Microbes
Someone once told me that a praying mantis in your home brings luck and good health. As for the one sitting on my kitchen countertop in Oakland, California, well, Jonathan Eisen certainly likes it. “That’s cool,” says the University of California at Davis microbiologist, lifting the tiny aluminum toy—with huge eyes and delicate clawlike front legs—off the cold marble. He sets it down only when something even smaller, a fruit fly, buzzes past. “Look,” he says admiringly, head cocked to my ceiling, “you have drosophilia.”
Eisen is a tall guy in his 40s with a mountain-man beard, and he has shown up at my home wearing a T-shirt with sparkly-pink block lettering that reads: “Ask me about fecal transplants.” He’s a firm believer that human health depends on bugs—not the six-legged variety, but the microbes that populate our guts and the environments in which we live, work, and play. Eisen explains that every time I open my door, a blast of air that has woven through the surrounding tree canopy carries microbes into my house—as do Amazon packages, pets, and muddy feet.
He’s musing about my oak trees when the forced-air heating clicks on. The furrows in his brow deepen. Hot, dry air shooting through a sealed house kills germs, he tells me. In fact, my whole house makes him deeply uncomfortable. It was extensively remodeled this past summer with antimicrobial fixtures, floors, and walls—now standard in many renovations. Eisen compares this practice to the overuse of antibiotics in medicine: Wipe out the natural balance of good bugs, and you might not like the organisms that survive.
A mounting body of research has shown the importance of the microbes that live inside us, and scientists have been slowly cataloguing species that live outside in nature. But little is known about the microbial ecosystem that surrounds us indoors, where we spend about 90 percent of our time. Recently a group of scientists, loosely connected through the Microbiology of the Built Environment Network that Eisen founded, has begun to probe it. The White House Office of Science and Technology Policy is looking into forming a national initiative to spur further research. Once we know what organisms we live with, we can begin to determine how we rely on them—and then we can tackle this question: To what extent do we need to stop protecting people from germs and instead protect germs from people?
Wipe out the natural balance of good bugs, and you might not like the organisms that survive.
I lead Eisen up a stairwell slathered in antimicrobial paint, and into a study with carpet treated with stain and odor guard. “You know that’s bad, right?” he asks. Then we pop into the bathroom. Eisen stares intensely at the tankless toilet. It appears to levitate off the floor like an antimicrobial spaceship. When I ask if he wants to step outside for fresh air, he looks relieved.
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Charles Darwin, in On the Origin of Species, charts evolution through the Tree of Life. Its branches and roots lift some species toward fecundity while knocking others down to extinction. But Darwin’s tree didn’t include microbes, perhaps the most successful life-forms of all. They make up roughly 60 percent of Earth’s biomass. There are more microbes in a teaspoon of soil than there are humans in the world.
By some measures, even we are more microbe than mammal. The trillions of microorganisms we harbor in our bodies, collectively known as our microbiome, outnumber human cells 10-to-1. Altogether, they weigh up to twice as much as the human brain, existing as a sort of sixth human superorgan whose function is linked to digesting our meals, preventing infection, and possibly even influencing our emotions and moods. Studies that describe new and essential roles for our microbiome are published almost daily. The reason for its breath-taking range is simple: Our germs have evolved with us.
Microbes appear to have prospered by making themselves incredibly useful, and we’ve gladly given up space in exchange for the vitamins, digestive enzymes, and metabolites they provide. And so the discovery that the urban gut harbors up to 40 percent less microbial diversity than that of indigenous people living in a remote jungle concerns scientists. These “missing microbes,” they say, may have been decimated by several decades of industrialized foods, which limited our diets, and antibiotic use, which extended our lives at the expense of theirs.
Eisen offers another explanation for why our internal real estate might be in subprime condition: The microbiome within us depends upon the microbiome that surrounds us. “Have you seen germ-free mice?” he asks me. “They are seriously messed-up animals.” Delivered by cesarean section and raised in sterile chambers, these rodents have inflamed lungs and colons, like those seen in asthma and colitis. They’re also prone to haywire immunity and weird social tics.
Until relatively recently, sterile chambers weren’t our environments either. “We didn’t evolve in closed rooms,” says Maria Gloria Dominguez-Bello, a microbiologist at New York University who led the indigenous microbiome study. “We evolved in nature.” Big families lived together on farms and in tenements, not exactly temples of hygiene. Livestock loped in the streets. Infectious disease rippled through cities. Roofs leaked. Sewers overflowed. Windows opened. But with modernization, we sealed ourselves away. In other words, we parted ways with the microbes that evolved with us. By redesigning our buildings, we redesigned ourselves.
