In a recent early-release article published in the journal Emerging Infectious Diseases, researchers review our current knowledge of fungal pathology and use it to discuss the plausibility of an impending catastrophic global fungal pandemic as depicted in the popular Home Box Office (HBO) television series, 'The Last of Us.' In the TV series and the game upon which it is based, a fungal pandemic caused a member of the Cordyceps species, reducing the world to a zombie-infested apocalypse. This article reveals that while the global lack of preparedness against a fungal pandemic is accurate, the slow rate of fungal evolution and pathologies of currently extant fungal strains make a scenario as portrayed in the series unlikely, at least for the next few 10,000 years.
The Last of Us and the Question of a Fungal Pandemic in Real Life. Image Credit: Hyde Peranitti / Shutterstock
The success of The Last of Us and how it affects public perception of fungal pandemics
The Last of Us is an American post-apocalyptic drama and horror television (TV) series starring Pedro Pascal and Bella Ramsey, aired on the Home Box Office (HBO) since January 2023. Based on the acclaimed video game franchise of the same name created by Naughty Dog, the series takes place against the backdrop of a global fungal pandemic that changes the infected into mind-controlled zombies.
The series has been met with unprecedented public interest, with its season one premiere being the second-biggest HBO series release since 2010 (4.7 million day-one viewers). Within two months of release, the show's average viewership rose to 40 million per episode, one of the highest for any series within the genre. Unfortunately, the series' detailed storytelling of the fungal pandemic has sparked public concern regarding the plausibility of a similar pandemic occurring in real life.
So great was the perceived public alarm, especially in the United States of America (US), that the US Centers for Disease Control and Prevention (CDC) felt compelled to debunk the series' scientific validity in a public Twitter (now X) post. The present article explores current immunological knowledge of fungal pathogens to scientifically substantiate why the likelihood of fungal-mind-controlled human zombies is much lower than a viewer would expect.
Do fungal pathogens have the potential for human annihilation?
Of the more than 5.1 million fungal species estimated to exist, approximately 148,000 have been characterized, only a few hundred of which are capable of causing infections in humans. The World Health Organization's (WHO's) recent fungal pathogen priority list attributes 1.6 million human deaths to fungi annually.
While the growing global number of immunosuppressed individuals results in a worrisome trend of increasing worldwide fungal susceptibility, the current potential of fungal infections pales to those of bacteria and viruses. For example, during the recent coronavirus disease 2019 (COVID-19) pandemic, a single viral species (SARS-CoV-2) was able to infect more than 700 million individuals and result in almost 7 million deaths in less than four years, many times the cumulative mortality and morbidity toll of all fungal pathogens put together.
However, while the likelihood of fungal pathogens directly wiping out humanity is extremely low, their potential to cause a collapse in human population size through other means is not. In particular, fungi represent the primary plant pathogens, with 80% of all known plant diseases being fungal in origin. This confers fungi with the ability to significantly affect food production, thereby severely escalating the already dire global food crisis.
" Cryphonectria parasitica eliminated almost 4 billion sweet chestnut trees in the eastern United States after its geographic introduction, Magnaporthe oryzae has destroyed rice crops, and Puccinia graminis has emerged as a major risk for grains. Panzootics can be caused by fungi, even threatening to evolve into extinction-level events; a recent example is the emergence of chytrid fungi that have menaced numerous amphibian species."
Can fungi make us zombies?
In short – no. While 'zombie fungi' do exist – The Last of Us portrays the species-jumping evolution of the zombie-ant fungus, Ophiocordyceps unilateralis or Cordyceps, a natural fungus that infects insects (mainly ants) in tropical forest ecosystems, hijacking their bodies to facilitate its reproduction and spread, fungal hijacking of human bodies remains unlikely. This is primarily due to none of the Cordyceps species infecting lower vertebrates, let alone humans.
"Cordyceps species are ubiquitous: >100 have been described, they are species-specific, and >35 of them perform "mind control" in their hosts. The Cordyceps name is derived both from Ancient Greek and Latin: κορδύλη means truncheon and ceps means head. O. unilateralis, upon infecting an ant, modifies the host's behavior, leading the ant to move to a specific tree-branch height before it dies; the fungus then destroys the host body and sheds fungal spores (from an ideal height) for further fungal dissemination in the environment."
Other brain-altering fungal human pathogens are prevalent, notably the rabies virus, the common cold virus, and, most accurately, the brain-eating Naegleria fowleri (which causes primary amoebic meningoencephalitis). However, none of these are fungi. Given fungi's extremely slow adaptation rates compared to bacteria and viruses, the plausibility of a species-jumping, human-infecting zombie fungus is close to zero.
So, we're safe, right?
Not entirely. While no publicly available military records on the weaponization of fungal pathogens exist, our clinical support in the event of a pandemic is alarmingly limited. Given their eukaryotic nature, anti-fungal clinical interventions are severely hampered, with only four known anti-fungal agents extant and no commercially available fungal vaccines currently available. Our diagnostic capacity for fungal infections, especially novel ones, remains disconcertingly limited.
The increasing emergence of drug-resistant fungal pathogenic strains and the global-warming-spurred evolution of novel pathogens (e.g., C. auris) means that we are not prepared in the unlikely event of a fungal human pandemic.
So, what do we take away from the series?
The current unprecedented COVID-19 pandemic and fears involving the emergence of the next devastating global disease present two major implications – increased viewer resonance between the premise underpinning The Last of Us and concern for the real-world consequences of a series-like pandemic. Fortunately, we do not need to believe everything television presents us.
"The Last of Us leave(s) viewers with a perhaps dangerous and misconstrued perception about how the preparedness of the scientific and public health community to deal with pathogens and pandemics could lead society into an Orwellian dystopia. The Last of Us is not upon us, neither biologically nor psychologically; humankind's response in reality might, we believe, be far kinder than what is portrayed here."
Emphasizing this, the WHO has not included fungi in its priority lists either for pandemic or biological weapon research, highlighting the implausibility of a human fungal pandemic, at least for the next 100 generations.
The Last of Us | Official Trailer | Max
The long-term cardiac impact of COVID-19