Is ‘The Final of Us’ Fungal Outbreak Potential? A Scientific Investigation

HBO’s Chernobyl was a masterful collection dramatizing the 1986 nuclear reactor meltdown on the eponymous energy plant. The Craig Mazin-directed restricted collection dominated the cultural dialog in our pre-pandemic world, incomes vital reward and a few Emmys. At Science we had been most serious about how carefully Mazin and co. had been capable of follow real-world science. Seems, they did a very good job.

Mazin’s subsequent HBO outing is The Final of Us, based mostly on the 2013 survival-horror online game of the identical identify.’s personal Sean Keane has described the present, which debuted on Sunday, as “the best online game adaptation ever made.”

The Final of Us imagines a world ravaged by a fungal apocalypse brought on by a creepy, mind-controlling fungus referred to as Cordyceps. That fungus is actual, so I’ve naturally been questioning simply how doubtless a fungi apocalypse actually is. 

The concept has been investigated within the context of the sport many instances, however HBO’s model of the Cordyceps mind an infection is barely totally different to the one sport developer Naughty Canine first conjured in 2013. 

What follows is an investigation of the plausibility of a fungal pandemic, brought on by a Cordyceps-like pathogen that adjustments human conduct. I will assume you are no less than considerably acquainted with the story of Joel and Ellie, the 2 protagonists making their means throughout the ruins of a post-apocalyptic USA. I am additionally going to say on the high that that is an examination of a fictional world, so there’s at all times wiggle room for the story to develop in sudden methods. It isn’t meant to be a medical doc, so hold that in thoughts and should you’re actually not within the underlying actual world inspiration for a fungal pandemic and simply need to see Pedro and Bella cook dinner (I am you, Andy Greenwald), this may not be for you.  

It additionally consists of some mild spoilers from episode 3 of The Final of Us, so should you’re making an attempt to maintain your viewing expertise spoiler-free, it is time so that you can bail. 


The actual world inspiration for The Final of Us

You may blame David Attenborough and nature documentaries for the shambling, clicking horrors that hang-out The Final of Us.

In a must-watch episode on jungles within the 2006 BBC collection Planet Earth, Attenborough and his documentary group encounter numerous behavior-manipulating fungi, together with one which parasitizes carpenter ants: Ophiocordyceps. In the clip, which has been seen on YouTube over 10 million instances, the digicam lingers on an ant with its jaws wrapped round a tree department. A ghostly violin performs as Attenborough narrates the scene.

“Like one thing out of science fiction, the fruiting physique of Cordyceps erupts from the ant’s head,” he says. 

The Planet Earth scene impressed Bruce Straley and Neil Druckmann, the director and artistic director respectively, on 2013’s The Final of Us. In a GamesBeat interview after the sport’s launch, Druckmann mentions “ripping off” the documentary and Straley says that zombie ants had been the “leaping off level” for the sport. And the sport does hew carefully to its real-world supply materials.

The life cycle of Ophiocordyceps is ugly however stunning. Ants that come into contact with Ophiocordyceps spores on the jungle flooring turn into contaminated. The fungus slips contained in the ant’s physique and begins to duplicate. It takes up residence specifically areas, just like the mind and muscle, releasing chemical compounds to control conduct of the ant. The ant is directed to the underside of a leaf, excessive above the bottom, and bites into it. Its jaw locks across the leaf due to some intelligent fungal compounds and it stays there till the fruiting physique erupts from its head. Ultimately it bursts open and releases extra spores to the bottom.

The method is extremely particular. One species of Ophiocordyceps usually infects and zombifies only one species of ant. This specificity extends to the way in which the fungus takes over the thoughts of its host. A 2014 paper explored the ant-fungus relationship, discovering that Ophiocordyceps had developed a selected set of compounds to affect conduct of 1 species of ant, however those self same compounds didn’t alter the conduct of various ant species (although the fungus will nonetheless typically kill these ants).

Our real-world understanding of the fungus has additionally modified since The Final of Us was launched in 2013.

The Planet Earth documentary was launched in 2006. On the time, the ant-infecting parasite was, scientifically, referred to as Cordyceps unilateralis. In 2007, most of the Cordyceps fungi that parasitize bugs, together with ants but additionally issues like caterpillars and spiders, had been reclassified into a special household of fungi — Ophiocordyceps. Whereas The Final of Us makes use of these two phrases interchangeably, they’re now classed as totally different genera of fungi and scientists nonetheless use Cordyceps as a form of generic identify for all of the species.

