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conulyStudies of Human Microbiome Yield New Insights
For a century, doctors have waged war against bacteria, using antibiotics as their weapons. But that relationship is changing as scientists become more familiar with the 100 trillion microbes that call us home — collectively known as the microbiome.
“I would like to lose the language of warfare,” said Julie Segre, a senior investigator at the National Human Genome Research Institute. “It does a disservice to all the bacteria that have co-evolved with us and are maintaining the health of our bodies.”
This new approach to health is known as medical ecology. Rather than conducting indiscriminate slaughter, Dr. Segre and like-minded scientists want to be microbial wildlife managers.
No one wants to abandon antibiotics outright. But by nurturing the invisible ecosystem in and on our bodies, doctors may be able to find other ways to fight infectious diseases, and with less harmful side effects. Tending the microbiome may also help in the treatment of disorders that may not seem to have anything to do with bacteria, including obesity and diabetes.
“I cannot wait for this to become a big area of science,” said Michael A. Fischbach, a microbiologist at the University of California, San Francisco, and an author of a medical ecology manifesto published this month in the journal Science Translational Medicine.
Judging from a flood of recent findings about our inner ecosystem, that appears to be happening. Last week, Dr. Segre and about 200 other scientists published the most ambitious survey of the human microbiome yet. Known as the Human Microbiome Project, it is based on examinations of 242 healthy people tracked over two years. The scientists sequenced the genetic material of bacteria recovered from 15 or more sites on their subjects’ bodies, recovering more than five million genes.
The project and other studies like it are revealing some of the ways in which our invisible residents shape our lives, from birth to death.
A number of recent reports shed light on how mothers promote the health of their children by shaping their microbiomes. In a study published last week in the journal PLoS One, Dr. Kjersti Aagaard-Tillery, an obstetrician at Baylor College of Medicine, and her colleagues described the vaginal microbiome in pregnant women. Before she started the study, Dr. Aagaard-Tillery expected this microbiome to be no different from that of women who weren’t pregnant.
“In fact, what we found is the exact opposite,” she said.
Early in the first trimester of pregnancy, she found, the diversity of vaginal bacteria changes significantly. Abundant species become rare, and vice versa.
One of the dominant species in the vagina of a pregnant woman, it turns out, is Lactobacillus johnsonii. It is usually found in the gut, where it produces enzymes that digest milk. It’s an odd species to find proliferating in the vagina, to say the least. Dr. Aagaard-Tillery speculates that changing conditions in the vagina encourage the bacteria to grow. During delivery, a baby will be coated by Lactobacillus johnsonii and ingest some of it. Dr. Aagaard-Tillery suggests that this inoculation prepares the infant to digest breast milk.
The baby’s microbiome continues to grow during breast-feeding. In a study of 16 lactating women published last year, Katherine M. Hunt of the University of Idaho and her colleagues reported that the women’s milk had up to 600 species of bacteria, as well as sugars called oligosaccharides that babies cannot digest. The sugars serve to nourish certain beneficial gut bacteria in the infants, the scientists said. The more the good bacteria thrive, the harder it is for harmful species to gain a foothold.
As the child grows and the microbiome becomes more ecologically complex, it also tutors the immune system. Ecological disruptions can halt this education. In March, Dr. Richard S. Blumberg of Harvard and his colleagues reported an experiment that demonstrates how important this education is.
The scientists reared mice that lacked any microbiome. In their guts and lungs, the germ-free mice developed abnormally high levels of immune cells called invariant natural killer T cells. Normally, these cells trigger a swift response from the immune system against viruses and other pathogens. In Dr. Blumberg’s microbe-free mice, however, they caused harmful inflammation. As adults, the mice were more likely to suffer from asthma and inflammatory bowel disease.
This experiment parallels studies of children in recent years. Children who take high levels of antibiotics may be at greater risk of developing allergies and asthma later on, many researchers have suggested.
Dr. Blumberg and his colleagues found that they could prevent the mice from becoming ill by giving them bacteria while they were still young. Acquiring a microbiome as an adult did not help the rodents.
The Good With the Bad
The diversity of species that make up the microbiome is hard to fathom. But it is even more difficult to understand how the immune system copes with this onslaught. In any one person’s mouth, for example, the scientists of the Human Microbiome Project found about 75 to 100 species. Some that predominate in one person’s mouth may be rare in another person’s. Still, the rate at which they are being discovered indicates that there may be as many as 5,000 species of bacteria that live in the human mouth.
“The closer you look, the more you find,” said Susan M. Huse of the Marine Biological Laboratory in Woods Hole, Mass., a contributor to the microbiome project.
Although the project has focused largely on bacteria, the microbiome’s diversity is wider. For example, our bodies also host viruses.
Many species in the human “virome” specialize in infecting our resident bacteria. But in the DNA samples stored in the Human Microbiome Project’s database, Kristine Wylie of Washington University and her colleagues are finding a wealth of viruses that target human cells. It is normal, it seems, for people to have a variety of viruses busily infecting their human hosts. “It’s really pretty striking that even in these healthy people, there really is a virome,” Dr. Wylie said.
The microbiome also includes fungi. In the June 8 issue of the journal Science, David Underhill, a research scientist at Cedars-Sinai hospital in Los Angeles, and his colleagues reported on a wealth of fungal species in the guts of humans and other mammals. In mice, for example, they cataloged 100 species of fungi that are new to science, along with 100 already known. This diversity is all the more remarkable when you consider that it is tolerated by an immune system that has evolved to fight off microbes. Scientists have only a dim understanding of how the system decides which to kill and which to tolerate.
Immune cells fight fungal infections, for example, with a protein called dectin-1, which attaches only to fungi. But Dr. Underhill and his colleagues found that dectin-1 is also essential for tolerating harmless fungi. When they engineered mice that couldn’t produce dectin-1, the mice responded to harmless fungi by producing so much inflammation that their own tissues were damaged.
It’s a good thing that the immune system can rein itself in, because the microbiome carries out many services for us. In the gut, microbes synthesize vitamins and break down tough plant compounds into digestible bits.
Skin bacteria are also essential, Dr. Segre said. “One of the most important functions of the skin is to serve as a barrier,” she said. Bacteria feed on the waxy secretions of skin cells, and then produce a moisturizing film that keeps our skin supple and prevents cracks — thus keeping out invading pathogens.
