Written by Will Broussard & Illustrated by Brit Weatherbee
Since its release in January, HBO’s hit show “The Last of Us” has inspired fear and fascination among audiences through its stunningly beautiful, post-apocalyptic American landscapes, touching human relationships, and most importantly, its terrifyingly-realistic fungified zombies. In this article we show how the infection at the center of the show is based on both fact and fiction and explore how existing fungal pathogens may lead to a global pandemic. Beware: spoilers to follow!
The infection
In The Last of Us, the fictional affliction is not a virus like in so many zombie films, but rather a fungal disease they call the Cordyceps Brain Infection or CBI. After quickly colonizing their hosts’ brain, the fungal invader directs their host to spread themselves to non-infected people through bites or direct contact with mycelial fibers emanating from the skin and mouth. We know that the infected progress through four stages: Runner, Stalker, Clicker and Bloater, each possessing an increase in physical strength and a multiplication of mushrooms sprouting from their head and body, giving them added protection from human firepower. There is no cure for CBI but one of the show’s main characters, Ellie, has a natural immunity against it.
The real zombie fungi
As novel as the show’s made-up disease sounds, it’s actually based on a living fungal parasite of insects known as Ophiocordyceps unilateralis, or the zombie-ant fungus. Rather than infecting the brain, the nimble predator invades the body of its host and takes control of their muscles. Once the right environmental conditions are met, the fungi directs its victim to leave the colony, climb up a nearby tree, and anchor itself, whereupon it kills its host, sprouts a mushroom from their body, and continues the life cycle. While freakish, Ophiocordyceps is one of many fungal predators that attack insects in this way, from flies to cicadas (see image).
A variety of fungal parasites attack insects such as flies, ants and cicadas.
Mushroom fact vs. fiction
The Cordyceps Brain Infection combines elements of numerous mushroom species.
The "Clicker" stage of infection resembles Chicken of the Woods mushrooms.
There are many differences between the depiction of those infected with CBI and the real-life organism(s) upon which it is based. Jon Carver, Lead Mycologist at North Spore points to the visually-pleasing but scientifically inaccurate representation of fungal anatomy, stating that the show’s creators “combined physical elements of slime mold, reishi, and cordyceps” into a single organism not found in nature. North Spore’s creative director Matt McInnis added to this, noting that the growths imparting blindness to the “Clicker” stage of infection “resemble chicken of the woods” mushrooms.
While the show excels at detailing life-like mushrooms emerging from people’s heads and torsos, some basic fungal anatomy is omitted. “Where are the spores?” asks North Spore’s laboratory manager Rachael Martin. Indeed, the reproductive structures produced by most fungi are absent from the show, for good reason. According to Polygon, the shows’ writers swapped out the spores from the original video game version for fungal networks. “If we wanted to treat it realistically,” writer and co-creator Neil Druckmann told them, “...characters would wear gas masks all the time,” greatly inhibiting opportunities for humanization between the audience and the on-screen characters. The idea of a “network that is interconnected,” he told Collider in an interview, worked for the show, as it “became very scary to think that they're all working against us in this unified way.” Either way, swapping spores for mycelial threads gives the infected a more visceral, touch-based vector of transmission and keeps audiences on their toes.
A main plot point in the show centers on the ability for a Cordyceps-like fungus to “jump” between its natural insect host and humans. Speaking to Forbes Magazine, João Araújo, assistant curator and researcher in mycology at the New York Botanical Garden, said that it would be “very unlikely” such a drastic change in predator/prey relationship could take place so suddenly. The physical differences between humans and insects preclude such a jump, with insects being so much smaller, cold-blooded, and having much simpler body plans with vastly different skeletal and circulatory systems. They are “not prepared to invade, establish within and transmit spores from a human body,” adding that they have been coevolving with insects for more than 130 million years and “cannot even establish themselves in any mammals or non-insect animal.” The bottom line is that we won’t be needing to fear a zombie apocalypse coming from mushrooms any time soon.