The Final of Us timeline

The pandemic’s origins are usually not revealed within the online game past a couple of stray newspaper clippings and notes, which appear to level to a South American origin. HBO’s adaptation dives just a little additional into the backstory, particularly in episodes 2 and three. This provides us just a little extra to work with when it comes to actual world plausibility.

Here is the timeline, as we perceive it.

On the morning of Sept. 23, 2003, a girl working at a flour and grain manufacturing facility on the western facet of Jakarta was bitten by an unknown human being. She grew to become violent, attacked 4 coworkers, biting three of them, earlier than being locked in a toilet and shot within the cranium.

The three coworkers who had been bitten had been executed a couple of hours later. Fourteen coworkers couldn’t be positioned.

A day later, on Sept. 24, 2003, two cops in Jakarta, Indonesia stroll right into a restaurant and interrupt Ms. Ratna, a professor of mycology on the College of Indonesia, as she’s consuming lunch. They take her to a laboratory on the Ministry of Well being the place she appears down a microscope and identifies a fungus: Ophiocordyceps. 

(Relying on the species Ratna noticed, the fungus would have doubtless been classed as a Cordyceps in 2003… a possible plot gap or pedantry?)

Ratna asks why it has been stained with chlorazol — which is usually used to determine fungal parts from human hair, nails or different specimens. “Cordyceps can not survive in people,” she tells the police officer. She then examines the corpse of the girl who labored on the flour and grain manufacturing facility. She cuts open the chunk wound on the girl’s leg and rummages round in her mouth, discovering the corpse has been colonized by Ophiocordyceps.

After making her discovery, she makes a suggestion: The officer ought to bomb the town and everybody in it. 

On Sept. 26, 2003, the outbreak hits the US. That is dubbed Outbreak Day. In Austin, Texas, the primary indications of bother are apparent as ambulances screech by the town at round 3:15 p.m. 

Within the early hours of Sept. 27, the outbreak reaches vital mass and the streets turn into chaotic. Planes are crashing into the bottom. Highways out of Austin turn into blocked by the navy. Members of the general public have, in opposition to the recommendation of the emergency broadcast system, fled their houses. 

By Monday, Sept. 29, Joel explains to Ellie, “every thing was gone.”

Ellie sits in room with grass on the floor as Tess talks to her in The Last of Us.

In The Final of Us, humanity tries to select itself up 20 years after a mutant Cordyceps fungus kickstarts a pandemic.


So, might it occur?

The brief reply is: It is unbelievable. The longer reply? Perhaps, however with a ton of caveats

There are two key plot units that underpin the fungal pandemic within the TV model of The Final of Us — local weather change and the way the fungi reproduce.

The Final of Us units up its first season with an interview section that takes place in 1968. Two fictional researchers are discussing pandemics on a chat present. One in every of them, Dr. Neumann, says he isn’t frightened of micro organism or viruses kickstarting a pandemic, in contrast to the opposite visitor. What scares him most is fungi. Principally as a result of they do not simply kill the host, however take it over. 

The viewers laughs (and after the previous three years, you would possibly too). Then 35 years later within the fictional world, that is precisely what occurs.

In the actual world, scientists have typically questioned why bugs, vegetation and amphibians are so inclined to fungal illnesses. Analysis has proven that regulating physique temperature, or homeothermy, is a good barrier in opposition to fungal an infection. Fungi thrive in cooler environments and that is why they’re potent enemies of bugs, amphibians and vegetation. It additionally means they don’t seem to be as massive a hazard to hot-blooded animals, like ourselves. Fungi even have to have the ability to take up human tissue, which they principally battle to do, and even when they handle to invade us, they nonetheless need to deal with a strong human immune system.

People can be contaminated by fungi, although. Candida, a yeast which causes thrush, is a potent species. A multidrug-resistant species, Candida auris, is of main concern in hospitals. There are additionally molds, which trigger athlete’s foot and ringworm. Generally, these fungi evade our defenses, particularly these of us with compromised immune techniques. 

