As I sat down today to play The Last Of Us, I thought, as I sometimes do, about the actual possibility of zombies. I have always been a big fan of the zombie genre. In movies, TV and video games, zombies can be broken down into two types. The first are the ones that are raised from the dead through some sort of magic. (See: Dead and Breakfast, Dead Snow, The Evil Dead). The second type are the result of natural causes (that is, not supernatural). Sometimes the cause is a toxin, but it is much more typically an infectious disease.* (See: 28 Days Later, Quarantine, Resident Evil.) As a biologist, this second type has always appealed more to me.
There is a certain degree of biological plausibility to this premise. The primary “goal” of pathogens, like all other life forms, is to reproduce.** To this end, many, if not most, pathogens further their goal by controlling the behavior and physiology of their hosts in ways that increase the chance of infecting other hosts. This is broadly called “host manipulation.”
Take the common cold, for example. As a respiratory virus, the cold is spread through exposure to fluids from the mouth, nose and throat. The symptoms of this virus include runny nose, sneezing and coughing. The sneezing and coughing cause the virus to be spewed into the air and onto nearby people and objects. The runny nose makes you touch your face frequently and get the virus particles (which are called “virions”) on your hands, which are then left on anything or anybody you touch.
Zombies are an example of a fictional parasite manipulating the host. Consider the properties of modern zombies in film, TV and video games: They are compelled to seek out uninfected humans and attempt to bite them. The bite transmits the infection and the bitten person becomes a zombie. Infected people only attack the uninfected. These behaviors all help to spread the infection. 28 Days Later (one of my favorites) went one further: the “rage virus” can be transmitted through any exposure to blood, not just a bite. The zombies in this film vomit blood everywhere so that an actual bite is not always necessary. (I couldn’t find a youtube clip of this. If you happen to find one, please post it in the comments.)
Here are some other real parasites that manipulate their host’s behavior:
Ophiocordyceps unilateralis: This fungus belongs to a larger group of fungal parasites that aggressively infect insects and arachnids, eventually killing the host. This particular species, which infects ants, controls the behavior of its hosts before it kills them. Ants infected with O. unilateralis will climb high into trees and bite into a leaf to anchor themselves against the wind. The ant will die, still clinging to the leaf, and the fungal spores will be released into the wind, where they can spread farther than they would have from an ant that died on the forest floor. In the video game The Last of Us, the zombies are caused by a fungal infection called “cordyceps,” which is presumably a relative of O. unilateralis.

Ants in the late stage of O. unilateralis infection. Image from wikipedia.org
Rabies: The rabies virus can infect many species of mammal. The virus is concentrated in the saliva of the infected animal and is transmitted by bite. Infected animals become very aggressive and try to bite other animals including humans. The characteristic “foaming at the mouth” is just an excess production of saliva, which contains the virus. A rabies infection causes the host to avoid water — another name for rabies is “hydrophobia.” If the animal were to drink water as normal, the virions concentrated in the host’s mouth could be washed away and the virus’s ability to infect others would be diminished. There are videos on youtube that purport to show this, but I cannot vouch for their authenticity. **minor spoiler alert** In the movie Quarantine, it turns out that the zombies are the result of a mutated strain of rabies. This was a good call, since rabies already has most of the characteristics of a zombie infection.
Toxoplasma gondii: Toxoplasma is a parasitic protist that has a multi-stage life cycle. One stage is in rodents, such as mice. The next stage is in cats, who contract the parasite by eating infected mice. Cats eat plenty of mice on their own, so they are at risk of contracting toxoplasmosis*** without any help. But it is better for the virus if the cats do get a little bit of help. Mice are normally pretty good about avoiding cats. After all, mice who are better than others at not being eaten will be alive longer and therefore able to produce more offspring — natural selection works. But mice which are infected with Toxoplasma do not fear cats. On the contrary, they are attracted to the smell of cats. A hungry cat is happy to eat an easy meal, but will unknowingly contract toxoplasmosis in the process. The parasite is subsequently spread by cat feces, so it does not need to manipulate the cat’s behavior.

Mice infected with T. gondii do not fear cats. This mouse appears to be healthy. Image from crossfit707.com
Dicrocoelium dendriticum: D. dendriticum is a parasitic flatworm that has a multi-stage life cycle a little bit like T. gondii. One stage is in an ant, and the next stage is in grazing herbivores like sheep or cattle. Being herbivores, sheep and cattle do not go out of their way to eat insects, but neither will they pick bugs out of their food if there are any in there. An ant infected with D. dendriticum will climb to the top of a blade of grass and hold on. By virtue of their location, they are more likely to be eaten by a herbivore. Unlike in T. gondii, the ant being eaten by the next host is incidental, not intentional — the cat wants to eat the mouse, but the sheep is indifferent to eating the ant. Once the ant has been eaten, the parasite will continue the next stage of its life cycle.

Crawling to the top of a blade of grass and holding on is not normal behavior for an ant. Image from en.citizendium.org
These are just a few interesting examples of host manipulation. There are many more.
All of this is not to suggest that the zombie apocalypse is imminent, but it is not particularly out of the question — there is precedent for diseases manipulating behavior in some fairly dramatic ways. The only primary aspect of zombies that is not plausible is for an infection to reanimate the dead, which some people consider to be a defining characteristic of zombies. If a disease is to control your behavior, it doesn’t need to kill you to do it. Death occurs because your body is no longer able to maintain homeostasis and fight entropy. No parasite has the energy or machinery to rebuild a dead body into working order. It is much more efficient to infect a living organism and to not kill it before the parasite has spread. People sometimes disregard 28 days later as not a real zombie movie because the people are just sick, not risen from the dead. I would argue that it is the most real zombie movie for exactly the same reason.
*There are also movies in which the cause of the zombies is not explained. Natural causes and supernatural causes are still the only possible options.
**Pathogens obviously lack the cognitive properties to have goals in the sense that we humans have goals. When I say that they have a goal, I mean that their physiology and behavior were designed by natural selection to accomplish a particular task.
*** Toxoplasma is the name of the disease-causing organism. Toxoplasmosis is the name of the condition caused by a Toxoplasma infection.
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