This article contains spoilers for The Last of Us, Episode 9, “Look for the Light.”
For its entire first season, The Last of Us attempts to sell the audience (and one of the show’s two protagonists, the teenage Ellie) on a promise: that her immunity to the Cordyceps fungus means that she is the cure to saving humanity. However, it isn’t until the series’ final episode, “Look for the Light,” that we hear about the actual plan to make that cure.
In the final episode, Ellie (Bella Ramsey) and Joel (Pedro Pascal), her protector and father figure, are ambushed and knocked out by patrols guarding the base of the insurgent Firefly faction, as they finally reach the goal they’ve been journeying to all season. When Joel eventually wakes up, he is without Ellie in a hospital room with Fireflies leader Marlene, who goes on to explain that they’ve taken Ellie to perform a surgery to make a cure.
This is what Joel expected, but the details of the plan are horrifying. The experimental design for making this cure, as Marlene explains it, is based on their doctor’s hypothesis that “the Cordyceps in Ellie has grown with her since birth.” At the start of the episode, we see a flashback of Ellie’s mother getting bitten by an infected near her femoral artery while she’s in labor, and then quickly cutting the umbilical cord after giving birth—meaning that infant Ellie got just enough of the Cordyceps infection in her bloodstream to render her immune but not enough to kill her. Marlene, Ellie’s mother’s close friend, came on the scene after the birth, and took charge of the orphaned infant.*
Marlene continues by explaining that the Cordyceps in Ellie “produces a kind of chemical messenger” that tricks any future Cordyceps her body encounters into thinking that she, too, is the fungus. The Fireflies’ plan, as Marlene describes it, is to remove the cells that produce this “messenger” in Ellie, multiply those cells in a lab to produce more of the same, and then administer them to everyone, bringing an end to the two-decade-long fungal pandemic.
The bad news is that Cordyceps grows inside the brain, and so the Fireflies are going to kill Ellie. But fear not, because Joel goes full Rambo, saving Ellie before she goes under the knife, leaving a mass grave of Fireflies in his wake.
But does any part of this unnamed doctor’s plan make any sense at all? Dr. Arturo Casadevall, fungi expert and chair of the department of molecular microbiology and immunology at Johns Hopkins Bloomberg School of Public Health, is pretty adamant that it does not. I read him Marlene’s speech, and he says, to start: “Trying to get a scientific explanation out of that is tough.” Casadevall takes Marlene’s description of the mechanism to mean that Cordyceps produces a molecule (the “chemical messenger”) in Ellie’s brain that signals that she is a zombie. “It is possible,” he’ll allow, “to elicit an antibody response to a small molecule.” In real life, “the way that [a vaccine] would be done is you would get the Cordyceps and you would grow it in a way that it produces the molecule. And then one would use analytical chemistry to isolate the molecule,” which an immunologist would use to create a vaccine formula that would allow someone to produce antibodies upon injection.
However, Casadevall stresses, you definitely wouldn’t need to kill anybody in order to obtain the sample. “You could just get a brain biopsy. You can get a good chunk,” or, even better, “you could get somebody who’s dead and infected. You could just get [the molecule] from that brain.” And as for getting ahold of this molecule, one would think you could use just a blood sample, but Casadevall is willing to play the show’s game: “If it was secured in the blood, you could just get it off the blood. But, I mean, it may be that it’s only produced [in the] brain tissue.”
But Dr. Stuart Levitz, professor of medicine and microbiology and physiological systems at UMass Chan Medical School, finds the idea that an immune response would be only in the brain to be, well, science fiction: “It really doesn’t make any medical sense to me, or immunologic sense. I mean, even with people with brain infections—and in my lab I study a fungus that mostly infects the brain—people have immune cells in the blood that have activity against the fungus. You wouldn’t have to remove a brain in order to study the cells.
“You could try to see what sort of antibodies she has in her blood or what the T-cells, the immune cells in her blood, are doing,” he offers. “I mean, it seems like a totally crazy idea [that] you’re going to find some chemical being made that leads to immunity that’s just in the brain and that’s nowhere else. It doesn’t hold up that she could have become immune from birth to this thing, and now you’re finding the cells that are being made and they’re only in the brain.”
