Who benefits?

There's an interesting idea from evolutionary theory called the cui bono principle.

Cui bono? is Latin for "who benefits?"  It started out as a legal concept; if a crime has been committed, and you're looking for the suspect, find out who benefitted.  That, very likely, will get you on the right path toward solving the mystery.

Cui bono in the evolutionary model has to do with explaining odd phenomena that seem to have no obvious underlying reason -- or which even induce organisms into self-destructive behavior.  One common example is the strange situation where certain ant species crawl up to the tops of blades of grass and basically just wait there to be eaten by herbivores.  It turns out that the bizarrely suicidal ants are infected with a parasite called a lancet worm that needs to complete its life cycle in the gut of a herbivorous mammal, so it damages the brain of the ant in just such a way as to turn its sense of direction upside down.  The parasitized ant then crawls upward instead of downward to safety, gets eaten -- and the lancet worm, of course, is the one who benefits.

Another, even creepier example, is Toxoplasma gondii, which I wrote about here at Skeptophilia a few years ago.  I encourage you to go back and read the post, but the upshot is this parasite -- which by some estimates infects half of the human population on Earth -- causes different symptoms in its three main hosts, cats, rats, and people.  Each set of symptoms is tailored to change behavior in very specific ways, with one end in mind; allowing the parasite to jump to its next host.

I just found out about another very peculiar (and convoluted) example of cui bono just yesterday, this one involving rice plants.  Many plants, it turns out, have pheromonal signaling, releasing chemicals into the air that then trigger responses in neighboring individuals, either of their own or of different species.  Acacia trees that are browsed by herbivores, for example, emit a signal that triggers nearby trees to produce bitter tannins, discouraging further snacking on the leaves.  Well, it turns out that rice plants have an even niftier strategy; attacked by insect pests, the rice plants emit a chemical called methyl salicylate (better known as oil of wintergreen), which attracts parasitoids -- insects like chalcid wasps that attack and kill the offending pests, usually by laying an egg in or on them and allowing the larvae to eat the pests for lunch.

Okay, but this has yet another layer of complexity, because there's a different set of organisms that have another take on cui bono.  Rice are subject to a group of plant viruses called tenuiviruses, which cause rice stripe disease, weakening or killing plants and severely reducing crop yield.  Tenuiviruses are spread by insect pests like planthoppers, which (much like mosquitoes with malaria, dengue fever, yellow fever, and chikungunya) suck up the sap of infected plants and the virus along with it, move on to an uninfected host, and spread the disease.

Rice stripe tenuivirus [Image credit: A. M. Espinoza]

And new research has found that the tenuiviruses, once in an infected plant's tissues, suppress the plant's ability to produce methyl salicylate.  The result?  The plant can't send a signal to the parasitoids, the planthoppers multiply, and the disease spreads.

The authors write:

[R]ice viruses inhibit methyl salicylate (MeSA) emission, impairing parasitoid recruitment and promoting vector persistence.  Field experiments demonstrate that MeSA, a key herbivore-induced volatile, suppresses vector populations by attracting egg parasitoids.  Viruses counter this by targeting basic-helix-loop-helix transcription factor OsMYC2, a jasmonic acid signaling hub, thereby down-regulating OsBSMT1 and MeSA biosynthesis, responses conserved across diverse rice viruses and vector species.

So once again, we have a parasitic microorganism that is engineering a response in its host that makes it more likely to be passed on, in this case by preventing the host from calling for help.

This kind of strategy brings Tennyson's observation that "nature is red in tooth and claw" to new heights, doesn't it?  Makes you wonder how many other examples there are out there of behavior being manipulated by parasites.  Further evidence that evolution is the Law of Whatever Works -- even if Whatever Works is kind of unsettling.

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Who benefits?

One of the most curious features of evolutionary biology is the cui bono principle.

