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Human Microbiome May Be Seeded Before Birth
We are each home to about 100 trillion bacteria, which we carry with us from birth till death. But when Juliette C. Madan was trained as a neonatologist in the mid-2000s, her teachers told her in no uncertain terms that we only acquire those bacteria after we are born. “It was clear as day, we were told, that fetuses were sterile,” she said. Dr. Madan is now an assistant professor of pediatrics at the Geisel School of Medicine at Dartmouth, and she’s come to a decidedly different view on the matter. “I think that the tenet that healthy fetuses are sterile is insane,” she said.
Dr. Madan and a number of other researchers are now convinced mothers seed their fetuses with microbes during pregnancy. They argue that this early inoculation may be important to the long-term health of babies. And manipulating these fetal microbes could open up new ways to treat medical conditions ranging from pre-term labor to allergies.
In 1900, the French pediatrician Henry Tissier declared unborn babies bacteria-free. Only when they started their journey down through the birth canal did they begin to get covered with microbes. The newborns then acquired more as they were handled and nursed.
“This was considered a kind of scientific dogma,” said Esther Jiménez Quintana of Complutense University of Madrid. This dogma gained strength from studies on babies born prematurely. Infections are a major risk factor in early labor. Many researchers saw this as evidence that the only bacteria in the uterus were dangerous ones.
But scientists came to this conclusion without finding out whether healthy fetuses had bacteria, too. “It became a self-fulfilling prophecy,” said Dr. Madan.
That has started to change in the past few years. In 2010, Josef Neu, a University of Florida pediatrician, examined the first stool from newborn babies, before they had their first meal. He found a diversity of bacteria in the stool, whether the babies were born on time or born prematurely.
“When we first saw this, we though it was an artifact,” said Dr. Neu. If the fetuses were indeed sterile, their stool should have been germ-free. But in follow-up studies, he has gotten the same results.
Other scientists have also found evidence indicating that healthy fetuses pick up bacteria in the womb. Dr. Quintana and her colleagues have found bacteria in the amniotic fluid of healthy babies, as well as in umbilical cord blood and placentas. If other animals are any guide, we shouldn’t be surprised if human fetuses are laced with bacteria. In an essay published last week in the journal PLOS Biology, Seth R. Bordenstein and Lisa J. Funkhouser of Vanderbilt University observed that mothers transmitting bacteria to their offspring is the rule rather than the exception in the animal kingdom. Studying other species may give scientists clues about how human mothers inoculate their unborn children.
One open question is the route that bacteria take from mothers to their fetuses. A number of researchers suspect that immune cells in the mother’s intestines swallow up bacteria there and ferry them into the bloodstream, where they eventually wind up in the uterus.
It’s also not clear whether mothers deliver a random collection of species or a special set that are beneficial to them. Studies on children and adults have shown that our resident bacteria — collectively known as the microbiome — help us in many ways. They digest compounds in our food that would otherwise be indigestible. Beneficial bacteria also help tutor the immune system, so that it attacks pathogens without overreacting and damaging the body itself. The microbiome can even fend of disease-causing bacteria.
Dr. Neu and other pediatricians are now investigating whether the microbiome helps fetuses before birth. He speculates that a healthy supply of bacteria in a fetus can reduce the chances of premature birth. If harmful bacteria manage to slip past those defenses, they may trigger an immune reaction that is sensed by the mother, prompting her to go into labor.
As scientists investigate the microbiome, they are also exploring ways of manipulating it to treat disorders ranging from gut infections to autoimmune disorders. Dr. Neu hopes it may be possible someday to bring the same medical help to fetuses. “We might provide mothers with a microbial cocktail,” he said. The bacteria would pass from a mother to her fetus. Doctors might prescribe certain species to protect the fetus from infections, warding off early labor. Nurturing the fetal microbiome could help babies in other ways, like boosting their immune system.
Some scientists don’t think the evidence supports these ideas, though. Bacteria in fetuses may not have any special role to play in their health. “It could just be part of the vulnerabilities that pregnancy poses on the maternal body,” said Maria Dominguez-Bello, an associate professor at N.Y.U. Langone Medical Center.
But figuring out which explanation is right will demand the careful study of healthy fetuses — something that has only barely begun.
