The Last of Us, HBO’s hit series that culminated its season finale on Sunday, is an adaptation of a video game that takes place in a dystopian post-apocalyptic world overrun by zombies. Smart-mouthed infected but immune teen, Ellie (Bella Ramsey), and short-tempered borderline-humorless smuggler, Joel (Pedro Pascal), fight their way from Boston, cross country, to the Fireflies, a rebel faction of freedom, all with the hopes for a possible cure.
The series is about their journey and fight for survival in a world that has been decimated by a parasitic fungus that turns humans into zombies. This review is not about whether or not the show is good (it is!), but more disturbingly, is it possible in the real world.
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A Fungus to Blame
The opening of the series is an aged video of Dr. Neuman on a talk show in 1968, smoking, and explaining how fungal infections have never happened on the pandemic level to humans because (in this fictional world) fungus does not typically survive in our bodies due to temperature. But the question he poses decades before it comes to fruition [in the show] is this: what if the world itself is warmer and fungus evolves, until it must survive in a higher temperature—a higher temperature that is exactly our body temp. Given the rate of climate change, this dystopia seems plausible.
In the real world, fungal infections are already a growing problem, as the pathogens are starting to evade the few antifungal medicines we have to treat them. Last year alone, over 7,000 people died from a fungal infection, according to the Center for Disease Control and Prevention. Scientists have been trying to find ways to tackle a similar problem, bacteria developing antibiotic resistance for years, with limited success. And not to be a downer, but as Belinda E. Ostrowsky, MD, field medical officer for the CDC, Division of Healthcare Quality Promotion in New York City, says, “antibiotic resistance is an epic problem.”
The opening episode introduces us to the main characters and their parallel storylines before they meet. The initial investment in Ellie and Joel pays dividends for all nine episodes in this inaugural season. Episode 1 is a sign of things to come, scenes that shatter your heart and give you nightmares. The series is not for the faint-hearted. It also takes creative license with scientific fact, but as we know only too well, a scientifically possible health crisis just needs a blip in collective hubris to go full on pandemic. In 1968, Dr. Neuman was speaking in hypotheticals. In 2003, in the opening of Episode 2, a mycology (the study of fungus) professor confirms cordyceps, the particular fungus he had warned about, in a human corpse.
Episode 2 opens with the calm of acclaimed mycology researcher, Professor Ratna (Christine Hakim), in Jakarta, Indonesia, eating her lunch in a restaurant, a lunch break reprieve that is ominous because it is the “before.”
Before soldiers come to whisk her away, before she looks under a microscope at a fungus that has never appeared in a human before, before she looks the military man dead in the eye and says the only option is to bomb the city, now.
And then she wipes her tears, and she asks to be taken to her family. Cordyceps infecting humans and turning humankind into zombies seems almost too real. Not the mushroom zombies, per se, but certainly the parasitic pandemic possibilities.
What Are Cordyceps?
Cordyceps is a Chinese caterpillar fungus. It also is an herb that humans take. Google it, and you’ll find claims that it works magic with nearly nonexistent side effects. Want to boost your immune system? Help your kidneys work better? Boost your strength in stamina? Take Cordyceps!
You don’t need the cautionary tale of The Last of Us to pause that thought, as any regular reader of MedShadow knows. Research side effects before you take any new medication or supplement. And of course, talk about it with your healthcare provider.
Outside of our medicine cabinets, cordyceps is also a parasitic fungus that “takes over” ants, and grows inside them until they literally explode.
But are these zombie-producing effects of cordyceps also possible in humans? With evolution, yes. But that would require potentially millions of years’ worth of genetic change. A remarkably rapid slew of mutations would have to occur in order for it to be “real” in the near future.
The Science Behind ‘Zombies’
In other words, it is highly unlikely. That’s the good news. What’s the bad news? Cordyceps are one of three million-plus fungi in the fungal kingdom, of which we’ve only identified only three to five percent. Perhaps cordyceps is not the one to be worried about after all.
To be clear, fungi, parasites, bacteria and viruses are all different things. A parasite is an organism that requires a living host in order to survive. Many—thought not all—fungi are also parasites. This is why in The Last of Us cordyceps, a parasitic fungus, uses the hive mind to search out potential hosts and overtake them and reproduce. Zombies have been “created” in the realm of sci-fi for years. This just happens to be the video game, and then television series, creators’ take on how it might happen.
On the other hand, non-parasitic pathogens, including some fungi and most bacteria and viruses, can survive on the living and the dead (think COVID-19 and germs on countertops). Antibiotics can destroy most bacteria and some parasites. However, antibiotics cannot destroy a virus or a fungus. Vaccines are for viruses. Usually. Antifungal medications are for fungi (though as mentioned above, some fungi are evolving to evade existing antifungal medications.)
In late 2021, the World Health Organization recommended the first vaccine for a parasite, malaria. While malaria is indeed a parasite, it is nothing like a fungal parasite. We are a long way from vaccines for parasites being as common as they are for viruses.
Ellie and Joel spend nine episodes traversing through dystopian hell to find a community that will save them all, with a cure using Ellie’s blood by creating a vaccine for cordyceps. In both our world and The Last of Us, this has yet to be achieved. But there is a “watchlist” of sorts, with the alarming title The WHO Fungal Priority Pathogens List (WHO FPP) that divvies up fungal pathogens into three categories; critical, high, or medium priority of concern.
