The Last of Us: How real is the threat?

The brain-controlling fungal pandemic in HBO's post-apocalyptic thriller is not fiction. It just doesn't affect humans

Within the first few minutes of The Last of Us — a video game masterpiece and an equally well-adapted post-apocalyptic thriller on HBO — a patrolling soldier finds protagonist Joel and his daughter Sarah fleeing Austin and is ordered to eliminate them. Though Joel survives, Sarah is wounded by bullets and dies in her father’s arms. What leads to this iconic, heart-wrenching scene is an outbreak of cordyceps fungal infection, which is turning humans into cannibalistic zombies.

The brain-controlling fungal pandemic — at the core of the video game and series — is not fiction, just it doesn’t affect humans; it affects insects. Arthropods infected with cordyceps fungi cede control of their nervous system and body to the parasite. These fungi then manipulate the behaviour of host insects and guide them to more humid locations, kill them, feed on their remains, and eventually launch new spores from the corpse.

According to a study published long back in The American Naturalist, Ophiocordyceps unilateralis fungus infects Camponotus leonardi ants that live in hot and humid rainforests. The study says: “Ant‐infecting Ophiocordyceps are known to make hosts bite onto vegetation before killing them… Dead ants were found under leaves, attached by their mandibles, on the northern side of saplings 25 cm above the soil, where temperature and humidity conditions were optimal for fungal growth.” It is noted that infected ants ended up in a location with temperatures between 20 and 30 degrees Celsius and 94-95 per cent humidity.

Fortunately, such a fungal pandemic among our species, as yet, is highly unlikely. Most fungi, including cordyceps, need a much colder environment than the human body, for which the average internal temperature is 36.8 degrees Celsius. That’s why most fungal infections for us are limited to the skin.

But adaptive parasite manipulation isn’t rare in nature. Not only fungi, but roundworms are also guilty of this. In Central America, the giant turtle ant Cephalotes atratus that eats bird droppings can end up ingesting a nematode parasite, which occupies the host’s gaster (ant-specific term for the terminal part of the abdomen), lays eggs there, turns the belly bright red and round, similar to local berries that birds like to eat. The parasite is thus passed onto another bird.

And not only insects, but mammals like rodents also fall victim to such adaptive, behavioural manipulation. Protozoa Toxoplasma gondii, which is capable of infecting rodents, but needs a cat gut to reproduce, blocks the innate aversion of rats to cat urine and instead triggers an attraction to the pheromone. This increases the likelihood of a cat killing and eating an infected rat.

So, such a threat to humanity is not only from fungus but from other parasites, too. Besides, fears of a fungal pandemic among humans are mounting.

The Last of Us, the HBO series, begins in the 1960s with a bleak speech by an epidemiologist about the fungal threat. “... what if, for instance, the world were to get slightly warmer, then there is reason to evolve. One gene mutates, and ascomycetes, candida, ergot, cordyceps, aspergillus: any one of them could be capable of burrowing into our brains and taking control of not millions of us, but billions.”

Though the show is based on an extreme outcome of such a pandemic with plenty of artistic licences, the threat can’t be shrugged off. The World Health Organization, which last year released its first-ever list of fungi posing threat to human health, noted fungal infections “increased significantly” among hospital patients during the Covid pandemic. It further outlined fungal “priority pathogens” and cautioned against some strains becoming increasingly drug-resistant and relatively widespread.

Among those in the critical priority group is Aspergillus fumigatus, the common black mould found in damp houses and outdoors which can cause “chronic and acute lung disease”. Another is Candida auris, “a globally distributed pathogenic yeast that can cause invasive candidiasis of the blood, heart, central nervous system, eyes, bones and internal organs”.

Cryptococcus neoformans causes cryptococcal meningitis; around 100,000 people die from this disease each year. No other fungal infection causes more deaths in humans. There are other human-killer fungi, too, and what’s common among these diverse types of pathogens is that they are able to grow at human body temperature.

Notedly, cordyceps, the villain in The Last of Us, is not on the WHO’s threat list. The Chinese use cordyceps — caterpillar fungus or “Dong Chong Xia Cao” — as a highly valued tonic herb to treat a wide range of disorders, including respiratory, renal, liver and cardiovascular diseases.

Though there’s no evidence of cordyceps causing disease in humans, barring mild allergic reactions, several fungi have evolved their capacity over time. Still, experts believe there is no imminent threat from such fungi as they will take thousands of years of evolution to overcome the human immune system.

While in The Last of Us, the only hope for humanity is 14-year-old Ellie, who is mysteriously immune to the parasitic effects of the fungus, we still have time to work on an antifungal vaccine research programme. Until then, if you encounter anyone who is covered in mushrooms aka a clicker, run away, run far!