Parasite's and the military conversation w/ROBERT SAPOLSKY

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Parasite's and the military conversation w/ROBERT SAPOLSKY

Postby Grizzly » Tue Jan 17, 2012 11:17 am

Parasite's, Toxoplasma and the military...? Have we found our Manchurian Candidate vetor?

TOXO [12.4.09]
A Conversation with Robert Sapolsky:

want to know something utterly terrifying? Here's something terrifying and not surprising. Folks who know about Toxo and its affect on behavior are in the U.S. military. They're interested in Toxo. They're officially intrigued. And I would think they would be intrigued, studying a parasite that makes mammals perhaps do things that everything in their fiber normally tells them not to because it's dangerous and ridiculous and stupid and don't do it. But suddenly with this parasite on board, the mammal is a little bit more likely you go and do it. Who knows? But they are aware of Toxo.


TOXO

[ROBERT SAPOLSKY:] In the endless sort of struggle that neurobiologists have — in terms of free will, determinism — my feeling has always been that there's not a whole lot of free will out there, and if there is, it's in the least interesting places and getting more sparse all the time. But there's a whole new realm of neuroscience which I've been thinking about, which I'm starting to do research on, that throws in another element of things going on below the surface affecting our behavior. And it's got to do with this utterly bizarre world of parasites manipulating our behavior. It turns out that this is not all that surprising. There are all sorts of parasites out there that get into some organism, and what they need to do is parasitize the organism and increase the likelihood that they, the parasite, will be fruitful and multiply, and in some cases they can manipulate the behavior of the host.

Some of these are pretty astounding. There's this barnacle that rides on the back of some crab and is able to inject estrogenic hormones into the crab if the crab is male, and at that point, the male's behavior becomes feminized. The male crab digs a hole in the sand for his eggs, except he has no eggs, but the barnacle sure does, and has just gotten this guy to build a nest for him. There are other ones where wasps parasitize caterpillars and get them to defend the wasp's nests for them. These are extraordinary examples.

The parasite my lab is beginning to focus on is one in the world of mammals, where parasites are changing mammalian behavior. It's got to do with this parasite, this protozoan called Toxoplasma. If you're ever pregnant, if you're ever around anyone who's pregnant, you know you immediately get skittish about cat feces, cat bedding, cat everything, because it could carry Toxo. And you do not want to get Toxoplasma into a fetal nervous system. It's a disaster.

The normal life cycle for Toxo is one of these amazing bits of natural history. Toxo can only reproduce sexually in the gut of a cat. It comes out in the cat feces, feces get eaten by rodents. And Toxo's evolutionary challenge at that point is to figure out how to get rodents inside cats' stomachs. Now it could have done this in really unsubtle ways, such as cripple the rodent or some such thing. Toxo instead has developed this amazing capacity to alter innate behavior in rodents.

If you take a lab rat who is 5,000 generations into being a lab rat, since the ancestor actually ran around in the real world, and you put some cat urine in one corner of their cage, they're going to move to the other side. Completely innate, hard-wired reaction to the smell of cats, the cat pheromones. But take a Toxo-infected rodent, and they're no longer afraid of the smell of cats. In fact they become attracted to it. The most damn amazing thing you can ever see, Toxo knows how to make cat urine smell attractive to rats. And rats go and check it out and that rat is now much more likely to wind up in the cat's stomach. Toxo's circle of life completed.

This was reported by a group in the UK about half a dozen years ago. Not a whole lot was known about what Toxo was doing in the brain, so ever since, part of my lab has been trying to figure out the neurobiological aspects. The first thing is that it's for real. The rodents, rats, mice, really do become attracted to cat urine when they've been infected with Toxo. And you might say, okay, well, this is a rodent doing just all sorts of screwy stuff because it's got this parasite turning its brain into Swiss cheese or something. It's just non-specific behavioral chaos. But no, these are incredibly normal animals. Their olfaction is normal, their social behavior is normal, their learning and memory is normal. All of that. It's not just a generically screwy animal.

You say, okay well, it's not that, but Toxo seems to know how to destroy fear and anxiety circuits. But it's not that, either. Because these are rats who are still innately afraid of bright lights. They're nocturnal animals. They're afraid of big, open spaces. You can condition them to be afraid of novel things. The system works perfectly well there. Somehow Toxo can laser out this one fear pathway, this aversion to predator odors.

We started looking at this. The first thing we did was introduce Toxo into a rat and it took about six weeks for it to migrate from its gut up into its nervous system. And at that point, we looked to see, where has it gone in the brain? It formed cysts, sort of latent, encapsulated cysts, and it wound up all over the brain. That was deeply disappointing.

But then we looked at how much winds up in different areas in the brain, and it turned out Toxo preferentially knows how to home in on the part of the brain that is all about fear and anxiety, a brain region called the amygdala. The amygdala is where you do your fear conditioning; the amygdala is what's hyperactive in people with post-traumatic stress disorder; the amygdala is all about pathways of predator aversion, and Toxo knows how to get in there.

Next, we then saw that Toxo would take the dendrites, the branch and cables that neurons have to connect to each other, and shriveled them up in the amygdala. It was disconnecting circuits. You wind up with fewer cells there. This is a parasite that is unwiring this stuff in the critical part of the brain for fear and anxiety. That's really interesting. That doesn't tell us a thing about why only its predator aversion has been knocked outwhereas fear of bright lights, et cetera, is still in there. It knows how to find that particular circuitry.

So what's going on from there? What's it doing? Because it's not just destroying this fear aversive response, it's creating something new. It's creating an attraction to the cat urine. And here is where this gets utterly bizarre. You look at circuitry in the brain, and there's a reasonably well-characterized circuit that activates neurons which become metabolically active circuits where they're talking to each other, a reasonably well-understood process that's involved in predator aversion. It involves neurons in the amygdala, the hypothalamus, and some other brain regions getting excited. This is a very well characterized circuit.

