‘The Last of Us’: Cordyceps explained by a parasitic mushroom expert

“The Last of Us” began its HBO Max story with a devastating prologue, stamped by Craig Mazin (“Chernobyl”), in which a scientist (John Hannah) explained on a 1968 talk show that humanity does not he would have won the battle against a pandemic caused by a fungus. He made a hypothesis: fungi can’t survive in humans because of our average body temperature, but what if the planet’s temperature rises and the fungus manages to adapt to warmer conditions? Is it possible that real-world civilization has succumbed to Cordyceps like the one in the Pedro Pascal and Bella Ramsey series?

Looking for answers, we spoke to Javier Diéguez Uribeondo, a CSIC researcher specializing in the biology, systematics and evolution of parasitic fungi. When we met him at the Real Jardín Botánico in Madrid, he told us he was pleasantly surprised by the scientific basis of the series: “It’s like ‘Jurassic Park.’ I remember at the time, when we were working on molecular biology and with the first sequencing we were wondering if it was really possible, and technically it is. In this case, theoretically what we see could happen, the times are another thing”.

We will see that time will be our ally in the fight against Cordyceps. But what is Cordyceps? “Cordyceps is a genus, a group of fungi. Fungi are the most successful organisms in evolution. It is the most successful kingdom by number of species: there are more than one and a half million of them, and Cordyceps is one of them “ explains Dieguez Uribeondo. In fact, Cordyceps is a real thing, a branch of the fungal kingdom that also includes many types. Some of these fungi are parasites that infect other species, such as insects, and turn them into lifeless “zombies”: «During the colonization phase they can produce enzymes that degrade the wall of the host, of the insect, in a sequential way. It’s a perfectly engineered genetic mechanism. It colonizes and invades different tissues, in this case the muscles, and secretes toxins that alter behavior. This change in behavior, the result of evolution, has meant that these toxins are the ones that allow the ant to have a behavior that favors the dispersion of the spores. The ant moves, anchors itself and bites the plant right where it allows it to disperse.”.

This process, which can be seen in David Attenborough’s documentary series ‘Our Planet’ (available on Netflix), was one of the sources of inspiration for Bruce Straley and Neil Druckmann, creators of the video game on which ‘The Last of us’. As Javier Diéguez Uribeondo explains to us, the hypha (the filament of the fungus) makes its way through the head of the host, “generate a sporangium and release spores to be dispersed”. In the series there are no spores, at least not for the moment, but the mushroom has hyphae in the form of the filaments that we have seen so well in “The kiss” of the second chapter. Diéguez comments that hyphae have mobility, but not at the speeds shown in the series. He also believes that the transmission of the fungus by bite is part of the “fiction” part of science fiction, but this would also serve to explain how the fungus can survive without the right conditions of temperature and humidity: “If transmitted by air, the fungus would need a warm temperature of 20-30 degrees, no more, and a very humid environment. In environments like Texas that would be unlikely”.

Our body temperature is one of our main protective barriers against most fungi, and it is a question that amazes the scientific community: “It is the key and the big evolutionary question: why do we have a constant high temperature? There is a hypothesis: mammals were able to spread and colonize the Earth thanks to the fact that the meteorite impact provided the conditions for the degradation of dead animals in the jungles that have disappeared, from the compost, and this has favored the growth of fungi. That mammals and birds, which are the only surviving dinosaurs, can regulate the temperature is an evolutionary key that is unknown born, but which has an answer and controls one of the most serious pathogens that exist, which are fungi. Mammals have virtually no fungal infections because they cannot live at our temperature”. Now, there are cases where we could be in danger: “In cases where our immune system is depressed or our body temperature is affected, such as immunosuppression due to chemotherapy or cases of burns. That’s why burn operating rooms are almost 40 degrees”.

The series blames climate change on the fact that the fungus has mutated to adapt to higher temperatures, such as those of the human body. However, Javier Diéguez Uribeondo points out that our immune system has more barriers to deal with a large number of fungi and that “the evolutionary machine” it doesn’t work that fast. Let’s talk about “millions of years” for a fungus to evolve to the point where it can survive in the human body.

Maybe not a Cordyceps, but there may be other fungi that could pose a problem for us. Arturo Casadevall, an expert in molecular microbiology and immunology at the Josh Hopkins Bloomberg School of Public Health, reports to National Geographic the case of Candida aurisThat “appeared out of nowhere” on three different continents and which is believed to have been caused by the increase in temperature. “The idea is that this fungus was there, and over the years it adapted to higher temperatures until it made it.” He says and concludes: “Am I concerned about an unknown disease emerging and infecting immunocompetent beings? Sure.”.

Diéguez Uribeondo points out other environmental conflicts that may be a closer problem than Cordyceps in humans, such as monocultures and globalization: “The alteration of the conditions can make some organisms predominate. It is the case of ‘Interstellar’, it is the scenario we are facing: monoculture of corn to feed an overpopulation, totally altered climate. If a pathogen manages to colonize that monoculture and specializes, ends with everything”. Do you think these issues should have been addressed? “last century”but don’t lose faith: “The hope is that, if we are intelligent beings, we find the solution and can control it”. He believes what happened with the coronavirus is a sign that we are capable of reacting, but he supports prevention and, above all, more funding for science: “COVID is an example of how biology has allowed a miracle to be performed, which is that vaccines were generated in a year. If something were to happen with the mushrooms, we are theoretically prepared to develop the antidotes, so to speak, but that requires a huge investment and right now we are looking into what the more immediate concerns are.What are bacterial diseases?.

There are also other weather emergencies that should concern us: “There are always so many complaints that we want to alarm the population. No, the point is to know what’s going on. Climate change has been happening for a long time and we have already passed the tipping point because something had to be done” says the biologist, who attributes the problem to “Absolute laziness, starting with the politicians, no matter what party they are. For example, they are about to make a decision on the issue of environmental impact: not making reports to speed up the implementation of solar and wind panels due to the energy crisis. Without relationships it is bread for today and hunger for tomorrow. This will bring another patch, and another, and another.”.

Returning to ‘The Last of Us’, asking him about that network of roots with which the infected communicate with each other, Diéguez Uribeondo theorizes about its possible inspiration: “I think this idea comes from a fact that occurs in a type of fungus called mycorrhizae, which are symbionts. In symbiosis with the roots of plants, they allow them to absorb certain nutrients and be more effective.”. And while there are types of mushrooms that can be a problem, also remember that thanks to other mushrooms we have bread, beer and there is also a type of Cordyceps which is used for medicinal purposes in China.

The ‘The Last of Us’ effect

At the beginning of our conversation, Javier Diéguez Uribeondo, who is also director of the Official Master’s Degree in Tropical Biodiversity and its Conservation at the CSIC, great that “The Last of Us” is a “Avalanche” of new aspiring mycologists in the future: “When we go out to preach, to recruit people for mycology, it’s difficult because it doesn’t have the same prestige as studying entomology or aquatic mammals, for example. The way we had to recruit them was ‘you will study the diseases of these animals and work with them, but in something new.” Several students have “fell into that trap”, but It’s a great choice because it’s something few people work on and it’s very necessary”. That’s why he appreciates so much the investigative component that he has noticed behind the series and the interest it can arouse: “It’s great to see that what you’re working on can have such importance and impact”. Finally, underline that we are calm, ‘The Last of Us’ will have a good basis, but none of us will see a similar scenario: “We can idly watch the series and think that maybe if we happen to put up with more than we seem to put up with, we are sufficiently investigated to be able to fight back”.

‘The Last of Us’ premieres a new chapter every Monday on HBO Max.