“The frontier is ahead of us,” said Dr. Bordenstein.
Did you know that drying your hands with paper towel will reduce the bacterial count by 45 – 60% on your hands…
U.S. researchers reported a breakthrough Thursday in the search for a vaccine for malaria
More than three dozen volunteers received multiple, intravenous doses of a vaccine produced with a weakened form of the disease, scientists from the National Institutes of Health, the Navy, Army and other organizations reported Thursday.
Though the results were promising, more extensive field testing will be required, the researchers wrote. Nevertheless, the it marks the first time any vaccine trial has shown 100% success in protecting subjects from the mosquito-borne tropical disease, which sickens more than 200 million a year and killed about 660,000 in 2010.
Dr. William Schaffner, head of the preventive medicine department at Vanderbilt University’s medical school, called the results “a scientific advance” — but cautioned that it’s “not ready yet for prime time.” This is not a vaccine that’s ready for travelers to the developing world anytime soon,” Schaffner told CNN. “However, from the point of view of science dealing with one of the big-three infectious causes of death around the world, it’s a notable advance. And everybody will be holding their breath, watching to see whether this next trial works and how well it works.”
The findings were published Thursday by the peer-reviewed journal Science. The trials involved 57 subjects, including 40 who received the vaccine, from October 2011 to October 2012.
The vaccine being tested was produced by Maryland company Sanaria Inc. and tested by the National Institute of Allergy and Infectious Diseases, the Walter Reed Army Institute of Research and the Naval Medical Research Center. Sanaria owns the patent, said Capt. Judith Epstein, the lead researcher for the Naval Medical Research Center.
Schaffner said the process of getting the vaccine scientifically proven, approved and distributed could take eight to 10 years. Sanaria and Epstein said they believe the process could be complete within three to four.
The vaccine was produced using samples of Plasmodium falciparum, thesingle-celled parasite that causes the disease. The samples were weakened by radiation and then frozen. The vaccine was “safe and well-tolerated” by the volunteers who received it, the study states.
Schaffner, who was not part of the study, said previous attempts using injections into skin or muscle didn’t work. Multiple, intravenous injections are “a heck of a way” to administer a vaccine, but “desperate times call for desperate measures,” he said.
Researchers reported that the six volunteers who received five intravenous doses of the vaccine did not contract malaria when exposed to the microscopic parasite. Of the nine who received four doses, three contracted the disease. Of 12 who received no vaccine, 11 became infected.
Dr. Anthony Fauci, the head of the infectious disease institute, called the results an “important step forward” in preventing malaria.
"The global burden of malaria is extraordinary and unacceptable," Fauci said in a statement issued by the institute. "Scientists and health care providers have made significant gains in characterizing, treating and preventing malaria; however, a vaccine has remained an elusive goal." Another possible vaccine, backed by the Bill and Melinda Gates Foundation, cut the number of malaria cases in half during a trial conducted among children in seven African countries. In a statement Thursday afternoon, Jessica Milman, a senior program officer for the foundation, said Thursday’s published results were promising despite the study’s small number of participants.
"The results provide further confirmation that a malaria vaccine is feasible, though this specific construct has hurdles to overcome," Millman said. "More evidence will be required to demonstrate that it could work among people living in malaria-endemic countries. It’s also likely that a number of manufacturing and presentation challenges would need to be addressed to ensure that the vaccine could be produced and delivered at scale."
Currently, available drugs can stave off malaria, but must be combined with other protective measures such as insect repellent or nets, according to the Centers for Disease Control and Prevention. None are 100% effective, the CDC notes.
Schaffner said future studies need to involve larger groups in field conditions and examinations of how long the vaccines stave off infection. Using multiple intravenous doses — a process unlike any other vaccine — “requires a great deal of aseptic practice and good training,” and the risk of infection is a possibility, he said.
"We don’t know how long this protection lasts yet. Lots of questions remain. But that should not diminish the fact that this is a scientific advance," Schaffner said.
Researchers Suspect That Camels Are Linked to a Middle East Virus
Camels may be a carrier of the mysterious virus that has infected at least 94 people in the Middle East and killed half of them, scientists are reporting. The virus, first detected last year in Saudi Arabia, causes Middle East respiratory syndrome, or MERS, which begins with flulike symptoms and can progress to severe pneumonia. Because the virus belongs to a family called coronaviruses, often found in bats, researchers suspect that it originally came from bats. The bats might infect people through droppings or saliva, but they might also infect other animals that could then transmit the virus to humans. But which animals? Researchers have been scrambling to find out.
