Transcript:

Paul Rand: Well, I’m going to start with the question that you’re probably sick of talking about. People might be familiar with what was a video game and then became a TV show called The Last Of Us. And I wonder if you could explain the premise of this show and why it’s connected to some of your work?

Arturo Casadevall: Let’s start by saying that I never watched the show, except for the opening trailer.

Tape: We haven’t seen the world, so you don’t know.

Samara West, we’re working on a cure.

Arturo Casadevall: And I was sitting in my couch at home answering emails and just watching TV and if you’re going to get emails from people saying, “Hey, were you one of the advisors to the show?” And I said, “What are you talking about?”

Paul Rand: That’s Arturo Casadevall, professor of Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. And he’s the author of the new book, What If Fungi Win?

Arturo Casadevall: The premise of the show is that a scientist in 1968, predicts that with global warming cordyceps could adapt to higher temperatures and thus become a human pathogen.

Paul Rand: Fungus.

Tape: Yes, that’s the usual response. Fungi seem harmless enough, many species know otherwise.

Arturo Casadevall: And that’s what the show is based on. And how is it connected to my work? Well, I’ve been working on why are the fungi pathogenic for a very long time.

Paul Rand: While the TV show is just science fiction, scientists like Casadevall who study fungi are already preparing for what they say might be inevitable.

Arturo Casadevall: Can we be dealing in the future with a fungal pandemic? And the answer to that is, yes.

Paul Rand: Most of us just think as fungi as a delicious pizza topping or an annoying itchy infection. Yet, we don’t usually think of fungi as something deadly.

Arturo Casadevall: To me, that was a very interesting question, because the plants, the fungi in the major pathogens are plants. So, plants are terrified of the fungi if they could think. The insects are terrified of the fungi, the frogs are terrified of the fungi. So, the question is, what makes us different?

Paul Rand: What makes humans different is that our internal body temperature provides natural immunity against fungi. But just like in the TV show, climate change is changing everything.

Tape: 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 were to get slightly warmer? Well, now there is reason to evolve.

Arturo Casadevall: The world is getting hotter. All life in this planet is going to have to adapt, period. So, here is the big concern. The big concern is the fungi are adapted, and if they adapt to higher temperatures they will defeat our temperature barrier.

Paul Rand: If fungi keep adapting to higher temperatures on Earth, a fungal pandemic like The Last Of Us wouldn’t just be science fiction.

Arturo Casadevall: You will need to have a fungal disease that is communicable, right? You need to be able to in fact go from person to person, or you need to have some event in the environment that showers humanity with spores and somehow. That is a possibility. There is nothing biologically to stop a fungus from making spores in the lung such that when you cough it out the spores will come out.

Paul Rand: But there is a glimmer of good news in what might seem catastrophic. We do have the foresight to prepare and possibly prevent a fungal pandemic.

Arturo Casadevall: We need to heighten awareness of this, because we can do something about it. Vaccines can be made, new drugs can be made, and we can be more aware of the threats so that we don’t get blindsided with a fungal pandemic.

Paul Rand: Welcome to Big Brains, the podcast where we translate the biggest ideas and complex discoveries into brain food you can use. I’m your host Paul Rand. On today’s episode, the Science of How Fungi are adapting and Why we need to prepare for a fungal epidemic. The University of Chicago Leadership & Society Initiative guides accomplished executive leaders in transitioning from their long-standing careers into purposeful encore chapters of leadership for society. The initiative is currently accepting candidates for its second cohort of fellows. Your next chapter matters for you and for society. Learn more about this unique fellowship experience at leadforsociety.uchicago.edu. Most people, of course, are probably giving thought to this thinking they know what fungi means, or fungi, and that’s something that they eat or will see in the woods on a walk. But I wonder if you can talk about the kinds of fungi that you are talking about and what a basic explanation of what they are?

Arturo Casadevall: Paul, that’s a great question. Most people don’t think about fungi, except in the supermarket or in the woods after big rains when they see mushrooms. But the majority of fungi are unicellular and microscopic. Those are the ones that cause disease.

Paul Rand: And my understanding from your book is there are about six million species of fungi, which is far more than probably most people ever thought possible.

