Interesting zombie blogs

There has been a lot of interest in my Zombie Protocol series so far, and for that I want to thank everyone who has wandered into the Dark Laboratory (even if you were just looking for the little girls' room).  Zombies are always hot around Comic Con, and there is always some new book or movie coming out.  It's easy to find pop culture information on the next apocalypse, but much harder to find scientific discussions about the phenomenon (hence, this blog!).

Tara Smith  had a nice piece yesterday in Science Blogs about teaching children science concepts using zombies as a backdrop (here's the link).  Disease transmission, pandemics, zombie bugs, neurobiology, and other biological topics were used to discuss what strategies the kids would use for different types of zombie outbreaks.  They also used watermelons as, um, volunteers, to compare the effectiveness of various weapons.  Where were these people when I was in school!!

Coolest logo EVER!

Anyhow, I'm also starting to include links on the right to various sources of zombie science.  Scott Kenemore's blog is doubly good as it also discusses new zombie books and movies.  He's also on the advisory board of the Zombie Research Society, which looks a little tongue-in-cheek but has some heavy hitter scientists on their Board. Coincidentally, Tara Smith is also on the Advisory Board.   Both sites have an occasional discussion about scientific literature and are worth a read.  If you know of other sites that have a scientific bent to zombie research, or any other topic that might be of interest to the Lab, please leave a note below.  Spam will, of course, be fed to the zombies...

The Zombie Protocol, Part 2

Bufotenine: Zombie Poison

With 'bath salts' in the news these days, there is suddenly a lot of interest in zombification.  If you recall, in part 1 of the Zombie Protocol, I described the role of tetrodotoxin in the creation of Haitian zombies.  There are, however, other ingredients in the zombie poison that have significant pharmacological activity.  Besides related TTX toxins from other species of fish, there can also be poisons from frogs, reptiles, and spiders.  The poison from the frog, Bufo marinus, is of particular interest as it contains bufotenine (5-hydroxy-N,N-dimethyltriptamine, or 5-OH-DMT).  Bufotenine is an alkaloid related to DMT and 5-MeO-DMT, as well as psilocin (one of the psychedelic molecules found in mushrooms).  It is also related to serotonin, a well-known neurotransmitter.

Serotonin: Important neurotransmitter

Therefore, it seems very plausible that bufotenine is present in the zombie powder to enhance the effect of the tetrodotoxin.  Remember from my last post that TTX is present at sub-lethal doses (in some studies, the amount of TTX is very low -- see Benedek and Rivier, Toxicon 27:473-480, 1989), so other components of the powder could be necessary to boost the effect of the mixture without killing the victim.  Psychoactive substances would also be very effective since the victim is likely to be conscious while under the influence of TTX.  I mentioned the Poe-like experience of being buried alive without any way to move or scream... now imagine that happening while having horrible hallucinations!  You talk about a bad trip!!

Seed pods from Mucuna pruriens (Wikapedia)

Plants known to be irritants were also added to some of the zombie powders.  In Wade's paper (abstract), he lists Urera baccifera, Dalechampia scandens, and Mucuna pruriens as some of the more common plants.  These plants all have irritating hairs or needles that cause contact dermatitis. In the case of M. pruriens, the hairs on the seed pods contain (interestingly enough) serotonin.  Why would irritants be important to a zombie poison?  Personally, I think this is one of the ingenious parts of the protocol... the irritants are there for delivery.  To pull off the zombification, a voodoo priest would have to administer this part of the poison without the victim's knowledge.  Poisoning food or using darts are quite tricky, but what about a chance encounter on the busy streets of Port-au-Prince?  You have the drug cocktail smeared on the end of a walking stick, or some other convenient device.  Following your target through the busy streets, you wait until you have a good opportunity.  He's distracted by a street vendor, so you bring the stick high and as you pass behind him, you gently poke him in the back of the neck.  He may not even notice but after you have left, he feels a burning sensation and scratches it.  The itching and burning intensifies until he scratches it raw.  The drugs are now able to enter the blood and begin the process of poisoning the victim.  He won't remember the chance encounter, but you know he will be at the hospital soon, and at the morgue not too long after that.

