Could ‘The Last of Us’ become a reality?

The fungal genus known as Ophiocordyceps has received a lot of publicity in the last 18 months thanks to the popular video game ‘The Last of Us’. It is set 20 years after an apocalyptic mutant strain of “Cordyceps” ravages human society, and either infects or kills over half of the human population. The game, inspired by the real fungus Ophiocordyceps unilateralis, complete with terrifyingly deformed ‘Clickers’ (highly aggressive infected humans covered in fungal growths) that prey on survivors, has led to nervousness among some in the gaming community that a fungal outbreak with the potential to devastate the human population, as depicted in The Last of Us, is possible. But could these nightmarish human mutants become a reality?

It is easy to see why Ophiocordyceps unilateralis has inspired the entertainment industry; the way that it manipulates its host is an extraordinary example of co evolution between host and pathogen. The fungal spores of O. unilateralis attach to the exoskeleton of the carpenter ant¹ (Camponotus sp., particularly C. leonardi), where they are then able to break through it using enzymes. Having entered the body, the hyphae begin to take over the ant’s nervous system by releasing a cocktail of ‘mind controlling’ chemicals that cause the ant to stumble away from the colony. The infected ant climbs up the stem of a plant, bites into a vein on the underside of a leaf, and hangs there, unable to release its grip due to the atrophy of its mandibular muscles, until it dies. The fungus grows inside the dead ant’s body until it emerges from the back of the head, matures and releases spores onto ants wandering the trails directly below, on the forest floor.

There are about 160 different species of fungus within the Ophiocordyceps genus, of which around 130 of them can grow on insects². There are no known species of Ophiocordyceps that grow on vertebrates; for 48 million years it has existed alongside arthropods³ without ever successfully mutating to infect anything other than insects such as wasps, ants and moths. It is therefore extremely unlikely that the fungus would mutate such that it would be viable in a human host, and even more unlikely that it would be able to ‘control’ a human in the way that O. unilateralis can control Camponotus leonardi. Not all Ophiocordyceps species can do this to their hosts; for example O. sinensis, which infects the ghost moth, does not4.

Already, it is clear that an Ophiocordyceps outbreak is not on the horizon, even for a fungus that can make an ant climb to its death against its will. But for the sake of argument let’s pretend that this mutation has occurred, and that a species of Ophiocordyceps exists that is capable of infecting humans.

Assuming the infectious fungal spores had entered a human host (either by inhalation, or through the skin, via a wound), they would still need to be able to overcome the immune system; while the immune response to different fungal pathogens varies, many small fungal spores can be destroyed by phagocytosis5. The average person inhales millions of spores in a normal day without them causing any harm.

If a Cordyceps outbreak were ever to occur among humans, would the spread of the fungus cause the devastating effects portrayed in the video game? Again, no.

Firstly, Ophiocordyceps populations can be kept under control by other fungi that attack it and prevent mature spores from being released. Sandra B Andersen et al.6 examined spores of O. camponoti-rufipedis on dead ants, and found that only around 6.5% of the spores were viable; the remaining spores were either immature, damaged, or had been hyperparasitized by other fungi that were not pathogens of ants. If Ophiocordyceps were to mutate and infect humans, hyperparasites such as those that can ‘castrate’ O. camponoti-rufipedis would reduce its spread by reducing the release of mature spores.

Mature fruiting bodies of O. unilateralis will not produce sexually mature spores if the temperature and humidity are not at their optimum levels and these are in a very specific range (at least 94-95% humidity and temperatures between 20°C and 30°C)7. In The Last of Us, this detail is depicted well enough; humans can only be infected by spores in the air in humid, warm and confined places (such as basements underground8) and this would reduce the spread of the fungus.

The second way that humans are infected in the game – by being bitten by infected individuals – is simply poetic license; the extreme aggression that infected hosts exhibit is just not seen in nature (the behaviour of ants infected with O. unilateralis is not noted as aggressive9) which also invalidates the ‘superhuman’ strength (fuelled by aggression) that the human hosts develop7 as the fungal hyphae gradually consume the tissues.

In addition, with carpenter ants, O. unilateralis must develop inside the cadaver for at least two weeks before sexual reproduction is possible7. Assuming this considerable time lag between host death and emergence of stromata would still be the case in humans, immediate disposal of the cadaver (for example by burning) would deny the fungus the ability to sexually mature and release infectious spores.