Cui bono? is Latin for "who benefits?" and is an idea that found its first expression in courts of law.  If a crime is committed, look for who benefitted from it.  In evolutionary biology, it's adjuring the researcher to look for an evolutionary explanation for seemingly odd, even self-harming behavior.  Somebody, the principle claims, must benefit from it.

A while back, I did a post on one of the strangest and most complex examples of cui bono; the pathogen Toxoplasma gondii, a protist that primarily infects humans, cats, rats, and mice.  In each, it triggers changes in behavior, but different ones.  It turns rats and mice fearless, and in fact, makes them attracted to the smell of cat urine.  Infected cats are more gregarious and needing of physical contact (either with other cats or with humans).  Humans are more likely to be neurotic and anxious, impelling them to seek comfort from others... including, of course, their pets.  Each of these behaviors increases the likelihood of the pathogen jumping to another host.

That this behavioral engineering is successful can be gauged by the fact that by some estimates three billion people are Toxoplasma-positive.  Yes, that's "billion" with a "b."  As in, one third of the human population.  I can pretty much guarantee that if you've ever owned a cat, you are Toxoplasma-positive.

What effects that has had on the collective behavior of humanity, I'll leave you to ponder.

I just ran into another cool example of cui bono a couple of days ago -- well, cool if you're not a tomato grower.  This is another one for which the answer to "who benefits?" turns out to be a pathogen, this time a virus called tomato yellow leaf curl virus, which has the obvious effect on infected plants.

Uninfected (top) and infected (bottom) tomato plants [Image credit: Zhe Yan et al., MDPI]

The researchers, led by Peng Liang of the Chinese Academy of Agricultural Sciences, noticed a strange pattern; there's a pest of tomato plants (and many other crops) called the silverwing whitefly (Bemisia tabaci) that shows a distinct preference for tomato plants depending on who is infected with what.  If the whitefly is uninfected with the virus, it's preferentially attracted to infected tomato plants; if the whitefly is already infected, it shows a preference for uninfected plants.

So cui bono?  The virus, of course.  Infected whiteflies pass the virus along to uninfected plants, and uninfected whiteflies pick the virus up from infected plants.  Clever.  Insidious, but damn clever.

Liang et al. found that the virus accomplishes this by meddling with a chemical signal from tomato plants called β-myrcene.  The virus actually up-regulates the β-myrcene gene -- essentially, turning the volume up to eleven on β-myrcene's production -- which attracts uninfected whiteflies.  Once the virus gets into the whiteflies, it dials down the sensitivity of the whiteflies' β-myrcene receptors, making them less attracted to it.  

No need to be lured in by the infected plants if you're already infected yourself.

So like with Toxoplasma, we have here a microscopic pathogen that is manipulating the behavior of more than one host species.  It's fascinating but creepy.  You have to wonder what other features of our behavior are being steered by pathogens we might not even be aware of.  Recent studies have found that between five and eight percent of our DNA is composed of endogenous retroviruses -- scraps of DNA left behind by viruses in the genomes of our forebears, and which are suspected to have a role in multiple sclerosis and some forms of schizophrenia.

Who knows what else they might be doing?

If you find this whole topic a little shudder-inducing, you're not alone.  Science is like that sometimes.  If there's one thing I've learned, it's that the universe is under no compulsion to make me feel comfortable.  If you agree, sorry I put you through reading this.  Go cuddle with your kitty.

I'm sure that'll make you feel better.

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Tooth and claw

Aficionados of The X Files will no doubt recall "Field Trip," which ranks amongst the creepiest, twistiest, most atmospheric episodes they ever did.  Fox Mulder and Dana Scully are charged with investigating the disappearance of a young couple while on a hiking trip -- and after that, their mantra "Trust nothing and no one" becomes literally true.