I know I promised zombie cucumbers in Part 2... but they will show up in Part 3, I promise.

T. gondii in the news again

     It's been bat shit crazy in the Not-So-Dark Laboratory (otherwise known as my day job), so my apologies for getting behind on the real crazy science.  One of my first posts (zombie science) talked about zombie science and the potential role of Toxoplasma gondii. T. gondii is a neurotropic protozoan parasite that has been linked to a variety of mental disorders. When rats are infected, they lose many of the behavioral adaptations that protect them from cats and aggressively try to get themselves eaten.  Sadly, the effect of T. gondii on humans seems more subtle. But there is a new paper out on the relationship between T. gondii and suicide, which provides stronger evidence that this parasite is a potentially serious global problem.

     Several recent studies have shown that T. gondii affects human behavior. A meta analysis published in 2007 (abstract) found that there is a correlation between schizophrenia and serum antibody levels against T. gondii.  The predictive power of the association was weak, since more that one third of the entire population is thought to be seropositive for T. gondii, and aside from a few ex-girlfriends and that driver on the 15 the other day, not all of them are crazy. One flaw with the meta-analysis is that it was not clear when the patients were infected relative to the onset of disease.  If they all got T. gondii after they became schizophrenic, then the association is meaningless.  The new study just published by Pedersen et al. (abstract) tries to account for that by measuring T. gondii antibody levels when women gave birth (using samples from heel-stick cards in the birth records) and then looking at the risk of depression and suicide later in their life. Seropositivity was 26.8% at delivery, consistent with the notion that 1/3 of the population has already been infected (remember that infants don't start making their own antibodies for about three months after birth, so these are the mom's antibodies).

From Pedersen et al, Arch. Gen. Psych. 2012.

Pedersen et al. found that seropositive women had a 1.53-fold greater risk of self-directed violence (ie, suicide) than seronegative.  Women with the highest antibody titers had nearly a 2-fold higher risk.  The risk is small, but significant and is also consistent with other recent studies on the relationship between T. gondii antibody titers and mental illness (for example, see this).  I'm generally not a big fan of these types of analyses, because the data could simply be a case of "true, true, and unrelated".  There is no mechanistic hypothesis for why antibodies against T. gondii would alter behavior, or whether the infection caused permanent damage to the brain.  However, evidence continues to accumulate that T. gondii infection can cause permanent changes in human behavior, and with billions of people having been infected at some point, it isn't too hard to see the beginnings of a zombie apocalypse.

The Zombie Protocol, Part 1

     As I mentioned in my previous post, some reports of zombies are more likely observations of people suffering from mental illness, long-term drug abuse, or both.  Given the loose definition of a zombie as somebody "acting strange" who had been missing and presumed dead, one wonders how many urban dwellers and street people in this country might be considered zombies.  I was at a conference in Barbados a few years back and walked past a homeless guy on Broad St. in Bridgetown.  He rose out of a pile of belongings to approach me, his legs stiff and his arms trembling. He was a pitiful sight, and communicated using grunts and various hand gestures.  He wound up following me for a block and even after I crossed the street and doubled back, he was still behind me.  I told everyone back home that I had seen a zombie, no doubt fulfilling my obligation to keep these legends alive.

  But what about "real" zombies? Is there a way to bring someone back from the dead?  Does the Zombie Protocol exist?  Without a doubt, the answer to this is 'yes'.  Although the legend of the zombie has existed in Haiti for generations, there is enough physical evidence to suggest that the process of zombification is likely rooted in scientific fact.  Please ignore the Hollywood ideas of brain-sucking zombies, and think instead about a circus act.  How would somebody make a zombie without learning all that dark magic (which, by all accounts, is very difficult)?  You fake it, but you fake it well.

