Watch this fascinating, hilarious, extremely well written TED Talk.
— excerpt of video transcript below —
Zombie roaches and other parasite tales
Posted Mar 2014 Rated Fascinating, Informative
A herd of wildebeests, a shoal of fish, a flock of birds. Many animals gather in large groups that are among the most wonderful spectacles in the natural world. But why do these groups form? The common answers include things like seeking safety in numbers or hunting in packs or gathering to mate or breed, and all of these explanations, while often true, make a huge assumption about animal behavior, that the animals are in control of their own actions, that they are in charge of their bodies. And that is often not the case.
This is Artemia, a brine shrimp. You probably know it better as a sea monkey. It’s small, and it typically lives alone, but it can gather in these large red swarms that span for meters, and these form because of a parasite. These shrimp are infected with a tapeworm. A tapeworm is effectively a long, living gut with genitals at one end and a hooked mouth at the other. As a freelance journalist, I sympathize. (Laughter) The tapeworm drains nutrients from Artemia’s body, but it also does other things. It castrates them, it changes their color from transparent to bright red, it makes them live longer, and as biologist Nicolas Rode has found, it makes them swim in groups. Why? Because the tapeworm, like many other parasites, has a complicated life cycle involving many different hosts. The shrimp are just one step on its journey. Its ultimate destination is this, the greater flamingo. Only in a flamingo can the tapeworm reproduce, so to get there, it manipulates its shrimp hosts into forming these conspicuous colored swarms that are easier for a flamingo to spot and to devour, and that is the secret of the Artemia swarm. They aren’t sociable through their own volition, but because they are being controlled. It’s not safety in numbers. It’s actually the exact opposite. The tapeworm hijacks their brains and their bodies, turning them into vehicles for getting itself into a flamingo.
And here is another example of a parasitic manipulation. This is a suicidal cricket. This cricket swallowed the larvae of a Gordian worm, or horsehair worm. The worm grew to adult size within it, but it needs to get into water in order to mate, and it does that by releasing proteins that addle the cricket’s brain, causing it to behave erratically. When the cricket nears a body of water, such as this swimming pool, it jumps in and drowns, and the worm wriggles out of its suicidal corpse. Crickets are really roomy. Who knew?
The tapeworm and the Gordian worm are not alone. They are part of an entire cavalcade of mind-controlling parasites, of fungi, viruses, and worms and insects and more that all specialize in subverting and overriding the wills of their hosts. Now, I first learned about this way of life through David Attenborough’s “Trials of Life” about 20 years ago, and then later through a wonderful book called “Parasite Rex” by my friend Carl Zimmer. And I’ve been writing about these creatures ever since. Few topics in biology enthrall me more. It’s like the parasites have subverted my own brain. Because after all, they are always compelling and they are delightfully macabre. When you write about parasites, your lexicon swells with phrases like “devoured alive” and “bursts out of its body.” (Laughter)
But there’s more to it than that. I’m a writer, and fellow writers in the audience will know that we love stories. Parasites invite us to resist the allure of obvious stories. Their world is one of plot twists and unexpected explanations. Why, for example, does this caterpillar start violently thrashing about when another insect gets close to it and those white cocoons that it seems to be standing guard over? Is it maybe protecting its siblings? No. This caterpillar was attacked by a parasitic wasp which laid eggs inside it. The eggs hatched and the young wasps devoured the caterpillar alive before bursting out of its body. See what I mean? Now, the caterpillar didn’t die. Some of the wasps seemed to stay behind and controlled it into defending their siblings which are metamorphosing into adults within those cocoons. This caterpillar is a head-banging zombie bodyguard defending the offspring of the creature that killed it.
We have a lot to get through. I only have 13 minutes. (Laughter)
Now, some of you are probably just desperately clawing for some solace in the idea that these things are oddities of the natural world, that they are outliers, and that point of view is understandable, because by their nature, parasites are quite small and they spend a lot of their time inside the bodies of other things. They’re easy to overlook, but that doesn’t mean that they aren’t important. A few years back, a man called Kevin Lafferty took a group of scientists into three Californian estuaries and they pretty much weighed and dissected and recorded everything they could find, and what they found were parasites in extreme abundance. Especially common were trematodes, tiny worms that specialize in castrating their hosts like this unfortunate snail. Now, a single trematode is tiny, microscopic, but collectively they weighed as much as all the fish in the estuaries and three to nine times more than all the birds. And remember the Gordian worm that I showed you, the cricket thing? One Japanese scientist called Takuya Sato found that in one stream, these things drive so many crickets and grasshoppers into the water that the drowned insects make up some 60 percent of the diet of local trout. Manipulation is not an oddity. It is a critical and common part of the world around us, and scientists have now found hundreds of examples of such manipulators, and more excitingly, they’re starting to understand exactly how these creatures control their hosts.
