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The Last of Us – HBO’s latest dramatic thriller – presents a dystopian world with humanity being taken over by a mutated parasitic fungus called cordyceps, leaving more than 60% of the world’s population either dead or infected and transformed into mindless zombies – ending the world as we knew it.

What if there was a way to detect cordyceps-contaminated food supply at the front-end, and even study the behavior of such fungi to devise preventative or treatment strategies? We present a fictionalized scenario wherein graphene-based biosensors could serve as an early-warning measure and a platform to allow mycologists to study the behavior of cordyceps in a dystopian resource-limited setting.

Cordyceps – Not Quite Science Fiction

While the dystopian aftermath left by a cordyceps outbreak is highly fictionalized, cordyceps does exist in the real-world and infects ants in a similar way to humans in The Last of Us.

Ophiocordyceps unilateralis is a real-world fungal infection commonly found in tropical locations with the nickname “zombie ant fungus”. This infection slowly hijacks an ant’s motor functions to compel it to leave its nest and seek a location favorable for fungi growth. The infected ant’s internal tissues are slowly consumed as the fungus grows and colonizes within the ant’s body. At this point, tendril-like structures explode out of the ant’s body and release spores that infect other ants of the same species. Unlike the Last of Us, infected ants do not suddenly begin attacking other ants and one species of Ophiocordyceps can typically only infect a specific ant species.[1]

However, in parallel with the portrayal of infected humans in The Last of Us, infected ants are compelled to behave in a way that encourages the spread of the fungus. Horrifyingly, the fungus takes all control away from its host while leaving their awareness intact – leaving the host in a helpless condition. The notion of mind-altering fungi is well established with LSD (made from ergot – a fungus that infects grains)[1] and naturally occurring psilocybin fungi[2] that can both induce hallucinogenic effects when consumed in high doses.

Figure 1: Cordyceps infected ant [3]

Like most fungi, cordyceps cannot spread from person-to-person or survive above 98.4 Fahrenheit – making it theoretically implausible for it to grow within a human host. However, in Last of Us’ dystopian universe, rising temperatures cause cordyceps to evolve and adapt to human body temperatures.
Somewhat concerningly, this parallels the world we live in today – with climate change and rising temperatures increasing the risk of fungal disease outbreaks.[3] In fact, it has been hypothesized that climate change is a key factor driving the emergence of a relatively new fungus, Candida auris (C. auris), in over 30 countries. Despite posing a greater threat to immunocompromised individuals, C. auris can alarmingly spread from person to person and often exhibits multidrug resistance, leading to outbreaks in healthcare facilities and leaving clinicians with limited or no treatment options.[4]

In the Last of Us’ dystopian portrayal, the cordyceps outbreak is shown to begin with a contaminated supply of flour, a common household substance, originating from Jakarta, Indonesia – where the world’s largest flour mill is located.[5] This makes Jakarta the perfect ground zero location from where contaminated flour is shipped across the world, with millions of people ingesting it in a day – leading to the collapse of human society. In the real-world, flour has been linked as a vector for illness– with several instances of E. coli outbreaks being linked to contaminated flour sources.[6]

Considering both climate change and contaminated food sources are contributing to rea-world bacterial and fungal infection outbreaks, it becomes evident that The Last of Us’ fictional depiction is closer to reality than we might have initially believed. In fact, history offers a notable precedent with the Great Famine, which devastated Ireland in the 1840s and 1850s, as it was triggered by a fungus-like organism, Phytophthora infestans, leading to the widespread destruction of potato crops.[7]

Does this mean humans can turn into mindless zombies?

No, but the potential for fungal infection through a contaminated food source presents several unknowns and dangers – necessitating the need for a front-end real-time fungi outbreak monitoring system. Mycotoxins are naturally occurring toxins produced by certain fungi that can be found in food due to their chemical stability. Typically, the detection of mycotoxins takes place in centralized laboratories using techniques such as surface plasma resonance (SPR), enzyme-linked immunosorbent assays (ELISA), and quartz crystal imbalance (QCM).