Tetrodotoxin structure: Note the guanidido group (NH2+)
 group on the left.

In Wade Davis' excellent article The Ethnobiology of the Haitian Zombi (abstract), he lists the composition of zombie poisons from five separate locations around Haiti.  Although there were many differences, based on what was available at the different geographical locations, there were several key ingredients.  One of the most important was the puffer fish (Diodon hystrix, Diodon holacanthus, and others).  Puffer fish in the region have very high levels of tetrodotoxin (TTX), which is, of course, the same toxin found in Japanese fugu fish.  Tetrodotoxins are extremely toxic molecules and act by blocking Na ion channels, presumably through the positively charged guanidido group, which competes for the Na binding site in the channel.  Without Na exchange, nerve impulses do not propagate which leads to paralysis, as well as cardiac and respiratory failure. The LD50 of TTX is estimated to be about 5 ug/kg in humans (less than1 mg of TTX), so what if a person ingested something a little less than that?  Respiratory function decreases, blood pressure drops to near zero, pupils are fixed and dilated, the body is paralyzed, but maybe, just maybe, they won't actually die.  This is the first trick of the Voodoo priests, namely, to make the family think the victim is dead by titrating the amount of puffer fish in the poison to near the LD50.
     What is interesting, and also horrifying, is that TTX does not usually affect cognitive function.  This means that the victim falls ill and becomes "dead" while remaining conscious.  They hear the doctors discussing the death, hear the family wailing in grief, hear the preparations for burial, and then find themselves in a box, quiet and still.  Imagine the terror of being buried alive but having no way to move, scream, or otherwise respond to the panic.  The fear is completely trapped in the victim's mind..  Poe couldn't have scripted that much better...

Next up in the Zombie Protocol, toad toxins and zombie cucumbers...

Two articles on zombification

While I was doing research for my first book, I read a lot of articles on zombies.  Not the brain-eating type that are often found in movies, but real reports of zombies.  It was sometimes difficult to differentiate a true case from an urban legend ("I swear I saw a zombie walk right into that bar!") or a case of mistaken identity ("I thought it was a zombie, but it turned out to be just my mother-in-law...").  However, I ran across a very interesting article published in 1997 in the Lancet, a highly respected medical journal, on clinical findings from several reported zombies (here's the reference... a search will turn up the pdf elsewhere).  The paper, published by Roland Littlewood, from University College, London and Chavannes Douyon, a Haitian doctor, makes a fairly shocking claim. Although the process of zombification has been attributed to both poisoning or sorcery, the empirical data from Haiti suggest that people demonstrating behaviors consistent with a zombie are on the order of a thousand cases per year.  This is truly staggering, if accurate.

The Lancet article studies three reported cases of zombies during 1996-1997.  Patients FI and WD, although described by relatives as becoming ill and dying prior to their return months or even years later, were probably not dead to begin with.  Both patients suffered from mental illness and it seems more likely that they had simply wandered away from their homes and were taken in by other families.  For FI, the Lancet study concluded that she suffered from catatonic schizophrenia, a syndrome that could be considered zombie-like by locals.  WD likely suffered from organic brain syndrome and epilepsy.  The Lancet article speculated that these conditions were due to an unspecified period of anoxia.  Perhaps WD had been buried alive?  Unlike FI's coffin, which was filled with stones, WD's family refused to open the grave to Littlewood and Douyon.

Patient MM was a 31-year old female who had disappeared at age 18 after attending a service for a friend who had been zombified.  She fell ill shortly after and died.  Thirteen years later, she reappeared in the town and claimed to have been a zombie slave at a distant farm.  Littlewood and Douyon found her to be of very low intelligence but were unable to diagnose a more specific mental illness.  Upon return to the town near her captivity, locals recognized her as a zombie and several people argued over their claim to her.  Interestingly, she had a round, 1cm scar on her back, similar to a scar found on patient WD.  What were these scars from?

