In the premiere of HBO’s big budget adaption of the 2013 video game “The Last of Us,” an infection caused by a parasitic fungus has turned most humans into ravenous, mind-controlled zombies, ending the world as we know it.
The premise of the series and the game that it’s based on might sound like pure fantasy, but it’s actually based on real, horrifying science.
The game’s developers took inspiration for their fungal zombies from the Cordyceps fungus and related species.
Cordyceps is a genus of ascomycete fungi (sac fungi) that includes about 600 species with worldwide distribution. Most Cordyceps species are endoparasitoids, infecting insects and other arthropods, and rarely plants. The classic zombie-ant fungus Ophiocordyceps unilateralis, was discovered by the British naturalist Alfred Russel Wallace in 1859, and currently found predominantly in tropical forest ecosystems.
The spores dispersed by theses fungi sit in the soil and attach to the bodies of insects. Over the course of 24 to 48 hours, the fungus sends his root-like structures into the body of the insect, before spreading throughout the body over the course of a few weeks. But the fungus not just simply consumes its victim, it also takes control over its body.
“It already starts changing the neurobiology of the host so that it basically makes it a zombie organism, meaning this parasite takes over, producing some kind of neurotoxins or neuromodulators that change the behavior of the host,” says Rebeca Rosengaus, associate professor of marine and environmental sciences at Northeastern University.
The parasite surrounds the muscles of an insect, affecting its motor neurons and turning the host into a marionette. David Hughes, an entomologist who consulted on The Last of Us game, says there are clear similarities between the fictional infected and how the parasite operates in the ants he studied.
“At first, infected humans in The Last of Us don’t immediately display signs of infection. However, that quickly changes. They start twitching and become hyperaggressive and overly energetic. Survivors in The Last of Us call those infected in this stage “runners.”
This behavior is somewhat based in reality, Hughes says. The Cordyceps parasite releases a chemical compound that causes insects to twitch and convulse.
“They do not enter the brain, but what they do is push chemicals into the brain across the blood-brain barrier so that they can control the brain at a distance.”
Ants infected with the parasite also start becoming more antisocial, a notable shift in highly social ant societies, and wander off from the rest of the colony. Similarly, the show’s infected humans lose all ability to speak and, instead, scream and shriek in rage and pain.
The parasite forces the host to change behavior for only one purpose – self-preservation, and that for at least the past 50 million years, as a fossil discovery from a few years ago shows.
In 2021, Oregon State University researchers have identified the earliest known specimen of a fungus parasitizing an ant. The Cordyceps-like fungus was growing out of a carpenter ant that died in the undergrowth of the Amber Forest, when a drop of tree resin engulfed them both.
“Ants of the tribe Camponotini, commonly known as carpenter ants, seem especially susceptible to fungal pathogens of the genus Ophiocordyceps, including one species that compels infected ants to bite into various erect plant parts just before they die.”
Doing so, study’s lead author George Poinar explains, puts the ants in a favorable position for allowing fungal spores to be released from cup-shaped ascomata—the fungi’s fruiting body –protruding from the ants’ head and neck.
“We can see a large, orange, cup-shaped ascoma with developing perithecia—flask-shaped structures that let the spores out—emerging from rectum of the ant,” Poinar said. “The vegetative part of the fungus is coming out of the abdomen and the base of the neck. We see freestanding fungal bodies also bearing what look like perithecia, and in addition we see what look like the sacs where spores develop.”
The scientists named the species Allocordyceps baltica combining the Greek word for new—alloios—with the name of known genus Cordyceps.
Will there ever be a fungal parasite evolved to mind-control humans, as imagined in the show? Unlikely. The nervous and motor systems of arthropods and vertebrates are different enough that the actual Cordyceps can’t make the leap into humans—but that doesn’t mean fungi can’t infect our bodies.
In 2022, the World Health Organization released its first list of health-threatening fungi, which included 19 fungi that “represent the greatest threat to public health.” According to the report, fungal infections kill about 1.6 million people per year and present a particular danger for severely ill patients who are already immunocompromised. The frequency and geographic range of fungal diseases are also on the rise, due to global warming and an increase in international travel and trade.