Friday, April 29, 2011

How to Make a Zombie Plague

Originally published over at SiMF.
Also picked up by io9!

Ah, the zombie plague! A Mad Scientist couldn’t ask for a better means for world domination. Not only would discrete application of your infectious agent eliminate your opposition, the rest of humanity will be far too busy fending of their recently deceased loved ones to notice when you swoop in and take control. The population is reduced to a more manageable size, and the ever-present zombie threat will keep any potential rebellions from forming. Everybody wins! Well, mostly I win but you get my point.

But how to make it happen? There’s a good reason no one has ever pulled off the ‘Take Over the World by Zombie Plague’ scheme before…it’s an awful lot to ask of a single infectious agent. It must be transmitted from person to person, or even across species, quickly and with a low infectious dose. It has to fend off the immune system and penetrate the blood-brain barrier to get at your delicious brain meats. It has to basically turn your body into a walking incubation chamber, dedicated solely to feeding and spreading the infection. Still, these obstacles are not insurmountable when one has the power of Mad Science.

To put things into perspective, it is important to understand that the things that make us sick – viruses, bacteria, parasites, what-have-you – have been around a lot longer than we have, and they’ve gotten very good at what they do. And what they do isn’t very nice…we certainly don’t think so, anyway. The pathogens causing the infection are just doing what they have to do to survive and replicate in a hostile environment: You. In many cases, the characteristics that make this possible are a lucky coincidence for the pathogen and an unfortunate side-effect for the host. For example, a surface protein that makes a bacteria more resilient in the soil may also protect it from your immune system. If that bacteria spends enough time in a human host, it’s going to get better and better at exploiting that characteristic so that it can survive longer and reproduce more.

The longer this process goes on, the more specifically attuned the pathogen has the potential to become. Humans haven’t really been around very long, evolutionarily speaking. Bacteria however are some of the oldest forms of life, and the viruses that infect them, known as bacteriophages, have been fine-tuning the process for an exceptionally long time. So much so that many bacteriophages only infect one species of bacteria. They have become so specialized in exploiting the characteristics of their favorite bacteria that they have lost the ability to infect others.

Pox viruses are some of the oldest viruses that infect mammalian cells, and they have developed a similar level of species-specificity. A human could drink a vial of rabbit pox and be completely unaffected. That level of control would be useful…but that isn’t really what we want, is it? No, we want something new and flashy and explosively infectious. The Ebola virus only broke onto the ‘human infectious agent’ scene in 1976 and it has already made quite the impact. The virus itself destroys blood vessels and prevents blood from coagulating, producing lots of infectious fluids and causing death through hypovolemic shock. Bats are the most likely animal reservoir for the virus as well, which is pretty badass. Can you imagine zombie bats? I can. It’s awesome.

Unfortunately, viruses that are capable of infecting multiple species don’t generally affect them in the same way. The bats infected with Ebola aren’t leaking blood everywhere and birds infected with influenza haven’t come down with the flu. That’s because these species are carriers. While the virus is still present, it isn’t causing disease. Like the bacteria living in the soil that happen to have an adaptation that causes disease in humans, these viruses have a stable existence within their animal reservoirs. They only cause disease when they jump to humans, a less familiar environment. This is actually what makes Bird Flu so potentially dangerous. Multiple strains of influenza can infect the same animal, allowing for exceptionally rapid genetic recombination and the development of new strains our immune system has never seen. Many different animal species are reservoirs for human disease including pigs, armadillos and deer…but while they may be useful in delivering your zombie plague to the masses, your undead horde wont be accompanied by zombie armadillos. I’ll give you a moment to recover from the crushing disappointment.

So how will our zombie plague be spread? There’s a lot to consider here. Not only does the infection have to reach a lot of people, it also has to reach their delicious brains. The human brain is a fairly important organ. The blood-brain barrier carefully restricts access to the cerebrospinal fluid, protecting your tender brain from most bacterial infections as well as inflammation. Inflammation is your immune systems first response to a potential invader, but in the brain this can cause swelling and tissue damage. To prevent this, the blood-brain barrier keeps out the cells and antibodies of your immune system as well as the bacteria. There is certainly precedent for overcoming this obstacle, however. Rabies virus is spread through infected saliva and can travel from a bite wound to the brain, bypassing this barrier. Sound familiar?

But once our virus gets to the brain, how would it go about turning your average person into a shambling virus factory? Well honestly, you don’t really need most of that big brain you have. Sure, that cerebellum helps you coordinate your movements but shambling is totally in this year. As a proud soldier in the undead horde, you don’t really need to make any complex decisions so screw that  frontal lobe. And all that memory processing and spatial navigation provided by your hippocampus? Bah. All you really need is your amygdala…the primitive reptile brain, that generates the ‘fight or flight’ response. Just get rid of the rest and you’re good to go. Well, figuratively speaking.

So we’re looking for an infectious agent that can be introduced to the population in a relatively innocuous way – such as through an animal reservoir – that can penetrate the blood-brain barrier, destroy all that unnecessary brain tissue, and leave the host a shambling plague factory….preferably oozing with infectious particles. Now I’m sure most of you are thinking viruses are the way to go here, but I’ve got one word for you: Prions.

Prions are basically infectious proteins. We don’t know a lot about them yet, but they are the causative agent behind spongiform encephalopathies such as Mad Cow disease and Creutzfeldt–Jakob disease. Mad Cow disease can be transmitted to humans who eat infected tissue, and there is some evidence that prions can become airborne and cause disease at a surprisingly low infectious dose (in mice, anyway). Since all they are is a single protein, they have no trouble slipping past the blood-brain barrier and wreaking havoc with your neurons. When the misfolded prion protein encounters other proteins in the brain, it acts as a template that causes the misfolding of these healthy proteins, thereby propagating itself. Prion diseases are currently untreatable, even. The only real downside is the long incubation time, but I’m still pretty confident that prions are the way to go in terms of zombie plague development.

Even if you aren’t trying to take over the world (and why wouldn’t you be?!?), the zombie plague is exceptionally useful as a modeling tool for the spread of highly infectious diseases. It’s also a powerful motivator for getting people interested in how diseases spread. You can try your hand at destroying the world with the zombie plague or building your own custom pathogen to see how fast you can infect the world. Preparing for the Zombie Apocalypse is also a fun way to be prepared for more routine disasters that people do face daily.

No comments:

Post a Comment