Some Pakistani people are real knockouts, a new DNA study finds. Knockouts in this sense doesn’t refer to boxing or a stunning appearance, but to natural mutations that inactivate, or “knock out” certain genes. The study suggests that human knockouts could prove valuable evidence for understanding how genes work and for developing drugs.

Among 10,503 adults participating in a heart disease study in Pakistan, 1,843 people have at least one gene of which both copies have been knocked out, researchers report online April 12 in Nature. Researchers also drew blood from many of the participants and used medical records to study more than 200 traits, such as heart rate, blood pressure and blood levels of sugar, cholesterol, hormones or other substances. Studying how the knockout mutations affect those traits and health could point to genes that are potentially safe and effective targets for new drugs.
Combining genetic data with medical information will provide “a rich dataset for many applications,” says Robert Plenge, a human geneticist formerly with the pharmaceutical company Merck.

Scientists have traditionally learned about genes’ roles by deleting the genes from mice and then cataloging abnormalities in how those mice developed and behaved. Such animal research will always be needed, but studies of people naturally lacking certain genes “will change the nature of the scientific investigation of the genetic basis of human disease,” Plenge wrote in a commentary in the same issue of Nature.

Often, a person will inherit a broken copy of a gene from one parent and a healthy copy from the other. But 39 percent of the people in this study had parents who were closely related — often first cousins — increasing the odds of inheriting two mutant copies of a gene. Of this study’s 1,843 participants, 1,504 had both copies of a single gene knocked out. The rest had more than one gene knocked out, including one person in whom six genes were predicted to be completely nonfunctional.
In one example from the new study, geneticist Sekar Kathiresan and colleagues found four people in which both copies of the APOC3 gene had inactivating mutations. Kathiresan and colleagues had previously found that people with one mutated copy of APOC3 are protected against heart disease. Normally, the ApoC3 protein made from the gene stops dietary fat from being cleared from the body. People who had one mutant copy of the gene were able to get rid of fat more quickly than normal, reducing the amount left to clog arteries, says Kathiresan, of the Broad Institute of MIT and Harvard. Scientists reasoned that drugs that inactivate the ApoC3 protein would also reduce heart attack risk in people who have two working copies of the gene.
But there was a problem. Scientists worried that drugs that completely abolish the activity of the ApoC3 protein might be dangerous. Previous genetic studies encompassing nearly 200,000 people had never found a person with both copies of APOC3 knocked out, indicating that people might not be able to do without the gene entirely. Finding people who have almost no ApoC3 protein in their blood indicates that it is probably safe to get rid of its activity.

Further tests on 28 family members of one man who had both copies of APOC3 knocked out showed that his wife (who was his first cousin) and all nine of the couple’s children also lacked APOC3. The researchers fed fat-filled milkshakes to 13 members of the family — six who lacked APOC3 and seven who had two functional copies of the gene. Within six hours after the milkshake, levels of triglyceride— a type of fat in the blood — shot up two to three times over premilkshake levels in people with two functional copies of the gene. But in people in which the gene was knocked out, “triglyceride levels didn’t go up. It didn’t budge at all,” Kathiresan says. That finding suggests APOC3 could be a good target for drugs that reduce triglyceride levels in the blood and fend off heart disease, he says.

The March for Science, Washington, D.C. — On April 22, 2017 — Earth Day — thousands of scientists, science advocates and general enthusiasts rallied on the grounds of the Washington Monument in Washington, D.C., at the first-ever March for Science. The organizers estimate that over 600 sister marches also occurred around the world.

The march may be “unprecedented,” sociologist Kelly Moore told Rachel Ehrenberg for a blog post giving a historical perspective on scientists’ activism. “This is the first time in American history where scientists have taken to the streets to collectively protest the government’s misuse and rejection of scientific expertise.”
The March for Science took place next to the Washington Monument, opposite the White House. Grounds opened at 8 a.m. and filled up quickly.
Astronaut Leland Melvin told an entertaining anecdote about getting his start in science in sixth grade when his mom gave him “an age-inappropriate, non-OSHA-approved chemistry set.” At one point, a chemical explosion blew up her living room. But, “that’s what got me hooked on science,” he said.
Pediatrician Mona Hanna-Attisha took the stage with Amariyanna “Mari” Copeny, aka “Little Miss Flint.”