And this is one of my favorite examples. This is Ampulex compressa, the emerald cockroach wasp, and it is a truth universally acknowledged that an emerald cockroach wasp in possession of some fertilized eggs must be in want of a cockroach. When she finds one, she stabs it with a stinger that is also a sense organ. This discovery came out three weeks ago. She stabs it with a stinger that is a sense organ equipped with small sensory bumps that allow her to feel the distinctive texture of a roach’s brain. So like a person blindly rooting about in a bag, she finds the brain, and she injects it with venom into two very specific clusters of neurons. Israeli scientists Frederic Libersat and Ram Gal found that the venom is a very specific chemical weapon. It doesn’t kill the roach, nor does it sedate it. The roach could walk away or fly or run if it chose to, but it doesn’t choose to, because the venom nixes its motivation to walk, and only that. The wasp basically un-checks the escape-from-danger box in the roach’s operating system, allowing her to lead her helpless victim back to her lair by its antennae like a person walking a dog. And once there, she lays an egg on it, egg hatches, devoured alive, bursts out of body, yadda yadda yadda, you know the drill. (Laughter) (Applause)
Now I would argue that, once stung, the cockroach isn’t a roach anymore. It’s more of an extension of the wasp, just like the cricket was an extension of the Gordian worm. These hosts won’t get to survive or reproduce. They have as much control over their own fates as my car. Once the parasites get in, the hosts don’t get a say.
Now humans, of course, are no stranger to manipulation. We take drugs to shift the chemistries of our brains and to change our moods, and what are arguments or advertising or big ideas if not an attempt to influence someone else’s mind? But our attempts at doing this are crude and blundering compared to the fine-grained specificity of the parasites. Don Draper only wishes he was as elegant and precise as the emerald cockroach wasp. Now, I think this is part of what makes parasites so sinister and so compelling. We place such a premium on our free will and our independence that the prospect of losing those qualities to forces unseen informs many of our deepest societal fears. Orwellian dystopias and shadowy cabals and mind-controlling supervillains — these are tropes that fill our darkest fiction, but in nature, they happen all the time.
Which leads me to an obvious and disquieting question: Are there dark, sinister parasites that are influencing our behavior without us knowing about it, besides the NSA? If there are any — (Laughter) (Applause) I’ve got a red dot on my forehead now, don’t I? (Laughter)
If there are any, this is a good candidate for them. This is Toxoplasma gondii, or Toxo, for short, because the terrifying creature always deserves a cute nickname. Toxo infects mammals, a wide variety of mammals, but it can only sexually reproduce in a cat. And scientists like Joanne Webster have shown that if Toxo gets into a rat or a mouse, it turns the rodent into a cat-seeking missile. If the infected rat smells the delightful odor of cat piss, it runs towards the source of the smell rather than the more sensible direction of away. The cat eats the rat. Toxo gets to have sex. It’s a classic tale of Eat, Prey, Love. (Laughter) (Applause)
You’re very charitable, generous people. Hi, Elizabeth, I loved your talk.
How does the parasite control its host in this way? We don’t really know. We know that Toxo releases an enzyme that makes dopamine, a substance involved in reward and motivation. We know it targets certain parts of a rodent’s brain, including those involved in sexual arousal. But how those puzzle pieces fit together is not immediately clear. What is clear is that this thing is a single cell. This has no nervous system. It has no consciousness. It doesn’t even have a body. But it’s manipulating a mammal? We are mammals. We are more intelligent than a mere rat, to be sure, but our brains have the same basic structure, the same types of cells, the same chemicals running through them, and the same parasites. Estimates vary a lot, but some figures suggest that one in three people around the world have Toxo in their brains. Now typically, this doesn’t lead to any overt illness. The parasite holds up in a dormant state for a long period of time. But there’s some evidence that those people who are carriers score slightly differently on personality questionnaires than other people, that they have a slightly higher risk of car accidents, and there’s some evidence that people with schizophrenia are more likely to be infected. Now, I think this evidence is still inconclusive, and even among Toxo researchers, opinion is divided as to whether the parasite is truly influencing our behavior. But given the widespread nature of such manipulations, it would be completely implausible for humans to be the only species that weren’t similarly affected.