Both scientists agree that there are many ways you could try to create a vaccine via less invasive and more ethically sound methodology, including the aforementioned suggestion of attempting to grow Cordyceps in the lab. That way, you could then attempt to figure out the “Achilles’ heel” for Cordyceps, or to “attenuate it and weaken it so it gave people an immune response but it didn’t kill them,” Levitz explains.
In order to know for sure how a vaccine could best be produced, Levitz explains, you’d need more knowledge “about the biology of the fungus. How does it get into people, how does it reproduce, and how does it eventually get into the brain? It has to get [to the brain] somehow. So, if there’s a bite, does it then get into the bloodstream and then from the blood to the brain?” Levitz continues: “It seems a little suspicious that on the basis of just one person who happens to be immune because of a weird thing that happened when she was being born, you would then latch on to this hypothesis that there were chemical messengers that were in the brain, and those were so potent that they were able to prevent the fungus from multiplying.”
There’s another problem—the Fireflies mention one doctor in their group who has this grand theory of immunology and, apparently, expertise in neurosurgery? Does it make any sense that this doctor would be able to pull off vaccine development, let alone in that abandoned hospital? Let’s say they successfully got the brain tissue, and the sample has everything they need. “You need to have advanced analytical chemistry to be able to take that material and break it down,” Casadevall explains. “And then you want to know, Did I get the right thing? Because you don’t even know what the molecule is. So, in an ideal world, you would have something [nonhuman] to test it on.” You’d also need a brain surgeon with a proper facility (“You’re not going to do that under a tree,” Casadevall states) and some (ideally ethically procured) test subjects. “And then you need a first-class or world-class lab. You need neuroscience people who understand the workings of the brain. And you would need immunologists to make the vaccine. You need a scientific enterprise. … This is not going to happen in a zombie apocalypse–destroyed library or anything,” he jokes.
Even if the Fireflies obtained the proper staff and equipment, the chances that the vaccine would work on the first try are incredibly slim. “Low but not zero,” Casadevall states. Levitz agrees: “I mean, almost nothing works on the first try, especially when you only have one person. It would be pretty unlikely.” That’s why it makes no scientific sense to kill Ellie. Levitz compares the Fireflies’ proposed methodology with a farmer killing a chicken that lays golden eggs. “The premise that you would need to sacrifice one person to save the human race is an OK science-fiction premise and all of that, but if you have one person that you knew was immune … wouldn’t you want to study that person first? Wouldn’t you want to first try these noninvasive things? Because once you kill her, that’s it. If you’re trying to isolate cells from the brain that makes [what you think is] a chemical messenger—what if you’re wrong? What if it’s not a chemical messenger and it’s [instead] antibodies that her lymph nodes are making that are in her bloodstream?”
Long story short: Ellie doesn’t need to die to save humanity—in fact, it’d be better if she didn’t. Real-life science would preclude the need for Joel’s rampage, a morally queasy deed that acts as both the culmination of Season 1’s plot and the instigating incident that defines the tone of the show’s future. But in a way, this fact-check of the show’s science only further proves the show’s artistic success.
All season long, The Last of Us has depicted a humanity that’s barely worth saving, where, though there are some exemplary people, nearly every attempt at banding together is corrupt and every solitary leader (and beloved gruff guardian) is some varying degree of murderous. The Fireflies’ plan being an awful one fits the show’s worldview perfectly. If you look at the Fireflies’ idea as ridiculous and ill-informed, as these scientists do, this ending is even grimmer. Living through this pandemic has bred a climate of desperation so strong that the hope that something could be the ticket out is more than enough to ignore ethical considerations to try the most fanciful plan. Marlene doesn’t regret killing her friend’s daughter for a chance at a vaccine that’s not likely to work, and Joel doesn’t regret killing the Fireflies to stop it from happening, even though there’s the slimmest chance it could. “Look for the Light” simply drives home the idea that The Last of Us isn’t about surviving a terrifying reality, but rather clinging to the dreams, and people, we use to cope with existing within it.
Correction, March 14, 2023: This piece originally misstated that Marlene was with Ellie’s mother during her birth.