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Wednesday, June 19, 2024

It's Time to Fear the Fungi

There are plenty of things in this world that might keep you up at night. There’s COVID-19, of course, but if you’re anxious like me you could probably rattle off a very long list of additional fears: getting hit by a car, cancer, being poisoned by an ill-advised gas station meal, getting caught in a wildfire, electrocuting yourself plugging your laptop in at a dodgy cafe. But what is likely not high on your list is fungi. Unfortunately, that might be changing.

In 2009, a patient in Japan developed a new fungal infection on their ear. The highly transmissible Candida auris fungus had been previously unknown to science (and resistant to the drugs available to treat it), but within a few years, cases started emerging in Venezuela, Iran, Russia, and South Africa.

Scientists assumed that the spread was due to human travel, but when they sequenced the cases, they were surprised to find that these strains weren’t closely related at all. Instead, scientists were seeing multiple, independent infections of an unknown fungal disease, emerging around the world, all at the same time. About a third of people infected with Candida auris die from the infection within 30 days, and there have now been thousands of cases in 47 countries. Some scientists think this sudden boom in global cases is a harbinger of things to come.

Humans should consider ourselves lucky that they don't have to constantly worry about fungal infections. “If you were a tree, you'd be terrified of fungi,” says Dr. Arturo Casadevall, a microbiologist at Johns Hopkins university who studies fungal diseases. And if you happened to be a fish, a reptile, or an amphibian, fungus would also be quite high on your list of fears, were you able to enumerate them. (Fungal infections are known to wipe out snakes, fish, corals, insects, and more.) In recent years, a fungal infection called Batrachochytrium dendrobatidis (chytrid) has decimated amphibian populations around the world, with some scientists estimating that chytrid is responsible for population decline in over 500 amphibian species. To put that into context, that’s around one out of every 16 amphibian species known to science.

One of the reasons fungal infections are so common in so many creatures is that fungi themselves are ubiquitous. “This is dating myself, but you know the Sting song “Every Breath You Take"? Well, every breath you take you inhale somewhere between 100 and 700,000 spores,” says Andrej Spec, a medical mycologist at Washington University School of Medicine in St. Louis. “They've made it to the space station. They are absolutely everywhere.”

Humans can and do get fungal infections (athlete’s foot, for starters, and fungal diseases are one of the leading causes of death for immunocompromised people with HIV). But people are generally unlikely to fall to a fungus for one big reason: humans are hot. (Although, if you want to be the pedant at a party, you might enjoy learning that humans are generally not, in fact, the commonly cited 98.6 degrees Fahrenheit. That number comes from a German study done in 1851. In fact, human body temperature seems to have been cooling recently, and the global average is between 97.5 and 97.9 degrees Fahrenheit.) Warm-blooded environments, in general, tend to be too warm for a fungus to survive. One of Casadevall’s studies estimated that 95 percent of fungal species simply cannot survive at average human internal temperature.

You can see this temperature barrier in action when you look at animals that hibernate, which requires dropping their internal temperatures to survive the winter. Bats, for example, have recently suffered huge declines due to white nose syndrome, which infects them while they’re hibernating and therefore cooler than usual.

For Casadevall, these findings support his theory about the animal world’s long history with fungi. He argues that perhaps our warm-blooded natures evolved specifically to avoid the kinds of fungal infections that can wipe out cold-blooded populations.

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Being warm-blooded has its costs. Keeping your body at such a high temperature takes a lot of energy, which requires a lot of food. In fact, some warm-blooded animals have to eat more in a single day than a cold-blooded reptile of the same size would in a whole month. Constantly seeking out food puts you at increased risk of predation (or that toxic gas station meal that could kill you). Why expend all that energy if you can simply bask in the sun?

Of the many benefits to being warm-blooded, one of them, Casadevall argues, is the fungal filter. He says that this could help explain one of evolution’s great mysteries: After the asteroid killed off the dinosaurs, why didn’t they simply repopulate and once again dominate the Earth? “If the reptiles were so fit, how come we didn't have a second reptilian age?” he asks. “The reason that we are the dominant animal is because it was a fungal filter,” he says. In other words, it was the warm-blooded creatures’ resistance to fungal infections that allowed them to become dominant, while the remaining cold-blooded dinosaurs fell to the infections.

