Could “The Last of Us” Really Happen?

For those who don’t know, The Last of Us is a dark, yet beautifully crafted survival horror game that explores what the world would be like if the majority of the human population were infected by a mutated strain of Ophiocordyceps unilateralis. This video game is critically acclaimed for its storytelling, graphics, and gameplay. It is considered a masterpiece by most of its reviewers and by its players. From the little bit I have played, I would absolutely agree. There are few developers that are able to take a real world scientific event, such as an insect being manipulated by a parasitic fungus, and implement the core concept realistically in a video game. Naughty Dog, the developer of The Last of Us, does this fantastically well.

Ophiocordyceps unilateralis is in fact a real fungus. This species specifically targets ants, generally of the Camponotus genus, and takes over their brains in order to move them to a location with ideal conditions for its reproduction. One of the most interesting things about this fungus is how precisely it manipulates its host. A 2009 study in The American Naturalist found that ants infected with O. unilateralis almost always died gripping a vein on the underside of a leaf (98%) and that this location was significantly more towards the north-northwest side of the plant than any other direction. Camponotus ants were found almost exclusively at a height of 25 centimeters from the forest floor, while closely related Polyrhachis ants were seen at a mean height of 78.43 centimeters. This kind of behavioral control is known as an extended phenotype. The gene expression of a parasite within a host’s tissue causes aberrant host behavior that solely increases the parasite’s fitness. Keep in mind that the ant species in the study colonize the canopy, not the forest floor, so this is extremely complex behavioral manipulation. These infected ants are traveling quite far from their initial position under the control of the fungus. Many infected ants will often die in areas where others already have, because the conditions in these places are favorable for O. unilateralis, leading to high densities of corpses called graveyards. Any healthy ant happening to walk through such an area will likely become infected by the deadly spores.

When O. unilateralis spores come into contact with an ant, they adhere to it and start to penetrate its cuticle. After this, fungal cells start to infest the ant’s entire body and begin to alter its behavior. An infected ant then leaves the colony and starts the trek down toward the forest floor. Once a perfect spot is reached, the ant will bite the vein of a leaf and die with its jaws locked in place. This is known as the death grip, and keeps the ant from falling from the leaf. Any ants that end up dying within the colony due to infection will be carried far away by other workers. Within a few days, the stroma, or stalk, of the fungus will erupt from the back of its host’s head and develop a stromal plate that releases spores when mature. At this point, most of the ant’s original tissue has been replaced by fungus.

Saggital section of a dead Camponotus ant filled with fungus from The American Natrualist – W = white, Bl = black, O = orange, and P = pareithecial plate, which is where the spores originate.

The ants in the video below are not Camponotus or Polyrhachis ants, and the fungus is not O. unilateralis so the hosts show a different behavior. However, it still illustrates the process well.

What a horror it would be if humans were susceptible to such a fate! The question is, could this actually happen? Let’s consider the ant brain for a moment. It has all the general features of a typical insect brain and is very simple compared to a vertebrate brain. However, ants have more well developed areas associated with memory and learning. These “higher” functions are controlled by the – get this – mushroom bodies (it’s funny because we’re talking about fungus taking over an ant brain here and they just happen to have structures called “mushroom” bodies. Oh, it’s not? It’s just me who finds that to be hilarious? Okay then…). Mushroom bodies are much larger in worker ants than they are in the male soldiers, which are more hard wired or pre-programmed. Workers must navigate varying spacio-temporal environments using multiple cues and also remember where food is and where home is. For ants, workers are the most “intelligent”. Still, one lone worker is of no use. It takes the whole colony to have a properly functioning and flourishing nest. An entire colony of ants, which can be up to millions of individuals, does not even come close to matching the complexity of a single human brain. If a fungus were to develop an ability to infect and alter the behavior of humans, this would probably take a ridiculous amount of time to evolve. Human beings would most likely not even be around any longer. But, let’s just roll with it and say that this could happen. What would it be like and how does The Last of Us compare?

Simplified ant brain from Recognition of social identity in ants (Bos and d’Ettorre, 2012).

We’ll start with the mode of infection. In the video game, people seem to become infected by breathing in the spores of the mutant O. unilateralis strain. Those who wear a gas mask in spore filled areas do not become infected. This appears to check out. Human skin is likely to be much less susceptible to becoming invaded by spores, simply because it is so much thicker and has many more layers than insect cuticle. Other fungi are able to infect hosts via inhalation (like some molds), so it would be no different for a mutant fungus; the infection would just result in a different pathology. So getting infected by this fungus is not in question if you breathe the spores in, but you can also fall victim if there is an exchange of bodily fluids, such as from a bite. This is logical as well. If the fungus has infiltrated an infected person’s system as in ants, bodily fluids like saliva and blood may contain fungal cells. These could easily be passed on to a healthy human.