What had happened (obviously, *spoiler alert*) is that first the couple, and then Mulder and Scully, had been attacked by an underground fungus that works in a particularly insidious way.  Inhaling the spores, which are released whenever you take a step on the ground, induces hallucinations intended to make you hold still while the fungus slowly digests you.  It stimulates your brain with images while dissolving away your body.  Every time the real reality -- the tendrils of slime mold creeping across your skin -- intrudes, the hallucinations become more intense, more engaging, more real.

Until there's nothing left of you to fight back.

While the details of the episode are fiction, nature itself has plenty of examples that are just as horrifying.  The pathogen Toxoplasma gondii, common not only in humans but in domestic cats, wild mice, and rats, alters the brains of the hosts, but each in its own way.  Rats and mice become unafraid of predators, and in fact become attracted to the scent of cat urine; cats and humans become more affectionate -- and neurotic.  Each of those alterations in behavior is engineered by the parasite to maximize its chances of jumping to another host.  Lancet worms (Dicrocoelium dendriticum) parasitize ground-dwelling ants, and induce them to climb blades of grass and simply wait there, because the worm has a second stage of its life cycle in which it has to pass through the digestive tract of a ruminant, like a deer or a cow.  So it basically triggers the ant to commit suicide so it can make the jump.  Worse of all -- and most like the fungus in "Field Trip" -- there are the baculoviruses, which infect caterpillars.  Once parasitized, the caterpillars become attracted to sunlight, so they climb to the very tops of tree branches, where they die.  And then explode, showering their comrades lower down in the tree with viral particles.

Another way that "Field Trip" got it right, though, was some of the nasty stuff pulled by members of kingdom Fungi.  You have to wonder how we ever figured out that any of them were edible:

Not only are some of them amongst the most toxic living things known (the closely-related death cap [Amanita phalloides] and destroying angel [Amanita bisporigera] mushrooms, for example), they have a lot of other insidious strategies.  Most fungi are decomposers, but like the fungus in "Field Trip," a few of them have developed methods for hastening their unfortunate prey into decomposition.

This, in fact, is why the topic comes up; a new study of oyster mushrooms (Pleurotus ostreatus) found that the underground mycelium (network of root-like tubes) of the species actually hunts and kills nematodes (roundworms) using something one of researchers described as "a lollipop filled with nerve gas."  The toxocysts, as the lollipops are called, are consumed by the nematodes, and when they burst, it releases a chemical called 3-octanone, which triggers calcium to flow into the muscles of the worm.  This paralyzes it -- and the fungus has dinner.

Oyster mushrooms aren't the only species that goes after nematodes.  It makes sense to choose them as prey; nematodes are one of most numerous animals in the world.  I still recall my invertebrate zoology professor grossing us all out (something he specialized in) by telling us that if you made all organic matter disappear except for nematodes, you could still see where all the other life forms were by the haze of parasitic nematodes they'd been carrying, outlining where they'd been like some kind of ghostly remnant of their bodies.

But the fungi still maintain the upper hand.  There are fungi which have evolved harpoons for skewering nematodes.  Others create what amount to glue traps.  One species produces something like a spiked collar -- with the spikes pointing inward.  The weirdest one is the fungus Arthrobotrys oligospora, which creates a noose.  When a nematode crawls through the noose, the loop suddenly inflates, strangling the hapless worm, which is then digested.

Nature is red in tooth and claw, man.  And it's not just the animals.  Remember the first line of Stephen King's wonderful novel The Girl Who Loved Tom Gordon: "The world had teeth, and could bite you with them any time it wanted."

Truer words never spoken.

Anyhow, I've probably skeeved you out sufficiently for one day.  Just think about all this next time you see innocent-looking little mushrooms popping up in your lawn. 

You never know what's going on beneath the surface.

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Nice smile!

Back in December, I completely skeeved out some of my readers with a discussion of parasites, more specifically the protist Toxoplasma gondii.  Toxoplasma causes the disease toxoplasmosis, and a number of mammalian species are hosts, most notably cats, humans, and rats.  It's the cat/human connection that is why you've probably heard that pregnant women shouldn't clean cat litter boxes; contact with an infected cat's urine can transmit the parasite to a human, and Toxoplasma is associated with birth defects in human infants.

