I do neuroscience research at Stanford on that cat-lady parasite, Toxoplasma gondii. AMA!

What are some of the projected positive outcomes of the research?

Ah, a non-skeptic! Thanks!

My major interest is in the potential link to schizophrenia. I think there are many social stigmas and misconceptions about mental illnesses where people think that, maybe, the disease is really just a lack of will to try, or perhaps a weakness of personality or constitution or effort. Mostly this is because we have no idea what diseases like schizophrenia or depression are. Once we do, perhaps some of the stigma will go away.

This cartoon sums it up nicely: http://imgur.com/CWFTYoV

As a good analogy, ulcers used to be thought of, too, as weakness in personality. One could be ulceric. But then we figured out it's just a bacteria and the stigma around ulcers disappeared overnight. My hope is that if some causes of schizophrenia turn out to be pathogenic -- caused by a parasite -- people will start seeing mental illness as less of a constitutional weakness and more like having a cold or other diseases that are Not Their Fault.

Doesn't most research associate depression with Serotonin imbalances?

Source: My mom is a doctor and I think one time she said words.

Yes, that's the Mad Libs answer...as in, if you had to fill in one & only one word for possible depression sources, you would say "imbalances in _(neurotransmitter)_" and the answer most people would put would be serotonin. That many anti-depressants target the serotonergic system is good evidence. But, as the adage goes: "a headache is not an absence of Advil"

What leads you to believe that toxo acts primarily upon DA neurons instead of glutaminergic ones (which have also been linked to schizophrenia)? Also, if it causes permanent damage to DA neurons, do you think that this effect is isolated to the VTA or might it also affect the SN?

There are a few reasons for a suspected link between Toxo and dopamine:

• Toxo increases dopamine levels in the brain, if you just look at the whole brain (Stibbs 1984)
• The parasite itself, if you look at its genome, has genes for tyrosine hydroxylase, which is a necessary enzyme in the creation of dopamine in brains. (McConkey 2009)
• The cysts themselves have been found to stain with dopamine, and neurons with cysts in them release more dopamine. (McConkey 2011)

So the theory involves something like: Toxo gets inside a neuron, releases tyrosine hydroxylase (TH) and the TH then leads to an increase in dopamine levels. Still an early theory, but certainly a compelling one given the evidence.

Cool, thanks for the reply. But if Tyrosine Hydroxylase levels increase throughout the whole brain and cause DA levels to rise throughout the whole brain, do you think it would still lead to schizophrenia? I thought that the current hypothesis was that schizophrenic symptoms are due to lowered dopaminergic activity in the mesocortical pathway and increased DA activity in the mesolimbic pathway?

Sorry if I'm uninformed on this, I'm still working on my Bachelor's in neuroscience but this is all super interesting.

Oh you're not uninformed, quite the contrary. The theories shift so often, it's hard to know what & when to believe. There are differences between what people think of as the positive symptoms of schizophrenia (hallucinations, delusions) and the negative symptoms (inability to feel pleasure, lack of desire to do all-that-much). So, the theories shift as to whether they lump the positive and negative together (for example: "Increased dopamine causes all the symptoms!") or if they try to separate out the positive and negative (for example: "Positive symptoms are caused by too much dopamine in mesolimbic, but negative symptoms too little dopamine in mesocortical")

There is reason to believe they should be separated, as many of the anti-dopamine anti-psychotic drugs only relieve the positive symptoms, and do very little for the negative ones. There's still a lot of work to do. Stick with it!

How likely are you to get this parasite of you have one or two cats you live with?

It totally depends, most especially on whether the cats are indoor cats or outdoor cats. I've heard domestic cat infection rates anywhere from 20% to 60% depending on the region.

But, a majority of people actually pick up Toxo through eating raw meat, not through cat poop. You certainly can get it through cat poop, but the poop tends to also be in fertilizer, which ends up in cows, which we then eat. Cooking properly kills Toxo, so, high heat!

The general consensus seems to be that searing meat is important because bacteria and viruses reside on the surface of the meat, while the inside is considered safe. Parasites tend to be a different matter, but they are thought to be extremely rare these days because of modern practices in raising livestock. Therefore it's generally thought to be safe to eat meat and fish that hasn't been cooked to pasteurization. (generalizing here)

How does toxoplasma gondii fit into this? Can it be found throughout pieces of meat? What temperatures for how long does it take to kill it?

Yes, parasites are a different matter indeed. In this study they found Toxo in 27/71 meat samples they tested from a normal, random supermarket. So, it is definitely getting into the food supply. It is thought that the relatively high country-wide rates of Toxo infection in France and Brazil are due to steak tartare & brazilian BBQ, respectively, both of which involve raw meat.

Had to look cooking instructions up myself. According to the CDC: "Beef, lamb, and veal roasts and steaks should be cooked to at least 145 F, and pork, ground meat, and wild game should be cooked to 160 F before eating. Whole poultry should be cooked to 180 F in the thigh to ensure doneness."

Are those temperatures specific to killing toxoplasma gondii? Trichinella (responsible for trichinosis) for example dies at considerably lower temperatures than that.

Cooking guidelines should be based on temperature and time, cooking temperatures recommended by various health agencies tend to recommend temperatures high enough to instantly kill any pathogens, which is unfortunately also high enough to completely ruin the meat.

I cook for a living and I think toxoplasma gondii is probably unknown (and maybe not serious enough?) that culinary professionals don't take it into account when considering food safety.

edit: Just read in Modernist Cuisine that the oocysts of T. Gondii dies from being exposed to 70 C for ten minutes, which is freakishly high. The text doesn't mention T. Gondii being present in meat, perhaps this is a more recent discovery? Is it the oocysts or actual parasites which are present in meat? Presumably oocysts should be in cat poop and the actual parasites in meat. Sorry for the barrage of questions, this is just very interesting.

edit2: Nevermind, the oocysts are in the meat, they perish at 70C for 10 minutes and there seems to be no way to be sure to avoid infection if you ever want to eat steak again.