Meanwhile, there is a well-characterized circuit that has to do with sexual attraction. And as it happens, part of this circuit courses through the amygdala, which is pretty interesting in and of itself, and then goes to different areas of the brain than the fear pathways.

When you look at normal rats, and expose them to cat urine, cat pheromones, exactly as you would expect, they have a stress response: their stress hormone levels go up, and they activate this classical fear circuitry in the brain. Now you take Toxo-infected rats, right around the time when they start liking the smell of cat urine, you expose them to cat pheromones, and you don't see the stress hormone release. What you see is that the fear circuit doesn't activate normally, and instead the sexual arousal activates some. In other words, Toxo knows how to hijack the sexual reward pathway. And you get males infected with Toxo and expose them to a lot of the cat pheromones, and their testes get bigger. Somehow, this damn parasite knows how to make cat urine smell sexually arousing to rodents, and they go and check it out. Totally amazing.

So on a certain level, that explains everything. Ah ha! It takes over sexual arousal circuitry. This is utterly bizarre. At this point, we don't know what the basis is of the attraction in the females. It's something we're working on.

Some extremely nice work has been done by a group at Leeds in the UK, who are looking at the Toxo genome, and we're picking up on this collaboratively. Okay, Toxo, it's a protozoan parasite. Toxo and mammals had a common ancestor, and the last they did was God knows, billions of years ago. And you look in the Toxo genome, and it's got two versions of the gene called tyrosine hydroxylase. And if you were a neuro-chemistry type, you would be leaping up in shock and excitement at this point.

Tyrosine hydroxylase is the critical enzyme for making dopamine: the neurotransmitter in the brain that's all about reward and anticipation of reward. Cocaine works on the dopamine system, all sorts of other euphoriants do. Dopamine is about pleasure, attraction and anticipation. And the Toxo genome has the mammalian gene for making the stuff. It's got a little tail on the gene that targets, specifies, that when this is turned into the actual enzyme, it gets secreted out of the Toxo and into neurons. This parasite doesn't need to learn how to make neurons act as if they are pleasurably anticipatory; it takes over the brain chemistry of it all on its own.

Again that issue of specificity comes up. Look at closely related parasites to Toxo: do they have this gene? Absolutely not. Now look at the Toxo genome and look at genes related to other brain messengers. Serotonin, acetylcholine, norepinephrine, and so on, and you go through every single gene you can think of. Zero. Toxo doesn't have them, Toxo's got this one gene which allows it to just plug into the whole world of mammalian reward systems. And at this point, that's what we know. It is utterly cool.

Of course, at this point, you say well, what about other species? What does Toxo do to humans? And there's some interesting stuff there that's reminiscent of what's going on in rodents. Clinical dogma is you first get a Toxo infection. If you're pregnant, it gets into the fetal nervous system, a huge disaster. Otherwise, if you get a Toxo infection, it has phases of inflammation, but eventually it goes into this latent asymptomatic stage, which is when these cysts form in the brain. Which is, in a rat, when it stops being anything boring like asymptomatic, and when the behavior starts occurring. Interestingly, that's when the parasite starts making this tyrosine hydroxylase.

So what about humans? A small literature is coming out now reporting neuropsychological testing on men who are Toxo-infected, showing that they get a little bit impulsive. Women less so, and this may have some parallels perhaps with this whole testosterone aspect of the story that we're seeing. And then the truly astonishing thing: two different groups independently have reported that people who are Toxo-infected have three to four times the likelihood of being killed in car accidents involving reckless speeding.

In other words, you take a Toxo-infected rat and it does some dumb-ass thing that it should be innately skittish about, like going right up to cat smells. Maybe you take a Toxo-infected human and they start having a proclivity towards doing dumb-ass things that we should be innately averse to, like having your body hurdle through space at high G-forces. Maybe this is the same neurobiology. This is not to say that Toxo has evolved the need to get humans into cat stomachs. It's just sheer convergence. It's the same nuts and bolts neurobiology in us and in a rodent, and does the same thing.

On a certain level, this is a protozoan parasite that knows more about the neurobiology of anxiety and fear than 25,000 neuroscientists standing on each other's shoulders, and this is not a rare pattern. Look at the rabies virus; rabies knows more about aggression than we neuroscientists do. It knows how to make you rabid. It knows how to make you want to bite someone, and that saliva of yours contains rabies virus particles, passed on to another person.

The Toxo story is, for me, completely new terrain — totally cool, interesting stuff, just in terms of this individual problem. And maybe it's got something to do with treatments for phobias down the line or whatever it is to make it seem like anything more than just the coolest gee whiz thing possible. But no doubt it's also a tip of the iceberg of God knows what other parasitic stuff is going on out there. Even in the larger sense, God knows what other unseen realms of biology make our behavior far less autonomous than lots of folks would like to think.

With regard to parasite infections like Toxo in humans, there is a big prevalence in certain parts of the world. There's a higher prevalence in the tropics, where typically more than 50 percent of people are infected. Lower rates in more temperate zones for reasons that I do not understand and do not choose to speculate on. France has really high rates of Toxo infection. In much of the developing world, it's bare feet, absorbing it through soil, where cats may have been. It's food that may not have been washed sufficiently and absorption through hands. It's the usual story that people in the developing world are more subject to all sorts of infectious stuff.

A few years ago, I sat down with a couple of the Toxo docs over in our hospital who do the Toxo testing in the Ob/Gyn clinics. And they hadn't heard about this behavioral story, and I'm going on about how cool and unexpected it is. And suddenly, one of them jumps up, flooded with 40-year-old memories, and says, "I just remembered back when I was a resident, I was doing a surgical transplant rotation. And there was an older surgeon, who said, if you ever get organs from a motorcycle accident death, check the organs for Toxo. I don't know why, but you find a lot of Toxo." And you could see this guy was having a rush of nostalgic memories from back when he was 25 and all because he was being told this weird factoid ... ooh, people who die in motorcycle accidents seem to have high rates of Toxo. Utterly bizarre.

