A series of essays on the science behind Resident Evil

By Hieronymus, The Doctor, and T-A.L.O.S.

For Project Umbrella www.projectumbrella.net

The authors claim full ownership and rights to this document. This document may be displayed at www.projectumbrella.net; this document may be reproduced elsewhere only with explicit permission from the authors. Project Umbrella is an unofficial fan site, and is in no way affiliated with Capcom or Resident Evil. We’re claiming “fair use” for all the images. We’re not making any money off of this. Please don’t sue us.

Contents

The G-Virus ...... 3 Massive growth ...... 3 Healing factor...... 5 Limb asymmetry ...... 7 Reproduction ...... 9 Extra body parts ...... 11 Stage V ...... 15 The “Devil” vaccine ...... 17 G subtypes ...... 18 The T+G Virus ...... 18 The blobs ...... 22 Lisa Trevor ...... 25 Nemesis ...... 26 The NE-α parasite ...... 26 Anatomy of a monster ...... 28 Nemesis subtypes ...... 32 The NE-β parasite ...... 32 Nyx ...... 33 The T-Veronica Virus ...... 34 Ants and Plants ...... 34 Blood ...... 37 Nosferatu and Steve ...... 39 Other T-Veronica organisms...... 41 Tentacles and the “Alexia-Pod” ...... 41 The Veronica Plant and the V-Complex ...... 43 The Jabberwock S3 ...... 44 References ...... 45

“Science isn’t about ‘why’ – it’s about ‘why not.’”

—Cave Johnson

For a series of games about viruses and medical experiments, Resident Evil is pretty light on actual scientific information. It’s a good thing, too, because whenever Capcom tries to get technical, it becomes obvious they wouldn’t know real SCIENCE if it bit out their throats.

We know Resident Evil is just fiction, and that the biological horrors of Umbrella and Tricell exist only to provide a story and a conflict for the protagonists to overcome. It’s equally obvious that a lot of what we see in the games is flat-out impossible. But as men of SCIENCE, we feel it is our duty and our privilege to dig through the evidence— the files, the dialogue, the gameplay itself— to determine how these viruses and monsters would work if they could work at all.

This third installment will examine the G-

Virus, the NE-α parasite and Nemesis T- Something like…I don’t know…basic scientific Type, the T-Veronica Virus, and the products literacy. Source: Code: Veronica and variants thereof. We’ve relied on speculation more than we would like, but we always tried to fit out theories to the evidence, utilizing real scientific data as much as possible. Handy scientific definitions have been provided at the bottom of each page, and literature citations are available at the end. It should be noted that this Report does assume a certain familiarity with the games, but most of the files and assorted game-related information can be accessed through Project Umbrella.

The G-Virus

G is one of our favorite viruses. It predates all of the Veronica silliness; infection doesn’t produce burning blood or green skin or weird gill slit things – just meat and eyes and teeth. It’s what all viruses should aspire to be (if they don’t already make people bleed from every orifice). William Birkin was right when he called it “sheer perfection.” One of the things that makes G perfect is its capacity to make a huge, nigh-indestructible monster with a single injection – as we discussed in the previous Report, comparable B.O.W.s like Tyrants take a lot of work to make. The logical place to begin, then, is to discuss just how G makes people into unstoppable meat- berzerkers.

Massive growth

Generally speaking, we believe that a lot of the massive growth we see in G-Types (that is, individuals successfully transformed by the virus) can be explained as a result of the same molecular processes that make a Tyrant huge. In the last Report, we discussed how the T-Virus, as a probable retrovirus, could be used to force expression of foreign genes in host cells. The G-Virus may carry transgenes which up-regulate certain thyroid hormones and hypothalamic trophic hormones, stimulating tissue growth on a general level. Additionally, the virus may encode genes related specifically to muscle growth, such as the growth factor PEPCK- C, the regulator FHL-1, and the transcription factor NFATc1, and the TGF-β protein follistatini,ii,iii. Some of these, especially PEPCK-C, would have to have their expression restricted to muscle tissue by coupling them to tissue-specific promoter sequences, lest the G-Type Entirely the wrong kind of massive. become massive in entirely the wrong way.

The G-Virus could also promote muscle growth by expressing small interfering RNA (siRNA) – tiny chunks of nucleic acid which can shut down other genes. By expressing (siRNA) that blocks expression of myostatin, G could remove a powerful constraint on muscle size. The body also makes its own siRNA, including one called MiR-206. MiR-206 can switch off a gene called Pax3, which blocks muscle cells from differentiating to their functional, adult forms.iv The G- Virus could encode this siRNA as well, allowing it to be expressed at a greater intensity, and allowing muscle stem cells to mature properly (or at least quickly).

In order to keep all of that muscle supplied with blood, one might express a gene like ERRγ, a nuclear receptor which promotes blood vessel formation in type I muscle tissue. Otherwise, this muscle could easily outgrow the ability of puny surrounding blood vessels to supply it.v

But all of that muscle won’t make a G-infected person bigger by itself; the skeleton also needs to grow. As we discussed last time in the section on the Tyrant, individual bones can grow thicker, but making the skeleton grow larger is not easy in adults. The bones of children possess what are called epiphyseal plates – cartilaginous regions near the ends of the long bones where cells can divide, making the bones longer. These cartilaginous sections slowly convert to bone as the child grows, making the bones stronger but losing the capacity to grow longer.

For Tyrants, we solved the problem by suggesting that Umbrella may have used a special strain of non-replicating virus to convert a small amount of hematopoietic, blood-making cells in bone marrow into chondroblasts and osteoblasts – the cell types that build cartilage and bone, respectivelyvi. Since bone marrow occurs mainly in the cancellous bone near the ends of the long bones, it’s in more or less the right place to make a new epiphyseal plate. Osteoclasts, cells

which break down bone, would be necessary to weaken the existing bone enough that the growth of cartilage could make the bone longer.

Unfortunately, since G is administered as a single injection, one virus has to do everything – it has to convert some hematopoietic cells to various osteogenerative cells, and it also has to leave the rest alone so they can continue to make blood. To explain how that happens, we’re considering a couple of theories. It may be that hematopoietic cells infected early on convert to the aforementioned bone cells, and also secrete some regulatory paracrine hormone preventing later-infected hematopoietic cells from doing the same – a form of quorum sensing in reverse. Another possibility holds that the G-Virus genes responsible for converting hematopoietic cells are controlled by promoter or regulatory regions which are strongly inhibited by heterochromatin – a form of DNA storage that happens to make the DNA harder to “read.” Since the viral genome would probably integrate into the host’s genome in a random location, some of the time it will end up in easy-to-read euchromatin regions, and these hematopoietic conversion genes will be expressed, making bone cells; other times, the viral genome will end up in heterochromatin regions, and these genes will be silent (but other, hardier genes will be expressed anyway).

While we’re on the subject of skeletal modification, we should probably discuss claw formation. We proposed some rather elaborate mechanisms for the Tyrants, involving some amount of surgery and (again) specialized strains of T-Virus administered directly to the bones of the hands. As described above, this is not an option for the G-Virus. Fortunately, we already covered the issue when discussing Lickers. The overexpression of general growth hormones, growth factors, and regenerative genes may lead to the formation of hyaline cartilage layers on the phalanges, the bones of the fingers and toes – particularly the tips of these bones, which would not be occupied by muscle or ligament attachment. These cartilage layers could act as epiphyseal plates on their own, promoting bone growth that ultimately leads to the formation of claws.

In Stage IV, Birkin goes from walking upright to a quadrupedal posture – or what would be quadrupedal if he were only using four limbs instead of six. In our first Report, we suggested that uncontrolled bone growth around the pelvic girdle might force Lickers into a quadrupedal posture; we believe the same thing is probably happening here.

Healing factor

The most iconic bosses of Resident Evil games, the Tyrants, are rather tenacious buggers. Most of them have to be defeated more than once – knock them down, and they get back up for more, and sometimes get bigger in the process. G-Types take this trait beyond the impossible. William Birkin gets ventilated about six times throughout the course of Resident Evil 2, and half the time, the next form the player fights will be big enough to eat the previous form. That takes some serious healing.

A lot of this regenerative capacity can be explained by the same hypothalamic and thyroidal growth factors we keep invoking again and again, only cranked up to eleven. The G-Virus may also throw in a few unique twists. At the molecular level, the G-Virus may block expression of

the genes ARF and Rb in response to an injuryvii. Blocking these genes allows muscle cells – which are normally terminally differentiated in mammals and unable to reproduce – to divide, repairing damaged muscle. Eventually though, Rb expression has to be restored as the body’s danger signals dissipate, or this regenerated muscle will fail to become functional and will just become a tumor. Increasing expression of Ezh2 could allow satellite cells – naturally-occurring muscle stem cells – to proliferate more freely. viii The virus might also modulate the expression of the genes Keap1 and Nrf2. Expressing Keap1 inhibits Nrf2, allowing adult stem cells normally present in the tissues to divide more freely. Turning Nrf2 back on at a later time would stop these cells from dividing out of control, allowing them to differentiate into healthy, functional tissue. G may also block transcription or activity of the genes MafB and cMaf, allowing increased activity of the transcription factors c-Myc and KLF4 – these transcription factors allow a cell to revert back to a simpler stage where it can divide, ultimately allowing for more adult cells.ix

An injured G-Type may be able to heal itself with a form of stem-cell therapy. Many cells in the G-Type’s body may revert to a pluripotent or multipotent state, becoming stem cells – a phenomenon which, incidentally, can happen by accident during a viral infection.x The G-Virus could also make this happen directly by switching on a gene called FOXP1, which keeps stem cells stemmy in developing embryos. The gene Sox2, and a modified form of the gene Sox17, have been shown to induce pluripotency; although the modified gene was only made in 2011, there’s no reason William Birkin couldn’t have stumbled on the mechanism that makes it work through research into Sox2.xi,xii Inhibiting the function of the chromatin- remodeling enzyme Hdac2 has been shown to induce pluripotency by making normally Oh no, don't do that, don't do that. If you shoot him, hidden genes visible to the cell, so the G- you'll just make him mad. Source: Darkside Virus could express some kind of siRNA or Chronicles microRNA to inhibit it.xiii The stem cells thus generated could then contribute to new tissue growth after injury, repairing damaged muscle and even damaged organs. The body cavities of the G-Type may be lined with a thick layer of dense parenchymal tissue rich in these stem cells. Parenchymal tissue being less organized than highly structured organ tissues, this material may also be able to rapidly fill in an injury such as a bullet wound – incidentally putting the embedded stem cells exactly where they’re needed.

A G-Type’s resilience may extend beyond the cellular level as well. The extra eyes and limbs of William Birkin’s later forms suggest a high degree of redundancy, and this redundancy may extend to the internal organs. A second heart, extra lungs and kidneys, or other such extra organs

might provide a backup that could keep the creature alive even in the face of extreme injury, giving it a chance to repair its damaged organs and recover fully.

But regenerated organs are worthless if they’re plugged up with scar tissue. Over the course of Resident Evil 2, William Birkin essentially takes an action movie to the face. He gets shot dozens of times by Leon, Claire, and a team of highly trained paramilitary operatives. Under normal circumstances, we might expect his body to be utterly webbed through with knots and cords of useless scar tissue, not only taking up space but getting in the way of essential functions like circulation and breathing. The fact that the later stages can move at all suggests that the G- Type is repairing this damage with healthy tissue rather than granulation tissue.

Limb asymmetry

When someone gets infected with the G-Virus, not all of his body gets bigger at the same time. In the two cases of G-infection we’ve seen to date – William Birkin in Resident Evil 2 and Curtis Miller in Degeneration, the right arm typically grows to absurd proportions before the left arm, and the rest of the body, catches up. Again, we can’t rely on human meddling to explain this phenomenon like we could with the Tyrants’ claws – the G-Virus does everything on its own.

The sort of limb asymmetry we see in Birkin and Miller has some precedent in nature – crustaceans often have one claw much larger than the other – but this asymmetry is dependent on usage, not genetics. The dominant claw gets used more, and hence, gets bigger as its muscles build. Something similar happens in humans – the dominant arm is very slightly longer than the other arm. The effect is much more subtle though; it’s hardly noticeable. Still, it gives us enough of a hook to explain the massive difference in arm sizes in early G infection with a little bit of creative biology. An excessively large right hand is a recurring theme of G-Virus infection. Source: Darkside As we explained earlier, a lot of developmental Chronicles and Degeneration biology, particularly the development of limbs and fingers and stuffxiv, depends on gradients of hormones and other chemicals across a piece of tissue. One chemical is secreted in one part, like the mesodermal tissue making up the bulk of the developing limb, and another is secreted in another part, like the apical ectodermal ridge – the leading edge of growth. Depending on the balance of these chemicals at any point (and other factors, obviously), a cell can determine whether it should be growing, differentiating, dying, or just staying put. This system can also be coupled to a negative feedback mechanism, as we propose to do, creating a local-activation, long-range-inhibition system.xv In negative feedback inhibition, one chemical can cause the cells

exposed to it to stop secreting the other chemical. Unless such a system is very carefully balanced, it can cause runaway effects.

