Rethinking an Icon of Manipulation

A rat that wants to meet cats, would be doomed, no? Agreed. A rat like this would have to be downright crazy. Yet that’s what’s purported to happen to rats infected with Toxoplasma gondiiToxoplasma is a single celled parasite that makes its home in the brain and is believed to change the behaviour of its rodent host.  Rats, or mice, with Toxoplasma have been shown to act favorably to cat urine, where as those without naturally avoid the scent of cat urine all together. And why would a parasite do that? Because it wants the rat to be eaten by a cat so it can live on and sexually reproduce in the cat.

Toxoplasma parasites inside a cyst on a mouse brain.

Toxoplasma parasites inside a cyst on a mouse brain.

Toxoplasma gondii  is a parasite that has a simple way of life. It also has little preference for hosts, meaning it can live in most any mammal on the planet and can reproduce asexually and sexually. However, it can only do the latter in a cat, after which the offspring are shed in cat feces. Any mammal that comes close to cat feces, or aren’t hygienic after handling feces ie. humans with cats are likely to get Toxoplasma.  The other two ways in which Toxoplasma is passed on to new hosts are from mother to child during pregnancy, which is why doctors warn pregnant mothers to avoid cat litter, or by eating meat of an infected animal. Most immune systems are able to suppress the parasite and keep it from causing damage; but those with compromised or naive immune systems, such as HIV patients, or unborn children whose mothers haven’t been previously exposed to and passed on antibodies to Toxoplasma, are at real risk for inflammation of the brain and death.

Once in a host Toxoplasma is carried through the blood stream, multiplying, and eventually getting shipped to the brain.  The fact it rests in the brain lends credence to the theory that it can change the behavior of the rats and make them more susceptible to predation by a cat.

Toxoplasma has been one of the most iconic examples of a parasite mind control.  A study went as far to say that humans infected with Toxoplasma, of which there are many, possibly up to one in six are infected, are more prone to risky behaviour, not unlike a rat that wants to smell cats.   That particular study was hotly debated but the idea that this tiny parasite is controlling rodents has remained, ingrained in parasitology and often used in undergraduate classrooms as an example of the spectacular phenomenon of host manipulation.

jack in litter

When my girlfriend got this guy, I got a really fast motorcycle. Connection?

Now what if it wasn’t quite true.   A recent paper by Amanda Worth from the lab of Andrew Thompson at the School of Veterinary and Biomedical Science in Murdoch, Australia has called for a re visiting of the research surrounding this iconic parasite system.  The paper, published in 2013 in Trends in Parasitology, is titled: Adaptive Host Manipulation by Toxoplasma gondii: fact or fiction? [1] The title here is catchy but also worded very aptly as it calls into question the ADAPTIVENESS of the host manipulation, not the fact that some hosts do appear to be manipulated and this is a big distinction.  In order for the parasite to have evolved this ability to manipulate its host there must be a payoff, evolutionary speaking, for the parasite otherwise the trait is not adaptive.  The alleged payoff for Toxoplasma making its rodent hosts more likely to be eaten by cats is sexual reproduction and transmission to new hosts.  Sex allows for the swapping and mixing of genes which can lead to novel genes, gene combinations and by extension traits that can be beneficial to the offspring.  The right environment for sex is only in a cat and this is believed to be a strong enough driver of selection to allow for adaptive host manipulation to occur.  The authors of this paper however raise some very good points suggesting that sexual reproduction may not be as important to these organisms as we once thought and that a review of past studies and their conclusions is warranted.

In this review the author poses the questions that Toxoplasma transmission to a cat may not increase the parasite fitness, meaning the benefits of sexual reproduction to the species and transmission of the parasite by cats is not necessary for the continued survival and spread of the species.  Toxoplasma, globally, has very little genetic variation as a species.  Despite the fact that sexual reproduction does exist in this system the majority of Toxoplasma populations have a clonal, meaning identical, genetic makeup, in fact only three main lineages dominant North America and Europe.  This lack of genetic variation indicates that the sexual cycle and the mixing of genes is not that important for the success of Toxoplasma species.  They seem to be doing fine without lots of genetic mixing.   The lack of variation may also occur because the majority of transmission that occurs in nature is not from cats that have shed the offspring of the sexual cycle.  The author proposes this scenario; a mouse can give birth to multiple pups in multiple litters throughout its life and could pass the parasite to a number of those offspring each pregnancy.  Conversely, offspring of sexual reproduction must pass through the cat, wait and survive long enough in the environment to encounter a host which is not even guaranteed.  Toxoplasma can infect many hosts from, cats, humans, elk, whales nearly every mammal.  It has even been found on an island that does not have cats.  With all these hosts passing Toxoplasma through the food chain and to their children, maybe cats aren’t the be all and all, despite what YouTube may indicate. The long term benefits of genetic mixing in a population are difficult at best to predict and measure, meaning there may be some as of yet unseen reason as to why the parasite has evolved to maximize transmission to cats but the authors lines of reasoning  at least make one think that sex may not be that important.