What about the behavioral and morphological alterations? In The Last of Us, any infected individual, even in the early stages, is being driven by the fungus’ gene expression and aims to spread the spores or cells to as many others as possible. There are four main stages of infection from this mutant O. unilateralis: Runners, Stalkers, Clickers, and Bloaters. All of these collectively are referred to as the Infected (noun) in the game. Individuals who have just been infected are classified as Runners. They still cling to a shred of their humanity, however small, and try to resist the fungus’ behavioral control. However, if they are startled or as the infection progresses, they will snap and attempt to attack anyone nearby who is healthy. Stalkers are fully controlled by O. unilateralis and start to show fungal growth on the face. This fungus strain attacks the eyes first, so they have poor vision and begin to exhibit primitive signs of echolocation. In Clickers, the face has been fully engulfed by fungal growth and rendered the host completely blind. These Infecteds use clicking and screeching to crudely survey their surroundings within a small radius. The growth on the head and face forms a roughly dish shaped plate that helps to direct the clicks. Bloaters are the final stage and can take 10-15 years to develop. The entire body of this Infected is now covered in fungus, some of it showing bioluminescence, and is therefore very physically hardy. Bloaters are also able to throw sacs of toxic powder both as a defense and an attack mechanism. Once the host finally dies, whatever tissue is left of the former person crumbles and is used by the parasite to complete its growth and release spores.

A Clicker.

Now to analyze the behavior of the Infected. All stages appear to seek out specific locations and stay there, unless stimulated to pass on the infection when a healthy individual is sensed nearby. This reflects the behavior of O. unilateralis controlled ants that travel until they find the optimal conditions for the fungus’ reproduction and then fix themselves to that spot. However, infected ants will leave the colony and do not show any aggressive behavior whatsoever toward other ants. Why would the Infected exhibit such aggression and drive to bite or kill? We actually have a disease in existence that does just this. It’s called rabies virus. If rabies can infiltrate the brains of mammals and stimulate this type of behavior, it would not be a stretch to think that a mutant fungus could affect humans this way. Rabies in humans doesn’t present the same way it does in other mammals; it resembles a bad flu, followed by agitated behavior and cognitive deficits, sometimes with hallucinations, delirium, and insomnia. Perhaps our mutant O. unilateralis would be able to incite the aggressive behavior seen in the games by affecting the brain in the same way rabies does in non-human mammals. This could explain the Infecteds’ responses to healthy humans.

Runners display behavioral tendencies that would be expected. Since the fungus has only just started infiltrating the brain, it is not surprising that the victim would be scared and confused by what is happening. It makes sense that a person in this state would be very volatile and dangerous to approach. Stalkers tend to hide out of sight and only engage when someone lets their guard down. This is presumably because their vision is extremely poor and they must wait until the opportune moment in order to successfully attack. Clickers are harder to explain realistically. It would be highly unlikely that an Infected would suddenly develop the ability to navigate using clicks. This is a skill that must utilize learning and memory, parts of the brain no longer accessible to the victim. Very few humans are able to echolocate and those who are have refined their technique over years. Real world O. unilateralis is not able to direct ants to do things they are not already capable of; it simply takes advantage of abilities the insect already possesses. The sense that would be most beneficial to a Clicker is touch. Of course, sound is still an effective way of interacting with surroundings, but it would not be used for spatial navigation as in The Last of Us. This can be extrapolated to the Bloaters in the game as well, because they also use echolocation. All of these Infected will attack to kill. This is presumably because the fungus cannot kill immediately on its own, but can reach maturity faster in a dead body. So, when controlling a living human, O. unilateralis uses that person to its advantage by driving them to help speed reproduction through the provision of corpses. If the host fails to make a kill, but manages to penetrate the skin of a healthy human, then the fungus still benefits because that person will become another Infected.

A Bloater.

Overall, the concept of The Last of Us is scientifically plausible, given enough time for O. unilateralis or a different species of Ophiocordyceps fungus to evolve the traits explored here. The intelligence and thought put into this game has given it so much more than most other video games can offer and make it different from your standard zombie apocalypse. It is scary because it feels like it could really happen, and this realness comes from its grounding in actual science. The infection seen in it is already a reality for many insects and other arthropods. They may not show the aggressiveness displayed by the Infected, but the behavioral manipulation seen in these animals is extremely effective at fulfilling the fungus’ needs. Maybe at some point in the future, the fictional scenario of The Last of Us could come to be. Who knows? The natural world is continually revealing so many things previously thought impossible.

References:
1. Gronenberg, Wulfila. “Structure and function of ant (Hymenoptera: Formicidae) brains: strength in numbers.” Myrmecological News 11 (2008): 25-36.

2. Evans, Harry C., Simon L. Elliot, and David P. Hughes. “Ophiocordyceps unilateralis: A keystone species for unraveling ecosystem functioning and biodiversity of fungi in tropical forests?.” Communicative & integrative biology 4.5 (2011): 598-602.

3. Hughes, David P., et al. “Behavioral mechanisms and morphological symptoms of zombie ants dying from fungal infection.” BMC ecology 11.1 (2011): 13.

4. Andersen, Sandra B., et al. “The life of a dead ant: the expression of an adaptive extended phenotype.” The American Naturalist 174.3 (2009): 424-433.

