If you see one of those things, no matter who they were, you can’t hesitate. Take them out if you can, or you run. *Tofu jumpscare* Hello Internet, Welcome to Game Theory, the only show online that could believably do an episode dedicated to the real-world possibilities of giant sapient tofu. In fact, huh, lemme write that down on my list of theory to-do’s, because guess what? Resident Evil 2 is back, and with it Capcom is sponsoring today’s episode. HOORRAAYYY!!! Which means it’s time to look at how the zombie apocalypse they created in game is much closer to being real now than it ever was back when the game first launched in 1998. You see, with this remake, Capcom has rebuilt one of history’s most iconic horror games from the ground up, and in the process, they’ve kept all the best parts while shaving away, you know, some of the less good parts of early 3D gaming. Out with the old tank controls and in with the over-the-shoulder camera that revolutionized the series back in RE 4. Out with the scariest polygons 1998 could muster and in with new 4k photorealistic visuals that take these unforgettably spine-tingling moments into the modern era, all while still telling the iconic stories of Leon and Claire. One’s a rookie cop having a bad case of the Mondays. The other is remarkably casual considering the horrific death around her. “How are you doing?” “You know, just.. surviving.” Even when surrounded by zombie hordes, Claire is out to get that man. And you see, that’s what I’ve always loved about RE 2: the characters and their stories. Leon on his first day, Claire trying to find her brother, a piece of tofu just trying to get by, all wrapped around this bigger conspiracy of a science experiment gone horrifically wrong, a super serum going off the rails causing a viral outbreak that throws the entirety of Raccoon City into chaos. So, now that I’m older and I get to dissect these sorts of things for a living, I wanted to ask the question that young MatPat always wanted to know: just how close to reality are we to a real Resident Evil style outbreak? Are the T and G viruses that we see transforming people into undead monsters the work of science fiction or science fact? I mean, science has changed a lot in the past 20 years. So should we start stocking up on healing sprays, in the hopes of not being made into Jill sandwiches? Let’s find out. So, the Resident Evil series is actually titled Bio Hazard in Japan, and as the name Bio Hazard suggests, these games revolve around the creation of bio-agents that turn people into monsters. These dangerous medical cocktails are engineered by the evil Umbrella Corporation to create bio-organic weapons that can be sold off to the highest bidder. But before we explore these viruses themselves, let’s actually start with Umbrella. Looking at the history of the company, their work in biological weapons actually begins with a mission to collect all the deadly viruses in the world. They’re kind of like a Pokemon trainer, but instead of Pikachu and Eevee, they’re capturing Ebola and Smallpox, and it’s here that we actually get our first disturbing crossover with reality. You see, in the game, the sort of bio-weapon collection that Umbrella is doing is banned, due to a treaty from the United Nations called the ‘1972 Biological Weapons Convention’, which outlaws countries developing or stockpiling biological agents that can be used as weapons. In the game, the loophole that Umbrella finds is collecting the viruses under the guise of researching cures for them. Funny thing about all that though is that none of it is fiction. The Biological Weapons Convention we see in Resident Evil is a real pact that really governs most of the world, including the US. And it was during the Nixon administration that the US was forced to destroy its offensive biological weaponry. But, just like we see in the game, certain deadly biological agents still exist purely under the guise of research. Smallpox is a great example of this exact loophole. You see, smallpox was a horrifically deadly disease with a 30% mortality rate and was the first-ever disease to be eradicated off the face of the planet thanks to science. However, despite its total eradication from the face of Planet Earth, 2 stocks of the disease still exist. One in the US, and one in Russia. The rationale? Further research, just like we see Umbrella argue in the game. Only here, the scientific community is heavily divided on whether there’s anything we can actually learn by keeping these things around. Back to the game, Umbrella Corp’s first major success, if you can call designing a viral mass weapon a point in the ‘win’ column, is the creation of the T-Virus, a bio weapon specifically engineered to infect and eliminate massive populations. It ends up achieving this goal by turning everyone into a zombie. Shortly there after came the Golgotha virus, or G-Virus, which is introduced in RE 2 and comes with a different goal: rapid cell growth, giving the injectee a kind of biological immortality. But too much, and you start to get mutations. It’s the G-virus that’s responsible for creating the horrific mutant that constantly threatens your life throughout the entirety of Resident Evil 2. Here’s looking at you, buddy. *wink* Now, before we get to the zombie and super growth half of these things, let’s take a minute to stop and look at the actual viral components first. You see, viruses are fascinating. One of the most interesting things about them is that they’re tiny, even when you compare them to cells, the smallest form of life. And I hear what you’re thinking. If cells are the smallest form of life and viruses are smaller than that, then are viruses alive? It’s a good question and the answer is technically