TLOU Tales – Episode 2: The Devil Is in the Details

Mind-controlling fungi, zombies, and a harrowing depiction of humanity on its knees.

If you’ve not heard of The Last of Us, you may have (understandably) started off 2023 hibernating under a rock. Brought to (Some of Us) by HBO, the show is based on the eponymous video game from 2013. In short, The Last of Us is set in a post-apocalyptic world where mass infection from a mutated strain of the Cordyceps fungus has turned victims into aggressive, cannibalistic creatures.

As someone who is more interested in the science behind these shows than the gruesome tales they tell, I was keen to find out more about the fungus in question – and whether parts of the story are scientifically plausible. To that end, who better to speak with than Elaine Cloutman-Green, a Consultant Clinical Scientist working in Infection Prevention and Control at Great Ormond Street Hospital NHS Foundation Trust, London, UK. Oh – and she’s also an avid gamer, TV, and movie fan.

Fungi in the limelight

Cordyceps are a diverse fungi and, as a species, are endoparasitoids, meaning they live inside the body of their insect host and feed from it until the host ultimately dies. Although there are hundreds of species in the Cordyceps genus, the most commonly known is Ophiocordyceps unilateralis – you may have heard it be referred to as the “zombie fungus.”

It’s no shock that the creators of The Last of Us chose this species out of the wide pool of fungi, but to choose a fungus in the first place is surprising. Fungal infections are often left on the backburner in the horror genre; viruses are the more common source of zombie apocalypses that have graced our screens over the years. Even in The Last of Us, the idea that the next threat could be from a fungus is laughed at – except by one epidemiologist – in the opening scenes. This foreshadowing trope quite closely reflects the current state of the field in that, within microbiology, mycology is an under-recognized and under-funded specialism. 

“This lack of attention is partly because fungal diseases are frequently associated with immunosuppressive conditions, such as AIDS, or linked to locations such as the tropics,” says Cloutman-Green. “There is an intrinsic bias that has historically meant it was not as high on the list of research priorities as those organisms that more directly impact western healthcare.”

In 2017, the World Health Organization (WHO) published its first list of “priority pathogens” – detailing 12 families of bacteria that posed the biggest threat to humanity (1). Recognizing the need to address the unmet needs in fungal research and development, in 2022, the organization published a list of 19 fungal priority pathogens (2). Such clear direction from WHO and the increasing frequency of detecting Candida auris outbreaks – a WHO “critical” priority – as the culprit of healthcare-associated infections will hopefully lead to more attention on mycology and fungal infections in future (3).

Another reason that fungi are frequently overlooked is because environmental sources are often behind disease transmission – in fact, direct person-to-person transmission of fungal diseases is quite infrequent. “It has also not generally fallen under the focus of infection control teams because the incubation periods are frequently prolonged and exposure usually occurs outside of healthcare,” says Cloutman-Green. “It is therefore much more difficult to manage and most options, in the cases linked to immunosuppression, focus on prophylaxis or managing the cause of the underlying immunosuppression rather than the potential resulting infection.”

Society’s obsession with apocalyptic and post-apocalyptic fiction continues to baffle me, given that our daily lives are already filled with the 24-hours news cycle of existential dread. (Though the genre has been around for centuries.) But the looming threat of World War III or another pandemic actually works in the favor of storytellers. “When people are writing fiction or designing games, they tend to hook onto things they have already heard of to generate more widespread understanding,” says Cloutman-Green. “And most people have personal experiences with viruses, which explains why they are the more frequent focus of zombie apocalypses.”

Fungi don’t take up much space in the minds of most people, which could offer up another reason as to why they aren’t the go-to pathogen for fictional outbreaks…

A bold leap

Visuals make or break shows like The Last of Us; after all, the devil is in the detail – and the science. When something is adapted for a new medium – from book to film or from game to streaming fodder – fans of the original can get antsy when certain details or storylines are omitted or changed. (I still have a personal vendetta against Netflix because of Shadowhunters.) In the case of The Last of Us, the show’s creators changed how the Cordyceps infection spread – in the game, the infection is transmitted through spores, but in the show they changed it to “tendrils.”

For me, the big question is: Why? Cloutman-Green has an answer: “The TV show creators altered one of the transmission routes for pragmatic reasons; it’s hard to act as well in a gas mask. That said, even though you don a gas mask when entering fungal areas in the game, the main transmission route that drives the narrative is still via bites or other barrier breach. In this respect, they kept more closely to the ‘standard’ zombie mythos than the fungal transmission; it felt, as a player, like it was more there for feel than game play.”

Does the show still stick to the science? “Cordyceps species do remain dormant in the soil until they get in contact with a host and this is demonstrated in the episodes we’ve seen so far, where the hyphal growths use the hyphal system to interact and send signals,” says Cloutman-Green. “This is how many fungal species survive as the growing end of the hyphae can signal when nutrient sources are identified.”

Read the rest of our TLOU Tales series here:
Episode 1: The Culprit of Humanity’s Downfall
Episode 3: The Realities of The Last of Us
Episode 4: Living with the Living Dead