Unfortunately, they ultimately state that none of the three were true zombies, and that much of their behavior could be explained by mental illness.  However, one of the references they cite is the now classic paper by Wade Davis, published in the Journal of Ethnopharmacology in 1983, titled "The ethnobiology of the Haitian zombi" (abstract).  Is that a cool title or what! In this little gem, he provides a pretty detailed 'zombie protocol' and this forms the basis for Davis' book The Serpent and the Rainbow.  In my next post, I'll discuss his findings and several other classic zombie manuscripts...

Zombie cockroaches

Just when you thought the zombie apocalypse couldn't get any worse... now we have roaches to worry about!  Fortunately, zombie roaches in the wild are not aggressive, brain-sucking insects. It turns out that the wasps that make the zombies are what we should really be concerned about.

Jewel Wasp (A. compressa)
Image courtesy of Morphbank.net

The Jewel Wasp (Ampulex compressa) has an elegant and extremely sophisticated method to secure a good home for its eggs.  It attacks and injects a cocktail of neurotransmitters into the brain of a roach, effectively turning it into the slave of the wasp (Educated Earth has a good video of this process, see here).  The wasp then drags the roach to a suitable location and lays its eggs in the abdomen. The roach is hypokinetic for several days until the larvae hatch and then they slowly consume the host.  Interestingly, the larvae eat the internal organs in a way that maximizes the lifespan of the roach.  It's a morbid process, but how the wasp achieves this zombification is truly incredible.

The wasp actually stings the roach twice.  The first sting is to the thorax and produces a mild and very transient anesthetic that paralyzes the front legs.  A study by Moore et al. (abstract) showed that the active components of the first sting activate GABA receptors (GABA itself, and receptor agonists beta-alanine and taurine).  During the minute or so of action, the wasp then stings the roach again, but in a very precise location within the brain.  In a sense, the wasp is acting like a brain surgeon, who needs their patient to remain still while a precise operation is done.  This second injection is a cocktail of neuroactive compounds that have very specific effects on the roach's brain.  After the anesthetic wears off, the roach grooms itself excessively and then becomes lethargic.  It is not paralyzed, just sluggish.  When the first studies on A. compressa were done, there was a great deal of controversy over whether the venom was delivered to the central nervous system, or directly to the site of action in the brain.  In an elegant study by Haspel et al. (abstract), they milked the venom from wasps and injected them with radiolabeled carbon (14C).  This meant that the fresh venom produced by the wasp would contain the radiolabel.  Haspel could then visualize the location of the venom in the roach brain by taking pictures of brain slices.  Those of you who think that would be cool as hell, raise your hand!!

  Anyhow, it was found that the neurotoxin attacks the brain directly, with the most venom at the supra-esophageal ganglia (SupEG) and the sub-esophageal ganglia (SEG).  In insects, these areas are thought to provide "higher order" brain function.  A recent study by Gal et al.(abstract) found that the venom affects the drive to initiate and maintain walking.  Other motor skills (like flying, swimming, self-righting) were not affected.  Based on the electrochemical difference between stung and unstung wasps, they concluded that stung wasps had a deficit in the ability to "reach a decision" to walk.  There must be human versions of this wasp because I swear, there are days when I have trouble reaching the decision to get off the couch.

A follow-up study by Gal et al in 2010 (PLoS article) made another very interesting discovery.  Roaches who had their brain ganglia removed were stung for a much longer period of time (196 sec) than normal roaches (39 sec).  Why?  Because the wasp was actively seeking this part of the brain and couldn't find it!  What does it search for?  A specific morphology?  A defined depth within the brain?  Nobody knows.  Furthermore, why is it so important for the wasp to target this region so specifically?  The answer is also still open to speculation but this has zombie written all over it.  The wasp needs the roach to be compliant to move it into the proper position for incubation of the larvae, but resist the urge to flee for several days.  So, the venom basically takes away whatever "freewill" the roach might have had.