Arturo Casadevall: At least, that’s an estimate. Most of the world has not been mapped, and very little work has been done to know what fungi in your backyard. But people don’t seem to fear the fungi. The fungi may harass them. They may give him a nail infection, they give them athlete’s foot, but people don’t walk around saying, “I’m really worried I’m going to die of a fungal disease.”

Paul Rand: Normally, and I guess maybe before we get into the idea of challenges or the bad parts of fungi, there are some really good parts of it.

Arturo Casadevall: Well, last night I had a glass of wine. You can’t have a glass of wine without fungi, basically fermentation. They are food stuffs. They make a lot of our medicines. How many of listeners may be taking statins? Well, they’re made by a fungus. Penicillin is made by a fungus. Many of the other antibiotics are made by fungi, but most important for the planet, what the fungi do is that they are the big degraders. When a tree falls down in the forest and rots, it is the fungi that return all those nutrients back into life. So, they are essential for life on Earth as we know it.

Paul Rand: We might not know just how many fungal species are out there, but we do know a lot about the ones we’ve already come into contact with. And Casadevall had personal experience with one fungal disease in the 1980s during the height of the AIDS epidemic.

Arturo Casadevall: What really changed my life was going into Bellevue Hospital in New York City in the mid-1980s. And what I saw there was a devastation that is hard to describe. The hospital was full of young people dying of a disease that we had never heard before. The idea that something can happen in medicine that was not known was shocking, and what was killing them was not so much the virus that we know now is HIV, but opportunistic infections. And these are infections like fungi was one of the big problems causing pneumocystis. We didn’t think in the mid-1980s that you could ever make drugs to control this virus. The idea was if we’re going to help these people, we got to work on what’s killing them, the fungi. And therefore that’s why I went into working on the fungi.

Paul Rand: The study of fungal disease has always been a backwater in the sciences. Viruses and bacteria have always sucked up all the energy in the room for one simple reason,

Arturo Casadevall: Most fungi are not pathogenic because you’re protected by your temperature. You’re hot.

Paul Rand: Fungi can’t survive above 97 degrees. Coincidentally, the average temperature of humans. So, fortunately for us, we’ve had a natural immunity.

Arturo Casadevall: And we don’t think about it, but our temperature, what we walk around every day with is enough to keep out most of the fungal world. So, we are getting a huge amount of protection. Basically they can’t replicate at our temperatures. They basically, once they go into us, they shut down and the immune system cleans him up. And that’s why most people don’t worry about dying of fungal diseases.

Paul Rand: That is until 2009 when everything changed. A fungus known as candida auris started doing something scientists thought wasn’t possible.

Arturo Casadevall: Here is something. This fungus was unknown to medicine until 2009. And then a couple of years later it begins to show up in patients in three different continents. And the isolates are not related. You can’t say, well happened in Venezuela, happened in South Africa, happened in the Indian subcontinent. You can’t say, “Well, did somebody brought her on a plane infected?” No, these things are not related. They’re in fact quite different. And now we have a major problem with candida auris, which is rapidly disseminating and causing problems throughout the United States.

Tape: Turned out it’s something you’ve been hearing a lot about lately, a fungus known as candida auris. The CDC is on alert citing a rapid spread, particularly in healthcare facilities.

Tape: Candida auris is a form of yeast. For a healthy person it’s usually not harmful, but for those with weakened immune systems, it can be deadly. More than half of the States have now reported cases of the drug-resistant fungus.

Arturo Casadevall: The first reports all happened in people who are very immunosuppressed, so the fungus almost found a way to adapt. Once it gets into a hospital it’s very tenacious and it’s very hard to clean. If you look, the CDC put out a paper a couple of years ago, it’s just showing that this thing was spreading state after state. And right now is primarily a problem for an immunocompromised patients, but we have seven million immunocompromised patients in this country, a lot of people potentially at risk. The question I pose to you and to our readers is, what’s going on here? A fungus not known to medicine shows up simultaneously in three continents and they’re not related. They appear to be independent eruptions. And I give you something, what is the one common denominator? It isn’t soils, it isn’t culture, it isn’t food, it is all three places are experiencing global warming.