In our proposed model, paracrine growth factors are secreted in either arm during the early stages of G-Virus infection. Being paracrine, these growth factors don’t diffuse very far – they stay in the arms, stimulating arm growth, while the rest of the body takes care of itself. Why the arms? It might have something to do with general tissue activation involving bone growth at the phalanges of the fingers, as we described above in our discussion on claws. Or it might have something to do with internal tentacles, which we’ll get to later. The important thing is, these growth factors aren’t the only things being secreted. We suspect that the arm tissues are also secreting inhibitory factors in a prohormonal, or inactive, form. Such inhibition might originally have been implemented to prevent the creature’s arms from growing too large, too fast. These prohormonal inhibitory factors diffuse across the body, slowly cleaving to an active form due to natural instability or interaction with some other chemical in the torso or something, and as they reach the opposite arm, they inhibit growth in that arm.

This system would be fine if the arms were exactly the same size – each arm would make the same amount of growth hormone, and would receive the same amount of inhibitor from the opposite arm, leading to balance. But as we mentioned above, one arm – the dominant arm, usually the right one – is very slightly longer due to greater use over a lifetime. Having more tissue mass, this arm will secrete more growth factor, allowing it to grow slightly faster than the opposite arm. It will also secrete more inhibitory prohormone, slowing down the growth of the other arm to a greater extent.

You can probably see where this is going. As the right arm keeps getting bigger, it’s going to secrete even more growth hormone for itself and more inhibitory hormone for the left arm. The left arm, for its part, will be comparatively smaller than the right, and won’t be able to generate enough of either hormone to keep up. It’s a race where every time the person in the lead gains a foot, someone kicks the person in last place in the shins – if you start ahead, you’ve already won. We have prepared a diagram demonstrating the relative flow of growth factors and Now, eventually this asymmetry balances out – by inhibitory hormones between arms, according Stage III of infection, the left and right arms (the to our theory. original arms, at least) are the same huge size. Presumably there’s a cutoff point, possibly controlled by secretion of another compound which tells the tissues of the arms when it builds to a sufficient concentration – which would largely be determined by the size of the arm. The right

arm would reach this cutoff point first, and would stop secreting both the growth hormone and the inhibitory prohormone, allowing the left arm to catch up.

Reproduction

This would be a great place to discuss the extra arms that William Birkin develops over the course of his mutation – but before we do that, we need to make a short detour over to creepytown, because we strongly suspect that these extra arms are tied directly to the peculiar manner of G-Type reproduction.

The G-Virus doesn’t spread the way that the T-Virus does. A T-infected zombie can just bite someone and spread the virus through its saliva, but a G-Type must deliberately infect a host with some kind of embryo in a mechanism that tends to produce failures except under the best conditions. The “Vaccine Synthesis” file in Resident Evil 2 states that a G-Type will reproduce by implanting an embryo into a new host, and that “the embryo will undertake a process of gradual cellular invasion, infecting the host's cells on a molecular level as it rewrites their DNA.” Scientifically, this doesn’t make a lot of sense. Infecting host cells and rewriting DNA sounds like something a virus does – but then, why would the G-Type need to inject an embryo at all if it can just inject a virus? We would really, really have liked to ignore this file and propose that G implants an embryo in its host, which hatches, end of story. But ignoring scientific material from the games is a bad habit for us to get into, no matter how ridiculous it is – so we came up with a rather round-about solution.

The need to implant an embryo, rather than just injecting a virus, suggests to us that the G-Virus is what we call non-replicative or replication-incompetent – that is, it doesn’t make more of itself under normal circumstances. It may lack a gene for some special characteristic like a capsid component, or some kind of regulatory region allowing it to replicate in animal cells, so that more virus could only be produced in cell cultures genetically engineered to express this capsid protein for the virus. That’s alright, though, because that sample Birkin injects himself with could easily contain enough virus to infect every cell in his body a thousand times over.

If a G-Type doesn’t make more virus, it can’t inject virus into new hosts – but, as we’ve described above, it would make lots and lots of stem cells, which can be implanted into new hosts in the form of disorganized embryonic tissue, loaded with stem cells. Based on the needs of the G-Type, these cells are likely to be pluripotent rather than totipotent, which means that they can form just about any cell type the body needs – but they can’t form extracorporeal tissues like the placenta or umbilical tissues. As a result, these cells won’t be able to grow into proper embryos – particularly if, as one recent study suggests, embryonic tissue separation depends on cells repelling one another more than adhering to one another, as in the classical model.xvi These cells can, however, disseminate from the implanted tissue into the host’s body to produce a new G-Type by either assimilating or replacing host tissues, cell by cell, and this model would probably be enhanced by such cellular repulsion. As these cells replicate and spread through the body, they might consume and replace host cells like something out of a John Carpenter movie. As another possibility, they might merge with host cells as virally-infected cells tend to do, forming syncytia. In order to remain viable, these cells would probably have to destroy or expel the original host nucleus, retaining the genetic material of the G-Type instead. That is to say, the

invading cell would infect a host cell and replace its DNA, much as described in the file (with a little fudging on our part). In either case, the G-cells would depend on existing tissue organization, including extracellular matrix scaffolding, to produce functional tissues and organs. This gradual replacement of cells, rather than development of an “embryo,” would mean that Sherry Birkin wasn’t going to hatch a G-Type; she was going to become one.

However, this process is only The product of aborted embryo development is big and successful if the host is genetically dangerous, but pretty badly deformed. Source: Darkside related to the original G-infected Chronicles human. In anyone else, the process spontaneously aborts and a G-embryo hatches prematurely from the host, growing into a G- Mutant which is, by all measures, a worthless by-product. The G-Mutants seen in Resident Evil 2 and Outbreak are not as strong, as fast, or as durable as bona fide G-Types, and while they produce embryos (lots and lots of them), these embryos are not viable and cannot grow to adulthood, even in a host.

Organ and tissue rejection typically has to do with an incompatibility in the different tissues’ MHC Class I markers. These markers are surface proteins present on every cell which basically identify the cells as being a part of the body. Not possessing these markers is a good way for dangerous or invading cells to get their asses kicked by the immune system. Special white blood cells called T-cells patrol the body like a psychopathic border patrol, checking every cell they encounter for these markers; if a cell has the wrong credentials, they release granules full of murder which destroy the offending cells. Incidentally, in our first Report, we discussed the possibility that Progenitor and the T-Virus have what’s called a superantigen – a compound designed to trigger this kill reaction indiscriminately, and we suggested that this explained why these viruses tend to kill people and make skin rot.

MHC markers are highly variable from one person to another, and the wrong marker may actually be worse than no marker at all, which is why doctors have to check for a tissue match before performing an organ transplant. Because of genetic similarities between close blood relatives, the best matches are probably going to be close family. It seems reasonable to assume that the embryonic cells a G-Type implants into a host are going to be a close genetic match (except for the G-Virus infection) to the host’s tissues, rather than a product of the G-Virus genome alone. As such, an embryo implanted into a host is going to face the same risk of rejection as any other foreign tissue unless the host is a close genetic match.

Under assault from an incompatible host’s immune system, the G-Type stem cells may take a page from the tuberculosis playbook in an attempt to survive. They may organize into compact

little bundles, exposing only the outermost layers to the immune system – and, in all likelihood, creating some kind of physical defense like a fibrous sheath or a wall of dead and dying immune cells.

These concentrations of cells may then develop more or less like embryos. The embryos would not develop correctly, however, in the absence of a placenta. Furthermore, as induced pluripotent cells rather than totipotent cells, they may have more subtle differences in gene expression which prevent them from developing truly viable embryos. The resulting organism would be a biological train wreck.

There remains something to be said about how the G-Type actually infects a host with these stem cells. Resident Evil 2 shows that infection occurs through a tentacle that extends from the hand or arm – much like the tentacle of Nemesis, which is also capable of transmitting an infectious fluid. We believe that there is a reason for this similarity, and it goes back to Lisa Trevor. William Birkin discovered the virus which he would eventually craft into G in Lisa’s body. He made this discovery after she absorbed an NE-α parasite and apparently assimilated it The tentacle emerges from the G-Type’s palm, implanting completely, leaving no detectable the embryonic tissue into the host through the mouth. It then erupts from the chest, suggesting it passes through the traces. In the Resident Evil remake, trachea and into a lung, rather than through the esophagus Lisa exhibits classic G-Virus traits, like to the stomach. Source: Resident Evil 2 a big ectopic eye, but in the final confrontation, she also develops flailing tentacles – a Nemesis trait if we ever saw one. This suggests to us that she didn’t just destroy the Nemesis parasite that entered her body – she took up some of its genetic material, allowing it to be expressed through the virus that would become G. Like Lisa’s tentacles, these G-tentacles may actually reside in the body, rather than wrapped around the arms as in the case of Nemesis.

There is one question we have not settled – whether reproduction is an intentional trait designed by Birkin, or a by-product of the virus’s other characteristics. Lisa Trevor does not appear to have the ability to implant people with embryos, suggesting that this trait was not extant in the most primitive forms of the G-Virus; however, if Birkin wanted to make a creature that could reproduce, a genius of his caliber should have been able to engineer parthenogenic reproduction into the G-Type’s physiology, or at least allow it to implant self-sufficient embryos into genetically non-related hosts.

Extra body parts

Let us return to the subject of anatomy. As William Birkin mutates in Resident Evil 2, he doesn’t just get bigger, he also gets…more. Birkin grows extra arms, extra eyes, and even a second head (though the old head is absorbed back into his body as the new one emerges). It’s true that many-limbed critters are born all the time, but that happens during embryogenesis – it’s a lot harder to grow extra limbs as an adult. As a result, we’ve had to get creative to explain how Birkin developed these extra features.

Let’s start with arms. Around Stage II of his mutation, it starts to become apparent that William Birkin is developing extra arms. By Stage III, these arms have reached full size and functionality; the original arms, now huge, seem to have rotated to the back, allowing these new arms to take their place.

Now, limb development typically occurs at the embryonic stage, and it is very difficult to impose at later stages of development. Perhaps the closest analog in nature would be regrowth of severed limbs in amphibians, since they must grow a complex, structured tissue from a stump which contains little structural information of its own. But Birkin didn’t even have stumps for his In Stage III (bottom), the smaller arms seem much more new arms to grow from; he had natural and “human” than the big arms – but they’re armpits. To explain how Birkin actually the new arms, which can be seen growing from the develops new arms, we have to abdomen as early as Stage I. Source: Darkside Chronicles propose a means of stimulating new growth in a very specific region of the body.

The answer, we believe, is tentacles. Neither Birkin, nor Miller, nor any of the G-Mutants we see ever use tentacles to attack, but in Resident Evil 2, something that looks an awful lot like a tentacle is implied to be involved in infecting others with G-embryos. Where do these tentacles come from? Well, the short answer, as we suggested above, is that they are probably genetic holdovers from Lisa Trevor, the source of the virus which William Birkin would craft into G. She probably got the tentacles from infection by, and assimilation of, the NE-α parasite. We’ll get to all of that later on; the important thing is that the G-infected Birkin possessed them.

If these tentacles are similar to those of Nemesis, they probably derive from the spinal column, for reasons we’ll get to later. The tentacles may then extend laterally through the fascial plane, or may follow spinal nerves or something, until they reach the skin.

The tentacles of the Nemesis can secrete a purple fluid containing trace quantities of the T-Virus. As we described above, we believe that the G-Virus is replication-incompetent under normal circumstances, so G-tentacles probably secrete infected stem cell-rich tissue rather than infectious virions. This tissue would be the source of G-embryo infection when a G-Type infects a sleazy reporter, the Chief of Police, or its own daughter, but when the tentacle is stowed, stem cells might be secreted into the G-Type’s own tissues at a low rate – presumably at the base of the arms. Being pluripotent stem cells, these might form the basis for new limb buds; their proximity to the rapidly-growing original arms means that they would be saturated with growth factors, perhaps including the FGF and BMP signals necessary to organize a developing limb. The presence of these signals might set these cells on a course to developing into limbs instead of developing into complete (if derpy) embryos, as they would in incompatible hosts, or spreading through the host body, as they would in compatible hosts.

