TLOU Tales – Episode 3: The Realities of The Last of Us

The Last of Us has taken the world by storm – and its close attention to scientific detail has impressed the masses. In this episode of our series, I delve into the science with Elaine Cloutman-Green, a Consultant Clinical Scientist working in Infection Prevention and Control at Great Ormond Street Hospital NHS Foundation Trust. Specifically, I wanted (or perhaps needed) to know the realities of natural immunity to fungal diseases, vaccine development, and the evolution of mind-controlling parasitic fungi – all major topics in the show’s storyline.

The plot of The Last of Us is driven by the character Ellie being immune to the virus – and Joel (the protagonist) must deliver her to a lab to try to create a vaccine. It’s an ideal scenario and classic trope – the saving grace. But what’s the likelihood of someone having natural immunity in this situation? “Humans and fungi are phylogenetically grouped together as Eukaryotes, meaning that human and fungal cells share many characteristics. The result of this is that treating and responding to fungal infections can be more challenging than responding to prokaryotic infections from bacteria,” says Cloutman-Green. “There are also some fungi that have co-evolved with humans and act as natural colonizers, such as the Candida species, although they can be opportunistic pathogens. In short, the immune dynamics of human–fungal interactions are often highly complex. Indeed, fungal disease is often a result of either a lack of immune recognition or over-activation of immune responses,” she says.

We can take it, Cloutman-Green – tell us straight. “Some people are therefore definitely more prone to fungal infections but natural immunity via, for example, not having receptors, is unlikely. However, because the infection process in The Last of Us is complex and includes immune modulation and other chemical changes, it is possible that some individuals may be less impacted.”

Cloutman-Green goes on to tell me that many of the issues encountered with developing fungal vaccines are similar to those with natural immunity, such as complex disease processes and shared biological traits between humans and fungi. “Some dimorphic fungi will even change structures from hyphal to yeast form during different infectious stages, and therefore even the cellular structures will change. There is also a risk of inducing immunological cross-reaction, where a fungal target could lead to autoimmunity in some people against their own cells.”

Moral of the story? You almost certainly do not have special immunity and developing fungal vaccines is challenging – and there’s a long way to go (1). Perhaps cross your fingers.

Keeping it real

Finally, we’ve left with the big, essential plot-driving question: Could a parasitic fungus realistically evolve to control humans – whether that’s Cordyceps or another culprit? Fortunately, Cloutman-Green doesn’t think so – and we have the “complexities of human behavioral processing” to thank for it. 

That said, she does cite the emerging knowledge of the link between specific microbiomes and depression, which suggests that microorganisms can influence brain chemistry and behavior. “We also know that rabies alters the way that humans respond to both light and hydration,” she adds. However, “I think the biggest barrier to environmental fungi evolving in this way is the temperature that humans and mammals work at versus insects, which means fungal growth would be inhibited or halted. If it did occur, it would likely require thousands of years of co-evolution rather than a dramatic overnight shift because there are far too many processes that would need to be overcome.”

In recent weeks, there has been an influx of articles (much like this one) covering The Last of Us – “The Threat is REAL” covers my Google search pages when all I’m looking for is background on the show and its scientific concepts. I asked Cloutman-Green what she thinks we should actually take away from fungi’s current spot in the limelight, which circles us back to the pathogen’s under-resourced and under-represented place in clinical microbiology.

“We need more recognition of how specialist an area this is – and we need investment to further develop that knowledge and expertise,” she emphasizes. “Although fungal zombies are highly unlikely, Candida auris has shown us that there are other fungal infections that will impact our hospitalized patients. We also know that millions of people around the world suffer life altering infections linked to fungi every year – and these patients are often overlooked.”

Read the rest of our TLOU Tales series here:
Episode 1: The Culprit of Humanity’s Downfall
Episode 2: The Devil Is in the Details
Episode 4: Living with the Living Dead