We have proposed that this is the canary in the coal mine. It is the first example of a fungus that was living in the environment, not bothering any humans, with the capacity to cause disease. But then it adapted. And even though we can treat it, I don’t want to scare any listeners off, and even though the likelihood of anybody getting it is very small, the bottom line is the fact that it happens should be a big warning signal. Here’s the big concern. The big concern is, the fungi are adapted, and if they adapt to higher temperatures they will defeat our temperature barrier. Because if you have a fungus that can’t grow, let’s say let’s use the Fahrenheit scale, above 95 degrees. Well, it’s not pathogenic today, but if in two or three years you can go to 98 degrees, well, you’re not going to keep them out.

Paul Rand: Speaking of life adapting, and this was news to me, but I didn’t realize that our body temperatures are actually getting a bit cooler.

Arturo Casadevall: That is an incredible result. It was a very interesting paper. What they did is they collected temperature readings for decades going back over 100 years now, and they showed that the average human temperature is dropping. In other words, your great-grandparents were warmer than you are. How can that be? After all, we are the same species. Well, it turns out that 100 years ago people were infected with a lot of things that they’re not infected in a clean world today. They had worms, many of them had tuberculosis. Even if it was latent, it would raise your temperature possibly, and anyway, they lived in a different world that where there was more inflammation. Inflammation is why you when you get an injury feels warm.

Paul Rand: Right.

Arturo Casadevall: So, in a more inflammatory world they have higher temperatures. Our world is cleaner. But this leads to a problem, because if the fungi are adapting or we’re getting colder, we’re going to meet earlier than we think. So, we have two things going on. We have adaptation, but if adaptation is not enough, then the temperature is also making them change, and it’s going to change them in very unexpected ways.

Paul Rand: But one of the other things is that climate change is not only making some of these fungi stronger, it’s actually helping them proliferate. Where we are today and where we are tomorrow just on a volume basis could actually be quite different. There’s been studies, including one from Duke University recently that was going on with mice that really brought this to life. Can you talk us a little bit about that study and what it helps show us?

Arturo Casadevall: What that study showed us is that we don’t have to worry only about adaptation, the situation gets worse, because when you take this fungi and you put them in a warmer environment, well, they have this mobile DNA elements that then begin to reassort their DNA. When they reassort their DNA, some of them come out drug resistant and some of them can acquire more virulence.

Paul Rand: If the fungi continue to adapt to our new climate becoming resistant not only to our natural temperature barrier, but also resistant to antifungal drugs, what will that mean for us? Well, Casadevall and other scientists hope to develop better antifungal drugs, and even possibly a one-size-fits-all antifungal vaccine. That is after the break.

If you’re getting a lot out of the important research shared on Big Brains, there’s another University of Chicago podcast network show you should check out. It’s called Not Another Politics Podcast. Not Another Politics Podcast provides a fresh perspective on the biggest political stories, not through opinions and anecdotes, but through rigorous scholarship, massive data sets, and a deep knowledge of theory. If you want to understand the political science behind the political headlines, then listen to Not Another Politics Podcast, part of the University of Chicago podcast network. Today we only have a number of antifungal drugs that are effective at killing fungi diseases. But the reason why we don’t have more of these drugs might actually surprise you.

Arturo Casadevall: When you look at the tree of life, animals, us, cows monkeys are closest to the fungi, rather than to the plants, rather than to the amoeba and things like that. The little ones, the microscopic and the big ones, the mushrooms are really the same type of organism. And what makes them really interesting is that they are your closest relatives. So, we share a lot of the biochemistry with them, and that actually becomes a problem when you try to make antifungal drugs.

Paul Rand: Essentially it becomes harder to make a drug that can fight your relatives and not you.

Arturo Casadevall: The fact that we are biochemically so similar to the fungi, what it means is that it is difficult to find a difference. And if it is difficult to find a difference, the difference is the target, you want to kill the fungus and not kill the person.

Paul Rand: There are also some implications of certainly some serious side effects of some, at least of some of the current antifungal medications.