And I think that this capacity to constantly subvert our way of thinking about the world makes parasites amazing. They’re constantly inviting us to look at the natural world sideways, and to ask if the behaviors we’re seeing, whether they’re simple and obvious or baffling and puzzling, are not the results of individuals acting through their own accord but because they are being bent to the control of something else. And while that idea may be disquieting, and while parasites’ habits may be very grisly, I think that ability to surprise us makes them as wonderful and as charismatic as any panda or butterfly or dolphin.
At the end of “On the Origin of Species,” Charles Darwin writes about the grandeur of life, and of endless forms most beautiful and most wonderful, and I like to think he could easily have been talking about a tapeworm that makes shrimp sociable or a wasp that takes cockroaches for walks.
But perhaps, that’s just a parasite talking.
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— excerpt below —
Arts + Design
For healthier buildings, just add bacteria?
Jan 24, 2017 / Ed Yong
Just like a human being, a house or office has its own microbiome, with good and bad microorganisms. One researcher has a targeted idea: to customize our spaces with the right microbes.
Right before the University of Chicago’s Center for Care and Discovery opened in 2013, a team of researchers — overseen by Jack Gilbert, microbial researcher and director of the Microbiome Center at the University of Chicago — went through the eerily empty hallways, armed with bags of Q-tips. None of the rooms were home to humans yet; their only residents were microbes, which the team was there to collect. They swabbed the pristine floors, the gleaming bedrails, the perfectly folded sheets. They collected samples from light switches, door handles, air vents and more. Finally, they fitted the rooms with data loggers to measure light, temperature, humidity and air pressure, carbon dioxide monitors that would automatically record if a room was occupied, and infrared sensors that could tell when people entered or left. After the hospital opened, the team collected weekly samples.
Just as others have catalogued the developing microbiome of a newborn baby, Gilbert has, for the first time, catalogued the developing microbiome of a newborn building. His team is analyzing the data to work out how the presence of humans has changed the building’s microbial character and whether those environmental microbes have flowed back into the occupants. Nowhere are those questions more important than in a hospital. There, the flow of microbes can mean life or death — a lot of deaths. In the developed world, around five to ten percent of people who check into hospitals and other health-care institutions pick up an infection during their stay, falling ill in the very places that are meant to make them healthier. In the United States alone, this means around 1.7 million infections and 90,000 deaths a year.
Ever since the 1860s, when Joseph Lister instigated sterile techniques in his hospital, cleaning regimes have helped curb the spread of pathogens. But just as we have gone overboard in taking unnecessary antibiotics or lathering ourselves in antibacterial sanitizers, we have also gone too far in cleaning our buildings, even our hospitals. As an example, one US hospital recently spent around $700,000 to install flooring that was impregnated with antibacterial substances, despite no evidence that such measures work. They might even make things worse. Perhaps the quest to sterilize our hospitals has created dysbiosis in the microbiomes of our buildings. By removing harmless bacteria that would otherwise impede the growth of pathogens, perhaps we have inadvertently constructed a more dangerous ecosystem.
Researcher Gilbert has visions of adding microbial spheres to neonatal intensive care units, to expose babies to a ‘rich microbial ecosystem’
Rather than trying to exclude microbes from our buildings and public spaces, perhaps it is time to lay the welcome mat out for them. One of Gilbert’s many microbial ideas: to deliberately seed buildings with bacteria. The microbes won’t be sprayed or plastered onto walls. Instead, they’ll come caged within tiny plastic spheres, created by engineer Ramille Shah. She will use three-dimensional printers to fashion balls that contain a warren of microscopic nooks and crannies. Gilbert will then impregnate these with useful bacteria like Clostridia, which digests fiber and quenches inflammation, as well as nutrients that nourish those microbes.
These bacteria should then jump over to anyone who interacts with the spheres. Gilbert is testing this with germ-free mice. He wants to see if the bacteria are stable in their cages, if they jump into rodents that play with the balls, if they last in their new hosts and if they can cure the rodents of inflammatory diseases. If that works, Gilbert has visions of testing the microbial spheres in office blocks or hospital wards. He imagines adding them to the cots in neonatal intensive care units, so that the infants would “be constantly exposed to a rich microbial ecosystem that we’ve designed to be beneficial.” He adds, “I want to create 3D-printable teething toys, too. You can imagine children playing with these.”
These spheres are effectively a different take on probiotics — a way of delivering beneficial microbes not through yogurt drinks or nutritional supplements, but via an animal’s surroundings. “I don’t want to put the microbes in their food and shove it down their gullet,” he says. “I want the microbes to interact with their nasal membranes, their mouths and their hands. I want them to experience that microbiome in a more natural way.”
