Short Wave - The Fungal Science Behind HBO's 'The Last of Us'

Episode Date: February 21, 2023

The video game series that spawned the new hit HBO drama, The Last of Us, is the zombie genre with a twist. Instead of the standard viral pandemic or bacterial disease that's pushed humanity to the brink, but a fungus that has evolved to survive in human bodies in part due to climate change. Short Wave's Aaron Scott talks with fungal researcher Asyia Gusa about the science that inspired The Last of Us and the real threats fungal researchers see in the ever-warming world.See pcm.adswizz.com for information about our collection and use of personal data for sponsorship and to manage your podcast sponsorship preferences.NPR Privacy Policy

You're listening to Shortwave from NPR. The first episode of HBO's hit new zombie show, The Last of Us, opens with two scientists being interviewed on a talk show in the 1960s. And Dr. Newman, you're also an epidemiologist. I presume the prospect of a viral pandemic keeps you up at night as well. No. No? No. All right.

Well, that's our show. It sets up that this show is going to be zombies with a new twist. Not bacteria. Not viruses. So fungus. Fungi seem harmless enough? Many species know otherwise because there are some fungi who seek not to kill, but to control. When I saw the opening few minutes, I nearly jumped off the couch and was yelling at the screen. This is like what I study. This is Asiagusa, a fungal researcher at Duke University. What threatens him the most is the idea of fungi,

evolving to be thermally adapted to survive at human body temperature and cause disease. And that, That's the biggest pandemic that he's worried about. Dr. Schoenheim, you're in distress. Fungal infection of this kind is real, but not in humans. True, fungi cannot survive if its host's internal temperature is over 94 degrees. And currently, there are no reasons for fungi to evolve to be able to withstand higher temperatures. But what if that were to change? What if, for instance, the world was to get slightly warmer?

Well, now there is reason to evolve. slightly warmer from, say, global warming? The idea of a large-scale fungal outbreak is not something new dreamed up by The Last of Us creators. It's something Asia says researchers in the field have been worried about for years. We're so much more familiar with hearing about bacteria and viruses causing the biggest threats. Even though fungal researchers have known about this threat for years, this was the first time we'd really seen it in popular culture, popular media takeoff. Fungal researchers often say we have a PR problem. People don't really associate fungi with disease, more so with mushrooms, or just something maybe like athletes' foot,

something that's not really that serious or invasive or causes death. But we know that it's responsible for a number of deaths, 1.5 million globally worldwide. Today on the show, we separate the science from the fiction in The Last of Us and get into the real threats that fungal researchers see in our ever-warmer world. I'm Aaron Scott. You're listening to Shortwave from NPR. Okay, Asia, before we go any deeper, let's clarify what is up with the fungus of the last of us. It is called cordyceps. I, like I'm guessing, a lot of people, first learned about it from the TV show Planet Earth, where you watch this fungus basically possess and then turn an ant into a zombie and force it to climb up a plant, and then the fungus erupts from the ant's head and rains down spores, and it is

terrifying. Now, this is not your area of focus. You focus on fungi that infects humans, but what can you tell us about cortisps? Yes. This is a fungus that infects insects and cause decomposition and sort of essentially take over the insect's body. And so it's a pretty interesting phenomenon that happens. We don't think this would happen in humans, at least we haven't seen anything like this. And what is standing in the way of something like cortis heps and a lot of other fungal pathogens from infecting humans? I can't speak to this from a medical perspective, but what I can say is that the human

body is so well adopted to deal with threats from bacteria, viruses, and even fungus, including our body temperature, number one, that's going to protect us from these fungus growing well or thriving in our bodies. And actually, I'd love if you'd say a little bit more about that. because they do talk about that kind of at the opening of the scene. I mean, a lot of these fungi like cortisps, can't actually survive at the human body temperature, right? Right. So largely, we think it's our body temperature that's been acting as a thermal barrier to fungal infections and fungal disease.

There's hundreds of thousands of different fungi in the environment, and we know that only a relatively small proportion are capable of causing human disease. So for the most part, we feel pretty protected from those fungi that are currently in the environment and maybe are not thermally adapted to grow at our body temperature. Because our bodies are warmer than most ecosystems across the world. Absolutely. But fungus are a major cause of disease in plants and crops. That's going to threaten our food supply. But for the most part, we're interested in finding out whether or not these rising global temperatures,

could they exert a stress on these fungi in the environment that, are normally not able to grow at human body temperature, but if they adapt to be able to survive those temperatures, they are more likely to be able to cause disease. One of the fungi that you focus on cryptococcus is able to grow in the human body temperature. Yes. I mean, it doesn't turn us into zombies. Can you tell us a little bit about what it does when it infects the human body and how deadly it is? Right. So it's actually the number one killer in humans that's caused by a fungus.

