Parasitic fungi turn animals into willing slaves, with gruesome consequences – but it could pay to get to grips with their powers
AS IT floats through the air, a spore of the fungus Ophiocordyceps camponoti-balzani seems benign. But when it encounters an ant its true nature is revealed. First, it punches its way through the insect’s exoskeleton. Once inside, it begins to grow, consuming just enough of its host’s tissues to leave it weakened but functional. Finally, when the fungus reaches sexual maturity, it releases chemicals into the ant’s brain. Under their influence, the hapless insect makes its way to a popular ant meeting place, climbs a plant and clamps its jaws onto the underside of a leaf, just as the parasite consumes its brain. Days later, elaborate fungal reproductive structures shoot out of the insect’s corpse, spores rain down onto the unsuspecting ants on the forest floor, and the cycle begins again.
Parasites come in all sorts of gruesome guises, from blood-sucking lice to eyeball-eating schistosomids. But there is something particularly disturbing about one that can control minds – and O. camponoti-balzani is by no means the only organism that can (see “More mind-controlling parasites”).
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What makes this fungus and its relatives particularly intriguing, though, is that their secrets are starting to be unravelled – a breakthrough that could help create new types of insecticide, open a new front in the fight against insect-borne diseases and perhaps even one day bring novel treatments for human psychological conditions. Finally, we are learning to harness these mind-benders for our own ends.
There are hundreds of fungi in the Ophiocordyceps genus and related groups that parasitise insects. As far back as the 1800s European farmers realised they had potential as insecticides. There was a problem, however: most of these fungi originate in the tropics of south-east Asia and prefer a humid environment. It was only in 1984 that mycologist Chris Prior found a way around this. By suspending spores of the fungi in vegetable oil before spraying them onto plants he was able to mimic the humid conditions in which they thrive. This method is used today in west Africa and Australia to kill swarms of locusts. “With most insecticides you have to worry about getting the toxin inside the insect,” says , an evolutionary biologist at Pennsylvania State University in University Park. “These fungi are great. They readily attack passing insects all on their own, doing the hard work for us.”
Working with Penn State colleagues Matt Thomas and David Hughes, Read has shown that a parasitic fungus of the genus Metarhizium kills malaria-transmitting mosquitoes as well as locusts (). But there’s a snag: using the most aggressive, fast-acting strains of the fungus would lead to resistance in the mosquito population, as only those individuals most able to tolerate fungal infection survive and pass on their genes to subsequent generations. “Killing mosquitoes outright pits us against evolution,” says Read. “We need to keep evolution on our side.” That’s why he plans instead to manipulate the manipulator.
“Killing mosquitoes outright pits us against evolution. We need to keep evolution on our side”
One way of doing this was highlighted in research by , also at Penn State, which revealed that some parasitic fungi can influence what their hosts feed on. In particular, they can stop insects biting humans by releasing chemicals that reduce their ability to smell us, but not other animals. Read, Thomas and Hughes are now isolating and selectively breeding those strains of fungi with the greatest ability to do this.
“If we could get infected mosquitoes to start feeding on pigs, dogs or goats, there would be no evolutionary resistance since mosquitoes would still be allowed to breed normally,” says Hughes. “We would just be changing their diet and sending the malaria parasite into another species.” As the most problematic malaria pathogen, Plasmodium falciparum, only infects humans, changing the mosquitoes’ diet would create a dead end for the disease.
Aware that selective breeding is quite a crude way to harness the fungi’s powers, Hughes is also taking another approach. “To really alter the parasites we need to know how the genomes of fungi that mind-control insects are different from those of fungi that just kill insects outright,” he says. He is now looking at the genome of the mind-bending fungus Ophiocordyceps unilateralis in the hope of finding genes that are linked with its ability to control the behaviour of its host.
Hughes is also hunting down other potentially useful genes, such as those that produce compounds called NMDA receptor antagonists. Released by some parasitic fungi, these are thought to cause the hosts’ jaw muscles to atrophy, causing them to clamp down into leaves. By isolating such genes before integrating them into fungal species that readily attack and infect problem insects such as mosquitoes, the hope is to render such insects harmless to humans.
That is not going to happen overnight. “This is extremely challenging work.” says parasitologist at the University of Otago in Dunedin, New Zealand. “Constructing fungi that can infect mosquitoes in the right way is certainly possible, but I think we are looking at a solution that is going to take a decade or so rather than a few years to sort out.”
While Hughes and his colleagues plug away at this problem, other researchers are putting the mind-bending properties of related fungi to a quite different use – as medicines for humans. One compound of particular interest is lysergic acid diethylamide, better known as LSD. The natural precursor to LSD is produced by the fungus Claviceps purpurea. , a medical biochemist who studies the effects of hallucinogens at Purdue University in West Lafayette, Indiana, points out that when people take LSD it fundamentally shifts the way their brain works. “They often have a powerful spiritual experience that functions like a brain reboot,” he says.