What is the bottom line on this? Well, it depends; if you want to overcome some of your inhibitions, Toxo might be a very good thing to have in your system. Not surprisingly, ever since we started studying Toxo in my lab, every lab meeting we sit around speculating about which people in the lab are Toxo-infected, and that might have something to do with one's level of recklessness. Who knows? It's very interesting stuff, though.

You want to know something utterly terrifying? Here's something terrifying and not surprising. Folks who know about Toxo and its affect on behavior are in the U.S. military. They're interested in Toxo. They're officially intrigued. And I would think they would be intrigued, studying a parasite that makes mammals perhaps do things that everything in their fiber normally tells them not to because it's dangerous and ridiculous and stupid and don't do it. But suddenly with this parasite on board, the mammal is a little bit more likely you go and do it. Who knows? But they are aware of Toxo.

There are two groups that collaborate in Toxo research. One is Joanne Webster, who was at Oxford at the time that she first saw this behavioral phenomenon. And I believe she's now at University College London. And the other is Glenn McConkey at University of Leeds. And they're on this. She's more of a behaviorist, he's more of an enzyme biochemist guy. We're doing the neurobiology end of it. We're all talking lots.

There's a long-standing literature that absolutely shows there's a statistical link between Toxo infection and schizophrenia. It's not a big link, but it's solidly there. Schizophrenics have higher than expected rates of having been infected with Toxo, and not particularly the case for other related parasites. Links between schizophrenia and mothers who had house cats during pregnancy. There's a whole literature on that. So where does this fit in?

Two really interesting things. Back to dopamine and the tyrosine hydroxylase gene that Toxo somehow ripped off from mammals, which allows it to make more dopamine. Dopamine levels are too high in schizophrenia. That's the leading suggestion of what schizophrenia is about neurochemically. You take Toxo-infected rodents and their brains have elevated levels of dopamine. Final deal is, and this came from Webster's group, you take a rat who's been Toxo-infected and is now at the state where it would find cat urine to be attractive, and you give it drugs that block dopamine receptors, the drugs that are used to treat schizophrenics, and it stops being attracted to the cat urine. There is some schizophrenia connection here with this.

Any time Toxo's picked up in the media, and this schizophrenia angle is brought in, the irresistible angle is the generic crazy cat lady, you know, living in the apartment with 43 cats and their detritus. And that's an irresistible one in terms of Toxo psychiatric status: cats. But God knows what stuff is lurking there.


http://edge.org/3rd_culture/sapolsky09/ ... html#video
Last edited by Grizzly on Tue Jan 17, 2012 11:49 am, edited 1 time in total.
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby NeonLX » Tue Jan 17, 2012 11:25 am

Darn it, I love cats.
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby slomo » Tue Jan 17, 2012 11:51 am

I have long held that our true overlords are the single-celled organisms. Bacteria is truly an amazing life form, as are the protozoa.

You don't know anything about the spirit world until you appreciate the biological domains of the Fungi, the Eubacteria, the Archaebacteria, and the Protista. Plantae and Animalia are late comers to the cosmic party.
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby slomo » Tue Jan 17, 2012 12:02 pm

I will add that the widespread use of antibiotics and antibacterials - especially the popularity of that singularly American abomination, antibacterial handsoap - is tantamount to a declaration of war on the spirit world.

Contemplate this idea in the context of the hygiene hypothesis, MRSA, and the perniciousness of purity metaphors and you'll begin to see what I mean.
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby Twyla LaSarc » Tue Jan 17, 2012 2:01 pm

Perhaps now we see the reason Egyptians worshipped cats- they substituted their own urine for that of rodents, and egyptians, looking only at the savings in wheat, thought this a good thing.

I for one welcome our feline overlords.

Slomo's observations above are food for thought, although I've, up to this point, merely thought antibacterial handsoap to be fussy and phobic anywhere outside of a purely medical setting.
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby crikkett » Tue Jan 17, 2012 2:22 pm

slomo wrote:I will add that the widespread use of antibiotics and antibacterials - especially the popularity of that singularly American abomination, antibacterial handsoap - is tantamount to a declaration of war on the spirit world.

Contemplate this idea in the context of the hygiene hypothesis, MRSA, and the perniciousness of purity metaphors and you'll begin to see what I mean.


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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby eyeno » Wed Jan 18, 2012 4:36 pm

I shall immediately cease using antiperspirant.



Might not be a bad idea. Much of it is full of aluminum and other harmful things that work their way through the pores of the skin and into the body. :shock2:
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby Wombaticus Rex » Wed Jan 18, 2012 9:18 pm

That's a wild little revelation. Thanks for this.
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby smoking since 1879 » Wed Jan 18, 2012 10:41 pm

http://cathealthcentral.org/cats-health-faq/are-parasites-messing-with-our-minds-461012.html

All in the mind? > New Scientist vol 176 issue 2366 – 26 October 2002, page 41 > Suspicion is growing that one of the most common human parasites in the > world is messing with our minds. James Randerson reports > HAVE you been acting out of character lately? Are you having trouble > concentrating? Don’t blame late nights or old age – you might be at the > mercy of a mind-altering parasite. A microscopic beast lying low in your > brain may be exercising a subtle form of thought control, turning you into > somebody slightly different.

I couldn't find an online version of the original, but some interesting info there nonetheless.

EDIT:
original is here if you have an account...
http://www.newscientist.com/article/mg17623665.200-all-in-the-mind.html
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby Luther Blissett » Thu Feb 09, 2012 11:07 am

I think McAuliffe is likely a coward – because the most interesting aspect of this subject, at least to me, is the military's interest (as per Savolsky). I'm sure he mentioned it to her, and even if he didn't, it should be a natural journalistic question.

Previous threads:
The Return of the Puppet Masters
Behold, again: Toxoplasma
Zombie ants controlled by parasitic fungus for 48m years

How Your Cat Is Making You Crazy

Jaroslav Flegr is no kook. And yet, for years, he suspected his mind had been taken over by parasites that had invaded his brain. Could tiny organisms carried by house cats be creeping into our brains, causing everything from car wrecks to schizophrenia? A biologist’s science- fiction hunch is gaining credence and shaping the emerging science of mind- controlling parasites.