So this is specifically cryptococcus neiformins. And what happens is you breathe the spores in through the air. And for the most part, our immune systems are equipped to clear them as we breathe them into our lungs. However, if you have a weakened immune system, it can travel to the brain and cross the blood-brain barrier. And so once it gets there, it causes an infection called cryptococcal meningitis, which is a swelling and inflammation of the brain. And that ultimately results in death. And actually, it causes 110,000 deaths every year. Mostly folks that are immunocompromised or maybe have transplants,

and they're taking immunosuppressive therapy or HIV-AIDS-infected. But we are seeing a growing number of cases in folks that we otherwise can't identify an underlying health condition. So that's quite concerning. You recently published a paper in the proceedings of the National Academy of Sciences, where you investigated how Cryptococcus would react to thermal stress, which is, you know, basically warmer temperatures. Can you tell us about this study and what you and your fellow researchers found? Yes.

We did a very simple experiment where we grew Cryptococcus in the laboratory for about 100 days at either conditions of 30 degrees, which is about like mid-80s versus 98.6 degrees Fahrenheit or 37 degrees Celsius, and that's our human body temperature. Then we wanted to actually sequence their entire genome and figure out what kinds of genetic changes had taken place comparing the two different temperatures. And we were really surprised to find that there was a certain category of mutations that occurred five times more likely at the higher temperature. And they were caused by these elements in the genome that we call jumping genes. And what they are is sort of selfish DNA elements that are able to move from one location to another or copy themselves. and move into a new location with the ability to disrupt function or also to alter the function.

So they have a lot of implications because if you get an insertion into a region that maybe then results in the ability to grow at higher temperatures, for example, then if that particular organism is grown at higher temperatures, it can then potentially adapt and will grow faster and outlive the rest. So, I mean, in some ways, it's like a little evolutionary secret weapon or something that helps speed up how the species can adapt to new challenges? Absolutely. Especially if you have heat trigger or some other stress in the environment as a trigger for these movements, you're going to get greater adaptation. Now, we still don't have direct evidence that this is leading to thermal adaptation. So that's what we're trying to figure out.

Wow. So you basically found that the last of us is on point. A warming world could help fungi adapt to a point where more of it could infect us humans. Great news. It's absolutely, you cannot rule it out. And it seems we're not really ready. Like I read it was only last year that the World Health Organization released its first ever list of fungal priority pathogens. What do the WHO and the CDC and other health institutions see as the main threat posed by fungi?

Right. Well, they are definitely concerned about the invasive fungal diseases and the rise that we're seeing in those. We actually have a rising population of people that are considered immunocompromised or with weakened immune system. So they're concerned about that, but also the spread. The geographic spread of fungus is increasing. And we do think that that may be also tied to climate change. So we've seen histoplasma and coxioides, which you've probably heard, Valley Fever. Valley Fever used to be relegated pretty much to the southwest. Now it's traveling up and outwards and hitting most of the United States. So we're definitely seeing the geographic spread of a number of these fungal diseases increasing.

And another of the major challenges is that we just don't have many antifungal drugs or any vaccines in our toolkit. That's right. We only sort of have about four, an arsenal of about four kinds of drugs that we tend to employ. And because fungus actually resemble more closely our own human cells, those targets are much harder to come up with. So we really need to increase the amount of research being done on which targets can be effective so that we have an arsenal and a backup. Got it. So do you have a sense of why it is fungal diseases haven't gotten this sort of attention and funding? I mean, why is it that the premise of The Last of Us is suddenly catching so many of us by surprise? Right. Well, I think that there can sometimes just be a bias in how we've tended to research organisms. And we probably would investigate those illnesses that are causing the most immediate threats and especially among healthy people or those. diseases that are infectious, you know, could be able to spread from human to human. A number of these invasive fungal infections are not spread human to human. And so, therefore, they maybe pose a lower threat as far as a pandemic is concerned. But the fact that you could have spores in the environment, that is a true concern.

A huge barrier has been, though, our diagnostic tools are very limited. So a lot of clinics probably don't even have a way of assessing whether or not a particular infection is caused by a fungal disease. These are quite, they cause a very high mortality rate because by the time they've ruled out that it's a bacteria or a virus, they really are too late in assessing it as a fungus and therefore don't have proper treatments available. All this, like, I hate to say it, it's priming me for feelings of apocalyptic, pandemic la last of us. It seems like we are ripe, like the creators of the video game in the show really picked up on a potent scientific concept for their horror series. Yes, I would agree with that.

I mean, this is exactly understudied. And whenever you have something that's understudied, under-researched, and we don't have the proper tools to fight it, well, that's a cause for concern. And so, you know, I don't want to sound alarm bells. But at the same time, there are already millions of people suffering from deadly fungal infections. and the attention has just not reached them. So, you know, as a fungal researcher, we definitely hope that this brings greater awareness, not to put people in a state of panic,

again, because it doesn't spread from person to person, it's just that whether or not a number of new fungus that we haven't even seen causing disease before starts to emerge, that's the real threat. Thank you so much, Aesia, for talking fungi with us. I appreciate. Thank you for having me on. Today's episode was produced by Liz Metzger, edited by supervising producer Rebecca Ramirez and fact-checked by Anil Oza.

Our audio engineer was Josh Newell. Brendan Crump is our podcast coordinator. Beth Donovan is the senior director of programming, and Anya Grundman is the senior vice president of programming. I'm Aaron Scott. Thanks for listening to Shortwave from NPR.