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Humans Can No Longer Ignore the Threat of Fungi

The Atlantic

www.theatlantic.com › health › archive › 2023 › 09 › fungal-disease-climate-change-threat › 675515

This article was originally published by Undark Magazine.

Back at the turn of the 21st century, valley fever was an obscure fungal disease in the United States, with fewer than 3,000 reported cases a year, mostly in California and Arizona. Two decades later, cases of valley fever have exploded, increasing roughly sevenfold by 2019.

And valley fever isn’t alone. Fungal diseases in general are appearing in places they have never been seen before, and previously harmless or mildly harmful fungi are becoming more dangerous for people. One likely reason for this worsening fungal situation, scientists say, is climate change. Shifts in temperature and rainfall patterns are expanding where disease-causing fungi occur; climate-triggered calamities can help fungi disperse and reach more people; and warmer temperatures create opportunities for fungi to evolve into more dangerous agents of disease.

For a long time, fungi have been a neglected group of pathogens. By the late 1990s, researchers were already warning that climate change would make bacterial, viral, and parasite-caused infectious diseases such as cholera, dengue, and malaria more widespread. “But people were not focused at all on the fungi,” says Arturo Casadevall, a microbiologist and an immunologist at the Johns Hopkins Bloomberg School of Public Health. That’s because, until recently, fungi have caused humans relatively little trouble.

Our high body temperature helps explain why. Many fungi grow best at about 12 to 30 degrees Celsius (roughly 54 to 86 degrees Fahrenheit). So though they find it easy to infect trees, crops, amphibians, fish, reptiles, and insects—organisms that do not maintain consistently high internal body temperatures—fungi usually don’t thrive inside the warm bodies of mammals, Casadevall wrote in an overview of immunity to invasive fungal diseases in the 2022 Annual Review of Immunology. Among the few fungi that do infect humans, some dangerous ones, such as species of Cryptococcus, Penicillium, and Aspergillus, have historically been reported more in tropical and subtropical regions than in cooler ones. This, too, suggests that climate may limit their reach.

Today, however, the planet’s warming climate may be helping some fungal pathogens spread to new areas. Take valley fever, for instance. The disease can cause flu-like symptoms in people who breathe in the microscopic spores of the fungus Coccidioides. The climatic conditions favoring valley fever may occur in 217 counties of 12 U.S. states today, according to a 2019 study by Morgan Gorris, an Earth-system scientist at the Los Alamos National Laboratory, in New Mexico.

But when Gorris modeled where the fungi could live in the future, the results were sobering. By 2100, in a scenario where greenhouse-gas emissions continue unabated, rising temperatures would allow Coccidioides to spread northward to 476 counties in 17 states. What was once thought to be a disease mostly restricted to the southwestern U.S. could expand as far as the U.S.-Canadian border in response to climate change, Gorris says. That was a real “wow moment,” she adds, because that would put millions more people at risk.

Some other fungal diseases of humans are also on the move, such as histoplasmosis and blastomycosis. Both, like valley fever, are seen more and more outside what was thought to be their historical range.

Such range extensions have also appeared in fungal pathogens of other species. The chytrid fungus that has contributed to declines in hundreds of amphibian species, for example, grows well at environmental temperatures from 17 to 25 degrees Celsius (63 to 77 degrees Fahrenheit). But the fungus is becoming an increasing problem at higher altitudes and latitudes, which likely is in part because rising temperatures are making previously cold regions more welcoming for the chytrid. Similarly, white-pine blister rust, a fungus that has devastated some species of white pines across Europe and North America, is expanding to higher elevations where conditions were previously unfavorable. This has put more pine forests at risk. Changing climatic conditions are also helping drive fungal pathogens of crops, like those infecting bananas and wheat, to new areas.

[Read: We’re giving up on the (frog) pandemic]

A warming climate also changes cycles of droughts and intense rains, which can increase the risk of fungal diseases in humans. One study of more than 81,000 cases of valley fever in California from 2000 to 2020 found that infections tended to surge in the two years immediately following prolonged droughts. Scientists don’t yet fully understand why this happens. But one hypothesis suggests that Coccidioides survives better than its microbial competitors during long droughts, then grows quickly once rains return and releases spores into the air when the soil begins to dry again. “So climate is not only going to affect where it is, but how many cases we have from year to year,” says Gorris.