Now, a scientific team from a dozen universities is reporting that dromedary camels (the kind with one hump) from Oman and the Canary Islands show signs of past infection with the MERS virus or one very much like it. Researchers tested blood samples from 50 female retired racing camels in Oman, and 105 used in the tourist industry in the Canary Islands. The blood tests did not find the virus itself, but did find antibodies to it — highly specific proteins that the immune system makes to fight off an infection — in all the camels from Oman, and 14 percent of the ones from the Canary Islands. Other animals were also tested — sheep, goats, camels, llamas and alpacas — but none had MERS antibodies.
Writing in The Lancet Infectious Diseases, the researchers say their findings need to be verified by other studies, but meanwhile, detailed case histories should be taken of people who have had MERS to find out if they had been exposed to camels or their milk or meat.
Some researchers praised the study. Dr. W. Ian Lipkin, a virus expert at Columbia University who has been studying MERS, said, “I think it’s compelling evidence that dromedaries are infected with MERS or a related coronavirus.” The study does not prove that the animals have infected humans, he added, but he said it was plausible because people in the Middle East have a great deal of contact with camels as racing animals, pets and sources of food.
William Karesh, a veterinarian and executive vice president of EcoHealth Alliance, a group also studying MERS, said that finding the virus itself in an animal would be stronger and more convincing evidence. But he said the new research was well done and added, “All the clues in a mystery are valuable.”
Changing View on Viruses: Not So Small After All
There was a time not that long ago when it was easy to tell the difference between viruses and the rest of life. Most obviously, viruses were tiny and genetically simple. The influenza virus, for example, measures about 100 nanometers across, and has just 13 genes. Those two standards, it’s now clear, belong in the trash. Over the past decade, scientists have discovered a vast menagerie of viruses that are far bigger, and which carry enormous arsenals of genes. French researchers are now reporting the discovery of the biggest virus yet. The pandoravirus, as they’ve dubbed it, is 1,000 times bigger than the flu virus by volume and has nearly 200 times as many genes — 2,556 all told.
Making the discovery all the more startling is the fact that, of all the genes that pandoraviruses carry, only six percent match any gene known to science. “We believe we’re opening a Pandora’s box – not so much for humanity but for dogma about viruses,” said Dr. Jean-Michel Claverie of the University of Mediterranée, co-author of the paper that was published online Thursday in the journal Science. “We believe we’re touching an alternative tree of life.” Giant viruses would be important enough simply for the way they have blurred the line between viruses and the rest of life. But they excite scientists for another reason. Utterly unknown a decade ago, they turn out to be everywhere, including in our own bodies. What effect they have on the world’s ecosystem — or our own health — is anyone’s guess right now. It was the very giant-ness of giant viruses that allowed them to be overlooked for so long. Scientists first discovered viruses in the late 1800s when they were puzzled by a disease that beset tobacco plants. They mashed up wilted tobacco leaves with water and passed the mixture through fine porcelain filters that trapped bacteria and fungi. The clear liquid could still make healthy tobacco leaves sick. The Dutch botanist Martinus Beijerinck dubbed it “a contagious living fluid.”In the 1930s, the invention of powerful microscopes finally allowed scientists to see viruses. They found that viruses were unlike ordinary cells: they didn’t generate their own fuel; they didn’t grow or divide. Instead, viruses invaded cells, hijacking their biochemistry to make new copies of themselves. Being small and simple seemed like part of the viral way of life, allowing them to replicate fast. It wasn’t until 2003 that a team of French researchers discovered the first giant virus. They had been puzzling over sphere-shaped objects that were the size of bacteria but contained no bacterial DNA. Eventually they realized that they were looking at a monstrously oversized virus, containing 979 genes.
Those first giant viruses were isolated from amoebae living in water from a cooling tower. Once scientists realized that viruses could be so large, they changed their search parameters and started finding other species in all manner of places, from swamps to rivers to contact lens fluid.
