Those of you who have followed the game or series The Last of Us will recognize the name Cordyceps. This is the fungus that causes a global pandemic of zombies to break out and start attacking their fellow humans. The writers, in this case, did a good job by using this infection in their story.
Cordyceps is a genus of over 600 fungal species spread around the world called endoparasitoids, meaning they must live and reproduce inside other living things—in this case, insects and other arthropods. Cordyceps produce a mycelium, or hair-like structure called hyphae that invade the host insect and replace its tissues. Then, they bear small “fruit” like sacs that contain spores, which become thread-like ascospores, breaking into fragments and believed to be infective. The really scary thing is what it does to the brain of the infected host.
According to an excellent article in Ars Technica, the fungus attaches to the ant and germinates. Like every good sci-fi monster, it starts to send long tendrils through the ant’s body, surprisingly avoiding the brain. Once in the body, the fungus releases chemicals that change the ant’s behavior. The ant is usually ejected from the nest by its companions, a quarantine if you will. Once out of the nest, the ant will find and climb to the top of a plant stem, stopping at precisely a height of 25 cm, which is the perfect temperature and humidity for the fungus to grow. Now, the fungus releases a chemical that causes the ant’s jaws to clamp down and lock onto the plant stalk, deactivating the muscles after contraction. Cordyceps then extends a stalk through the ant’s brain, killing it, and grows into a large bulb on the head. It waits for a ruminant, like a cow, to come along and eat the grass, which is where the fungus can continue its life cycle—the entire purpose for its control of the ant.
Now let’s move to Chordodes formosanus, also called the horsehair worm. These worms are obligate parasites that usually reside in the intestines of the praying mantis. They are unable to complete their life cycle without infecting a suitable host like the mantis. To get to the mantis, the worm lays eggs in ponds and streams. These eggs stick to aquatic insects, which are then eaten by crickets and mantises. Once inside the host, the eggs start to grow and release chemicals that affect the mind of the infected insect. It can do this because the worms, over their evolutionary history, have captured the necessary genes from the hosts and incorporated the DNA into their own genomes. This is called horizontal gene transfer and really complicates our understanding of evolution. Known to be responsible for antibiotic resistance and thought before to only occur in bacteria, we have now found it happening between snakes and frogs through shared parasites like leeches. Over 1,400 crossover genes stolen from the mantis have been identified so far in the worm. Closely related horsehair worms that can live independently don’t have these genes. Being able to produce chemicals that the brain uses as neurotransmitters or other control chemicals allows the parasite to operate the mantis-like a game controller. The mantis goes from avoiding shiny surfaces so it won’t collide with water and get stuck to being attracted to shiny surfaces, causing the mantis to suicide in water, allowing the worms to start laying their eggs again.
There is another worm called Leucochloridium paradoxum, which eats waste products in the intestines of birds and then lays eggs that are excreted with the bird’s waste. Snails come in contact with the droppings and ingest the eggs. The eggs hatch and develop into larvae, moving into the snail’s tentacles/eye stalks, forming a sac that blinds the snail and replaces the eyestalk entirely. It then makes the eyestalks become colorful and pulsates them at a rate of up to 80 contractions per second. It also takes over the snail’s brain and controls its behavior, forcing the snail to go to a well-lit area where the dancing eyestalks look like a caterpillar to a bird. The bird eats the snail, or at least the tentacles, and once ingested, the parasite matures to adulthood in the bird, mates with other adults, and starts producing more eggs, repeating the cycle.
Now, we come to mammals, mice specifically. Mice are normally afraid of the dark and terrified of cats. Putting cat urine in an area will usually ensure that mice will avoid it like the plague, so to speak. Unless, however, the mouse has been infected with a protozoan parasite called Toxoplasma gondii. This parasite can only reproduce in the intestines of a member of the cat family. They are limited to cats because cats don’t produce delta-6-desaturase in their intestines as almost all other mammals do. Once the parasite reproduces sexually in the cat, it produces a thick-walled cyst called an oocyst. Think of this like an eggshell with a zygote inside. Other animals, including mice, will ingest these. It is one of the most common parasitic infections in the world. Once ingested, it goes into an asexual phase. When this phase occurs in mice, it migrates to the central nervous system, muscles, and eyes. Once in the central nervous system, the parasites infect the hippocampus and amygdala. These structures allow brains to store memories and recognize threats. Cysts form in these regions that change the mouse’s mind, so to speak. It causes the mice to fear cats no longer, though they will still fear other predators. In fact, the mice will be attracted to the smell of cats, particularly feline urine. And they will no longer fear the dark. This leads to a much higher chance that the mouse will be eaten by a cat, which is what the parasite needs to survive. According to an excellent study from Parasitology Research, it is believed these behavioral changes take place through the manipulation of neurotransmitters in the brain, though the exact mechanism is not clear.
And this all brings us to the scary part. It is well known that the symbiotic intestinal flora in the human digestive system is critical to health, producing some vitamins we cannot make and even serotonin, an important neurotransmitter believed to be important in depression, obsessive-compulsive disorder, and other mental conditions. Changes in these flora may lead to pathological conditions such as mood disorders and obesity. What is also well known is that about sixty million Americans are infected with Toxoplasmosis gondii. This infection has been associated with many human mental diseases, including impulsivity, schizophrenia, and even suicidal behavior. About 800,000 people worldwide die by suicide every year after about ten million attempts. In the case of “successful” suicides, three meta-analyses confirmed that there is an association between successful suicide attempts and this parasite, both in those with schizophrenia and those without. Other studies have confirmed a clear association between this infection and impulsive behavior in general, finding that “The widespread dissemination of toxoplasmosis around the entire globe, concerning the research carried out so far, indicates that T. gondii may contribute to hundreds of thousands of deaths worldwide, including deaths in road accidents, accidents at work, and suicides.”
In light of this research, should we test everyone? And who should we treat? Right now, the treatment is about $20,000 and is limited to pregnant women, as Toxoplasmosis during pregnancy is often fatal for the fetus and to the immunocompromised. So, should we treat only those who display these behaviors and test positive for the parasite? Or just leave well enough alone? Further study needs to be done, but I have a suggestion for you. We could genetically alter all domestic cats with CRISPR technology, requiring it like a rabies vaccine so that they produce delta-6-desaturase like almost every other mammal, wiping out T. gondii. Since humans rarely interact with wild felids, our infection rate would drop dramatically, possibly wiping it out entirely in humans. What do you think?
L. Joseph Parker is a distinguished professional with a diverse and accomplished career spanning the fields of science, military service, and medical practice. He currently serves as the chief science officer and operations officer, Advanced Research Concepts LLC, a pioneering company dedicated to propelling humanity into the realms of space exploration. At Advanced Research Concepts LLC, Dr. Parker leads a team of experts committed to developing innovative solutions for the complex challenges of space travel, including space transportation, energy storage, radiation shielding, artificial gravity, and space-related medical issues.
He can be reached on LinkedIn and YouTube.