By triggering more intense and frequent storms and fires, climate change can also help fungal spores spread over longer distances. Researchers have found a surge in valley-fever infections in California hospitals after large wildfires as far as 200 miles away. Scientists have seen this phenomenon in other species too: Dust storms originating in Africa may be implicated in helping move a coral-killing soil fungus to the Caribbean.

Researchers are now sampling the air in dust storms and wildfires to see if these events can actually carry viable, disease-causing fungi for long distances and bring them to people, causing infections. Understanding such dispersal is key to figuring out how diseases spread, says Bala Chaudhary, a fungal ecologist at Dartmouth who co-authored an overview of fungal dispersal in the 2022 Annual Review of Ecology, Evolution, and Systematics. But there’s a long road ahead: Scientists still don’t have answers to several basic questions, such as where various pathogenic fungi live in the environment or the exact triggers that liberate fungal spores out of soil and transport them over long distances to become established in new places.

Helping existing fungal diseases reach new places isn’t the only effect of climate change. Warming temperatures can also help previously innocuous fungi evolve tolerance for heat. Researchers have long known that fungi are capable of this. In 2009, for example, researchers showed that a fungus—in this case, a pathogen that infects insects—could evolve to grow at nearly 37 degrees Celsius, some five degrees higher than its previous upper thermal limit, after just four months. More recently, researchers grew a dangerous human pathogen, Cryptococcus deneoformans, at both 37 degrees Celsius (similar to human body temperature) and 30 degrees Celsius in the lab. The higher temperature triggered a fivefold rise in a certain type of mutation in the fungus’s DNA compared with the lower temperature. Rising global temperatures, the researchers speculate, could thus help some fungi rapidly adapt, increasing their ability to infect people.

[Read: The bigger this fungus gets, the worse we’re doing]

There are examples from the real world too. Before 2000, the stripe-rust fungus, which devastates wheat crops, preferred cool, wet parts of the world. But since 2000, some strains of the fungus have become better adapted to higher temperatures. These sturdier strains have been replacing the older strains and spreading to new regions.

This is worrying, says Casadevall, especially with hotter days and heat waves becoming more frequent and intense. “Microbes really have two choices: adapt or die,” he says. “Most of them have some capacity to adapt.” As climate change increases the number of hot days, evolution will likely select more strongly for heat-resistant fungi.

And as fungi in the environment adapt to tolerate heat, some might even become capable of breaching the human temperature barrier.

This may have happened already. In 2009, doctors in Japan isolated an unknown fungus from the ear discharge of a 70-year-old woman. This new-to-medicine fungus, which was given the name Candida auris, soon spread to hospitals around the world, causing severe bloodstream infections in already sick patients. The World Health Organization now lists Candida auris in its most dangerous group of fungal pathogens, partly because the fungus is showing increasing resistance to common antifungal drugs.

“In the case of India, it’s really a nightmare,” says Arunaloke Chakrabarti, a medical mycologist at the Postgraduate Institute of Medical Education and Research in Chandigarh, India. When C. auris was first reported in India more than a decade ago, it was low on the list of Candida species threatening patients, Chakrabarti says, but now, it’s the leading cause of Candida infections. In the U.S., clinical cases rose sharply from 63 in the period from 2013 to 2016 to more than 2,300 in 2022.

Where did C. auris come from so suddenly? The fungus appeared simultaneously across three different continents. Each continent’s version of the fungus was genetically distinct, suggesting that it emerged independently on each continent. “It’s not like somebody took a plane and carried them,” says Casadevall. “The isolates are not related.”

Because all continents are exposed to the effects of climate change, Casadevall and his colleagues think that human-induced global warming may have played a role. C. auris may always have existed somewhere in the environment—potentially in wetlands, where researchers have recovered other pathogenic species of Candida. Climate change, they argued in 2019, may have exposed the fungus to hotter conditions over and over again, allowing some strains to become heat-tolerant enough to infect people—although the researchers cautioned that many other factors are also likely at play.

Subsequently, scientists from India and Canada found C. auris in nature on the Andaman Islands in the Bay of Bengal. This “wild” version of C. auris grew much slower at human body temperature than did the hospital versions. “What that suggests to me is that this stuff is all over the environment and some of the isolates are adapting faster than others,” says Casadevall.

Like other explanations for C. auris’s origin, Casadevall’s is only a hypothesis, says Chakrabarti, and still needs to be proved.

One way to establish the climate-change link, Casadevall says, would be to review old soil samples and see whether they have C. auris in them. If the older versions of the fungus don’t grow well at higher temperatures, but over time they start to, that would be good evidence that they’re adapting to heat.