The tentacle tips may also secrete a developmental cocktail including compounds like myoseverin and reversine, and siRNA against the CDK inhibitor p21 – this combination of substances would cause differentiated tissues already present in the area to dissociate into a stem- like state suitable for the generation of new limbs.xvii De-differentiation of these cells would allow them to form new musculoskeletal structures attached to the spine and rib cage, necessary for anchoring the new arms.

It’s probably worth noting that although Curtis Miller exhibited other G-Type traits such as right- arm-dominant asymmetry and ectopic eyes, he never developed extra arms. Any number of factors could result in this deficiency – Miller’s reproductive tentacles may have been longer or shorter than Birkin’s, putting them in the wrong place to plant the seeds of Curtis Miller didn’t grow extra arms; he grew a tail with odd extra arms. Development of little flaps. We’re still trying to work that one out. Source: these arms may be contingent Resident Evil: Degeneration upon using the reproductive tentacles at least once, establishing a flow of pluripotent stem cells from them; Curtis Miller never had the opportunity, but according to some theories, William Birkin infected backstabbing subordinate Monica in Outbreak prior to his appearance in Resident Evil 2. (There is an alternate theory that Monica was infected by the G-embryo she was trying to steal after it was released when a giant moth attacked her. We don’t want to get into that here.)

Finally, it’s possible that the virus itself was different. Frederic Downing, former Umbrella employee and cad, obtained his sample of the G-Virus on the black market – which means he probably obtained it either from Ada Wong or Albert Wesker. According to Umbrella Chronicles, Ada provided Wesker with a sample of G from the tissues of William Birkin’s body, which she obtained…somehow. (Resident Evil 2 allows Ada to retrieve a pure sample of G. It’s possible that she did both, giving her true employers the pure sample and Wesker the tissue sample.) We proposed above that the G-Virus is replication-incompetent, which means that it would be impossible to retrieve intact virus from a tissue sample – one would have to extract genomic DNA containing the integrated provirus and use that in conjunction with a recombinant cell line to produce infectious virus. Any number of G-Virus genes could be lost, or extraneous host genes gained, during the extraction process, depending on the methods used. Furthermore, without William Birkin’s notes or stocks, any transgenic cell line used to produce G from these samples would be pretty different from the ones Birkin used, and may produce a less-optimized virus. The result could be a loss of function such as a lack of awesome but impractical extra arms.

Even more than the arms, the G-Virus is known for creating lots of eyes, some of them pretty big, in places where eyes do not usually go. These eyes can get fairly large; both William Birkin and Curtis Miller developed eyes the size of beach balls on the shoulders of their dominant arms. This trait is already present in Lisa Trevor, who carries a primitive form of the G-Virus; during the final confrontation in the crypt, she displays a big ectopic eye on one shoulder. In Stages III and IV, Birkin possesses other eyes all over his body.

These eyes could result from overexpression of a gene like E- NTPDase 2.xviii,xix When this ectoenzyme is expressed on the surfaces of cells, it reacts to extracellular ATP in a way that signals cells to start developing into eyes. It turns out that overexpressing this gene in tadpoles can lead to extra eyes, and can put those eyes just about anywhere from head to tail. Mechanical stresses on stretching tissues, which one might expect in The first and most noticeable eye tends to show up on the something growing as rapidly as a shoulder, probably benefiting from whatever processes make G-infected individual, could one arm disproportionately huge. Source: Resident Evil: increase ecto-ATPase expression, Degeneration possibly including expression of E- NTPDase 2.xx

These eyes tend to be pretty big – fist sized or better. This is not unexpected; developing eyes are going to be much more sensitive to growth factors than the fully-formed eyes Birkin

possessed before becoming infected. As we’ve described above, his body would be saturated with such growth factors, far more even than the body of a developing embryo or fetus. The developing eyes on his body would inevitably grow to prodigious size. As we described earlier, the dominant arm would boast an even greater concentration of growth hormones due to runaway hormonal feedback mechanisms, so an eye growing on the shoulder of this arm would inevitably grow largest of all, at least during the early stages of infection.

Of course, an eye is worthless without an optic nerve to feed visual information to the brain. The stem cells becoming abundant throughout a G-Type’s tissues might be able to take care of that; alternately, the eyes might hijack existing afferent nerve bundles which send physical sensations to the brain. Owing to the distance between some of these eyes and the brain, even de novo- developed ectopic optic nerves would probably run up through the spinal column rather than bypassing it as normal optic nerves do. The brain itself shows an immense plasticity, and would probably be able to reorganize to recognize new visual information fairly quickly. It would be aided in this by the fact that, by about Stage II of infection, it would no longer be the only brain.

As Birkin mutates from Stage I to Stage II, his face is absorbed into his body, leaving a misshapen, defleshed skull. Given the limitations of Resident Evil 2’s graphics, it’s hard to say whether this is Birkin’s original skull or whether that skull was absorbed into his chest along with his face and this is a new skull. Given its unusual shape, it would be easier to suggest that this is a newly-developed skull rather than the old one somehow restructured, but either way, Resident Evil Archives confirms that the G-Virus does create a new brain in its host.

It seems likely to us that this “new brain” doesn’t develop entirely on its own, the way an embryonic brain would, due to the difficulties in establishing embryonic developmental programming at the organ level in an adult organism. More likely, this brain begins as replicative expansion of neural cells in the upper spinal cord.

It was once believed that brain cells, and by extension, spinal cord cells, could never divide, but we now know that they can and do. Overexpression of peptides like C3a could increase cell division in the central nervous system. xxi This gene could have been incorporated into the primitive G-Virus in Lisa Trevor’s body after she assimilated the Nemesis parasite, or it could have been engineered into the perfected G-Virus by William Birkin. G could also use siRNA to block genes like netrin-1 could allow stem cells to accumulate and proliferate.,xxii Alternately, the G-Virus could take a brute-force approach and reprogram astroglial cells to form new neurons.xxiii,xxiv In these cases, these properties would have had to be engineered deliberately.

Stage V

During the final stage of his existence, William Birkin abandons shape and form entirely, becoming an enormous, bulging sac of flesh with a huge mouth, a disproportionately small head, and no semblance whatsoever of anatomical organization. The Birkin-Blob moves by drawing itself forward with tentacles; it isn’t that it no longer has legs – he seems to have an abundance of useless limbs, based on concept art, and Darkside Chronicles shows at least one arm remaining – but his incredible mass makes his limbs useless for locomotion.

Such growth could easily be an inevitable consequence of accelerated growth of the kind we discussed above proceeding totally out of control. We believe that, with tissue growth ramped up so much, and with abnormally large populations of stem cells in all tissues, the infected cells in Birkin’s body start to behave like tumor cells at some point. Much of developmental biology depends on chemical gradients across the developing organism, telling stem cells when to grow and in which directions – but more importantly, when to stop growing, and even when to die. This stoppage and dying-back of replicating cells is the reason we have fingers instead of flippers, and is why we have a Becoming a giant tumor is apparently a humanoid shape in general. In a G-Type, these problem for all G-Types, not just Birkin. organizing signals again become important Source: Resident Evil 2 because of all the tissue growth going on, but their expression has been tampered with on a massive scale. Disruption of this delicate balance leads to a loss of organizational control, causing growth in all the wrong places. Add to that the fact that these chemical gradients have to develop across an adult body much larger and denser than an embryo or fetus, and this body keeps getting bigger.

Bone growth depends not just on cell division and protein synthesis, but also on the deposition of certain minerals such as calcium phosphate. As a result, bone growth and skeletal expansion are going to occur much more slowly than the growth of muscle and other tissues. The G-Type’s skeleton would most likely come apart as the creature’s flesh continues to expand, with individual bones getting lost in the mess. These bones may even get reabsorbed to provide nutrients and minerals for new structures elsewhere. The result is a giant, boneless blob of meat, and allowing it to explode was probably the most merciful option.

Stage V does have a couple of identifiable anatomical traits, including tentacles and a circular, lamprey-like mouth. We established before that the G-Type does appear to have tentacles during all stages of its existence, even if they are normally internal and visible only during embryo implantation. These same tentacles may be, or may develop into, the structures which allow the The circular mouth with concentric rows of creature to drag itself forward. The circular mouth teeth suggests lamprey-like traits, but we think there’s a non-lamprey explanation. Source: may be an inevitable consequence of the disruption Darkside Chronicles of the skeleton – a circular mouth being more or

less the default when one’s jawbone dissolves inside one’s face. Alternately, this may well be an engineered trait. William Birkin may have perceived during early experiments that a G-Type would eventually grow so rapidly that a mouth constrained by a relatively inflexible mandible and maxilla would be too small to permit the necessary rate of feeding. He might, then, have thrown in some developmental characteristics of jawless fish or sharks, on the argument that a funnel lined with multiple rows of teeth is the most efficient way to take in food. This trait would probably manifest beginning with the development of the second head and the subduction of the original head into the body, and would explain at least in part the unusual appearance of the G-Type’s head and jaws in Stage IV of development as well.

The “Devil” vaccine

Resident Evil 2 has two story modes; in one of them, William Birkin successfully infects his daughter Sherry with a G-embryo. It then falls upon Claire to find a vaccine to cure Sherry before the parasite consumes her (and generates another giant monster for her to fight). We described vaccines quite a bit in our first Report, but it’s worth mentioning again that vaccines take days, if not weeks, to make someone immune to something. This vaccine, like most of the T-Virus treatments we’ve covered, has to work pretty much instantly.

One treatment that would work quickly is an injection of monoclonal antibodies against various G-Virus antigens. Monoclonal antibodies are generated by hybridomas – ungodly fusions of antibody-producing B-cells and immortal cancer cells – that produce only a single kind of antibody, which targets only a single kind of molecule. These antibodies can then muster the body’s own defenses against the invader, or block the viral proteins which would allow the virus to infect cells (or in this case, the proteins which would allow the mutant cells to fuse to healthy cells). Cultures of hybridomas can make a lot of antibodies quickly – hopefully enough to kill whatever virus, bacterium, or invading mutant cell which happens to be the problem at the time. Unfortunately, monoclonal antibodies are not “true” vaccines, because the immunity they provide does not last for long. A true vaccine must train the body to fight its own infections.

The “Devil” vaccine, then, probably contains monoclonal antibodies to allow it to work quickly, but, being a vaccine, it probably contains a few other ingredients. Most vaccines today include either “attenuated” pathogens, which are alive but too weak to do much harm; or killed pathogens, which are dead, but can still teach the immune The vaccine has to be made in several stages, which probably reflects its composition. system what to watch out for. The unique nature Activation in the V.A.M. could involve the of the G-embryo infection, however, calls for a addition of monoclonal antibodies for third type of vaccine – a subunit vaccine. Subunit opsonization and prophylaxis. Source: vaccines include only a few components of the Resident Evil 2 pathogen – the ones most likely to cause an immune response. In this case, the subunit in question is probably the surface glycoprotein of the G-Virus. Viral glycoproteins are often used by viruses to attach to cells, and can often show up on the surfaces of infected cells as the virus inside starts to replicate. Even when a virus fails to replicate, these glycoproteins on the cell surface can cause the cell to attach to and fuse with

neighboring cells as if it were a virus itself – which is exactly what we proposed happens during the development of the G-embryo.

In the vaccine, these glycoproteins would probably be opsonized by antibodies – coated with them to allow the immune system to recognize them quickly, and to take them seriously. These antibodies coating the glycoproteins would also prevent the proteins from soaking up the monoclonal antibodies already in the vaccine, which are needed to fight the infection right away.

G subtypes

A G-Type is probably the closest thing in the world of Resident Evil to a perfect organism. Unfortunately for Umbrella, its structural perfection is matched only by its hostility – it cannot be controlled and it lives only to put smaller indestructible monsters inside the guts of anyone it thinks would make a good surrogate womb. But the scientists at Umbrella aren’t the types to take “My God, what have we done?” for an answer – and hence, several variations of the G- Virus were created.

The T+G Virus

The T+G Virus is the first deliberately modified form of the G-Virus we encounter in the series. Appearing for the first and only time in the awesomely titled Resident Evil: Dead Aim: Heroes Never Die, this virus was the product of an attempt by the Umbrella Corporation to control the random mutations which reduce the effectiveness of the G-Virus as a biological weapon. Also, they kind of wanted to give the monster electrical superpowers. We don’t get it either.

Let’s start by discussing exactly what the T-Virus has to do with this and why. Depending on whom one talks to and what languages one reads, the nature of the virus is different. The English-language file “Research report #220329” claims that T+G is actually a fusion of the T- Virus and the G-Virus. The Japanese version states that the G-Virus was fused with a T-Virus antibody “on a genetic level.”

