Sunday, August 11, 2013

Nasal Invasion: The Ticket to Summer Escapism

There is no better way to beat the oppressive heat and humidity of a New Jersey summer than to head into an air conditioned theater and watch a schlocky horror movie. Three years ago, Piranha in 3D had all the key elements: gratuitous toplessness, gore, and a cast of has-beens (Richard Dreyfuss, Christopher Lloyd) and B-listers (Jerry O’Connell, Elisabeth Shue).

This year World War Z filled the bill with tons of gore, thousands of rampaging zombies, and Brad Pitt atop a cast of nobodies. It was a little short on gratuitous toplessness, but entertaining and thoroughly forgettable.

A key plot point in WWZ (yes, spoiler alert, but honestly, if you haven’t seen it yet what are the odds you ever will?) is that the flesh-eating zombies eat only healthy people—those infected with deadly diseases are functionally invisible to them. That got me thinking: there’s a lot of good horror movie material lurking in the olfactory system.

Consider this: the olfactory nerves, which run from the sensory membrane of the nose to the olfactory bulbs at the base of the brain, are unmyelinated. The absence of a myelin sheath leaves the nerve cells especially vulnerable to infection by viruses (e.g., influenza) and by that creepy quasi-life form know as the prion, which causes brain disease and dementia (e.g., Creutzfeld-Jakob and kuru). In other words—high concept alert for Hollywood screen writers!—the nose is a pathogen’s freeway to the brain. The point was driven home recently by Japanese scientists who squirted radioisotope into the nose of test subjects and watched it get transported up the olfactory nerves and into the brain within 24 hours.

It’s also been pointed out that the vomeronasal system (a.k.a. the accessory olfactory pathway) is a potential route for neuroinvasion by neurotropic microbes. [Neuroinvasion! Great movie title.—Ed.] The vomeronasal system is the neural pathway activated by sex pheromones. Right there you have all the plot elements for a summer blockbuster: zombifying microbes from the deep mud in Crystal Lake hitch a ride up the noses of randy, pheromone-drenched summer camp counselors. [Gratuitous toplessness!—Ed.] Only Brad the nature counselor and Cindy the vain, slutty cheer squad counselor, remain immune. (He has runny-nose ragweed allergy, and her vomeronasal organ was severed during a nose job.) Together, can they save Camp Runamucky from the Zombie Pheromone Massacre?

Okay, I can already hear grumbling from the Universal lot that zombifying microbes are not visually dramatic enough to attract the target demo. To that I say: Ferrets! That’s right—nasty, weasel-like ferrets. An Australian research team has demonstrated that the H5N1 or bird flu virus travels up the ferret olfactory nerve pathway from the nose to brain. The nose is “a major infection route for this virus strain.” Once up the nose, the virus gets into the cerebrospinal fluid. [That’s when you turn zombie.—Ed.]

So here’s the idea (Hollywood High Concept Alert!): A group of animal rights activists acquire a mutant, zombifying strain of H5N1 virus while liberating chickens at a factory farm. Before going zombie, they liberate hundreds of mink from a nearby fur farm. After Brad, the local sheriff, guns down the animal rights zombies, he gets called to the nudist resort at Crystal Lake where vacationers are being attacked by infected minks. Can Brad and his deputies save the world from Rampaging Nudist Zombies?

Every once in a while, the science nerd plays a critical role in a summer monster movie (think Jeff Goldblum in Independence Day). For that to work, you need a plot twist that only a scientist character can provide. Writing in the journal Virulence, German scientists at the Centre for Experimental and Clinical Infection Research note there are biological mechanisms that fight neurotropic viruses coming up the olfactory nerves. For example, there is a Type I interferon-dependent response in the glomerular layer of the olfactory bulb. [Boooooring.—Ed.] The take-away for the aspiring screen writer is that Brad, the brilliant and ridiculously good-looking immunologist at UCLA, can be shown working his Pipetman with furrowed brow as he comes up with an ingenious cure for the zombie virus that began with pole dancers in West Hollywood. [Pole dancers. Yes.—Ed.]

