Is 'The Last of Us' Fungal Pandemic Possible? A Scientific Investigation - CNET

Back successful 2019, Craig Mazin and HBO released Chernobyl, a masterful bid dramatizing the 1986 atomic reactor meltdown astatine the eponymous powerfulness plant. The TV amusement earned captious praise and a mates of Emmys but astatine CNET Science we were astir funny successful however intimately Mazin and co. were capable to instrumentality to real-world science. Turns out, they did a bully job.

Mazin's adjacent HBO outing is The Last of Us, based connected the 2013 survival-horror video game of the aforesaid name. CNET's ain Sean Keane has described the show, which debuted connected Sunday, arsenic "the top video crippled adaptation ever made."

The Last of Us imagines a satellite ravaged by a fungal apocalypse caused by a creepy, mind-controlling fungus known arsenic Cordyceps. That fungus is real, truthful I've people been wondering conscionable however apt a fungi apocalypse truly is. 

The thought has been investigated successful the discourse of the crippled galore times, but HBO's mentation of the Cordyceps encephalon corruption is somewhat antithetic to the 1 crippled developer Naughty Dog archetypal conjured successful 2013. 

What follows is an probe of the plausibility of a fungal pandemic, caused by a Cordyceps-like pathogen that changes quality behavior. I'm going to presume you're astatine slightest somewhat acquainted with the communicative of Joel and Ellie, the 2 protagonists making their mode crossed the ruins of a post-apocalyptic USA. I'm besides going to accidental astatine the apical that this is an introspection of a fictional world, truthful there's ever wiggle country for the communicative to make successful unexpected ways.

This includes immoderate airy spoilers from episodes 2 and 3 of The Last of Us, truthful if you're trying to support your viewing acquisition spoiler-free, it's clip for you to bail. 

The existent satellite inspiration for The Last of Us

You tin blasted David Attenborough and quality documentaries for the shambling, clicking horrors that haunt The Last of Us.

In a must-watch occurrence connected jungles successful the 2006 BBC bid Planet Earth, Attenborough and his documentary squad brushwood assorted behavior-manipulating fungi, including 1 that parasitizes carpenter ants: Ophiocordyceps. In the clip, which has been viewed connected YouTube implicit 10 cardinal times, the camera lingers connected an ant with its jaws wrapped astir a histrion branch. A ghostly violin plays arsenic Attenborough narrates the scene.

"Like thing retired of subject fiction, the fruiting assemblage of Cordyceps erupts from the ant's head," helium says. 

The Planet Earth country inspired Bruce Straley and Neil Druckmann, the manager and originative manager respectively, connected 2013's The Last of Us. In a GamesBeat interrogation aft the game's release, Druckmann mentions "ripping off" the documentary and Straley says that zombie ants were the "jumping disconnected point" for the game. And the crippled does hew intimately to its real-world root material.

The beingness rhythm of Ophiocordyceps is gruesome but beautiful. Ants that travel into interaction with Ophiocordyceps spores connected the jungle level go infected. The fungus slips wrong the ant's assemblage and begins to replicate. It takes up residence successful peculiar regions, similar the encephalon and muscle, releasing chemic compounds to manipulate behaviour of the ant. The ant is directed to the underside of a leaf, precocious supra the ground, and bites into it. Its jaw locks astir the leafage acknowledgment to immoderate clever fungal compounds and it stays determination until the fruiting assemblage erupts from its head. Eventually it bursts unfastened and releases much spores to the ground.

The process is highly specific. One taxon of Ophiocordyceps typically infects and zombifies conscionable 1 taxon of ant. This specificity extends to the mode the fungus takes implicit the caput of its host. A 2014 insubstantial explored the ant-fungus relationship, uncovering that Ophiocordyceps had evolved a peculiar acceptable of compounds to power behaviour of 1 taxon of ant, but those aforesaid compounds did not change the behaviour of antithetic ant taxon (though the fungus volition inactive often termination those ants).

Our real-world knowing of the fungus has besides changed since The Last of Us was released successful 2013.

The Planet Earth documentary was released successful 2006. At the time, the ant-infecting parasite was, scientifically, known arsenic Cordyceps unilateralis. In 2007, galore of the Cordyceps fungi that parasitize insects, including ants but besides things similar caterpillars and spiders, were reclassified into a antithetic household of fungi -- Ophiocordyceps. While The Last of Us uses these 2 words interchangeably, they are present classed arsenic antithetic genera of fungi and scientists inactive usage Cordyceps arsenic a benignant of generic sanction for each the species.

The Last of Us timeline

The pandemic's origins are not revealed successful the video crippled beyond a fewer stray paper clippings and notes, which look to constituent to a South American origin. HBO's adaptation dives a small further into the backstory, specifically successful episodes 2 and 3. This gives america a small much to enactment with successful presumption of existent satellite plausibility.

Here's the timeline, arsenic we recognize it.

On the greeting of Sept. 23, 2003, a pistillate moving astatine a flour and atom mill connected the occidental broadside of Jakarta was bitten by an chartless quality being. She became violent, attacked 4 coworkers, biting 3 of them, earlier being locked successful a bath and changeable successful the skull.

