A deadly fungal plague swept the world of The Last of Us — is it realistic?

A global disease outbreak is on everyone’s minds right now— and not just because of the Covid-19 pandemic.

The Last of Us TV show, based on the popular video game, debuted this month on HBO, and its deadly pandemic is teased in the opening moments of the show. Two scientists debate whether a fungus or a virus is more likely to cause a pandemic.

(Spoilers ahead for The Last of Us!)

“Viruses can make us ill, but fungi can alter our very minds,” one scientist explains, arguing the right fungus could create “billions of puppets with poisoned minds, permanently fixed on one unifying goal: to spread the infection to every last human alive by any means necessary.”

Cut to later in the show, and we learn that the cordyceps fungus has caused a deadly global pandemic which few have survived twenty years after the initial outbreak. The fungus appears to affect the brain, manipulating the human body to attack, eat and infect others.

But is it really fungi we need to fear — not viruses — when it comes to disease outbreaks? While that question is debatable, there’s one thing scientists are clear on.

“There's no infectious agent that turns you into a zombie,” William Schaffner, a professor of infectious diseases at Vanderbilt University, tells Inverse. But that’s not the case for all living things ...

Reel Science is an Inverse series that reveals the real (and fake) science behind your favorite movies and TV.

What is the cordyceps fungus and can it infect humans?

The show portrays the cordyceps fungus as the source of the global zombie outbreak. Turns out: this fictional portrayal actually stems from a real-life parasitic fungus known as Ophiocordyceps.

“Ophiocordyceps is a genus of behavior-manipulating fungi closely related to the Cordyceps fungi starring in the new HBO series The Last of Us,” William C. Beckerson, a postdoctoral research fellow who studies Ophiocordyceps at Utrecht University, tells Inverse.

The fungus is widely used as a traditional Chinese medicinal supplement due to its supposedly anti-inflammatory properties, but it also has a more gruesome reputation for its parasitic ability to infect and manipulate ants’ behavior through its spores. It falls into a category of fungal parasites known as “entomopathogens” that turn insects into zombie-like beings.

“Many of these ‘zombie-making’ entomopathogens cause their hosts to exhibit heightened activity, seek out elevated positions, and display body postures that promote spore dispersal,” the authors of a 2021 paper published in mBio.

“Fungi can clearly cause human illnesses”

So: if the fungus can infect and manipulate ants, could it do the same for humans?

“In terms of infection, one of the biggest barriers for fungi like Ophiocordyceps is the difference in body temperature between us and their usual insect hosts,” Beckerson says.

Humans are endothermic, which means we have an internally regulated body temperature that hovers around 98.6 degrees Fahrenheit. Ants, on the other hand, are exothermic, meaning their body temperature depends on the outside environment. Therefore, fungi like Ophiocordyceps evolved to infect ants when temperatures are between 60 degrees Fahrenheit (16 degrees Celsius) and 75 degrees Fahrenheit (24 degrees Celsius). So this specific fungus is unlikely to infect a human.

“This does not mean, however, that some of the compounds made by Ophiocordyceps could not affect humans,” Beckerson says.

Beckerson is currently studying a molecule made by Ophiocordyceps — similar to the plant pathogenic fungus Aspergillus mentioned briefly in the show — which causes tremors in cows that eat fungus-tainted grain feed. He hopes such research will one day lead scientists to develop better therapeutic drugs for behavioral disorders.

‘This is at least one example of a chemical that can affect both insects and mammals and highlights the value of scientific research into these fascinating fungi,” Beckerson adds.

Is the show’s depiction of the cordyceps fungus realistic?

In the opening scene of the show, a scientist in the 1960s states that fungus cannot survive if the host’s internal temperature is above 94 degrees Fahrenheit. But the scientist goes on to suggest fungi could evolve to withstand higher host body temperatures — like those of humans — in a slightly warmer world.

Cut to decades later, and we are indeed living in a slightly warmer world due to climate change.

“I was very impressed with the scientific accuracy of this opening scene. One of the indirect consequences of global warming is indeed the emergence of new fungal pathogens,” Beckerson says.

Beckerson explains that as environmental temperatures rise closer to 98.6 degrees Fahrenheit — the body temperature of humans — humans become a more likely host candidate for fungal pathogens. He says microorganisms like fungi are “particularly good at adapting to increasing temperatures, and at a strikingly fast pace.”

“As the planet continues to warm, we will see more and more cases of fungal infections,” Beckerson says.

But even in a hypothetical scenario where a zombie fungal cordyceps pathogen — the same that infects ants — could infect humans in a warmer world, it would still be difficult for the fungus to turn us into mindless zombies. Most zombie ants get infected by a specific Ophiocordyceps fungus that is incapable of infecting other ant species. Beckerson explains:

If you consider how these fungi are unable to manipulate organisms with very similar biology and behaviors... it becomes clear that it would be extremely unlikely that — even in the event that humans become infected by such a fungus — that it would be able to manipulate our behavior in the ways depicted in The Last of Us.

Could fungi cause a global disease outbreak?

Fungi can infect humans and have done so for millennia. Athletes’ foot and vaginal yeast infections are common types of fungal infections.

“Fungi can clearly cause human illnesses,” says Schaffner, the infectious disease expert at Vanderbilt University.

Yet, he doesn’t necessarily agree with the scientist in The Last of Us that a fungus could cause a global pandemic. The main reason: fungi — especially ones that cause serious disease — do not transmit easily from person to person.

“You would have to create something that fungi currently absolutely don't know how to do, which is get transmitted rather rapidly,” Schaffner says.

But Schaffner says there is one fungus that is causing serious outbreaks in hospitals around the world — even if it’s unlikely to explode into a full-scale pandemic. That fungus is called Candida auris, which the CDC says “presents a serious global health risk.”

Some sick individuals in hospitals take antibiotics that suppress bacteria in the body, leaving them vulnerable to the drug-resistant Candida auris, Schaffner explains.

“It was thought to be a benign fungus for a long time, but it's suddenly in more than one place around the world. How did this happen? That's still unknown and a big mystery,” Schaffner says.

So while we’re unlikely to turn into flesh-eating zombies anytime soon, The Last of Us offers a timely reminder not to overlook the very real threat fungi can pose to the world.

The Last of Us is currently streaming on HBO Max.