Could Cordyceps infect humans and make The Last Of Us into a reality?

Much has been said about The Last of Us, an action/adventure/survival game developed by Naughty Dog and published in 2013 for the PlayStation 3 platform (with a remastered version in 2014 for the PlayStation 4 and an upcoming second part in development). This game not only was widely anticipated by the public since its announcement in 2011, but just after its release had a quite positive criticism obtaining a 95/100 (based on 98 reviews) by Metacritic (with a label of “universal acclaim”) and a score of 95% (based on 68 reviews) from Game Rankings. Even considered by some critics and entertainment portals as one of the best video games of all time.

In The Last of Us, most of the time the player controls Joel, a man who has the task of protecting and escorting the young Ellie across the United States in a dark post-apocalyptic future. Much of the game plot is centered on the relationship between Joel and Ellie, along with other elements of mystery and horror that revolve around them. There, players use all kinds of weapons and stealth techniques to defend themselves from other humans and zombie-like creatures that emerged from the infection of a virulent mutated strain of the fungus Cordyceps.

In the game, Cordyceps and the infection caused by this (Cordyceps Brain Infection, abbreviated as CBI) has eradicated humanity as we know it. The game story states how the infection began to spread through the United States in 2013 and how, in just a few months, 60% of the global population died or was infected by the pathogen. As events unfold, further information on the origin, development, and epidemiology of infection by the fungus is shown (divided into 4 stages development).

Art of a human in stage 3 of CBI

In the first 2-3 days after the infection, either by inhalation of spores or bite by an infected individual, the fungus grows rapidly taking control of the main functions of the host brain.

Changes in the cerebral cortex trigger a hyper-aggressiveness state to other human individuals (stage 1). Past 1-2 weeks the infection progresses and fungus tissue grows within the cranial cavity, partially affecting the visual cortex (step 2). Within 1-2 years of infection, vision is completely replaced by a tracking sound mechanism or echolocation, the same mechanism that is present in dolphins and bats (step 3).

Finally, after 1-2 decades of infection, the hosts develop “plates” made of fungus tissue throughout their bodies (step 4). If the host dies, the fungus forms stakes that can liberate spores that have the ability to infect other humans and reinitiate the biological cycle of the parasite.

We must celebrate that the game not only has a good plot, its creativity regarding the effect of a highly infectious disease affecting a species is worthy of admiration for which, obviously, It is necessary to give credit to the creative director of Naughty Dog, Neil Druckmann. 

Druckmann revealed that the idea of using the fungus Cordyceps as a means to destroy humanity appeared when he watched an episode of a documentary series called Planet Earth (narrated by David Attenborough a famous naturalist). In addition to the documentary, Naughty Dog included as scientific advisor to the disease biologist David Hughes, of Penn State University. “It was, therefore, a wonderful opportunity to teach them and their audience about pandemics and zoonotic diseases which are transmitted to humans from animals.

It was also, of course, great to tell them about Cordyceps – the fungus our lab works on in rain forests – which was the inspiration for the game” Professor Hughes said.

Now, in real life, things are not boring respecting parasites. Natural populations, including humans, have always struggled to survive infections. A classic example is the bubonic plague, or Black Death (so far one of the most devastating epidemics in human history).

This pandemic was caused by a virulent strain of the bacterium Yersinia pestis, which had as natural host rodents and is transmitted through fleas. The bubonic plague emerged in Europe in the fourteenth century and it is estimated that eliminated around one-third of the continental population.

Physician attire for protection from the Bubonic plague or Black Death.

Another more contemporary and common example where a pathogen “jump” from infecting one organism to another, is the Human Immunodeficiency Virus (HIV). In this case, the HIV virus went from populations of common chimpanzees (where infection does not produce any kind of immunodeficiency) to humans, causing the epidemic we know today which leads to Acquired Immune Deficiency Syndrome (AIDS).

As a result of this epidemic 39 million people have died because of HIV-related diseases and by 2013, there are 35 million people infected with HIV.

In nature, the Cordyceps fungi (some of them renamed as Ophiocordyceps) are part of a group of organisms that are specific parasites of arachnids and insects (think about this, Spiderman is not much concerned about parasites, or maybe Venom could count as one). Some species of Cordyceps are able to affect the behavior of the host insect.

One of the most interesting species is the Ophiocordyceps unilateralis: When a spore of the fungus infects certain types of ants, the host behavior changes. The infected ant leaves its nest and trails on the forest floor, later it looks for a suitable area in terms of temperature and humidity for the growth of fungus. There, the ant uses its jaws to tightly hold on to the nerves in the lower part of the leaves, where the ant stays until it dies.

This process takes between 4 and 10 days and includes a stage where the body of the fungus grows pointy stakes just behind the head (as is as seen in the video game). These structures contain the spores that will be released and fall on the forest floor ready to infect a new host and begin their life cycle again. Terrifying and exciting at the same time.

Wasp parasitized by the fungus Cordyceps

So the question everyone is asking is, could Cordyceps infect people and be a problem for humanity? Well, sorry to disappoint you guys, but the odds are very low (It is enough with infectious diseases of our time, no?). In our surroundings, there are billions of spores of different fungi. These spores are inhaled or land on our skin constantly. The immune system of our body has evolved to deal with these and other threats (viruses, bacteria), and only immunocompromised individuals (patients with AIDS or under cancer treatment) are really sensitive to yeast infections.

On the other hand, jumps off the species barrier, even though something common in nature, is a phenomenon governed by tightly related variables between different hosts (spatial interaction between organisms, ecology, strategy parasite evolutionary relationship, just to mention a few).

This makes it difficult and unlikely a jump from an ant parasite, that we rarely see or are in contact with, to cells of other organisms like animals or humans. Cases such as toxoplasmosis, bird flu, and Dengue Fever show a really close relationship between humans and organisms (cats, poultry, and mosquitoes respectively).

However, although infection Cordyceps seems unlikely, we must not forget that humanity has been through dark times where a pathogen put an end to thousands or millions of people.

Our reality now includes things like overpopulation, accelerated movement of microorganisms by aircraft and ships, pollution, global warming and destruction of natural habitats, variables that ultimately are essential ingredients for future epidemics.

At the far end, we decide whether we want to be The Last of Us.