Correct, there is no good way to 100% avoid it if you want to eat good steak. :) Even the freezing guidelines might not be accurate -- in our lab, we freeze the parasites & then thaw them out and they are slow for a while but totally viable in a few days. The oocysts will not be in meat, but consuming the other lifecycle stages will also lead to infection.

So, really, the thing to do is nationwide (world-wide?) prevention of Toxo in livestock. There are many many groups working on vaccines for livestock, partly because such a success would mean billions of dollars and partly because it is such a world-wide problem.

But, a majority of people actually pick up Toxo through eating raw meat, not through cat poop.

THANK YOU for this, and for having it be in your top comment. Why do you think this information is so relatively unknown about Toxo, while the cat = infected idea is so widespread?

(BTW, favorite parasite.)

Partly I think it is because for the group of people where the timing of Toxo really, really matters -- pregnant women & HIV patients -- they will be having active conversations with their Dr.s about how best to avoid getting the parasite right now. As in, you or your baby might die if you get this parasite in the next year, so, here's all the things to avoid. In that sense, it's a damn good idea to stay away from cat litter boxes, or be extra super careful with washing hands after.

Also, the internet likes cats. A lot. Cows, a little, but less so.

Where do you think T. gondii ranks in terms of parasites that alter the behavior of their indirect hosts? Say, as compared to Dicrocoelem dendriticum or cestodes that make shrimp swim near the surface where they're targets for birds?

Does toxo have a big difference in risk-aversion between men and women?

I think what makes it different is that Toxo is getting into the brains of mammals. The blood brain barrier that protects the brains of mammals (and humans) is very, very good at what it does. There are very few organisms or viruses that can make it into the brain, and when they do (tapeworm cysts, rabies) they can be fatal quickly. So Toxo is special in that it has figured out a way to both find it's way into the brain and (potentially) manipulate neurons of mammals while keeping the host alive. This is, as far as I know, the only parasite that does this, and does it so well.

First of all, go Cardinals!

My question is, does this parasite effect the brains process of depolarization/hyperpolarization (messes with the process of ions)? Or does it effect the brain in a different way?

I know the CNS does not have the best ability to fight off diseases but does the body try to fight the parasite out?

Thanks!

Ah, great question. The field of Toxo research is actually pretty young, so it is unknown what the parasite does to neurons on an individual neuron level. It's simply that noone has done that study yet, but I'm sure it will be done soon. We don't know how it affects the brain, but can only guess. A leading theory right now is that it alters dopamine levels in neurons it infects, which then can change dopamine signaling throughout the brain, and, potentially, the fear response of the rodents.

And to the second question, the body can fight it off, but Toxo has a lot of defenses for itself. For instance, just in the brain, the parasite either hides inside neurons themselves or in spherical cysts containing collections of dozens of individual parasite. We know the immune system is doing something to keep the parasite in check because of the sad cases where HIV patients -- who lack certain T cells necessary to fight off Toxo -- can get Toxo encephalitis in the brain which can sometimes be fatal.

Your explanation of Toxo encephalitis in HIV patients confuses me a bit. Are T-cells present in neural tissue? Otherwise if Toxo passes the BBB, how would the lack of adaptive immunity predict a worse outcome since there are only innate immune cells (microglia) in the brain? This may be outside the scope of your study, but it's interesting nonetheless.

Also, were you responsible for sacrificing the mice from your study upon its conclusion? If so, how did you handle it (physically and emotionally)?

Good luck on your defense.

Hi, I think this is how it works:

HIV infects and depletes the number of CD4+ cells, which are otherwise known as T Helper cells.

I don't know the exact mechanism, only that when CD4+ cells are low (as in HIV), this allows Toxo in the brain to proliferate. Because of this, Toxo is the leading cause of focal CNS damage in AIDS -- currently occuring in 3-15% of patients with AIDS in the United States.

One of the treatments for Toxo encephalitis in HIV patients is the use of antiretroviral meds to up the number of CD4+ cells -- I don't know exactly how this keeps Toxo in check, only that it works occasionally & it is the best we can do.

I have a few methodological/design questions! To preface, I'm a fellow PhD student, so greetings, fellow impoverished workhorse =). Also, I'm a functional MRI guy, so some of my questions may arise from ignorance of some of the techniques.

1) Are you at all concerned about whether c-fos expression has different temporal profiles across the regions you examined? Put another way, do you feel that the same sac and slice protocol equally captures c-fos expression across these regions? The reason I ask is because previous work has shown that c-fos expression has different temporal profiles in different subfields of the hippocampus (sorry, I'm not on my work computer so I don't have the citation handy), so it stands to reason that the hypothalamus and amygdala may also show this discrepancy.

2) In your data (Fig. 1), it appears you're testing for significance against a threshold. Following a significant ANOVA, you seem to have done post hoc t-tests to compare individual datapoints (e.g., BLA vs. threshold). Did you correct for multiple comparisons? I'm not trying to be a stickler, but some of your significance values in the p=0.02-0.04 range might not survive familywise correction, and I'm wondering whether you considered this.

3) Did you do any behavioral testing in this experiment? Sorry if this is obvious, but I didn't see this in the paper...I may have just dummied up and overlooked it. If not, it may be a powerful next step to first show the behavioral consequences of infection and follow up with indices of change in neural activity.

