Real-World Origin of the Cordyceps Fungus Zombie From 'The Last of Us'

The consequences of climate change are numerous, but viewers of HBO's The Last of Us might have been surprised to learn that it could lead to a post-apocalyptic world taken over by zombies that were infected because a fungus adapted to warmer temperatures.

The Last of Us, based on the bestselling video game of the same name, imagines a world in a pandemic where a cordyceps fungus has evolved to infect humans, taking over our brains and turning us into puppets hell-bent on infecting others.

Could this science fiction ever become science fact?

Zombie-Ant Fungus

In nature, there is a species of Cordyceps fungi that infects ants, sometimes called the zombie-ant fungus. This species, Ophiocordyceps unilateralis, infects ants and takes over their bodies, controlling their behavior entirely.

"Once the fungal spore has germinated into the ant, it begins to divide into individual yeast-like cells that grow and multiply in the hemolymph (the fluid that contains the blood of insects) and spreads throughout the body," William C. Beckerson, a molecular biology and genetics postdoctoral research fellow at Utrecht University in the Netherlands, told Newsweek.

"Initially, the insect goes on with its life as normal; however, after a few days, the fungal cells begin to secrete many different chemicals that change the behavior of their hosts. These ants, which are typically very social creatures with defined jobs in the nest, suddenly wander away from the nest and their roles, exhibit changes in motor skills including twitching and a staggered walking, disrupted [...] cycles leading them to wander continuously regardless of day or night [...]."

Evolving to Infect Humans

In the show, the fungus evolved to infect humans due to climate change heating the planet, which allowed it to adapt to the higher body temperature of humans. This in particular could happen in real life, Beckerson said.

"Just as the Ophiocordyceps have evolved to manipulate ant behavior through a long evolutionary history of trial and error, so can microorganisms like bacteria and fungi adapt to higher temperature through random mutation, and at astonishingly fast pace," Beckerson said. "There have been many experiments to test the 'thermal tolerance' of fungi and other microbes (aka, how hot can they survive) that show survival at temperatures even up to 42 C [107.6 F] is possible if grown in increasingly warm conditions. That's 5 C warmer than the average 37 C [98.6 F] body temperature of humans."

Two species of fungus, Aspergillus and Candida, are already known to infect humans as opportunistic pathogens in people with weakened immune systems.

"It is very likely that these types of fungal infections will become increasingly more common as the planet continues to warm, so yes, it is possible that parasites like Ophiocordyceps could infect humans," Beckerson said.

However, the zombie-ant fungus is generally specialized in one specific species of ant, meaning that a jump from ant to human may be evolutionarily very hard.

"They are so host-specific that nearly every species of zombie ant we find is infected by a different species of Ophiocordyceps, and if you try to grow them on a different host, even in lab settings, they do not manipulate their behavior," Beckerson said.

Ian Will, a parasitic fungus researcher at the University of Central Florida, told Newsweek that this one-fungus-one-ant rule of thumb suggests that the fine mechanisms of behavior modification rely on tight co-evolution to work properly.

"If jumping ant species is tricky, it'd be a special Ophiocordyceps that jumps to other animals like humans," he said.

Additionally, if the fungus evolved to infect humans, that doesn't necessarily mean that it would be able to control human behavior as it does with the ants.

"Infection and manipulation are two completely different stories," Beckerson said. "It is quite obvious that human and ant behaviors are different, and while some of the chemicals made by these fungi could affect behavior in mammals, as seen by the effects of Aflatrem [a chemical made by some fungi] on ants and cows, manipulation of behavior in a way that is reminiscent of The Last of Us is not likely."

Fungus Controls Behavior

Scientists aren't entirely sure how the fungus controls the ants' behavior. Robbie Rae, a parasite expert at Liverpool John Moores University in the U.K., told Newsweek that other parasites that change the behavior of hosts have evolved to manipulate the expression of neurotransmitters that make serotonin and dopamine, which are involved in behavior regulation.

However, that doesn't seem to be the case with Cordyceps.

"Molecular work from multiple Ophiocordyceps species have suggested a combination of fungal toxins and other compounds that could interfere with host (ant) physiology and behavior control," Ian Will said. "At least in part, this may take advantage of pre-existing ant behaviors and behavior-regulating processes rather than creating 'new' behaviors that are completely outside what a healthy ant could do."

Beckerson's lab has recently published work on identifying potential candidates that could play a role in behavior manipulation in ants, with one promising candidate being an "Aflatrem-like" compound.

"[This "Aflatrem-like" compound is] related to previously known Aflatrem made by the plant pathogen Aspergillus flavus that, when consumed by animals, such as cows that eat contaminated grain feed, can cause some of the staggering symptoms that are also seen in the zombie ants," Beckerson said.

Zombie Fungus Spores

One thing that the series does well so far is to show what happens when the fungus is done with its host's body: the end stage of a fungal infection involves the spreading of fungal spores to infect other organisms. In the zombie-ant fungus, the ant is made to climb up to a high point, bite down on a leaf—this is called the "death grip"—and release these spores from a large snake-shaped fruiting body that bursts from its head.

"The fungus then reproduces in the ant and new fungal spores fall to the ground and infect more ants," Rae said. "It is beneficial for the fungus to change the behavior of the ant to make it crawl up to the top of the tree canopy as it then has more chance of infecting more ants by increasing the dispersal of spores."

Some other species of fungus rely on outgrowths of fungal mycelium to anchor their hosts to the surface, Beckerson said. This is seen in the first episode of The Last of Us, when infected people attack and bite others to spread the infection, furthering the life cycle.

According to the lore of the game, once the fungus has been in the host's body for over a decade, the body will eventually die and release spores, similar to the ants in real life. This is seen in the show, where a skeleton is stuck against a wall with a huge bloom of fungal outgrowths bursting out of it.

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