The author also points out that no studies have shown that infected rats actually do get eaten more often than uninfected counterparts. This is a central piece of the puzzle, if the behaviour isn’t going to be of use why would the parasite evolve to manipulate it.  It is possible that this behaviour may just be a by-product of having a parasite in your brain and not at all directed by the parasite specifically.  This paper references one study showing that the mice infected with Eimeria vermiformis, also show a decreased aversion to cat urine, even though this parasite does not require predation to complete its life cycle.  Continuing on with this line of thought, being more comfortable around cat urine does not necessarily mean rats will run into live cats more.  The paper also references studies showing rodents typically respond much stronger to the scent of cat fur than urine. It is entirely possible that this response to fur may be un affected by Toxoplamsa even if the response to urine is.  A sure way to test that infected rats get eaten more would be to set up an experiment in which infected and uninfected rats are put in a closed environment and hunted by cats a la Gladiotor or the Hunger Gamess, and see whose left; but as the author points out this would be highly difficult to do due to ethical reasons.

cat gladiotor

The internet, where cats are gods.

This paper also speaks to the pasts studies that have been done on this system and point out that the conclusions are not unanimous.  Some studies show no affect, some show the altered behaviour but also show a number of  other affected behaviours, meaning the overall cognitive function of a host is impaired, not just the supposed parasite controlled functions.   Papers like these are few and invaluable because they look at things many assume to be true and remind us all that science is all about looking at all possible explanations.  It also reminds us that we cannot let preconceived conclusions influence the interpretation of results and those results need to be adequately reproduced in order to draw stronger conclusions.  Maybe Toxoplasma is affecting our brains but maybe it isn’t and these are the types of questions that need to be explored.  Or maybe I have a parasite in my brain, urging me to write this so we forget all about this silly little parasite and its sinister mind control. Yeah, that’s right, don’t worry everything’s fine, I wouldn’t dream of taking over your brain…



1.            Worth, A.R., A.J. Lymbery, and R.C.A. Thompson, Adaptive host manipulation by Toxoplasma gondii: fact or fiction? Trends in Parasitology. 29(4): p. 150-155.


Field Work: A Walk in The Park

This blog post was originally posted on The HPI  Parasite Blog. Check me out on twitter, @bvanparidon for more information about this great graduate student blogging project.  It also appeared on Science Borealis  a Canadian science blogging community, check them out and here is my piece about field work titled Field Work: A walk in the park.

One of the great things about working with parasites and especially those using wildlife hosts is the chance to leave the lab and do some field work.  For me, a PhD student working at both the University of Lethbridge and Calgary, this means a trip to the Cypress Hills Interprovincial Park in southeastern Alberta.  This park spans the border between Alberta and Saskatchewan and is somewhat of an anomaly as it is an island of sorts in the middle of the vast prairie landscape of the Canadian west.  Cypress Hills is an area that was not covered and flattened by the glaciers of the last ice age, resulting in hills that rise 1400 meters above the prairies.  This creates an island ecosystem protruding from the seas of wheat and suitable habitat for many species of animals.  The park boasts a large population of elk and deer, which in turn feeds a healthy population of roughly 30 cougars.  It also houses many species of birds and is a welcome stopover in the migratory routes of many bird species each year.  Arguably the most interesting inhabitant to the park however is the liver fluke (Trematoda) Dicrocoelium dendriticum.