Microbes that prevent dandruff and dermatitis might be used to stop mold from developing in homes
But Gilbert is interested in implementing his ideas on a much larger scale. He wants to shape the microbiomes of entire cities, starting with Chicago. He has been talking to architect Luke Leung, who designed the world’s tallest building, Dubai’s Burj Khalifa. Since meeting Gilbert, Leung has also become something of a microbiome fanatic. In several of his buildings, Leung has routed the ventilation system so that it flows through a wall of plants, which not only pleases the eye but also filters the air. To him, Gilbert’s idea of lacing walls with microbial spheres — which I’ve suggested should be called Baccy Balls — makes perfect sense. Karen Weigert, Chicago’s chief sustainability officer, has also become a microbiome enthusiast.
The four of us — Leung, Gilbert, Weigert and me — are meeting for lunch at a Chicago restaurant overlooking Lake Michigan. Like Leung, Weigert is excited about using bacteria in architecture, and she asks Gilbert if the Baccy Balls would work in low-income housing, as well as in skyscrapers. Yes, he says. He wants to make them as cheaply as possible.
She switches the conversation to Chicago’s perennial problem with flooding. The sewer system backs up a lot and will probably do so more and more as the global climate changes. “Is there something we can do to manage flooding, or after-effects like mold?” she asks. “There actually is,” says Gilbert.
In a different project, he has been working with L’Oréal to identify bacteria that can prevent dandruff and dermatitis, by stopping fungi from germinating on the scalp. These microbes could form the basis of anti-dandruff probiotic shampoos, but they could also be used to create “micro-wetlands” that stop flooded homes from becoming overrun by mold. So if a home floods, fungi would get a bonanza of water, but also face a bloom of antifungal microbes. “You’d get automatic built-in mold control,” says Gilbert.
“So how real is all of this? Where are you with it?” asks Weigert.
“We’ve got the fungal control agents, and we’re trying to work out how to implant them into plastics,” says Gilbert. “We’re probably two or three years off from having something that we’d feel comfortable inserting in somebody’s home — someone who wasn’t a colleague. And it may be three or four years before we have something reliable we can roll out.”
“We’ve been getting pretty good at killing bacteria, but we want to revitalize that relationship,” Leung says. “We want to understand how the bacteria can help us in the built environment.”
It’s the start of a new era, when people are finally able to embrace the microbial world.
Manipulating the microbiomes of buildings and cities is just the start of Gilbert’s ambitions. As well as the hospital and aquarium initiatives, he is also studying the microbiomes of a local gym and a college dorm. He and microbial researcher Rob Knight at UC San Diego (TED Talk: How our microbes make us who we are) are looking into forensic applications. He is studying the microbiomes of a wastewater treatment plant, floodplains, oil-contaminated waters in the Gulf of Mexico, prairies, a neonatal intensive care unit and Merlot grapes. He is studying how gut microbes change over the course of the day and whether that affects our risk of becoming fat. He is analyzing samples from several dozen wild baboons to see if the females that are most successful at rearing young have anything distinctive in their microbiomes.
Finally, together with Knight and Janet Jansson (of the Pacific Northwest National Laboratory), Gilbert is coordinating the Earth Microbiome Project — a breathtakingly ambitious plan to take full stock of the planet’s microbes. The team are making contact with people who work on oceans or grasslands or floodplains, and persuading them to share their samples and their data. Ultimately, they want to be able to predict the kinds of microbes that live in a given ecosystem by plugging in basic factors like temperature, vegetation, wind speed or levels of sunlight. And they want to predict how those species would respond to environmental changes, like the flooding of a river, or the passage from night to day. As goals go, it is ludicrously ambitious; some would say, unachievably so. But Gilbert and his colleagues are undeterred.
Now is a time for thinking big. It’s a time when families can be persuaded to swab their houses for researchers, when aquarium managers are as concerned about the invisible life in their waters as they are about the charismatic dolphins, when hospitals are seriously considering adding microbes to walls rather than removing them. It’s the start of a new era, when people are finally ready to embrace the microbial world.
Excerpted from the new book I Contain Multitudes: The Microbes Within Us and a Grander View on Life by Ed Yong. Copyright 2016 Ed Yong. Reprinted with permission from Ecco, an imprint of HarperCollins Publishers.
About the author
Ed Yong writes the award-winning blog Not Exactly Rocket Science (hosted by National Geographic). He also contributes to Nature, Wired, Scientific American and many other web and print outlets.
baccy ballsbacteriabook excerptearth microbiome projectEd Yongjack gilbertJoseph ListerKaren WeigertLuke LeungmicrobesmicrobiologymicrobiomeRamille ShahRob Knight
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Newfound respect and Awe for Cats as an amazing creature: Cat vs (Racoon, Aligator, Dog, Snake, Poosum, etc..)