“The one factor it’s a must to bear in mind with fungal infections is that they predominantly infect folks with an underlying situation,” Julianne Djordjevic, an affiliate professor on the College of Sydney who research fungal an infection of people, tells

Issues are altering, although. The world, ours and the one in The Final of Us, is heating up. “What if, as an illustration, the world had been to get barely hotter?” the fictional Dr. Neumann asks within the premiere. Increased temperatures might see fungi slowly adapt and evolve to resist the varieties of warmth they may expertise inside a human physique. Some scientists imagine that is why Candida infections is likely to be on the rise

One other species referred to as Ophiocordyceps sinensis, discovered on the Tibetan plateau, supplies a possible counter. The species has lengthy been utilized in Chinese language medication and a number of the compounds it creates have been studied for his or her anti-cancer properties. Nevertheless, in 2018, mycologists confirmed local weather change — along with overharvesting — was resulting in a decline within the species. The Himalayas are significantly susceptible because the world warms and, no less than for this species, adaptation and evolution aren’t protecting tempo. Maybe we’re warming the world too rapidly for fungi to adapt.

Spores and tendrils

However how does Cordyceps unfold? And so quick? As an ascomycetes, or sac fungi, the Ophiocordyceps that inhabit Earth’s temperate jungles propagate and survive by way of spores. It is a part of their life cycle: infect an ant, take it over, create a fruiting physique, launch the spores, begin once more.

HBO’s adaptation makes one big change from the online game: spores aren’t the way in which Cordyceps strikes between folks. Mazin has mentioned that is principally as a result of spores would imply all people must put on a masks on a regular basis (I am unsure that is significantly true however it will be fairly clunky in a TV present). Nonetheless, the variation replaces spores with “tendrils” and bites from contaminated folks, two issues we’ve not seen as infectious brokers in the actual world. They’re additionally affected by proximity. Whereas spores can journey a whole lot of miles, tendrils and bites want shut contact.

That is the hardest a part of this pandemic to sq., however The Final of Us tries to supply a artistic resolution as to how society collapsed. 

Joel wearing a gas masks punches an Infected in a dimly lit room. Torchlight provides a silhouette of the Infected against a green and white wall.

Within the online game, Joel and Ellie generally don gasoline masks in areas of dense Cordyceps spores.

Naughty Canine

Early within the collection, as Joel and Ellie are wandering by the wreckage of civilization, Joel briefly touches on the accepted narrative of the pandemic’s origins: Cordyceps mutated. Then the fungi obtained into the meals provide — issues like bread, sugar and cereal all carried the mutated pressure — and that meals provide was shuttled across the globe. 

There may be precedent for this type of factor. The Nice Famine, which ravaged Eire within the 1840s and 1850s, was brought on by an organism just like a fungus, referred to as Phytophthora infestans, destroying potato crops. Although it did not instantly infect and kill (or “thoughts management”) people, it reveals we’re no less than inclined to fungi in ways in which don’t get a lot consideration.

However the tendrils are nonetheless an issue for plausibility, even when their benefits for contaminated group are partially defined in an early episode.

“The fungus additionally grows underground,” Tess, one other survivor who companions with Joel, explains to Ellie in an early episode. “Lengthy fibers like wires, a few of them stretching over a mile. You step on a patch of Cordyceps in a single place and you’ll wake a dozen contaminated from elsewhere.” This connection might alert contaminated to uninfected and make it close to inconceivable to keep away from them, however within the early phases of the pandemic it will take some extraordinarily inept authorities responses to actually take off.

Perhaps not so unlikely, given what we find out about the newest pandemics…

Nevertheless, this alteration would require a significant evolutionary deviation for Ophiocordyceps. Supplied the Cordyceps that Ratna sees down her microscope and the Cordyceps in the actual world are essentially the identical, it will imply the fungus has essentially modified on a genetic degree to one thing solely alien. It will even be uncommon for these fungi to then be in meals crops except these crops are extremely contaminated with ants or spiders or moths. 

Overcoming these challenges we nonetheless need to get to a spot the place the fungus can management the conduct of a human being. Whereas fungal compounds can alter the human thoughts (suppose LSD, as an illustration, which was remoted from a rye fungus), the precise compounds required to make people extra aggressive and assist unfold the an infection would require a miraculous evolutionary leap for Ophiocordyceps.

Regardless, there a number of challenges for a mutated fungus to beat. Maybe these shall be defined in later episodes.  