DNA from 2,000-year-old stallions is helping rewrite the story of horse domestication.

Ancient domesticated horses had much more genetic diversity than their present-day descendants do, researchers report in the April 28 Science. In particular, these ancient horses had many more varieties of Y chromosomes and fewer harmful mutations than horses do now. Previous studies based on the genetics of modern horses concluded that domestication must have squeezed out much of the diversity seen in wild horses before the Ice Age. But the new findings suggest that the lack of diversity is a more recent development.
“Today, Y chromosomes of all horses are pretty much the same,” says evolutionary geneticist Ludovic Orlando of the Natural History Museum of Denmark in Copenhagen. As a result, scientists thought that ancient people started domesticating horses by breeding only a few stallions to many different mares.

“But when we look in the past — wow! — this is a whole new planet,” Orlando says.

Horses are thought to have been domesticated by about 5,500 years ago. Orlando’s group examined DNA from the bones of 15 Iron Age stallions from the ancient Scythian civilization: Two stallions were from a 2,700-year-old grave site in Russia and 13 were sacrificed in a burial ritual about 2,300 years ago in Kazakhstan. The team also looked at a 4,100-year-old Bronze Age mare from the Sintashta culture in Russia. Nearly all of the stallions had a different type of Y chromosome, Orlando says.

That finding challenges the idea that only a few stallions participated in the early stages of domestication. Loss of Y chromosome diversity among horses must have happened within the last 2,300 years, Orlando says, and maybe as recently as 200 to 300 years ago, when people started creating specific horse breeds.
Using genetic data from modern animals to figure out what went on in the past is like flipping to the end of a novel and reading only the ending; it shows how things ended up but doesn’t indicate how the story started or unfolded. Examining ancient DNA can fill in those gaps to give a better indication of how domestication took place and how ancient people interacted with animals, says Laurent Frantz, an evolutionary biologist at Queen Mary University of London.
Modern horses also carry mutations that can be harmful (SN: 1/10/15, p. 16), including ones involved in dementia and seizures. But the ancient horses didn’t have those mutations, indicating that those DNA changes happened sometime within the last 2,300 years.

“It really shows an awful lot has changed very recently, and it’s incredibly dangerous to model the deep past from modern genetics,” says zooarchaeologist Alan Outram of the University of Exeter in England. “You really need to carry out the ancient DNA studies.”

Orlando and colleagues also determined some genetic traits that were cultivated by the Scythians. Genes involved in mammary gland development and function had variants associated with greater milk production, perhaps indicating that the Scythians milked their horses. Outram and others have evidence that horse milking started at least 5,000 years ago (SN: 3/28/09, p. 15).

Also changed were genes involved in the function of neural crest cells. Those embryonic cells migrate to different parts of the body during early development and help form parts of the brain, some facial features and other tissues. One recent hypothesis is that changes in how neural crest cells work could lead to common characteristics shared by domestic animals, such as floppy ears, juvenile faces and spotted coats (SN: 8/23/14, p. 7).

Genetic results from the ancient horses provide evidence that the hypothesis might be true, says Frantz. Geneticists will have to work with experimental biologists to confirm that neural crest cells are involved in changing the appearance of domesticated animals. But, Frantz says, “this is the first step toward testing that hypothesis correctly.”

Certain stealthy spacetime curiosities might be less hidden than thought, potentially exposing themselves to observers in some curved universes.

These oddities, known as singularities, are points in space where the standard laws of physics break down. Found at the centers of black holes, singularities are generally expected to be hidden from view, shielding the universe from their problematic properties. Now, scientists report in the May 5 Physical Review Letters that a singularity could be revealed in a hypothetical, saddle-shaped universe.
Previously, scientists found that singularities might not be concealed in hypothetical universes with more than three spatial dimensions. The new result marks the first time the possibility of such a “naked” singularity has been demonstrated in a three-dimensional universe. “That’s extremely important,” says physicist Gary Horowitz of the University of California, Santa Barbara. Horowitz, who was not involved with the new study, has conducted previous research that implied that a naked singularity could probably appear in such saddle-shaped universes.