One plot point the show did get right was the lack of a vaccine even 20 years after the CBI first appeared. Fungal infections are notoriously difficult to combat due to the similarity between fungal and human cells. Both being eukaryotic organisms, fungi also possess cells with nuclei and other membrane-bound structures making it difficult to develop specialized treatments that leave human cells unharmed. Additionally, just like bacteria and viral infections, fungi can develop resistance to treatments as new strains evolve. These infections can last a long time and be difficult to eradicate completely, especially for infections of the skin and nails which are difficult to reach with topical or oral medications. It is important to note that symptoms can be similar to other types of infections, and the infection might not be visible on the surface of the skin, leading to a failure in identification. Healthcare professionals need to identify diseases in order to develop the right treatments.
Real fungal invaders
While mammals are generally highly resistant to systemic fungal diseases, we still have to contend with harmful fungi, most of which are opportunistic and infect people with weakened immune systems. Regardless, the CDC reports fungal infections kill over 1.5 million people annually, with 75,000 people in the U.S. hospitalized each year due to a fungal infection. Here are nine fungal pathogens of concern currently affecting humans across the globe:
Common Fungal Infections in Humans
| Fungal Pathogen | Description |
|
Candida species |
Candida is a type of yeast that can cause infections in the mouth, throat, esophagus, and genital area. In severe cases, it can also spread to the bloodstream and cause systemic infections. |
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An emerging fungal pathogen first appearing in Brazil in 1998, spreading between people and cats throughout South America, leading to facial lesions and sores. Between 1998–2016, over 4,500 human cases spread by cats were identified. |
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Coccidiomycosis |
A debilitating disease called Valley Fever. It used to be thought it could exist only in the arid Southwest and California, but now it's appearing as far north as Washington state. This fungus usually infects the lungs and can cause respiratory symptoms including cough, fever, chest pain, and tiredness. |
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Found in moist soils throughout the northeast United States, including Minnesota, Wisconsin and Indiana, and can be a serious progressive illness involving multiple organ systems. It has been hypothesized that drier summers and wetter winters, associated with climate change, may create optimal conditions for its dispersal. |
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Aspergillus is a type of mold that can cause lung infections in people with weakened immune systems or lung diseases such as asthma or cystic fibrosis. It can also cause invasive infections in other parts of the body |
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Cryptococcus is a type of fungus that can cause lung infections and meningitis in people with weakened immune systems, such as those with HIV/AIDS. It was found that increased temperatures drive increases in genetic changes, some of which might presumably lead to higher heat resistance, and others perhaps toward greater disease-causing potential. |
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Histoplasma is a type of fungus that can cause lung infections in people who breathe in its spores. It is found in soil contaminated with bird or bat droppings. |
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Pneumocystis is a type of fungus that can cause severe pneumonia in people with weakened immune systems, such as those with HIV/AIDS. |
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Dermatophytes are a group of fungi that can cause skin, hair, and nail infections, such as athlete's foot, jock itch, and ringworm. |
Candida species
Candida is a type of yeast that can cause infections in the mouth, throat, esophagus, and genital area. In severe cases, it can also spread to the bloodstream and cause systemic infections.
An emerging fungal pathogen first appearing in Brazil in 1998, spreading between people and cats throughout South America, leading to facial lesions and sores. Between 1998–2016, over 4,500 human cases spread by cats were identified.
A debilitating disease called Valley Fever. It used to be thought it could exist only in the arid Southwest and California, but now it's appearing as far north as Washington state. This fungus usually infects the lungs and can cause respiratory symptoms including cough, fever, chest pain, and tiredness.
Found in moist soils throughout the northeast United States, including Minnesota, Wisconsin and Indiana, and can be a serious progressive illness involving multiple organ systems. It has been hypothesized that drier summers and wetter winters, associated with climate change, may create optimal conditions for its dispersal.
Aspergillus is a type of mold that can cause lung infections in people with weakened immune systems or lung diseases such as asthma or cystic fibrosis. It can also cause invasive infections in other parts of the body.
Cryptococcus is a type of fungus that can cause lung infections and meningitis in people with weakened immune systems, such as those with HIV/AIDS. It was found that increased temperatures drive increases in genetic changes, some of which might presumably lead to higher heat resistance, and others perhaps toward greater disease-causing potential.