Restoring Order to the System
Antibiotics kill off harmful bacteria, but broad-spectrum forms can kill off many desirable species, too. Dr. Fischbach likens antibiotics to herbicides sprayed on a garden. The herbicide kills the unwanted plants, but also kills off the tomatoes and the roses. The gardener assumes that the tomatoes and roses will grow back on their own.
In fact, there’s no guarantee the microbial ecosystem will automatically return to normal. “It’s one of those assumptions we make today that will seem silly in retrospect,” Dr. Fischbach said. Indeed, some bacteria are adapted for invading and establishing themselves in disrupted ecosystems. A species called Clostridium difficile will sometimes invade a person’s gut after a course of antibiotics. From 2000 to 2009, the number of hospitalized patients in the United States found to have C. difficile more than doubled, to 336,600 from 139,000. Once established, the antibiotic-resistant C. difficile can be hard to eradicate.
Now that scientists are gaining a picture of healthy microbiomes, they are optimistic about restoring devastated ones. “I don’t know that we’re quite on the cusp of being able to do that well at this point. But I think at least the data is starting to argue that these might be possibilities,” said Barbara Methé of the J. Craig Venter Institute, a principal investigator on the microbiome project.
One way to restore microbiomes may be to selectively foster beneficial bacteria. To ward off dangerous skin pathogens like Staphylococcus aureus, for instance, Dr. Segre envisions applying a cream infused with nutrients for harmless skin bacteria to feed on. “It’s promoting the growth of the healthy bacteria that can then overtake the staph,” she said.
Bacterial Transplants
Adding the bacteria directly may also help. Unfortunately, the science of so-called probiotics lags far behind their growth in sales. In 2011, people bought $28 billion of probiotic foods and supplements, according to the research firm EuroMonitor International. But few of them have been tested as rigorously as conventional drugs.
“I think the science has been shoddy and flimsy,” said Dr. Fischbach (who is on the scientific advisory board of Schiff Nutrition International).
Nonetheless, he sees a few promising probiotic treatments. A growing number of doctors are treating C. difficile with fecal transplants: Stool from a healthy donor is delivered like a suppository to an infected patient. The idea is that the good bacteria in the stool establish themselves in the gut and begin to compete with C. difficile. This year, researchers at the University of Alberta reviewed 124 fecal transplants and concluded that the procedure is safe and effective, with 83 percent of patients experiencing immediate improvement as their internal ecosystems were restored.
Dr. Alexander Khoruts of the University of Minnesota and his colleagues want to make fecal transplants standard practice. They can now extract bacteria from stool, “removing the ‘ick’ factor,” as he puts it.
Dr. Khoruts and his colleagues have federal approval to start formal clinical trials on fecal transplants. Eventually, he would like to develop probiotic pills that contain just a few key species required to build the intestinal ecosystem.
“People are starting to take this seriously,” Dr. Fischbach said. “This is a therapy that’s going to help a lot of people.”
Other conditions potentially could be treated by manipulating the microbiome. Scientists have linked obesity, for example, to changes to the gut’s ecosystem. When scientists transfer bacteria from obese mice to lean ones, the lean mice put on weight.
How this happens is still unclear, but some studies suggest that an “obese” microbiome sends signals to the body, changing how cells use sugar for energy and leading the body to store extra fat.
Researchers at the Academic Medical Center in Amsterdam are running a clinical trial to see if fecal transplants can help treat obesity. They have recruited 45 obese men; some are getting transplants from their own stool, while others get transplants from lean donors. The scientists are finding that the transplants from lean donors are changing how the obese subjects metabolize sugar.
While these initial results are promising, there is no evidence yet that the obese subjects are losing weight. Dr. Fischbach cautions that it may take a while to figure out how to manipulate the microbiome to make people healthy.
And it may take even longer to persuade doctors to think like ecologists.
“The physicians I know really like things that are clear and crisp,” Dr. Fischbach said. “But like any ecosystem, the microbiome is not the kind of place to find simple answers.”
To Tackle an Invasive Weed, Bringing In the Hooved Pros
On a sweltering afternoon on Staten Island, the New York City parks department unveiled its latest weapon in the war on phragmites, an invasive weed that chokes the shoreline: goats. Twenty Anglo-Nubians, to be exact. With names like Mozart, Haydn and Van Goat, and with floppy ears and plaintive bleats, they did not seem fearsome. But on Thursday they were already munching inexorably through the long pale leaves in the first phase of a wetland restoration at what will soon be Freshkills Park.
Known for their unending, indiscriminate appetites, the goats are being rented by the city for the next six weeks from a farmer in the Hudson Valley. Parks officials are counting on the goats to clear the phragmites across two acres of wetlands that will eventually be cultivated with native grasses like spartina and black needle rush. The hope is that the goats will weaken the phragmites, setting the stage for another series of assaults on their stubborn rhizomes — applying herbicide, scarifying the earth and laying down sand.
In the short term, the goats are part of an unusual experiment to eradicate the pesky reeds, which were introduced from Europe in the late 19th century and which, once rooted, are almost impossible to eliminate. They have fueled brush fires across the region and pushed out other species along the East Coast.
But the farm animals are also being tested for their lawn-mowing prowess, especially at Freshkills Park, which is in transition from its former life as the world’s largest landfill to its future one — as the largest park to be developed in New York City in more than a century.
“We want to introduce the idea of using goats to help in vegetation management,” Eloise L. Hirsh, the administrator of the park, said. “The sanitation department mows us once a year. But this is 2,200 acres. We need help.”
The goats are perhaps the most vivid example of the lengths to which the city is going to turn a symbol of environmental degradation into one of ecological redemption. As Freshkills Park is developed in phases over the next three decades, it will be a laboratory for green practices; there are plans for composting toilets, green roofs, rain gardens and a native seed farm.
The official opening of the park is two or three years off, though it is open periodically for tours. Three of the four giant mounds formed by garbage are now capped, and the parks department will soon solicit bids on the first stage of development — 21 acres with walking paths and a bird observation tower overlooking the wetlands. Already, the landscape looks impossibly bucolic, with dragonflies and swallows darting amid lanky grasses and the occasional tree.
The goats only add to the pastoral image. On Thursday, Beethoven, with long white ears and a black body, and Van Goat, sporting a black stripe down his chestnut back, were contentedly exploring their new territory, plunging their mouths into dense stands of phragmites. Others trotted down to the shore of Main Creek, a tributary of the Fresh Kill. (In yet another act of environmental rectitude, parks workers will soon arrange logs made of coconut fiber along the banks to attract mussels, which prevent erosion.)