Nichols admits that the nature of this “reboot” is not known, but says that it seems to be particularly effective at helping people with mental disorders that may stem from “beliefs and personality rather than physical destruction of the brain”, such as post-traumatic stress, obsessive-compulsion, depression and addictions. “The resulting effect of these drugs is that awareness of the world is dramatically changed and people such as drug addicts can see themselves and the pain they are causing with a powerful perspective that they did not have prior to the psychedelic experience,” Nichols says.
Nichols also believes that mind-altering chemicals produced by parasitic fungi could help terminally ill people. He points to a pilot study by at the University of California, Los Angeles, and colleagues, showing that the fungal-derived hallucinogenic compound psilocybin can help people with terminal cancer (). “We are finding that the hallucinogens give people a way to see their remaining time positively,” says Grob.
Of course there are potential risks. “At very high dosages you get some anxiety,” says Grob, but this may not be a problem. “High dosages are not at all required to get positive results.”
Some might find the use of mind-altering compounds as medicines a step too far, but the idea has supporters. “These guys are touching the third rail by studying these banned drugs and that is not an inherently bad thing,” says H. Lee Kagan of the University of Southern California in Los Angeles. He points out that thalidomide, a drug banned in the 1960s because it caused birth defects, has found a new use inhibiting blood vessel growth in certain cancers. “These [hallucinogenic] drugs may have real potential,” he says.
We still have a lot to learn if we are to successfully harness parasitic fungi for our own ends. Nevertheless, the prospects are very exciting. “The diverse instances of mind-altering behaviour are not only entertaining examples of complex biology,” says Hughes, “they also, by virtue of their action on nerves and brains, hold the potential for major benefits to medical and agricultural science.”
If we are to exploit that potential, we may have to act fast. In the past few decades, global warming and human activities have destroyed over 90 per cent of South America’s Atlantic rainforests, home to many of the fungi that Hughes studies. “It is deeply troubling,” he says. “Upon returning to some of these sites we are finding dramatic decreases in the presence of these parasites.” As so often, the key to improving the lot of mankind lies in conserving the diversity of life around us. Parasitic fungi may indulge in some distasteful behaviour – but even the seemingly bad can ultimately be turned to good.
More mind-controlling parasites
Gordian worms (Nematomorpha) look innocent as they swim about in fresh water, breed and lay eggs that hatch into larvae – but then their life cycle takes a sinister twist. The larvae end up inside crickets and other insects, where they set about consuming their host’s soft tissues and release proteins that mimic the signalling molecules produced in the insects’ brains. As the larvae grow into worms, the concentration of these proteins increases. Eventually it is high enough to affect the insect’s central nervous system and manipulate its behaviour, causing it to travel towards water and leap to its death. The adult worm then wriggles out of the insect’s anus and the cycle repeats.
Entomophthora fungi also make zombies of their hosts. Their spores infect houseflies, pushing their way through the cuticle and growing inside the host. Once the parasite reaches sexual maturity, it releases mind-manipulating chemicals, which somehow force the fly to seek out an exposed location in which to die. This puts the fungus in an ideal position from which to shoot spores out into the air and infect more flies.
The method used by the parasitic barnacle Sacculina to perpetuate itself is even more fiendish. Its free-swimming larvae infect crabs and, once inside, develop into a structure on the animal’s abdomen that resembles a regular egg sac. If the infected crab is female, the presence of the false egg sac and the fact that the parasite releases hormones mimicking the ones that make her broody cause her to care for the barnacle as if it were her own offspring. Manipulation of males is more cunning still. Hormones released by the parasite change both his morphology and behaviour: the abdomen becomes wider and flatter, resembling a female’s, and he becomes sterile and develops egg-caring behaviours to nurture the barnacle.
Cat and mouse game
Toxoplasma gondii is a parasitic protozoan that most commonly infects rodents, either via raw meat or cat faeces. Once inside its host, the parasite develops to maturity without causing any real harm, but to complete its life cycle it must find its way into the gut of a cat. To do this, it increases the dopamine levels in the host’s amygdala, the region of the brain associated with fear. This seems to make danger pleasurable and, before long, the reckless rodent puts itself in harm’s way and is eaten by a cat, placing the parasite exactly where it needs to be for its continued survival.
T. gondii can also infect humans. Over the past decade researchers have noticed that populations where many people are infected with the protozoan have different behavioural characteristics than those where toxoplasmosis is relatively rare.
For example, infected men tend to be more dogmatic, less trusting of others, less respectful of rules, more jealous and more wary than the non-infected. The effects are subtle and might not be apparent to an observer or even to infected individuals, says at the University of California, Santa Barbara. Nevertheless, he has been exploring the possibility that they may explain some cultural differences between men from different parts of the world (). “To say that toxoplasmosis makes men more macho may be oversimplifying it, but it is definitely associated with neurotic behaviour, which is related to strongly differentiated gender roles,” he says.
This is intriguing, given how T. gondii makes rodents more reckless. Is the parasite also manipulating humans to its own ends – and if so to what benefit? Alongside intensifying gender roles, the protozoan causes infected individuals to have longer reaction times, leading to an increased risk of traffic accidents (). Lafferty speculates that by impairing alertness, the parasite may once have made ancient humans easier prey for big cats, allowing it to complete its life cycle using humans, not rodents, as an intermediate host.