The 3 coworkers who were bitten were executed a fewer hours later. Fourteen coworkers could not beryllium located.

A time later, connected Sept. 24, 2003, 2 constabulary officers successful Jakarta, Indonesia locomotion into a edifice and interrupt Ibu Ratna, a prof of mycology astatine the University of Indonesia, arsenic she's eating lunch. They instrumentality her to a laboratory astatine the Ministry of Health wherever she looks down a microscope and identifies a fungus: Ophiocordyceps. 

(Depending connected the taxon Ratna saw, the fungus would person apt been classed arsenic a Cordyceps in 2003… a imaginable crippled spread oregon pedantry?)

Ratna asks wherefore it's been stained with chlorazol -- which is commonly utilized to place fungal elements from quality hair, nails oregon different specimens. "Cordyceps cannot past successful humans," she tells the constabulary officer. She past examines the corpse of the pistillate who worked astatine the flour and atom factory. She cuts unfastened the wound coiled connected the woman's limb and rummages astir successful her mouth, discovering the corpse has been colonized by Ophiocordyceps.

After making her discovery, she makes a recommendation: The serviceman should weaponry the metropolis and everyone successful it. 

On Sept. 26, 2003, the outbreak hits the US. This is dubbed Outbreak Day. In Austin, Texas, the archetypal indications of occupation are evident arsenic ambulances screech done the metropolis astatine astir 3:15 p.m. 

In the aboriginal hours of Sept. 27, the outbreak reaches captious wide and the streets go chaotic. Planes are crashing into the ground. Highways retired of Austin go blocked by the military. Members of the nationalist have, against the proposal of the exigency broadcast system, fled their homes. 

By Monday, Sept. 29, Joel explains to Ellie, "everything was gone."

In The Last of Us, humanity tries to prime itself up 2 decades aft a mutant Cordyceps fungus kickstarts a pandemic.

HBO

So, could it happen?

The abbreviated reply is: It's improbable. The longer answer? Maybe, but with a ton of caveats. 

There are 2 cardinal crippled devices that underpin the fungal pandemic successful the TV mentation of The Last of Us -- clime alteration and however the fungi reproduce.

The Last of Us sets up its archetypal play with an interrogation conception that takes spot successful 1968. Two fictional researchers are discussing pandemics connected a speech show. One of them, Dr. Neumann, says he's not frightened of bacteria oregon viruses kickstarting a pandemic, dissimilar the different guest. What scares him astir is fungi. Mostly due to the fact that they don't conscionable termination the host, but instrumentality it over. 

The assemblage laughs (and aft the past 3 years, you mightiness too). Then 35 years aboriginal successful the fictional world, that's precisely what happens.

In the existent world, scientists person often wondered wherefore insects, plants and amphibians are truthful susceptible to fungal diseases. Research has shown that regulating assemblage temperature, oregon homeothermy, is simply a large obstruction against fungal infection. Fungi thrive successful cooler environments and that's wherefore they're potent enemies of insects, amphibians and plants. It besides means they're not arsenic large a information to hot-blooded animals, similar ourselves. Fungi besides person to beryllium capable to sorb quality tissue, which they mostly conflict to do, and adjacent if they negociate to invade us, they inactive person to contend with a robust quality immune system.

Humans can be infected by fungi, though. Candida, a yeast which causes thrush, is simply a potent species. A multidrug-resistant species, Candida auris, is of large interest successful hospitals. There are besides molds, which origin athlete's ft and ringworm. Sometimes, these fungi evade our defenses, particularly those of america with compromised immune systems. 

"The 1 happening you person to retrieve with fungal infections is that they predominantly infect radical with an underlying condition," Julianne Djordjevic, an subordinate prof astatine the University of Sydney who studies fungal corruption of humans, tells CNET.

Things are changing, though. The world, ours and the 1 successful The Last of Us, is heating up. "What if, for instance, the satellite were to get somewhat warmer?" the fictional Dr. Neumann asks successful the premiere. Higher temperatures could spot fungi dilatory accommodate and germinate to withstand the types of vigor they mightiness acquisition wrong a quality body. Some scientists judge this is wherefore Candida infections mightiness beryllium connected the rise. 

Another taxon known arsenic Ophiocordyceps sinensis, found connected the Tibetan plateau, provides a imaginable counter. The taxon has agelong been utilized successful Chinese medicine and immoderate of the compounds it creates person been studied for their anti-cancer properties. However, successful 2018, mycologists showed clime alteration -- successful summation to overharvesting -- was leading to a diminution successful the species. The Himalayas are peculiarly susceptible arsenic the satellite warms and, astatine slightest for this species, adaptation and improvement aren't keeping pace. Perhaps we're warming the satellite excessively rapidly for fungi to adapt.

Spores and tendrils

But however does Cordyceps spread? And truthful fast? As an ascomycetes, oregon sac fungi, the Ophiocordyceps that inhabit Earth's temperate jungles propagate and past done spores. It's portion of their beingness cycle: infect an ant, instrumentality it over, make a fruiting body, merchandise the spores, commencement again.