5. Pontoppidan, Maj-Britt, et al. “Graveyards on the move: the spatio-temporal distribution of dead Ophiocordyceps-infected ants.” PloS one 4.3 (2009): e4835.

6. “The Infected.” The Last of Us Wiki. Wikia, 2013. Web. 7 Oct. 2015. <http://thelastofus.wikia.com/wiki/The_Infected>.

7. “Signs and Symptoms – Rabies.” Centers for Disease Control and Prevention. Centers for Disease Control and Prevention, 15 Feb. 2012. Web. 08 Oct. 2015.

Photo and Video Links:
1. http://static.giantbomb.com/uploads/scale_large/9/93770/2419553-397060_386577108098888_427807760_n.jpg

2. https://i.guim.co.uk/img/static/sys-images/Guardian/Pix/pictures/2010/12/21/1292935214310/a-dead-worker-ant-004.jpg

3. http://ento.psu.edu/publications/DH1

4. https://www.youtube.com/watch?v=XuKjBIBBAL8

5. http://journal.frontiersin.org/article/10.3389/fpsyg.2012.00083/full

6. http://vignette4.wikia.nocookie.net/thelastofus/images/9/9d/Clicker.jpg/revision/latest?cb=20150928101722

7. http://vignette4.wikia.nocookie.net/thelastofus/images/8/8f/Bloater.jpg/revision/latest?cb=20150928101859

There’s Nothing Funny About These – Stinkhorns

Phallus hadriani:

What? Why are you laughing? Get your mind out of the gutter! Jeez!

Stinkhorns are not at all hilarious looking mushrooms from the fungus family, Phallaceae. They are found all over the world, though more so in tropical environments. They start out as what are called “eggs” under the ground. As they grow, these eggs rise to the surface and develop into their fruiting body form within just a few hours. This fruiting body is the mushroom that is visible to us on the surface and is used for reproduction. There are many different species of stinkhorns and they come in a multitude of differing shapes, colors, and sizes. Most have long, whitish and spongy shafts with a brown to puke green cap or “head”. Some, like the “ornate stinkhorns”, can look like anything from a beached octopus to a children’s climbing dome from hell. The egg-like start to the fruiting body is shared by all these species as is a gross looking spore slime, called gleba, that smells strongly of excrement and attracts insects to carry away the spores.

Mutinus ravenelii:

Stinkhorns are not particular about where they pop out of the ground, and will often show up in people’s gardens, lawns, or other places where ripe smells aren’t generally appreciated. Most species fruit in summer and only last for a short period of time, however. Despite this, there are many internet articles on how to get rid of and prevent stinkhorn invasions. Stinkhorns can actually be beneficial to gardeners because they break down dead matter into nutrients that sustain plant life, and are self-sufficient. If only they didn’t smell so awful.
Strange as these fungi are, some people still consider them to be a delicacy. One stinkhorn in particular, the long net stinkhorn (Phallus indusiatus), is especially coveted in parts of China where it is eaten in egg form, dried mushroom form, pickled, stewed, and many other ways. This species tries to be a little fancier than its relatives by wearing a lacy skirt.

To the American palate, P. industiatus is described as “markedly unpleasant” in texture and bland in flavor. Personally, I’m not a huge fan of eating mushrooms to begin with, let alone one that is naturally covered in goopey, butt scented spore slime. But hey, if that’s what you’re into, then more power to you. Just don’t mistake the stinkhorn egg stage for the eggs of the poisonous Amanita mushroom.

Penis.

References:
1. Kuo, M. “Stinkhorns: Phallaceae and Clathraceae”. MushroomExpert.Com. Mushroom Expert, April 2011. Web. 10 July 2015. http://www.mushroomexpert.com/phallaceae.html

2. Williamson, Joey. “Stinkhorn Fungi – What Is That Smell?” Clemson Cooperative Extension. Clemson University, Nov. 2008. Web. 10 July 2015. <http://www.clemson.edu/extension/hgic/hot_topics/2008/11stinkhorns.html&gt;.

3. Hodge, Kathie T. “An Unlikely Delicacy: The Basket Stinkhorn :.” Cornell Mushroom Blog. Cornell University, 18 Feb. 2015. Web. 10 July 2015. <https://blog.mycology.cornell.edu/2015/02/18/an-unlikely-delicacy-the-basket-stinkhorn/&gt;.

4. Armstrong, W. P. “The Amazing Kingdom of Fungi.” The Amazing Fungi. Polamer College, 25 Jan. 2010. Web. 10 July 2015. <http://waynesword.palomar.edu/ww0504.htm&gt;.

Photo Links:
1. http://www.mushroomexpert.com/images/contrib/robertson_phallus_hadriani.jpg

2. https://upload.wikimedia.org/wikipedia/commons/thumb/3/3e/Mutinus_ravenelii_01.jpg/220px-Mutinus_ravenelii_01.jpg

3. https://upload.wikimedia.org/wikipedia/commons/b/b7/Phallus_indusiatus_02.JPG

4. http://31.media.tumblr.com/06eb892cc3fa8b494f8a4a521ad94c2f/tumblr_mwoq5otGWw1r3clqao1_500.gif