XXII. Tying things up – what else is in store?
A lot. Many results that we were unable to finalize and publish relate to the health of the test subjects. In a number of studies, we asked the people how often they get the common cold, whether they suffer from allergies or headaches, whether they feel physically and mentally well. So far it seems that there’s no statistical significance to be found between these characteristics and toxoplasmosis. But in several subject groups, we observed a correlation between Toxo and smoking. For example, Toxo positive soldiers of mandatory military service smoked less than did uninfected soldiers. A possible explanation is that Toxo positive people have a lower tendency towards novelty seeking (a decreased Cloninger’s factor NS). And it’s known that people with a lower NS factor have a significantly lower tendency to seek out various kinds of risky behavior. There are fewer alcoholics, drug users and apparently fewer smokers among them.
Using a very detailed questionnaire, we determined how satisfied the people were with various aspects of their lives. It turns out that infected men were significantly less satisfied with almost all aspects of their lives than were uninfected men; but the biggest difference was between the answers regarding health. On the other hand, infected women are generally more satisfied with their lives than are uninfected women. The effect of Toxoplasma-gender on satisfaction with one’s health had a statistical significance of up to 0.003; the effect on overall satisfaction had a statistical significance of 0.040. But it’s not clear whether Toxo positive men are always negative whiners, and Toxo positive women happy-go-lucky, or whether men with latent toxoplasmosis really have worse health.
It’ll also be important to experimentally verify whether Toxo infected individuals really startle less than Toxo negative people. So far we’re relying only on what they told us in the Toxo questionnaire, but such subjective statements don’t necessarily represent reality. We’ll have to create a “startling” computerprogram (we’re already excited), and test whether infected persons are really startled more easily. Similarly, we need to verify that infected persons are less fearful. So far we’re planning to show horror films to small groups of students in the dark basement of the natural sciences building, and use an ECG (electrocardiograph) machine to monitor how afraid they are.
Speaking of scaring, we must also try to verify how the prepulse inhibition (PPI) of the startle response works in Toxo positive people. What does this mean? When we run background noise interspersed with irregular intervals of loud sound around 120 dB through the headphones of test subjects, the people are startled each time and blink. This movement can easily be recorded with an electrode placed in the vicinity of the eye. But if a softer acoustic impulse – in other words, a prepulse – precedes the loud sound, the people will not be as startled. From our perspective, the ability to measure PPI allows us to more meticulously observe the difference in the startling reaction of Toxo-infected people. Furthermore, it’s known that people with schizophrenia have significantly different results from PPI tests. Schizophrenia patients (probably not all, and to various extents) don’t have PPI of startling reaction, and react more to sound pulses with a prepulse than to those without. But recently we discovered that morphological differences in the brains of schizophrenics are actually present only in Toxo positive patients. You already know that these morphological differences don’t occur in Toxo positive non-schizophrenics (Chapter XV). Therefore, we should determine whether the differences in PPI of schizophrenics and non-schizophrenics could also be caused by toxoplasmosis, which we know to be more prevalent in the schizophrenic than in the normal population.
Another issue we’d like to revisit regards the effect of toxoplasmosis on the levels of steroid hormones. So far, it’s a mystery why Toxo affects testosterone levels in students – increasing them in males and decreasing them in females – but does not affect them in the patients of the immunology clinic. First off, we must try to confirm the results observed in the students on other groups (at the time you’re reading this, we’ll have tested the soldiers) as well as on lab animals. In mice it seems that toxoplasmosis lowers testosterone levels in both males and females (60). Furthermore, we must look at the levels of other steroid hormones, such as the female hormone estradiol and the stress hormone cortisol. The fact that infected women give birth to more sons indicates that they might have increased levels of estrogen. So far, our results haven’t confirmed this hypothesis (the observed difference in estrogen levels was in the predicted direction, but not statistically significant). But I must remind you that we studied hormone levels on a group of patients attending an immunology clinic, who might differ from in hormone levels from the general population. Once again, the truth is that we have data from other groups to test the hypothesis, but haven’t grasped the time to analyze them. And so that I have an alibi beforehand, the hypothesis explaining the increased sex ratio in Toxo positive mothers by a higher concentration of estrogen isn’t actually ours, but one which William H. James (96) suggested to explain our sex ratio data – at least we won’t be so disappointed, if we don’t manage to prove it.