HBO's adaptation makes 1 immense alteration from the video game: spores aren't the mode Cordyceps moves betwixt people. Mazin has said this is mostly due to the fact that spores would mean everybody would person to deterioration a disguise each the clip (I'm not definite that's peculiarly existent but it would beryllium beauteous clunky successful a TV show). Nevertheless, the adaptation replaces spores with "tendrils" and bites from infected people, 2 things we haven't seen arsenic infectious agents successful the existent world. They're besides affected by proximity. Whereas spores tin question hundreds of miles, tendrils and bites request adjacent contact.

That's the toughest portion of this pandemic to square, but The Last of Us tries to supply a originative solution arsenic to however nine collapsed. 

In the video game, Joel and Ellie sometimes don state masks successful areas of dense Cordyceps spores.

Naughty Dog

Early successful the series, arsenic Joel and Ellie are wandering done the wreckage of civilization, Joel concisely touches connected the accepted communicative of the pandemic's origins: Cordyceps mutated. Then the fungi got into the nutrient proviso -- things similar bread, sweetener and cereal each carried the mutated strain -- and that nutrient proviso was shuttled astir the globe. 

There is precedent for this benignant of thing. The Great Famine, which ravaged Ireland successful the 1840s and 1850s, was caused by an organism akin to a fungus, known arsenic Phytophthora infestans, destroying murphy crops. Though it didn't straight infect and termination (or "mind control") humans, it shows we're astatine slightest susceptible to fungi successful ways that aren't getting overmuch attention.

But the tendrils are inactive a occupation for plausibility, adjacent if their advantages for infected enactment are partially explained successful an aboriginal episode.

"The fungus besides grows underground," Tess, different subsister who partners with Joel, explains to Ellie successful an aboriginal episode. "Long fibers similar wires, immoderate of them stretching implicit a mile. You measurement connected a spot of Cordyceps successful 1 spot and you tin aftermath a twelve infected from determination else." This transportation could alert infected to uninfected and marque it adjacent intolerable to debar them, but successful the aboriginal stages of the pandemic it would instrumentality immoderate highly inept authorities responses to genuinely instrumentality off.

Maybe not truthful unlikely, fixed what we cognize astir the astir caller pandemics.

However, this alteration would necessitate a large evolutionary deviation for Ophiocordyceps. Provided the Cordyceps that Ibu Ratna sees down her microscope and the Cordyceps successful the existent satellite are fundamentally the same, it would mean the fungus has fundamentally changed connected a familial level to thing wholly alien. It would besides beryllium antithetic for those fungi to past beryllium successful nutrient crops unless those crops are highly contaminated with ants oregon spiders oregon moths. 

Overcoming these challenges we inactive person to get to a spot wherever the fungus tin control the behaviour of a quality being. While fungal compounds tin change the quality caput (think LSD, for instance, which was isolated from a rye fungus), the circumstantial compounds required to marque humans much assertive and assistance dispersed the corruption would necessitate a miraculous evolutionary leap for Ophiocordyceps.

There's conscionable a batch of challenges for a mutated fungus to overcome. Perhaps these volition beryllium explained successful a 2nd season.

Whenever I spot an insect with Ophiocordyceps stalks protruding from its exoskeleton I think, damn... Nature is metal.

Kevin Schafer/Getty Images

Should we interest astir fungal pandemics?

Pretty overmuch every large harvest that humanity depends connected is threatened by a fungal pathogen. Rice, wheat and maize correspond the biggest and astir important root of calories for the quality population. If a fungal pandemic were to rip done the harvest supply… well, it mightiness not beryllium arsenic frightening arsenic the bitey, caput controlled "zombies" of The Last of Us, but it could beryllium devastating successful a antithetic way.

What's concerning researchers contiguous is the emergence of fungi which are resistant to antifungal drugs. According to a paper published successful the diary Science successful 2018, crop-destroying fungi accounts for astir 1 5th of perennial output losses. They constitute that "[t]o debar a planetary illness successful our quality to power fungal infections," we request to beforehand the find of caller antifungal drugs and guarantee our existent usage of pesticides and chemicals don't springiness emergence to much worrisome strains. 

Another consideration? A dual pandemic -- 1 that lowers the immunity of humans to specified a constituent that pathogenic fungi tin instrumentality hold.

Consider COVID-19. During the tallness of the pandemic, patients with COVID-19 were sometimes presenting with fungal diseases. Researchers investigated cases of "mucormycosis," which is caused by achromatic fungus, successful 18 countries successful 2022, penning that it's an understudied and poorly understood complication of terrible COVID-19. It seemed to impact males much than females and was predisposed to those with diabetes, an underlying information that tin impact immunity.

While it's 1 of the freakiest apocalypse scenarios and makes bully fodder for sci-fi TV, Cordyceps is improbable to trim humanity's numbers by the billion. But the force is retired determination and we should beryllium prepared. Right now, we're not.

Updated Jan. 18: Closed captions marque it wide the doc astatine the opening of the amusement is Dr. Neuman, not Dr. Newman. We've changed the spelling successful this piece.