Cat vs R(acoon, Aligator, Dog, Snake, Poosum, etc…)
Animals rescue animals of a different species.
Cross species animals as friends
Cat acts as guard dog to keep alligators away.
Young Cheetah mothers baby monkey.
This one has some annoying parts, but just skip forward at that point. There is amazing footage intermixed, through to the end.
His “Best Friend” is a Bear
Anderson worked for the Montana Department of Fish, Wildlife and Parks as a wildlife rehabilitation technician, and for several privately owned wildlife parks as an animal keeper and trainer. In 2002, he adopted an orphaned grizzly bear cub, Brutus, from an overcrowded wildlife park where the cub was destined to spend his life in captivity or be euthanized. This led to Anderson’s future career as trainer to Brutus and co-owner of Montana Grizzly Encounter which is a sanctuary that rehabilitates grizzlies rescued from bad captivity situations and which aids in the study of grizzlies.
Cat Scares Bear Away
A very strange cat pic (video) – I didn’t know a cat could sit like this. Interesting to see how he does it.
The question is, why? Very odd. Almost disturbing.
or, human like.
Can the Bacteria in Your Gut Explain Your Mood?
The rich array of microbiota in our intestines can tell us more than you might think.
By PETER ANDREY SMITH
JUNE 23, 2015
Eighteen vials were rocking back and forth on a squeaky mechanical device the shape of a butcher scale, and Mark Lyte was beside himself with excitement. ‘‘We actually got some fresh yesterday — freshly frozen,’’ Lyte said to a lab technician.
Each vial contained a tiny nugget of monkey feces that were collected at the Harlow primate lab near Madison, Wis., the day before and shipped to Lyte’s lab on the Texas Tech University Health Sciences Center campus in Abilene, Tex.
Lyte’s interest was not in the feces per se but in the hidden form of life they harbor. The digestive tube of a monkey, like that of all vertebrates, contains vast quantities of what biologists call gut microbiota. The genetic material of these trillions of microbes, as well as others living elsewhere in and on the body, is collectively known as the microbiome. Taken together, these bacteria can weigh as much as six pounds, and they make up a sort of organ whose functions have only begun to reveal themselves to science. Lyte has spent his career trying to prove that gut microbes communicate with the nervous system using some of the same neurochemicals that relay messages in the brain.Inside a closet-size room at his lab that afternoon, Lyte hunched over to inspect the vials, whose samples had been spun down in a centrifuge to a radiant, golden broth. Lyte, 60, spoke fast and emphatically. ‘‘You wouldn’t believe what we’re extracting out of poop,’’ he told me. ‘‘We found that the guys here in the gut make neurochemicals. We didn’t know that. Now, if they make this stuff here, does it have an influence there? Guess what? We make the same stuff. Maybe all this communication has an influence on our behavior.’
’Since 2007, when scientists announced plans for a Human Microbiome Project to catalog the micro-organisms living in our body, the profound appreciation for the influence of such organisms has grown rapidly with each passing year. Bacteria in the gut produce vitamins and break down our food; their presence or absence has been linked to obesity, inflammatory bowel disease and the toxic side effects of prescription drugs. Biologists now believe that much of what makes us human depends on microbial activity. The two million unique bacterial genes found in each human microbiome can make the 23,000 genes in our cells seem paltry, almost negligible, by comparison. ‘‘It has enormous implications for the sense of self,’’ Tom Insel, the director of the National Institute of Mental Health, told me. ‘‘We are, at least from the standpoint of DNA, more microbial than human. That’s a phenomenal insight and one that we have to take seriously when we think about human development.’’Given the extent to which bacteria are now understood to influence human physiology, it is hardly surprising that scientists have turned their attention to how bacteria might affect the brain. Micro-organisms in our gut secrete a profound number of chemicals, and researchers like Lyte have found that among those chemicals are the same substances used by our neurons to communicate and regulate mood, like dopamine, serotonin and gamma-aminobutyric acid (GABA). These, in turn, appear to play a function in intestinal disorders, which coincide with high levels of major depression and anxiety.
Last year, for example, a group in Norway examined feces from 55 people and found certain bacteria were more likely to be associated with depressive patients.At the time of my visit to Lyte’s lab, he was nearly six months into an experiment that he hoped would better establish how certain gut microbes influenced the brain, functioning, in effect, as psychiatric drugs. He was currently compiling a list of the psychoactive compounds found in the feces of infant monkeys. Once that was established, he planned to transfer the microbes found in one newborn monkey’s feces into another’s intestine, so that the recipient would end up with a completely new set of microbes — and, if all went as predicted, change their neurodevelopment.