Thanks! Cool paper. I like PLOS ONE a lot...haven't submitted there yet, but I would really like to someday. I hear their review process is a relief compared to most journals.

Ah, methods questions! Lovely.

• Certain neurons will be more susceptible than others to the stress of saccing and slicing -- for instance, hippocampal neurons, basal ganglia neurons or any neuron with high, high metabolic rates will be the first to 'go' if you are trying to preserve the function of the neurons. c-Fos is different in a way because it is more like taking a snapshot of the brain 90 min prior to saccing, in that that is how long it takes the immediate early genes to start expressing. You would not want to compare amygdala levels to hypothalamic levels in a single rat, as per what you're saying, because it's likely c-Fos expressions are different. BUT, you can compare amygdala (uninfected) to amygdala (infected) because on a region by region basis you can assume that if c-Fos expression is altered in one rat it will be true for the next one too.

• Yes, there is no way the p values would survive multiple comparisons outside just a few brain regions, which is actually why we looked at a very, very small part of the brain that we knew had to do with fear and attraction. As in, I just looked at a few subregions that we knew apriori were related to fear and the smell of the female rat. If it were completely an exploratory study, we would have had to divide alpha by # of regions studied, but, well, there were hypothesis hidden in there. It's not the best logic, and likely is why it is a PLoS One paper.

• No good behavior in the PloS study (for the c-Fos nerd in you, the behavior would muck with the c-Fos signal to the point of making it useless). My thesis work though, which is being written up now, has in depth, careful behavior work & a link to individual neurons, as you say! That first PLoS One study was a while ago, and I'd say was quite preliminary.

What were your findings? Are the mice less afraid of cats?

They are! But, not all of them. My findings (not published yet) mostly involve looking at the differences between individual mice that get Toxo. As in, some mice that get Toxo are less afraid of cats, but some are the exact same amount of afraid. This makes sense, because Toxo can go anywhere in the brain, so it probably matters where it ends up.

So, I looked in the brains and found where all the Toxo was. Abstractly, the idea was: maybe those mice that had Toxo in 'brain region X' were all not afraid, and those mice that didn't have Toxo in 'brain region X' were still just as afraid. That would greatly implicate brain region X and argue that maybe Toxo is doing something in that brain region. I did indeed find this, but I need to keep my lips sealed until it's actually published.

My father was infected with this parasite at a very young age, it attacked his eyes and rendered him legally (and at times totally) blind his entire life. How common is it for toxo to attack the eyes? And could it have contributed towards his death? (Heart attack at 63)

First, sorry to hear that. :/

Funny thing about the eye, it is kind of just a jutting-out extension of the central nervous system. So when we say Toxo infects the brain, it can also infect the eye & hide in neurons there & cause more obvious damage. If a Toxo parasite is sitting in one of the 100 billion neurons in the brain it is unlikely to be noticeable, but if it's sitting in the optic nerve it can be quite obvious & symptomatic & impair vision. Usually Toxo related eye diseases spread from the brain or are acquired congenitally (i.e. from one's mother during pregnancy). Unlikely to relate to heart health.

After his death they were able to transplant his corneas and lenses to help restore the vision of a burn victim, so that was nice. I made sure they knew he had toxo when I filled out the paperwork though. Just out of curiosity how small is a parasite?

They are about 7 microns X 1 micron. They look like little crescent bananas. For reference, a typical neuron is maybe 20 microns in diameter (ranging from <10 microns to >50 microns). So, they fit inside neurons!

How long can they live and propagate inside a human? Would the parasites my dad contracted as a young child still have been present in his eyes at his death over sixty years later?

From what I know, it's possible. Toxo can lie dormant for a long time, a very long time, but there isn't really an upper range on how long, or whether there is a maximum. It is found in brains when people die though (old & young alike), so presumably in some people it has lasted as long as they have.

I would assume & hope the transplant Dr.'s know more about this than we do, though.

I hope so, they used a lot of his tissues but his organs were all destroyed from years of pain medicine. Does toxo only infect nervous tissue?

No, it can encyst in muscle tissue too. This is why it's a major problem in livestock -- we eat the muscle tissue of cows, pigs, etc. which can contain Toxo cysts.

I just realized I'm asking you a lot of questions that can be easily googled.

But everytime I get a new message it makes me happy, whereas Google doesn't have feelings.

I am a college freshman studying biology, so forgive for a lack of general knowledge. How can the parasite only reproduce in cats? Wouldnt one mammal system be closely enough related to another?

It is unknown exactly what factors in the cat make it the only ideal host for sexual reproduction. Toxo can reproduce asexually in all other mammals, but only sexually in the cat. Also, strangely, Toxo does not in general go to the brains of cats, although it will goto the brains of all other mammals it infects. So, there is something unique about cats (all felines, actually) that Toxo can detect and causes it to stay in the GI tract and never migrate out to the brain. It's an obviously good research question that hopefully someone answers soon.

One could maybe imagine a vaccine you give to humans that makes the GI tract of humans look like a cat GI tract to the parasite, meaning that Toxo would never leave & therefore never get into the brain, where it does its damage.

Dang!You respond fast! You've introduced me to my new favorite parasite(wow i have a favorite parasite).

My hope is that everyone, one day, has a favorite parasite.

How can I find out if I have it? How can I get rid of it if I have it? Do I need to incinerate my brain?

Thank you.

Hah, please don't incinerate your brain, for multiple reasons; the first of which being that then we would never know if you had Toxo.

The test for Toxo is a simple blood test.

If you're a woman, Toxo is always tested for if pregnancy is either at hand or something the woman is thinking about. Toxo can be quite bad for the fetus, and there are things women need to know if they are pregnant to prevent getting Toxo during pregnancy.