No one would accuse Jaroslav Flegr of being a conformist. A self-described “sloppy dresser,” the 63-year-old Czech scientist has the contemplative air of someone habitually lost in thought, and his still-youthful, square-jawed face is framed by frizzy red hair that encircles his head like a ring of fire.

Certainly Flegr’s thinking is jarringly unconventional. Starting in the early 1990s, he began to suspect that a single-celled parasite in the protozoan family was subtly manipulating his personality, causing him to behave in strange, often self-destructive ways. And if it was messing with his mind, he reasoned, it was probably doing the same to others.

The parasite, which is excreted by cats in their feces, is called Toxoplasma gondii (T. gondii or Toxo for short) and is the microbe that causes toxoplasmosis—the reason pregnant women are told to avoid cats’ litter boxes. Since the 1920s, doctors have recognized that a woman who becomes infected during pregnancy can transmit the disease to the fetus, in some cases resulting in severe brain damage or death. T. gondii is also a major threat to people with weakened immunity: in the early days of the AIDS epidemic, before good antiretroviral drugs were developed, it was to blame for the dementia that afflicted many patients at the disease’s end stage. Healthy children and adults, however, usually experience nothing worse than brief flu-like symptoms before quickly fighting off the protozoan, which thereafter lies dormant inside brain cells—or at least that’s the standard medical wisdom.

But if Flegr is right, the “latent” parasite may be quietly tweaking the connections between our neurons, changing our response to frightening situations, our trust in others, how outgoing we are, and even our preference for certain scents. And that’s not all. He also believes that the organism contributes to car crashes, suicides, and mental disorders such as schizophrenia. When you add up all the different ways it can harm us, says Flegr, “Toxoplasma might even kill as many people as malaria, or at least a million people a year.”

An evolutionary biologist at Charles University in Prague, Flegr has pursued this theory for decades in relative obscurity. Because he struggles with English and is not much of a conversationalist even in his native tongue, he rarely travels to scientific conferences. That “may be one of the reasons my theory is not better known,” he says. And, he believes, his views may invite deep-seated opposition. “There is strong psychological resistance to the possibility that human behavior can be influenced by some stupid parasite,” he says. “Nobody likes to feel like a puppet. Reviewers [of my scientific papers] may have been offended.” Another more obvious reason for resistance, of course, is that Flegr’s notions sound an awful lot like fringe science, right up there with UFO sightings and claims of dolphins telepathically communicating with humans.

But after years of being ignored or discounted, Flegr is starting to gain respectability. Psychedelic as his claims may sound, many researchers, including such big names in neuroscience as Stanford’s Robert Sapolsky, think he could well be onto something. Flegr’s “studies are well conducted, and I can see no reason to doubt them,” Sapolsky tells me. Indeed, recent findings from Sapolsky’s lab and British groups suggest that the parasite is capable of extraordinary shenanigans. T. gondii, reports Sapolsky, can turn a rat’s strong innate aversion to cats into an attraction, luring it into the jaws of its No. 1 predator. Even more amazing is how it does this: the organism rewires circuits in parts of the brain that deal with such primal emotions as fear, anxiety, and sexual arousal. “Overall,” says Sapolsky, “this is wild, bizarre neurobiology.” Another academic heavyweight who takes Flegr seriously is the schizophrenia expert E. Fuller Torrey, director of the Stanley Medical Research Institute, in Maryland. “I admire Jaroslav for doing [this research],” he says. “It’s obviously not politically correct, in the sense that not many labs are doing it. He’s done it mostly on his own, with very little support. I think it bears looking at. I find it completely credible.”

What’s more, many experts think T. gondii may be far from the only microscopic puppeteer capable of pulling our strings. “My guess is that there are scads more examples of this going on in mammals, with parasites we’ve never even heard of,” says Sapolsky.

Familiar to most of us, of course, is the rabies virus. On the verge of killing a dog, bat, or other warm-blooded host, it stirs the animal into a rage while simultaneously migrating from the nervous system to the creature’s saliva, ensuring that when the host bites, the virus will live on in a new carrier. But aside from rabies, stories of parasites commandeering the behavior of large-brained mammals are rare. The far more common victims of parasitic mind control—at least the ones we know about—are fish, crustaceans, and legions of insects, according to Janice Moore, a behavioral biologist at Colorado State University. “Flies, ants, caterpillars, wasps, you name it—there are truckloads of them behaving weirdly as a result of parasites,” she says.

Consider Polysphincta gutfreundi, a parasitic wasp that grabs hold of an orb spider and attaches a tiny egg to its belly. A wormlike larva emerges from the egg, and then releases chemicals that prompt the spider to abandon weaving its familiar spiral web and instead spin its silk thread into a special pattern that will hold the cocoon in which the larva matures. The “possessed” spider even crochets a specific geometric design in the net, camouflaging the cocoon from the wasp’s predators.

Flegr himself traces his life’s work to another master of mind control. Almost 30 years ago, as he was reading a book by the British evolutionary biologist Richard Dawkins, Flegr was captivated by a passage describing how a flatworm turns an ant into its slave by invading the ant’s nervous system. A drop in temperature normally causes ants to head underground, but the infected insect instead climbs to the top of a blade of grass and clamps down on it, becoming easy prey for a grazing sheep. “Its mandibles actually become locked in that position, so there’s nothing the ant can do except hang there in the air,” says Flegr. The sheep grazes on the grass and eats the ant; the worm gains entrance into the ungulate’s gut, which is exactly where it needs to be in order to complete—as the Lion King song goes—the circle of life. “It was the first I learned about this kind of manipulation, so it made a big impression on me,” Flegr says.