More interesting, though, are its behavioral effects.  In December's post, I described how toxoplasmosis alters the behavior of all three of its main hosts -- it makes cats more affectionate, humans more neurotic, and rats more fearless, all three of which serve the evolutionary function of increasing the likelihood that the pathogen will jump to another host.  (The cats seek out human company; the humans crave the comfort that pets can give; and the rats become unafraid of predators.  In fact, some studies have even shown that infected rats are actively attracted to the scent of cat urine.)

Which is creepy enough.  The idea that a brain parasite is, at least in some respects, in the driver's seat of our emotional state is a little unsettling.  Or maybe I'm only saying that because I've got it myself, having had cats off and on for pretty much my entire adult life.  But I'm not indulging in hypochondria, here; if you've ever owned a cat, especially one allowed outdoors, your chances of having a Toxoplasma infection is nearly 100%.  Kevin Lafferty, a microbiologist who is one of leading experts on Toxoplasma, estimates that there are three billion people in the world who have it.

Yes, that's "billion" with a "b."  As in just shy of 40% of the world's population,

But now another filigree of "holy shit, that is freaky" has been added to this already bizarre pathogen.  A team made up of Javier Borráz-Léon and Markus Rantala (of the University of Turku), Indrikis Krams (of the University of Latvia), and Ana Lilia Cerda-Molina (of the Instituto Nacional de Psiquiatría of Mexico City) found out that not only does Toxoplasma change our personalities, it changes our appearance.

The idea came from the fact that in other mammals, Toxoplasma can be spread through sexual contact, so there was no reason to believe the same couldn't be true of humans.  The researchers wondered if -- given that the parasite is pretty damn good at engineering its hosts to do things that pass it on -- there might be some way that being Toxoplasma-positive increased your likelihood of having sex.

And hoo boy, what they found.

They took a large test sample of infected and uninfected individuals, and rated them (or had others rate them, as the case may be) for a variety of features -- attractiveness (both self-perceived and as perceived by others), perception of healthiness, number of sexual partners, number of minor ailments, body mass index, mate value, handgrip strength, facial fluctuating asymmetry (i.e. asymmetry in features that change, such as how you smile), and facial width-to-height ratio, all of which could feasibly connect to sexual attractiveness.  

Some of the features (like handgrip strength and minor ailment susceptibility) showed no statistically significant difference.  But... well, let me quote you directly from the paper, so you don't think I'm making this up:

[We] found that infected men had lower facial fluctuating asymmetry whereas infected women had lower body mass, lower body mass index, a tendency for lower facial fluctuating asymmetry, higher self-perceived attractiveness, and a higher number of sexual partners than non-infected ones.  Then, we found that infected men and women were rated as more attractive and healthier than non-infected ones...  The present study offers novel evidence supporting the idea that some sexually transmitted parasites such as T. gondii may produce changes in the appearance and behavior of the human host, either as a by-product of the infection or as a result of the manipulation of the parasite to increase its spread to new hosts.

Which is probably why everyone finds me so dashingly handsome, and why my entire adult life I've had to fight off people trying to break down my bedroom door.

(Maybe having toxoplasmosis also makes you more sarcastic, I dunno.)

So.  Yeah.  That's not creepy at all.  Having a brain parasite causes you to look healthier and have a more attractive smile, and makes it more likely you'll get laid.  Who would have thought something that completely bizarre could be real?

Yeah, look at that smile. I bet you a hundred bucks David Tennant has toxoplasmosis. Maybe it even accounts for his amazing hair. [Image licensed under the Creative Commons Rach from Tadcaster, York, England, 2009 07 31 David Tennant smile 09, CC BY 2.0]

Interestingly, I wrote a short story called "The Germ Theory of Disease" (which you can read for free at the link provided) that riffs on this very idea -- a pathogen that makes you more social.  Unfortunately, it also turns you into a werewolf.  (C'mon, it's me we're talking about here, you had to know there'd be a paranormal twist.)