Octopamine
 (image courtesy of Wikidocs)

So, what is this supernatural cocktail?  Not a whole lot is known about the composition of the venom (another great project for biohackers or kids looking for obscure science fair projects). I will post more details later but one key component appears to be an antagonist of the octopamine receptor.  Octopamine is a monoamine neurotransmitter that is specific to invertebrates and OA levels are known to be associated with the hypokinetic state.  Several years ago, Rosenberg et al. (abstract) gave roaches a octopamine receptor agonist and found that motor activity in stung subjects was at least partially restored.  Other receptor agonists and antagonists had little effect.  This is certainly one clue about how A. compressa makes zombie cockroaches but for now, the rest of the process is all voodoo.

A gene important for creating zombie caterpillars

Advancements in zombie science are coming fast and furious!  An email from a colleague (and fellow reader) noted that I missed a recent article in the journal Science concerning zombies.  The article, titled "A Gene for an Extended Phenotype", seemed pretty innocuous, however, after going back and reading it more carefully it turned out to be a pretty cool discovery.

First, a bit about zombie caterpillars.  There have been several documented reports of zombie-like behavior in moth larvae.  This report is focused on the infection of the gypsy moth (Lymantria dispar) by a baculovirus (known as LdMNPV).  During the various stages of molting, larvae typically hang out on the ground and away from The Very Hungry Birdie, but climb up into the trees at night to feed on leaves.  After infection by the baculovirus, their behavior changes (noticing a pattern here?).  As the virus replicates and ravages the inside of the caterpillar, the infected host climbs up into the leaves during the daylight hours and eventually dies.  The body then liquefies, and virus-laden particles rain down on the uninfected victims below.  Yeah, you can't script horror much better than that.

Ok, so Hoover et al. (from Penn State, see abstract) were interested in identifying which genes were important for the change in behavior.  To do this, they infected caterpillars with wild type baculovirus, as well as virus that had been genetically engineered to be missing certain genes.  The caterpillars were placed in 1 liter soda bottles equipped with a fiberglass screen for climbing (in true DIYbio fashion!!).  Interestingly, when a gene called egt was removed, the caterpillars died at ground level, suggesting that the behavioral control of the virus had been altered.  To make sure it wasn't an artifact of the mutated virus, they re-engineered the mutated constructs so that the egt gene was present again and the zombie caterpillars climbed up the mesh and died.  It would appear that the egt gene in the virus has evolved to make the caterpillars engage in high-risk behavior, and to place the caterpillars in a location where rain/gravity/hungry birdies can maximize viral spread. Genius.

The next step is to figure out the mechanism.  Interestingly, Hoover et al. mention that the egt gene encodes an enzyme which deactivates a hormone (20-hydroxyecdysone) involved in the process of molting.  It is intriguing that the virus blocks the molting process in order to give itself time to replicate inside the host, but it was hard for me to understand how the modification of the hormone leads to behavioral changes.  Perhaps entomologists already know that part.  Coincidentally, the hormone is also reported to have a variety of biological effects in humans, even though we do not molt and lack the endogenous receptor. What would the modified enzyme do in a human?  Until we find this stuff out, it's probably a good idea to check the trees around your house, particularly if you hear a dripping sound... and if your neighbor has been missing awhile.

Yes, there are zombies all around us.

Can gut bacteria make zombies?



L. rhamnosus: Not a zombie-
producing bacteria...yet.



If T. gondii weren't enough to worry about, now there is evidence that bacteria in our gut can influence brain function.  Lactobacillus and other probiotic organisms have long been speculated to have beneficial in vivo effects, and are most commonly known for improving the health of the digestive tract.  L. acidophilus is probably the most widely known, since it is used to make yogurt, but there are many other types of lactobacilli with alleged health benefits ranging from lowered cholesterol to improved mood.  Some of these benefits are speculative, and for many years any benefit (such as improved gut health) was thought to be due to local effects or secreted chemicals.  However, the impact of these bacterial colonies may be much more far-reaching.