“The first test was to see if they would eat the phragmites, and they’re eating it, so they passed,” said Terry Doss, an ecologist with Biohabitats, a company specializing in ecological restoration that is advising the parks department.
The city received a grant of $350,000 from the state for the wetlands project. (The cost of renting the goats from Larry Cihanek of Rhinebeck, N.Y., is $20,625 for the six weeks.) If the goats prove successful, Freshkills Park may one day have a permanent herd. “It’s exciting to be able to replace what would be a carbon-polluting mowing strategy with a more natural approach,” said Andrew Deer, a landscape architect for the parks department.
While goats have been deployed for phragmite duty elsewhere, some ecologists are skeptical.
“I’m not a big fan of goats,” said Bernd Blossey, an associate professor of natural resources at Cornell University. “I understand why people are desperate to try them. But they will eat the leaves but not the stems, and they also don’t like getting their hooves wet.”
Professor Blossey is experimenting with moth caterpillars, which can weaken phragmites. In the 1990s, he was successful in unleashing leaf beetles against another plant invader, purple loosestrife, which is not nearly the scourge it once was.
But as the goats made their debut this week at Freshkills Park, any such doubts were pushed to the background. Ms. Hirsh was already looking ahead to a day when goats not only keep phragmites in check, but also put Staten Island on the artisanal food map. “We would like to have a cheese manufacturer here,” she said. “I know there will be lots of skepticism. But it would be a pretty eloquent statement about how you really can restore land that was formerly very damaged.”
Learning Hebrew on the Streets, With Walls as Assigned Reading
The texts, written on metal grates, stone walls and neon signs, sometimes disappear from one class to the next. The themes are pluralism, economic justice and the Israeli-Palestinian conflict — and grammar, always a little grammar thrown in.
Guy Sharett’s Hebrew lessons are taught in a walking classroom, on the streets and alleys of Florentin, his neighborhood here, where new vocabulary words are mixed into an ever-changing curriculum.
“Get out from the TV, start to live,” Mr. Sharett translated one scrawled Hebrew slogan at the start of class one recent evening, trailed by a dozen students thirsty to understand the life of the Tel Aviv street as much as the revived ancient language spoken on it.
He pulled out a little white board to break down the graffiti before him. The first part of the slogan, “Tzay mayhatelevizia,” used the imperative — get out — while “tatchil lichayot,” start to live, was in the future tense. “It sounds to us too pompous and too archaic,” he explained, “so we just use the future.”
A few minutes earlier, they had analyzed a sign exhorting dog owners not to permit their animals to relieve themselves near a certain building. Next, a picture of Theodor Herzl, the father of Zionism, with his famous mantra, “If you will it, it is no dream,” twisted into “If you don’t want, you don’t need.” Here, a verse by the street artist and poet Nitzan Mintz. There, the iconic image of a forlorn child from the Warsaw ghetto, captioned “Don’t Deport Me,” repurposed to the current crisis of migrant workers from Africa flooding south Tel Aviv.
“They depend on a cultural knowledge that you don’t necessarily have,” said one of the students, Marcela Sulak, who has been here two years as director of the creative writing program at Bar-Ilan University. “He teaches you the tools so you can figure it out on your own. You’re learning the Hebrew you need every single day by looking at the neighborhood.”
The hourlong classes, which cost 50 shekels, or about $12, are organized on Facebook. They grew out of last summer’s protests, when Mr. Sharett’s traditional Hebrew students were mystified by the signs at the encampment along Rothschild Boulevard, so he started taking them — and his little white board — outside for lessons. After the protest tents came down, he decided to make the graffiti-pocked walls of his gentrifying neighborhood the new syllabus.
“It’s not only to teach language, it’s also to teach the culture,” Mr. Sharett explained. “Someone took a line from a song we all know and changed one word; it’s very hard to understand that if you don’t have someone local to explain, ‘That’s a take on...’ ”
Mr. Sharett, 40, has a day job at a television company, but has been giving private Hebrew lessons for several years. Besides the graffiti course, he offers one-offs touring the city’s spice market (“Wake up and smell the Zatar”); shopping and cooking with a famous chef (“While chopping, we learn the names of the vegetables”); and watching the local version of “American Idol,” with frequent use of the pause button to translate slang and jokes (“This is Israeliness 101,” he said).
The son of an artist and a tugboat skipper whose home in Ashdod was “like a French salon,” Mr. Sharett is something of a language savant. “There was a Turkish neighbor, so I started learning Turkish; there was a German au pair, so I started learning German,” he said. At 16, he got a job in the control tower of the port, “so I was able to talk on the radio with captains in different languages and tell them to heave up the anchor — but only maritime terms that I can’t really use in regular life.”
The students on his tours want terms they can use in everyday life; many are dropouts from ulpan, the immersion classes that are free for new immigrants. A recent graffiti tour included a Chinese postdoctoral fellow; a 28-year-old Google employee from Rhode Island; a financial analyst and poet who is married to an Israeli; a British teacher who has lived here 20 years; Ms. Sulak, whose 5-year-old daughter slept the entire hour in her stroller; and a Middle Eastern politics professor at the City University of New York who is on sabbatical.
“Street politics is where it’s happening,” said the professor, Dov Waxman, 37. “Most places, graffiti is tagging or art. Here, you can really read the politics. I wander around and look at it myself, but I don’t always understand it all.”
Xiaoyun Wu, the postdoctoral fellow, has been studying Hebrew with Mr. Sharett for three months, and was the first to answer most of his grammar questions. “You get more contextualized memory,” she said of on-the-street learning. “The good thing is I can come back to review any time.”
Here, one finds a lesson on how easy it is to make up words — a tattoo parlor called, essentially, “tattooism,” using the Hebrew letters yud, zayin, mem to add “ism.” There, a black door features the ubiquitous road signs pointing one way to Tel Aviv and the other to Jerusalem, only the Jerusalem arrow leads to an ultra-Orthodox man at prayer. A tag declares “Jews and Arabs refuse to be enemies.” A sign uses the word “agudah,” association, which Mr. Sharett pointed out has the same root as the Israeli bus company, Egged, because buses link places together.