That being said, if you are male, I don't actually know of how to get tested other than maybe asking your Dr. nicely or enrolling in a study that tests for Toxo.

Almost of the data about how many humans have Toxo is inferred from pregnant women statistics.

Wow, you're quick.

So I guess if you got it, you got it for life then?

As of right now, yes, if you have it you have it for life. At least, you'll test positive of it for life. The tricky thing is that the parasite is hiding in neurons in your brain, so we certainly don't want to go in there & muck with anything given how important seeming neurons are to, well, everything.

We don't actually know if, in some people, the parasite disappears on its own. But we assume that if someone tests positive, they have it in their brains, too.

I have read so much about this parasite!

Do you have it? What are its effects on humans?

I don't have it -- at least, I didn't when I started doing the research. As to the effects on humans, it is ongoing work. I think the major impact is clinical -- in that, if you have Toxo & are immunocompromised from, say, HIV, Toxo can be really really bad and even fatal. For some of the more speculative work on Toxo and human behavior I would read the Atlantic article above, talking about all kinds of potential personality trait changes in infected humans.

Are there any viruses that go after Toxo, that could be used to treat it in people? Are we at the point where we could create or modify a virus to do this?

Once you snuff the poor little mousey, how do you find the Toxo protozoa in the brain? Staining or something?

There's currently no vaccine or treatment for Toxo once it is in the brain. That sounds blunt, only because it's true -- there's really nothing you can do once it is in the brain.

I find the parasite using a genetically-modified Toxo parasite & a genetically-modified mouse. The short of it is, with this special Toxo and the special mouse, when the parasite invades a neuron it makes that neuron fluoresce, so it becomes easy to see. So when we look in the mouse brian, we have an exact map of where the parasite has gone, down to the individual neuron.

*There's currently no vaccine or treatment for Toxo once it is in the brain. That sounds blunt, only because it's true -- there's really nothing you can do once it is in the brain. *

I understand. From very briefly poking around, it looks like people are working on phage therapy for protozoa, but it's still in the research phase: Beyond phage therapy: virotherapy of protozoal diseases., Generation of Anti-Giardia Antibodies by Bacteriophage Antibody Display (this last one's a little bit related).

Here's a neat review article on Toxo imagine I need to read: http://www.parasitesandvectors.com/content/6/1/334

Using viruses to target any & all medically relevant targets is a great idea, & is likely to be more & more useful every year. For instance, viral gene therapy is obviously where things are heading: it can cure color blindness in primates, not to mention all the many potential benefits for genetic disorders in humans, some proven, some hypothetical. Viruses are 100% the future of medicine.

But a viral cure for Toxo in humans would be at least a decade away even if today -- Feb 9th, 2014 -- there was a Nature paper showing that it worked in mice. We are a long way from the FDA allowing us to inject virus into human brains to fix things, let alone target Toxo, which is not just sitting in the brain but is actually hiding inside neurons.

It's great forward thinking, and we need people to think big like this, but my lord is it a hard problem.

Almost Dr House!

So glad you are here and I hope I'm not too late to get my questions in.

A little background: About 14 months ago I suffered an acute toxoplasma infection that has left me partially blind in my left eye. That fucking sucked but I'll spare everyone the sympathy votes and just say that I have adjusted to as normal a life as I could. Coincidentally, I'm also almost dr sleepfuriousidea (Linguistics, though. There's a clue in my name for bonus points). My biggest fear was that I wouldn't be able to read normally again and my career would go off the rails. Fortunately my brain has adjusted to the retinal scar I was left with and I can read and write again with relative comfort.

One of the hardest things to deal with at the time, however, were uncertainties over where/when I got infected. I had seen a few ophthalmologists in New Zealand, Korea and Mexico while I was infected (long story) and one infectious disease specialist. None could be sure of where I got it from but thought it was likely from raw meat, something I've grown up eating since my childhood in arctic Canada. This happened in NZ, where I'm studying and I definitely had a small chunk of raw beef within weeks of my infection. I was in contact with a toxo specialist there who also suggested that it would likely be from meat. However, I've also come across literature documenting infections from water sources (for humans in Victoria BC, Brazil). Also, marine mammals (otters in Cali; dolphins in NZ) have been found with toxo. Quite stupidly I also had water in NZ while camping that may not have been pure. I am wondering, is there a (relatively straight forward) way of testing meat and water for toxo. For example, I know the exact farm that the raw meat came from and also the location where I drank from a mountain stream. If I brought my colleagues in a medical department samples would they be able to check for toxo without having to infect rodents and dissect their brains? I was struck by the complex methodologies in the literature for toxo and would be shocked if there wasn't a simpler way to find toxo. Also, are symptoms of acute toxo infections indicative of source in any way?

Many thanks!

TL;DR How can someone test for toxo in meat and water?

First, I'm sorry about that, that sounds rough. I'm glad your vision is okay though.

As to the riddle, I would guess your last name is a color, opposite red on the color wheel?

As to Toxo source, oh boy. First, the only thing the blood test for Toxo can tell you is one of two things: either (1) you got Toxo in the last six months or (2) you got Toxo prior to six months ago. Nothing more. It has to do with two types of antibodies: as soon as you get infected you have antibody A for about six months, and then it goes away and you are left with antibody B. So if, when they test you and they find either antibody A or B (as in, you test positive) they can only tell between those two possibilities.

I would guess, based on your Dr.s assessment, that you did not show antibody A, and therefore they ruled out the most recent New Zealand related activities. Which means it was likely a reactivation of an already existing Toxo infection that you had, possibly from childhood, possibly from who knows where.