This small fluke is believed to have been introduced to North America and subsequently Cypress Hills from Europe where it is reported to be endemic.  The incredible thing about this parasite though is the life cycle. Dicrocoelium has a complex life cycle involving three hosts.  Adults living in the livers of final hosts produce eggs that end up in the hosts feces where they are ingested by a terrestrial snail.  In the snail the parasite develops, grows and divides into many individual cercaria (tiny, fork-tailed trematode life cycle stage produced through asexual division) and are coughed out of the snail in a mucous encased “slime ball” (it is actually referred to as a slim ball in some of the literature).  Now this is where it gets truly interesting.  Ants will come along and presumably bring this slime ball back to the nest where they all chow down on it.  Once inside the ant the majority of the parasites move to the abdomen and encyst there as meteceracia (the stage infective to the final hosts) where they wait to get passed on to the final host.  The final host in this case is any number of grazing ruminants and in the park specifically it can be deer, elk or domestic cattle that are grazed there.   So how do trematodes in ants get into the livers elk?  Remember how I just said that the majority of parasites in an ant go to the abdomen? The minority, in this case one, makes its way to the bundle of nerves in the ants head that constitutes the ant brain.  Here it sets up shop by wrapping around the nerve bundle.  Ants infected with Dicrocoelium all have a parasite in the brain and all begin to act shall we say, clingy but not towards other ants they may have a crush on but rather towards plants.  During parts of the day that are cool and won’t dry out an ant sitting in the open the infected ants climb up plants and lock onto leaves and flowers with their jaws.  Here they remain waiting to be accidentally ingested by a grazing animal so they can get to the oh so tasty liver.  This is an amazing example of host manipulation by a parasite and yes, this guy exists in Alberta less than an hour south of Medicine Hat.

dandeliiondandelion 2

Infected ants clinging to dandelions in Cypress Hills (Brad van Paridon)

Naturally someone needs to be investigating this oddball and that means someone has to get out there and collect samples of this thing from the park.   Naturally that sounds like a pretty sweet time so I took up the cause and have been working on this system since 2011, which brings me back to the joys of field work.  My latest trip to the park was November 2013 and the goal was to collect fresh livers and adult parasites from elk that are killed in the annual elk management hunt.  We do so with lots of help from the Alberta Parks Staff, Conservation Officers and of course the hunters themselves.  Basically any time an animal is shot in the park it needs to be called in to the CO’s who come out an verify the tag.  We just tag along, show up at the kill and get a fresh liver.

gut pile

Myself next to the gut pile from a recently deceased elk, and you thought they smelt bad on the outside. (Brad van Paridon)

I have been touting the joys of field work this whole post and we always have a great time. How could we not with scenery such as this to enjoy.

scenery 1              scenery 4

However, during one foray out into the park to find some hunters that had just called in a kill, things became slightly less pleasant.  As is normal in the park a thick fog descended onto the flat prairie like plateau of the hills.  The three photos above that look as though they could have been snapped on the prairies are actually the plateau of the hills and are at an elevation of 1400 m where fog and clouds come and go quickly. Blanketed in fog it looks something like this.


Aside from the obvious driving hazards associated with travelling in thick fog, we must remember that hunting is also going on in these areas and although it is technically illegal to shoot into fog, poor decisions are made on a daily basis.  So this is where we found ourselves.  Outside the truck, standing in the middle of a field, surrounded by fog so thick we can’t see more than a few meters in any direction and trying in vain to locate the hunting party that has just taken down an elk.  Just then we got in touch with the hunters via cell phone and things were looking up.  We concluded we were in the right area but then the man on the other end of the phone stops and says” I gotta go they’re (meaning the elk herd) are coming back around and we are going to take another shot” and then he hangs up.  Well, we quickly put it together that this was for sure time to leave the area as we might get caught in the middle of a live fire exercise.  Needless to say we made a quick exit and upon returning to the area in an hour so found three kills about 100 m apart and no more than 200 m from where we were originally standing.  One of these kills too had not been claimed and was being investigated by the officers present, a situation that might occur if someone did not know they had killed multiple animals until the fog lifted. Hmmmm, makes you think.

Now, I don’t think we ever really came close to being shot, I never heard gunfire while out in that field, but it did make me think that field work really  isn’t just a walk in the park.  It also made me reflect on other situations I got myself into in the name of field work.  One time while searching for infected ants I disturbed a wasp nest and was stung more than seven times on my face, chest and neck while running away.  I have exposed myself to swimmers itch while collecting aquatic snails, thankfully never got it though.  There was the time I stumbled across what appeared to be an ideal cougar den complete with bones from the last meal.  This time I was thankful that no one was home.  But these things could happen to anyone who frequents the outdoors right?  That is what I told myself as walked through the pitch black of the Cypress Hills night, alone, carrying bags of liver sections, that would surely entice one of the many cougars in the park, over to the cougar garbage bins.  On second thought maybe I am bringing some of this on myself.

Bradley van Paridon