Strip Club Zombie Apocalypse will need some intense Michael Crichton-style visuals to establish Brad’s science cred and that’s where a recent PLoS ONE paper comes in handy. Cue titles:
Division of Vector-Borne Infectious Diseases
Centers for Disease Control
Fort Collins, Colorado
11:45 a.m.
The research team tracked the progress of Western equine encephalitis virus up the nose of lab mice, using in vivo bioluminescence. In other words, they genetically engineered the virus with the firefly luciferase gene; when they applied luciferin to the infected mouse brain tissue, the virus particles would glow. [Neato.—Ed.]

[via PLoS ONE]

Every summer blockbuster needs a sequel or two, and the neuroscience literature on neuroinvasion provides ample material. For example, human herpesvirus-6 is associated with “a wide variety of neurological disorders” [Including zombie-ism?—Ed.] and appears to infect the brain via the olfactory pathway. Even more fiendishly, the virus may replicate within the glial cells that usually protect the olfactory neurons. Then there is the Neisseria meningitidis bacterium, which “is able to pass directly from nasopharynx to meninges through the olfactory nerve system.” It leaves around 50% of survivors with lasting neurological damage. [And a taste for human flesh?—Ed.]

And let’s not forget about Nipah virus: “During the first documented Nipah virus outbreak in Malaysia and Singapore in 1998-1999, 276 cases of Nipah virus encephalitis were observed, with 106 fatalities.” A recent experiment with Syrian hamsters found that the virus gets into the brain via the olfactory epithelium. “Entry of Nipah virus into the CNS occurred rapidly, within 4 days of inoculation.” That’s great thriller material: Brad has 96 hours to save his girlfriend from the zombie virus.

But I think the perfect nasal neuroinvasive sequel is the one that takes us back to Crystal Lake, in whose warm water we are likely to find the thermophilic ameba Naegleria fowleri. This is the pathogen that causes primary amebic meningoencephalitis which, as a recent paper reminds us, “is almost universally fatal.” You can get it by diving into a lake and getting water up your nose. [Ameba! Everyone out of the water!—Ed.] Or, you can get it trying to be healthy and using a Neti pot full of N. fowleri-contaminated water to irrigate your sinuses.

Anyway, it’s been fun spitballing script ideas. Enjoy your stay at Crystal Lake. Keep your nose clean and don’t worry about that guy in the hockey mask.


Peter Apps said...

A human version of this would have all kinds of plot possibilities -

Avery Gilbert said...

Peter Apps,

Good one!

First of all, whoever named the parasitical protozoan Toxoplasma is a film marketing genius.

As for a brain parasite that changes a rat’s fear of cat urine odor into attraction, thereby getting the parasite into the cat’s digestive tract for the next state of its life cycle, well that’s so warped that only evolution could come up with it.

I think the key plot element is that a third of female cat owners are also infected by Toxoplasma. All we need is a mutant version of the protozoan that causes nubile women to be attracted to the otherwise gross odor of zombies. It's Humanoids from the Deep in reverse.

Peter Apps said...

Better yet, let those who believe in the sort of human mating pheromones that you can put into a bottle and sell for a profit engineer an infectious agent that alters female's brains so that they really do behave like newly hatched butterflies when exposed to the synthetic version of a pig's preputial secretions.

Avery Gilbert said...

Peter Apps:

So the most terrifying plot twist is that human sex pheromones actually work as advertised.


cf. Roald Dahl's story "Bitch."

Peter Apps said...

Avery Gilbert:

"So the most terrifying plot twist is that human sex pheromones actually work as advertised."

I should have mentioned that the genre would be science fantasy; light on the science, heavy on the fantasy.

... and there is nothing new under the sun: ... without the infectious agent.