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Meet the real zombifying fungus behind the fictional Last of Us outbreak

Enlarge / HBO’s The Last of Us provides a vivid visual imagining of what a Cordyceps infected human might become.
YouTube/HBO Max

HBO’s new sci-fi series The Last of Us debuted earlier this week and is already a massive hit. Based on the critically acclaimed video game of the same name, the series takes place in the 20-year aftermath of a deadly outbreak of mutant fungus that turns humans into monstrous zombie-like creatures (the Infected, or Clickers). While the premise is entirely fictional, it’s based on some very real, and fascinating, science.

(Minor spoilers for the series below.)

The first episode showed us the initial outbreak and devastation. Fast forward 20 years, and the world has become a series of separate totalitarian quarantine zones and independent settlements, with a thriving black market and a rebel militia known as the Fireflies making life complicated for the survivors. A hardened smuggler named Joel (Pedro Pascal) is tasked with escorting a teenage girl named Ellie (Bella Ramsey) across the devastated US, battling hostile forces and hordes of zombies, to a Fireflies unit outside the quarantine zone. Ellie is special: She is immune to the deadly fungus, and the hope is that her immunity holds the key to beating the disease.

The basic premise for the fictional pandemic is neatly laid out in the cold open. Two epidemiologists are guests on a 1968 talk show in the vein of The Dick Cavett Show, discussing the possibility of a future pandemic. One cites viruses (specifically an airborne virus, like, say, COVID-19) as the threat that keeps him up at night. The other (played by one of my favorite British actors, John Hannah) insists the real threat will come from fungus, and proceeds to make a very convincing case.

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As Hannah’s Dr. Neuman explains, there really is a family of zombifying parasitic fungi called Cordyceps—more than 400 different species, each targeting a particular species of insect, whether it be ants, dragonflies, cockroaches, aphids, or beetles. In fact, game co-creator Neil Druckmann has said his premise for The Last of Us was inspired in part by an episode of the BBC nature documentary Planet Earth (narrated by Sir Richard Attenborough) portraying the “zombification” of an ant in vivid detail.

Cordyceps in the Rio Claro Reserve in Colombia. “>
Enlarge / John Hannah’s Dr. Neuman explains how fungi could kill us all.
YouTube/HBO Max

The fictional Neuman posits that rising global temperatures could spur mutations among fungi to adapt to higher temperatures. The result: “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.” Hughes rather liked that idea as a fictional premise, “But it is wrong,” he said. “The fungus grows in the body, and to be a mammalian body, it must adapt to higher temperatures. Not impossible. Happens all the time.” That said, Michael Wall, an entomologist at the San Diego Natural History Museum, told The Washington Post that “jumping from the insect world to the human world is highly unlikely.”

What makes the fictional outbreak in The Last of Us so apocalyptic for the human race is the exponential rate of infection—a common feature of the zombie genre. In 2009, a Canadian epidemiologist named Robert Smith? (yes, the question mark is part of his name) of the University of Ottawa adapted a basic epidemiological model to the spread of a fictitious zombie infection. A key assumption was that because the zombie virus victims don’t technically die, they can keep infecting more humans for much longer, leading to uncontrolled exponential growth. Everyone would be turned into zombies very quickly, at which point the population would become unsustainable. In the worst-case scenario, Smith? estimated it would take four days to wipe out humans. The same is true of the fungus in The Last of Us: it “keeps its puppet alive by preventing decomposition,” Neuman tells us—penicillin, after all, also comes from fungus.

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Enlarge / KILL IT WITH FIRE! But the fungus keeps the host body alive as long as possible to maximize its spread.
YouTube/HBO Max

Fortunately, nature typically has its own population control mechanism to ensure that eco-balance is maintained. The fungus proliferates when there is a large supply of hosts—for instance, when the ant population flourishes and becomes so large it threatens to overwhelm the resources available to the colony. As more ants fall victim to zombifying spores, their numbers dwindle until (a) there are once again sufficient resources to support what remains of the colony, and (b) there are far fewer ants available to serve as hosts, making it more difficult for the fungi to reproduce, so their numbers dwindle as well. Then the whole population growth and decline cycle begins all over again.

Hughes has created his own epidemiological models, notably one showing how a so-called hyperparasite that targets Cordyceps (specifically Ophiocordyceps) helps keep the latter in check. But eventually, the host has to die; the point is to keep the host alive long enough to reach the best spots for maximum dispersal of new spores. “Our work showed [Cordyceps] don’t invade the brain, which likely is critical to get the ants to where they need to die to ensure spores are distributed effectively,” said Hughes. “This is what happened, I assume, in the subway scene in episode 1.” That’s the scene where Joel and Tess (Anna Torv) encounter the remains of an infected human exploded onto the walls of a subway tunnel, with the fungi spreading its tendrils further outward.

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It’s also entirely believable that a human like Ellie could develop an immunity to the fungus even on a relatively short timescale of 20 or so years. “Evolution by natural selection is wonderful,” said Hughes. “If the selection pressure is there, then yes, this is possible.” And a devastating global pandemic such as that depicted in The Last of Us would certainly apply a great deal of selection pressure.

Scientists will continue to learn more about Cordyceps, and The Last of Us has certainly brought popular attention to just how powerful a parasitic fungus can be, especially given its networking ability—another focus of Hughes’ past research. But Hughes has now shifted his focus to climate change and food security, via Penn State’s PlantVillage project. “Faced with climate change, the evolutionary biology of parasites that manipulate ant behavior, while fascinating and fun to do, is, to me, a complete distraction,” he said. “Like rearranging the deck chairs as the Titanic sank or Nero fiddling as Rome burned. We are fucked if we don’t get our act together and solve climate change.”