Then there is a new ampm convenience store, one of many chains now dotting the once-gritty streets of Florentin. “We pronounce it Ahm-Pahm,” Mr. Sharett told the group. “If you want to impress your Israeli friends, say, ‘Ani holech l’ahm pahm,’ ” which means “I’m going to the ampm.”
Ultra-Orthodox Men Charged With Trying to Silence Accuser
The Brooklyn district attorney, facing a wave of public criticism about his handling of sexual abuse allegations in the ultra-Orthodox Jewish community, on Thursday charged four men with attempting to silence an accuser by offering her and her boyfriend a $500,000 bribe, and threatening her boyfriend’s business.
The district attorney, Charles J. Hynes, alleged that the men were part of an effort to protect a prominent member of the Satmar Hasidic community, Nechemya Weberman, who has been accused of 88 counts of sexual misconduct, including oral sex with a child younger than 13 years old. The charges all involve one girl, now 17, who was referred by her school to get counseling by Mr. Weberman, and then alleged she was abused by him during therapy sessions.
The charges are the first time in at least two decades that Mr. Hynes has charged Hasidic Jews with intimidation of a witness in a sexual abuse case, even though victims, their advocates and prosecutors say intimidation has long been a major obstacle to prosecution of abuse among the ultra-Orthodox. In recent weeks, Mr. Hynes has been saying that the intimidation of witnesses in the ultra-Orthodox community is worse than in the world of organized crime.
“I’m hoping that this will be a message to those who are intimidated that they should come forward and help us,” Mr. Hynes said at a news conference. “No one can engage in this kind of conduct and feel free that, based on prior experience, nothing can happen to them.”
Prosecutors charged Abraham Rubin, 48, of Williamsburg with bribery, witness tampering and coercion. They said that he had been recorded offering the accuser’s boyfriend the money, and he suggested that the young couple could flee to Israel to avoid testifying. He also offered to provide them with a lawyer who could help them avoid cooperating with prosecutors.
Prosecutors also charged three brothers, Jacob, Joseph and Hertzka Berger, with coercion, saying they threatened and then removed the kosher certification of a restaurant run by the accuser’s boyfriend. The brothers are sons of a local rabbi who issues kosher certifications to stores.
The four men pleaded not guilty on Thursday in a Brooklyn courtroom packed with benches full of their supporters, dressed in the dark clothing worn by Hasidic men.
Hertzka Berger’s lawyer, Bruce Wenger, said after the arraignment that the four men “all deny the allegations.”
“They are all obviously going to be fighting these cases vehemently,” he said. “They are looking forward to their day in court.”
But a prosecutor, Josh Hanshaft, said the men had been “telling witnesses to forget what they know, not to come to court, to disappear,” and said prosecutors had “clear, substantial evidence” that part of the plan to silence witnesses involved offering money to dissuade their testimony.
If convicted, Mr. Rubin faces up to seven years in prison. Joseph and Hertzka Berger each face a year in jail, and Jacob Berger faces up to four years.
Mr. Weberman has denied the abuse allegations, and his lawyer, George Farkas, said Mr. Weberman knew nothing of the alleged intimidation.
“Mr. Weberman, and his attorneys, are appalled by these allegations, which if true, are reprehensible,” Mr. Farkas said. The intimidation charges, a moment of triumph for Mr. Hynes, come as his office has been criticized by victims, victims’ advocates, former Mayor Ed Koch and others for an insufficiently aggressive response to the sexual abuse of minors within the ultra-Orthodox community.
And this week, Mr. Hynes’s office is suffering an embarrassing reversal in another abuse case involving an Orthodox Jewish accuser. After revelations that Mr. Hynes’s office had failed to share exculpatory evidence with defense attorneys, lawyers said Monday that all charges against four men accused of raping and forcibly prostituting a Chabad Lubavitch woman from Crown Heights for nearly a decade would be dropped.
In the Williamsburg case, the accuser was in sixth grade when she was referred to Mr. Weberman, an unlicensed therapist, by her Williamsburg religious school, a close family member said in an interview last month. Her parents were told she would be expelled from school unless they paid $150 an hour for him to provide her with therapy.
Instead, Mr. Weberman, who is now 53, repeatedly sexually molested her over three years, when she was 12 to 15, and told her that she would be expelled from school if she told anyone, the relative said. The girl then changed schools and told a licensed therapist what had happened. The therapist reported the girl’s allegations to the police.
After Mr. Weberman’s arrest in 2011, a campaign of intimidation is alleged to have begun against the accuser, her boyfriend and her family members. Prominent Hasidic Jews publicly proclaimed their support for Mr. Weberman, and, on May 16, hosted hundreds of Hasidic men at a local wedding hall to raise money for Mr. Weberman’s legal defense. To promote the fund-raiser, his supporters hung posters on lampposts and brick walls around the neighborhood, accusing the young woman, in Yiddish, of libel.
The girl’s boyfriend, 24-year-old Hershy Deutsch, organized a demonstration outside the fund-raiser. In an interview at the time, he said that he had faced intimidation because of his girlfriend’s allegations, and that he had decided to speak out. He said that a restaurant he manages in Williamsburg, the Old Williamsburg Cafe on Lee Avenue, was targeted by a flood of false complaints to city authorities in late April. And, he said, men from the neighborhood had offered him $500,000 if he could persuade the girl to drop her case.
“For those of you questioning the credibility of the victim’s story,” Mr. Deutsch wrote in a letter he posted on his Facebook page, “ask yourself the following question: Would a nonguilty person offer someone a half a million dollars if they drop the charges?”
“Speak up!” he wrote. “Face the facts, our community has been covering up these stories for way too long. We have to put an end to this!”
On Thursday afternoon a metal gate was rolled down over the entrance to the Old Williamsburg Cafe, and a sign taped to the door said that the store “will be closed until further notice.”
Victims’ advocates said Thursday that they were glad that Mr. Hynes had brought an intimidation case, and hoped it would begin to ease the problem. While some ultra-Orthodox rabbis now say that a child molester should be reported to the police, others strictly adhere to an ancient Jewish prohibition against mesirah, the turning in of a Jew to non-Jewish authorities, and instruct victims to either remain silent or let rabbinical authorities quietly handle the allegations.
“This is a big threshold,” said Mark Appel, the founder of Voice of Justice, a nonprofit agency that helps ultra-Orthodox victims. And Joel Engelman, the founder of the Jewish Survivors Network, also praised Mr. Hynes for bringing the intimidation case, because, he said, “in the Williamsburg Hasidic community, intimidation is rampant.”
