The Real Science Behind The Last of Us, According to a Biologist

IMAGE HBO

At the beginning of the first episode of The Last Of Us, there’s a fictional 1968 TV broadcast in which an epidemiologist talks eerily about the likelihood of a fungus-driven pandemic.

“One [fungi] gene could mutate, any one of them could be capable of burrowing in our brains and taking control not of millions of us but billions of us; puppets with poisoned minds, permanently fixed on one unifying goal, to spread the infection to every last human alive by any means necessary. And there are no treatments for this, no preventatives, no cures, they don’t exist and it’s not even possible to make them. We lose.”

Gulp.

It sets a suitably ominous tone for the dystopian series, a relentlessly dangerous world in which humans are being infected by the cordyceps fungus, turning them into blood-thirsty zombies. Blood-thirsty zombies that can run. Fast.

Dr. Neumann could very well be based on the equally knowledgeable and straight-talking Professor David Hughes. The renowned entomologist and biologist specialises in the subject of parasites, especially the cordyceps variety that causes the ‘zombie ant’ phenomenon, in which fungus takes over ants’ bodies to spread their spores. The makers of the original The Last of Us videogame saw this phenomenon on a David Attenborough documentary and brought in Hughes, one of the world’s leading experts in this subject, to work with them on the launch of the title.

One of the talks Hughes gave at this time, almost a decade ago, is as fascinating and scary as you'd imagine, but one part stands out as incredibly prescient. He talks about the risk of a global pandemic, likely coming from zoonosis: when a virus jumps from an animal to humans.

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Esquire caught up with Hughes (who now focuses his work on tackling the climate crisis, as, in his words, we’re “fucked”) for a Zoom chat about the science behind The Last Of Us and how worried we need to be about a real-world fungus epidemic:

How did you get involved with the biology behind The Last Of Us?

Naughty Dog [the game production company] were really interested in mycology and fungi in general and when they were close to production they drafted me in to give talks explaining that [their storyline] wasn’t too fanciful; that parasites can jump from one organism to another. I talked about zoological infections and how 70 percent of all our diseases come from parasites, but that it’s not the case that we’re going to be having parasites controlling our behaviour; that bit is not there, so I talked about the biology of cordyceps, how it beautifully manipulates the behaviour and how it’s a really great example of the evolution of natural selection.

In the show, the fungus gets into the food chain through grain, which eventually turns people into crazed mushroom-headed killers. How possible is that, really?

The fungal group that caused this, cordyceps, do go into plants and grain. There’s one called rye ergot. And when humans eat infected rye, they have psychotic episodes. It’s a good historical background to suggest that the Salem witch trials were caused by people eating infected rye. There’s lots of other documented cases, like St Anthony’s Fire, which occurred in Europe, and was an example of convulsive behaviour. The last case was in 1951 in France, when somebody sold infected bread with the fungus in it. A whole town went hysterical and a 14-year-old girl tried to kill her mother with a carving knife. Also, LSD and ketamine come from this group of fungi, so the idea the fungus can cause convulsive, abhorrent behaviour is correct, the idea that you can eat a pathogen and it will infect you, that’s also correct.

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Yikes.

Over the course of this interview, you’ve breathed in a couple of billion spores, but you’re fine because your immune system is constantly surveilling it, but if you’re compromised, the fungus will grow in your body and kill you. Fungi kill more humans a year than malaria.

The doctor in the series says this wouldn’t be treatable, is he right? How quick moving are the fungi?

It’s very slow moving, but fungi are more related to humans than they are to plants, and what kills the fungus, kills you. We haven’t developed a good arsenal of cocktails, so it’s quite easy to kill bacteria because they're very different and the chemicals that kill them won’t kill you. It’s a little bit like trying to kill cancer in your body – the chemotherapy might kill you. So that’s the problem.

You correctly predicted that the next pandemic would be something like Covid. What should we be worried about, if not cordyceps?

It’s obviously the viruses; viruses evolve much more quickly, they grow more rapidly, they buy more lottery tickets to overcome our defences. So if you have a food market in Wuhan, then you've got huge amounts of food coming in from the wildlife, something’s going to jump off from a bat, a civet, an armadillo… it’s absolutely guaranteed to happen. That’s where we got Covid from, it’s where we got Influenza from, Ebola, AIDS, all of these things were jumping, so viruses are what we need to worry about.

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How do we protect ourselves?

Well, as my T-shirt says: ‘Every disaster movie starts with somebody ignoring a scientist’. We should listen to technical experts. Technically we can stop these things, but we then break the rules. That’s the problem with human societies, we act selfishly, rather than collectively. So ants are really good at controlling cordyceps because they have that collective immune system inside the colony, they can even wall off their collective siblings who are infected, and the sibling is completely fine with this because her genes are in the ones who are going to survive, and is happy to be walled off. But people aren’t happy to be walled off.

So the animal world is more protected against the threat than humans, because we’re essentially selfish?

Exactly!

Wait… does that make us the worst parasite on earth?

Yes. Changing the climate is clearly the worst of all possible actions.

Have you worked on any other zombie-plague movies or TV shows?

Yes, I worked on World War Z, and I suggested the idea of the zombies moving in concert, in tandem, based upon kin selection. Every zombie movie that you look at… let’s say I’m infected, we’re in a room, I attack you, then there’s someone else, you and I are pushing each other to get out of the way to get to that third person. That doesn’t make any sense whatsoever from an evolutionary perspective, because the virus will make itself identical to you, it doesn’t matter which one of us bites the next person, it only matters that we collaborate and the next person is bitten. So when you look at the Jerusalem wall in World War Z, the zombies climb up on top of each other to go over the wall and that’s what evolution biology predicted. That was a good example of bringing better science into play for educating the audience.

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I have to ask: have you watched Parasite, and, from a biologist’s point of view, was it true to the nature of a parasite?

It was phenomenal. Parasite the word comes from the Ancient Greek parásitos, which means to eat at another person’s table. So this is the concept of the word and the family is living downstairs, being on the periphery… these are all the factors of a parasite. Parasites are the most common life form to evolve on planet Earth. It’s evolved more than predators, and most things in the world are parasites, because there’s always a way to get more food from another organism, so I thought it was a really interesting take on it.

FromEsquire UK

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