Source: University of Otago, used with permission

"What's in your head, in your head

Zombie, zombie, zombie"

— The Cranberries, "Zombie"

Zombies have been a fixture in American pop culture dating back at least as far as the 1968 cult movie classic The Night of the Living Dead. Currently, the zombie drama The Walking Dead has the highest total viewership of any show in cable television history, with an additional 10 million viewers tuning in for the new spin-off Fear the Walking Dead. Zombies have even managed to insinuate themselves into Jane Austen’s literary landscape, spawning the bestselling novel Price and Prejudice and Zombies. Just what is our fascination with the idea that human beings could transform into hordes of slow-moving, night-loving, brain-eating, automatons of decomposing flesh?

Maybe that very transformation, with its underlying premise that zombies represent our former selves and might even retain some sliver of personhood, gives zombies a kind of humanity that sets them apart from the average monster. This somewhat novel aspect of the zombie experience has been given life in the 2013 film Warm Bodies, about a teenage zombie who regains his humanity by falling in love, as well as in the current TV show iZombie, about a medical student who uses her unique zombie attributes to help the police solve murders.

With the zombies of The Walking Dead and World War Z (or for that matter, the vampires of The Strain) supposedly arising from some infectious source, maybe our obsession with zombies in fiction is linked to deep-seated fears about the real-life potential for mass infection. It would seem that those anxieties are played out not only in entertainment, but in routine worries about the next year’s coming flu, public health concerns about the anti-vaccination movement, and the sparked by the 2014 appearance of the Ebola virus in the US.

And then there’s the possibility that zombies aren’t just a fictional metaphor for worries about sickness and death, but are actually a reality — a reality in which our brains are in fact routinely high-jacked by micro-organisms that cause actual sickness, influence our behavior, and remove our .

If that sounds preposterous, let’s start with a quick survey of the animal kingdom, where examples of just that abound.

Take Polysphincta boops, the parasitic wasp that stings spiders, paralyzing them long enough to lay eggs inside their bodies, which then hatch. From within, larval wasps cause the spiders to weave unusual webs seemingly designed to provide shelter as opposed to catching insects for food. Sure enough, upon devouring the spider from the inside, the larva emerge and nestle into the cocoons where they mature into adults.

Then there’s the baculovirus Lymantria dispar, which infects leaves that are eaten by caterpillars. Once consumed, the virus causes the caterpillars to climb to the highest treetop leaves without cover of darkness such that they’re either eaten by predators, or literally melt as a result of their infection, raining down millions of viral copies far below. Similarly, the fungus Ophiocordyceps unilateralis compels infected ants to permanently attach their jaws to the underside of leaves where they hang inanimately, growing mushroom-like protuberances out of their heads that eventually explode, sending fungal spores airborne to propagate (have a look at a YouTube video of this process here). And finally, there are horse-hair worms whose infection causes crickets and grasshoppers to leap into water, where they drown, allowing the foot-long worms to emerge and find a mate.

According to the “parasite manipulation hypothesis,” the idea here is that some organisms have evolved ways of survival that include not only infecting a host, but taking control of its body or its brain, altering its behavior, and rendering it into a zombie-like state that benefits the parasite’s life cycle in one way or another. Unfortunately for the examples detailed thus far, such zombification results in the end of life as the host knew it, often leading to an eventual demise that amounts to suicide. In the insect world, parasitic manipulation has been implicated in death on such a large scale as to attract the of human beings, whether by sharp declines in the annual migrations of monarch butterflies or in colony collapse disorder among bees.

Lest you think this phenomenon is limited to the lowly domain of entomology, consider the flatworm Leucochloridium paradoxum. When the eggs of the flatworm are eaten by snails, they hatch and migrate into the snail’s eyestalks where they grow into bulbous, colorful “broodsacs." The snails go blind and, contrary to their normal behavior, they move into unprotected open space, twitching their swollen eyestalks with a kind of pulsating rhythm that renders them irresistible to birds who come along and gobble them up (see a YouTube video of this remarkable transformation here).

In much the same way, the thorny-headed worm acanthocephalans causes a small crustacean called a gammarid to swim into light and up near the water’s surface, sometimes even latching onto rocks where it is devoured by ducks. The flatworm Euhaplorchis californiensis likewise infects the brain of the killifish, inducing it to swim to the water’s surface with jerky, shimmering movements that make it more noticeable and likely to be eaten by birds. Another flatworm, Curtuteria australis (pictured above), prevents clams from burrowing into sand for shelter, leaving them exposed and vulnerable to predation, thus condemning them to a similar fate of zombie suicide.

These examples illustrate some differences between parasite behavior in “definitive” and “intermediate” hosts. When parasites find themselves in an intermediate host, compelling that host to effectively commit suicide by being eaten by the definitive host is an evolutionary advantage. In contrast, when parasites find their way into their definitive host, they are “content” to live out their life cycle and reproduce, such that facilitating the death of the host would not be in their best interest. But they can still wreak havoc. Such is the case with Sacculina, a small barnacle that enters the shell of crabs, their definitive host, causing them to become infertile and lose interest in mating. After growing rampant inside the crab’s shell, Sacculina lays eggs on the underside of the crab, which is then tricked into caring for barnacle eggs as if they were its own.