Figure 2: Mycotoxin contamination supply chain illustration[8]

Despite being sensitive and selective, none of these methods are suited for monitoring on-site or in resource-limited settings, due to the need for bulky instrumentation, elaborate sample preparation, skilled operators, and their high cost.[9]

In The Last of Us’ dystopian world, inexpensive real-time monitoring platforms have become the need of the hour to ensure humanity’s survival.

Enter Graphene-Based Biosensors

Graphene-based biosensor platforms have demonstrated significant potential with their high sensitivity and selectivity, real-time field monitoring capabilities, portability, ease-of-use, and broad surface conjugation and modification potential. In our fictionalized account of Last of Us’ dystopian world, graphene-based biosensors are a crucial enabling component across several dimensions. They serve as early-warning signals and real-time monitoring tools for potential cordyceps infection sources across humans and environmental factors.

While humanity has developed a way to detect cordyceps using simple non-invasive handheld scanners[10], these tools are unable to detect early-stage infections due to their relatively high detection limits when compared to laboratory-based methods. Survivors turn to graphene-based biosensors that support low detection limits to enable the detection of early-stage cordyceps infections within seconds. Graphene-based biosensors have also been integrated into portable handheld environmental monitoring devices capable of detecting cordyceps-linked metabolites in food and water – providing a key platform to help maintain the integrity of established quarantine zones (QZs).

Advanced scientific laboratories have been left abandoned and it has become near impossible to procure expensive laboratory screening equipment, leaving surviving scientists and mycology researchers with graphene-based biosensors to study and analyze the behavior of cordyceps. Groups of survivors venture out into infected zones to collect samples of cordyceps fungi, which are then analyzed using graphene-based biosensors to gain insights into the behavior, growth patterns, and mutations of cordyceps fungi. This information is used to devise effective protective measures against the fungi and serves as a key first step in developing a potential treatment strategy or cure.

In a bleak world where survival is constant struggle, graphene-based biosensors offer a ray of hope by providing humanity with a platform that serves as an effective real-time monitoring solution to help contain the cordyceps outbreak and provides surviving mycology researchers with a convenient and effective tool to study the fungi with renewed hope around the development of a potential treatment or cure to ensure humanity’s survival.

Disclaimer: The account above is a work of science-fiction. Claims and capabilities reported do not represent any real-world developments by General Graphene Corporation or its partners.

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[1] https://www.cnet.com/science/biology/features/a-scientific-investigation-of-the-last-of-us-fungal-pandemic/
[2] https://www.npr.org/2023/01/30/1151868673/the-last-of-us-cordyceps-zombie-fungus-real
[3] https://owlcation.com/stem/Zombie-Ants
[4] https://medicine.yale.edu/news-article/the-last-of-us-apocalypse-is-not-realistic-but-rising-threat-of-fungal-pathogens-is/
[5] https://www.unconventionalag.com/post/2019/02/26/the-world-s-largest-flour-mill-gets-even-larger
[6] https://www.cdc.gov/ecoli/2019/flour-05-19/index.html
[7] Goss, E. M., Tabima, J. F., Cooke, D. E., Restrepo, S., Fry, W. E., Forbes, G. A., … & Grünwald, N. J. (2014). The Irish potato famine pathogen Phytophthora infestans originated in central Mexico rather than the Andes. Proceedings of the National Academy of Sciences, 111(24), 8791-8796.
[8] Ganesan, A. R., Mohan, K., Karthick Rajan, D., Pillay, A. A., Palanisami, T., Sathishkumar, P., & Conterno, L. (2022). Distribution, toxicity, interactive effects, and detection of ochratoxin and deoxynivalenol in food: A review. Food chemistry, 378, 131978. https://doi.org/10.1016/j.foodchem.2021.131978
[9] Vasseghian, Y., Dragoi, E. N., Moradi, M., & Khaneghah, A. M. (2021). A review on graphene-based electrochemical sensor for mycotoxins detection. Food and Chemical Toxicology, 148, 111931.
[10] https://www.thewrap.com/the-last-of-us-fungus-explained-cordyceps/#:~:text=By%202023%2C%20mankind%20has%20developed,red%2C%20showing%20he%20is%20infected.

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