There are many reasons why a Cordyceps outbreak wouldn’t be successful enough to affect humanity on a global scale – not least because the spores would only be able to proliferate in temperate climates. The dystopian vision shown in The Last of Us, while entertaining, just isn’t feasible. I think it’s fair to say that there is no reason to fear a pandemic Cordyceps infection that destroys humanity and slowly turns its victims into blind, limping mushrooms. Frankly, I’d be more afraid of athlete’s foot… it isn’t particularly dangerous, but at least it’s real.

To see Ophiocordyceps in action, click here: https://www.youtube.com/watch?v=XuKjBIBBAL8

 

 

  1. Hurd, H. (2015) “Ant brains manipulated by a fungus”. Microbiology Today. 18-21
  2. Wikipedia “Ophiocordyceps unilateralis”. [ONLINE] Available at: http://en.wikipedia.org/wiki/Ophiocordyceps_unilateralis. [Accessed 07 March 15].
  3. University of Exeter – Biosciences (2010) “Fossil reveals 48 million year history of zombie-ants”. Available at: http://biosciences.exeter.ac.uk/news/research/title_96180_en.html [Accessed 07 March 15]
  4. Wikipedia “Ophiocordyceps sinensis”. [ONLINE] Available at: http://en.wikipedia.org/wiki/Ophiocordyceps_sinensis [Accessed 07 March 15]
  5. Levitz S.M. and Shoham S. (2005) “The immune response to fungal infections” British Journal of Haematology. 129, 569-582. Available at: http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2005.05397.x/epdf [Accessed 07 March 15]
  6. 6. Andersen S.B, Boomsma J.J, Elliot S.L, Evans H.C. Ferrari M, Hughes D.P (2012) “Disease Dynamics in a Specialized Parasite of Ant Societies” 7 (5), 1-8. Available at: http://www.plosone.org/article/fetchObject.action?uri=info:doi/10.1371/journal.pone.0036352&representation=PDF [Accessed 07 March 15]
  7. Andersen S.B, Billen J, Boomsma J.J, Gerritsma S, Hughes D.P, Hywel‐Jones N.L, Mayntz D and Yusah K.M. (2009) “The Life of a Dead Ant: The Expression of an Adaptive Extended Phenotype” The American Naturalist. 174 (3), 424-433. Available at: http://www.jstor.org/stable/10.1086/603640 [Accessed 07 March 15]
  8. ‘The Last of Us’ Wiki “The Infected” [ONLINE] Available at: http://thelastofus.wikia.com/wiki/The_Infected [Accessed 07 March 15]
  9. Andersen S.B, Billen J, Boomsma J.J, Elliot S.L, Evans H.C. Ferrari M, Himaman W, Hughes D.P, Hywel‐Jones N.L (2011) “Behavioral mechanisms and morphological symptoms of zombie ants dying from fungal infection” BMC Ecology 11 (13), 1-10. Available at: http://www.biomedcentral.com/content/pdf/1472-6785-11-13.pdf [Accessed 07 March 15]

 

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1 Comment

  1. Toxoplasma gondii is estimated to infect 80% of the human population, and it is suggested that this parasite may affect human behaviour. It has been shown that infected mice and rats show noticable altered behaviour, for example they are more adventurous, eg frequently exploring open areas, and being attracted to cat urine, which is unlike usual rodent behaviour. In the life cycle of Toxoplasma gondii, the cat is the definitive host, and other species of mammal are intermediate hosts, so once the mammal has been infected, the parasite ‘wants’ to return to the definitive host, the cat, so to increase the chances it alters the behaviour of mice and rats to put them into situations where they are more likely to infect cats. It is not understood how the parasite can cause these changes in behaviour, however it is thought that the parasite may increase the level of dopamine in the brain, thus increasing adrenaline, which may cause the adventurous behaviour.
    The argument following this is that the parasite may therefore affect human behaviour, as infection with this parasite has been linked with depression, schizophrenia, and risk taking behaviour, however researchers are unsure whether the infection really does cause increase risk taking behaviour, or those who are already more adventurous and risk taking may be those who are more likely to become infected in the first place, eg if they do not wash their vegetables.
    In my opinion, if, as one estimate suggests, 80% of the human population is affected, and it does alter our behaviour, surely it can not have that much of an affect as we all seem to be functioning ‘normally’. Furthermore, perhaps the behaviour changes are exclusive to these rodents, as it would serve little purpose for the parasite to have these increased risk taking affects in humans, or perhaps the parasite does have an effect on human brains, but it is so small that we barely notice it.
    Although this parasite poses little threat to the majority of humans, it is interesting to see that altering behaviour is not only possible in ants, but also mammals and potentially humans.

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