The experiment reflected an intriguing hypothesis. Anxiety, depression and several pediatric disorders, including autism and hyperactivity, have been linked with gastrointestinal abnormalities. Microbial transplants were not invasive brain surgery, and that was the point: Changing a patient’s bacteria might be difficult but it still seemed more straightforward than altering his genes.
When Lyte began his work on the link between microbes and the brain three decades ago, it was dismissed as a curiosity. By contrast, last September, the National Institute of Mental Health awarded four grants worth up to $1 million each to spur new research on the gut microbiome’s role in mental disorders, affirming the legitimacy of a field that had long struggled to attract serious scientific credibility. Lyte and one of his longtime colleagues, Christopher Coe, at the Harlow primate lab, received one of the four. ‘‘What Mark proposed going back almost 25 years now has come to fruition,’’ Coe told me. ‘‘Now what we’re struggling to do is to figure out the logic of it.’’ It seems plausible, if not yet proved, that we might one day use microbes to diagnose neurodevelopmental disorders, treat mental illnesses and perhaps even fix them in the brain.
In 2011, a team of researchers at University College Cork, in Ireland, and McMaster University, in Ontario, published a study in Proceedings of the National Academy of Science that has become one of the best-known experiments linking bacteria in the gut to the brain. Laboratory mice were dropped into tall, cylindrical columns of water in what is known as a forced-swim test, which measures over six minutes how long the mice swim before they realize that they can neither touch the bottom nor climb out, and instead collapse into a forlorn float. Researchers use the amount of time a mouse floats as a way to measure what they call ‘‘behavioral despair.’’ (Antidepressant drugs, like Zoloft and Prozac, were initially tested using this forced-swim test.)
For several weeks, the team, led by John Cryan, the neuroscientist who designed the study, fed a small group of healthy rodents a broth infused with Lactobacillus rhamnosus, a common bacterium that is found in humans and also used to ferment milk into probiotic yogurt. Lactobacilli are one of the dominant organisms babies ingest as they pass through the birth canal. Recent studies have shown that mice stressed during pregnancy pass on lowered levels of the bacterium to their pups. This type of bacteria is known to release immense quantities of GABA; as an inhibitory neurotransmitter, GABA calms nervous activity, which explains why the most common anti-anxiety drugs, like Valium and Xanax, work by targeting GABA receptors.Cryan found that the mice that had been fed the bacteria-laden broth kept swimming longer and spent less time in a state of immobilized woe. ‘‘They behaved as if they were on Prozac,’’ he said. ‘‘They were more chilled out and more relaxed.’’
The results suggested that the bacteria were somehow altering the neural chemistry of mice.Until he joined his colleagues at Cork 10 years ago, Cryan thought about microbiology in terms of pathology: the neurological damage created by diseases like syphilis or H.I.V. ‘‘There are certain fields that just don’t seem to interact well,’’ he said. ‘‘Microbiology and neuroscience, as whole disciplines, don’t tend to have had much interaction, largely because the brain is somewhat protected.’’ He was referring to the fact that the brain is anatomically isolated, guarded by a blood-brain barrier that allows nutrients in but keeps out pathogens and inflammation, the immune system’s typical response to germs. Cryan’s study added to the growing evidence that signals from beneficial bacteria nonetheless find a way through the barrier. Somehow — though his 2011 paper could not pinpoint exactly how — micro-organisms in the gut tickle a sensory nerve ending in the fingerlike protrusion lining the intestine and carry that electrical impulse up the vagus nerve and into the deep-brain structures thought to be responsible for elemental emotions like anxiety. Soon after that, Cryan and a co-author, Ted Dinan, published a theory paper in Biological Psychiatry calling these potentially mind-altering microbes ‘‘psychobiotics.’’
It has long been known that much of our supply of neurochemicals — an estimated 50 percent of the dopamine, for example, and a vast majority of the serotonin — originate in the intestine, where these chemical signals regulate appetite, feelings of fullness and digestion. But only in recent years has mainstream psychiatric research given serious consideration to the role microbes might play in creating those chemicals. Lyte’s own interest in the question dates back to his time as a postdoctoral fellow at the University of Pittsburgh in 1985, when he found himself immersed in an emerging field with an unwieldy name: psychoneuroimmunology, or PNI, for short. The central theory, quite controversial at the time, suggested that stress worsened disease by suppressing our immune system.By 1990, at a lab in Mankato, Minn., Lyte distilled the theory into three words, which he wrote on a chalkboard in his office: Stress->Immune->Disease. In the course of several experiments, he homed in on a paradox. When he dropped an intruder mouse in the cage of an animal that lived alone, the intruder ramped up its immune system — a boost, he suspected, intended to fight off germ-ridden bites or scratches. Surprisingly, though, this did not stop infections. It instead had the opposite effect: Stressed animals got sick. Lyte walked up to the board and scratched a line through the word ‘‘Immune.’’ Stress, he suspected, directly affected the bacterial bugs that caused infections.