not. Viruses do have DNA, but they don’t have the biological hardware that’s required to reproduce, and instead they have to rely on hijacking living cells to reproduce. Basically, they inject a living cell with their own DNA, that DNA then modifies the DNA of the cell, and it creates copies of the virus. They’re actually kinda like zombies in that way. Both viruses and zombies seem alive, but they’re really not. They require infecting other living creatures to reproduce. So, Umbrella Corps choice of a viral zombie outbreak is surprisingly fitting. But none of this is answering the question of whether a real-life virus could cause the kind of mindless hordes that we see from the T-Virus, or the extreme mutations that you get with the G-Virus. The answers here though are, again, yes and yes. Let’s take a look at them one at a time. First, it’s important to note that the zombies created by the T-Virus aren’t your typical reanimated dead. If they were, there’s no way a virus (or anything, for that matter) could replicate what we see in the game. But that’s not the zombies we’re dealing with in Resident Evil. According to the Wesker reports, the goal of the T-Virus was to mutate the infected, but for most it just ended up causing severe brain damage, resulting in mindlessly aggressive hungry creatures. Zombies. And this is important, because there’s already a real-world virus that, through some tweaking, could very easily fit the bill as a real-world stand in for the T-Virus. And that’s rabies. Just like zombie-ism, the Rabies virus gets passed through infected saliva. You ever wonder why Claire can take a bite or two and not get infected? Because saliva infection is far from perfect and has a high miss ratio. Rabies? The same way. And that’s far from the only similarity. Rabies absolutely infects animals and causes them to become more aggressive, which matches perfectly with the infected dogs that we see throughout the Resident Evil franchise. In fact, it’s not just limited to dogs either. All warm-blooded species can be infected with the Rabies virus. The virus is even adapted to grow in the cells of cold blooded vertebrates too! And in one of those classic moves that make you go “what were they thinking?” humans even infected birds with the stuff, you know, just for the heck of it. So the next time you see infected alligators or bats attacking you in the bowels of Raccoon City, rest assured as you drift off to your game over screen that that is entirely plausible. And, when a human is infected, some of the symptoms that we see line up perfectly with behavior we see in Resident Evil zombie horde. Partial paralysis, which would explain the shambling. Brain inflammation, which would cause the mental impairment. Even the hunger and desire to bite. You see, Rabies infects the Central Nervous System in three stages. Prodromal, Excitative, and Paralytic, but it’s that second stage, also known as the quote on quote “Furious Stage,” where the host becomes hyper reactive and more prone to bite. In fact, Rabies is almost always transmitted through bites, which is why it causes the infected host to turn aggressive. It’s forcing the host’s nervous system to pass the Rabies virus along. Tricky, tricky, you scary infectious virus. But, in an ironic twist, that’s also one of the main things that holds it back from causing a true zombie outbreak. You see, in game we see the T-Virus primarily spread through bites and injections, which perfectly lines up with Rabies. However, there’s a third option: water. Both the Arklay Dam and the Raccoon Sewage Treatment Plant were contaminated with the virus, which led to the city’s water supply rapidly spreading it and infecting more civilians. And here’s the thing: viruses can absolutely be spread that way. SARS, Hepatitis, even Polio are waterborne viruses. An infected poop emoji makes its way down into the water and that water winds up back in your mouth and BOOM! you’re on a one-way trip to Infection Village, population you. The trick though is that Rabies isn’t one of those sorts of viruses. It’s not waterborne. It’s not airborne either. It’s primarily biteborne, which limits its ability to infect large amounts of the population. However, that’s not to say that it isn’t possible to change that. You see, viruses can be specially engineered. According to Samita Andreanski, a virologist at the University of Miami’s Miller School of Medicine, quote: “Sure, I could imagine a scenario where you mix Rabies with a Flu virus to get airborne transmission, a Measles virus to get personality changes, then Encephalitis virus to cook your brain with fever, and thus increase your aggression even further, and throw in the Ebola virus to cause you to bleed from your guts. Combine all these things and you’ll get something like a zombie virus.” End quote. So, the long story short here is that, with medicine where we are today, should a company like Umbrella want to fuse together Rabies with the traits of other viruses that are waterborne, you’d pretty much have the T-Virus ready to go, which is definitely scary enough, but while we’re talking about mutations and medical engineering, let’s also talk about the Big Bertha in the room: RE 2’s Golgotha, or G-Virus. How could a virus possibly cause mutations like the ones we see throughout this game? Well, look no further than Epidermodysplasia Verruciformis – also known as Tree-man Syndrome. And if you’re in any way squeamish or sensitive to scary imagery, you might want to hang out for a bit in the comments right now. Strike up a conversation. Make a new friend. Everyone down there who wants to be down there? Good. So this is Tree-Man Syndrome. It’s a rare genetic disorder that causes people to be vulnerable to human papillomavirus