12 March 2023

Hope from the apocalypse: The secrets behind 'The Last of Us'

How the fungus behind the zombie hit is already among us, and helping in some unexpected ways.

By Eddie Johnston

Countless white threads growing organically on a black background

If you’ve been watching HBO’s The Last of Us, or played the game that inspired the series, you’ll be more than familiar with the Cordyceps fungus.

In both the show and game, the fungus infects humans, slowly taking over their bodies and turning them into aggressive zombie-like monsters that seek out other hosts, through either spores or a mycelial network.

While it makes for compelling science fiction, this type of fungal infection is science fact, but perhaps not in the way you know it.

So, how do these real-world fungi compare to their on-screen counterparts? And how on Earth could they actually be a good thing?

A humanoid figure embedded into a wall covered with fungal growths
A fungus zombie from 'The Last of Us' transformed into a large fungal network. Photograph by Liane Hentscher/HBO
A large humanoid figure covered in fungal growths standing before a large flame
A large fungus zombie from 'The Last of Us', Courtesy of HBO

Putting a name to the infamous fungus

In The Last of Us, a mutated species of the so-called ‘zombie fungus’ moves from infecting ants to infecting humans, as a result of climate change.

The fungus in question is Ophiocordyceps unilateralis, a species first discovered in 1859 by Alfred Russel Wallace, a British naturalist who help contribute towards our understanding of evolution through natural selection.

But O. unilateralis is only one of many fungi capable of infecting insects, collectively known as entomopathogenic fungi. The Ophiocordyceps genus has around 100 species, and Cordyceps has nearly 500 species.

These fungi infect a wide variety of different insects, including butterflies, moths, ants and cicadas. Some species also target spiders, including large tarantulas.

Luckily for us, being warm-blooded stops us from being infected by this sort of fungus. Entomopathogenic fungi have evolved over the course of millions of years to infect the cold-blooded systems of insects, and would struggle with our toasty body temperature.

The Last of Us gets around this by explaining that the effects of climate change influence the evolution of the O. unilateralis fungus, allowing it to infect humans. In the real world, this is a process that would take thousands of years, so there’s no risk of it occurring any time soon!

A large red and white fungal growth coming from a hairy tarantula being held by a human hand
Ophiocordyceps caloceroides infecting a tarantula, Ian Suzuki on Wikimedia Commons CC BY 3.0
A large locust with creamy white fungal tendrils growing from its body
Cordyceps locustiphila infecting a locust, Susanne Sourell on Wikimedia Commons CC BY-SA 3.0

Keeping balance

Entomopathogenic fungi are perfect for an apocalyptic scenario, infecting and consuming as they go. But in the real world, Ophiocordyceps and Cordyceps are hard at work keeping delicate ecosystems in balance.

Many fungi only infect one particular species of insect, like leaf-cutting ants. As the fungus spreads, it reduces the number of available hosts, keeping numbers of both species in check, stopping either from over-running their habitats.

Humans have actually made use of the insect control properties of Cordyceps to help protect crops from pests. Rather than using pesticides which can cause damage to local biodiversity, fungi like Cordyceps can target the insects pests, while leaving everything else unharmed.

Plenty of organic fruit and veg rely on the hard work of these fungi to keep them safe while they grow.

But one of the most exciting uses of Cordyceps fungi is tackling the spread of malaria.

Malaria is responsible for over half a million deaths every year, caused by parasites passed to humans through the bite of Anopheles mosquitoes. To help bring this number down, scientists are trying to reduce numbers of mosquitoes to reduce the spread of the disease.

In the past, synthetic pesticides have been used, but many species are developing resistance to them. That’s why scientists at the Chinese Academy of Science in Shanghai are investigating how Cordyceps could be used to limit the numbers of Anopheles mosquitoes.

A close up image of a mosquito full of blood on human skin
Anopheles minimus, one of the many species of mosquito that can transmit malaria to humans, James Gathany/CDC on Wikimedia Commons

Transplant transformation

Along with playing a key role in our ecosystems, entomopathogenic fungi, like many other fungi species, are changing medical science.

One of the most incredible contributions is a drug that has revolutionised a surgical procedure and gone on to save countless lives across the world.

This incredible drug was found in a fungus from the same group as Ophiocordyceps called Tolypocladium inflatum, a mould that’s found in soil that parasitises scarab beetle larvae.

To infect these beetles, the fungus produces chemicals that suppress the immune system of the insect. One of these is ciclosporin, which reduces the production of inflammatory cytokines, proteins that play a key part in the immune response of insects and humans alike.

Sounds like a pretty bad chemical, right? In some cases, it’s literally just what the doctor ordered.

In transplantation, when an organ like a liver or a kidney is moved into a new body, the immune system will attack it as a foreign object, causing it to be rejected. Ciclosporin, in the correct amounts, can suppress the body’s immune response, giving the new organ a chance to settle in.

A white base with small yellow heads growing in dark soil
Tolypocladium inflatum, Richard Tehan CC BY-NC-SA 4.0
A black and white image of a lumpy fungal growth
Electron microscope image of Tolypocladium inflatum, Reumatismo CC BY-NC 4.0

Fungi foes

It’s clear we’ve got far more to gain from our entomopathogenic friends than we have to lose. But there are a few fungi that can cause trouble for us humans.

A group of fungi called the Onygenales are some of the few fungi that infect healthy humans. These fungi can break down keratin, a protein found in skin, causing skin conditions like athlete’s foot and ringworm.

Some other fungi tend to present more of a problem to people who are immunocompromised. Aspergillus fumigatus is a fungus so incredibly common that we inhale hundreds of its spores every day.

This fungus is usually found breaking down dead plant matter, but can cause potentially life-threatening lung infections in someone with a compromised immune system.

Other fungi that can infect humans are those in the genus Cryptococcus, which can cause a lethal infection known as cryptococcosis. A particularly resilient fungus, Cryptococcus can live in soil, bird droppings and even as a parasite on other fungi.

In fact, they’re so resistant, they can grow in the melted reactor of the Chernobyl Nuclear Power Plant, within high levels of deadly radiation.

Perhaps not quite as scary as a fungus zombie, but still a tough customer!

A large brown mass growing in lines and circles across a white background
A species of Aspergillus fungus under a microscope, Vyzhdova V on Wikimedia Commons CC BY 4.0
Many small white circular growths of fungus
A microscope image of Cryptococcus neoformans, CDC/Dr. Leanor Haley on Wikimedia Commons

The future is fungal

The Last of Us uses an incredible real-world fungus as the basis for unique tale of the end of humanity.

These fungi are already among us, and while terrifying if you’re an ant, have so much potential to help humanity.

Who knows what they could help us with next?

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