'The Last of Us' is based on real science: A fungus pandemic is unlikely, but not impossible

• "The Last of Us" on HBO Max depicts a zombie apocalypse caused by a fungus pandemic.
• Experts say mind-controlling mushrooms aren't an imminent threat, but anti-fungal drug resistance is.

The first season of HBO's "The Last of Us" ends on Sunday, but there's still much to learn from the science that inspired it.

In most ways, the show depicts a classic zombie apocalypse.

One morning, everybody is going about their normal life. There's a mention on the radio of chaos in Jakarta. And by nightfall, twitchy, possessed once-humans are sprinting after the main character.

This time, though, it's a fungus turning people into zombies.

The new scenario, first realized in the video game that the show is based on, is making viewers wonder whether a fungus pandemic can happen in real life.

"A fungal pandemic is definitely possible," Norman Van Rhijn, a mycologist researching fungal infections at the University of Manchester, told Insider in an email.

No species of fungus currently known to science poses an immediate pandemic threat for humans — especially not the way the show portrays it. Still, fungal infections are on the rise worldwide, and researchers are concerned that more and more people are at risk.

Some even worry that new super-pathogens could arise from the fungus kingdom.

"The potential is huge for what can emerge and become a pathogen," Tom Chiller, chief of the fungal disease branch of the US Centers for Disease Control and Prevention, told Insider. "I am not going to be surprised that more fungi emerge as human pathogens, that become more challenging to treat and more infectious."

Here's the science fact and science fiction behind "The Last of Us," and the threats that fungi pose.

FACT: There is a zombie fungus — in ants

Zombies in "The Last of Us" bloom with tendrils of a fungus called Cordyceps, which sprout from their heads and mouths, reaching out for fresh victims.

Cordyceps is real, but it only overtakes the brains and bodies of insects — most famously, ants.

The fungus grows inside an ant's body, causes the ant to climb upwards, and then sprouts from its head and releases spores, attempting to spread itself far and wide.

Cordyceps can't survive at human body temperature, so it can't infect us. But other species of fungus produce substances with mind-altering qualities that can affect human behavior.

FACT: Some fungus can affect human brains and behavior

Perhaps the most obvious example is psilocybin, the hallucinogenic compound in magic mushrooms. The fungus ergot also has a reputation for altering the human mind.

Some historians attribute the Salem Witch Trials to ergot poisoning, saying that women began behaving strangely and accusing each other of witchcraft after eating infected rye. The psychoactive substance LSD is derived from ergot.

"Every time you have a beer, your behavior is affected by the byproduct of a fungus, which is ethanol," David Hughes, who has studied Cordyceps and consulted on the video game "The Last of Us," told Insider.

The fungus Cryptococcus can also spread from the lungs to the brain and cause meningitis — inflammation — that can alter behavior.

Unlike on TV, though, mind-altering fungus "doesn't jump into our body and affect a behavior that enables future transmission," Hughes said.

FICTION: Mind-controlling zombie fungus can make the jump into humans

Fungal diseases can jump from animals to humans. But the idea that a fungus like Cordyceps could mutate enough to make the giant leap from insects to humans, and still keep its ability to effectively manipulate behavior, is far-fetched.

In the infectious-disease world, "never say never," Chiller said.

"But I will say that there's a lot, a lot of hurdles that need to be overcome," he continued. "An ant and a human are dramatically different. We have immune systems, we live at different temperatures, you know, our body temperature is much higher. So there are just some fundamental things that are going to be exceedingly hard for that particular fungus to overcome."

FACT: There is no vaccine for killer fungus

In "The Last of Us," the first cases of fictional human Cordyceps appear in Jakarta, Indonesia, where the government asks a leading mycologist to identify the fungus under a microscope and wriggling in the mouth of a dead civilian. Horrified, she learns that 14 people who worked with the victim have disappeared.

"There is no medicine. There is no vaccine," she grimly informs a government official. She recommends that the government bomb the entire city to contain the fungus.

In real life, it's true that there is no vaccine for deadly fungal infections (though experts don't recommend bombing as a substitute). There are only a few classes of drugs to treat them, and they aren't always reliable cures.

In fact, because fungi are so similar to humans at the cellular level, many of the drugs that fight them are also toxic to human bodies.

According to Global Action for Fungal Infections, fungi kill more people than malaria.

"The problem with fungi is we don't have a lot of things in our toolkit to control them," Hughes said.

Some deadly fungi, like Candida auris, which emerged in 2009, have even developed a powerful resistance to the anti-fungal drugs we do have. In hospital outbreaks, Candida auris has killed anywhere from 29% to 53% of its victims, according to the World Health Organization.

Most fungal pathogens are opportunists, Chiller said, and they only cause severe illness in people who are immunocompromised.

"But there are now fungi that aren't opportunists and can infect any of us. And if those become more infectious, if those become more resistant, that's really what I'm worried about," Chiller said.

FICTION: Human bites and 'tendrils' spread killer fungus

In the HBO series, zombies have to bite their victims or inject tendrils of fungus into them in order to spread the disease.

That's not at all how fungal transmission works in real life. Fungal infections largely spread through touch or surfaces — think of athlete's foot or ringworm.

That's why Hughes doesn't think fungi pose a pandemic threat.

"The extent to which we will see a pandemic, meaning the whole world is affected by a single species ... that doesn't seem probable for fungi, just by nature of their transmission pathways," he said.

Most fungal pathogens come from the environment, rather than contact with other humans. You're inhaling fungal spores all the time. Usually, the human immune system takes care of that. But if your immune system is weak — due to illness or drugs — that fungus can grow inside you.

That's why hospitals and prisons are particularly prone to outbreaks. Most human-infecting fungi spread best when immunocompromised people cluster together, or when many people are in close contact and sharing common surfaces.

Some more dangerous fungal diseases, like Valley Fever, come from spores in the air and can even sicken healthy people.

"The real-life nightmare scenario is that fungi like this cause more damage and turn from relatively mild infections to life threatening infection," Van Rhijn said.

FACT: Rising temperatures could increase the threat of fungal pathogens

Mysteriously, Candida auris outbreaks emerged independently on three different continents at the same time in the 2010s. There was no clear link or contact between the outbreaks.

Some scientists believe the connecting thread is climate change. As global temperatures rise, fungi have to adapt just like everything else. As more fungi adapt to higher temperatures, more of them may be able to survive and proliferate at human body temperatures — even when human bodies try to kill them off with fever.

The opening scene of "The Last of Us" hints at this, with a 1968 scientist telling a TV host that slight global warming could breed new fungal super-pathogens.

Alongside Cryptococcus, the World Health Organization ranked Candida auris as one of the top four priorities in its first-ever ranking of fungal pathogens last October.

Climate change is just one factor that could increase the toll fungi take on humanity.

The COVID-19 pandemic, like prior viral illnesses such as HIV/AIDS, left more people susceptible to fungal infections.

Another risk factor comes from improving medical technology, which allows more people to get life-saving surgery at the cost of taking medicines that suppress their immune systems and make them more vulnerable to other infections, like fungi.

"We're talking about a show that is really wanting to grab the attention of folks and extrapolate some really cool sci fi possibilities here. And that's great," Chiller said.

"We just need to think fungus," especially with immunocompromised or hospitalized people, he added. "Early diagnosis and early treatment is the best way to save lives."

You can watch all available episodes of "The Last of Us" on HBO Max:

This story has been updated. It was originally published on January 29, 2023.