We’re very excited for the results of scent testing on humans. It’ll be interested to verify whether some of the differences in the olfactory preferences observed in infected mice will also apply to people. So far, our results are quite promising, but I’d hate to jinx it (Fig. 48). It’s a shame that currently the department of natural sciences is not supportive of keeping infected animals. In the past we conducted a number of interesting experiments on mice, and found that, under certain circumstances, infected females prefer the scent of infected males above that uninfected males. The differences in the attractiveness of male scent seem to relate to an effect discovered and meticulously studied by Denisa Hladovcová during her undergrad work in the department of zoology. Her results show that in infected males, the production of proteins
Fig. 48 The effect of Toxoplasma infection on the perception of the odor of cat urine. Toxoplasma-infected and uninfected students evaluated on a 7 point scale the pleasantness or repulsiveness of the urine odor of various animals (cat, horse, dog, hyena, and tiger). Only in case of cat urine was there a substantial effect – infected men liked the smell of cat urine more than did uninfected men, whereas infected women disliked it more than uninfected women. Our results demonstrate that Toxoplasma significantly changes the olfactory preferences of infected people; and that the phenomenon of fatal attraction, described originally on Toxo-infected Norwegian rats and mice, is also true for humans. It is interesting that the originally described attraction occurs only in men, whereas women react in the opposite way. The Z score calculated for individual evaluators (y axis) represents unpleasant odors with negative numbers, and pleasant with positive numbers. The evaluators were exposed only to small amounts of each sample, so the intensity of the odor was very low. For this reason, very few students actually guessed the true nature of the samples. For example, they usually guessed horse urine to be mushrooms or manure, and cat urine to be from the hospital or sea.
known as major urinary proteins (MUPs) decreases over the long-term. Mice use these proteins to release pheromones, molecules used for scent communication. Interestingly, the effect of toxoplasmosis on MUP production is incredibly strong – for the studied strains of mouse and Toxoplasma, it was comparable to the effect of castrating the male mouse. Males seem perfectly healthy eight weeks after infection, but they’re no longer too keen on rolling in the hay.
What currently interests me the most is the role of the Rh factor in protecting against the negative effects of latent toxoplasmosis. I’d like to know which effects are influenced by the Rh factor; how Rh positivity can be beneficial or harmful whether the protective effect of Rh positivity is due to the gene for Rh positivity or other genes closely associated with it. And above all, I’d like to know if Rh positivity protects against further negative effects, not just those of toxoplasmosis. Then, of course, we’re interested in discovering the mechanism behind all this. But I’m afraid that unraveling this mystery will have to wait for a physiologist or molecular biologist. Until the function of the RhD molecule is discovered, we evolutionary biologists cannot explain how Rh positivity can protect against Toxoplasma. So fellow scientists, hop to it – I’m eager to see what we’ll find
As I’m nearing old age and growing forgetful, it might be in my own interest to explore the possibility that toxoplasmosis is associated with Alzheimer’s. There is evidence to suggest that dopamine production – specifically, the death of dopamine-producing cells – plays an important role in the disease. According to our results, latent toxoplasmosis in both mice and humans is accompanied by an increase in dopamine levels in the brain, which may be related to the presence of two genes coding for enzymes involved in dopamine formation. It’s possible that when dopamine is produced excessively in the brain, the dopamine-producing cells die off more quickly. A similar mechanism might also cause Parkinson’s disease, since dopamine is known to play an important role in its onset. So far results are ambiguous: in 2010 two independent articles were published by Turkish researchers, one proving and the other refuting a relationship between latent toxoplasmosis and Parkinson’s disease (97) (98).
Toxoplasmosis is involved in other neurological effects, too. Aside from migraines, Toxoplasma plays a role in some forms of epilepsy (99). So far, this disease has but a few studies to its name. One of the more convincing articles comes from Turkish authors, and found that the frequency of toxoplasmosis was 52% among 50 patients with cryptic epilepsy, 22% among 50 patients with other forms of epilepsy, and 18% among 50 persons without epilepsy (100100). Other studies show that toxoplasmosis could trigger obsessive compulsive disorder in some people; and several articles indicate a connection between Toxoplasma and autism (101).
Don’t think that I’m blaming toxoplasmosis for all the health problems we face today. (That’s why I haven’t mentioned the opinions of Ukrainian doctor Vladimir Krivonos, who claims that this parasite is even responsible for balding – which could be explained by the increased synthesis of testosterone in infected men – and primarily for some kinds of cancer, including prostate cancer. Since I’m writing this in parentheses, it doesn’t actually count, and I am free to distance myself at any time.) I try to be as objective as possible, and judge Toxoplasma fairly, so I readily confess that there exist a number of diseases for which no connection to Toxo has been proven. But even objectivity and fairness can’t be overdone: one could argue that no connection has been proven simply because these diseases have never been tested for a connection to Toxo. Well, at least we have a despicable suspect, as our most famous playwright, poet, composer, teacher, traveller, philosopher, inventor, detective, mathematician and sportsman (of course not Vaclav Havel, but Jara da Cimrman) says in the play “Murder in a Chair Carriage.”