Here at Project Umbrella, whenever there’s a discrepancy between the English and Japanese versions, we tend to go with the Japanese – not so much out of some hipster-like desire to be more “authentic” than everyone else, but simply because we’ve noticed that most of the contradictions and plot holes, and even some of the scientific impossibilities which have plagued these Reports so much, tend to be absent from the original Japanese version. They’re inexplicably introduced by the English-language localization team, and we will never forgive them for that. Anyway, even though we prefer the Japanese version for several reasons, we’re going to try to explain things both ways in this case. Just this once.

The English version, with which most of our readers will be familiar, states that T+G is literally just that – the T-Virus plus the G-Virus, genetically combined. It’s not out of the question – T and G were both derived from the Progenitor Virus, and they should be similar enough that most genes and proteins from one could be swapped out for their equivalent from the other. As we’ve described above, G most likely expresses a lot of the same growth factors that T encodes, only expressed far more strongly, and constitutively when many such genes in T are expressed only in response to injury. Replacing these genes in the G-Virus with their equivalents from the T-Virus would result in a virus with some of the characteristics of the G-Virus – for instance, the capability to generate epiphyseal plates, allowing expansion of the skeletal frame – but not other traits, like the tendency to transform the host into a shapeless blob. Anyway, that’s We would remind our readers that the virus was designed the theory. specifically to avoid this. Source: Resident Evil: Dead Aim

That was fairly simple and we’d like to leave it there, but duty compels us to examine the rather more complicated Japanese version. According to Japan, the T+G Virus combines the G-Virus at the genetic level with an antibody against the T-Virus. Now, antibodies are secreted proteins that don’t carry any DNA of their own, so it should, in theory, be impossible to combine them with anything at the genetic level. Even if it were possible, it shouldn’t do anything but slow the virus down. But we wouldn’t be writing this if we hadn’t found a way to make it work.

Antibodies are useful little tools of the immune system because they can be made to target very specific things – for instance, one cell can make an antibody that only targets the anthrax bacterium and absolutely nothing else. This is useful because if a person gets anthrax, this system allows the body to pump out tons of these antibodies, safe in the knowledge that they’re not going to destroy anything important, like the lungs. Of course, since anthrax is only one of thousands of different microbes which can attack the body, it’s necessary to be able to make thousands of different kinds of antibodies. The body does this by producing an inordinately huge number of cells called B-cells, which make antibodies. During their development, each B-cell undergoes a very specific kind of mutation called V(D)J recombination, which randomly alters the genes that make antibodies. In short, antibodies can have all of these different specificities because at the genetic level, each B-cell is a unique and beautiful snowflake.

We have the technology to immunize an animal against something, extract its precious B- cells, and then select only for the ones that make antibodies specific against the target of interest. This is how one makes the monoclonal antibodies we described above and as we explained in our first Report, Umbrella seems to have done this already with the T-Virus in an attempt to make a protective treatment for the UBCS. With these anti-T B-cells, it should also be possible to extract the genes for their unique antibodies and reinsert The arrows point to the antigen-binding sites – the parts that these genes into the G-Virus, so that are specific for particular kinds of molecules, and which make the G-Virus expresses these every antibody different. antibodies itself.

There is still a problem with this scenario, however. The T-Virus antibodies didn’t save the UBCS, and being less specific for the G-Virus, they’re going to be even less effective in this context. Even if they blocked G-Virus infection nearly completely, limiting infection to only a very small percentage of the body’s cells, G-infected cells have a tendency to proliferate rapidly, and they would eventually take over the host’s body. Fortunately, we are once again one step ahead of the game. Whereas B-cells secrete their antibodies into the surrounding fluid, we think it might be more useful to have the G-Virus express its anti-T antibodies in the cytoplasm of infected cells – the goo where everything happens. Here, these antibodies would bind not to virus particles, but to viral proteins like trans-activators which allow expression of the virus’s transformative genes. In this way, these antibodies wouldn’t slow down infection much, but they would severely curtail the rate of the host’s transformation, and possibly even eliminate some of the more extreme transformations.

Dead Aim actually showed two subjects created with the T+G Virus – a prototype Tyrant, T-091, and Morpheus Duvall, who injected himself with the more advanced strain 0.9.2. The prototype Tyrant actually looks fairly typical for a tyrant, presenting as an oversized, vaguely human- shaped creature. The fact that it has Tyrant-like proportions rather than G-Type-like proportions suggests that Umbrella did a pretty good job of keeping its mutations in check, despite the fact that the virus had to modify the subject’s skeletal system more or less on its own. T-091 diverges from normal Tyrants in a couple of important ways, though. First, its hands possess tentacles rather than claws. This difference is easy to explain; as we’ve described above, G- Types seem to have some internal tentacles which extend into their limbs. In this case, the tentacles just extend a bit further, a condition perhaps exacerbated in that the more temperate mutations induced by the T+G Virus result in a creature that lacks gigantic claws.

The other major difference is that T- 091 has a bizarre, pulsating organ on the back of its neck which appears to be important to its survival. This trait is harder to explain, but we believe it is connected to Umbrella’s attempts to create a Tyrant with electrogenic properties. By all appearances, this organ seems to be a heart – it has what looks like chambers; it’s asymmetrical; it pumps; and when you shoot it, the creature dies. Now, an animal’s heart is rather peculiar in that it generates its own electrical current in a little bundle of tissue called the sinoatrial node. This tissue, and this electrical current, The Tyrant-091 has pulsing neck-meats which may be are what actually cause the heart to ontogenically related to the heart. Source: Dead Aim pump. If Umbrella wanted to make a creature that could generate its own electrical current, they might do so by tinkering with the genes which regulate the formation of the heart and the sinoatrial node – genes like Nodal, Cerberus, and Dickkopf-1 (the last of which we believe was named by a German with a sense of humor). Add to that the fact that they’re tinkering with these genes using a form of the G-Virus, which has a documented tendency to put things like eyes and arms where they don’t belong. Umbrella may have wanted to create sinoatrial nodes throughout the body; instead, they put a heart on the back of a creature’s neck.

Morpheus displays a more complicated (and irritating) set of mutations. Shortly after injecting himself with T+G strain 0.9.2, Morpheus develops into a more-or-less female-looking Tyrant with full human intelligence and the ability to generate electricity. Let’s tackle the electricity first. According to Umbrella’s own notes, Umbrella wanted to create a Tyrant which could produce an electrical field so powerful that it would repel bullets. Technically, this is impossible unless the bullets were positively charged (and typically, they’re not); if anything, the bullets might actually be attracted to the subject thanks to principles of electrostatic induction. Funny thing is, it actually seems to work in the game. But this is The Biology of Evil, not The Physics of Evil, which would be a lot more boring and mathematical,xxv so we’re going to let that slide for now.

We’ve already described how Umbrella might make a creature electrogenic by turning its body into one big sinoatrial node, but that’s not the only way to do it. We know that Umbrella has played with electricity before, when creating the Albinoids; it’s not outside of the realm of possibility that they used some of the same transgenes in T+G. Alternately, the fact that both viruses increase expression of muscle tissue can be used to increase expression of proteins found in the neuromuscular junction – the connection between nerve cells and muscles. It is precisely these sorts of proteins that electric eels use to build electroplaques, the structures which they use to generate electricityxxvi. The virus may also tweak expression of ion channels in nerves; the

function of electroplaques depends on maintaining an ionic gradient across the cell membrane, just like the action potential in a nerve cell.

There’s also the matter of intelligence. Most Progenitor-family viruses tend to damage the brains of all but a select group of individuals; Morpheus retains at least enough intelligence to speak and order a missile launch. We hypothesize that T+G expresses certain small interfering RNA molecules driven by promoters exclusive to brain tissue – these siRNA molecules would inhibit viral activity in the brain, hopefully preserving at least some cognitive capability.

Finally, perhaps the most frustrating aspect of T+G 0.9.2, worse even than the fact that it’s a stupid lightning virus, is the fact that it induces a wholly unexplained sex change in its host. Former Project Umbrella member El Bastardo wrote a clever report on Dead Aim proposing that Morpheus had already had some of the surgeries involved in gender reassignment Regardless of where Morpheus got his – in particular, breast implants. This wouldn’t, breasts, those child-bearing hips came however, explain the widened, feminine hips. The from the virus. Source: Dead Aim answer may lie in a gene called Dmrt1, which is expressed constitutively in the gonads of males. Shutting this gene down turns testicular cells into ovary cellsxxvii. If T+G were to express siRNA molecules to interfere with this gene, and others like it expressed throughout the body, then Morpheus’s body might take on a more feminine shape as the virus restructured his skeleton and musculature in ways described elsewhere. Why would Umbrella put this sort of thing into T+G? Honestly, we have no idea. Maybe Morpheus put it there himself after he obtained the virus. Maybe Umbrella was just trying new things in a misguided attempt to break into the Tyrant-fetishist market. We kind of don’t want to know.

The blobs

A new monster called the “Blob” is introduced in Lost in Nightmares, a downloadable scenario for Resident Evil 5. The game never states definitively that the Blobs were created using the G- Virus or anything like it; the closest we get is a vague statement from Spencer’s manservant Patrick, who stated in his memoirs that he’d helped his boss infect a bunch of prisoners with a virus. Nonetheless, we concluded from several aspects of the creatures themselves that a form of the G-Virus was likely involved.

First, Patrick’s memoirs seem to suggest that a single injection of a virus transformed these creatures into hulking, indestructible brutes. As we discussed in the second Report, the T-Virus can’t normally achieve that kind of growth and transformation on its own, at least in humans. The G-Virus, on the other hand, was designed to do exactly that. Second, the Blobs have

anatomical characteristics reminiscent of those displayed by G-Types. They possess ectopic eyes, for instance, and they have circular, lamprey-like mouths similar to William Birkin’s mouth in his final form. Third, the Blobs are peculiarly asymmetrical – but this asymmetry develops not in the form of an oversized arm, but in the form of a huge, hideous tumor on the shoulder. A very similar tumor has been observed on certain G-Mutants – particularly the one which birthed from Monica in Resident Evil: Outbreak. And finally, Spencer is a cold, calculating monster, but he’s not a scientist. He doesn’t create viruses – he simply steals them from his colleagues, or from the protégés of his colleagues, or from Africa. Whatever this Blob virus is, Spencer didn’t make it on his own.

Yet it seems obvious that these creatures were not created by the G-Virus as we know it. The G- Virus causes mutations which progress through drastically changing forms, and this occurs at different rates in different subjects, judging from its effects on William Birkin and Curtis Miller. The Blobs all look more or less identical, as if they developed to a certain point and all just stayed there. Furthermore, none of the Blobs display any anatomical idiosyncrasies from one another. Curtis Miller grew a weird little tail and a face like a bug; William Birkin had none of that, but he grew an extra set of arms instead. Blobs also lack the resilience of true G-Types as well; shoot them enough, or drop slabs of rock on them, and they don’t mutate into stronger forms – they just die.

We choose to explain this by proposing that the Blobs were created with a weakened form of the G-Virus, in which certain genes were removed or weakened, or even programmed to go silent shortly after infection. Removing genes for various growth hormones, or altering their promoter regions to reduce expression, might shift the organism away from a positive feedback loop of unrestricted growth toward a more stable, self-regulating pattern of gene expression. These genes might also be programmed to become silent in response to certain chemical factors which reach a high concentration in the “mature” form of the organism. It is even possible that these genes even delete themselves – if the genes are flanked by stretches of DNA called lox sites, then inhibitory factors produced by the mature form of the organism might induce expression of Cre recombinase elsewhere in the viral genome, which would then snip out the lox-flanked (“floxed” being the technical term) genes and patch up the genome like they had never been there at all. So, while certain late phenotypes, like the lamprey-mouth, would eventually develop, the monster itself would never get any bigger or more misshapen than it is at this intermediate stage.

It may also be possible to control the Blobs’ development by replacing certain G developmental genes with similar genes from the T-Virus. Creating the Blobs may be a two-stage process in which subjects are first treated with a butchered form of the G-Virus, lacking certain activators needed to express its transformative genes. In the second stage, the subjects might be treated with the T-Virus or something similar, which – being closely related to the G-Virus – expresses these activators and allows the transformative genes from G to be expressed. As we’ve mentioned before, the T-Virus expresses a lot of growth factors, much like the G-Virus, but at a lower level. This system effectively replaces some of the genes in G with genes from T, which may contribute to control of the Blobs’ development. This may even explain another anatomical feature of the Blobs – that peculiar tumor they all seem to have on their left shoulders.

