Mind-Controlling Parasites
Toxoplasma gondii and The Extended Phenotype
Imagine waking up one morning and all your fears are gone. You are suddenly no longer afraid of heights, closed spaces, clowns, or (in my case) cattle — embarrassing, I know. Of course, in contrast to fears based on realistic dangers, phobias are considered irrational and getting over them is commendable. Now imagine not only no longer fearing realistic dangers, but also actively seeking them. That has got to raise eyebrows. Besides the interesting relationship between Tom and Jerry, have you ever seen or heard of a mouse so fearless in the face of a cat? Well, buckle up then.
Unless you are a scientist conducting experiments, people are not particularly fond of rats and mice. They are, indiscriminately, considered vermin. House cats, on the other hand, are not only furry and cute, but also natural predators of these rodents. It therefore comes as no surprise that rats have an innate fear of cats and anything cat-related — urine and odor. Studies have further shown that rats are neophobic, i.e., they exhibit an intense fear of anything new. Interestingly, however, all this changes when these rodents are infected with Toxoplasma gondii, a protozoan iconic for manipulating the behavior of its hosts. Rats infected with T. gondii are suddenly attracted to cats and everything that comes with them. They even lose the neophobia, scurrying about all over the place. Fascinating studies by Webster (2007) and Tong et al (2021) demonstrated that infected rats preferred cat-treated areas, in stark contrast to their uninfected counterparts that avoided areas with even a few drops of cat urine.
But why does this parasite manipulate the behavior of these poor rodents? To what end? To make some sense of this, I call upon [perhaps] the most famous celebrity biologist of our times, Richard Dawkins. In 1982, Dawkins gave the biological community the idea that genes can act outside of the bodies of their possessors, i.e., genes can influence the organism’s immediate environment (including other organisms). He dubbed this The Extended Phenotype, a sequel to his 1976 book, The Selfish Gene. One of the best-known examples of an extended phenotype Dawkins gives is dams built by beavers. He contends that beaver dams are a product of beaver genes, ergo variation in ‘dam-making’ alleles leads to variation in the quality of dams. The caveat is that an extended phenotype must increase the overall fitness of the organism and should equally be subject to natural selection. Dawkins’ view of evolutionary biology is guilty of reductionism, but we will make do with what we have.
T. gondii undergoes both sexual and asexual reproduction, but it can only reproduce sexually in its definitive host, i.e., cats. Therefore, it needs a way to get transmitted to the cats to complete its life cycle. This is where our unfortunate rodents come in. The whole point of T. gondii making the rodents so cat-loving (let’s call it felinophilia) is so they can be an easy meal for the cat. Cruel, right? In an extended phenotype fashion, the rodent behavior we are observing is not due to the expression of rodent genes, but due to the genes of the manipulative Toxoplasma gondii.
Some investigators have questioned whether there truly is an adaptive value in T. gondii manipulating its rodent victims. In their paper, Worth et al (2013) demonstrated that another mouse parasite, Eimeria vermiformis, shows similar behavioral changes in the infected mice yet it does not require this predation to complete its life cycle. It has further been argued that T. gondii can maintain the asexual phase of its life cycle without any need for the sexual phase.
So, is there any weight to the adaptive value of T. gondii’s manipulation? Is it really an extended phenotype? National Geographic does a good job at showing us that lions and hyenas do not exactly ‘like’ each other. A three-decade study on the interactions between lions and hyena cubs may be insightful here. The evidence by Gering et al (2021) showed that, on average, hyena cubs infected with T. gondii exhibited costly behavioral boldness when interacting with lions and were thus more likely to be killed than their uninfected counterparts. Coincidence? Not if you recall that, broadly speaking, lions are cats, i.e., they belong in the family Felidae. The paper by Gering et al (2021) is wonderful, but I cannot do it justice in a sentence. Appreciate it here.
Now, since we humans are among the many intermediate hosts, would we exhibit some signs of being manipulated by this parasite? At what cost? We obviously are too big to be on our house cat’s menu and a majority of us do not spatially overlap with the big cats. We are a dead end. Webster (2001) argues that it is less likely that T. gondii would possess a recognition mechanism to restrict expression of its extended phenotype. That is too costly. The heuristic is for T. gondii to express the extended phenotype in whatever organism it finds itself in until it finds itself in the right organism. Although, it is worth noting that a study from two decades ago correlated toxoplasmosis in humans to an increase in the prevalence of road traffic accidents. I have not had the luxury to check if this has been corroborated, but if it has some merit, it is a scary prospect.
There are many more organisms known to manipulate the behavior of other organisms for their own fitness. One of my colleagues is obsessed with fungi and seizes every opportunity to casually mention Ophiocordyceps unilateralis. This fungus leads infected ants to a gruesome death. Another fungus, Entomophthora muscae, infects and kills female houseflies (Musca domestica) and releases chemical signals that entice male houseflies to mate with the dead female. A lancet fluke, Dicrocelium dendriticum, forces infected ants to climb to the top of a blade of grass so they can be eaten by the fluke’s definitive host. Insane, right? The list is inexhaustible. The extended phenotype strikes with no remorse. ’Tis true what they say, nature is stranger than fiction.
