The science of The Last of Us: should we fear a fungal zombie pandemic? Natália Pasternak The Skeptic

In the premiere of “The Last of Us,” a TV series based on the computer game of the same name, a fungus causes a pandemic that turns people into zombies and changes their behavior. The show instilled the following question into popular imagination: could such a pandemic actually happen in real life? Let’s face it, the prospect of a new pandemic, in which a microorganism devours the brain of its victims, sounds quite frightening – especially after having just emerged from a pandemic, during which the political discourse of denialism turned a significant portion of the Brazilian population into yellow-and-green-clad zombies.

The series begins with a talk show from the 1960s, in which a scientist claims that viruses and bacteria are not so menacing for the future of humanity, and that what we should really be afraid of are fungi. According to this scientist, because of global warming, some of the fungi capable of controlling the behavior of insects could “easily” adapt to a temperature closer to that of the human body and infect us. We would then be doomed, since there is no way to develop drugs or vaccines against fungi.

Is there any fact behind the fiction? Well, there are fungi that infect and disrupt the behaviour of insects. One of these, Ophiocordyceps unilateralis, inspired the creator of “Last of Us” (the computer game). Popularly known as cordyceps, this fungus produces spores — reproductive cells — that infect ants and develop in haemolymph, the blood of insects. After a few days, the ants begin to exhibit behavioural changes.

A study published by the team led by Professor David Hughes, who acted as a consultant for the game and other zombie films, explains this process well: the infected ants move away from the nest, start having muscle spasms, and climb on leaves or branches at about 25 cm from the ground. Then they clench their jaws into these leaves and remain there while the fungus devours them from the inside, and forms filaments that will produce more spores. These ants, “possessed” by the fungus and hanging over a path where healthy insects pass, will then increase the probability of new spores falling on top of other ants.

This highly specialised and successful strategy is the result of thousands of years of parasite-insect co-evolution — successful for the fungus, mind you, because hanging with your jaw locked into a leaf while another creature controls your muscles doesn’t strike me as a success story for the ant. Here, natural selection has given the fungus a greater chance of reproduction. For example, the fact that infected ants leave the anthill to hang in a nearby location is essential. If they had shown symptoms of the disease while still inside the anthills, they would have probably been eliminated by the colony. In addition, the ideal environment for fungus growth is cooler and more humid than the inside of an anthill. Finally, by keeping its victim hanging from a leaf, the fungus ensures that its spores will fall on other passing ants, thus infecting a greater number of new hosts. If the ant had died on the ground, the chances of the spores spreading would have been significantly lower.

It’s still not entirely clear how the fungus manages to take control over the host’s body; however, contrary to how the story plays out in the TV show, the parasite does not invade the brain. According to recent studies, a more likely explanation involves some substance interfering with muscle contractions. Professor Hughes’ team detected an increased production of toxins, and greater activation of genes related to the production of ergot alkaloids, compounds produced by fungi that can change behavior, and cause seizures and hallucinations. Fungi produce psilocybin and LSD precursors, compounds that are potent psychedelics.

Historical cases of ergotism – or “St. Anthony’s Fire,” a disease caused by eating rye contaminated by fungi – are well documented in the literature, and produce symptoms of epilepsy, convulsions, hallucinations, and gangrene. Ergot alkaloids are structurally similar to neurotransmitters, such as serotonin. They also cause reduced blood flow, and sometimes tissue necrosis, particularly in the extremities. In addition, they can stimulate the central nervous system, triggering a range of changes in one’s mental state, ranging from hallucinations to depression.

Several ergotism “epidemics” are described in the literature. The most recent ones occurred in 1928, in England, and in 1951, in France, both caused by rye bread contaminated with the Claviceps purpurea fungus. The observed effects were a state of delirium, suicidal thoughts, intense pain and burning sensations, gangrene, and loss of limbs.

Zombie-creating fungi that attack cicadas of the Massospora cicadina species deploy a hallucinogenic compound that makes the insects fly wildly, releasing spores in every direction. And that’s only after the fungus has literally eaten the insect’s genitals and butt! The male cicadas usually sing to attract females. Once infected, and even after losing their genitals, they continue to make music, and, if they manage to attract a female, they transmit the fungus to her. The male’s behavior also changes: he flaps his wings in a way that imitates females, thus attracting other unsuspecting males who also end up becoming infected. The fungus is so successful that it manages to spread its spores not only through the flight of the cicadas, but also through their sexual activity.

So much for insects, but what about us?