In any case, the possibility of warmer temperatures bringing new fungal pathogens to humans needs to be taken seriously, says Casadevall—especially if drug-resistant fungi that currently infect species of insects and plants become capable of growing at human body temperature. “Then we find ourselves with organisms that we never knew before, like Candida auris.”

Doctors are already encountering novel fungal infections in people, such as multiple new-to-medicine species of Emergomyces that have appeared mostly in HIV-infected patients across four continents, and the first record of Chondrostereum purpureum—a fungus that infects some plants of the rose family—infecting a plant mycologist in India. Even though these emerging diseases haven’t been directly linked to climate change, they highlight the threat that fungal diseases might pose. For Casadevall, the message is clear: It’s time to pay more attention.

The Science of Consciousness Is Having a Rumble

The Atlantic

www.theatlantic.com › technology › archive › 2023 › 09 › integrated-information-theory-consciousness-scientific-explanation › 675503

For years now, Hakwan Lau has suffered from an inner torment. Lau is a neuroscientist who studies the sense of awareness that all of us experience during our every waking moment. How this awareness arises from ordinary matter is an ancient mystery. Several scientific theories purport to explain it, and Lau feels that one of them, called integrated information theory (IIT), has received a disproportionate amount of media attention. He’s annoyed that its proponents tout it as the dominant theory in the press. He’s disturbed by their apparent affinity with New Age figures, such as Deepak Chopra. Worst of all, he complains, the theory doesn’t even rise to the level of “science.”

IIT was first formulated by Giulio Tononi in 2004. It’s meant to quantify the consciousness that exists in any system, based on the total information that is brought together by its constituent parts. Other theories of consciousness tell more of a general story about how the brain generates consciousness; IIT gives it a mathematical expression. Controversially, IIT also suggests that there is consciousness in systems that we wouldn’t usually think of as being aware, including photodiodes and thermostats. Anil Seth, a neuroscientist who is not himself opposed to IIT, nonetheless described it to me as “kind of a bonkers theory.”

Lau has expressed his many concerns to colleagues at conferences, in the hallways between sessions and afterward over drinks at the bar. Many of them have been sympathetic, he told me, and share his fear that their whole field would be a laughingstock if a theory that deems smoke alarms conscious were to be taken as its public face. Lau also worries that naive students could be deluded into thinking that the theory is stronger—or perhaps less bonkers—than it really is. This summer, Lau set about convincing his colleagues that they should express their contempt for IIT as a group, in print. He succeeded: On September 16, more than 100 of them released an open letter. Within 24 hours, a full-blown brawl had broken out on social media.

Scientists who study consciousness are touchy about the way the field is perceived. They’ve been fighting for respectability for decades. “It wasn’t always treated as a particularly legitimate thing to do,” Seth told me. The field has been largely isolated from mainstream psychology and neuroscience, and as a result, researchers can have trouble attracting funding. Consciousness research has gradually become more accepted, but even today it’s not often bankrolled by the National Science Foundation or the National Institutes of Health. Many scientists must instead rely on private donors.

In 2020, a consortium of scientists and philosophers secured $3.2 million from one such donor, the Templeton World Charity Foundation, for a series of “adversarial” experiments. The idea was for proponents of different theories of consciousness to design experiments using neuroimaging technology, and to agree, in advance, which results would support which theory. In June of this year, they announced the first results from a showdown that pitted IIT against the theory that consciousness arises from something called a “workspace” that brings together information from the senses and other cognitive processes into a coherent whole and broadcasts it to other neural regions. The outcome was largely unsatisfying.

[Read: A famous argument against free will has been debunked]

Existing technology is still too crude to test either theory’s most meaningful hypotheses, but the experiment did suggest that conscious experience involves continual activity of neurons at the back of the brain. According to the experts, this finding fits IIT better than the alternative, but only narrowly, and not in a way that could be said to elevate it above all other theories of consciousness. Still, any public perception that IIT had achieved an empirical triumph galled Lau, and when the results were covered in Science, Nature, and The New York Times, it tipped him over the edge.

“I didn’t want to act alone,” Lau told me. He drafted a letter criticizing IIT and sent it to another scientist who shared his dim view of the theory. Over the next six weeks, they worked on revisions, before passing the letter on to eight more scientists for further edits. After this core group had settled on a final version, they began distributing it more widely. This time, there was no request for edits; just signatures. Word of the letter began to spread, even among those who had not been asked to sign. When at last the preprint was released, its 124 signatories included neuroscientists, behavioral scientists, philosophers, and psychologists.