Your medical friends could certainly test samples for Toxo if they wanted (without infecting mice -- there are kits or one can do a PCR or a few various techniques) but they would not be likely to want to, mostly because, well, it wouldn't change anything & wouldn't be able to tell you where you got it from (as in, they can't match Toxo to Toxo like a fingerprint or anything -- they could only tell you that you have it and that the meat has it, not that you necessarily got it from the meat).

As to likelihoods, water borne is highly unlikely, though possible. Raw meat is definitely a main source, but even if raw meat from NZ tested positive you wouldn't know definitely if it was that or some time during your childhood. I know you want to know, badly (I would too), but I'm sorry to say there isn't a foolproof way to know.

So then, AmostDr. House, do you own any cats yourself? Would you ever adopt one?

I don't own any because (a) I have a rabbit (see picture) that is one step above grass on the food chain & would likely freak out, and (b) I am allergic. But I would totally own a cat -- care is all that is needed to prevent getting Toxo from the cat.

What care is needed to avoid getting infected from your cat?

Personally I'm a veggie, so I would be unlikely to get it from meat. How likely am I to get it from breathing in litter box dust?

Not via breathing -- Toxo is not aerosolized at all. People get it from their house cats after cleaning the litter box & not washing their hands properly -- the parasite is tiny, single-celled & invisible. Then they eat little bits of it if they eat food with their hands. Good cat hygiene & proper litter disposal should fix everything on that end.

Is there any way to treat Toxo in either rats or humans?

None currently. You can treat if if you know you got it in the past few days. Like, say, if you're a Toxo researcher (!!) & you accidentally stick yourself with a Toxo-laden needle, you can goto the hospital and get treated. But that is only because there are at that time so few Toxo. Wait a couple days & the Toxo have proliferated and are maybe already in your brain.

What is the treatment? An antibiotic?

No treatment. :/

The parasite is a protozoan, not a bacteria, so there is nothing to do once it is in the brain.

do you still get in awe about how fucking insane the world of parasites are? I always get a little/lot hypochondriacal when i hear about parasites. couldn't even finish parasite rex by C. Zimmer

I do! Parasite Rex is what made me study Toxo in the first place. C. Zimmer even put me in his blog once when I told him that: http://blogs.discovermagazine.com/loom/2011/08/18/science-writers-you-have-great-powers/

How did you get accepted to Stanford?

Worked in a neuroscience lab for a year before. It convinces both you & the schools you apply to that research is actually what you (one) want(s) to do. research is really quite arduous and unpleasant at times, & a lot of people don't like doing it. There is a lot of failure -- failed projects, experiments that don't work, etc. You need a high tolerance for failure.

Does that make you good in the pickup/seduction scene?

Not un-similar tolerances.

How long does it take for the mice to crave feline scents after infection? How long do the behavioral changes last?

A lot of the researchers tend to test the mice about -- I kid you not -- 4 weeks (i.e. 28 days later, ala the movie) after infection. This is mostly because the parasite needs to migrate to the brain, and this can take, estimates are, anywhere from 10 days to about 28 days.

How long it lasts is a still unanswered question, and a really good one. I think that for many reasons people have not tested the mice or rats into old age. I believe the longest anyone has shown the effect in published literature is 6 months after Toxo infection.

Fascinating stuff. Have enjoyed watching Sapolsky lecture (online and thru audiobooks, not at Stanford) and read a couple of his books.

1) He as cool as his persona?

2) Do you have any hunches how much human (and other animal behavior) might be controlled or affected by parasites or other infections. For example, I recently read a little about Greg Cochran's theory that homosexuality is more likely to caused by an infection than genes. I don't have the expertise to evaluate that argument, but do you think there are lots of other parasites or germs that fundamentally alter behavior that we have no idea about yet?

1) Yes, he is. Always says the most insightful thing in the room, especially if we're the only two in the room.

2) I really don't think so, for a few reasons. Basically, the human blood brain barrier is very good at what it does. Things that get across it (tapeworm cysts, rabies) tend to either be noticed quickly, bring with it strong symptoms or kill the person. Also, the medical community has been doing post-mortems on human brains for decades now, and it stands to reason that larger (i.e. single-celled) organisms that were hiding in brains might have been spotted by now.

Is it possible that there are ones we haven't noticed? yes. Might a new virus or organism find a way to cross the blood-brain barrier & stick around? Yes. But I don't think there is one as prevalent as Toxo (~ a quarter to a third of the world) that is still waiting for us to find in brains.

I heard about your work through Nerd Nite.

Are the behavioral changes shown to be advantageous for the germ or are they an incidental side effect of infection?

Well, the idea is that Toxo can only reproduce in cats, so it has to get from one cat to another cat. In that sense, if it gets into a mouse brain, mucks things around, and that mouse is then eaten by a cat, this would be advantageous for Toxo.

Humans, though, since we don't get eaten by cats (except in that one movie with Val Kilmer) are pretty much dead-end hosts.

Oh interesting! Are there many species of toxoplasmosa in other felines? What's the evolutionary origin of the one in domestic cats?

Toxoplasma can infect all felines, but there are different strains of Toxoplasma around the world, generally falling into three categories (Type I, Type II, & Type III). Some labs are working on characterizing the differences between strains, which appears to be significant.

The evolutionary origin is unknown, but is likely simply that there are many types of parasites out there specific for specific animals, but this particular strain of Toxo that requires cats is the only one that survived. For instance, there is another parasite that infects dogs, neospora caninum. People used to think it was Toxo because of how similar it looked, but it turned out to be entirely different. So, it is probably the case that there are lots of these types of parasites, but the question is whether they also (a) goto the brain and (b) manipulate intermediate hosts to advance their own lifecycle. It does not appear n. caninum does this, for example.

Can you give us a scientifically accurate paragraph about Toxo that otherwise is in the style of Joe Rogan?