Would the emergence of a zombie-creating fungus capable of infecting humans be possible, perhaps as a result of climate change, as suggested by the scientist’s character in the TV series?

It’s unlikely. These parasites are highly specialised, they infect one and only one host species. Fungi that infect certain ants are not the same as those that infect caterpillars or cicadas, or even other ant species. Bear in mind that a parasite needs thousands or even millions of years of co-evolution before it can dominate its host. Furthermore, the warming of the planet seems to be quite detrimental to the parasite.

The cordyceps that infects ants is not the only fungus of its kind. There are hundreds of species of cordyceps that infect different insects, and more than 30 that cause behavioural changes. A well-known type, which became popular for very different reasons, is Ophiocordyceps sinensis, also known as the “Viagra of the Himalayas.” This fungus parasitises caterpillars, and is used in traditional Chinese medicine not only as an aphrodisiac and a remedy for sexual impotence, but also to allegedly cure cancer and diabetes. In addition, it’s sold as an energy booster in natural supplement stores, where it may cost as much as $125 a gram. Although it has created a multimillion dollar market, its effectiveness for anything other than parasitising caterpillars has never been confirmed by science. Nevertheless, high demand and global warming have placed the fungus on the endangered species list. The parasite thrives in low temperatures, and its numbers have plummeted owing to climate change and overexploitation.

The TV series was right in attributing the origin of the pandemic to grain contaminated by the fungus, but it changed the mode of transmission of the spores — achieved through dispersion in nature — into one effected by the bites and aggressive behavior of human zombies. Insects infected by fungi do not show aggressive behavior, and the only thing resembling a bite is the ant jaw clutching the leaf to attach itself. The spores are dispersed through the air and fall to the ground. In this respect, the microorganism causing the infection in the TV series more closely resembles the rabies virus than a zombie-creating fungus. The creators of the series justify that they made the change to prevent the actors from having to wear masks all the time (in the computer game, the spores are dispersed through the air, as expected).

Hope for a cure?

Another doomsday prediction made by the epidemiologist in the series is that we would certainly lose a war against fungi, because it would be “impossible” to develop a cure. It is true that our cells are much more similar to those of a fungus than to bacterial cells, which makes it difficult to develop a drug capable of killing the fungus while preserving human cells. There are few antifungals on the market. However, given the right incentives — such as a global health emergency — it would certainly not be impossible to find a cure or invent a medicine, and, ironically, the solution might perhaps come from another fungus.

Researchers working with the zombie-creating fungus of ants have recently discovered two species of different fungus that infect the zombie-creating fungus itself. The mechanism is still not well understood, but the researchers report that cordyceps is consumed by these parasitic fungi, and that, in some cases, the new fungus “castrates” the cordyceps, rendering it unable to reproduce, and then devours it. Fungi and bacteria compete for space and nutrients, and it’s not uncommon for them to produce compounds that kill their competitors. That’s how we discovered most antibiotics produced by bacteria.

A non-fictional threat

While the zombie pandemic may only be fictional, global warming can indeed render the world more susceptible to emerging diseases, not diseases caused by highly specialised fungi, but rather — and much more likely — by viruses transmitted by mosquitoes that can become endemic in regions that were previously very cold, or simply by facilitating the encounter between species that can exchange microorganisms.

The regions of the world where mosquitoes can exist comfortably are expanding, thereby increasing the opportunities for disease-carrying insects (e.g. dengue, zika, yellow fever, chikungunya, and malaria) to become endemic in places where they were not endemic before. Warming also reduces the habitat of species accustomed to milder climates, and these then tend to migrate to more favorable areas. The encounter of several species that had previously been separated geographically can favor the spread of viruses and bacteria—and fungi for that matter—from one species to another, thus increasing the number of potential hosts.

Confined animal breeding facilitates the transmission of diseases, and contact with humans makes it easier for microorganisms to “jump” from animals to humans, and adapt. This is what happened with the bird flu and the swine flu. Illegal wild animal markets also put us in contact with species acting as reservoirs of microorganisms, which we would otherwise hardly cross paths with in nature.

The apocalypse, whether or not it is caused by an uncontrollable and much more aggressive pandemic than that of COVID-19, is much more likely to result from this set of irresponsible human actions than from a fungus that turns ants into zombies.

This article was translated from the original Portuguese by Ricardo Borges Costa.

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The hit TV show The Last of Us depicts a world hit by a fungal-caused pandemic that turns the infected to zombies – but could it happen in real life?
The post The science of The Last of Us: should we fear a fungal zombie pandemic? appeared first on The Skeptic.

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