And along the way the biggest viruses got bigger. In 2011, Dr. Claverie and his colleagues set a new record with megaviruses, a type of giant virus with 1,120 genes they discovered in sea water off the coast of Chile. They then dug into the sediment below that sea water and discovered pandoravirsues, with more than twice as many genes.
Dr. Claverie speculates that pandoraviruses and other giant viruses evolved from free-living microbes that branched off from other life several billion years ago. “The type of cells they may have evolved from may have disappeared,” he said.
The idea that giant viruses represent separate branches on the tree of life is a controversial one that many other experts aren’t ready to embrace. “They provide no evidence for that notion, so it seems a distraction to me,” said T. Martin Embley, a professor of evolutionary molecular biology at Newcastle University.
Despite those reservations, Dr. Embley and other researchers hail pandoraviruses as an important discovery. “I think it’s wonderful that such crazy and divergent lifeforms continue to be discovered,” said Tom Williams, Dr. Embley’s colleague at Newcastle University.
The new study also drives home the fact that giant viruses are far from rare. Shortly after discovering pandoraviruses in sea floor sediment, Dr. Claverie and his colleagues found them in water from a lake in Australia, 10,000 miles away. “It definitely indicates that they must not be rare at all,” said Dr. Claverie.
Giant viruses may be so common, in fact, that they may be hiding inside of us, too. In a paper published online on July 2 in The Journal of Infectious Diseases, French researchers offered evidence that giant viruses dwell in healthy people. They isolated a new giant virus from blood donated by a healthy volunteer, and then found antibodies and other signs of the virus in four other donors.
Giant viruses may lurk harmlessly in our bodies, invading the amoebae we harbor. Whether they can make us sick is an open question. “I don’t believe we have the proof at the moment that these viruses could infect humans,” said Dr. Claverie.
“But again,” he added, “never say never.”
That’s wise advice when it comes to giant viruses.
Hint To A Cure? Two Men Remain HIV Free After Bone Marrow Transplants
Two patients in whom HIV seemed to vanish after they were given bone marrow transplants to treat cancer remained free of the virus even after stopping treatment with HIV medicines. The result yields growing hope that the virus could someday be cured, not just kept in check with a cocktail of medicines as it is now. The results of the study are being presented at a meeting of the International AIDS Society in Kuala Lumpur, Malaysia.
Data on the same two patients was presented a year ago at a conference in Washington D.C. by the same researchers, Timothy Henrich and Daniel Kuritzkes. But at the time the patients had not stopped taking their AIDS medicines.
Bone marrow transplants are grueling and expensive procedures, and are not likely to be used for patients whose disease can be controlled with existing drug cocktails. But scientists hope that these cases could provide clues to new ways of trying to eradicate the virus from the body.
Both went to Brigham and Women’s Hospital in Boston for treatment for blood cancer, and eventually required that the stem cells in their bone marrow — which create the immune cells that fight disease and that are infected with the human immunodeficiency virus — be replaced as a treatment. Unlike most bone marrow transplant recipients, they did not ever stop taking their AIDS medicines to take chemotherapy. Doctors have theorized that this kept HIV levels low enough that their new immune cells were never infected.
Now the patients have stopped taking their AIDS drugs, one for 7 weeks and the other for 15 weeks. So far, the virus has not returned. The researchers warn in two press releases and a scientific abstract that were made available to Forbes before publication that the patients cannot yet be said to be cured and that the virus might still come back.
One man, Timothy Brown, an American treated in Berlin, is thought to have been cured by a stem cell transplant. His transplanted bone marrow cells had a mutation in a gene called CCR5 that prevented the HIV virus from infecting them. It had been thought this might explain the cure, and that helped lead Sangamo, a U.S. biotechnology company, to develop an experimental gene therapy that tries to modify that gene. The Brigham cases seem to indicate that a cure may not require a mutation in CCR5.
“There was a sense that Timothy Brown’s immune system had been given an armor coating,” says Kevin Robert Frost, chief executive of amfAR: The Foundation for AIDS Research. But the new data suggest that changing CCR5 may not be the critical piece to clearing the HIV virus. Tim Brown’s cure may have made him immune to HIV forever because it gave him immune cells with this mutation, though, while the two men treated at the Brigham could be infected again, Frost says. He says that many companies are trying different techniques to try and cure HIV.