"You’re just talking about researching a stupid fucking parasite… you’re not saving the world, you’re not time traveling, you didn’t invent a nuclear weapons, you didn’t invent a faster internet. It isn’t like you came up with ’5g’. You played a scientist during a PhD, and you were good at it. Thankyou. thankyou for distracting me for an hour and a half while I read your paper, because that’s all the fuck you did, okay? You made me sit down, and I enjoyed your performance, and it made me not think about my life and I got some thrills out of it. It was very exciting and enjoyable to follow along. That’s it. That’s all you did. You didn’t fucking change the world, you’re not awesome, you’re just good at pretending.”

Have you read this: http://booksonmars.blogspot.com/2009/04/new-novelette-steak-tartare-and-cats-of.html ? Sci fi story of a toxo infection in a human colony on Mars.

No! Thank you. Have you read Purr, the novel ?? Now we're even.

Toxoplasmosa Gondii; Not just for cat-ladies, but now the immuno suppressed and pregnant as well! Can you elaborate on the alteration of brain chemistry that leads to fugue state-like suicide endeavors? Are the rats conscious of their dangerous behavior, and are they able to recognize it as dangerous? Is the autonomous NS muted, to allow for a dissolution of the F or F mechanism/response? Zombie virus of the future, anyone?

Well, the infected mice & rats are certainly conscious, though it's hard to know what of.

One of the fun things I like thinking about when I see someone who really, really likes their cats is -- if you ask them why they liked their cats-- that they would give you their list:

1. cat-liking reason #1
2. cat-liking reason #2
3. purring
4. cat-liking reason #4

...but, they'll never say Toxo. Because, well, they couldn't. You can't introspect about something that is a physical entity in your brain. If it is changing one's preferences, one wouldn't know. Then the scary bit: you can extrapolate that out to all the other things you think you like & know and ask yourself if you really like them for the reasons you think you do.

Perception is amazing. I bet the gondii got a hold of me, and is causing me to ask these questions in order to adjust it's behavior to better take over the world. On a serious note, there are so many situational/contextual/relational/and biological motivations behind what we think is OUR choice of behavior and belief, how is one to ever be able to explicitly state: I 'am' and I 'do' because I ________. Since we are so influenced by known and unknown factors, life can be equated to a bunch of drunk children stumbling through all of the hoops that come together to form the human condition with no regard to their immediate environment. Perhaps we should stop calling that condition 'human'.

One of my favorite studies involves a girl who, during epilepsy surgery for which she was wide awake, had a part of her brain stimulated which made her laugh. She was then asked why she laughed, and, to quote the paper:

"Thus, laughter was attributed to the particular object seen during naming ('the horse is funny')"

So, basically, she made up a reason why she laughed. Every time. The brain is good at tricking itself.

Damn, late to the party. I'll try anyway:

Seriously true or false: T. gondii makes women more promiscuous.

Because if the internet rumors are true then I kinda foresee de-funding in your future...

It is true that it is published in a research article that Toxo makes women more promiscuous. But like many, many results in science (including my own, to be fair) we must wait until things get repeated many, many times to say it is a Fact.

For instance, Toxo has been linked to schizophrenia in over 50 studies & scientists on both sides are still cautious to say whether the link is real. The Toxo & female promiscuity result is in 1 study that I know of.

It's a compelling result, the kind that grabs headlines quickly (as a Toxo-infected woman grabs ___ quickly).

we must wait until things get repeated many, many times to say it is a Fact.

Hi, could you dedicate your life to educating people on this basic premise? It seems utterly incomprehensible to most people.

Thanks!

Alas, I've dedicated myself to a career which commits me to say the opposite to have any chance at funding, jobs, or future success. You don't get a grant by saying your preliminary results have an incredibly low likelihood of repeating.

That... was painful to read. What a broken system we have.

Well, many if not all researchers themselves know this too. It's a tricky matter of selling ourselves: how to justify to the public that they should spend so, so much money investing in something that produces, at best, probabilistic statements of facts. But genuine good does come from it -- we know more than we ever have, and the rate at which we are advancing is boggling. So, it's not broken at all -- just a tiny, tiny bit disingenuous.

Public health and nutrition is broken, though. Some really bad science is being done in those fields.

Well, it is also mind-boggingly difficult. Other than simple cases like "Stop obtaining Vitamin C and you will get scurvy" the ridiculously complex body of an individual multiplied by all 7 billion people each with their own weights & metabolisms & upbringing & sun exposure & water intake & mood & HDL level & sugar intake & sleep cycle & etc etc just makes me want to give up. I can't say I agree with every published nutrition or epidemiological study, but you can't fault them trying to figure out a super complex system.

I'd say bad reporting is being done before I'd say bad science is being done.

I understand, I never bothered trying to find literature on it, but then I run into this AMA and figured it was an easy way to get a real answer from an expert on the matter.

So basically it's a solid "Maybe". If there needs to be more research done in this area I can definitely lend myself in helping you guys gauge levels of promiscuity, I don't even care if you put me in the control group.

Ah, this is where grass roots science can be useful. Ask if said woman is a proto crazy cat lady & then try to sleep with her. Tally results. Do stats. Make graph.

Are cats only infectious during the early stage of infection after they eat their first infected rodent? What are the odds that a outdoor cat has toxo in the USA?

In Latin America there seems to be a greater aversion to having cats as pets. I wonder if this is an an evolutionary survival trait.

Right you are, cat feces are only infectious during a very small window after parasite replication. But, I think public health researchers tend to overlook this during their PSAs simply because one can never know whether a cat is infectious at any given time, so a blanket "WASH YOUR HANDS" serves all interests.