This is a tricky theory because it’s almost impossible to prove. There are very few places where evidence of fungi, or fungal infections, has been preserved in the fossil record—not because they weren’t present, but because fungi tend to be squishy and degradable, not ideal for turning into fossils. “I think it's definitely a fringe theory at this point to say that that's the only thing that happened,” says Spec. “But did it contribute? I think it's fascinating, and we probably will never know until we start sequencing stuff and we find invasive mold and things like that in dinosaur fossils, if we ever do.

But even if fungi had nothing to do with the modern age of mammalian dominance, we should still be paying a lot more attention to them. Throughout history, at least according to this theory, we’ve been protected from fungi because they haven’t adapted to live at the temperatures inside our bodies. But as the planet warms, that could change. The most recent global estimates say that without serious intervention, the Earth's temperature could rise 5 degrees Fahrenheit by the end of the century. And those five degrees could be the difference between fungal resistance and fungal death.

To be sure, fungal infections are already more common in warm locations—the rates of a fungus called cryptococcosis, which can be deadly to people with AIDS, can reach 30 percent in Africa, compared to just 5-10 percent in more temperate regions. But there’s still a fine yet crucial line between internal human body temperature and the conditions in tropical environments. For a fungus to live or die, even a few degrees can make all the difference. As the world continues to warm, a growing number of places will approach internal human body temperature more of the time. Sooner or later, the fungi will learn to adapt. And if they do, they might find a whole new set of hosts in us.

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This is what Casadevall thinks is happening, at least in part, with the recent surge in Candida auris cases all over the globe. In one study, scientists showed that the fungus is capable of growing and reproducing at higher temperatures than its close relatives. And it might not be the last fungal infection to emerge in our age of climate change—Casadevall estimates that for every 1 degree increase in global temperature, the thermal gradient barrier between our guts and fungi could decrease by 5 percent.

Right now, Casadevall and his colleagues are trying to come up with a list of the most likely fungal species to be able to cross over to humans—species that already live on the threshold of our body temperatures. We’re a long way from having that information, as it’s not even clear which species we need to worry about most, and where those species live.

If all of that wasn’t scary enough, doctors don’t currently have great tools to fight fungal infections, for a variety of reasons. For one thing, since life-threatening fungal infections have historically been relatively rare in humans, the field is tragically underfunded. In Africa, for example, cryptococcosis kills more people than tuberculosis, but research into cryptococcosis received just 1 percent of the funding allocated to tuberculosis. (In fact, some researchers argue that fungal pathogens should be considered “neglected diseases.”) Doctors aren’t generally trained in identifying these kinds of infections, and often miss them until it’s too late. And even when they do identify them, only three kinds of anti-fungal drugs exist. Fungi are more closely related to humans than they are to viruses or bacteria, which means that, in general, things that kill them also kill us.

Plus, the fungal infections we’re talking about here aren’t athlete’s foot or dandruff—they’re infections within the body that can wreak havoc. Already, over 300 million people globally contract serious fungal infection each year and over 1.5 million of them die. People with certain kinds of infections can develop “fungal balls” inside their lungs. “I have taken care of many patients who've gotten wound infections and horrible, incurable musculoskeletal infections, where the fungus will eventually burrow out and drain,” says Spec. And he often has no way of treating these patients. “I can only refer them to hospice because there absolutely is nothing that works against them.”

So what happens next, and what should we do? Casadevall gave the same answer every scientist gives to this question: The field needs more funding. “Humanity should be investing more in learning about what is the largest kingdom on the planet,” he says. 

If the Covid pandemic has shown us anything, it’s that we should be better prepared for disease outbreaks. It’s relatively clear that we’re not ready for the next pandemic, even if it were another coronavirus. Yet we knew far more about coronaviruses as a class than we do about many of these potentially risky fungi. The world of things that could kill us is larger than we thought, and very possibly growing.


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