As we described above, we believe the G-Virus cannot actually replicate in human cells, and must be injected in quantities sufficient to infect every cell in the body in a single generation; in this system, that wouldn’t be necessary. Because of their close genetic relationship, G-Virus genomes might actually be able to incorporate themselves into capsids produced from T-Virus genes, thereby generating new virus which can infect other cells. It could be, then, that only a relatively small quantity of Blob Virus was injected into the subjects’ hearts, infecting endothelial cells lining the arteries as the virus moves into the subject’s bloodstream. In the absence of the described activators, these cells would “transform” in the cancerous sense, but wouldn’t grow with the full power of the G-Virus. If the T-Virus is administered days or weeks later, these “transformed” cells would have plenty of time to detach from their Blobs are characterized by big, lumpy left shoulders and a fondness for surroundings – as cancer cells often do. Now, it so anchors. Source: Resident Evil 5: Lost happens that the main artery coming out of the heart – in Nightmares the aorta – not only moves more blood per minute than any other blood vessel in the body, but it also has a sharp turn in the upper left of the chest. Some of these circulating cells are bound to take that turn a little too fast and may come in contact with the wall of the aorta. Then, they’ll do what cancer cells do – invade the neighboring tissue. The host may then wind up with a preponderance of cancerous cells in the upper left of the chest. When the T-Virus is administered, the G-infected cells in the upper-left chest not only begin to divide and expand rapidly; they also become sites of viral replication, creating viruses which can then spread through the rest of the body.

The tumors, once they finally develop, may be a form of tumor called a teratoma; these tumors are special because they contain otherwise-normal cells and tissues in places where they really ought not be. Teratomas excised from human patients have often been found to contain teeth and hair, for instance. These teratomas may contain a cell type called a parietal cell, which is responsible for secreting acid into the stomach.

Alongside the Blobs, another enemy is present – decrepit-looking humans lying prostrate on the ground who grapple anyone who gets too close. These subjects look rather like zombies and act mindless like them, but are incapable of walking or crawling. It’s possible that they were test subjects for a failed virus – after all, similar subjects can be seen on their way to an incinerator in Resident Evil 5, far removed from Spencer’s dungeons. Alternately, they could be part of the same experiment as the Blobs. We described a two-stage process of infection for the Blobs, first involving a weakened form of the G-Virus, followed by infection with the T-Virus – either in a weakened form or in its full glory. Every experiment, however, has its control group – a group in which subjects don’t get the actual treatment, giving scientists a baseline to compare the effects of their experiment against. Experiments involving multiple treatments have multiple control groups, some getting one treatment but not the other. In this case, one control group may not have gotten the G-Virus treatment, but definitely got the later T-Virus treatment, turning

them into zombies. As for why they’re floor zombies, we’re not sure. A modified form of the T- Virus may have left them without the metabolic capability to sustain all of their muscle tissue. Alternately, Spencer had their spines broken on those medieval racks in his dungeon as part of an experiment designed to make him walk again. We’ll probably never know.

Lisa Trevor

We would like to take this opportunity to discuss Lisa Trevor. Strictly speaking, she was not “developed” by Umbrella so much as injected with dozens of viruses and left to fester; likewise, the most important virus in her body was not a modification of the G-Virus so much as a precursor of it. Nonetheless, she exhibits some interesting G-Type traits and her body was the source of what would ultimately become the G-Virus, so she merits some consideration here.

Lisa is (almost) unique in the Resident Evil canon in that she can never, strictly speaking, be killed by the player. When she was first introduced in the remake of Resident Evil, she was utterly bulletproof and no amount of firepower could even knock her down – ultimately, the player did not kill her so much as knock her off of a ledge and forget about her. She made a reappearance in Umbrella Chronicles, where even Wesker failed to kill her; the best he could do was to trap her in a mansion that was about to explode. Frankly, we’re not even certain that the exploding mansion killed her, but we’re hoping that the nuclear annihilation of Raccoon City and the surrounding forest did.

There is one other monster in the Resident Evil series who displayed that kind of tenacity – William Birkin. The observant reader will recall that, even after Birkin was defeated for the final time in game-play, he shook if off quickly and it took a tunnel full of exploding train to (presumably, hopefully) kill him for good.

Lisa never demonstrated the full range of mutations that William Birkin did, but it’s highly probable that she displayed at least some of the same characteristics that kept Birkin alive in the face of massive injury. Given her large size and somewhat irregular form, it’s likely that the same factors which reshaped Birkin’s skeleton also acted on Lisa’s, albeit in a less pronounced fashion; similarly, her strength suggests that her muscle mass increased in much the same way. In our second Report, we mentioned special strains of the T-Virus that we suspect were used to promote skeletal growth and develop the massive claws of the original Tyrants; Lisa Trevor being the serial guinea pig that she was, it’s probable that she was infected with such viruses during the development of the Tyrant program. The precursor virus in her body might well have incorporated such genes from these viruses through recombination in co-infected cells.

Lisa may also possess a preponderance of stem cells, like a traditional G-Type, as well as the growth factors which promote rapid tissue regeneration in those creatures. As we proposed for the G-Types, Lisa may also possess some redundancy of her internal organs, particularly the heart.

In addition to her invulnerability, Lisa displays two traits which manifest suddenly during the battle in the crypt, and which stand out to those who have played other games in the Resident Evil series. One such trait is a random shoulder eyeball, which we would again attribute to E-NTPDase 2 overexpression. The other trait is a group of tentacles which emerge from her back. According to Wesker’s

Report II and the “Observation Note” Like Nemesis, Lisa Trevor has tentacles. Like G, Lisa file in the Resident Evil remake, the Trevor has eyes where eyes should not be. Source: virus in Lisa’s body was not discovered Resident Evil Remake until after she was infected with the Nemesis parasite, and said parasite disappeared. The files are a little ambiguous as to whether the parasite was simply destroyed, or whether the virus in Lisa’s body was able to appropriate some of its genetic material through recombination. These tentacles, we believe, indicate the latter, and they are one of the reasons we are confident in proposing the existence of similar tentacles in the bodies of G-Types. We will discuss these tentacles in further detail in the section on the Nemesis itself.

Nemesis

The creature known as “Nemesis,” which made its first (and last canonical) appearance in Resident Evil 3, is a smarter, more dangerous variant of the Tyrants with which we grew familiar in earlier games. Nemesis is unique in the pre-Resident Evil 4 canon in that it owes its most singular traits to a parasite, rather than a virus. According to Wesker’s Report II, this parasite was created to bypass the problem of Tyrant intelligence – as we discussed in the previous Report, most humans have a genetic incompatibility with the T-Virus, leading to Tyrants no more intelligent than your average zombie. Below, we shall discuss just what kind of parasite could solve that problem, and how it might go about it.

The NE-α parasite

Some people have suggested that the NE-α parasite, as it is known, is somehow derived from the parasitic Las Plagas which first appeared much later, in Resident Evil 4. These people are silly and wrong – putting aside the fact that Las Plagas were still sealed away beneath Salazar’s castle in 1988, when Wesker’s Report II indicates the project began, we know from the aforementioned report that early strains of the NE-α parasite killed their hosts within minutes. Las Plagas produces a productive infection fresh out of the box, as it were. NE-α, then, appears to be entirely artificial.

Resident Evil Archives indicates that the NE-α parasite is injected into the spinal cord “at the cellular level.” This sentence probably reflects someone at Capcom trying to sound like he knew what he was talking about, and failing hard. However, it doesn’t have to be meaningless – there are some parasites which exist as single-celled organisms, allowing for some interpretations of “injecting at the cellular level.” Some of them, such as Plasmodium and Leishmania, the causative agents of malaria and leishmaniasis respectively, can even enter live host cells – literally infecting at the cellular level.

We’re going to settle for a less stringent interpretation – for what we have in mind, injection of a single-celled organism would work, but injection into living cells would not be feasible. We think that NE-α is a suspension of genetically modified human tumor cells. Parasitic cancers (also called clonally transmissible cancers) are rare, but they do exist in nature. Dogs and Tasmanian devils are afflicted by two such diseases – canine transmissible venereal tumor (that’s right, it’s an STD) and devil facial-tumour diseasexxviii. This latter disease – the satanic one – is a neuroendocrine tumor, believed to be derived from glial cells found in the peripheral nervous systemxxix.

A cancer derived from nerve cells gives us the best chance of producing a parasite capable of connecting to the host’s nervous system, so that’s where we looked for viable candidates. Brain tumors, surprisingly, don’t make good candidates – most of them form from nerve-associated cells like glial cells, which don’t actually form the synaptic connections needed to send messages to the nervous system. Two slightly more promising possibilities are neuroblastomas and primitive neurectodermal tumors, both of which derive from neural crest cells – the cells which contribute to the formation of many tissues in the head, including a wide variety of nerve ganglia. Neuroblastomas are interesting in that they have a peculiar ability to spontaneously revert to a benign state that won’t actually kill the host; this has obvious implications for something like the NE-α parasitexxx. Primitive neurectodermal tumors are so-named because they resemble “primitive,” undifferentiated neural crest cells – suggesting the possibility of differentiating into more derived neurectodermal cells, including neurons. These tumors in particular could give NE-α the much-desired capacity to interface directly with the host’s nervous system, possibly coaxing new synaptic formation using surface-bound proteins like ephrins, neurolipins, and neurexinsxxxi,xxxii.

Any tumor cells used as source material would, of course, need to be modified rather drastically to suit NE-α has no defined shape or recognizable sensory organs Umbrella’s needs – in particular, the and, in fact, kind of looks like a tumor with tentacles. Source: need to keep the host alive, and the Wesker’s Report II

need to organize into some kind of useful neural tissue. Getting meat to grow into brain is still a bit beyond the ken of modern science, although we’re starting to unravel how nature does it; for now, it’s best left to the tumors to take care of that on their own. Engineering a non-lethal cancer may be slightly less difficult. A lot of different mutations are capable of turning normal cells into cancer cells – sometimes it’s caused by damage to the p53 gene, which is involved in repairing DNA or killing borked cells before they start replicating out of control; sometimes it’s caused by loss of the Rb gene, which keeps cell replication at the proper pace and stops it when no new cells are needed. Sometimes entirely new genes get made by accident and throw the cell into overdrive, like Bcr-abl. The point is, while it’s hard to cure a human being, it might be possible to “cure” a culture of isolated tumor cells through genetic manipulation, or tamp down their replicative friskiness just enough to keep them from metastasizing all over the body. Missing or broken genes like p53 and Rb could be replaced with low-efficiency transgenes, or a point mutation could be induced to reduce the function of Bcr-abl without eliminating it completely.

It’s all well and good for NE-α to not kill its host, but it also needs to grow through the nervous system. Once injected into a host, NE-α may take advantage of certain compounds in the cerebrospinal fluid like Igf2 as a guide in order to send nerve shoots into the brain. Excessive Igf2 in the cerebrospinal fluid has been linked to the migration of glioblastomas, brain tumors consisting of glial cellsxxxiii. In the process, it has to get nutrition; we would have been happy to say that it takes up glucose from the circulatory system like everything else, but Capcom has other plans. An obscure little source called the Biohazard 3 Last Escape Official Guidebook indicates that, after infection, the parasite will “devour the T-Virus cells to reproduce.” We don’t know what this is supposed to mean, or whether the concept of “meaning” can even apply to this sentence. The T-Virus isn’t a cell; it’s a virus – and why would the T-Virus have anything to do with the parasite’s reproduction? We have chosen to assume that NE-α consumes host cells as it proliferates, both providing it with space to occupy and the nutrients it needs to grow. In a T- Virus-infected subject, every cell would express viral DNA to a certain extent, and could be described as a “T-Virus cell.” Some of these cells might even produce growth factors a normal cell wouldn’t, giving NE-α extra stimulation.

Incidentally, if the NE-α parasite is a tumor, then it shouldn’t be too hard to extract a sample of it from a host with an oversized syringe if, for example, one wanted to implant the parasite into a malfunctioning Nemesis T-Type. Extracting enough parasitic tissue in this way would necessarily disrupt the parasite’s neural networks, interfering with its control of the original host and possibly causing it to indiscriminately attack anything around it. For all of its other flaws, Operation: Raccoon City at least does us the favor of not completely invalidating our theories.