Despite all the effort that went into its creation, the letter was, admittedly, thin on substance. Running just five paragraphs in all, its first half takes aim not at the scientific underpinnings of IIT, but rather at the ways in which the theory is portrayed in news media. It complains that the reporters who covered the initial findings from the adversarial experiments falsely anointed IIT the “dominant” theory of consciousness; and it describes the public as having been victimized by “scientific misinformation.” But as Erik Hoel, who completed his doctorate in neuroscience under Tononi, has pointed out, none of the five media sources cited in the letter say anything of the kind. The first news story mentioned is headlined “Consciousness Hunt Yields Results, but Not Clarity.” Hoel told me that he read through each of the others, and although one did say that IIT “has a leg up,” it qualified that there were still “continuing doubts” about the results.”

The letter’s second half calls out IIT for having “panpsychist commitments,” and says that because the theory’s core claims are untestable it should be thought of as a “pseudoscience,” like astrology. “A lot of the people who signed on to the letter were a little uncomfortable with the use of that word,” one of the signatories, Joshua Shepherd, a philosophy professor at Carleton University, in Canada, told me. “If you’re going to make a strong claim like that, then you have to give some very strong evidence,” David Chalmers, a professor at NYU and one of the foremost philosophers of consciousness, told me. “Given the 100-plus very well-known figures who signed the letter, I was expecting something more solid, and I think a lot of people had reactions like that.” Seth told me he was surprised by the list of names at the bottom of the letter. “I know that some of them know nothing about IIT and probably didn’t know what they were signing,” he said.

[Read: Most popular theories of consciousness are worse than wrong]

The online backlash was immediate. On X (formerly Twitter), scientists derided the letter as a “childish” product of “intellectual dishonesty.” It was called “shameless mudslinging” and a “hit” job. One scientist complained that cancel culture had now come for ideas. Others suggested that the letter had been motivated by politics or even financial interests. The conflict spilled over into dueling edits on Wikipedia, concerning whether IIT should be tagged as a pseudoscience. At least one scientist who signed the letter says that he received an email warning of “personal and professional consequences.” Lau himself complained that an angry mob was out to get him, and was in turn accused of playing the victim.

Several experts told me that the letter’s inclusion of Daniel Dennett, a longtime heavyweight in the field, was significant. Hoel was unfazed, however. “Dennett is not really on the front lines anymore,” he said. IIT was being punished, he continued, for daring to be a formal mathematical theory. Other, story-based theories of consciousness don’t offer any precise mathematical model of consciousness that an experiment could locate. How is someone supposed to tell which theory is pseudoscience and which isn’t? One observer likened the situation to a bunch of people standing on step ladders in a field arguing over who is closest to the moon.

Critics of the letter argued that the field should be keeping up appearances, for the sake of continued funding. (In a way, their concern mirrors Lau’s own.) Seth told me that claims of pseudoscience risk giving ammunition to people who are already skeptical. Chalmers agreed: “If funders look on and they say, ‘This is a field where half the people are calling the other half pseudoscientists,’ I worry that this could have implications for everybody.” On social media, he went so far as to compare using the “pseudoscience” tag to dropping a nuclear bomb in order to settle a regional dispute.

Lau, who lives in Japan, called this talk of nuclear war “unhinged” and insensitive. He said that he’d tried taking a more diplomatic tack before drafting the letter, but it didn’t work. Some years ago, he told me, he’d written to Christof Koch, an investigator at the Allen Institute, in Seattle, and one of the most visible proponents of IIT, to try to clear the air. (Among other things, Lau hadn’t liked it when Koch told The New York Times that IIT is “the only really promising fundamental theory of consciousness.”) Lau suggested a Zoom call, and even offered to fly to Seattle for a meeting face-to-face. “Koch said he was too busy.”

Lau does feel bad that the letter sowed such chaos, but he stopped short of expressing regrets. “I stand by everything,” he said. On our last call, he was still insisting that the scientists who work on IIT are the ones who should be soul-searching. “If one-third of the community told me my work is pseudoscience, I would do some reflection,” he said. “Oh?” I asked. “Maybe I would get angry first,” he acknowledged, “but then I would reflect.”

So far, there’s little evidence of reflection, on anyone’s part. I asked Chalmers, who has a wider network in the field than just about anybody, when the conflict might be resolved. He said that he didn’t know, and that emotions are still running high: “I don’t think [we’re] ready for a kumbaya moment just yet.”