Consider the Fungus: Mycologists Talk the Realities of ‘The Last of Us’

On a show about bloodthirsty zombies and a shattered, post-apocalyptic world—particularly one based on a video game perhaps best known for the constant, low-grade stress it instilled in players, for whom dying so many times that they contemplated ditching the game altogether appears to be a near universal experience—you wouldn’t think that flashbacks to a rosier, pre-pandemic past would constitute the scariest scenes.

But so they have. In the first two episodes of HBO’s The Last of Us, it’s not the sprinting homicidal grandmas or clicker jump scares that have proved most haunting. For many viewers, it’s instead been the first scene of each installment, which both laid out the threat posed by that most fearsome of threats: mushrooms.

OK, OK, not mushrooms, per se, but fungi generally. The series premiere featured epidemiologists on a fictional 1960s talk show discussing pandemic dangers. One proclaims—to laughter, and then to a chill as the audience comprehends what he’s saying—that he fears neither viruses nor bacteria, but fungi, which alone could have the power to 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.”

“There are no treatments for this,” he continues. “No preventatives, no cures. They don’t exist. It’s not even possible to make them.”

Sunday’s episode jumped to the earliest days of the pandemic that would soon turn most humans into vicious spore mongers. Called in to a government facility in Jakarta to consult on the corpse of one of the first infected victims, a mycology professor from the University of Indonesia (a stirring cameo by Christine Hakim) slowly discerns the threat posed by the newly emerged, human-hosted ophiocordyceps fungus. She grimly advises the soldier who brought her in, “Bomb. Bomb the city.”

It turns out those crashing jets and dark museum halls have nothing on the specter of fungus. To watch The Last of Us is to radicalize against the humble kingdom of eukaryotes, to detest their pilei, to fear their wicked mycelia. If you take it from the responses of some viewers, many are unlikely to sample porcini ever again.

To nurse my nascent mycophobia, I turned to Jonathan Cale, an assistant professor at the University of Northern British Columbia who studies fungus-tree interactions in forests, and Matthew Kasson, an assistant professor of mycology at West Virginia University whose work has focused on Massospora cicadina, a parasitic fungus that—gulp—infects cicadas, alters their behavior to spread itself, and eventually seals their doom.

“It’s not far-fetched for me,” Kasson says of The Last of Us’s nefarious fungi. “They are stranger than fiction.”

The Virgin Fungus vs. the Chad 94 Degrees

The opening scene of The Last of Us features the second epidemiologist attempting to wave off the first’s concerns about a fungal pandemic by reminding his colleague that fungus can’t survive in temperatures above 94 degrees—leaving us toasty humans safe from their spongy clutches.

Alas: “That’s untrue,” Kasson says. “There are a number of fungi that can persist. In fact, we know the limit of fungal growth is about 62 degrees Celsius”—around 143 degrees Fahrenheit, and more than enough heat to cause a burn—“after which many or most eukaryotes, including fungi, can’t grow.”

“No Preventatives, No Cure”

The Last of Us makes much of the idea that because cordyceps is a fungus, it can’t be treated with medicine. That’s not true: Antifungals abound to treat common fungal conditions like athlete’s foot, yeast infections, ringworm, and dandruff.

But the show is right that fungi are uniquely difficult to battle, Kasson says. “Fungi are more closely related to animals than they are plants. But it’s really hard to get rid of dandruff because they’re eukaryotes and animals and fungi share a lot of similarities. It’s hard to combat them without combating ourselves. So they have to come up with specialized types of compounds that can kill the fungi without harming the host.”

Options remain scant, even if the doctors and scientists in The Last of Us would probably not have immediately given up on fighting cordyceps. Take it from microbiologist Arturo Casadevall, who last year told the Hopkins Bloomberg Public Health magazine, “Because we don’t worry about the fungi, not a lot of work is done with the fungi. So, we don’t have too many drugs. We don’t have any fungal vaccines, and it all becomes kind of circular.”

Further nightmare fodder: Casadevall believes that we’ve already seen a fungus, Candida auris, adapt to the heat of the human body. “As the world is getting warmer, the fungi will have to adapt,” he said. “Every hot day is a selection event.”