To test how micro-organisms reacted to stress, he filled petri plates with a bovine-serum-based medium and laced the dishes with a strain of bacterium. In some, he dropped norepinephrine, a neurochemical that mammals produce when stressed. The next day, he snapped a Polaroid. The results were visible and obvious: The control plates were nearly barren, but those with the norepinephrine bloomed with bacteria that filigreed in frostlike patterns. Bacteria clearly responded to stress.Then, to see if bacteria could induce stress, Lyte fed white mice a liquid solution of Campylobacter jejuni, a bacterium that can cause food poisoning in humans but generally doesn’t prompt an immune response in mice. To the trained eye, his treated mice were as healthy as the controls. But when he ran them through a plexiglass maze raised several feet above the lab floor, the bacteria-fed mice were less likely to venture out on the high, unprotected ledges of the maze. In human terms, they seemed anxious. Without the bacteria, they walked the narrow, elevated planks.Each of these results was fascinating, but Lyte had a difficult time finding microbiology journals that would publish either. ‘‘It was so anathema to them,’’ he told me. When the mouse study finally appeared in the journal Physiology & Behavior in 1998, it garnered little attention. And yet as Stephen Collins, a gastroenterologist at McMaster University, told me, those first papers contained the seeds of an entire new field of research. ‘‘Mark showed, quite clearly, in elegant studies that are not often cited, that introducing a pathological bacterium into the gut will cause a change in behavior.’’
Lyte went on to show how stressful conditions for newborn cattle worsened deadly E. coli infections. In another experiment, he fed mice lean ground hamburger that appeared to improve memory and learning — a conceptual proof that by changing diet, he could change gut microbes and change behavior. After accumulating nearly a decade’s worth of evidence, in July 2008, he flew to Washington to present his research. He was a finalist for the National Institutes of Health’s Pioneer Award, a $2.5 million grant for so-called blue-sky biomedical research. Finally, it seemed, his time had come. When he got up to speak, Lyte described a dialogue between the bacterial organ and our central nervous system. At the two-minute mark, a prominent scientist in the audience did a spit
‘‘Dr. Lyte,’’ he later asked at a question-and-answer session, ‘‘if what you’re saying is right, then why is it when we give antibiotics to patients to kill bacteria, they are not running around crazy on the wards?’’
Lyte knew it was a dismissive question. And when he lost out on the grant, it confirmed to him that the scientific community was still unwilling to imagine that any part of our neural circuitry could be influenced by single-celled organisms. Lyte published his theory in Medical Hypotheses, a low-ranking journal that served as a forum for unconventional ideas. The response, predictably, was underwhelming. ‘‘I had people call me crazy,’’ he said.
But by 2011 — when he published a second theory paper in Bioessays, proposing that probiotic bacteria could be tailored to treat specific psychological diseases — the scientific community had become much more receptive to the idea. A Canadian team, led by Stephen Collins, had demonstrated that antibiotics could be linked to less cautious behavior in mice, and only a few months before Lyte, Sven Pettersson, a microbiologist at the Karolinska Institute in Stockholm, published a landmark paper in Proceedings of the National Academy of Science that showed that mice raised without microbes spent far more time running around outside than healthy mice in a control group; without the microbes, the mice showed less apparent anxiety and were more daring. In Ireland, Cryan published his forced-swim-test study on psychobiotics. There was now a groundswell of new research. In short order, an implausible idea had become a hypothesis in need of serious validation.Late last year, Sarkis Mazmanian, a microbiologist at the California Institute of Technology, gave a presentation at the Society for Neuroscience, ‘‘Gut Microbes and the Brain: Paradigm Shift in Neuroscience.’’ Someone had inadvertently dropped a question mark from the end, so the speculation appeared to be a definitive statement of fact. But if anyone has a chance of delivering on that promise, it’s Mazmanian, whose research has moved beyond the basic neurochemicals to focus on a broader class of molecules called metabolites: small, equally druglike chemicals that are produced by micro-organisms. Using high-powered computational tools, he also hopes to move beyond the suggestive correlations that have typified psychobiotic research to date, and instead make decisive discoveries about the mechanisms by which microbes affect brain function.