A Proceeding of the National Academy of Sciences (PNAS) paper published by Heujtz et al. last January (abstract) showed that microbial colonization in the mouse gut led to the activation of signaling pathways involved with motor control and emotional response.  This was the latest in a growing body of literature that suggests gut bacteria could influence how we think and act.  Now, in the August edition of PNAS, Bravo and colleagues take this one step further (abstract).  They show that Lactobacillus rhamnosus can directly influence the expression of GABA receptors in the brain.  GABA is the primary neurotransmitter for regulating many physiological and psychological activities in humans.  For example, caffeine inhibits GABA and results in an overall increase in neurotransmitter activity.  In contrast, alcohol and sedatives tend to increase GABA activity, leading to reduced neurotransmitter activity. Bravo et al. showed that feeding mice L. rhamnosus reduced GABA expression in some areas of the brain, while increasing it in others.  The overall effect was to make the mice more calm.  Here in the Dark Lab, we would test this by subjecting the rats to endless episodes of Jersey Shore, Barney and Friends, and The Jonas Brothers, and then asking how long it takes before they fall into convulsions.  Bravo measured stress-induced hyperthermia (rise in core body temperature from stress) after a battery of different tests, including  forced swimming and mazes (less barbaric than listening to the Barney jingle, but presumably effective at producing stress) and showed that the L. rhamnosus-fed animals exhibited less stress during these activities.

The final point of the paper was what I found most interesting.  Some of the animals had the vagus nerve cut prior to the start of the experiment.  This nerve is a direct link between the gut and the brain and is responsible for transmitting signals about hunger and satiation.  In these animals,there was absolutely no effect from consuming L. rhamnosus.  No changes in GABA expression and no behavior changes versus the control animals.  This means that the probiotic bacteria that colonize in the gut might actually use this nerve to signal directly to the brain.  Although these bacteria appear to provide a health benefit, I can certainly imagine other strains that are more nefarious.  Yeah, I'm talking about zombies again.  This phenomenon is not all that different from what is seen in T. gondii or the zombie ants... microbial agents that manipulate the brain function of the host.  If a probiotic strain can mimic the effect of caffeine-overstimulation or, even worse, caffeine-deprivation, then that would be a whole new kind of scary.  Anyone who has seen me before that first cup of coffee knows what I'm talking about... it's bad enough to give a zombie nightmares!

Zombie rats are horny!

You may remember a very early post on zombies, where I talked about a parasite known as Toxoplasma gondii.  I just read a new article published in PLoS that is really mind-blowing.  It also should fall in the category of science known as what-kind-of-PhD-do-I-need-to-study-this-shit.  Very interesting, very strange, and very cool.  Here's the abstract to check out for yourself (abstract).  As you know, rats that are infected with T. gondii lose their fear of cats.  This is important for the parasite because part of its life-cycle occurs in the gut of the cat.  This report takes that one step further.  House et al. show that as part of this shift in rat behavior, the rats are actually attracted to cat urine.  Not attracted like "this smells like roses" but rather "yowsa, hot babes" (rats do say 'yowsa'... I've heard them).  Yes, the parasite changes the way the rat brain responds to the smell of cat urine.  Neurons in the ventromedial hypothalmus, dorsomedial part (mercifully abbreviated as VMHdm), which normally are active in response to fear, are silent when infected rats are exposed to urine.  In contrast, the area in the brain the DOES light up is the posterodorsal medial amygdala.  These are the same neurons that light up when rats watch porn (or are exposed to estrous females, but somehow that doesn't sound as sexy).  Their conclusion is that T. gondii makes rats think that if they follow the cat pee, they will get laid.  Although that may work in some dive bars, for these rats it ultimately leads to just a single dinner date.

These results are also consistent with other findings that show an increased level of dopamine in infected rats.  Dopamine is, of course, the primary molecule in behavioral reward so it seems reasonable that this pathway would also be effective at shifting rat behaviors.  They cite a 2006 paper by Webster et al. (abstract) where it was shown that dopamine receptor antagonists prevent the attraction to cat urine.  Could this receptor be the first therapeutic target for treating zombies?  I'll have to propose that at the next New Target meeting. 

