How can you control a parasite

evolution : Darwin's demons - how parasites turn their hosts into zombies

David Hughes is a zombie researcher. In his laboratory at the State University of Pennsylvania, the biologist is studying a gruesome spectacle that he has observed in the rainforest in Thailand: wood ants, which have been possessed by a tiny yeast, leave their nests high up in the trees as if remote-controlled. Half climbing, half falling, they are drawn down to the forest floor. There they climb smaller plants and bite into a vein on the underside of a leaf. Only then does the fungus, Ophiocordyceps unilateralis, kill the zombie ant with a cocktail of chemicals. Fungal threads grow from the feet of the carcass, attaching it tightly to the leaf, and a stalk grows from the head of the dead animal. A fruiting body forms at the tip of the stem, from which spores rain down on the ground, infecting new ants.

The ant's crazy behavior is only for the fungus. Because it can only thrive near the forest floor, where it is damp and cool. “This microbe is no fundamentally different from the yeast in your beer,” says Hughes. "That she can control such complex animal behavior is absolutely fascinating."

And Ophiocordyceps isn't the only parasite that controls its host's brain. In recent years, researchers have discovered more and more examples of mind control: a wasp larva causes a spider, for example, not to stretch its normal web, but rather one that the larva uses to build its cocoon. Then she sucks the spider out. And a worm that grows in crickets finally makes them jump into the water, where the now six-inch-tall animal snakes away to find a partner while the insect drowns.

For a while it was like collecting stamps, says Joanne Webster of Imperial College London: "There were some nice examples and then researchers came and said 'Oh, here's another one'." Now it's about more: Scientists want understand how exactly the parasites take possession of their host's mind. At the beginning of the year, the journal "Journal of Experimental Biology" published a special issue on the subject. “The whole field has moved on,” says Webster, who worked on the special issue.

For a long time, parasites were considered to be the lowest level of evolution, as degenerate living beings that are dependent on other, higher living beings for survival and reproduction. In reality, parasitism is an evolutionary success story. Scientists estimate that almost half of all living things on earth are parasites.

In his book "The Selfish Gene", the biologist Richard Dawkins described living beings as machines, built by genes to ensure their own survival. The survival machines eat and court and fight and cooperate, but in the end they are just machines that serve the result for a single purpose: to make new copies of themselves.

Parasites have brought this evolutionary craft to perfidious perfection. With hooks and claws, suction cups and drill heads, they hijack the machines that have built other genes, castrate, direct, in short: manipulate them. Parasites are the secret rulers in nature. They are Darwin's demons.

But how can a fungus control an ant? "If the mind is just a machine, then it can be controlled by any being who understands the code and has access to the machinery," wrote Webster in the introduction to the special issue of the Journal of Experimental Biology. Many parasites have access. They prefer to settle in the brain because the host's immune system cannot fight them there without endangering the brain itself. And the code? Chemistry, says Hughes. "After all, there are no switches and levers that the parasite can simply sit on."

It now seems clear that ophiocordyceps cause the ant to have seizures that prevent it from climbing back up to its nest. Hughes tries to decipher which substances lead to it. He shipped the fungus and ants from Thailand to his laboratory in the USA. In Petri dishes, he can keep ant brains alive long enough to infect them with the fungus and study the effects. The genome of the fungus has also been deciphered in the meantime. “The question is: does the fungus produce certain substances that the ant's brain otherwise uses, or are these completely new substances?” After all, a related fungus produces the forerunner of LSD.

Sometimes the explanation is amazingly simple. In the "canopy disease" a virus attacks the caterpillars of some moths. The pathogen guides the caterpillar to the top of the tree and multiplies until it is completely filled with virus particles. Then it slowly dissolves the caterpillar so that millions of virus particles rain down on the leaves, where they can infect other caterpillars.

In an elegant experiment in 2011, researchers were able to show that the virus only causes the caterpillars to climb if it carries the gene “egt”. These are the building instructions for a protein that intervenes in the hormone metabolism of the caterpillar. It destroys the hormone ecdysone, which normally causes the young caterpillar to withdraw and molt for a few hours at night. Without this signal, the caterpillars would possibly be put into a kind of "eating flash" that makes them climb higher and higher, says Hughes.

Other parasites seem to intervene in the brain in much more complicated ways. Toxoplasma gondii is a protozoan that lives in the intestines of many cats and reproduces there sexually. Other animals such as pigs or mice, but especially rats, become infected through the faeces. In the brain and muscles of rats, Toxoplasma forms round clusters of cells. If the rat is eaten by a cat, these cysts infect the cat and the cycle starts all over again.

Obviously, the parasite doesn't leave that to chance. Rats that have Toxoplasma cysts in their brains lose their innate fear of the smell of cat urine. Instead, she seems to be drawn to the smell. Researchers led by Robert Sapolsky from Stanford University in the United States have shown that the circuits in the rat brain are changed by toxoplasma in such a way that the smell of cat urine does not activate the fear circuits, but rather neighboring circuits that convey sexual attraction. In addition, Toxoplasma also increases the amount of the neurotransmitter dopamine in the brain and produces testosterone, says Webster. "There are very different mechanisms involved, and it is bizarre that this can lead to such a targeted behavioral change."

Humans can also become infected with Toxoplasma, for example when cleaning the litter box or when eating meat that contains cysts. Around a third of human beings carry the pathogen in their bodies. And more and more data suggests that this third differs from the other two thirds in subtle but statistically significant ways. In studies from the Czech Republic and Turkey, people with Toxoplasma had a higher risk of being involved in a traffic accident. A study of 45,000 women in Denmark found that those infected with Toxoplasma were more likely to have attempted suicide. Other work has found a link to schizophrenia, depression, or brain tumors. None of these studies prove that Toxoplasma is the cause. "But when you put all of this together, it's a long list of serious problems that shows we should be concerned," says US parasite researcher Kevin Lafferty. Two of his colleagues called this week in the journal “Trends in Parasitology” to take the risks from Toxoplasma more seriously and to secure sandboxes from cats, for example.

That a parasite like Toxoplasma could also influence human behavior is not as unlikely as it sounds, says Hughes. “Why should a pathogen that has evolved to control the brain of a rat not also control our brain?” And there are other examples such as rabies. The virus makes infected animals aggressive and is transmitted through saliva when bitten. Although man is actually the wrong host, it can turn him into a biting beast too.

Perhaps it is precisely the fear that humans could be just a machine, manipulable by a tiny parasite, that explains the fascination for pathogens such as ophiocordyceps. No other of his research projects get so much attention, says Hughes. The makers of the recently released zombie film "World War Z" even hired Hughes as a scientific advisor. Rabies also had a major effect on culture, says Lafferty. "Large parts of our mythology about werewolves, vampires and zombies can be traced back to it." Apparently Darwin's demons have long taken hold of our thoughts.

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