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Soft of heart and loud of mouth, Eisen enjoys a good jab. When I first met him at a Thai restaurant in Davis, he lifted up his shirt and stabbed himself with an insulin syringe. I flinched, but he grinned. “When I was a kid, I did this to freak people out,” he said. Now, he’s illustrating how his work in the field of microbiology is personal. Eisen has type 1 diabetes, an autoimmune disease linked to, among other things, changes in the microbiome.
To understand how seriously Eisen takes his position as the defender of microbial diversity, it’s useful to know where he got his career start: in an undergraduate internship at the D.C. Public Defender Service. It fostered a lifelong ardor for justice and an impulse to, whenever possible, stick it to the bullies. He argues that microbial communities—whether in our bodies or in buildings—function as complex ecosystems, not unlike tropical rainforests. “That doesn’t mean microbes don’t kill some people and make others sick,” he says. “But if you’re afraid of a tiger, you don’t clear-cut the rainforest. Well, you do in some cases, but that’s crazy.”
“If you’re afraid of a tiger, you don’t clear-cut the rainforest.”
Until last year, Eisen was a member of the Forum on Microbial Threats. (He quit, saying both beneficial microbes and female scientists were underrepresented.) At the time the National Academy of Sciences first convened the forum, the prevailing narrative was that microbes were an enemy of public health and we were at war with them. The approach backfired: Germs adapt to whatever drugs are thrown at them, swapping genes with neighbors to accrue antibiotic resistance. The rise of superbugs, coupled with growing awareness of the human microbiome, has led many scientists, including the forum, to rethink the merits of germ warfare.
Eisen takes a bite of stir-fry and suggests we ditch the word pathogen altogether. “Sometimes germs are good, sometimes they’re bad,” he says, sounding unusually Yoda-like. “Nothing is good or bad all the time.”
As someone who has spent 20 years studying microbial evolution, Eisen is in a good position to explain the paradigm shift. In 2007 he helped launch a “genomic encyclopedia” of microbes—a splashy debut whose biggest point was all of the blank pages: We have no idea who the vast majority of our microbial neighbors are.
That hasn’t stopped us from trying to kick them out. There are now thousands of antimicrobial products on the market, which range from clothing to cutting boards. One industry report forecasts that the $1.9 billion coating market alone will more than double in 2020. Rolf Halden, an Arizona State University environmental engineer, says the marketing preys on consumers’ fears. “There’s ample evidence we use too many antimicrobials,” he says, “and without judgment.”
Halden has found that triclosan, a common antimicrobial, makes its way from products like hand soap into sewage, where it breeds antibiotic resistance. Studies have also detected high levels of triclosan in house dust. One found it counterintuitively helps Staphylococcus—a common source of infection—adhere to plastic and glass surfaces. What we don’t know is how it or other antimicrobials affect the organisms that might actually help us.
This topic makes Eisen visibly agitated. He waves his fist like a trial lawyer itching to clock opposing counsel. He brings up a company hawking a new indoor sanitation technology on Twitter—a 24-hour, Purell-like system that purportedly kills everything, including Ebola. It’s an indiscrimate weapon in the old war. Struggling for composure, he says: “That doesn’t sound good.”
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In order to understand what happens when a built environment’s microbial ecosystem is wiped out, scientists have begun to study the most sterile structures on Earth—and off. For astronauts, the International Space Station (ISS) is like living inside a giant antibiotic pill. HEPA filters remove airborne germs, surfaces deter bacterial growth, and iodine and biocidal nano-silver cull microbes from water. “Everything is sterilized, except for the humans,” says Hernan Lorenzi of the J. Craig Venter Institute, which has been studying the ISS for four years.
As a result, the microbial ecosystem in the station is made up mostly of the organisms the astronauts themselves shed daily. There are no Amazon deliveries, no windows to crack—no influx of fresh microbes to balance the ecosystem. And so Lorenzi’s team is sampling the microbiome of astronauts to see how it changes after a stint in the station. A loss of gut diversity, he says, correlates with many diseases and could raise concerns for long-term space travel. Astronauts often have impaired immunity, and “if you lose your gut microflora,” Lorenzi says, “the immune system goes dormant.” It takes a space vacation. “Can you imagine a trip to Mars?” asks Eisen. “They’ve gotta be screwed.”
