Faculty Fungus Expert Puts ‘The Last of Us’ Under the Microscope

Who better than a developer of a people-protecting, malaria-fighting fungus to turn to for reassurance that the TV series is nothing more than ludicrous, scary fun? Well, that’s not exactly what St. Leger told Maryland Today.

His reaction to the fungal mayhem depicted on "The Last of Us"—from the unpredictable impacts of global warming on infections to the very slim possibility of a poisoned food supply—might have you looking at the toppings on your next pizza a little differently.

Read on to not be wholly reassured.

Have you seen “The Last of Us?” What do you think?
The fungus in this program is really a nice touch, and if it increased interest in real fungal diseases that would be a good thing. I hadn’t seen a zombie movie for many, many years. What I found quite interesting is the survivors; it seems to be survival of the Trumpiest. They’re very territorial and tribal. They love their guns. They look kind of like people who might storm the Capitol, don’t they? I do wonder why this dystopian view of humanity speaks to us so much. Clearly, the remnants of humanity in this show would do much better working together.

Obviously, the show takes liberties with science—but are they liberties that make you groan, or clever liberties?
It’s quite clever. I’m not groaning at all. The point of storytelling since the ancient Greeks is that suspension of disbelief, and people do enjoy a delicious shudder of fear. It’s implausible, and there are many reasons this scenario wouldn’t happen with that particular fungus, which is very specialized and evolved over millions of years to infect particular insect species. Pandemics are of course common; ever since we domesticated herd animals and got their diseases, we’ve had whole masses of viruses and bacteria jumping onto us. That idea, at least, is very feasible.

As an expert in fungi, you must be flattered HBO didn’t just do another deadly virus show.
Fungi do have an advantage for television that viruses and bacteria don’t have quite so much—that element of the grotesque. The filmmakers must have been influenced by the famous David Attenborough “Life on Earth” segment when the fungus responsible for the zombies in this program begins to get hold of a carpenter ant. It begins shaking and displaying the strange zombie behavior. And then this fungus, which doesn’t have a brain, directs the ant, which does have one, to climb up a plant and take a death grip.

Did you study the fungus that makes real-life zombie ants and fictional HBO zombies?
Yes, it’s called Orthiocordyceps. (Former entomology Ph.D. student and postdoc) Brian Lovett and I wrote a paper recently suggesting that all the fungus is doing is manipulating the natural behavior of the ant. Many insects when they sleep will clasp onto something with their jaw so they don’t fall in the middle of the night. So, the zombie ant is doing all of this, and then the strange mushroom comes out of the back of its head to infect other ants. It’s ripe for being made into a movie. You just make a host shift—where fungi begin infecting humans.

How realistic is the show’s sudden host shift to humans?
It’s extremely implausible with these particular fungi. But history is replete with examples of aging scientists declaring that something is impossible, and then it turns out not to be—so I’ll refrain from certitude and say that there is a tiny possibility but with a huge number of caveats, and many evolutionary hurdles to cross.

For example, there’s a theory out there that high body temperatures like ours evolved as an adaption to avoid fungal attacks. So, the fungus would have to first of all adapt to attacking something warm-blooded. An ant’s immune system is very simple compared to ours, so the fungus would also have to adapt to that overnight. Then there’s still the question of the behavior—in the show, the infected are very aggressive. In ants, the infected ants became less aggressive, and in fact, other ants become more aggressive to them. This idea of the fungi jumping straight from attacking insects to attacking us would require a huge rewiring of the genome whereas the show seems to be implying you could do it with a single mutation.

Is the human neurological system too complex to be hot-wired like that?
Perhaps, but fungal products including ethanol and LSD can certainly do a number on our personalities.  Also, rabies does something similar with dogs. It creates aggression and increases the likelihood of biting, which allows the virus to spread. But that’s another unrealistic point—in the program, the fungus spreads by biting, or by these weird tendril things that come out of you. The way fungi really infect multitudes is through spores being released in the air; we are breathing fungal spores in all the time.

I’ve read the producers didn’t want to have a show where everyone was constantly in gas masks. But the point is, this is all fiction, and athlete’s foot aside, we are pretty safe from fungi, right?
Well, one of the interesting things about fungi is that they likely kill more flora and fauna than viruses and bacteria put together; that’s because they are the major pathogens of both plants and insects. If your temperature is controlled by the environment, like plants or cold-blooded animals, fungi are probably going to be your major pathogen. There’s an amphibian apocalypse occurring right now because of a fungal pandemic.

But there are also a tiny minority of fungi already adapted to human body temperature, and together they kill about 1.7 million people a year, so more than malaria or TB. One such is Aspergillus fumigatus, which I’ve done a bit of work on. It’s an opportunist that lives in rotting vegetation, and causes something called “farmer’s lung” in healthy people, but particularly if you’re  immunocompromised, it can disseminate through your body and kill you. There’s also “valley fever,” or coccidioidomycosis, on our West Coast. This is a fungus adapted to hot conditions, desert conditions. And it happens to be spreading across America as the country gets hotter.

That doesn’t sound good. What does it do?
The CDC calls Valley fever a hidden epidemic. We’ve probably got thousands infected with it. It’s normally a mild infection, but some people are getting much worse disseminated infections, and they don’t need to be immunocompromised. You don’t get people-to-people infections yet; you pick spores up by digging in the soil. But you would need far fewer mutations of this fungus to begin spreading between people than you’d need Cordyceps mutations to get human zombies. This would be a much more feasible way for a fungal pandemic to begin.

So while fungi are not dangerous in the precise way they’re dangerous in the show, there is a risk to humanity?
There is an awful lot we don’t know yet. Here’s another example: If you’ve had many sexual partners, or have had a partner who has, you’re probably hosting numerous strains of Candida albicans, which normally don’t do much except for causing thrush. But in 2009, something we’d never met before called Candida auris began spreading in hospitals through contact with surfaces. If you’re immunocompromised, there’s about a 50% chance it will kill you. It’s developed resistance to the few drugs we have available against fungi. We still don’t know where it came from. Did we encounter this because humans are encroaching more and more into new areas as our populations keep growing, or did climate change select for a new fungus able to live at human body temperature?

Climate change is how the disease in the show arose. Sounds like another mark in the “potentially realistic” column.
If global warming does cause fungi to adapt to hotter temperatures, then we could be in trouble. People might say, “Well, the world’s not going to heat up to 37 degrees Celsius like our bodies,” but it doesn’t necessarily need to—it just needs to reach extreme temperatures in some places sometimes, enough to select for fungi that can survive that hurdle and propagate, maybe to infect us.

Last question: The fungi on “The Last of Us” apparently spread worldwide through flour. That’s a flight of fancy, right?
Not necessarily. Google the term “Ergot,” or “St. Anthony’s fire.” There are theories that the Salem witch trials were caused by people becoming hysterical after eating rye flour contaminated with ergot fungus and its psychedelic chemicals. I bet the filmmakers knew of this, and it was quite smart of them to use that mechanism.