For a century, doctors have waged war against bacteria, using antibiotics as their weapons. But that relationship is changing as scientists become more familiar with the 100 trillion microbes that call us home — collectively known as the microbiome.
“I would like to lose the language of warfare,” said Julie Segre, a senior investigator at the National Human Genome Research Institute. “It does a disservice to all the bacteria that have co-evolved with us and are maintaining the health of our bodies.”
This new approach to health is known as medical ecology. Rather than conducting indiscriminate slaughter, Dr. Segre and like-minded scientists want to be microbial wildlife managers.
No one wants to abandon antibiotics outright. But by nurturing the invisible ecosystem in and on our bodies, doctors may be able to find other ways to fight infectious diseases, and with less harmful side effects. Tending the microbiome may also help in the treatment of disorders that may not seem to have anything to do with bacteria, including obesity and diabetes.
“I cannot wait for this to become a big area of science,” said Michael A. Fischbach, a microbiologist at the University of California, San Francisco, and an author of a medical ecology manifesto published this month in the journal Science Translational Medicine.
Judging from a flood of recent findings about our inner ecosystem, that appears to be happening. Last week, Dr. Segre and about 200 other scientists published the most ambitious survey of the human microbiome yet. Known as the Human Microbiome Project, it is based on examinations of 242 healthy people tracked over two years. The scientists sequenced the genetic material of bacteria recovered from 15 or more sites on their subjects’ bodies, recovering more than five million genes.
The project and other studies like it are revealing some of the ways in which our invisible residents shape our lives, from birth to death.
A number of recent reports shed light on how mothers promote the health of their children by shaping their microbiomes. In a study published last week in the journal PLoS One, Dr. Kjersti Aagaard-Tillery, an obstetrician at Baylor College of Medicine, and her colleagues described the vaginal microbiome in pregnant women. Before she started the study, Dr. Aagaard-Tillery expected this microbiome to be no different from that of women who weren’t pregnant.
“In fact, what we found is the exact opposite,” she said.
Early in the first trimester of pregnancy, she found, the diversity of vaginal bacteria changes significantly. Abundant species become rare, and vice versa.
One of the dominant species in the vagina of a pregnant woman, it turns out, is Lactobacillus johnsonii. It is usually found in the gut, where it produces enzymes that digest milk. It’s an odd species to find proliferating in the vagina, to say the least. Dr. Aagaard-Tillery speculates that changing conditions in the vagina encourage the bacteria to grow. During delivery, a baby will be coated by Lactobacillus johnsonii and ingest some of it. Dr. Aagaard-Tillery suggests that this inoculation prepares the infant to digest breast milk.
The baby’s microbiome continues to grow during breast-feeding. In a study of 16 lactating women published last year, Katherine M. Hunt of the University of Idaho and her colleagues reported that the women’s milk had up to 600 species of bacteria, as well as sugars called oligosaccharides that babies cannot digest. The sugars serve to nourish certain beneficial gut bacteria in the infants, the scientists said. The more the good bacteria thrive, the harder it is for harmful species to gain a foothold.
As the child grows and the microbiome becomes more ecologically complex, it also tutors the immune system. Ecological disruptions can halt this education. In March, Dr. Richard S. Blumberg of Harvard and his colleagues reported an experiment that demonstrates how important this education is.
The scientists reared mice that lacked any microbiome. In their guts and lungs, the germ-free mice developed abnormally high levels of immune cells called invariant natural killer T cells. Normally, these cells trigger a swift response from the immune system against viruses and other pathogens. In Dr. Blumberg’s microbe-free mice, however, they caused harmful inflammation. As adults, the mice were more likely to suffer from asthma and inflammatory bowel disease.
This experiment parallels studies of children in recent years. Children who take high levels of antibiotics may be at greater risk of developing allergies and asthma later on, many researchers have suggested.
Dr. Blumberg and his colleagues found that they could prevent the mice from becoming ill by giving them bacteria while they were still young. Acquiring a microbiome as an adult did not help the rodents.
The Good With the Bad
The diversity of species that make up the microbiome is hard to fathom. But it is even more difficult to understand how the immune system copes with this onslaught. In any one person’s mouth, for example, the scientists of the Human Microbiome Project found about 75 to 100 species. Some that predominate in one person’s mouth may be rare in another person’s. Still, the rate at which they are being discovered indicates that there may be as many as 5,000 species of bacteria that live in the human mouth.
“The closer you look, the more you find,” said Susan M. Huse of the Marine Biological Laboratory in Woods Hole, Mass., a contributor to the microbiome project.
Although the project has focused largely on bacteria, the microbiome’s diversity is wider. For example, our bodies also host viruses.
Many species in the human “virome” specialize in infecting our resident bacteria. But in the DNA samples stored in the Human Microbiome Project’s database, Kristine Wylie of Washington University and her colleagues are finding a wealth of viruses that target human cells. It is normal, it seems, for people to have a variety of viruses busily infecting their human hosts. “It’s really pretty striking that even in these healthy people, there really is a virome,” Dr. Wylie said.
The microbiome also includes fungi. In the June 8 issue of the journal Science, David Underhill, a research scientist at Cedars-Sinai hospital in Los Angeles, and his colleagues reported on a wealth of fungal species in the guts of humans and other mammals. In mice, for example, they cataloged 100 species of fungi that are new to science, along with 100 already known. This diversity is all the more remarkable when you consider that it is tolerated by an immune system that has evolved to fight off microbes. Scientists have only a dim understanding of how the system decides which to kill and which to tolerate.
Immune cells fight fungal infections, for example, with a protein called dectin-1, which attaches only to fungi. But Dr. Underhill and his colleagues found that dectin-1 is also essential for tolerating harmless fungi. When they engineered mice that couldn’t produce dectin-1, the mice responded to harmless fungi by producing so much inflammation that their own tissues were damaged.
It’s a good thing that the immune system can rein itself in, because the microbiome carries out many services for us. In the gut, microbes synthesize vitamins and break down tough plant compounds into digestible bits.
Skin bacteria are also essential, Dr. Segre said. “One of the most important functions of the skin is to serve as a barrier,” she said. Bacteria feed on the waxy secretions of skin cells, and then produce a moisturizing film that keeps our skin supple and prevents cracks — thus keeping out invading pathogens.