On Earth, the same phenomenon occurs in hospitals, only sick patients are the ones shedding microbes. Despite extensive sanitation, infections acquired in U.S. hospitals kill about 75,000 people annually—more deaths than from breast cancer and HIV/AIDs combined. The Chicago-based Hospital Microbiome Project, led by Argonne National Laboratory’s Jack Gilbert, studied the ecology of one hospital for a year and found microbes everywhere. “You can do as much cleaning as you want,” says Gilbert. “The hospital is a bloody sterile place, and a pathogen might still make you sick.”
That sounds terrifying, but everyone harbors pathogens. The dreaded Clostridium difficile, which can cause life-threatening diarrhea, is found in 66 percent of infants. Staphylococcus aureus is carried by 20 percent of adults. People who seem perfectly healthy harbor the influenza virus. These germs don’t do much harm when they’re kept in check by other organisms. Studies suggest, for instance, that the flu virus can be contained through competition with Lactobacillus.
“The hospital is a bloody sterile place, and a pathogen might still make you sick.”
And so Gilbert thinks the notion that we “catch” things is flawed. In a study of intensive-care units, his group observed otherwise harmless microbes go rogue in four patients after drugs decimated their gut flora. “You put humans through the ringer, and we’re surprised their germs are stressed too?” he asks. Scientists suspect that in hospital rooms, sanitization can likewise pressure microbes to evolve into virulent pathogens, which then colonize surfaces cleared of competitive bacteria. Recycled-air systems help concentrate them. “We’ve gone too far,” says Gilbert. “Hygiene is good; sterility may not be.”
For Sandra Bauder, an architect in Houston, the zealous sanitation trend brings to mind a fancy horse her uncle kept in Venezuela. “He babied it—with special food, an air-conditioned barn, never let any bugs get on it. And it was always sick. Then he got a mutt horse. It lived in a pasture. It didn’t get anything, not even a stomachache. I think it’s the same for people.”
After my son was born, I received an Evite for a party entitled “Please don’t lick the baby.” Further instructions asked guests to wash their hands before arrival and not to touch the baby anyway. This seemed sensible. Parenthood can make anyone a hormonal germophobe, and I was no different. I had visitors apply botanical hand sanitizer (we lived in San Francisco, where there was hippie Purell) and remove their shoes at the door. Yet despite my vigilance, my son grew into an allergic toddler. His eyes swelled shut, his bottom turned red, and his body erupted with hives after exposure to a litany of foods, dust, pollen, and even the house cat he was raised with. Doctors warned me to prepare for a lifetime of severe immune dysfunction.
The devastating irony is that the rise of diseases of inflammation in children—often called “modern plagues”—is most likely not caused by picking up the pathogens we fear. Rather, it’s the result of not being exposed to the microbes that are key to maturing immunity. And how we enter the world determines our first colonizers.
In the birth canal, babies acquire Lactobacillus, which helps them digest milk and begins the process of lowering the gut’s pH to the normal range. But babies born by cesarean miss out. Studies show they instead often end up with bacteria that are commonly found on the skin (sometimes not even the mother’s), such as Staphylococcus—and in the case of one neonatal intensive-care unit, antibiotic- and disinfectant-resistant bacteria. Abnormal colonization may explain why C-section babies seem to have a heightened risk for obesity, allergies, and asthma, which are linked to gut inflammation.
My son was not a C-section baby. But he did grow up in an apartment that might have been too clean. According to one theory, environmental exposures contribute to our development after birth, and recent studies seem to back that up. They suggest germs might actually help prevent children from developing various maladies.
“A house with a more bacteria-rich environment is a healthier one,” says Susan Lynch, a microbiologist at the University of California at San Francisco. Her group profiled 104 infants inside their homes and found that the babies exposed to house dust with the greatest bacterial diversity before age 1 were the least likely to have asthma symptoms as 3-year-olds. In addition to mouse and cockroach droppings, the dust was heavily colonized with microbes found in a healthy Western gut. Toddlers exposed to fewer types of bacteria, on the other hand, turned into hyperallergic wheezers. “We found that in homes with very little bacterial diversity,” she says, “there was a very large number of fungi present.”