Histoplasma is a type of fungus that can cause lung infections in people who breathe in its spores. It is found in soil contaminated with bird or bat droppings.
Pneumocystis is a type of fungus that can cause severe pneumonia in people with weakened immune systems, such as those with HIV/AIDS.
Dermatophytes are a group of fungi that can cause skin, hair, and nail infections, such as athlete's foot, jock itch, and ringworm.
Fungal pandemics
Of the species mentioned above, Candida auris gives global health authorities the greatest concern. Discovered in Japan in 2006 and primarily found in healthcare settings such as hospitals and nursing homes, it is spread through direct contact and can cause infections in the blood and internal organs like the kidney, heart and brain. It is often multi-drug resistant, difficult to remove from the hospital environment, and has a 60% mortality rate. Some have hypothesized that the emergence of fungi like Candida are a result of a warming climate, as evolution favors fungi better adapted to handle mammalian body temperatures. Whether or not Candida becomes a real-life CBI, the future will include more pathogenic fungi, as two current fungal epidemics raging in the animal kingdom have recently taught us.
What has been described as “perhaps the most devastating disease the world has ever recorded, in terms of its species scope and death toll,” the chytrid fungus, Batrachochytrium dendrobatidis, discovered in 1998, has contributed to the global decline of nearly 500 amphibian species, 90 of which have been driven to extinction. In 2006, the fungus Pseudogymnoascus destructans appeared in hibernating bats in New York, and has since killed over 90% of northern long-eared, little brown and tri-colored bats across North America. While both fungal diseases invade and consume the skin of their host and have no known treatments, a glimmer of hope exists in the fact that a number of individual bats and frogs possess natural immunity against their fungal invaders.
Candida auris culture on a petri dish.
A chytrid-infected frog1
Hibernating bat showing signs of fungal infection.
Can “healthy” mushroom spores hurt you?
It is important to note that while many pathogenic, toxic and otherwise non-edible mushroom species can cause health problems ranging from skin infections to multiple system failure and gastric upset, repeated exposure to high concentrations of “safe” mushroom spores can cause a variety of lung-related inflammatory conditions. Colloquially known as “Spore Lung,” these ailments can be avoided through the proper use of appropriate personal protective equipment (PPE) such as a face mask and by limiting exposure to mushrooms during sporulation. Also keep in mind that spores are not the same thing as spawn (mycelium grown on substrate) as our recent article explains.
Final thoughts
The imagined Cordyceps Brain Infection, or CBI in The Last of Us is a blend of fact and fiction, combining physical traits of numerous extant, or currently living, fungi rendering it both beautiful and terrifying. While we shouldn’t worry about future fungal outbreaks controlling our minds, we should consider how our current environmental impacts may be generating novel pathogenic fungi, and the current limits to developing antifungal treatments due to their structural similarity to ourselves. The great irony is that anthropogenic climate change may be eroding the natural protection a higher internal temperature affords humanity, bringing us closer to the point where a mutated fungus makes The Last of Us look like a lighthearted documentary.
References
Carpenter, Nicole. Why The Last of Us creators swapped spores for Cordyceps networks. The short answer: An HBO version had to be watchable. 1/22/23. https://www.polygon.com/entertainment/23562421/last-of-us-cordyceps-spores-tv-show-hbo
Parshall, Allison. Could the Zombie Fungus in TV’s The Last of Us Really Infect People? Scientific American: 2/10/23. https://www.scientificamerican.com/article/could-the-zombie-fungus-in-tvs-the-last-of-us-really-infect-people/#:~:text=Now%20clearly%2C%20some%20fungi%20have,for%20Ophiocordyceps%2C%20there's%20no%20chance.
WHO fungal priority pathogens list to guide research, development and public health action. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/publications/i/item/9789240060241
Photo Citation
1Brem, Forrest. 2008. This file was published in a Public Library of Science journal. Their website states that the content of all PLOS journals is published under the Creative Commons Attribution 4.0 license (or its previous version depending on the publication date), unless indicated otherwise.