Cordyceps are not on the list. Cryptococcus neoformans, Candida auris, Aspergillus fumigatus, and Candida albicans all make the critical list. If there is a sequel to The Last of Us or another blockbuster iteration, these four might be the parasitic star of the show. Or perhaps mucormycosis, one of the newest in a wave of deadly fungi that kills up to half of COVID patients who also contract mucormycosis, often while already hospitalized. The intention of WHO FPP is to bring awareness and research funding to combat invasive fungal diseases (IFD). I, for one, am rooting for pharmaceutical success.
Mushrooms and Their Spread
If fungi had a popularity contest the probable winner would be the mushroom. It is what the zombies transform into in The Last of Us, infected humans turned to zombies with mushroom-cap-like heads, and definitely not a shiitake.
The zombies are “breathing into” their victims for a reason in this show. Their contaminated breath “poisons” a healthy person, converting them into an infected, zombie-like creature. A mushroom is a fruiting body. The stalk and the mushroom cap are its reproductive structure, and it releases spores into potential hosts in order to reproduce.
The show, as it does at several points, decides to deviate from the video game when it comes to the fungus-spreading methods. Instead of airborne spores, yellow dust clouds, and rooms so thick with particles you cannot see, the show opts for a mouth-to-mouth or bite transfer. The change makes cinematic sense (it is tough to watch scenes if the spores make it too dense to see). But it also gives writers some liberty in how the zombie pandemic spreads.
What is the best protection? Unsurprisingly, a mask. No one in The Last of Us is wearing a mask (although they do in the video game), but fair enough because masked characters may be harder to visualize and empathize with overall? It would also make the zombies’ spooky and gross mouth-to-mouth a moot point.
Joel is probably escorting the survival of humanity. Ellie has a natural immunity, presumably since she has been infected via bites and is the only person we know of to not turn into a zombie. Spoiler alert: you will see in the season’s finale how she possibly obtained the immunity.
Very real innate and adaptive immunity adapted for a fictive evolved bacterial infection is not exactly backed by scientific research. In a video game or television show it is more like scientific conjecture. However, it is more likely that, if we follow the scientific conjecture route, we would arrive at Ellie helping to discover The Last of Us antibiotic.
Ellie’s blood has a mutated version of the parasite, one that actually fights off its ability to infect its host by inhibiting the synthesis through cell walls. The show seems to combine the scientific strategies behind both vaccines and antibiotics to explain how Ellie developed her immunity. But really, who is paying attention to the scientific probabilities by the halfway point of battling The Infected?
A Cure for Zombies
In Episode 5, Ellie and newfound friend, the young Sam (Keivonn Woodard), sit in a dimly lit abandoned and disheveled hotel room. This is their second episode together, with Ellie, Joel, Sam, and his older brother Henry (Lamar Johnson) surviving a shoot-out with vengeful resistance leader Kathleen (Melanie Lynskey) and her militia, only to endure a horrific all-out battle scene with The Infected. After a previously aired emotionally gutting Episode 3, viewers are probably looking for a little redemption.
As Ellie is about to turn off the lights in the hotel room, Sam, who is deaf (in the show but not the game), writes Ellie his question on his dry-erase board, “Are you ever scared?” He then shows Ellie that during the battle with The Infected, he was bitten on the leg. Ellie assures him it will be alright, that her blood is medicine, and then proceeds to cut herself and press her blood into Sam’s open wound.
Ellie perhaps feels a sense of love and family with Sam, and she is also a teenager. The unbridled, yet baseless, self-confidence is brimming. In a post-apocalyptic world with a mostly destroyed historical record, there is no reason for Ellie to know about blood-transmissible diseases, let alone of a historical epidemic like AIDS. We know, of course, that the science is more complicated, that blood banks screen donated blood before they use it for transfusions, and that what Ellie was doing was probably more dangerous than helpful. And yet we believe as we watch. We hope.
With yet another spoiler alert, Episode 5 is a heart wrenching reminder that while Ellie’s blood may be the basis for a cordyceps cure to be developed; it is not, unfortunately, the cure alone.
Could Zombies Be Real?
Between a wave of deadly fungi, growing antibiotic resistance, and the lack of vaccines for parasites, our current medical climate is why the imagined future in The Last of Us may keep us binging the series for months to come, not to mention keep us up at night. And if that is ever to come to pass, rest assured that MedShadow will have its Side Effect Tracker to help you balance the pros and cons of vaccines, their efficacy, and their side effects!
The Last of Us season finale attempts to come full circle, by describing the origin story of Ellie’s infection and immunity. Yes, spoiler alert three: Ellie’s mom was bitten by an Infected during labor, and cordyceps entered Ellie right before she was born, essentially positing that the parasite “grew up” with Ellie, evolving into a less virulent variant.
That variant also prevents the wild, pandemic cordyceps from infecting her. For us, prior to COVID, the fastest vaccine created was for mumps in the 1960s in a mere four years. Fast forward to 2020, and the COVID vaccine was an incredible success using existing mRNA research to propel a vaccine through trials in seemingly record time.
It was with research and science decades in the making, as well as with world-wide pharmaceutical and governmental coordination. In other words, these vaccines were created in a very different set of circumstances than The Last of Us. This leads to the conclusion that the parasitic possibilities in The Last of Us definitely warrant a second season, and the vaccine possibilities, well, that’s best left to a suspension of disbelief.
When it is all said and done, the thread that keeps The Last of Us together is its humanity. Characters are trying their best in an end-of-days reality, and despite the kill or be killed narrative of a zombie dystopia, the greatest side effect of a potential cordyceps cure might be humanity itself. In the most dire and soul-splitting of scenarios, the best possible chance for survival may be the very thing that kills us all: the sense of humanity the living hold on to, fatal flaws and all.