Restoring Order to the System
Antibiotics kill off harmful bacteria, but broad-spectrum forms can kill off many desirable species, too. Dr. Fischbach likens antibiotics to herbicides sprayed on a garden. The herbicide kills the unwanted plants, but also kills off the tomatoes and the roses. The gardener assumes that the tomatoes and roses will grow back on their own.
In fact, there’s no guarantee the microbial ecosystem will automatically return to normal. “It’s one of those assumptions we make today that will seem silly in retrospect,” Dr. Fischbach said. Indeed, some bacteria are adapted for invading and establishing themselves in disrupted ecosystems. A species called Clostridium difficile will sometimes invade a person’s gut after a course of antibiotics. From 2000 to 2009, the number of hospitalized patients in the United States found to have C. difficile more than doubled, to 336,600 from 139,000. Once established, the antibiotic-resistant C. difficile can be hard to eradicate.
Now that scientists are gaining a picture of healthy microbiomes, they are optimistic about restoring devastated ones. “I don’t know that we’re quite on the cusp of being able to do that well at this point. But I think at least the data is starting to argue that these might be possibilities,” said Barbara Methé of the J. Craig Venter Institute, a principal investigator on the microbiome project.
One way to restore microbiomes may be to selectively foster beneficial bacteria. To ward off dangerous skin pathogens like Staphylococcus aureus, for instance, Dr. Segre envisions applying a cream infused with nutrients for harmless skin bacteria to feed on. “It’s promoting the growth of the healthy bacteria that can then overtake the staph,” she said.
Bacterial Transplants
Adding the bacteria directly may also help. Unfortunately, the science of so-called probiotics lags far behind their growth in sales. In 2011, people bought $28 billion of probiotic foods and supplements, according to the research firm EuroMonitor International. But few of them have been tested as rigorously as conventional drugs.
“I think the science has been shoddy and flimsy,” said Dr. Fischbach (who is on the scientific advisory board of Schiff Nutrition International).
Nonetheless, he sees a few promising probiotic treatments. A growing number of doctors are treating C. difficile with fecal transplants: Stool from a healthy donor is delivered like a suppository to an infected patient. The idea is that the good bacteria in the stool establish themselves in the gut and begin to compete with C. difficile. This year, researchers at the University of Alberta reviewed 124 fecal transplants and concluded that the procedure is safe and effective, with 83 percent of patients experiencing immediate improvement as their internal ecosystems were restored.
Dr. Alexander Khoruts of the University of Minnesota and his colleagues want to make fecal transplants standard practice. They can now extract bacteria from stool, “removing the ‘ick’ factor,” as he puts it.
Dr. Khoruts and his colleagues have federal approval to start formal clinical trials on fecal transplants. Eventually, he would like to develop probiotic pills that contain just a few key species required to build the intestinal ecosystem.
“People are starting to take this seriously,” Dr. Fischbach said. “This is a therapy that’s going to help a lot of people.”
Other conditions potentially could be treated by manipulating the microbiome. Scientists have linked obesity, for example, to changes to the gut’s ecosystem. When scientists transfer bacteria from obese mice to lean ones, the lean mice put on weight.
How this happens is still unclear, but some studies suggest that an “obese” microbiome sends signals to the body, changing how cells use sugar for energy and leading the body to store extra fat.
Researchers at the Academic Medical Center in Amsterdam are running a clinical trial to see if fecal transplants can help treat obesity. They have recruited 45 obese men; some are getting transplants from their own stool, while others get transplants from lean donors. The scientists are finding that the transplants from lean donors are changing how the obese subjects metabolize sugar.
While these initial results are promising, there is no evidence yet that the obese subjects are losing weight. Dr. Fischbach cautions that it may take a while to figure out how to manipulate the microbiome to make people healthy.
And it may take even longer to persuade doctors to think like ecologists.
“The physicians I know really like things that are clear and crisp,” Dr. Fischbach said. “But like any ecosystem, the microbiome is not the kind of place to find simple answers.”
To Tackle an Invasive Weed, Bringing In the Hooved Pros
On a sweltering afternoon on Staten Island, the New York City parks department unveiled its latest weapon in the war on phragmites, an invasive weed that chokes the shoreline: goats. Twenty Anglo-Nubians, to be exact. With names like Mozart, Haydn and Van Goat, and with floppy ears and plaintive bleats, they did not seem fearsome. But on Thursday they were already munching inexorably through the long pale leaves in the first phase of a wetland restoration at what will soon be Freshkills Park.
Known for their unending, indiscriminate appetites, the goats are being rented by the city for the next six weeks from a farmer in the Hudson Valley. Parks officials are counting on the goats to clear the phragmites across two acres of wetlands that will eventually be cultivated with native grasses like spartina and black needle rush. The hope is that the goats will weaken the phragmites, setting the stage for another series of assaults on their stubborn rhizomes — applying herbicide, scarifying the earth and laying down sand.
In the short term, the goats are part of an unusual experiment to eradicate the pesky reeds, which were introduced from Europe in the late 19th century and which, once rooted, are almost impossible to eliminate. They have fueled brush fires across the region and pushed out other species along the East Coast.
But the farm animals are also being tested for their lawn-mowing prowess, especially at Freshkills Park, which is in transition from its former life as the world’s largest landfill to its future one — as the largest park to be developed in New York City in more than a century.
“We want to introduce the idea of using goats to help in vegetation management,” Eloise L. Hirsh, the administrator of the park, said. “The sanitation department mows us once a year. But this is 2,200 acres. We need help.”
The goats are perhaps the most vivid example of the lengths to which the city is going to turn a symbol of environmental degradation into one of ecological redemption. As Freshkills Park is developed in phases over the next three decades, it will be a laboratory for green practices; there are plans for composting toilets, green roofs, rain gardens and a native seed farm.
The official opening of the park is two or three years off, though it is open periodically for tours. Three of the four giant mounds formed by garbage are now capped, and the parks department will soon solicit bids on the first stage of development — 21 acres with walking paths and a bird observation tower overlooking the wetlands. Already, the landscape looks impossibly bucolic, with dragonflies and swallows darting amid lanky grasses and the occasional tree.
The goats only add to the pastoral image. On Thursday, Beethoven, with long white ears and a black body, and Van Goat, sporting a black stripe down his chestnut back, were contentedly exploring their new territory, plunging their mouths into dense stands of phragmites. Others trotted down to the shore of Main Creek, a tributary of the Fresh Kill. (In yet another act of environmental rectitude, parks workers will soon arrange logs made of coconut fiber along the banks to attract mussels, which prevent erosion.)
