Sunday, 30 March 2014

LAB GROWN MONSTER: THE ZOMBIE

Usually when I watch movies or read stories or play games that are set on earth, in the present, I want them to be realistic. I do like fantasy/ science fiction, but if you bring it to our world, it has to adhere to our rules. Because I'm a biologist, I get especially annoyed if writers use the words like cells, genes and mutations wrongly to create an explanation for a supernatural phenomenon that does not make sense. In some cases it's the explanation for the myth that is inconsistent with the world, not necessarily the thing itself. Therefore I'm starting with this series of posts in which I try to provide good scientific explanations of mythological creatures by showing how they could be created in a lab. Board up your windows and stockpile supplies, because the first lab grown monster is the zombie!

Nazi zombies from the movie 'Død snø' (Dead snow).

INTRODUCTION

Originally, zombies were corpses reanimated by voodoo sorcerers to do their bidding. In popular culture, these mindless creatures are driven only by hunger for manflesh, and are often very difficult to kill. While not extremely dangerous as a single individual, they tend to form deadly hordes, because 'zombieness' is often contagious.


CONTAGIOUS TRANSFORMATION

Let's start with the contagious transformation, a recurrent feature in many movies and games. In the movie 'Last man on earth', an air-borne infectious agent causes people to become zombies. In Dawn of the dead those who are bitten by zombies will share their fate. The T-virus of resident evil is transmitted by contact (blood, saliva, etc.). Corprus is contracted after contact with an infected, and also rarely with 'infected' air.

Transformation of the body is possible, and occurs pretty frequently in reality. Various parasites alter the shape and or function of its host' body. The Toxoplasma gondii protozoan changes the brain of its host, so that its behaviour becomes more risk-seeking. The flatworm Leucochloridium paradoxum changes the appearance of the tentacles of its snail host, so that they resemble caterpillars. The roundworm Myrmeconema neotropicum changes the abdomen of its ant host so that it resembles a red berry.

Viruses can change the genetic material of the host, allowing for changes that remain even after disappearance of the transforming agent. Viruses are used regularly by (mainly medical) scientists. And a virus is most contagious of all contagious agents, because of its small size, and low survival requirements. For those reasons I think that the virus would be the best tool for creating infectious zombies. From this point onward it is assumed that we have adult human subjects available, and use a virus to change them into zombies.


CANNIBALISM

The strong appetite by zombies for flesh is not very difficult to realize, but the specificity for humans could be problematic. While most people wouldn't consider eating other people, and don't find humans particularly appetizing, sane people have been observed eating people during a period of extreme famine. So when people are really hungry, the inhibition to eating humans disappears. We can increase the appetite of our subjects by increasing the production of a positive regulator for appetite. One of such regulators is the Agouti-related peptide. Mice in which this protein is overexpressed (produced in higher amounts than in normal individuals), suffer from hyperphagia; extreme eating.

But we want more specificity. We know that an unlearned specific appetite for proteins exists, and the increased production of a regulator stimulating this appetite will increase appetite for meat. Our virus can easily add copies of the gene coding for that regulator, resulting in increased production of that regulator. We could edit the gene in such a way that the regulator will not be inhibited after food consumption, to have a permanently high activity. After eating, our zombies should remain frenzied.

The focus on (eating) humans could come from increased sexual desire. While zombies are not often sexually active, this drive might give the increased appetite a direction. I think that it is not a coincidence that cannibalism (or vore) is a sexual fetish. Substances that increase the dopamine activity in the brain (like crystal meth, or medication for Parkinson's disease) can cause hypersexuality and obsessive eating. This might be something that we're looking for, although such drugs often affect a lot of other things, as dopamine is such an important molecule in the brain. Perhaps some substance downstream of the dopamine system exists, one that increases libido more specifically.


MINDLESSNESS

Mindlessness is a true hallmark of zombies. People that act mindless are often called zombies for that reason only. Mindlessness can be explained as the absence of intelligence. In zombies, this is apparent through their completely instinct-driven behaviour, you cannot talk a zombie out of eating you. The increased appetites for protein and sex will already reduce the rationality of the subject. See instinct and the rational mind as two opposing forces, each competing for power in the cranium. When the instinct gets stronger, the ratio loses ground.

Because our virus needs to infect the brain, it will probably cause inflammation of the brain (encephalitis). Especially if our virus is based on say the rabies virus (which is known to infect the brain). The mental problems associated with encephalitis reduces both the rationality as the instincts of the brain, resulting in a greater degree of absentmindedness.


UNDEATH

Zombies are difficult to kill. According to virtually all sources this is caused by their undead state. In reality no such alternative state exists, so our zombies have to be perfectly alive. You can, however, increase our subject's 'death resistance' in a few different ways. The easiest way is removing all pain sensation. When a person does not feel pain, he is not immobilized by relative minor injuries, and continues going until incapacitated by some major injury. People that have a mutation in the SCN9A gene cannot feel pain at all. The mutation prevents the pain nerve cells from propagating the signals after sensing pain. Ssm6a, a substance derived from centipede venom, specifically inhibits SCN9A, causing the same effect. If our virus were to insert the Ssm6a gene in cells throughout the body, our subjects would be completely resistant to pain. We could also use some other method that is commonly used to switch off genes, such as RNAi.

With a lot of effort, we might also enhance our zombies' (long term) resistance by removing the inhibition on our regeneration system. We know that many animals can regenerate (regrow) lost body parts, but only do so when not yet born, or only in certain tissues. Only some creatures like urodele salamanders can regenerate virtually all parts of their bodies. Instead of regeneration, our bodies produce scar tissue, which only really functions as a cork to stop the blood from leaking out of the body. The production of scar tissue is thought to inhibit the regeneration process. Most likely the inactivation of the regeneration system evolved because people without it developed cancer sooner. When every cell can potentially become a stem cell again (a cell with unlimited dividing potential), every cell has a much higher chance of becoming a cancer cell. For this reason it might be a lot of work to change the system so that we get increased regenerative potential without the increased risk of cancer. But this is not an issue for us now, because we do not care if the zombies die of cancer after some years. Most of the zombies will have died much sooner anyway.


CONCLUSION

Is it possible to produce a virus that transforms people into unstoppable cannibalistic psychopaths? Yes. Will they be immortal? No. But even undead creatures can often be killed in most stories. Our zombies also need water and food like regular living human beings. And if the bullets do not kill them, then perhaps a secondary infection would. Our zombies will seem like undead in the short term, but in the long term they will show their mortality. No headless zombies will ever chase you. No severed limb will ever grab you when you least expect it. Furthermore, our zombies will attack and eat other zombies. A true zombie apocalypse is possible. But after spending a few years in a zombieproof bunker, you will not have to face hordes of zombies, but only the immense desolation and ruin.

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