A fly goes about its day, buzzing here, buzzing there – but then, it starts behaving strangely. His movements become slow and his abdomen swells. Its body sprouts white fluff.

Around sunset, there is a sudden burst of movement as the fly climbs—or “snuffs”—to an elevated location, such as the top of a small plant or stick, and extends its mouthparts. He lets out a sticky puff that holds him firmly to the perch – then he lifts his wings and dies.

Below, other unsuspecting flies are hit by a shower of white spores that emerge from the corpse of the dead fly. And the cycle starts all over again.

The white stuff that swallows these flies is a fungus called Entomophthora muscaewhich translates to “insect killer.” It is an obligate pathogen – entirely dependent on its host – that infects bite and turns them into “zombies” who execute their will.

Discovered more than 160 years agothe mushroom’s actions are as astonishing as they are macabre. Scientists have long wondered how the fungus manages to control the fly brain? How does it “know” to do it at a certain time of day? What genes in his genome help him become a master manipulator?

Today, a series of experiments are beginning to reveal the science behind this strange mind control.

Fatal necrophilia

Henrik H. De Fine Licht, an evolutionary biologist at the University of Copenhagen, is one of the few people in the world who works with “zombie” houseflies. The domestic fly. Although initially attracted to the mushroom E. muscae because he wanted to study obligate pathogens, “I was of course also fascinated by aspects of behavioral manipulation and how it works,” he says.

Those details are like fodder for a horror movie. After the fungus infects the fly, it does not directly reach the vital organs, but first begins to consume fat and other nutrients, gradually starving the fly but keeping it alive. Only when it runs out of non-vital organs to eat does it begin to control the behavior of the fly, thus ensuring its continuity: By forcing the fly to seek some height and get stuck there, it ensures a wide distribution of its spores.

De Fine Licht was particularly intrigued by reports describing how the fungus manipulates flies by making female fly carcasses attractive to healthy males. The males fly and try to mate with the infected corpses – and immediately become infected themselves. To explore the nature of this fatal attraction, De Fine Licht and his team crushed the carcasses of infected and uninfected flies to extract and analyze the chemicals, and analyzed the air around the corpses. They reported in 2022 that the fungus releases volatile chemicals which draws the males in.

It’s not entirely clear, however, whether the volatiles attract male flies with the promise of sex or nutrition, says De Fine Licht. A working hypothesis is that they might be attracted just because they think it’s food. “But when they come into close proximity, they start to smell some of the less volatile compounds of the corpses—and that drives the sexual behavior.”

Annette Jensen, an organismal biologist at the University of Copenhagen, also noticed something intriguing about how other insects reacted to the smell of dead flies. She and one of her students discovered that the earwig—an insect that feeds on other insects—is attracted to the corpses of sporulated flies infected with E. muscae and prefer to feed on them over uninfected corpses or corpses infected with other types of fungi. The scientists reached their conclusions after conducting experiments in which ears were placed between two types of corpses and could select which one to move towards.

“It could be something with the volatiles in Entomophthora muscae which also attracts predators,” says Jensen, who co-wrote an overview of fungi that are pathogenic to insects in Annual Review of Entomology. “It’s probably super nutritious!”

Fruit flies join the list of victims

Most of the zombie fly work has focused on houseflies, but Harvard molecular biologist and zombiologist Carolyn Elya set her research sights on fruit flies after she chanced upon a few zombies in her backyard when she was a student at PhD at UC Berkeley. She pulled out rotten fruit as bait to capture wild fruit flies for experiments and was surprised to see several dead with their wings up in that telltale pose, with fuzzy white spores on their abdomens. She quickly sequenced some DNA from the spores and confirmed her hunch: These fruit flies were victims of E. muscae.

Elya continued to infect Drosophila melanogastera well-established laboratory model that researchers around the world have studied for over a century. With this E. muscae-D. melanogaster systemshe is eager to use the powerful Drosophila genetic toolkit and study the fly’s brain to understand how the fungus does its manipulation.

In a 2023 report, Elya and her colleagues showed that the fungus could secrete something into the fly’s “blood”—its hemolymph— which helps manipulate fly neurons. When he injected hemolymph from infected flies into uninfected ones, the latter began to behave as if they had been zombified.

Elya also found that the fly’s circadian neurons—those that help it keep track of daily rhythms—may be involved in time-sensitive height-seeking behavior. Silencing specific sets of these neurons in the brain inhibited summiting activity in infected flies.

Elya also wants to understand this mind control from the perspective of the fungus—and to that end, she, De Fine Licht, and others recently sequenced the giant E. muscae genome. Focusing on the strain that infects fruit flies, the scientists reported finding genes similar to the one called white collar 1which contains instructions for making a blue light sensor in a mold called Neurospora crassa. In N. crassa, white collar 1 it plays a role in circadian rhythms—and so the scientists hypothesize that this gene might be involved in determining the precise timing of infected flies’ takeover behavior around sunset, followed by their death.

The scientists also discovered a host of genes that could help the fungus make full use of the fly’s tissues and nutrients. These include specialized genes that encode trehalase enzymes, which digest trehalose, the primary sugar in hemolymph; proteins such as chitinases that break down chitin in the fly’s exoskeleton; and lipases, which break down fats.

“That makes sense, right? Because these fungi are highly specialized in the way they use their hosts—not by killing them first and then eating them later, which is a strategy used by many generalist pathogens—but instead, they grow inside the insects. . Elya says. “It’s important to be able to specifically target each tissue in their host.”

The search for more clues continues, with researchers moving beyond the static genome to study the RNA copies of genes that are made when certain genes are active. In a research paper that has not yet been peer-reviewed, Sam Edwards, a postdoctoral researcher at Wageningen University in the Netherlands, De Fine Licht and colleagues reported their analysis of RNA from fly heads at different times after the year E. muscae infection. By finding out which fly and fungus genes were active in the fly’s head, they hoped to see how the fungus manipulated the fly’s behavior.

The team detected the activity of a fungal gene that is similar to the one named e.g which is present in certain zombifying viruses. These viruses, such as E. muscae, force their infected victims – in this case, caterpillars – to move to high placesand in a move creepier than that of their fungal counterparts, causes the caterpillars to molt and release the viral particles below. The e.g gene plays a role in this virus-induced lifting behavior of the caterpillarso the researchers now want to know if the gene in E. muscae is the key to summit induction in infected flies.

In a further twist, both De Fine Licht’s preprint and a recent UC Berkeley study that Elya co-authored find that E. muscae may not operate alone. Mushroom seems to be infected with a virus at the same time that they parasitize house flies and fruit flies. However, it remains to be seen whether this virus helps the fungus control the fly.

Elya, De Fine Licht and others still want to know how the fungus begins to manipulate itself. One hypothesis is that E. muscae it directly releases a chemical that activates the neurons involved in the fly’s spiking behavior. However, another hypothesis is that the consuming presence of the fungus and subsequent physiological changes in the fly trigger the fly’s own neurons to release chemicals to start the process.

De Fine Licht is keen for the zombie-mushroom system to be taught in schools to attract young science enthusiasts. He and Edwards recently published instructions on how to observe the zombifying fungus in the laboratory. “They could encourage high school teachers and others to try this if they want to,” says De Fine Licht.

Some of these involve collecting fly corpses from the field and isolating the fungus from them.

“Or you could try to infect some healthy flies in the lab by putting them together with the corpse,” says De Fine Licht. “Could be the most fun, right? Trying to observe zombie behavior in a small box.”

This article originally appeared in Knowable magazinean independent journalistic effort from Annual Reviews. Sign up for the newsletter.