Of course, we’re still only talking about mollusks, crabs, and fish, so let’s take a giant leap into the world of mammals. Stanford Robert Sapolsky has argued that the rabies virus is not merely an infectious agent, but a zombifying parasite that gets into the brains of mammals, causing excessive salivation, unbridled aggression, and a tendency to bite. So infected, a raccoon, bat, or dog takes on a new mode of uncharacteristic behavior that fosters the spread of the virus along to another organism. In humans, rabies infection can be associated with confusion, , and , but no reports of human-to-human transmission have ever occurred. Instead, death usually occurs within a week or two, limiting the zombifying potential of the rabies virus in humans.

Perhaps we human beings, supposedly in possession of free will, are immune to behavioral manipulation by parasites. Or maybe not.

Finally, we come to the story of Toxoplasma gondii (or just T. gondii, for short).

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Source: wikipedia commons

T. gondii is a protozoan parasite whose definitive host is the cat. Once inside a cat, T. gondii appears to be relatively innocuous, completing its life cycle by maturing, reproducing, and shedding eggs into the cat’s feces, which are spread to other organisms from there. But T. gondii can infect almost any warm-blooded animal and when it does, it appears to use behavioral manipulation — like so many of the examples above — in order to increase the chances of an intermediate host being eaten by a cat. This has been best studied in rats, which when infected by T. gondii, become more active, less vigilant for predators, and seem to lose their natural aversion to the odor of cat urine (this has been called “fatal feline .”)

In humans, T. gondii can cause flu-like symptoms during an initial infection, but is most commonly associated with long-term “latent” infection that is asymptomatic (good thing, because no medical treatment is available to eradicate the parasite once its been passed on). As a result, T. gondii has usually been a clinical concern only in unborn babies ( women are cautioned to avoid litter boxes), infants, and immune-compromised people in whom infection can cause more serious problems like stillbirth, encephalitis, or the growth of large cysts in the brain.

But in the last 20 years, research has increasingly shown that latent T. gondii infection might be associated with subtle changes in , more conspicuous changes in behavior, and an increased risk of illness. Much of this research has been performed by Jaroslav Fleger, a Czechoslovakian biologist who believes that T. gondii is responsible for a wide variety of human morbidity (see this article from The Atlantic covering Flegr and his work with T. gondii). While his opinions have not quite achieved widespread acceptance, some of his findings have withstood the test of time and replication.

Most of Flegr’s research has involved testing for the presence of antibodies to T. gondii that are consistent with latent infection. The rate of T. gondii antibody seropositivity ranges from about 11-23 percent overall in the U.S. up to 80 percent or more in countries where exposure to cats is higher and the practice of eating raw meat (or eating cats, for that matter) is common. It’s estimated that about a third of the developed world’s population may be infected (Flegr himself has tested positive for the T. gondii antibody). Once tested, research subjects can be divided into those with and without evidence of infection, so that researchers can look for differences between the two groups. For example, in one study, Flegr’s research group found that men with T. gondii infection rated the smell of cat urine more favorably that non-infected men, suggesting a feline fatal attraction mirroring that of rats (although the opposite effect was found among women).1 Looking at personality traits, Flegr reported that T. gondii-infected men were more likely to be suspicious, , dogmatic, and to disregard rules compared to non-infected men. Women with T. gondii infection appeared to be more warm-hearted, , conscientious, persistent, and moralistic compared to non-infected women.2

Several studies performed in the different countries (many of them done by researchers other than Flegr) have determined that T. gondii infection is associated with a greater risk — as much as a 6-fold increase — of being involved in a traffic accident.3 Likewise, a few studies have found that T. gondii infection is associated with a greater risk of suicide or suicide attempts.4

The most replicated finding, and therefore the one that’s given the most credence within psychiatric research, is that the risk of having is greater among those with T. gondii infection. In 2012, E. Fuller Torrey, a psychiatric researcher with a longstanding interest in infectious causes of schizophrenia, reviewed 38 studies and found that T. gondii infection is associated with a 2.7-fold increased risk of schizophrenia.5 A more recent analysis of 50 studies found that T. gondii increases the risk of not only schizophrenia, but also , , and .6

What kind of story do these research findings outline about the parasitic behavioral manipulation and zombifying potential of T. gondii? To hear Flegr tell it, while human beings aren’t currently under significant threat of being eaten by cats, we were from a historic and evolutionary perspective. Therefore, as intermediate hosts, our brains are changed by T. gondii in a way that might have put us at greater risk of being eaten by something like a lion. In the modern world outside of the savanna, those same brain changes might now place us at greater risk of mental illness, suicide, or death by car accident. Flegr has suggested that T. gondii’s influence on human behavior is profound and that it could even be responsible for more human deaths than malaria (usually considered to be the most deadly parasite on the planet).7

According to this view, a zombie apocalypse courtesy of T. gondii might currently be more fact than future fiction. Certainly, if we accept that behavioral manipulation by T. gondii might be occurring in anywhere from 10-80 percent of human beings, we’re at least talking about a pretty convincing argument against free will (see my previous blog post on the illusion of free will here). For example, it has been argued that suicide represents the ultimate example of free will, since it goes against our strongest innate instinct for survival. But maybe it’s by the will of the T. gondii parasite that we do ourselves in, so that our pet cats might have the chance to feast on our dead bodies. That’s not a bad argument in favor of T. gondii-infected zombies.

