Zombie in "The Last Of Us"
Let's face it: having just gone through a pandemic where denialist political discourse turned a significant part of the population into something resembling zombies, the prospect of a new pandemic where a microorganism itself devours the victims' brains is an unsettlingly real prospect.
The TV series, based on the video game of the same name, begins with an interview program from the 1960s, where a scientist argues that humans should be less concerned about viruses and bacteria, and more afraid of fungi, which can control the behavior of insects, and with global warming, could in theory adapt to a temperature closer to the human body and infect us.
With no current way to develop drugs or vaccines for such an infection, we would be lost.How much of this is a true story? There really are fungi that infect and alter the behavior of insects. One of these, the Ophiocordyceps unilateralis, inspired the creator of the videogame "The Last of Us." Popularly known as Cordyceps, the fungus produces spores – reproductive cells – that infect ants and multiply in the haemolymph, an insect's blood. After a few days, ants begin to show changes in behavior.
A study published by biologist David Hughes, a consultant for the game and for other zombie films, explains this process: the infected ants move away from the anthill, show muscle spasms and climb onto leaves or branches about 25 centimeters from the ground, sinking their jaws into the branch and remaining there, while the fungus eats them from the inside and eventually forms filaments that project out of their bodies and produce more spores. With the “possessed” ant hanging over the path where healthy insects pass, the probability of new spores falling on more ants is high.
Reality or fiction?
This highly specialized strategy is the result of a co-evolution between parasite and insect that took thousands of years to achieve such success – for the fungus, that is, because hanging with its jaw locked on a leaf while another organism controls its muscles does not seem to be good for the ant. Natural selection has ensured the greatest chance of reproduction for the fungus. For example, the fact that infected ants leave the anthill to hang nearby is essential. If they showed symptoms of the disease while still inside the nests, the colony would probably dispose of them. The ideal environment for fungus to grow is also cooler and wetter than the anthill's interior. And keeping the victim hanging from a leaf or branch ensures the fungus that its spores will land on passing ants, infecting a greater number of new hosts. If the ant died on the ground, the chances of the spores spreading would be much lower.
It's still not clear how the fungus takes control of the host's body; but contrary to fiction, the parasite does not invade the brain. Instead, according to recent studies, it's likely that some substance interferes with muscle contraction. Hughes research detected an increase in the production of toxins, and greater activation of the genes related to the production of ergot alkaloids, which are compounds produced by fungi that can change behavior and cause seizures and hallucinations.
Altered behavior
Fungi produce compounds including psilocybin and the chemical precursors to LSD, both of which are potent psychedelics. Historical cases of ergotism, also called St. Anthony's Fire, caused by eating rye contaminated with fungi are well documented. Ergotism causes epilepsy, convulsions, hallucinations and gangrene.
The fungus is successful at spreading its spores by taking advantage of the cicadas' flight, and by sexual activity.
The ergot alkaloids are structurally similar to neurotransmitters like serotonin, and can cause reduced blood flow and sometimes tissue necrosis, especially in the extremities. They can also stimulate the central nervous system, which can trigger changes to the mental state including hallucinations and depression.
Literature documents several “epidemics” of ergotism. The most recent reports are from 1928 in England and 1951 in France, both caused by rye bread contaminated with the fungus Claviceps purpurea. The effects were a state of delirium, suicidal thoughts, a feeling of intense pain and burning, gangrene and loss of limbs.
A zombie fungus that attacks cicadas, of the Massospora cicadina species, uses a hallucinogenic compound that makes insects fly madly, spreading spores widely. And that's only after the fungus eats away the cicada's genitals and buttocks!
Male cicadas usually sing to attract females. Even after losing their genitals, infected males continue to make music and, if they attract a female, transmit the fungus. The male's behavior is also altered: he moves 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 by taking advantage of the cicadas' flight, but also their sexual activity.
Global warming to the rescue?
Is it possible, then, for a zombie fungus to infect humans – maybe as a result of climate change, as "The Last of Us" suggests?
It's unlikely. These parasites are highly specialized: one species of parasite infects only one species of host. Fungi that infect certain ants are not the same as those that infect caterpillars or cicadas. They are not even the same ones that infect other species of ants. Remember that the parasite needs thousands or millions of years of co-evolution before it can take over the host.
Furthermore, global warming seems unfavorable to the parasite.
Ophiocordyceps unilateralis of ants is not the only fungus of this type. Hundreds of species of Cordyceps infect different insects, and more than 30 cause changes in behavior. A well-known type, which became popular for quite different reasons, is the Ophiocordyceps sinensis, also called “Himalayan Viagra.” This fungus, which attacks caterpillars, is used in traditional Chinese medicine as an aphrodisiac and remedy for sexual impotence, and is also claimed to cure cancer and diabetes. It is also found in health food stores as an energy booster, at an average price of $125 USD per gram (although its effectiveness for anything other than parasitizing caterpillars has never been confirmed by science). Demand and global warming, however, have landed the fungus on the endangered species list. The parasite thrives in low temperatures, and with climate change and overexploitation, its numbers have plummeted.
The series was right in attributing the origin of the pandemic to grains contaminated with the fungus. But in nature, spores are transmitted by wide disperson; in the series, the infection is spread through bites and aggressive behavior of human zombies. In real life, infected insects do not show this kind of behavior: the only thing resembling a bite is the ant's jaw, stuck in a leaf, and spores are dispersed through the air and fall to the ground. In this sense, the series' infection is more like the rabies virus than zombie fungus. The creators of the series justified this change (in the game, spores are dispersed through the air) to avoid having actors wear masks all the time.
No cure?
Another part of the series' doomsday prediction: the idea that humanity would lose a war against fungi because it would be impossible to develop a cure. It is true that our cells are much more like those of a fungus than a bacterium, which makes it difficult to develop a drug that kills the fungus but preserves human cells. There are few antifungals on the market. But it's certainly not impossible, given the right incentives – such as a global health emergency – to find or invent more. And the solution may come from another fungus.
The regions of the world where mosquitoes can comfortably exist are expanding.
Researchers working with the zombie ant fungus have recently discovered two species of fungus that infect the zombie fungus. The mechanism is still not well understood, but researchers report that the Cordyceps is consumed by parasitic fungi, and that in some cases, the new fungus “castrates” the Cordyceps, leaving 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 competitors. That's how we discovered most antibiotics, which are produced by bacteria.
While the zombie pandemic is just fiction, global warming may indeed make the world more conducive to emerging diseases – caused not by highly specialized fungi, but more likely by mosquito-borne viruses becoming endemic in regions that were once too cold, or by bringing people into more regular contact with other species that can exchange microorganisms with us.
The regions of the world where mosquitoes can comfortably exist are expanding, creating new possibilities for insects that transmit diseases such as dengue, Zika, yellow fever, chikungunya and malaria to become endemic where they once couldn't survive.
Global warming also reduces the habitat of species accustomed to milder climates, which tend to migrate to more favorable regions. If species that were once geographically separated are forced into closer contact, this could favor the passage of viruses and bacteria – and fungi – from one species to another, increasing the number of possible hosts.
Close-quarters animal husbandry also facilitates the transmission of disease, and contact with humans facilitates the "leap," or spillover, of microorganisms that can adapt to a human host. This was the case with avian and swine influenza. Illegal markets of wild animals also put humans in contact with animals that can be reservoirs of microorganisms, which we wouldn't otherwise encounter in nature.
The apocalypse, if it comes from a pandemic more uncontrollable and aggressive than COVID-19, is much more likely to result from this set of irresponsible human attitudes than from a zombie that attacks ants.