After he read the book, Flegr began to make a connection that, he readily admits, others might find crazy: his behavior, he noticed, shared similarities with that of the reckless ant. For example, he says, he thought nothing of crossing the street in the middle of dense traffic, “and if cars honked at me, I didn’t jump out of the way.” He also made no effort to hide his scorn for the Communists who ruled Czechoslovakia for most of his early adulthood. “It was very risky to openly speak your mind at that time,” he says. “I was lucky I wasn’t imprisoned.” And during a research stint in eastern Turkey, when the strife-torn region frequently erupted in gunfire, he recalls being “very calm.” In contrast, he says, “my colleagues were terrified. I wondered what was wrong with myself.”

His bewilderment continued until 1990, when he joined the biology faculty of Charles University. As it happened, the 650-year-old institution had long been a world leader in documenting the health effects of T. gondii, as well as developing methods for detecting the parasite. In fact, just as Flegr was arriving, his colleagues were searching for infected individuals on whom to test their improved diagnostic kits, which is how he came to be asked one day to roll up his sleeve and donate blood. He discovered that he had the parasite—and just possibly, he thought, the key to his baffling self-destructive streak.

He delved into T. gondii’s life cycle. After an infected cat defecates, Flegr learned, the parasite is typically picked up from the soil by scavenging or grazing animals—notably rodents, pigs, and cattle—all of which then harbor it in their brain and other body tissues. Humans, on the other hand, are exposed not only by coming into contact with litter boxes, but also, he found, by drinking water contaminated with cat feces, eating unwashed vegetables, or, especially in Europe, by consuming raw or undercooked meat. Hence the French, according to Flegr, with their love of steak prepared saignant—literally, “bleeding”—can have infection rates as high as 55 percent. (Americans will be happy to hear that the parasite resides in far fewer of them, though a still substantial portion: 10 to 20 percent.) Once inside an animal or human host, the parasite then needs to get back into the cat, the only place where it can sexually reproduce—and this is when, Flegr believed, behavioral manipulation might come into play.

Researchers had already observed a few peculiarities about rodents with T. gondii that bolstered Flegr’s theory. The infected rodents were much more active in running wheels than uninfected rodents were, suggesting that they would be more-attractive targets for cats, which are drawn to fast-moving objects. They also were less wary of predators in exposed spaces. Little, however, was known about how the latent infection might influence humans, because we and other large mammals were widely presumed to be accidental hosts, or, as scientists are fond of putting it, a “dead end” for the parasite. But even if we were never part of the parasite’s life cycle, Flegr reasoned, mammals from mouse to man share the vast majority of their genes, so we might, in a case of mistaken identity, still be vulnerable to manipulations by the parasite.

In the Soviet-stunted economy, animal studies were way beyond Flegr’s research budget. But fortunately for him, 30 to 40 percent of Czechs had the latent form of the disease, so plenty of students were available “to serve as very cheap experimental animals.” He began by giving them and their parasite-free peers standardized personality tests—an inexpensive, if somewhat crude, method of measuring differences between the groups. In addition, he used a computer-based test to assess the reaction times of participants, who were instructed to press a button as soon as a white square popped up anywhere against the dark background of the monitor.

The subjects who tested positive for the parasite had significantly delayed reaction times. Flegr was especially surprised to learn, though, that the protozoan appeared to cause many sex-specific changes in personality. Compared with uninfected men, males who had the parasite were more introverted, suspicious, oblivious to other people’s opinions of them, and inclined to disregard rules. Infected women, on the other hand, presented in exactly the opposite way: they were more outgoing, trusting, image-conscious, and rule-abiding than uninfected women.

The findings were so bizarre that Flegr initially assumed his data must be flawed. So he tested other groups—civilian and military populations. Again, the same results. Then, in search of more corroborating evidence, he brought subjects in for further observation and a battery of tests, in which they were rated by someone ignorant of their infection status. To assess whether participants valued the opinions of others, the rater judged how well dressed they appeared to be. As a measure of gregariousness, participants were asked about the number of friends they’d interacted with over the past two weeks. To test whether they were prone to being suspicious, they were asked, among other things, to drink an unidentified liquid.

The results meshed well with the questionnaire findings. Compared with uninfected people of the same sex, infected men were more likely to wear rumpled old clothes; infected women tended to be more meticulously attired, many showing up for the study in expensive, designer-brand clothing. Infected men tended to have fewer friends, while infected women tended to have more. And when it came to downing the mystery fluid, reports Flegr, “the infected males were much more hesitant than uninfected men. They wanted to know why they had to do it. Would it harm them?” In contrast, the infected women were the most trusting of all subjects. “They just did what they were told,” he says.

Why men and women reacted so differently to the parasite still mystified him. After consulting the psychological literature, he started to suspect that heightened anxiety might be the common denominator underlying their responses. When under emotional strain, he read, women seek solace through social bonding and nurturing. In the lingo of psychologists, they’re inclined to “tend and befriend.” Anxious men, on the other hand, typically respond by withdrawing and becoming hostile or antisocial. Perhaps he was looking at flip sides of the same coin.

Closer inspection of Flegr’s reaction-time results revealed that infected subjects became less attentive and slowed down a minute or so into the test. This suggested to him that Toxoplasma might have an adverse impact on driving, where constant vigilance and fast reflexes are critical. He launched two major epidemiological studies in the Czech Republic, one of men and women in the general population and another of mostly male drivers in the military. Those who tested positive for the parasite, both studies showed, were about two and a half times as likely to be in a traffic accident as their uninfected peers.

When I met Flegr for the first time, last September, at his office on the third floor of Charles University’s Biological Sciences building, I was expecting something of a wild man. But once you get past the riotous red hair, his style is understated. Thin and slight of build, he’s soft-spoken, precise with his facts, and—true to his Toxo status—clad in old sneakers, faded bell-bottom jeans, and a loose-fitting button-up shirt. As our conversation proceeds, I discover that his latest findings have become—to quote Alice in Wonderland—“curiouser and curiouser,” which may explain why his forehead has the deep ruts of a chronic worrier, or someone perpetually perplexed.