But hell's bells, I thought it was fiction.

And little did I know that I'm very likely to be carrying around a pathogen myself that does just that.  (Well, not the werewolf part.  I hope.)  Sometimes, as Oscar Wilde pointed out, life imitates art just as much as art imitates life.  Or, to quote Mark Twain, "The difference between reality and fiction is that fiction has to be believable."

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Catty behavior

Ever heard of the cui bono principle?

Cui bono? is Latin for "who benefits?"  It's been used for centuries as a central question in criminal cases; to figure out who's guilty of a crime, the first thing to determine is who benefitted from it.  But it is also critical to questions of evolutionary biology.  There are behaviors in the biological world that seem unnecessarily risky, or even suicidal, and it's hard to imagine how they'd be selected for.

So... who benefits?

Take, for example, the strange behavior of certain ants.  Ground-dwelling ants, when threatened, usually have one of two responses; rush out and try to sting or bite whatever's threatening them, or move downward (and underground) to hide.  But some ants were observed to have a third, and bizarre, response: faced with a threat, they climb upwards on plant stems, and then just docilely sit there -- and, frequently, get eaten (along with the plant) by herbivorous animals.

The reason for this weird behavior is positively grotesque.  It turns out that the seemingly-suicidal ants were infected with a brain parasite called a lancet worm (Dicrocoelium dendriticum) that, in order to complete its life cycle, has to pass through the digestive tract and liver of a ruminant (sheep, cow, or goat).  So the worm reprograms the ant's brain to make it do something that will ultimately end up with its being turned into lunch.  

Too bad for the ant.  But cui bono?  The worm, of course.  It hijacked the ant's brain to make it an unwilling participant in the worm's life cycle.

This is hardly the only example of the cui bono principle, and far from the creepiest one.  Ready to get completely skeeved out?

You may know of the pathogen Toxoplasma gondii in its connection to the recommendation by doctors that pregnant women not clean cat litter boxes.  The pathogen, which is neither a bacteria nor a virus but a protist, is carried by cats and excreted with the urine; and a pregnant woman who contracts toxoplasmosis risks birth defects in her unborn child.

Toxoplasma, however, is found in other animals besides cats, and in fact it was some recent research into hyenas that brought it to mind today.  A study out of the University of Colorado that appeared in Nature Communications a few months ago showed that wild populations of hyenas have a high rate of infection, and the weirdest result is seen in infected hyena cubs.  They, like the unfortunate ants, have a behavioral consequence of infection; they become bold, and seem to lose their perception of lions and other predators as dangerous.  They're far more likely to be killed than healthy, uninfected hyena cubs -- which, of course, benefits the pathogen because it then passes on to the lion.  The pathogen, in essence, is programming its host to engage in behavior that will make it more likely to jump to another host.

[Image licensed under the Creative Commons New Jersey Birds, Spotted hyena cubs in Limpopo, CC BY-SA 2.0]

So, a weird and gruesome outcome of being infected with a tropical disease, right?  Nothing for us humans to worry about, right?  Well, what you may not know is that there is a significant likelihood that you have toxoplasmosis right now.  In fact, if you have ever owned a cat, the probability stands close to 100%.

A study done a while back by Kevin Lafferty, of the University of California, suggests that as many as three billion people may have a dormant Toxoplasma infection.  Yes, dear readers, you read that right; that's three billion with a "b," as in a little less than half of the human population.  Turns out that Lafferty's research indicated that when you get toxoplasmosis, you get flu-like symptoms for a couple of days, and then the symptoms abate -- but for most of us, the protist goes dormant, and we carry around the parasite for life.

This is creepy enough, but wait'll you hear what it does to you.

