Frightened by fungal zombies in The Last of Us? The real-life threat is terrifying, too | CBC News

This is an excerpt from Second Opinion, an analysis of health and medical science news emailed to subscribers weekly. If you haven’t subscribed, you can do that by clicking here.

During the pilot episode of HBO’s The Last of Us, a scientist on a talk show lays out a grim possibility: What if more types of mind-altering fungi evolved to survive the high temperatures within the human body?

“What if, for instance, the world were to get slightly warmer?” the fictional researcher continued, in front of a perplexed studio audience. “Well, now there is reason to evolve.”

The scene kicks off the apocalyptic saga to come — a world decimated by a fungal pathogen which takes over its human hosts, effectively turning them into zombies.

Unfortunately, the Cordyceps fungus family is real, and some are already capable of invading certain insects, replacing their host tissue and leaving them in a zombie-like state.

Is there a chance a fungi could one day mutate in a manner that could take over our brains and bodies, too?

That’s a stretch, scientists say. But actual fungal evolution, and the very real threat these pathogens pose to human health, is almost as concerning as science fiction.

“People most often think about fungi as foot infections, or something kind of trivial, as opposed to a deadly disease. But what we have seen is — now that people are actually paying attention — fungi are killing more than 1.5 million people every year,” said Leah Cowen, a professor in molecular genetics at the University of Toronto and co-director of the fungal kingdom program at the Canadian Institute for Advanced Research (CIFAR).

Many of them, she added, are likely mutating in the face of climate change, spreading to new regions of the world, and becoming increasingly drug-resistant — all while scientists are scrambling to diagnose and identify rapidly emerging fungal threats.

“We really have, almost, a silent pandemic,” Cowen said.

Thousands of fungal threats exist

It’s long been known that fungi can alter minds and, under some circumstances, kill their hosts.

Think of recreational drugs like magic mushrooms or LSD: Both come from fungi, and both can cause hallucinations or other brain-bending side effects.

Then there are a host of life-threatening fungi, including close to 20 priority pathogens outlined last fall in a report from the World Health Organization (WHO).

One of those, Candida auris, was first discovered in a patient’s ear in Japan in 2009.

 “And no one knew what it was,” said Dr. Hatim Sati, the technical lead on the WHO’s last fungal report. “Fast forward to today, and Candida auris has been reported in over 55 countries.”

Capable of causing severe infections, it’s also tricky to identify and known for causing hospital outbreaks — and some strains are resistant to every available drug. 

“There are over 700,000 species of fungi, and many of them have everything that they need in order to successfully kill a human being,” said Dr. Andrej Spec, a researcher into fungal infections and an associate professor of medicine at the Washington University School of Medicine in St. Louis, Missouri.

Those kinds of dangerous pathogens, including many rarely seen by the medical community, are often found inside the patients that come through his clinic. In one bizarre case study, a fungus known for causing cankers in locust trees randomly appeared inside his 78-year-old patient’s knee, causing months of mysterious pain and swelling before the man was eventually diagnosed.

For people who are more vulnerable, including anyone immunocompromised or suffering from conditions like cancer, the infections are far more likely to turn deadly. There are also countless unknown fungal threats lurking around the world, which can impact plants and insects, but not humans — at least not yet.

Links between heat, fungal evolution

“The main difference between them and the fungi that do cause our disease is that they don’t tolerate our body temperature [of 37 C],” Spec said.

As the climate warms up, and the world experiences more extreme weather events, it’s “changing the evolutionary pathway of these fungi to become more heat tolerant,” he added.

Spec’s own research, published last winter in the journal Clinical Infectious Diseases, suggests several types of fungi that were once thought to be confirmed to certain regions of the U.S. are now far more widespread — while another study in the Annals of Internal Medicine found more than 10 per cent of fungal infections are now being diagnosed outside regions where those threats were known to circulate.

“I think we’re going to see more unusual fungi emerge over the next few decades as well, ones which we’ve not traditionally seen infect patients,” said one of the authors, University of California-Davis researcher Dr. George Thompson. “I think climate change will play a role in that.”

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A new paper, out this week in the journal PNAS, pushes the theories around fungi and climate change one step further, by gauging the impact of heat on one species in a lab. 

The Duke University team studied the human fungal pathogen Cryptococcus — a “big killer,” said researcher Asiya Gusa —  and assessed its genome under different conditions.

“We found that genetic changes in the fungus occurred more rapidly when cells were grown under heat stress,” Gusa told CBC News.

While a laboratory setting doesn’t directly apply to the real world, the University of Toronto’s Cowen — who wasn’t involved in the research — said the study does offer a glimpse at the potential mechanisms at play in allowing fungi to evolve in ways that might, in some cases, pose a bigger threat to human health. 

“If heat stress acts as a trigger for mutation adaptation,” Gusa said, “then it’s just a little bit scary that this could happen faster than we anticipated.”

Fungal infections remain tough to treat

Also concerning, scientists say, is that fungal infections are notoriously tough to treat.

That’s largely because fungi and humans have more in common than you’d think. Both are eukaryotic organisms, part of a diverse array of species — including all animals and plants — whose cells contain a nucleus and a host of other components which perform different functions. 

Viruses, in contrast, aren’t cellular organisms at all, which means medical treatments are targeting a totally different type of threat.

But when you’re trying to target a fungi while it’s living inside a human host, things get tricky.

“The problem is that most anti-fungals are also pretty good anti-humans,” Spec explained. “And it’s a balancing act of finding a drug that kills the fungus, but doesn’t kill the patient.”

As more fungi become resistant to the drugs that do work against them, and their global reach grows, scientists are concerned we’re reaching a tipping point where fungal pathogens will have a growing impact on human health — no televised zombies required.

The reality is fungi are already capable of thriving in a multitude of environments. Fungal spores can exist in the soil, inside hospital ductwork, or in people’s homes, and various forms of fungi can also colonize human skin. Mould even grows within the International Space Station, far from their typical environments on earth.

“Fungi are mobile, many of them dispersed by spores, and those are very much airborne and move all over the place,” said Cowen.

That means if the world witnessed the rise of a highly-contagious fungus, the protective measures used against other pathogens might not work, warned Spec. 

“Outside, you’re not safe. In your house, you’re not safe. If you have a HEPA filter, you’re not safe,” he said. “In ‘Bubble Boy’ rooms, they still get fungus in there. And so fungus cannot be kept out of an environment. So that’s the part that’s really scary.”

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Pandemic potential

So, do fungi have pandemic potential? Maybe not like the catastrophic scenes in The Last of Us. 

But the answer is still “yes,” said Dr. Arturo Casadevall, a professor of microbiology at the Johns Hopkins Bloomberg School of Public Health, and a longtime researcher into fungal threats.

While there’s no record of a fungal pandemic impacting humans, other animals, including frogs, have been decimated by certain fungi. A U.S. bat species has also been driven to the brink of extinction by white-nose syndrome, a fungal disease. So don’t rule out something similar happening to us, Casadevall said.

“Just because it doesn’t happen, doesn’t mean it can’t happen,” he added. “When I went to medical school, in the beginning, retroviruses were not thought to be pathogens to humans — and HIV gave us a pandemic. And when I was in medical school, coronaviruses were supposed to give you a cold … now we have had SARS, MERS and the great pandemic of 2019.”

All rooted in reality — not a TV show or video game.

“We need to be concerned [about] threats from the fungal world,” Casadevall said. “And just because they haven’t happened is no sense for complacency.”