As to cat infection rates, it varies around the world and in the US: for example, just looking at a few studies: 2% in Korea, 17% in China and 30% of feral cats in Prince Edward Island, Canada. Free range cats caught in Iowa were at 80% Toxo rates.

It all depends. The quick answer is outdoor cats have much higher rates than indoor cats. That's really the only general statement that can be made.

As to Latin America -- Brazil has one of the highest rates of Toxo in the world. A culture encouraging eating raw meat is much worse, from a Toxo infectivity point of view, than a cat-owning culture.

I've read a few conflicting studies about whether Toxo tries to concentrate itself in the amygdala and frontal lobe of rats in order to alter host behaviour, with a lot of different areas highlighted in the realm of possibility, but nothing certain. Do you think it targets specific regions in terms of cyst density? Has this been explored much in humans?

It's very hard to test this in humans, as one can only do this in post-mortem brains &, honestly, no one has been much interested in looking. There are more pressing things that institutions are using human brain researchers for. I imagine that in the coming decade or decades there will be research into this, though, so we will know soon enough.

The question of where Toxo ends up is much more testable in mice and rats and, sadly, the early excitement about specific localization of Toxo to, say, the amygdala (which even came from my lab) seems to be waning a bit. As in, Toxo appears to go a lot of places, and fairly indiscriminately, at least in mice. My PhD thesis addresses this very issue, so - wait a few months & I'll tell you more when the paper is out! :)

the early excitement about specific localization of Toxo to, say, the amygdala (which even came from my lab)

That was your 2011 paper right? I did a literature review broadly looking at Toxoplasma a while back and used it as a source. Seriously interesting subject (if not somewhat confusingly technical in places for a lowly undergrad), and helped pique my interest in choosing the direction of a neuroscience major. What's the job scene like in the US? And based on how most studies into toxoplasma have been in the past decade and less, would you say it's gaining more momentum as an area of research?

Toxo is absolutely gaining momentum. The studies looking at behavior have only been around since 2000 and looking in the brain only since 2007. So, it's only been 6 years since someone first looked in the brain of Toxo infected mice. In academic research years, that's infancy. It's just getting started.

My paper showed that there were changes in the neurons in the amygdala after infection and exposure to cat urine, but I never myself looked for where Toxo was. I was interested not in the location but wanted to be agnostic to the location -- as in, to ask "Not even caring where it went, do we see changes in neural activity in fear-related regions?" And I found that yes, there were changes in circuits related to both fear and attraction in the rats.

My mom just had lymph node surgery and found out it was because of this. Very scary stuff. It probably doesn't help my parents have 6 cats.

The silver lining there being that her lymph nodes presumably swollen because they were doing their job & taking care of the infection. It's when the immune system is compromised and one has Toxo that the potential life-ending trouble begins. I hope she's okay.

She recovered quite well, besides the scar. That's exactly what the doctors said too. Luckily she has a mostly healthy immune system. Great post and keep up the amazing research!

Glad to hear it.

When i first read the title i imagined you researching a woman with a parasitic cat growing out of her like a parasitic twin...sort of.

Im almost disappointed that isnt the case...

http://www.anorak.co.uk/wp-content/uploads/2013/05/scan-cat-pregnancy.jpg comes to mind

1. What is the most important thing you could pass on to a dumb teenager who wants to be a neuroscientist someday?
2. What's the coolest thing you have ever studied in the world of psychology and neuroscience?
3. Pancakes or waffles?
4. How much do you make AFTER TAXES?
5. This isn't a question but damn this toxo study is cool. Good work, Sir.

• I've seen a lot of people get into my program with diverse academic backgrounds: some did physics, math, philosophy, computer science. Not everyone said "I want to be a neuroscientist" at 18 and did nothing else. The major, major thing I think is GPA in undergrad -- if you ace that, no matter the field of study -- graduate programs trust your work ethic. Also, if you want to try to do undergraduate research with a professor, take their class and do well in it. Be the top grade in the class if possible. Or, send emails as soon as you can to show interest in working in their labs. Be stubborn. I didn't get a research job until after undergrad despite persistent trying.

• I think something called blindsight is the most fascinating thing in neuroscience. People who have lose their visual cortex and cannot, subjectively, 'see' can still avoid obstacles as they walk down a hallway because a small visual pathway that does not require the visual cortex is still active. Here is the video. The crazy thing being they can't tell you what they see & don't themselves actually experience seeing. Makes me not believe in anything anymore, really.

• Duh.

• Let's just say I barely make, in thousands of dollars, my age. It's not pretty at all.

• Thanks!

As a university student who really struggles academically, I want to know if there is a neurological explanation for that? Is it because I have too much Toxo in my brain?

I highly doubt Toxo has anything to do with intellect. There is no evidence to link the two. At the very least, no studies have ever been done on it to my knowledge. Don't give up though just because it's not Toxo!

Could this in part explain why women are more attracted to cats than men? And if infected is someone likely to want to own more cats?

The idea that there are crazy cat 'ladies' and not crazy cat 'men' has been asked of me an infinite amount of times, & I simply have no idea. There are many published differences between male and female mice with Toxo, so given molecular and structural differences between male and female brains (yes, even in humans) it is likely to do different things to different sexes, but honestly we have no idea what those differences are.

A seemingly logical leap of thought would be that this would explain the 'crazy cat lady' stereotype. Does it?

It's certainly a compelling thing to think, and it keeps coming up (see Atlantic article linked above): there's something vaguely satisfying when things that we had previously observed find some ultimate, sinister, microscopic cause.

