The year was 2013, and the release of a hotly anticipated zombie-apocalypse video game was on the horizon.
The game, called The Last of Us, invited players to explore what then seemed a fanciful scenario: a world devastated by a pandemic in which a pathogen kills millions of people.
Unlike in many apocalypse fictions, the pathogen responsible wasn’t a bacterium or a virus, but a fungus called Cordyceps that infects humans and takes over their brains.
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The writers at game studio Naughty Dog, based in Santa Monica, California, were inspired by real fungi — particularly Ophiocordyceps unilateralis, known as the zombie-ant fungus. The fungus infects insects and releases chemicals into the animals’ brains to change their behaviour. Ahead of the game’s release, Naughty Dog turned to scientists, including behavioural ecologist David Hughes, a specialist in zombie-ant fungi (he named one after his wife), to field questions from the media about the fungal and pandemic science that inspired the story. Hughes, who is at the Pennsylvania State University in University Park, has since moved to studying climate change and food security.
The Last of Us spawned a sequel game in 2020 and a critically acclaimed television show, the second season of which concludes on 25 May on HBO.
Hughes spoke to Nature about his experience consulting on the game and why COVID-19 changed our appetite for zombies.
What was your involvement with the game?
Naughty Dog studios asked me and a few other people who were notable in this space, including psychologists, to talk about whether we could have a global pandemic. Of course, in the intervening period, we all learnt that the answer was yes.
They asked us to go around Europe and do a series of lectures to stave off critique and provide support to the idea that infections that jump from one species into another — zoonotic infections — are not only possible, but actually they’re the predominant mechanism by which humans are infected with new parasites that cause disease. I had the good fortune to go to the studios and see the artistry that was involved, and meet the team and the voice actors of the video game.
What did you make of the science in the game?
I was really impressed by how much the game’s writers got into the science of it and started to understand things like fungi and slime moulds, and just trying to think about the ways in which these organisms do their business. They really took it by themselves and incorporated those elements into the game.
I think they were even mail-ordering slime moulds so they could just leave it out on a petri dish and examine it. And you see that throughout the game. And now in the TV programme, in the intros, they have these slime balls. The writers were geeky, and understanding fungi is not complex, so they ran with it.
The Last of Us is set in a post-apocalyptic world where millions of people are infected with a fungus that takes over their brains.
Did you play the games?
I tried and I failed miserably! I’m just a typical hopeless scientist.
Is the idea of a Cordyceps pandemic realistic?
It is not unrealistic that fungi can infect humans if they come from animals. It is unrealistic to think that they could cause the behavioural changes in humans. The writers took liberties. They had different stages about how the infection changes over time. That’s all fanciful, of course.
Looking at the second season of the TV show, it was interesting that they have this communicative nature of the spores or the fungal hyphae. That’s interesting because we know fungi are connected like that over many kilometres — for example, the mycorrhizal fungi, which are underneath root systems in trees, do that effectively.
Have you been impressed by the science in the TV show?
I often find that’s the wrong question, because I dont think the job of the entertainment industry is to impress scientists. Scientists are highly problematic individuals. It’s called the Carl Sagan effect. The more you popularize science, the less good your science is. It’s an inverse relationship. I think it doesn’t really matter. Science belongs to society, and people should tell stories about that. And, you know, snooty scientists saying, ‘Oh, you didn’t get this exactly right,’ — like, who cares?
What was your reaction when the COVID-19 pandemic happened?
I told you so! In The Last of Us lectures, I talk about the same thing. I said, the problem is not whether we’ll have zombie-ant fungi manipulating humans. It’s not going to happen. The problem is if we lose 5% of our population, and the global economy shuts down, which we saw.
Do you think the COVID-19 pandemic changed our appetite for zombie-apocalypse media?
It’s very interesting. You build a game about a dystopian future based on a pandemic, you live through a pandemic, and then what’s the relevance of the game or the movie? I think our appetite for being scared by pandemics has receded because we all have PTSD. Or, we don’t have PTSD and realized that some of us just don’t care about other people.
So it’s interesting to look at the history of zombie lore. Back in the 1950s and 60s, it was all about nuclear weapons, because we were all collectively fearful of that. And then it moved into diseases, because we had an over-populated society. Then we had a pandemic, and we shrugged and moved on. So the fascinating thing is, The Last of Us is nice, but it’s not what it used to be.
This interview has been edited for length and clarity.
This article is reproduced with permission and was first published on May 23, 2025.