Petri Dish
Because studies show pet exposure might protect kids from allergies, Lynch also fed young mice meals from homes with germ-rich dogs. The mice grew up to be less allergic than those used as controls. She isolated one of their gut microbes, Lactobacillus johnsonii , and fed it to more mice. They were protected too, but less so. Lynch suspects that L. johnsonii is a “keystone” species: It has an outsize role in determining which microbes move in and how they behave—guiding the immune response.
I’ve met Lynch before, when my son was morphing into one of her asthmatic superwheezers. She helped line up a medical referral. “How’s he doing?” she now asks. I tell her we moved to Oakland, where I countered my son’s rather unscientific medical diagnosis of “allergic gut” with an equally unscientific prescription of dirt, dogs, chickens, and cultured foods. After school he tends to his bean tepee, and grows the strawberries he once couldn’t eat. A fine sprinkling of soil often rings his mouth, like cookie crumbs. Surprisingly, most of his allergies have disappeared.
“He sounds like a perfect case study,” Lynch says, completely nonplussed. “I would have liked to have gotten samples from him before and after. My guess is that his microbiome looks more like a normal gut.” Lynch recently left San Francisco too; it turns out we’re neighbors. “We have a great picture of our 10-month-old daughter eating soil off a rock,” she says.
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In a remote corner of northern California, on a steep slope of knotty oaks, sulfur and steam rise in plumes from Wilbur Hot Springs. It’s the perfect place, says Eisen, to investigate the ghost limbs on the tree of life, the ones that contain multitudes of microbes we haven’t yet identified. This microbial dark matter, as he calls it, is best pursued in isolated locales, such as deep mines and underground aquifers—or a nearby pool of absinthe-colored spring water, by which a sunbather lounges in a broad hat, and not much else.
This place is weird, and it is Eisen’s milieu. He enters a creaky wooden shack, where water from a spigot feeds the pool. His colleagues from the Department of Energy’s Joint Genome Institute, where he is an adjunct scientist, were here months earlier with collection jars. They were taking the waters, to echo an old phrase referring to the devotees of spa towns—only quite literally. They took samples back to the lab, where they amplified the microbial DNA a billionfold.
“A house with a more bacteria-rich environment is a healthier one.”
As we hike along a creek toward the source water, Eisen is in a good mood. The view’s nice; the chapparal smells great. Here, he makes his final case for microbial diversity: Dark matter is special, he tells me. By 2009, scientists had sequenced the DNA of only about a thousand microbes, those important to medicine or with clear applications. They mainly came from the same three branches of the evolutionary tree. And so Eisen led a team that set out to sequence a thousand more, with an emphasis on “neglected” species. The work has begun to fill in the tree with many more branches, revealing how microbes evolved and how species are related.
Ultimately, Eisen hopes, this knowledge will provide “a field guide to all microbes, including what is normally seen in the built environment.” Much of the DNA found in recent studies lacks context. In addition, many microbes have genes with completely unknown functions. Finding similar genes on different branches could explain what they do—and eventually help us select microbes to create healthier surroundings. Emily Landon, an epidemiologist at the University of Chicago, envisions one day replacing antimicrobial paint with probiotics-infused walls. She calls it a fecal transplant for the built environment, wherein we infuse a space with beneficial bacteria that outcompete harmful ones. Or somewhere in Lynch’s pile of anonymous DNA could be a clue to a microbe that eliminates my son’s remaining allergy, to our cat.
Near the ruins of a bathhouse, milky bubbles well up from an aquifer. Garishly colored films have formed on rocks poking out of the water. “This is pretty awesome,” Eisen says, wading toward a red-and-purple blob. “That’s a nice mat. Touch that.” As he inspects the photosynthetic bacteria, a cloud of tiny winged insects hovers at his ankles. These bugs too are taking the waters. Chances are they evolved to be at home with their own set of microbes. As we have.
This article was originally published in the August 2015 issue of Popular Science, under the title “Bugged.”
The Pop Sciome
We painstakingly swabbed a dozen sites around the Popular Science office for a week in March. Here, below, is a sliver of our microbiome, analyzed by a lab at Weill Cornell Medical College. Scroll over the image to get more information.
All bacteria found at the three sample sites appear as circles. The trees show how the bacteria are related, from phylum (center) to family (outer edge). For each site, bigger circles represent more abundant species.
Data visualization by Elizabeth Hénaff, based on analysis by the Mason Lab, Weill Cornell Medical College.