Anatomy of a monster

According to Resident Evil Archives, the monster known as “Nemesis” or the “Nemesis T-Type” was a T-103 Tyrant infected with the NE-α parasite. Shortly after infection, the parasite generates a novel central nervous system which takes over most of the voluntary functions of the host’s body – that is, it drives the host like a damned Buick. This brain doesn’t appear to be located in the head – mainly because it is visible on the Nemesis T-Type’s misshapen body during the final battle in the incinerator room, after the creature has been decapitated (it’s a very

persistent monster). According to the Official Guidebook mentioned above, this extra brain forms around the medulla – presumably the spinal medulla. Examination of the final, mutated form of the Nemesis T-Type suggests that this brain – the “body” of the NE-α parasite, if it can be said to have one – can get pretty big, but it remains localized to the region of the thoracic cavity.

The Nemesis T-Type’s body is run through with tentacles, which extend at least through the right arm, and which emerge from the torso at various points. At least one tentacle emerges from the shoulder only to reenter the body nearby, creating an odd loop. After the upper portion of Nemesis’s coat is burned away, one can see that many of these tentacles have their origin at the creature’s upper back – precisely where we concluded the brain was located. The tentacles have a segmented appearance, almost like the body of an earthworm – but we’re fairly confident that annelid genes did It’s hard to tell from this image, but the big fella flipped not provide the source of these over earlier and is actually crawling around belly-up there. tentacles. The parasite isn’t likely to Source: Resident Evil 3 grow the better part of another organism’s entire body as one of its appendages, any more than it’s likely to grow daschunds for feet. Rather, these tentacles appear to be novel organized structures incorporating smooth muscle tissue, which can normally be found in diverse body parts like arteries and the intestines. Smooth muscle tissue can grow in an annular (ring-like) pattern in order to generate constrictive force, and this pattern could well explain the tentacles’ striated appearance. A combination of circular muscles and longitudinal muscles would allow the tentacles to generate intense hydrostatic pressure, which could be used not only to move the tentacles, but also to project them with the kind of force necessary to impale someone.

In addition to the tentacles, the Nemesis T-Type’s body is marred with big, ugly surgical scars. The most obvious of these is the laceration that runs down its face, held closed with surgical staples and obscuring the creature’s right eye. The loss of the limiter coat, late in the game, reveals scars with characteristic suture marks down the back, on the abdomen, and down the left arm, suggesting possible surgical alterations. It may be that the NE-α parasite causes a lot of damage when it first grows its tentacles through the host’s body, and these injuries were repaired somewhat haphazardly by Umbrella scientists. Given that the left arm bears a long scar and never deploys any tentacles, it may be that the tentacles were surgically removed from this arm for some reason, such as anatomical study. The scar down the face might be a result of a massive cranial fracture incurred by tentacles or neural bundles growing into the host’s brain; this would explain the use of surgical staples instead of mere heavy sutures. Alternately, the host

may have undergone a partial frontal lobotomy of the extremely messy and invasive kind for unknown reasons, perhaps relating to behavioral control.

The Nemesis T-Type appears to be missing its lips and nose. We have never developed a satisfactory explanation for this, but it appears to be surgical in nature, given that its Tyrant host almost certainly had a nose before infection.

According to Resident Evil Archives, the NE-α parasite secretes materials which grant its host increased strength and durability. These secretions probably include a lot of the substances we’ve described several times before, such as thyroid hormones and growth factors; the parasite might also secrete hormones such as epinephrine to keep its host in a perpetual state of alertness. Beyond making the host tougher and meaner, we also suspect that the parasite’s secretions include a number of neurotropic factors, at least during the early stages of Visible here are some of the lesser-known scars on Nemesis’ body – evidence of extensive surgery. Source: infection. Such factors might include Resident Evil 3 neuroligin and SynCAM 1 to promote synaptic formation, both in the parasite’s own tissues and between the nervous systems of the parasite and its hostxxxiv. Other substances might include neurotrophins, nerve growth factor, and brain-derived neurotrophic factor, all of which play a role in brain development.

Other secretions may include live cells – the Biohazard 3 Last Escape Official Guidebook also describes the NE-α parasite as producing “competent cells” which changed its host’s appearance. Other than the tentacles, which we believe are part of the parasite itself, these changes in appearance seem to be limited to mottling of the host’s skin. This may be caused by the cells integrating themselves into the basal layer of the host’s skin as keratinocytes; if these new, parasite-derived keratinocytes produce more keratin than the host’s cells, then they would generate tougher skin, making the Nemesis T-Type more resistant to minor injury. In the process, they would also change the appearance of the skin where they localize, leading to a mottled appearance. The phrase “competent cells” still needs to be explained, though. In biological parlance, “competence” refers to the capacity to take up and express foreign DNA. While animal cells don’t normally do this, we’re not going to put it past a creation of the Umbrella Corporation, and they might even have a reason to make it possible. As these cells spread through the host’s body, they’re going to draw the attention of the host’s immune system – much more so than the rest of the parasite, sitting as it is in the central nervous system, which

is an immunoprivileged location. By taking up host DNA, these “competent cells” might be able to express host MHC Class I on their surfaces, essentially disguising themselves as host cells.

Late in the game, the Nemesis T-Type is flushed into a pool of industrial solvent, and the next time we see it, it’s lost its left arm, its right leg, its head, and a considerable volume of its internal organs. At this point, the original brain is completely gone, meaning that the NE-α parasite is capable of sustaining the host body’s autonomous processes on its own. It’s also worth noting that the parasite had to grow itself some new mouthparts, because it somehow manages to feed on a dead Tyrant without the benefit of its head. Immediately afterward, it grows into The striations in some of those limbs indicate that they a…thing. The missing limbs regenerate, originated from the parasite rather than from the Tyrant apparently consisting largely of the host body. Source: Resident Evil 3 parasite’s own tissue, and the body increases in size. We’ve seen Tyrants transform before, as well as a few other transformations, and we’ve attributed most of them to a tweaked version of the stress-activated protein kinase (SAPK) pathway activating in response to injury. This particular transformation seems to suggest that the NE-α parasite itself is capable of the same transformation, likely involving the same SAPK activation, which started shortly after the Nemesis T-Type was partially dissolved and only kicked into high gear when it got some protein into its body to replace its missing biomass. We can conclude that the parasite is either created using the T-Virus to mediate the genetic manipulations described above, or it becomes infected subsequent to its implantation in the host, and somehow manages to retain its normal function.

The transformed Nemesis also develops big, fluid-filled sacs on its upper body which allow it to project a caustic secretion at its prey. As mentioned before, the abdominal and thoracic cavities appear to have been hollowed out during Nemesis’s bath in the waste disposal sludge, so these sacs might be the NE-α’s attempt to regenerate digestive organs. Why they look nothing like the gastrointestinal tract, and why they grow from the upper body rather than the abdomen, we don’t know. If thus substance resembles the secretions of the stomach, then that would make the creature’s acidic effluence a mixture of hydrochloric acid and pepsin, an acid-activated enzyme which breaks down protein. It’s also possible that this fluid more closely resembles the secretions of the pancreas and intestine, in which case it would contain trypsin, chymotrypsin, elastase, and carboxypeptidase – some other enzymes which break down proteins. Unfortunately, these enzymes won’t work at the low pH of stomach acid, so we can’t mix everything together.

Nemesis subtypes

Canonically, the Nemesis T-Type, and hence, the NE-α parasite, appear only in Resident Evil 3 (barring the retelling of that game in Umbrella Chronicles and the Nemesis’s appearance in the non-canonical Gun Survivor 2). Nonetheless, as with the G-Virus, Capcom has given us a known modified variant in the NE-β parasite, and one…thing…that we suspect to be related to Nemesis, in Nyx.

The NE-β parasite

The NE-β parasite appears only in Operation Raccoon City. Unlike the NE- α parasite used to create the Nemesis T- Type, this parasite appears to be an arthropod with a thick, chitinous exoskeleton, making it able to operate independently of a host and highly resistant to damage. Like certain organisms known to harass crowbar- wielding theoretical physicists, this organism attacks its prey directly, then integrates itself into the central nervous This is the only image we have of the thing right now. system while transforming the host into a Source: Operation Raccoon City dangerous freak of nature. The difference here is that this creature decapitates its host and replaces the brain completely, and makes its new body extremely resistant to damage.

We believe that the arthropod-like nature of the NE-β parasite is specific to that strain, and absent from the NE-α parasite, mainly because we have a picture of NE-α, and it looks like a meatball, not a tarantula. How, then, does one transform a meatball into a tarantula?

It is possible that the NE-β is a symbiote in several senses of the word. Obviously, it has the capability to coexist with, maintain, and even alter a human or zombie host – but it may have a smaller parasite riding inside its own body. Certain species of wasp which lay their eggs in other animals have a persistent and very special kind of viral infection – their cells produce a type of virus called a polydnavirus. The viral DNA is encoded in the wasp’s own genome, making it practically a part of the wasp itself. The virus is incapable of infecting the wasp’s cells, but when the wasp lays its eggs in a spider or a caterpillar, it also injects a hearty dose of this virus, obliterating the bug’s immune system so that the eggs can survive. NE-β may be doing something similar. This parasite may be a hybrid of some other monstrosity – something like a Plague Crawler, Web Spinner, or Chimera, or maybe something totally new – and the NE-α virus. In this case, the bug may produce NE-α cells in a stinger or in its saliva, and may inject them into a host’s spinal cord after decapitating it; it may even have a nervous system derived from something very much like NE-α (which we believe to be derived from neural tumor cells, as we described above). These cells would then establish a neurological connection between the bug and the host’s central nervous system (or what’s left of it), putting the bug in control.

NE-β also makes its host extremely strong and resistant to injury. We’ve described several times how the T-Virus and similar viruses can increase muscle growth and regenerative capability, and how alternate metabolic pathways encoded by the virus can reduce an infected subject’s need for things like blood flow and vital organs. This parasite may carry a strain of the T-Virus, generated either in the arthropod body or by the injected cells, which accomplish the same thing. This virus may even be modified to constitutively express the V-ACT phenotype, much like the modified zombies created by Javier Hidalgo in Darkside Chronicles. If the injected cells produce T-Virus growth factors without releasing the virus itself, then the necrotic properties of the virus in humans would be minimized – although a human host would still need its organs.

The NE-β parasite is capable of secreting a sort of bile which can not only suffocate and incapacitate humans, but can also attract other Bio-Organic Weapons. This adaptation could indicate the presence of genes from something like a stink bug, which sprays a noxious fluid (often containing cyanide compounds) when disturbed; or an assassin bug, which sprays a nasty mix of proteases, hyaluronidases, and phospholipases which digest tissue – or possibly both. It also seems to contain some kind of chemical attractant that draws creatures, including zombies, infected by the T-Virus. Given the wide range of organisms which can be attracted by this substance, a pheromone is unlikely; however, as Operation Raccoon City shows that zombies are attracted to the scent of blood, a set of volatile organics mimicking the scent of a wounded animal is not out of the question.

Nyx

Like the Blobs, Nyx is an organism which cannot be tied to any particular existing virus or organism, but which we can infer (with some stretching) might be related to something we’ve already seen. Appearing only in Outbreak: File #2, Nyx is a mostly-formless mass of flesh whose only identifiable features are thin red tentacles and a central core which comprises its only vulnerable point. By the time the players encounter it, it has absorbed the bodies of several UBCS soldiers and one Tyrant through the use of the aforementioned tentacles.

The lack of anything like Nyx anywhere else in the series suggests to us that it was not part of a particularly large or important project; therefore, it was almost certainly a small-scale experiment associated with one of the big Umbrella projects. Its formlessness and willingness to invade other bodies suggests a similarity to the Nemesis parasite, at least as we’ve envisioned it above.

If we ignore, for now, the fact that Nyx can build itself a body using cadavers like Legos, what remains is basically a spheroid core with tentacles – much like the NE-α parasite, at least after it grows itself a shape in the body of its host. Nyx might be, then, an attempt to create a B.O.W. from NE-α that was free from dependence on a host, able to move about and seek prey under its own power. It might even be considered an aborted precursor to the NE-β parasite, which accomplished the same thing with less mess.

We’ve discussed the anatomy of the Nemesis’s tentacles above, so there’s little need to go into that here. The difference between the Nemesis’s tentacles and Nyx’s is how they’re used. Like the Nemesis T-Type, Nyx has a propensity for stabbing people with its tentacles, but the

tentacles never actually leave these bodies. Instead, Nyx draws the bodies toward itself, and, we believe, starts to digest them. It may secrete digestive enzymes into the bodies, much as Nemesis secreted a T-Virus-laden fluid into Jill’s body; it may also seed these bodies with its own cells, allowing them to grow into the muscle tissue needed to heave around mounds of corpses like limbs. The process is not quick; by the time the heroes of Outbreak reach the creature, the bodies of the UBCS and the Tyrant are still intact, and they can be distinguished easily from the loose tissue of Nyx’s outer form after the creature is finally destroyed. In fact, we believe that most of that loose tissue was from earlier meals in whatever laboratory Nyx was stored in before it was stolen, and was already associated with the parasite before it ever left its crate.