He’s published some data, he tells me, that suggest infected males might have elevated testosterone levels. Possibly for that reason, women shown photos of these men rate them as more masculine than pictures of uninfected men. “I want to investigate this more closely to see if it’s true,” he says. “Also, it could be women find infected men more attractive. That’s something else we hope to test.”

Meanwhile, two Turkish studies have replicated his studies linking Toxoplasma to traffic accidents. With up to one-third of the world infected with the parasite, Flegr now calculates that T. gondii is a likely factor in several hundred thousand road deaths each year. In addition, reanalysis of his personality-questionnaire data revealed that, just like him, many other people who have the latent infection feel intrepid in dangerous situations. “Maybe,” he says, “that’s another reason they get into traffic accidents. They don’t have a normal fear response.”

It’s almost impossible to hear about Flegr’s research without wondering whether you’re infected—especially if, like me, you’re a cat owner, favor very rare meat, and identify even a little bit with your Toxo sex stereotype. So before coming to Prague, I’d gotten tested for the parasite, but I didn’t yet know the results. It seemed a good time to see what his intuition would tell me. “Can you guess from observing someone whether they have the parasite—myself, for example?,” I ask.

“No,” he says, “the parasite’s effects on personality are very subtle.” If, as a woman, you were introverted before being infected, he says, the parasite won’t turn you into a raving extrovert. It might just make you a little less introverted. “I’m very typical of Toxoplasma males,” he continues. “But I don’t know whether my personality traits have anything to do with the infection. It’s impossible to say for any one individual. You usually need about 50 people who are infected and 50 who are not, in order to see a statistically significant difference. The vast majority of people will have no idea they’re infected.”

Still, he concedes, the parasite could be very bad news for a small percentage of people—and not just those who might be at greater risk for car accidents. Many schizophrenia patients show shrinkage in parts of their cerebral cortex, and Flegr thinks the protozoan may be to blame for that. He hands me a recently published paper on the topic that he co-authored with colleagues at Charles University, including a psychiatrist named Jiri Horacek. Twelve of 44 schizophrenia patients who underwent MRI scans, the team found, had reduced gray matter in the brain—and the decrease occurred almost exclusively in those who tested positive for T. gondii. After reading the abstract, I must look stunned, because Flegr smiles and says, “Jiri had the same response. I don’t think he believed it could be true.” When I later speak with Horacek, he admits to having been skeptical about Flegr’s theory at the outset. When they merged the MRI results with the infection data, however, he went from being a doubter to being a believer. “I was amazed at how pronounced the effect was,” he says. “To me that suggests the parasite may trigger schizophrenia in genetically susceptible people.”

One might be tempted to dismiss the bulk of Flegr’s work as hokum—the fanciful imaginings of a lone, eccentric scholar—were it not for the pioneering research of Joanne Webster, a parasitologist at Imperial College London. Just as Flegr was embarking on his human trials, Webster, then a freshly minted Ph.D., was launching studies of Toxo-infected rodents, reasoning, just as Flegr did, that as hosts of the parasite, they would be likely targets for behavioral manipulation.

She quickly confirmed, as previous researchers had shown, that infected rats were more active and less cautious in areas where predators lurk. But then, in a simple, elegant experiment, she and her colleagues demonstrated that the parasite did something much more remarkable. They treated one corner of each rat’s enclosure with the animal’s own odor, a second with water, a third with cat urine, and the last corner with the urine of a rabbit, a creature that does not prey on rodents. “We thought the parasite might reduce the rats’ aversion to cat odor,” she told me. “Not only did it do that, but it actually increased their attraction. They spent more time in the cat-treated areas.” She and other scientists repeated the experiment with the urine of dogs and minks, which also prey on rodents. The effect was so specific to cat urine, she says, that “we call it ‘fatal feline attraction.’”

She began tagging the parasite with fluorescent markers and tracking its progress in the rats’ bodies. Given the surgically precise way the microbe alters behavior, Webster anticipated that it would end up in localized regions of the brain. But the results defied expectations. “We were quite surprised to find the cysts—the parasite’s dormant form—all over the brain in what otherwise appeared to be a happy, healthy rat,” she says. Nonetheless, the cysts were most abundant in a part of the brain that deals with pleasure (in human terms, we’re talking sex, drugs, and rock and roll) and in another area that’s involved in fear and anxiety (post-traumatic stress disorder affects this region of the brain). Perhaps, she thought, T. gondii uses a scattershot approach, disseminating cysts far and wide, enabling a few of them to zero in on the right targets.

To gain more clarity on the matter, she sought the aid of the parasitologist Glenn McConkey, whose team at the University of Leeds was probing the protozoan’s genome for signs of what it might be doing. The approach brought to light a striking talent of the parasite: it has two genes that allow it to crank up production of the neurotransmitter dopamine in the host brain. “We never cease to be amazed by the sophistication of these parasites,” Webster says.

Their findings, reported last summer, created immediate buzz. Dopamine is a critical signaling molecule involved in fear, pleasure, and attention. Furthermore, the neurotransmitter is known to be jacked up in people with schizophrenia—another one of those strange observations about the disease, like its tendency to erode gray matter, that have long puzzled medical researchers. Antipsychotic medicine designed to quell schizophrenic delusions apparently blocks the action of dopamine, which had suggested to Webster that what it might really be doing is thwarting the parasite. Scientists had already shown that adding the medicine to a petri dish where T. gondii is happily dividing will stunt the organism’s growth. So Webster decided to feed the antipsychotic drug to newly infected rats to see how they reacted. Lo and behold, they didn’t develop fatal feline attraction. Suddenly, attributing behavioral changes to the microbe seemed much more plausible.