Arturo Casadevall: Well, our best antifungal was made on the year that I was born. It is known as Amphotericin B. If you want to know my age, 1957 I was born. And the drug was known for many years as Amphoterrible.

Paul Rand: Okay.

Arturo Casadevall: Now, over the years physicians have figured out how to make it less toxic, but it tells you something that the most effective drug that we have for some fungal disease we now have others, is a drug that was developed a long time ago with a lot of toxicity.

Paul Rand: Not only do we not have many antifungal drugs in the event of a pandemic, but there’s another growing problem. Antifungal resistance is on the rise, meaning fungi are becoming so strong that they can actually defeat the drugs that are designed to kill them.

Arturo Casadevall: That’s right. Resistance like everything else continues to be an increasing problem. Although, some of the current fungal diseases are so resistant that it’s just very hard to treat.

Paul Rand: But it’s not just people who are facing antifungal resistance. Scientists are also seeing the same problem in the wild with animals and agriculture.

Arturo Casadevall: The fungi responsible for losing an enormous amount of the volume of our crops. Every major crop has a major fungal pathogen.

Speaker 6: Officials in Colombia confirmed a fungus destroyed banana plantations in Asia and Australia, and it has now reached South America.

Arturo Casadevall: So, the wheat have a fungal pathogen, the rice have a fungal pathogen, you name it. Agriculture fights a constant battle with the fungi just to make sure that we have our food at the table. This is obviously an area that is of tremendous importance to society, I mean, maintaining the food supply. And it doesn’t make the news, but the fungi are destroying entire ecosystems today. In our lifetimes we have seen an amphibian catastrophe. A single fungus has spread throughout the world and has killed untold numbers of frogs and driven many to extinction. In North America we’ve seen a problem with the bats. The bats were well until 2006 and then a fungus got into this country somehow. The bats are like you, they’re 37 degrees in the summer. They’re resistant to this fungus, but in the winter there are no insects, they need to hibernate. So, their temperature drops and this fungus kills them. Millions of bats are being killed.

Speaker 8: For nearly two decades bats across North America have been decimated by a deadly disease called White Nose Syndrome. Patches of pale white fuzz caused by a fungus appear on infected bats.

Arturo Casadevall: There was an amazing paper recently in science associating the declines in bats with increases in baby infant deaths. And the way this happens is a single individual by tracking data sets was able to show that as the bats go down, the pests go up, and people use more pest control and the pest control gets into everywhere and there’s an association. So, it just shows you all this is connected. When I tell you that there are catastrophes going on in the frog ecosystems, in the bat ecosystems, they will affect us.

Paul Rand: If we were to look out a few years here and check back with you in five years, what kind of progress do you think you and some of your colleagues will be making?

Arturo Casadevall: One of the things that we want to do, and we were working on this and this was put on hold by the COVID pandemic, is to try to construct a threat chart. In other words, you got six million species out there, right? Which ones do you think we should worry about most? Well, I would say something that is close to your temperature, something that can cause disease in another animal or a plant, because the fact that it can cause disease in an insect means that it can defeat an insect immune system. So, I’d be looking for things like that. I would worry more about something that can grow up to 35 then something that can only grow up to 30 degree. You are 37, so the closer you are, it can grow to your temperature, the more I worry about it. So, that to construct that, because I think that if we had that we may begin to look at where future threats are, and that could become very important for preparedness.

Doctors often don’t think of fungal disease, because it is rare. But what’s interesting about the fungi is the fungi don’t kill you rapidly. When they tend to cause disease, it tends to be chronic, like chronic sinusitis. So, fungal diseases are not reportable, the majority of them. They’re not reportable. Why? Because they’re not usually communicable. There’s a colleague of my, David Denning, but he’s made a remarkable effort to try to document of how many people are dying of fungal disease in any one country. And every few years he publishes a paper in the media journal, and I think the numbers are in the millions that are dying from fungal disease. I looked at up relatively recently. So, we are not talking about something that caused only a few cases. When you put the human population together, we’re talking about an untold amount of human death and suffering. But the one thing is, when you look at the numbers, the problem of fungal diseases gets worse every year.