Smooching the Wood-Wide Web

Hear me out: What if the grossest kiss in recent television history was the equivalent of a randy Avatar tail touch?

Please, come back! The two are, for better or worse, related: Both play off of a phenomenon known by the name “the wood-wide web,” in which fungi purportedly allow disparate trees in the same forest to communicate. As the cat-people and light motes of Avatar unite under a single fibrous connection dubbed “Eywa,” so too do the infected and their creepy vines. (Theirs might not involve a Tree of Souls.)

In recent years, the theory has appeared as scientific fact in everything from 2019 Pulitzer Prize winner The Overstory to Ted Lasso. More recently, a number of mycologists have spoken out against the concept, which they say is overblown.

But fungi do communicate, in a manner of speaking. “There is lots of evidence that chemicals emitted by one fungus influence the growth and development of fungi of the same or different species. Many of these chemicals are volatile, diffusing through the air and modifying the behavior of other, separate fungi,” says Cale, who has studied the phenomenon.

In The Last of Us, Joel kills an infected person in the State House. As the newly (re-)dead infected falls to the ground, tendrils spread over the corpse’s fingers, alerting dozens of nearby infected to the group’s location. It’s not clear whether it’s a defensive mechanism or a hunt for fresh victims, but there’s real-world evidence of the former in some plants, Cale says.

“The types and amounts of volatile chemicals emitted by fungi change when a fungus is wounded or fed upon by predators (e.g., soil-inhabiting insects),” he says. “These modified chemical profiles can reduce or even completely deter additional predation. Thus, protecting the fungus from further harm.”

Cale cautions that it’s unknown whether the response can affect other fungi—but it has been seen in plants. “Chemicals emitted by plants attacked by insects or pathogens stimulate the production of defense chemicals in distant, non-attacked plants.”

Cordyceps, Carpenter Ants, and the Zombie Need to Chomp

On The Last of Us, people are infected with cordyceps if they’re bitten by an already infected person. (The game also features infection via spores, though they have yet to appear in the HBO edition.)

Let’s call it a creative liberty. The choice of cordyceps as the series’ fungal foe is inspired by the real behavior of carpenter ants. A cordyceps infection will indeed turn an ant into the fungus’s puppet, prompting it to climb to a high location, affix itself to a leaf or twig, and die. “Once the ant is dead, the fungus will erupt out violently, usually from the head of the ant,” Kasson says. “And then spores will rain down from that fruiting body onto unsuspecting ant victims below.”

But what we see on The Last of Us is a different form of spread altogether: active host transmission, which requires direct contact with a host to become infected. This, alas, has at least some basis in reality.

Kassen specializes in the zombie cicada fungus, in which cicadas infected with Massospora cicadina have the back ends of their bodies gradually killed by the fungus, which also produces a psychoactive compound “that make them hypersexual and super, super focused.”

“They continue to mate and fly around as if nothing’s wrong,” Kasson says. “So in that way, it’s spread from cicada to cicada as a sexually transmissible disease.”

… Is a Devastating Fungus Mankind’s Greatest Threat?

So should we, like the epidemiologist from The Last of Us’s premiere, lie in bed at night fearing the day a particularly nasty fungus adapts to thrive in humans?

Recent studies have documented an increase in some fungal infections, which is thought to be the result of the COVID-19 pandemic. In particular, patients sick with COVID, receiving common treatments like steroids that can suppress immune response, and those suffering from the lingering effects of long COVID may be immunocompromised, opening the door to fungi they might otherwise have fended off.

“It’s not that there are super-fungi emerging,” Kasson says. “These are common soil-dwelling fungi, common sink-drain-dwelling fungi, that are just taking advantage of weakened immune systems that can’t stage a response against them.”

“So do I suspect we’ll see higher incidence of fungi in a warming world? I think we can. But it’s going to be some of the same fungi that we’ve been battling quietly in the hospitals and clinics for a long time. It’s just that people are becoming more aware of them because maybe a larger portion of the population will be immunocompromised due to things like COVID-19 and other viruses that may predispose us to subsequent invasion by these generally pervasive fungi.”

In other words: Fear the virus and the fungus.