The ability of T. gondii to alter brain function and behavioral response is incredibly cool and a little bit scary.  Why scary?  Because it is estimated that at least one third of the human population has been exposed to the zombie-inducing T. gondii (and no, it's not just pop stars and politicians).  Even subtle changes in behavior on that scale can lead to massive changes in society.  Although it is unclear how well this study translates to humans, it does suggest that in the event of a zombie apocalypse, it's probably not a good idea to hide out in the girls' bathroom.

Amazing new paper on Zombie Ants

As some of you may know, I’m a big fan of zombies.  Not the feet-dragging, flesh-rotting stereotypes found on B-grade horror movies (although they can be cool too) but the ones found in real life.  The ones that make you wonder whether human zombies are for real.  The science behind these phenomena is fascinating but absolutely terrifying.  Creatures that suddenly exhibit irrational behavior or complete odd and highly specific tasks.  (Don’t worry, your girlfriend is (probably) not a zombie.)  I already wrote a bit about T. gondii (link) but a recent article in the journal BMC Ecology (abstract) describes an even more horrifying example. Zombie ants. I’m thinking this would make a great sequel to A Bug’s Life.

 



Zombie ant with fruiting body



It starts with a simple fungal infection and before long the ant is no longer following the well-marked ant trails through the Thai rainforest.  It starts staggering and has the occasional convulsion but instead of heading to rehab, it falls out of the tree and onto the forest floor.  At solar noon, the ant stops its random stagger and makes a bee-line to a nearby sapling.  It clamps its mandibles into a leaf (almost always a primary vein, under the leaf, facing NNW, about 25 cm high) and dies.  Bizarre? Yes, but to the fungus it is all part of a diabolical plan (cue music).  In order to reproduce, the fungus (Ophiocordyceps unilateralis) requires a very specific temperature and humidity.  An environment not present in the canopy (where the ants are) but uniformly at about 25 cm from the forest floor.  What’s an evil fungus to do? In order to get there, the fungus hijacks the ant and manipulates its brain by releasing various chemicals and poisons as well as making specific morphological changes to the mandibles.  All of these activities are designed to get the ant out of the canopy, go to a specific environment, and have the ant remain attached there after death.  Then the fungus sprouts a fruiting body out of the ant’s head to release spores.  All in all, the amazing transformation from ant to fruiting body takes about 2-3 weeks.  Many of the details are still a mystery but the Hughes paper begins to shed some light on this process.  A process, incidentally, that is very ancient.  Another paper by Hughes (abstract) describes fossils from the Tertiary Period (from about 50 million years ago) that bear mandible scars on primary veins of leaves.  Could these be the echoes of ancient zombie ants?  Could our own legends be the echoes of human zombies?  I wouldn’t worry too much unless your spouse’s ‘honey-do’ list becomes very bizarre or your girlfriend’s new hat looks suspiciously like a fruiting body.

Zombie science!

In addition to my day job as a scientist, I am also an aspiring writer of Young Adult fiction.  I like the concept of the teenage biohacker, because there is so much fertile ground to work with.  Science fair projects that go horribly wrong or the biology teacher who has an odd obsession with road kill.  In my first novel, a group of teens create primitive life in their basement lab.  The protagonist’s mom is a scientist studying extremophilic bacteria, and he learns from her that it is pretty easy to make long chains of amino acids (ie, proteins) using a temperature cycler.  When he tries to do this himself, disaster strikes and they force the system to evolve into an organized, self-replicating structure with life-like characteristics.  A prominent scientist learns about their discovery and steals it for his secret research on zombies. 