As the scientific community digested the British team’s dopamine discoveries, Robert Sapolsky’s lab at Stanford announced still more attention-grabbing news. The neuroscientist and his colleagues found that T. gondii disconnects fear circuits in the brain, which might help to explain why infected rats lose their aversion to cat odor. Just as startling, reports Sapolsky, the parasite simultaneously is “able to hijack some of the circuitry related to sexual arousal” in the male rat—probably, he theorizes, by boosting dopamine levels in the reward-processing part of the brain. So when the animal catches a whiff of cat scent, the fear center fails to fully light up, as it would in a normal rat, and instead the area governing sexual pleasure begins to glow. “In other words,” he says, “Toxo makes cat odor smell sexy to male rats.”

The neurobiologist Ajai Vyas, after working with Sapolsky on this study as a postdoctoral student, decided to inspect infected rats’ testicles for signs of cysts. Sure enough, he found them there—as well as in the animals’ semen. And when the rat copulates, Vyas discovered, the protozoan moves into the female’s womb, typically infecting 60 percent of her pups, before traveling on up to her own brain—creating still more vehicles for ferrying the parasite back into the belly of a cat.

Could T. gondii be a sexually transmitted disease in humans too? “That’s what we hope to find out,” says Vyas, who now works at Nanyang Technological University, in Singapore. The researchers also discovered that infected male rats suddenly become much more attractive to females. “It’s a very strong effect,” says Vyas. “Seventy-five percent of the females would rather spend time with the infected male.”

After I return from Prague, Flegr informs me that he’s just had a paper accepted for publication that, he claims, “proves fatal feline attraction in humans.” By that he means that infected men like the smell of cat pee—or at least they rank its scent much more favorably than uninfected men do. Displaying the characteristic sex differences that define many Toxo traits, infected women have the reverse response, ranking the scent even more offensive than do women free of the parasite. The sniff test was done blind and also included urine collected from a dog, horse, hyena, and tiger. Infection did not affect how subjects rated these other samples.

“Is it possible cat urine may be an aphrodisiac for infected men?,” I ask. “Yes. It’s possible. Why not?” says Flegr. I think he’s smiling at the other end of the phone line, but I’m not sure, which leaves me wondering whether I’ve stumbled onto a topic ripe for a Saturday Night Live skit, or a matter worthy of medical concern. When I ask Sapolsky about Flegr’s most recent research, he says the effects Flegr is reporting “are incredibly cool. However, I’m not too worried, in that the effects on humans are not gigantic. If you want to reduce serious car accidents, and you had to choose between curing people of Toxo infections versus getting people not to drive drunk or while texting, go for the latter in terms of impact.”

In fact, Sapolsky thinks that Toxo’s inventiveness might even offer us some benefits. If we can figure out how the parasite makes animals less fearful, he says, it might give us insights into how to devise treatments for people plagued by social-anxiety disorder, phobias, PTSD, and the like. “But frankly,” he adds, “this mostly falls into the ‘Get a load of this, can you believe what nature has come up with?’ category.”

Webster is more circumspect, if not downright troubled. “I don’t want to cause any panic,” she tells me. “In the vast majority of people, there will be no ill effects, and those who are affected will mostly demonstrate subtle shifts of behavior. But in a small number of cases, [Toxo infection] may be linked to schizophrenia and other disturbances associated with altered dopamine levels—for example, obsessive-compulsive disorder, attention-deficit hyperactivity disorder, and mood disorders. The rat may live two or three years, while humans can be infected for many decades, which is why we may be seeing these severe side effects in people. We should be cautious of dismissing such a prevalent parasite.”

The psychiatrist E. Fuller Torrey agrees—though he came to this viewpoint from a completely different angle than either Webster or Flegr. His opinion stems from decades of research into the root causes of schizophrenia. “Textbooks today still make silly statements that schizophrenia has always been around, it’s about the same incidence all over the world, and it’s existed since time immemorial,” he says. “The epidemiology literature contradicts that completely.” In fact, he says, schizophrenia did not rise in prevalence until the latter half of the 18th century, when for the first time people in Paris and London started keeping cats as pets. The so-called cat craze began among “poets and left-wing avant-garde Greenwich Village types,” says Torrey, but the trend spread rapidly—and coinciding with that development, the incidence of schizophrenia soared.

Since the 1950s, he notes, about 70 epidemiology studies have explored a link between schizophrenia and T. gondii. When he and his colleague Robert Yolken, a neurovirologist at Johns Hopkins University, surveyed a subset of these papers that met rigorous scientific standards, their conclusion complemented the Prague group’s discovery that schizophrenic patients with Toxo are missing gray matter in their brains. Torrey and Yolken found that the mental illness is two to three times as common in people who have the parasite as in controls from the same region.

Human-genome studies, both scientists believe, are also in keeping with that finding—and might explain why schizophrenia runs in families. The most replicated result from that line of investigation, they say, suggests that the genes most commonly associated with schizophrenia relate to the immune system and how it reacts to infectious agents. So in many cases where the disease appears to be hereditary, they theorize, what may in fact be passed down is an aberrant or deficient immune response to invaders like T. gondii.

Epstein-Barr virus, mumps, rubella, and other infectious agents, they point out, have also been linked to schizophrenia—and there are probably more as yet unidentified triggers, including many that have nothing to do with pathogens. But for now, they say, Toxo remains the strongest environmental factor implicated in the disorder. “If I had to guess,” says Torrey, “I’d say 75 percent of cases of schizophrenia are associated with infectious agents, and Toxo would be involved in a significant subset of those.”

Just as worrisome, says Torrey, the parasite may also increase the risk of suicide. In a 2011 study of 20 European countries, the national suicide rate among women increased in direct proportion to the prevalence of the latent Toxo infection in each nation’s female population. According to Teodor Postolache, a psychiatrist and the director of the Mood and Anxiety Program at the University of Maryland School of Medicine, a flurry of other studies, several conducted by his own team, offers further support of T. gondii’s link to higher rates of suicidal behavior. These include investigations of general populations as well as groups made up of patients with bipolar disorder, severe depression, and schizophrenia, and in places as diverse as Turkey, Germany, and the Baltimore/Washington area. Exactly how the parasite may push vulnerable people over the edge is yet to be determined. Postolache theorizes that what disrupts mood and the ability to control violent impulses may not be the organism per se, but rather neurochemical changes associated with the body’s immune response to it. “As far-fetched as these ideas may sound,” says Postolache, “the American Foundation for Suicide Prevention was willing to put money behind this research.”