Lafferty's research showed that in mammalian hosts, the Toxoplasma organism invades, and becomes dormant in, the host's brain cells.  Not only hyenas become bolder around predators; mice and rats do, as well, aiding in the passage of the germ between rodents and domestic cats.  Lafferty's study, though, goes a step further, and looks at what latent Toxoplasma infection does to humans -- and he found  it seems to cause significant personality changes.

Now, it doesn't make us have a high affinity for cats, which would make sense, and would explain Crazy Cat Lady Syndrome, in which some people think it's normal to own thirty cats, and somehow seem immune to the truly cataclysmic odor that their houses attain.  No, what actually happens is more subtle.  Apparently, if you have Toxoplasma, you're more likely to be neurotic.  People who tested positive for antibodies for Toxoplasma scored far higher on personality assessments in the areas of guilt-proneness, anxiety, and risk of depression.  These effects were so pronounced that Lafferty speculates that it could account for certain differences between cultures.

"In some cultures, infection is very rare," Lafferty said, "while in others, virtually everyone is infected.  The distribution of Toxoplasma gondii could explain differences in cultural aspects that relate to ego, money, material possessions, work, and rules."

I find this speculation fascinating.  The idea that my neuroses might not be due to my genes or upbringing, but because I'm carrying around a parasite in my brain, doesn't create the level of Icky-Poo Factor that you might expect.  Of course, I'm a biologist, and so I'm at least on some level accustomed to thinking about creepy-crawlies.  But the idea that some sort of a microorganism could affect my behavior strikes me as weirdly interesting, particularly since I've had at least one cat in my household for a significant chunk of the past forty years.

So, maybe our personalities aren't as static as we'd like to think -- they can be influenced by a great many circumstances outside of our control.  Add parasite infestations to that list.  And if that whole idea upsets you too much, take comfort in the fact that Lafferty's research has spurred medical researchers to try to find a drug that can destroy the germ.  Nothing's been certified for human use so far, so don't cancel your appointment with your therapist just yet, but there are a couple that are looking promising.  What's uncertain is whether, if the pathogen were eradicated, it would reverse the changes in the brain -- if, for example, nervous, neurotic people would find themselves less anxiety-prone -- or if the alterations in the brain are more or less permanent.  But I, for one, would volunteer to give it a try, once (or if) the medication becomes available.

Until then, you should probably shouldn't worry.  What's a few brain parasites among friends, after all?  In fact, just forget I brought it up.  Relax, go and sit in your recliner, and pet your cat, Mr. Fluffkins, for a while.

You'll feel better.  Trust me.

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I've mentioned before how fascinated I am with the parts of history that still are largely mysterious -- the top of the list being the European Dark Ages, between the fall of Rome and the re-consolidation of central government under people like Charlemagne and Alfred the Great.  Not all that much was being written down in the interim, and much of the history we have comes from much later (such as History of the Kings of Britain, by Geoffrey of Monmouth, chronicling the events of the fourth through the eighth centuries C.E. -- but written in the twelfth century).

"Dark Ages," though, may be an unfair appellation, according to the new book Matthew Gabriele and David Perry called The Bright Ages: A New History of Medieval Europe.  Gabriele and Perry look at what is known of those years, and their contention is that it wasn't the savage, ignorant hotbed of backwards superstition many of us picture, but a rich and complex world, including the majesty of Byzantium, the beauty and scientific advancements of Moorish Spain, and the artistic genius of the master illuminators found in just about every Christian abbey in Europe.

It's an interesting perspective.  It certainly doesn't settle all the questions; we're still relying on a paucity of actual records, and the ones we have (Geoffrey's work being a case in point) sometimes being as full of legends, myths, and folk tales as they are of actual history.  But The Bright Ages goes a long way toward dispelling the sense that medieval Europe was seven hundred years of nothing but human misery.  It's a fascinating look at humanity's distant, and shadowed, past.

[Note: if you purchase this book using the image/link below, part of the proceeds goes to support Skeptophilia!]