Sound crazy?  Check out the new book by Dr. Steven Schlozman called The Zombie Autopsies.  CNN interviewed the Harvard/Mass Gen psychiatrist about the book (see link) and I think it should be essential reading for any high school AP Biology class.  He uses a very scientific framework to discuss the pathogenesis of the disease, the mathematical models that predict how fast it could spread, and, of course, offensive and defensive strategies for our survival.  (Spoiler alert: The odds are pretty good for the zombies.) 

So, what is his take for the root cause?  Interestingly, he uses infectious proteins called prions as a source.   A paper published in 1982 by Stanley Prusiner first described these infectious proteins, and at the time it violated many dogmas of molecular biology (he won the Nobel Prize in 1997 for this work).  Prions are the culprit behind Creutzfeldt-Jakob disease, fatal insomnia (how awful!), Gerstmann-Straussler-Scheinker (GSS) disease, bovine spongiform encephalopathy (the technical term for Mad Cow disease), and probably other diseases and conditions that have not been linked yet.  Infectious prions are simply misfolded proteins that get into the brain and result in amyloids (aka ginormous blobs) that destroy brain tissue.  But they aren’t just any ginormous blob, they actually have a pretty well-defined structure and are quite stable.  The current thinking is that the infectious prion serves as a template that allows normal prion proteins in the brain to structurally convert to the infectious form.  However, even today the exact mechanism remains controversial.   What is known, however, is that as the infection spreads the brain disintegrates.  In CJD, this results in the slow death of the patient but in Schlozman’s book, it results in a zombie.  He makes a compelling case that if a different prion variant were to evolve such that the brain gets chewed down to the core, the patient would remain alive but would no longer be capable of cognitive thought.  All that would be left is basic brain function, an unquenchable hunger, and a dysfunctional fight-or-flight response (a “drunk crocodile” was Schlozman’s description). 

So does this mean that future college biology majors will be using Schlozman’s book for courses in Zombie Biology?  Maybe.  Although prions make for a compelling zombie disease, there are also other pathogens that have been suggested to turn your awkward, hormone-crazed, teenage neighbor into a clumsy, teenage zombie.  (Trust me, there’s a difference.)  In many zombie apocalypse movies, a virus causes people to wig-out and, just like rabies, is transmitted to hapless store clerks (and other minor characters) through a bite or a scratch.  This is also a very real possibility, since there are many brain-damaging viruses in circulation.  A few mutations in one of these guys and the brain buffet is open for business.  There are some scientists who also speculate that prion diseases are initially triggered by viruses. 

Then there is Toxoplasma gondii.  T. gondii is a parasitic protozoa whose primary host is the cat but requires a rat host as part of the full lifecycle.  Rats have a natural aversion to cats and are hard-wired to avoid areas with evidence of feline activity.  So how in the world does T. gondii manage to thrive?  Yup. Zombies.  When rats are infected with T. gondii, the infection affects brain function.  Instead of aversion, there is strong scientific evidence that rats become attracted to cats and lose their sense of risk aversion (for example, see Berdoy et al, “Fatal attraction in rats infected with Toxoplasma gondii.” Proc. Biol. Sci, Vol 267 pp1591-4, 2000).  If they could write, these zombie rats would carry little signs that say “Eat me… nom, nom, nom”.  Human infection by T. gondii usually has mild, flu-like symptoms but in some cases, it can produce symptoms very similar to schizophrenia (for a recent review, see Henriquez, et al., 2009 “Neuropsychiatric disease and Toxoplasma gondii infection.” Neuroimmunomodulation, Vol 16, pp122-133).  Crazy, unihibited humans?  Only a small step from zombies... or college freshmen.

Anyhow, this is a great example of some really cool, but offbeat, science. Yeah, this is on the fringe and is half-entertainment and half-science, but in reality, zombies are not only plausible, but something we may actually have to contend with someday.  A  prion-like protein that my protagonist discovered may be one of the catalysts.  Will he and his friends find a way to stop the zombie apocalypse?  Will his girlfriend become the first victim… or the first zombie!?  Let’s just hope she doesn’t own a cat.