“The first test was to see if they would eat the phragmites, and they’re eating it, so they passed,” said Terry Doss, an ecologist with Biohabitats, a company specializing in ecological restoration that is advising the parks department.
The city received a grant of $350,000 from the state for the wetlands project. (The cost of renting the goats from Larry Cihanek of Rhinebeck, N.Y., is $20,625 for the six weeks.) If the goats prove successful, Freshkills Park may one day have a permanent herd. “It’s exciting to be able to replace what would be a carbon-polluting mowing strategy with a more natural approach,” said Andrew Deer, a landscape architect for the parks department.
While goats have been deployed for phragmite duty elsewhere, some ecologists are skeptical.
“I’m not a big fan of goats,” said Bernd Blossey, an associate professor of natural resources at Cornell University. “I understand why people are desperate to try them. But they will eat the leaves but not the stems, and they also don’t like getting their hooves wet.”
Professor Blossey is experimenting with moth caterpillars, which can weaken phragmites. In the 1990s, he was successful in unleashing leaf beetles against another plant invader, purple loosestrife, which is not nearly the scourge it once was.
But as the goats made their debut this week at Freshkills Park, any such doubts were pushed to the background. Ms. Hirsh was already looking ahead to a day when goats not only keep phragmites in check, but also put Staten Island on the artisanal food map. “We would like to have a cheese manufacturer here,” she said. “I know there will be lots of skepticism. But it would be a pretty eloquent statement about how you really can restore land that was formerly very damaged.”
Learning Hebrew on the Streets, With Walls as Assigned Reading
The texts, written on metal grates, stone walls and neon signs, sometimes disappear from one class to the next. The themes are pluralism, economic justice and the Israeli-Palestinian conflict — and grammar, always a little grammar thrown in.
Guy Sharett’s Hebrew lessons are taught in a walking classroom, on the streets and alleys of Florentin, his neighborhood here, where new vocabulary words are mixed into an ever-changing curriculum.
“Get out from the TV, start to live,” Mr. Sharett translated one scrawled Hebrew slogan at the start of class one recent evening, trailed by a dozen students thirsty to understand the life of the Tel Aviv street as much as the revived ancient language spoken on it.
He pulled out a little white board to break down the graffiti before him. The first part of the slogan, “Tzay mayhatelevizia,” used the imperative — get out — while “tatchil lichayot,” start to live, was in the future tense. “It sounds to us too pompous and too archaic,” he explained, “so we just use the future.”
A few minutes earlier, they had analyzed a sign exhorting dog owners not to permit their animals to relieve themselves near a certain building. Next, a picture of Theodor Herzl, the father of Zionism, with his famous mantra, “If you will it, it is no dream,” twisted into “If you don’t want, you don’t need.” Here, a verse by the street artist and poet Nitzan Mintz. There, the iconic image of a forlorn child from the Warsaw ghetto, captioned “Don’t Deport Me,” repurposed to the current crisis of migrant workers from Africa flooding south Tel Aviv.
“They depend on a cultural knowledge that you don’t necessarily have,” said one of the students, Marcela Sulak, who has been here two years as director of the creative writing program at Bar-Ilan University. “He teaches you the tools so you can figure it out on your own. You’re learning the Hebrew you need every single day by looking at the neighborhood.”
The hourlong classes, which cost 50 shekels, or about $12, are organized on Facebook. They grew out of last summer’s protests, when Mr. Sharett’s traditional Hebrew students were mystified by the signs at the encampment along Rothschild Boulevard, so he started taking them — and his little white board — outside for lessons. After the protest tents came down, he decided to make the graffiti-pocked walls of his gentrifying neighborhood the new syllabus.
“It’s not only to teach language, it’s also to teach the culture,” Mr. Sharett explained. “Someone took a line from a song we all know and changed one word; it’s very hard to understand that if you don’t have someone local to explain, ‘That’s a take on...’ ”
Mr. Sharett, 40, has a day job at a television company, but has been giving private Hebrew lessons for several years. Besides the graffiti course, he offers one-offs touring the city’s spice market (“Wake up and smell the Zatar”); shopping and cooking with a famous chef (“While chopping, we learn the names of the vegetables”); and watching the local version of “American Idol,” with frequent use of the pause button to translate slang and jokes (“This is Israeliness 101,” he said).
The son of an artist and a tugboat skipper whose home in Ashdod was “like a French salon,” Mr. Sharett is something of a language savant. “There was a Turkish neighbor, so I started learning Turkish; there was a German au pair, so I started learning German,” he said. At 16, he got a job in the control tower of the port, “so I was able to talk on the radio with captains in different languages and tell them to heave up the anchor — but only maritime terms that I can’t really use in regular life.”
The students on his tours want terms they can use in everyday life; many are dropouts from ulpan, the immersion classes that are free for new immigrants. A recent graffiti tour included a Chinese postdoctoral fellow; a 28-year-old Google employee from Rhode Island; a financial analyst and poet who is married to an Israeli; a British teacher who has lived here 20 years; Ms. Sulak, whose 5-year-old daughter slept the entire hour in her stroller; and a Middle Eastern politics professor at the City University of New York who is on sabbatical.
“Street politics is where it’s happening,” said the professor, Dov Waxman, 37. “Most places, graffiti is tagging or art. Here, you can really read the politics. I wander around and look at it myself, but I don’t always understand it all.”
Xiaoyun Wu, the postdoctoral fellow, has been studying Hebrew with Mr. Sharett for three months, and was the first to answer most of his grammar questions. “You get more contextualized memory,” she said of on-the-street learning. “The good thing is I can come back to review any time.”
Here, one finds a lesson on how easy it is to make up words — a tattoo parlor called, essentially, “tattooism,” using the Hebrew letters yud, zayin, mem to add “ism.” There, a black door features the ubiquitous road signs pointing one way to Tel Aviv and the other to Jerusalem, only the Jerusalem arrow leads to an ultra-Orthodox man at prayer. A tag declares “Jews and Arabs refuse to be enemies.” A sign uses the word “agudah,” association, which Mr. Sharett pointed out has the same root as the Israeli bus company, Egged, because buses link places together.
Then there is a new ampm convenience store, one of many chains now dotting the once-gritty streets of Florentin. “We pronounce it Ahm-Pahm,” Mr. Sharett told the group. “If you want to impress your Israeli friends, say, ‘Ani holech l’ahm pahm,’ ” which means “I’m going to the ampm.”