Oh and a closing word: It isn’t that spores do not exist in HBO’s The Final of Us actuality. In episode 2, Ellie asks “so there aren’t tremendous contaminated that explode spores on you?” The response comes from Tess: “Shit, I hope not.” If spores aren’t a difficulty for an infection then why are they talked about on this means? Plot gap or potential unexplored an infection pathway?

a cordyceps infected wasp species with two yellow, budding stalks protruding from its back

At any time when I see an insect with Ophiocordyceps stalks protruding from its exoskeleton I believe, rattling… Nature is steel.

Kevin Schafer/Getty Pictures

Life and dying 

One of many under-examined parts of the Final of Us fungal pandemic is the decades-long survival of sure varieties of Contaminated. Let’s put the “Clickers,” an contaminated that first seems in episode 2, below our microscope.

In episode 2, Ellie asks Joel and Tess about contaminated with “break up open heads that keep at nighttime like bats” as they’re strolling towards their rendezvous level in Boston. Joel and Tess keep silent, giving a understanding look at one another. They know precisely what Ellie is referring to: the Clickers.

Clickers are usually present in damp, darkish locations like deserted buildings, sewers and basements. Locations with none mild. There is a good in-game motive for this: Daylight and airflow do not create the best situations for spores to contaminate somebody sufficient to show them into Clickers. With the spores being eliminated within the TV present as an an infection mechanism, the pathophysiology of Clicker an infection is just a little tougher to discern.

Clicker’s skulls have fully been overtaken by Ophiocordyceps — to the purpose the place they not have eyes — due to the mind an infection. The bat analogy Ellie makes use of is apt as a result of Clickers are named for the blood-curdling sounds they use to navigate the world. With out eyes, they should echolocate, similar to a bat or a dolphin. 

Whereas Clickers provide up essentially the most horrifying instance of the Contaminated within the present to date (maybe, apart from one other sort of contaminated Ellie makes reference to in episode 2), additionally they current essentially the most issues for a scientific eye. For one, Contaminated take months to years to turn into Clickers — how is a fungus going to forestall human tissue from breaking down?

Dr. Neuman, the scientist within the opening episode, supplies one thing of a solution, suggesting that sure sorts of fungus do produce compounds that we use medicinally. As an example, penicillin. Micro organism, that are a key element of tissue degradation after dying, have been at warfare with fungi for eons. Because of this some fungi have developed defenses that people have co-opted. Penicillin is one, Cyclosporin — an immune inhibitor — is one other.

So, theoretically, fungus can make chemical compounds which can be helpful for people however we’re once more in Excessive Evolutionary Leap territory. The Clickers and different long-term contaminated ought to be falling aside 20 years after the pandemic started. 

Ought to we fear about fungal pandemics?

Just about each main crop that humanity is determined by is threatened by a fungal pathogen. Rice, wheat and maize symbolize the largest and most vital supply of energy for the human inhabitants. If a fungal pandemic had been to tear by the crop provide… effectively, it may not be as scary because the bitey, thoughts managed “zombies” of The Final of Us, nevertheless it could possibly be devastating differently.

What’s regarding researchers at present is the rise of fungi that are proof against antifungal medicine. In accordance with a paper printed within the journal Science in 2018, crop-destroying fungi accounts for about one fifth of perennial yield losses. They write that “[t]o keep away from a world collapse in our capability to regulate fungal infections,” we have to promote the invention of latest antifungal medicine and guarantee our present use of pesticides and chemical compounds do not give rise to extra worrisome strains. 

One other consideration? A twin pandemic — one which lowers the immunity of people to such a degree that pathogenic fungi can take maintain.

Contemplate COVID-19. In the course of the peak of the pandemic, sufferers with COVID-19 had been generally presenting with fungal illnesses. Researchers investigated instances of “mucormycosis,” which is brought on by black fungus, in 18 nations in 2022, writing that it is an understudied and poorly understood complication of extreme COVID-19. It appeared to have an effect on males greater than females and was predisposed to these with diabetes, an underlying situation that may have an effect on immunity.

Whereas it is one of many freakiest apocalypse eventualities and makes good fodder for sci-fi TV, Cordyceps is unlikely to scale back humanity’s numbers by the billion. However the enemy is on the market and we ought to be ready. Proper now, we’re not.

Up to date Jan. 18: Closed captions make it clear the physician in the beginning of the present is Dr. Neuman, not Dr. Newman. We have modified the spelling on this piece.   
Up to date Jan. 22: Ibu is an honorific for girl in Indonesian, fairly than Prof. Ratna’s first identify. Added the part “life and dying” after Clickers first look.

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