Paul Rand: Is this a likelihood that we will not have a medication to treat it once symptoms arrive, but actually could be a vaccine that could prevent that infection from even coming?

Arturo Casadevall: There is so much criticism of what happened with COVID. It’s important to remember that within one year, within one year we had vaccines, we had drugs, and we had monoclonal antibodies. But vaccines is a completely different strategy. And here is the problem, Paul, who would you vaccinate? You want to vaccinate the people at risk. The people at risk are often immunosuppressed, but guess what? Because they’re immunosuppressed they may not make a good response to the vaccine. So, it becomes much harder to make a vaccine. Can you make it? Yes, we have vaccines for the immunosuppressed, but again, you think about it from the pharmaceutical company point of view. You’re making a vaccine for a niche population that is going to be harder to test and harder to respond. There will have to be a major societal effort to basically get this done.

There are people today working very hard to make vaccines for bats. For example, my colleague Bruce Klein and his colleagues at the University of Wisconsin, people are working on these problems. But what people need to know is, the efforts and minuscule compared to what’s going on for other more pressing diseases. And this is normal human nature. The fungi get worse every year, but incrementally. COVID hits us and turns the society upside down.

Paul Rand: At this point you’re probably thinking to yourself, “Okay, I need to fear all fungi and even worry about the prospect of a fungal pandemic.” But there is another side to fungi that has a lot of promising potential. Surprisingly, they could just as easily usher in a new area of development, and it turns out they may be the key to revolutionizing our modern industrial world.

Arturo Casadevall: What we haven’t talked about is all this stuff that’s going on in trying to develop the fungi as new materials. For example, I invite your listeners to google fungal leather. It turns out that certain fungi, you can grow them in the shape of a handbag. And you can grow things and then you compress the mycelium. And this stuff is actually biodegradable. It doesn’t come from animals. We’re working with NASA and using some of the properties of fungi for shielding. The biggest problem out in space is radiation. Are you going to be shipping lead up there? It turns out that they make melanin, and this melanin is a very powerful shielding material. Fungal construction materials. Some people are using compressing the fungus into some sort of bricks. And you know what? Our civilization depends on materials. If you think about Stone Age, Bronx Age, Iron Age, Silicon Age, well imagine an age, the biological age, and I believe that the fungal world has a lot of new stuff that it’s going to give us.

Paul Rand: It’s also whether it’s air conditioning, construction materials, fungi is present in all of these different areas that are impacting our lives.

Arturo Casadevall: Let’s just talk about air conditioning. It turns out that when you buy mushrooms they’re cooler. The reason that they’re cooler is because they have a lot of water, and as long as the water evaporates, the fungi are cooler. This is the same phenomenon why you feel cold when you step out of the shower, even though your bathroom is full of steam. Even a little water that evaporating makes you feel cooler. One of the things, and it was one of those really fun things that you do in the world of science that we made a prototype air conditioner in which we went and bought some of these mushrooms from the supermarket. We put in a fan that came from a computer cooling fan, drove air through and it dropped the temperature almost 10 degrees centigrade. That’s a big drop. As long as those mushrooms had water, the air going out of it was cooler.

Now, eventually they will dry up, but what I would say is, you could scoop them and cook them at that point. To those who cook, the best example of how much water mushrooms have is you go to the supermarket and you buy all these big mushrooms and then you cook them and they little tiny things and you say, “What happened to this?” Well, the water went out. So, there’s examples and there are all the people thinking about water, fungi as filtration systems. You can put them in areas in which the water is flowing and they will absorb out of the water many of these things that we want to get out. So, there is a lot people experimenting. I think there’s going to be a lot more fungi in our world in our future.

Matt Hodapp: Big Brains is a production of the University of Chicago Podcast Network. We’re sponsored by the Graham School. Are you a lifelong learner with an insatiable curiosity? Access more than 50 open enrollment courses every quarter. Learn more at gram.uchicago.edu/bigbrains. If you like what you heard on our podcast, please leave us a rating and review. The show is hosted by Paul M. Rand, and produced by Lea Ceasrine, and me, Matt Hodapp. Thanks for listening.

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