The tissue that forms from, within, and around the corpses Nyx collects appears to be loosely organized, for the most part – it sloughs off when Nyx is killed, and it is detached easily enough that Nyx doesn’t seem to mind lobbing it around as a projectile. The fact that Nyx is willing to part with it also suggests a lack of structure; organized tissues like skeletal muscle are expensive to generate and dear to part with. Nyx probably does not form its own internal skeleton; we don’t see one when the creature comes apart, and it is probable that Nyx is able to use the skeletons of the bodies it absorbs, held together by Note that the main body is fleshy and indistinct, and that some of the bodies in the arm are coated with meaty goo. strips of sinew, as a rough structural Source: Outbreak: File #2 framework.

The T-Veronica Virus

Finally, we come to the last of Umbrella’s viruses – the bizarre T-Veronica Virus. T-Veronica first appeared in Code: Veronica, which is the first game where the story of the series started to shift away from medical experiments gone horribly wrong to villains plotting to take over the world. Perhaps not coincidentally, it’s also the point at which Capcom’s enemy designers stopped looking to surgery and birth defects for inspiration and started looking to psilocybin and peyote. As a result, teasing out a scientific basis for the properties of T-Veronica has proven…problematic. Fortunately, Code: Veronica does give us a little bit of information to work with pertaining to the origins of the virus, and so that is where we shall begin.

Ants and Plants

The T-Veronica Virus was created, according to numerous sources, through the splicing of the Progenitor Virus with a unique virus isolated from the genome of a queen ant. The T-Veronica

Notes in Darkside Chronicles are a little more vague, indicating the source only as “queen ant DNA,” and Resident Evil Archives adds that the virus incorporates plant genetic material as well. The combination of traits from these organisms imbued the virus with an unparalleled potential to spread worldwide, and would have given Alexia complete control over most other infected organisms. It also gave her kerosene for blood and turned her father into a troll, but let’s take this one thing at a time.

Let’s start with a discussion of the “Queen Ant Virus.” According to the Queen Ant Report, Alexia discovered “the remains of an ancient virus within the genes of a queen ant.” Surprisingly, this is actually fairly plausible. Every genome on Earth is absolutely lousy with what we call endogenous retroviruses – ancient viruses which wriggled into their hosts’ DNA and refused to leave. Over time, the genes of these viruses became damaged by random mutations, leaving them unable to produce new viruses to spread to new hosts. The viral genes themselves never left though, and were transferred along with the host’s genes from one generation to the next. In our first Report, we suggested that Progenitor actually got its start when a plant virus recombined with one of these in a human host, creating a new and fully functional virus.

No source so far indicates exactly what was so special about the Queen Ant Virus, but we can make some guesses. Alexia’s notes indicate fulminant megalomania and a perception of other human beings as her servants. Communities of eusocial insects like ants and bees are commonly depicted in a similar fashion, although the reality is somewhat different – the queen’s condition may best be described as reproductive slavery; she has no control over anything. Smart as she was, Alexia was no entomologist. However, the extreme specialization of ant castes may have been useful to her as a starting point in engineering a new world with herself at the top. Queen ants can also live for decades – an eternity by insect standards – and that The queen ant, source of the eponymous xxxv trait would have had obvious appeal to her. Queen Ant Virus. Source: Code: Veronica X

The genes of a queen ant are identical to those of her workers; the only differences between them are epigenetic, probably involving DNA methylation and the like.xxxvi,xxxvii Nonetheless, genetic differences between ants and other insects probably account for the ants’ ability to develop eusociality at all.xxxviii Given that endogenous retroviruses physically alter the DNA of their hosts, it’s not inconceivable that the genetic traits necessary for eusociality (and longevity of queens) might actually have been delivered to the ant genome by just such a virus. Similar phenomena occur in bacteria – a number of disease-causing bacteria are dangerous in part because they have received virulence factors from bacteriophage viruses. To our knowledge, this sort of thing has never been observed in anything large enough to observe without a microscope, but there’s a first time for everything.

It’s also possible that Alexia got the necessary genes for eusociality from the ant genome proper rather than from the endogenous retrovirus, and that the virus imparted some other important quality – perhaps one or more components of her flammable blood, which we’ll get to shortly. Either way, eusociality is a key component of Alexia’s plan, and hence, part of the T-Veronica Virus. However, she would still need to establish a system of control, and this may be where some other parts of the ant genome – and the plants – come in. Many species of ant have a very close, mutualistic relationship with a corresponding species of plant – the plant provides food and a home, and the ants kill anything that tries to eat their plant – indeed, they even kill other plants growing too close by which might compete with their plant for nutrients or sunlight. The plants manage this relationship in part with complex chemical signals that draw the ants to them and compels the ants to defend them, and which send the ants into a berserker rage when ass- kicking is in order.xxxix,xl If Alexia could ensure that infection in her body produced the appropriate plant genes, and infection in everyone else produced the appropriate ant genes, she would then be able to chemically control any infected organism at will. How would Alexia ensure that only she expresses the correct genes? Her decision to freeze herself might have had something to do with it, but we doubt it, as the “Virus Research Report” describes her self- induced cryonic hibernation as a response to the virus unexpectedly transforming her father into a monster. It’s more likely that Alexia would have treated herself with certain drugs designed to express particular viral genes, and possibly to suppress others.

The last part of Alexia’s scheme would have involved spreading the virus worldwide, and once again, both plants and ants show us the way. Anyone with a lawn or a garden knows that many We know how you feel, Chris. Source: Resident Evil: Code: Veronica X types of plants are very, very good at getting where we don’t want them, which is everywhere. More ominously, we can’t even keep plants that we’ve created from spreading – like an extremely slowly-paced sequel to Jurassic Park, genetically engineered crops escape the confines of their test plots all the time.xli As for the ants, they’re pretty much in charge – they’re on every continent except Antarctica, and about 20% of animal life on land is ant by weight. A single, cooperative ant colony has been shown to wrap around more than half the planet.xlii Kent Brockman was wrong to welcome our “new” ant overlords; they’ve been ruling over us with tiny iron fists for 130 million years.

Between them, the ant and plant genes explain quite a bit about the appearance of Alexia’s various forms. Those green growths over her body in her first, mostly-human form are probably plant-like parenchymal tissue; at the very least, they probably contain chloroplasts, explaining

their coloration. Her grayish skin, by contrast, may be the result of chitin building up in her skin. Her final form takes quite a bit from ants and their evolutionary uncles, the wasps – it’s worth noting that queen ants (and male drones) do grow wings when the time comes for mating. We have absolutely no idea what’s going on with Alexia’s second form, and we wish to keep it that way.

Blood

Alexia’s blood has the remarkable characteristic that it spontaneously combusts on contact with air. While this trait did contribute directly to one of the most awesome FMV sequences of any Playstation 2 game – Albert Wesker punching a monster in the face while in midair and on fire – it has proven singularly difficult to explain. While some animals can use their blood to distract predators (like the Texas horned lizard), and some insects can produce violent chemical reactions inside their bodies to use as weapons (like the bombardier beetle), no animal in the world actually possesses combustible blood, let alone blood that spontaneously combusts. Frankly, we’re not surprised, because it sounds like a terrible idea. An injury that causes bleeding is bad enough; the same injury causing burns would just make things worse.

We believe that Alexia’s blood is closely related to the poison secreted by Nosferatu, given that both are deployed in similar ways, and both are described in various files as reacting with air. Such a relationship might also help explain why Alexia could not secrete poison, and Nosferatu could not set people on fire – it would be one or the other, rather than two independent These phenomena may be related. Source: Code: Veronica X phenomena. With this in mind, we considered a number of possible explanations for the toxicity of Nosferatu’s blood and the flammability of Alexia’s. A class of chemicals known as metalorganic compounds has the distinction of being pyrophoric, meaning that these chemicals burst into flame on contact with oxygen. We considered that Alexia might be producing such a substance in her body, and that defective metabolic processes in Nosferatu’s body might have led to the buildup of toxic, but non-flammable, precursors. Unfortunately, we couldn’t come up with any metalorganic substance with biological relevance. We also considered the possibility that Alexia may have taken advantage of some unusual biochemical reaction like the defensive mechanism of the bombardier beetle – but the hydroquinones involved are not particularly toxic. We also looked for inspiration to the fascinating death of Gloria Ramirez, who flooded an emergency room with poisonous gas. Unfortunately, the compounds believed to be involved in that case are not flammable – though they are very toxic.

Ultimately, we settled on an enzymatic reaction. The fuel for this reaction – the substrate – might be produced in the liver. The liver is one of the most commonly transplanted organs (this will be important later), and most of its mass is made up of a substance called glycogen – a storage form of glucose, the simple sugar that the human body uses for energy. T-Veronica may pervert a biochemical pathway called glycogenesis, in which the body converts glucose into glycogen, and the result might be a compound that’s both energy-rich and highly soluble, like glucose. That would allow it to leave the liver to circulate through the blood. This substance might be toxic on its own, and may contribute to the sort of brain damage we see in Nosferatu.

Having dumped an energy-rich molecule into the blood, we now need an enzyme to ignite it. The enzyme in question may be a metalloprotein similar to hemoglobin – the protein which acts as an oxygen carrier in blood. Unlike hemoglobin, this enzyme would have a relatively high oxygen partial pressure, meaning that a much higher concentration of oxygen would be needed for oxygen to actually bind to it – otherwise, it would bind to oxygen in Alexia’s lungs and she would explode. Under normal circumstances, this enzyme would probably associate with the substrate – keeping the substrate molecule close enough to ignite it when oxygen comes along, but in the meantime, preventing it from acting as a poison.

However, it might be months or years before a T-Veronica-infected subject has adapted enough to make this enzyme. In the meantime, the subject’s body would be pumped full of this slightly toxic substrate. The substrate might not only damage the subject’s brain, but might also damage the cells which would eventually produce the enzyme. As a result of this damage, the enzyme, when it is finally produced, might misfold – it might come out wrong. Instead of igniting the substrate on contact with oxygen, it might instead merely cleave it into a small, volatile form more easily inhaled – and far more toxic.

There are two ways you could prevent the substrate from accumulating before the body is ready. First, you could put a subject into cryonic suspension, slowing down some – but not all – metabolic processes. Glycogenesis would drop sharply, as it typically does during hibernation or long periods of convalescence, but the processes of viral transformation would continue, and eventually the body would be ready to produce this protective enzyme. That’s what Alexia did. The other method would be to keep replacing the liver as it gets infected. A temporarily uninfected liver is a liver that isn’t producing poisonous substrate. This appears to be the method that Javier Hidalgo chose for his daughter Manuela.

A quick note about Nosferatu’s poison – it’s one of two types of poison in the series that can’t be treated by the blue herb. As we described in the previous Report, the blue herb probably works by fighting the symptoms of most poisons and letting the body deal with the poisonous The serum looks like it’s intended for intravenous use, based on the packaging molecules themselves. We can propose, then, that – which also has a warning that says whatever Nosferatu’s poison is, it probably can’t be “Watch Out!” for some reason. Source: processed by the liver, where poisons are usually broken Code: Veronica X

down. It can, however, be treated by a special serum. Serum is processed blood plasma typically used for its antibodies – if a person or animal is exposed to a poison or bacterium in the past, then serum made from their blood will contain antibodies against that poison or bacterium. Antibodies in this serum may block the poison from acting on its target, effectively neutralizing it.

Nosferatu and Steve

T-Veronica is most effective when something is done to control the virus’s effects on the body – either by freezing the infected subject for years, or by continually replacing organs. Alexander Ashford, also known as Nosferatu, and Steve Burnside, also known as worthless, show us what happens when these precautions are not employed. Both gain size and a gray pigmentation which, as before, might be due to chitin deposition in the skin. In addition, they each have a couple of unique characteristics.

The changes in the elder Ashford’s body are actually fairly easy to explain. He retains a mostly- human shape, gaining only a few big insect arms, an exposed heart, and a couple of feet in height. The insect arm is a completely new appendage, and is probably derived from the ant genes in T-Veronica. Due to probably random circumstances, they appear to have been expressed a little too strongly in one particular locus of his body – something that could easily have occurred due to somatic mutation in a single cell which then replicated out of control, like a cancer.