Meanwhile, Toxoplasma flourishes under the disinterested eye of the public. In most European countries, it’s decreasing in the population, which may be due to the fact the kids who once played in the sandbox now spend their days in front of a computer screen. But whatever we may tell ourselves, the events in the western-most periphery of Asia supercontinent are not so important. Unless current trends are rudely interrupted, China and India will finally achieve a consumer society. Then their households will not only get 3D television, but also housecats. I’d be surprised if they didn’t – having a cat makes life much more enjoyable than owning a 3D TV (I know from experience, because recently I had six of them in my house – six cats, that is, not TVs). As a result, the global prevalence of toxoplasmosis certainly isn’t decreasing. And be warned, today’s 30% world-wide prevalence includes everybody, including infants – which means that every other individual will become infected with Toxoplasma sometime in his life. Latent toxoplasmosis cannot be cured. To be honest, no one (aside from the before-mentioned Vladimir Krivonos) has actually tried it – and why would they, since the latent form is officially harmless. Actually, already infected woman aren’t at risk from catching Toxoplasma during pregnancy, so their children are safe from congenital toxoplasmosis. It would probably be worthwhile to see if latent toxoplasmosis can be treated by certain antipsychotics, which have been shown to specifically and strongly inhibit the reproduction of Toxoplasma in tissue cultures. It would also be advisable to see if the temporary health problems in a significant number of people given preventative anti-malaria drugs aren’t actually the side-effect of dying Toxoplasma cysts. Toxoplasma is closely related to the Plasmodium which causes malaria (both of them are sort of like strange plants – their cells actually contained modified chloroplasts known as apicoplasts). Therefore, it’s quite likely that the same drugs may kill both of these parasites. We certainly should look at the levels Toxoplasma specific antibodies in people using various anti-malaria drugs.
But the most important weapon against Toxoplasma should be prevention. Cats – and primarily today’s domestic cats – are the definitive hosts of Toxoplasma. The spread of toxoplasmosis in the human population could probably be contained using an oral vaccination, which would immunize even feral cat populations around human settlements. Getting rid of Toxoplasma isn’t feasible, since it’s too clever a parasite with a wide range of intermediate hosts. The only way might be too kill off the entire cat population – but I wouldn’t dare to suggest this even jokingly, for fear that my family would disinherit me and perhaps even tell our tomcat Freddy (he already suspects me; whenever I’m typing this book in bed, he decides to interfere by lying on the keyboard). But it would be feasible, through a good vaccination program, to decrease the global prevalence of toxoplasmosis to under 5%, a prevalence seen in many parts of Asia. With an effective form of chemotherapy, it might even be possible to significantly decrease the health and subsequent economic effects of all forms of toxoplasmosis. In a world without Toxoplasma, women might be less social, friendly and stylish, men about three centimeters shorter and have lower levels of testosterone; but when we consider that lack of Toxo would also decrease the number of car accidents, suicides and schizophrenics, I think that it would be worth it. In a world without the lovely Toxoplasma, I’d have to find another similarly controversial and exciting research topic. Attentive readers* of this book might think that this would be an endeavor, the difficulty of which would only be comparable to that of developing a Toxoplasma vaccine. But you needn’t worry about me. The other day I was returning to Prague after giving a lecture in Brno. At home, I realized that I wasn’t at all tired from the long bus ride, although I’m usually weary after traveling more comfortably in a train. I’ve observed a similar thing when coming home from the university. I push away from the computer at five thirty, still chipper, but after a forty minute ride home in the subway, I have to stretch out on the bed and the most difficult task I can accomplish in the next half hour is to lend my body heat to the above-mentioned Freddy, who lays on my belly while purring in sympathy. What if my two observations were related? And what if this meant that... But someone surely would have discovered already. Although... It wouldn’t be too much trouble to quickly run a questionnaire... Tomorrow a hundred of my students are taking an exam, and I could give them a short questionnaire to complete afterwards to determine when they feel tired. In a couple of hours, I’d know whether there’s a grain of truth in my hypothesis. And if I discovered a statistically significant effect or at least some trend, I can put a similar questionnaire on my blog and the frequently-visited blogs of my friends; likewise, I can post a questionnaire on a popular web page devoted to health. Furthermore, I could organize an entertaining experiment on the Prague metro with volunteers who sign up on my Facebook page, Guinea pigs... Do want to hear our results? I won’t tell you them just yet, but get ready – it’s gonna be the bomb!
The end (for now, at least)...
* A mythical creature that appears in the particularly fantastical dreams (of a slightly erotic character) of the authors of science popularization books.