in the skin. You may have referred to these as HPVs. Well, that ‘V’ is for Virus. These viruses can cause skin tumors that resemble horns, have the texture of wood or coral. It’s basically warts that grow horrifically out of control. That being said though, there may be an even closer real-world parallel that’s not, strictly speaking, a virus, but rather virus-like. The G-Virus, just like the T before it, was not initially created with the intention of transforming people into hideous monsters. The G-Virus instead was meant to improve our genetics, to give us a sort of biological immortality, basically advancing us to the next stage of human evolution. While this quest to genetically engineer our cells into some kind of death-proof life form might seem like the kind of stuff from science fiction, it actually has parallels to a real-world technology that works in a way similar to the way real-life viruses do. Remember when I said that a virus can inject a cell with its own DNA? Well, there’s also a process where the cell will, as part of a method for fighting viruses in the future, actually store that virus’s DNA in a blank part of the DNA sequence – that way it doesn’t infect itself – but it also remembers it for a time that it encounters that same sequence. The DNA sequence that stores this viral information is called CRISPR: Clustered Regularly-Interspaced Short Palindromic Repeats. Super-sexy name, I know. If you’re a regular viewer of Film Theory, I’ve actually mentioned this briefly before when we talked about Luke Cage’s super skin. Technically speaking, the CRISPR process is not a virus. It inserts a DNA sequence into the cell, the same way a virus’s DNA would, essentially hijacking that part of cell that’s designed to react to viruses, and then from there it modifies the DNA of the cell leaving behind an altered sequence that’ll go on to replicate blah, blah, blah. Etc, etc, TL;DR, this procedure works the same way that a virus does. Basically. CRISPR uses a mix of crRNA, which naturally occurs, and tracrRNA, which Steph: I’m already Tracer! Mat: No, not that Tracer. Steph: I SAID- I’m already Tracer! Matt: I said tracrRNA! Steph: I’M ALREADY RNA! Anyway, the whole mechanism is called tracrRNA-crRNA Chimera, but that’s a real mouthful so instead they just shortened it to – get this – Guide RNA or, more commonly, gRNA. Sounds a bit similar to G-virus, don’t you think? Maybe Capcom just wanted to shorten ‘nuclease complexed with a synthetic gRNA’ to just ‘G-virus.’ Honestly, I can’t blame them. It’s especially impressive considering that Resident Evil 2 came out 17 years before this real-world technology was even developed. Good on you guys for predicting the future. But here’s the kicker: the first successful experiments using CRISPR for genetic enhancement has already been done on animals in China. They’ve created a beagle with double the amount of muscle mass as a normal beagle. And get ready, because tests of CRISPR on humans are already rolling out, with a Chinese scientist genetically modifying babies using the exact same method. 2 girls, who apparently survived the experiment, are now living with their mom and dad. This experiment has drawn widespread criticism from other geneticists, and ethics boards who are worried that this might be too much, too soon with the quote, “Off-target effects brought by CRISPR” as their primary concern. A.k.a, maybe tampering with gene editing is a bit new, and a bit dangerous, and might cause some weird unexpected mutations, just like we see happen in Resident Evil 2. When Derya Unutmaz – a Connecticut-based immunologist at Jackson Laboratory, was asked about whether this kind of technology would pave the way for genetic enhancement, his response was, quote: “Oh, that’s gonna happen for sure. At the military level, you can imagine you want to create super-soldiers that can withstand all kinds of diseases and tough weather and carry hundreds of kilograms. These were science fiction, but now we have the tools that could enable them.” End quote. Sounds eerily similar to the kinds of things the Umbrella Corporation was experimenting with throughout the Resident Evil series. So there you go friends. Back in 1998, the premise of stockpiling and engineering viruses to create genetically enhanced humans was the stuff of fantasies or hugely successful sci-fi horror video game franchises. But today, Resident Evil 2’s plot is far more realistic than I think any of us could have ever imagined back then. And in the end, isn’t that now the scariest part of these games? But hey, that’s just a theory, a Game Theory. Thanks for watching! And hey, once again, if you are indeed interested in playing Resident Evil 2 for yourself, the download link is at the top of the description, and while yes, this episode is sponsored by Capcom, I do highly recommend checking it out. RE 2 is one of those iconic video game titles that just forever changed the face of gaming. And now you get the chance to play the two iconic storylines of Claire and Leon with all the modernization of beautiful 4k graphics, and game play optimizations like over-the-shoulder third-person perspective. I tell you, as someone who played the original and is now playing through this new version, the realism of the graphics is just out of this world. The lickers? Oh, ho man! They gave me bad dreams back then, they are giving me nightmares now. So if you’re a fan of horror, heck, if you’re just a fan of all-time great video game stories that withstand the test of time and helped shape the industry, you cannot go wrong with the new Resident Evil 2 remake. Again, the link is right there, top line in the description. And now, if you’ll excuse me, I have some herbs to combine. See you next week.