The exposed heart may be an extreme manifestation of dilated cardiomyopathy – a condition in which the heart becomes enlarged and its walls become thin and weak. This condition could have occurred as a result of T-Veronica tinkering with various chromatin-remodeling genes – chromatin remodeling is supposed to be involved in eusociality in insects, which as we mentioned above, would be a big part of Alexia’s scheme. At least one gene involved in chromatin The heart looks like it’s splitting open the chest along old remodeling, DOT1L, has been linked autopsy incisions, explaining how it got through the to dilated cardiomyopathy – knock it sternum and rib cage. Source: Code: Veronica X out, and the disease condition develops.

We’ve complained before about the fact that bones in adults don’t get longer. Fortunately, we explained in the section on the G-Virus exactly how a virus might circumvent that little problem. T-Veronica might do exactly the same thing, converting a limited subset of hematopoietic stem cells to bone-generating cells and re-establishing epiphyseal plates.

Steve, on the other hand, exhibits a rather more bizarre appearance. During his transformation, he grows much larger; following transformation, he displays a hunched posture, growths on his face, and what appear to be pharyngeal arches on his back. The hunched posture is probably a result of musculoskeletal rearrangement during his expansion phase – overall, he gets much bulkier than Nosferatu. Irregularities in the growth rate along the anterior-posterior axis, due in part to the more rapid and pronounced growth, could account for that. The little spikes on his face could be keloids which also developed secondary to rapid uncontrolled growth and cell division; alternately, they could represent the random expression of plant genes producing thorns where thorns ought not be. As for the pharyngeal arches, they should not occur in an adult; they depend on chemical patterning only present during the embryonic and fetal stages of development, involving hormones like Wnt, Notch, and FGF, and they oughtn’t be on the back anyway. We could presume, however, that the big hunch of Steve’s back isn’t actually his spine, but an undefined mass of embryonic parenchymal tissue; the appropriate chemical gradients could develop in such a structure. This would also explain what these structures are doing on Steve’s back.

What really worries us about Steve’s mutation is that it’s impossible. As we explained in the section on the G-Mutant, getting bigger isn’t just a matter of growing faster. An increase in mass requires an intake of matter – food, water, sand; we don’t really care what, but stuff has to go in. Steve goes from pipsqueak to giant in ten seconds flat, with no visible intake of food or water. We considered a number of explanations for Steve’s violation of well-characterized physics – hollow spaces in his body, such as dramatically enlarged lungs, may increase his apparent bulk without increasing his actual mass, for instance, although that means his enormous arms would be We weren’t really fond of Steve to begin with. This just heavier than his chest. Alexia may have makes it worse – so much worse. Source: Code: Veronica X pumped Steve full of an amino acid slurry before Claire arrived, giving him some of the biomass needed to transform (and perhaps explaining why his mutant form was so much bigger than Nosferatu) – but it would take over a thousand pounds of the stuff to achieve the results we see. Steve may also have had an intravenous or intraperitoneal fluid drip running into his body somewhere we couldn’t see, but that seems unlikely and, again, an immense amount of fluid would be needed. As with the G- Mutant, we are forced to concede that the effect is totally impossible as shown.

It gets even worse when Steve changes back to normal just before he dies. The best explanations we could come up with were a combination of massive proteolytic degradation destroying the bulk of his new tissues, and leakage of whatever air or fluids were contributing to an apparent increase in size. At the same time, his remaining cells may de-differentiate as a result of extreme

physical stress,xliii and might re-differentiate using cues from the extracellular matrix to put him back into something resembling human form. The process wouldn’t be very precise, and in fact, it doesn’t need to be for our purposes – Steve dies immediately thereafter.

Good riddance.

Other T-Veronica organisms

As if to spite us, T-Veronica shows the same infectious versatility of Umbrella’s other viruses, and several unusual cases of infection appear in Code: Veronica and Darkside Chronicles. One is a normal, practical (if silly) B.O.W.; one is part of Alexia Ashford’s cockamamie scheme to make the world one big anthill; and one is…well, it just is. Let’s just get on with it.

Tentacles and the “Alexia-Pod”

About halfway through Code: Veronica, Claire Redfield and Steve Burnside were just about to escape from the Antarctic Research Facility when a random tentacle out of nowhere races across kilometers of snow and ice to flip their snowmobile upside- down. The game never fully explained where this tentacle came from – or any of the others which appeared later – but the The bud-like tips and green fluid are indicators of the tentacles’ tentacles seemed to be under plant origins. Source: Code: Veronica X Alexia’s control. Naturally, this confused some people, who wondered what the tentacles were and whether they were part of Alexia’s body or something completely different.

Fortunately, Resident Evil Archives and the retelling game Darkside Chronicles explained the matter in some further detail. According to these sources, the tentacles are part of a plant-like organism called the “Alexia-Pod” which resides at the center of the Antarctic Research Facility. This pod seems to bear some relationship to the giant anthill below the site of the final battle with Alexia; in fact, it may actually be that anthill – many species of ants have a symbiotic relationship with an associated species of plants, and will take up residence in and around them.

In our previous Report, we discussed Drosera as a plant species capable of rapid movement, and suggested that genes from this plant may have been involved in creating the motile vines of the plants of the abandoned hospital in Outbreak: File #2 and Plant 42 in Resident Evil. It may be playing the same role here. However, those plants were created largely by accident; Alexia’s deliberate tinkering gives us another alternative here. These vines may have something like animal muscle tissue powering them – making them, like the various T-Virus plants we discussed last time, a product of rather outlandish genetic recombination. Based on the way the

vines move, they don’t have anything like an internal skeleton, so they probably rely heavily on intrinsic muscles for movement and structure, much like the human tongue.

If we assume the presence of animal muscle tissue in these vines, then we also need to explain how these muscles get their oxygen. Human muscles rely on hemoglobin in blood to carry oxygen to them from the lungs, and they rely on myoglobin in the muscle itself to store this oxygen long enough for it to be useful. Both of these molecules impart a red color to blood and muscle – but when the vines are damaged, the fluid that comes out is distinctly the opposite of red. To address this problem, we look to that other component of T-Veronica, insect DNA. The muscles powering these vines (if they be muscles at all) may be insect muscle, not mammal muscle. Many species of insects use a protein called hemocyanin to carry oxygen to their tissues in place of hemoglobin. Hemocyanin tends to be either colorless or blue; in combination with whatever other fluids the vines are full of, it should explain the color of whatever leaks out when the vines get shot.

The tentacles – and by extension, the Alexia- Pod – seem able to seek out prey, and carry out orders, even when said prey is far outside of Alexia’s sight. This implies at least a primitive nervous system, much as we suggested for the T-Virus plants in the previous Report. At least here, we can rely on Alexia engineering these traits into the plant, rather than betting on some kind of genetic roulette to do it for us. As we mentioned in the previous Report, at least one botanist, František Baluška, suspects that signaling molecules between phloem cells in plants bear at least a superficial resemblance to synaptic connections in nerve cellsxliv,xlv. We also need to explain how the tentacles are able to sense prey at all. In the previous report, we called upon the powers of Cuscuta, a parasitic vine that could actually smell its preyxlvi,xlvii. As with Drosera, we need not rely on one particular plant here; Alexia’s tampering with nature opens the whole of the animal kingdom to us. The tentacles could express a variety of olfactory receptors on their surfaces, similar to those in animal noses. They may even possess setae, tiny hairs used by insects to detect vibration and sound. Chemoreceptors on the We cheated a bit with the angles here, but this giant central bulb might make the organism anthill may also be the core of the Alexia-Pod. Source: receptive to simple commands put out by Code: Veronica X Alexia in the form of pheromones.

The tentacles are connected to a core, which seems to be related to a certain giant anthill. If the anthill is itself the Alexia-Pod and hence a giant plantlike organism, it probably takes one of two forms. It may be a giant member of the Solanum genus – specifically, Solanum tuberosum, the humble potato. The shape and color are about right for a tuber, even if the size would shame the state of Idaho. Another, less delicious possibility is that the mass is a plant callus the size of a skyscraper. Plant calluses have very little in common with human calluses; they are essentially masses of undifferentiated plant cells, often used in botanical research and cell biology. These uses might be of particular interest in the T-Veronica project.

The Veronica Plant and the V-Complex

We see another T-Veronica-generated plant appear in Darkside Chronicles. This one, which initially appears to be a giant flower, was created by Javier Hidalgo for…well, we don’t know. It’s possible that he created it in order to extract the T-Veronica Virus from it on demand for research, rather than purchasing batch after batch from Albert Wesker. We were unable to come up with a perfect match as to species, suggesting that it’s probably a hybrid or transgenic of some kind, but the closest match was, amusingly enough, in the genus Veronica, which can be found in South America, among other locations. Though Veronica flowers normally have a blue hue, we can cheat a little bit; plant genes present in T-Veronica may alter glycosylation steps in the development of flavonoids present in these flowers, switching their blue hue to an orange onexlviii. The species of the plant isn’t particularly important; what is important is that a cutscene seems to suggest that the flower ate Javier (indicating, perhaps, genes from the carnivorous Drosera again) and turned him into a giant mass of plant and meat called the V-Complex.

The V-Complex resembles nothing so much as a giant, spiky meatball with legs and claws. The central meatball body is almost completely formless and lacks anything suggesting texture, or even skin; we can almost certainly attribute this to random tissue growth, like the growth of a tumor. The legs and claws are almost certainly a product of the insect genes in T- Veronica, judging by their joint structure. The spikes emerging from its body have the same texture, so they are …What? Source: Darkside Chronicles probably composed of a chitinous material, like the exoskeleton of an insect. The V-Complex has a skull, which is somewhat harder to explain, as it contains Javier’s head within it. The best explanation we can come up with for that is the suggestion that this skull may have been derived from Javier's own DNA, but formed as a bizarre shape due to the unusual pressures on it during development. Why a new skull formed surrounding Javier's intact head, we don't know. It could be that a layer of mesoderm-inclined tumorous tissue grew over his actual head, and somehow chemically detected the presence of a brain and treated his head like neurectoderm, growing a skull over it, especially if rampant T-Veronica infection forced some of Javier’s brain cells back into an immature

phenotype. Such a transformation might even explain Javier’s eventual loss of mental composure and control.

The V-Complex is capable of projecting a poisonous or corrosive fluid from its mouth and attacking with explosive spores. The acid-spitting attack is almost certainly derived from ant genes; some ants are capable of spraying formic acid as a defense against predators. Typically, they spray the acid from their abdomens, but given the disorganized body plan of the V- Complex, it’s not unlikely that this particular defensive mechanism found itself attached to the wrong orifice. The spores are likely to be among the few plant-derived traits of the V-Complex, which seems surprising, as its creation involved a giant plant. The spores may be a combination of fertilized and unfertilized seeds (yes, plants can fertilize themselves, and no, they won’t go blind). Underdeveloped, unfertilized seeds (or ovules, similar to the white seeds in a watermelon) may be the source of the blue clouds of poison. Fertilized seeds, by contrast, would be full of nutritive tissue, which may well be saturated with whatever it is that makes the blood of a T-Veronica subject flammable.

The Jabberwock S3

There is one product of the T-Veronica Virus which doesn’t give us headaches, and that is the Jabberwock S3. This organism, encountered only in Darkside Chronicles (and then only once), is the only genuine B.O.W. produced using T-Veronica. Files from the game give us very little information on the creature, save that it is apparently a continuation of the research which produced the Bandersnatch, this time using the T-Veronica Virus. In the previous Report, we suggested that Bandersnatches are probably grown from an embryonic state like Hunters, rather than produced through infection of adult humans, like Tyrants. We make the same presumption here.

Unlike Bandersnatches, the Jabberwock S3 seems to have arms on both sides of its body, so we can presume that the apical ectodermal ridge translocation we suggested for the Bandersnatches has been discontinued for this weapon. The insect genes from the T-Veronica Virus caused its limbs to terminate in sickle-like claws rather than hands, so giving the creature a single, elongated limb would probably not have been quite as useful here anyway. The sheer abundance of limbs can also probably be attributed to the insect genes; There. We’re done with this stupid virus. Source: likewise, the creature’s green Darkside Chronicles pigmentation can be attributed to expression of chlorophyll, as we proposed for Alexia. The Jabberwock has a large, exposed heart, much like Nosferatu, and as in the case of Nosferatu, we attribute it to DOT1L overexpression – aided in this case by the fact that the heart could grow to hypertrophic proportions before the ribcage even solidified.

References

This is the part that makes it SCIENCE.

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Thanks to Project Umbrella for hosting this report; additional thanks for images to the Let’s Play Archive, Resident Evil Center (www.residentevilcenter.net), and www.the-last- escape.biohazardfrance.com; and a very special thanks to Google, Wikipedia, and PubMed.

We didn’t care for T-Veronica either.