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 gondii. Toxoplasma 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 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.
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?  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.
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.