At this point however, the truth is that the T. gondii zombie story remains a bit of a stretch. Almost all of the research thus far is based on correlational associations (as in, correlation doesn’t prove causation). And some of the other more provocative findings — such as the increased risk of traffic accidents and suicide — have not been replicated in more recent studies. Flegr himself recently reviewed data from 87 countries and found no correlation between traffic accidents and T. gondii after controlling for other factors like wealth and population health.8 A 2013 study found no association with T. gondii seropositivity and suicide attempts.9 As usual then, more studies are needed to confirm the replicability of the data thus far.

Flegr’s theory is far from complete. It isn’t clear, for example, how differences between men and women figure in. Why would T. gondii cause different personality changes in men and women? And while it’s tempting to invoke T. gondii as an explanation for “crazy cat ladies” who hoard cats, it was T. gondii-infected men and not women who found the odor of cat urine appealing in Flegr’s study.

Among parasitic brain manipulation researchers, it’s also well recognized that changes in brain and behavior might arise from a non-specific inflammatory response as opposed to any actual manipulation by a parasite. It’s just as likely that behavioral effects in an intermediate host might be accidental or random, without a specific evolutionary advantage (for example, why would T. gondii benefit from people getting schizophrenia?) It’s therefore possible that T. gondii isn’t nearly so clever or diabolical as it might seem.

University of California Santa Barbara biologist Kevin Lafferty has taken this in another direction altogether, noting that the personality traits that Flegr found to be associated with women with T. gondii infection — warm-heartedness, , and outgoingness — are in fact desirable features. “Could a dose of toxoplasmosis improve your life?” he muses.10 Looking more broadly at personality traits in proportion to different rates of T. gondii infection in different countries, Lafferty believes that T. gondii might even help to shape cultural diversity across the globe.

On the one hand then, T. gondii might indeed be capable of transforming us into zombies of a sort, with compromised free will, a predilection for mental illness, and a greater risk of early death by suicide. But on the other hand, maybe those infected with T. gondii are less like the zombies of The Walking Dead and more like the zombies of Warm Bodies. In other words, just the kind of warm-hearted, cat-loving, humanity-retaining zombies that we have all come to know and love.

Dr. Joe Pierre and Psych Unseen can be followed on Twitter at https://twitter.com/psychunseen. To check out some of my fiction, click here to read the short story "Thermidor," published in Westwind earlier this year.

References

1. Flegr J, Lenochova P, Hodny Z et al. Fatal attraction phenomenon in humans – cat odour increased for Toxoplasma-infected men while decreased for infected women. PLoS Neglected Tropical Disease 2001; 5(11):e1389.

2. Flegr J. Effects of Toxoplasma on human behavior. Schizophrenia Bulletin 2007; 33:757-760.

3. Flegr J, Klose J, Novotna M, et al. Increased incidence of traffic accidents in Toxoplasma-infected military drivers and protective effect RhD molecule revealed by a large-scale prospective cohort study. BMC Infectious Disease 2009; 9:72.

4. Postolache TT, Cook TB. Is latent infection with Toxoplasma gondii a risk factor for behavior? Expert Review of Anti-infective 2013; 11:339-342.

5. Fuller Torrey E, Bartko JJ, Yolken RH. Toxoplasma gondii and other risk factors for schizophrenia: An update. Schizophrenia Bulletin 2012:38:642-647.

6. Sutterland AL, Fond , Kuin A, et al. Beyond the association. Toxoplasma gondii in schizophrenia, bipolar disorder, and addiction: systematic review and meta-analysis. Acta Psychiatrica Scandinavica 2015; 132:161-179.

7. Flegr J. How and why Toxoplasma makes us crazy. Trends in Parasitology 2013; 29:156-163.

8. Flegr J, Dama M. Does the prevalence of latent toxoplasmosis and frequency of Rhesus-negative subjects correlated with the nationwide rate of traffic accidents? Folia Parasitologica 2014; 61:485-494.

9. Alvarado-Esquivel C, Sanchez-Anguiano LF, Arnaud-Gil CA, et al. Toxoplasma gondii infection and suicide attempts: A case-control study in psychiatric outpatients. Journal of Nervous and Mental Disease 2013; 201:948-952.

10. Lafferty KD. Look what the cat dragged in: do parasites contribute to human cultural diversity? Behavioural Processes 2005; 68:279-282.