Ultra-Orthodox Men Charged With Trying to Silence Accuser
The Brooklyn district attorney, facing a wave of public criticism about his handling of sexual abuse allegations in the ultra-Orthodox Jewish community, on Thursday charged four men with attempting to silence an accuser by offering her and her boyfriend a $500,000 bribe, and threatening her boyfriend’s business.
The district attorney, Charles J. Hynes, alleged that the men were part of an effort to protect a prominent member of the Satmar Hasidic community, Nechemya Weberman, who has been accused of 88 counts of sexual misconduct, including oral sex with a child younger than 13 years old. The charges all involve one girl, now 17, who was referred by her school to get counseling by Mr. Weberman, and then alleged she was abused by him during therapy sessions.
The charges are the first time in at least two decades that Mr. Hynes has charged Hasidic Jews with intimidation of a witness in a sexual abuse case, even though victims, their advocates and prosecutors say intimidation has long been a major obstacle to prosecution of abuse among the ultra-Orthodox. In recent weeks, Mr. Hynes has been saying that the intimidation of witnesses in the ultra-Orthodox community is worse than in the world of organized crime.
“I’m hoping that this will be a message to those who are intimidated that they should come forward and help us,” Mr. Hynes said at a news conference. “No one can engage in this kind of conduct and feel free that, based on prior experience, nothing can happen to them.”
Prosecutors charged Abraham Rubin, 48, of Williamsburg with bribery, witness tampering and coercion. They said that he had been recorded offering the accuser’s boyfriend the money, and he suggested that the young couple could flee to Israel to avoid testifying. He also offered to provide them with a lawyer who could help them avoid cooperating with prosecutors.
Prosecutors also charged three brothers, Jacob, Joseph and Hertzka Berger, with coercion, saying they threatened and then removed the kosher certification of a restaurant run by the accuser’s boyfriend. The brothers are sons of a local rabbi who issues kosher certifications to stores.
The four men pleaded not guilty on Thursday in a Brooklyn courtroom packed with benches full of their supporters, dressed in the dark clothing worn by Hasidic men.
Hertzka Berger’s lawyer, Bruce Wenger, said after the arraignment that the four men “all deny the allegations.”
“They are all obviously going to be fighting these cases vehemently,” he said. “They are looking forward to their day in court.”
But a prosecutor, Josh Hanshaft, said the men had been “telling witnesses to forget what they know, not to come to court, to disappear,” and said prosecutors had “clear, substantial evidence” that part of the plan to silence witnesses involved offering money to dissuade their testimony.
If convicted, Mr. Rubin faces up to seven years in prison. Joseph and Hertzka Berger each face a year in jail, and Jacob Berger faces up to four years.
Mr. Weberman has denied the abuse allegations, and his lawyer, George Farkas, said Mr. Weberman knew nothing of the alleged intimidation.
“Mr. Weberman, and his attorneys, are appalled by these allegations, which if true, are reprehensible,” Mr. Farkas said. The intimidation charges, a moment of triumph for Mr. Hynes, come as his office has been criticized by victims, victims’ advocates, former Mayor Ed Koch and others for an insufficiently aggressive response to the sexual abuse of minors within the ultra-Orthodox community.
And this week, Mr. Hynes’s office is suffering an embarrassing reversal in another abuse case involving an Orthodox Jewish accuser. After revelations that Mr. Hynes’s office had failed to share exculpatory evidence with defense attorneys, lawyers said Monday that all charges against four men accused of raping and forcibly prostituting a Chabad Lubavitch woman from Crown Heights for nearly a decade would be dropped.
In the Williamsburg case, the accuser was in sixth grade when she was referred to Mr. Weberman, an unlicensed therapist, by her Williamsburg religious school, a close family member said in an interview last month. Her parents were told she would be expelled from school unless they paid $150 an hour for him to provide her with therapy.
Instead, Mr. Weberman, who is now 53, repeatedly sexually molested her over three years, when she was 12 to 15, and told her that she would be expelled from school if she told anyone, the relative said. The girl then changed schools and told a licensed therapist what had happened. The therapist reported the girl’s allegations to the police.
After Mr. Weberman’s arrest in 2011, a campaign of intimidation is alleged to have begun against the accuser, her boyfriend and her family members. Prominent Hasidic Jews publicly proclaimed their support for Mr. Weberman, and, on May 16, hosted hundreds of Hasidic men at a local wedding hall to raise money for Mr. Weberman’s legal defense. To promote the fund-raiser, his supporters hung posters on lampposts and brick walls around the neighborhood, accusing the young woman, in Yiddish, of libel.
The girl’s boyfriend, 24-year-old Hershy Deutsch, organized a demonstration outside the fund-raiser. In an interview at the time, he said that he had faced intimidation because of his girlfriend’s allegations, and that he had decided to speak out. He said that a restaurant he manages in Williamsburg, the Old Williamsburg Cafe on Lee Avenue, was targeted by a flood of false complaints to city authorities in late April. And, he said, men from the neighborhood had offered him $500,000 if he could persuade the girl to drop her case.
“For those of you questioning the credibility of the victim’s story,” Mr. Deutsch wrote in a letter he posted on his Facebook page, “ask yourself the following question: Would a nonguilty person offer someone a half a million dollars if they drop the charges?”
“Speak up!” he wrote. “Face the facts, our community has been covering up these stories for way too long. We have to put an end to this!”
On Thursday afternoon a metal gate was rolled down over the entrance to the Old Williamsburg Cafe, and a sign taped to the door said that the store “will be closed until further notice.”
Victims’ advocates said Thursday that they were glad that Mr. Hynes had brought an intimidation case, and hoped it would begin to ease the problem. While some ultra-Orthodox rabbis now say that a child molester should be reported to the police, others strictly adhere to an ancient Jewish prohibition against mesirah, the turning in of a Jew to non-Jewish authorities, and instruct victims to either remain silent or let rabbinical authorities quietly handle the allegations.
“This is a big threshold,” said Mark Appel, the founder of Voice of Justice, a nonprofit agency that helps ultra-Orthodox victims. And Joel Engelman, the founder of the Jewish Survivors Network, also praised Mr. Hynes for bringing the intimidation case, because, he said, “in the Williamsburg Hasidic community, intimidation is rampant.”