Given all the nasty science swirling around this parasite, is it time for cat lovers to switch their allegiance to other animals?

Even Flegr would advise against that. Indoor cats pose no threat, he says, because they don’t carry the parasite. As for outdoor cats, they shed the parasite for only three weeks of their life, typically when they’re young and have just begun hunting. During that brief period, Flegr simply recommends taking care to keep kitchen counters and tables wiped clean. (He practices what he preaches: he and his wife have two school-age children, and two outdoor cats that have free roam of their home.) Much more important for preventing exposure, he says, is to scrub vegetables thoroughly and avoid drinking water that has not been properly purified, especially in the developing world, where infection rates can reach 95 percent in some places. Also, he advises eating meat on the well-done side—or, if that’s not to your taste, freezing it before cooking, to kill the cysts.

As concerns about the latent infection mount, however, experts have begun thinking about more-aggressive steps to counter the parasite’s spread. Inoculating cats or livestock against T. gondii might be one way to interrupt its life cycle, offers Johns Hopkins’ Robert Yolken. Moving beyond prevention to treatment is a taller order. Once the parasite becomes deeply ensconced in brain cells, routing it out of the body is virtually impossible: the thick-walled cysts are impregnable to antibiotics. Because T. gondii and the malaria protozoan are related, however, Yolken and other researchers are looking among antimalarial agents for more-effective drugs to attack the cysts. But for now, medicine has no therapy to offer people who want to rid themselves of the latent infection; and until solid proof exists that Toxo is as dangerous as some scientists now fear, pharmaceutical companies don’t have much incentive to develop anti-Toxo drugs.

Yolken hopes that will change. “To explain where we are in Toxo research today,” he says, “the analogy I always give is the ulcer bacteria. We first needed to find ways of treating the organism and showing that the disease went away when you did that. We will have to show that when we very effectively treat Toxoplasma, some portion of psychiatric illness goes away.”

But T. gondii is just one of an untold number of infectious agents that prey on us. And if the rest of the animal kingdom is anything to go by, says Colorado State University’s Janice Moore, plenty of them may be capable of tinkering with our minds. For example, she and Chris Reiber, a biomedical anthropologist at Binghamton University, in New York, strongly suspected that the flu virus might boost our desire to socialize. Why? Because it spreads through close physical contact, often before symptoms emerge—meaning that it must find a new host quickly. To explore this hunch, Moore and Reiber tracked 36 subjects who received a flu vaccine, reasoning that it contains many of the same chemical components as the live virus and would thus cause the subjects’ immune systems to react as if they’d encountered the real pathogen.

The difference in the subjects’ behavior before and after vaccination was pronounced: the flu shot had the effect of nearly doubling the number of people with whom the participants came in close contact during the brief window when the live virus was maximally contagious. “People who had very limited or simple social lives were suddenly deciding that they needed to go out to bars or parties, or invite a bunch of people over,” says Reiber. “This happened with lots of our subjects. It wasn’t just one or two outliers.”

Reiber has her eye trained on other human pathogens that she thinks may well be playing similar games, if only science could prove it. For example, she says, many people at the end stages of AIDS and syphilis express an intense craving for sex. So, too, do individuals at the beginning of a herpes outbreak. These may just be anecdotal accounts, she concedes, but based on her own findings, she wouldn’t be surprised if these urges come from the pathogen making known its will to survive.

“We’ve found all kinds of excuses for why we do the things we do,” observes Moore. “‘My genes made me do it.’ ‘My parents are to blame.’ I’m afraid we may have reached the point where parasites may have to be added to the laundry list of excuses.”

She has a point. In fact, I’ve been wondering whether T. gondii might in some small way be contributing to my extreme extroversion—why I can’t resist striking up conversations everywhere I go, even when I’m short of time or with strangers I’ll never see again. Then it occurs to me that cysts in my brain might be behind my seesaw moods or even my splurges on expensive clothes. Maybe, I think with mounting conviction, the real me would have displayed better self-control, had I not been forced to swim upstream against the will of an insidious parasite. With my feline pal Pixie on my lap (for the record, she’s an outdoor cat), I call to get the results of my Toxo test. Negative. I don’t have the latent infection.

I call to tell Flegr the good news. Even though I’m relieved, I know my voice sounds flat. “It’s strange to admit,” I say, “but I think I’m a little disappointed.” He laughs. “People who have cats often feel that way, because they think the parasite explains why they behave this way or that,” he says. “But,” I protest, “you thought the same way.” Then it hits me. I may have dodged T. gondii, but given our knack for fooling ourselves—plus all those parasites out there that may also be playing tricks on our minds—can anyone really know who’s running the show?
The Rich and the Corporate remain in their hundred-year fever visions of Bolsheviks taking their stuff - JackRiddler
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby Sounder » Thu Feb 09, 2012 11:16 am

But then we looked at how much winds up in different areas in the brain, and it turned out Toxo preferentially knows how to home in on the part of the brain that is all about fear and anxiety, a brain region called the amygdala. The amygdala is where you do your fear conditioning; the amygdala is what's hyperactive in people with post-traumatic stress disorder; the amygdala is all about pathways of predator aversion, and Toxo knows how to get in there.


Wow, is that not the section of the brain that fires more in conservatives?

Maybe another reason for compassion.
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby Wombaticus Rex » Thu Feb 09, 2012 12:19 pm

YES AND NO. Be wary of neurorealism.

http://www.humpjones.com/rear/entry/the ... _of_shit1/
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Re: Parasite's and the military conversation w/ROBERT SAPOLS

Postby Sounder » Thu Feb 09, 2012 12:40 pm

Fine article Wombat and you also have a pretty cool writing voice. It must be all that rap training.
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