Two years ago, Mazmanian published a study in the journal Cell with Elaine Hsiao, then a graduate student and now a neuroscientist at Caltech, and others, that made a provocative link between a single molecule and behavior. Their research found that mice exhibiting abnormal communication and repetitive behaviors, like obsessively burying marbles, were mollified when they were given one of two strains of the bacterium Bacteroides fragilis.The study added to a working hypothesis in the field that microbes don’t just affect the permeability of the barrier around the brain but also influence the intestinal lining, which normally prevents certain bacteria from leaking out and others from getting in. When the intestinal barrier was compromised in his model, normally ‘‘beneficial’’ bacteria and the toxins they produce seeped into the bloodstream and raised the possibility they could slip past the blood-brain barrier. As one of his colleagues, Michael Fischbach, a microbiologist at the University of California, San Francisco, said: ‘‘The scientific community has a way of remaining skeptical until every last arrow has been drawn, until the entire picture is colored in. Other scientists drew the pencil outlines, and Sarkis is filling in a lot of the color.’’
Mazmanian knew the results offered only a provisional explanation for why restrictive diets and antibacterial treatments seemed to help some children with autism: Altering the microbial composition might be changing the permeability of the intestine. ‘‘The larger concept is, and this is pure speculation: Is a disease like autism really a disease of the brain or maybe a disease of the gut or some other aspect of physiology?’’ Mazmanian said. For any disease in which such a link could be proved, he saw a future in drugs derived from these small molecules found inside microbes. (A company he co-founded, Symbiotix Biotherapies, is developing a complex sugar called PSA, which is associated with Bacteroides fragilis, into treatments for intestinal disease and multiple sclerosis.) In his view, the prescriptive solutions probably involve more than increasing our exposure to environmental microbes in soil, dogs or even fermented foods; he believed there were wholesale failures in the way we shared our microbes and inoculated children with these bacteria. So far, though, the only conclusion he could draw was that disorders once thought to be conditions of the brain might be symptoms of microbial disruptions, and it was the careful defining of these disruptions that promised to be helpful in the coming decades.
The list of potential treatments incubating in labs around the world is startling. Several international groups have found that psychobiotics had subtle yet perceptible effects in healthy volunteers in a battery of brain-scanning and psychological tests. Another team in Arizona recently finished an open trial on fecal transplants in children with autism. (Simultaneously, at least two offshore clinics, in Australia and England, began offering fecal microbiota treatments to treat neurological disorders, like multiple sclerosis.) Mazmanian, however, cautions that this research is still in its infancy. ‘‘We’ve reached the stage where there’s a lot of, you know, ‘The microbiome is the cure for everything,’ ’’ he said. ‘‘I have a vested interest if it does. But I’d be shocked if it did.’’Lyte issues the same caveat. ‘‘People are obviously desperate for solutions,’’ Lyte said when I visited him in Abilene. (He has since moved to Iowa State’s College of Veterinary Medicine.) ‘‘My main fear is the hype is running ahead of the science.’’ He knew that parents emailing him for answers meant they had exhausted every option offered by modern medicine. ‘‘It’s the Wild West out there,’’ he said. ‘‘You can go online and buy any amount of probiotics for any number of conditions now, and my paper is one of those cited. I never said go out and take probiotics.’’ He added, ‘‘We really need a lot more research done before we actually have people trying therapies out.’’
If the idea of psychobiotics had now, in some ways, eclipsed him, it was nevertheless a curious kind of affirmation, even redemption: an old-school microbiologist thrust into the midst of one of the most promising aspects of neuroscience. At the moment, he had a rough map in his head and a freezer full of monkey fecals that might translate, somehow, into telling differences between gregarious or shy monkeys later in life. I asked him if what amounted to a personality transplant still sounded a bit far-fetched. He seemed no closer to unlocking exactly what brain functions could be traced to the same organ that produced feces. ‘‘If you transfer the microbiota from one animal to another, you can transfer the behavior,’’ Lyte said. ‘‘What we’re trying to understand are the mechanisms by which the microbiota can influence the brain and development. If you believe that, are you now out on the precipice? The answer is yes. Do I think it’s the future? I think it’s a long way away.’’
Correction: July 12, 2015An article on June 28 about microbiota and the brain described incorrectly the affiliation of Elaine Hsiao, an author of a study published in the journal Cell that linked bacteria to behavioral changes. At the time, she was a graduate student in the lab of Paul Patterson, another author of the study, not in the lab of Sarkis Mazmanian.
Peter Andrey Smith is a reporter living in Brooklyn.
He frequently writes about the microbial world.Reporting for this article was supported by the UC Berkeley-11th Hour Food and Farming Journalism Fellowship.
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