COVID continues to go around the globe, wave after wave, because millions of people getting it means billions (or trillions) of opportunities for one virus to mutate into a new strain. This is also why we have yearly influenza epidemics. The viruses mutate when their genetic sequences are altered. Lacking a "proofreading" mechanism like we have in our more complex cells, those mutations change the virus's surface. This results in a virus that is more or less infectious, more or less capable of causing disease, but definitely more able to evade the immune system.

The horror we're dreaming up would have both HIV's ability to bud off with the host cell membrane covering it and a high mutation rate. This would almost guarantee a continuous game of whack-a-mole, or cat-and-mouse, between the pathogen and the scientists trying to create a therapeutic against it.

The Human Factor

Perhaps most importantly in this whole scenario is the role we humans play in allowing or preventing this from becoming reality. On the one hand, we are big apes with big brains that can figure things out and keep diseases from wiping us out. We've done it with things like sulfa drugs before antibiotics, antibiotics before other therapeutics, and with vaccines since the late 1700s.

However, never before has an openly anti-vaccine activist been Secretary of Health and Human Services in the United States. To my recollection, no President of the United States has been elected on a platform of getting rid of vaccines until this last election cycle. And there has never been such a network of interconnected influencers to disinform the public about all sorts of scientific and medical topics.

Not only that, but we continue to accelerate the increase in global climate change. This is leading to more powerful storms more often in places that are not ready for it. We are also polluting the air and water in ways that make people sick, predisposing them to bad outcomes from any infection, let alone the "Wender" virus we've dreamed up.

And then there is our bellicose nature as humans. What would Russia be willing to do to stop infected people from entering its borders? How about Europe? The United States? Places in the developing world with long-running wars would probably be decimated immediately when the pandemic starts. And places where the rule of law is weak will likely collapse quickly as well.

Could It Happen? Yes… Will It Happen? Maybe.

Here's how it could all play out… A coastal state (or nation) with a lush jungle away from the coast is hit by one natural disaster after another. When that happens, animals from the jungle come into contact with humans as the animals escape floods. Or the humans expand their settlements into the jungle to escape the coast. That causes a new type of virus to jump from animals to humans.

People in that place want to escape the poverty and social strife caused by the disasters and ensuing collapse of their local economy, which was based on tourism and fishing. No boats means no food and no money. No hotels from hurricanes means no tourists. So the people migrate with the virus they've just encountered. They go somewhere else, even within their own country.

Because of the actions of the American Government, disease surveillance is in shambles in the United States. No one notices the few people at a shelter for the unhoused who come down with a severe fever and cough. No one takes samples and notices the virus's special qualities. No one raises the alarm at seeing the long incubation period and the fact that secondary cases are popping up miles and miles away from the primary ones, showing that exposure happened weeks before the migrants' arrival. There are no good lab tests.

By the time the first cases start dying, almost a day after their symptom onset, some of the people with the virus have traveled around the world. Jet planes can now go from one side of the planet to the other in a matter of hours. Because the people are asymptomatic but contagious, they look okay getting into a plane or riding the bus. There's nothing instinctively to make others stay away. No rash. No hacking cough. No bloodshot eyes.

Those who are not killed by the virus are left with severe cognitive deficiencies. They can't work. They can't care for themselves. As the population dwindles, there are fewer people to work in service industries to serve those survivors. People who run electric plants also fall ill, also die at about a 50% rate. Power stations start to go offline.

When the power stations go, so do the water pumps for the cities. Half of all cops are dead. Half of all firefighters are gone. Half of the hospital staff don't report to work all of a sudden. And the other half? They go through two weeks of intense fever and pain, and come out on the other side, mostly unable to get out of bed.

No one is spared. Everyone catches the virus one way or another, even the most powerful men with the biggest wallets and bank accounts. They can't buy their way out of this one. Food is no longer picked in the fields or produced from live animals because the virus has taken out the workers and the animals to kill.

Large cities collapse as they were the first ones to mass-infect everyone within their boundaries. The lack of services causes riots that are not sustained because the people who would be rioting are too sick or dead to do so. Some people try to get out of the cities, but the lack of electricity also means the stoppage of transport. Gas pumps don't work. Trains are not moving.

Those who do walk away come down with the disease. Half of them dying. The other half struggles to find a place to lie and wishes they were dead.

Smaller towns and villages also succumb to death and disability.

In a matter of weeks, there are half as many people.

Then half that in a few months.

Then half in a year.

Famine strikes.

Everyone dies.

The end.

It doesn't have to be this way, though. We can stop climate change and reverse some of its trends, albeit slowly. We can continue to fund research and development into epidemiological surveillance systems that can give us early warnings of disease spread, medications and treatments if it happens, and capacity building for when it does. We can leave wild and undisturbed areas alone, lowering the risk of animal-to-human spillover events.

We can also be healthier in our own lives to have a better shot at surviving an infectious disease. And we can advocate for clean water and safe food, and the conditions needed for them. We can also participate in fair trade, allowing people "over there" to have living wages so they don't have to migrate and can be resilient in their own communities, on their own land.

These are much more possible and probable than the extinction-level event I just dreamed up. But it seems like we are in a race to make that nightmare a reality, more so than the easy and cheaper things we can do to make it just a passing thought experiment.