I would say we should not go beyond the data, though, because it can lead to people with mental illness potentially being even more ostracized and stigmatized than than they already are. There are some really interesting findings, though -- at least fifty studies now find that schizophrenics have higher rates of Toxo. Although we don't either how they acquired Toxo (from cats or eating raw meet, for instance) nor whether they got the parasite before or after their schizophrenic episodes. So, it's a really hard question.

Yeah correlation doesn't prove causaton. Maybe schizophrenics just don't wash their hands after handling cat feces and like to eat raw meat... or something like that.

Also what do the rate differences look like between schizophrenics and non-schizophrenics.

It's a subtle but important point, but: most of the studies will take a group of schizophrenic people and a group of non-schizophrenic people and ask the question "What are the group rates of Toxo?" In these it depends, but schizophrenic people tend have somewhere between 50%-300% increases in Toxo rates. So, if the normal U.S. rate of Toxo is about 20%, schizophrenics will have rates between 30-60%.

There are a lot of people with schizophrenia that do not have Toxo and a whole hell of a lot of people with Toxo that don't have schizophrenia, so it is not a 1 to 1 link. But, the basic finding that schizophrenics have higher rates of Toxo has been replicated over 50 times in various places around the world, so it's really starting to get public health people to take notice.

Hi Patrick, interesting stuff!

Kind of off topic but what do you know about Lyme Disease (Borrelia) and/or the coinfections including Babesia and Bartonella? I know Bartonella is also known as "cat scratch fever"

I only know that it's very different. Cat scratch fever is caused by bacteria, where Toxo is a protozoa (actually, very closely related to the tiny protozoa that causes Malaria). Protozoan are single-celled organisms, but they have a nucleus & all the good things that fancy single-celled (eukaryote) organisms have. So, it is very different. The brain is very good at keeping out bacteria, so Cat scratch fever does not goto the brain, as Toxo does.

How prevalent is this among cat owners? How can a person tell if their cat, or their own self, is infected?

(I asked you in the last thread and you said to ask you here)

I don't mean this to be a cop-out, but the rate in cat owners is really hard to assess. Some studies have found positive connections between cat ownership & Toxo, but others have not. What I can say is that it is generally thought that most people get Toxo through eating raw meat, not via cats. Cats certainly do carry it, and are a risk for pregnant women, but contamination in water supplies and in livestock is probably the major reason it is in 1/4 to 1/3 of humans.

The test for Toxo is a simple blood test. Vets will test cats if you ask.

If you're a woman, Toxo is always tested for if pregnancy is either at hand or something the woman is thinking about. Toxo can be quite bad for the fetus, and there are things women need to know if they are pregnant to prevent getting Toxo during pregnancy.

That being said, if you are male, I don't actually know of how to get tested other than maybe asking your Dr. nicely or enrolling in a study that tests for Toxo.

Why does it only reproduce in cats? How does it know when it's in a cat and not a large rodent or small dog?(Arguably all the same thing)

Not sure I'm allowed to plagiarize my own answer from earlier, but, because it's such a good question:

It is unknown exactly what factors in the cat make it the only ideal host for sexual reproduction. Toxo can reproduce asexually in all other mammals, but only sexually in the cat. Also, strangely, Toxo does not in general go to the brains of cats, although it will goto the brains of all other mammals it infects. So, there is something unique about cats (all felines, actually) that Toxo can detect and causes it to stay in the GI tract and never migrate out to the brain. It's an obviously good research question that hopefully someone answers soon.

One could maybe imagine a vaccine you give to humans that makes the GI tract of humans look like a cat GI tract to the parasite, meaning that Toxo would never leave & therefore never get into the brain, where it does its damage.

Can you get me into Stanford?

Seriously though, white, milk or dark chocolate?

Sure can. I can even get you a guest pass to the library and some nice free visitor wi-fi. :)

Is it really true that this parasite causes heightened aggression in men?

There are a ton of differences between mice & men, but testosterone is actually one of the nice similarities. As in, male mice have it, male humans have it and it fluctuates in the same way and probably relates to aggression. So, the testosterone and Toxo literature is some of the most compelling if only because the same effect (increase in T in those infected) has been found in both mice & men. I know of a study in mice and a few in humans, so -- it needs to be expanded a bit and repeated a few more times, but it's certainly interesting.

I recall reading higher levels of testosterone slightly impair the immune system, so those individuals would be more susceptible to Tox. G. instead of the parasite increasing testosterone. Do you know if pre and post infection testosterone experiments have been run in mice and what the results were?

Quite true, the studies in humans could be confused by order. Perhaps those high testosterone individuals eat raw meat because they can or don't wash their hands because they don't wish to.

In rodents, at least, where you can control cause & effect to some degree, we know the baseline levels of testosterone increase after Toxo infection. At least, a study or two has shown that.

What do you think about this finding? http://protomyxzoa.org/

I think it's not a finding until it is in a paper of some sort. Especially when something is so surprising (i.e. discovery of new organism) you want to be extra careful what you believe in.

How do you like being a graduate student at Stanford? How would you describe that culture?

It's all I know, in so far as it's the only place I've ever been a grad student. An unseen force is the surrounding tech industry being so close by. I've seen quite a few people in my program and others drop out to work on a startup, do a little startup on the side or go straight to a tech company after graduating. These are people that would have never dreamt of such a thing a few years ago, but academia is hard, often thankless and there are not many jobs. Tech is hard and also often thankless, but there are lots of jobs.

No questions and nothing personal, but seriously fuck all stanford people. You are the reason why 280 is a god damn parking lot by 7:30 am. I work off of page mill and seriously have to get to work by 6:40 am at the latest otherwise I have to spend close to an hour each way to go 20 miles.

I do like the idea of having parking spots on 280 to solve the problem. Also, I live on campus, so, actually you're the reason. :)