In Einstein’s theory of gravity, the general theory of relativity, spacetime itself can be curved (SN: 10/17/15, p. 16). Massive objects such as stars bend the fabric of space, causing planets to orbit around them. A singularity occurs when the warping is so extreme that the equations of general relativity become nonsensical — as occurs in the center of a black hole. But black holes’ singularities are hidden by an event horizon, which encompasses a region around the singularity from which light can’t escape. The cosmic censorship conjecture, put forth in 1969 by mathematician and physicist Roger Penrose, proposes that all singularities will be similarly cloaked.

According to general relativity, hypothetical universes can take on various shapes. The known universe is nearly flat on large scales, meaning that the rules of standard textbook geometry apply and light travels in a straight line. But in universes that are curved, those rules go out the window. To demonstrate the violation of cosmic censorship, the researchers started with a curved geometry known as anti-de Sitter space, which is warped such that a light beam sent out into space will eventually return to the spot it came from. The researchers deformed the boundaries of this curved spacetime and observed that a region formed in which the curvature increased over time to arbitrarily large values, producing a naked singularity.

“I was very surprised,” says physicist Jorge Santos of the University of Cambridge, a coauthor of the study. “I always thought that gravity would somehow find a way” to maintain cosmic censorship.

Scientists have previously shown that cosmic censorship could be violated if a universe’s conditions were precisely arranged to conspire to produce a naked singularity. But the researchers’ new result is more general. “There’s nothing finely tuned or unnatural about their starting point,” says physicist Ruth Gregory of Durham University in England. That, she says, is “really interesting.”
But, Horowitz notes, there is a caveat. Because the violation occurs in a curved universe, not a flat one, the result “is not yet a completely convincing counterexample to the original idea.”

Despite the reliance on a curved universe, the result does have broader implications. That’s because gravity in anti-de Sitter space is thought to have connections to other theories. The physics of gravity in anti-de Sitter space seems to parallel that of some types of particle physics theories, set in fewer dimensions. So cosmic censorship violation in this realm could have consequences for seemingly unrelated ideas.

Chemical transformations in minerals deep beneath the seafloor could explain why Indonesia’s 2004 mega-earthquake was unexpectedly destructive, researchers report in the May 26 Science.

The magnitude 9.2 quake and the tsunami that it triggered killed more than 250,000 people, flattened villages, and swept homes out to sea across Southeast Asia. It was one of the deadliest tsunamis in recorded history.

“It raised a whole bunch of questions, because that wasn’t a place in the world where we thought a magnitude 9 earthquake would occur,” says study coauthor Brandon Dugan, a geophysicist at the Colorado School of Mines in Golden.

The thick but stable layer of sediment where tectonic plates meet off the coast of the Indonesian island of Sumatra should have limited the power of an earthquake, seismologists had predicted. But instead, this quake was the third-strongest on record worldwide.
Dugan spent two months aboard a boat with 30 other scientists collaborating through the International Ocean Discovery Program. The researchers drilled down 1,500 meters below the seafloor in two places off the coast of Sumatra, extracting narrow cylinders of sediment. This sediment is very slowly moving toward the fault where the 2004 earthquake occurred — a zone where one massive tectonic plate slides over another, pushing that plate downward.

Analyzing how sediment changes with depth can give scientists a snapshot of the geological processes at play near the fault zone.

In particular, deep down, the researchers identified a layer of sediment where the water had a lower salinity than the water in the sediment above or below. Since seawater seeping into the sediment would be salty, the evidence of freshwater suggests that the water must have instead been released from within minerals in the sediment.

For tens of millions of years, Dugan proposes, minerals sat on the seafloor taking in water — baking it into their crystal structure. Then, more sediment settled on top. It got toasty under such a thick blanket of sediment, heating up the minerals beneath. The temperature increase triggered a chemical transformation within the sediment, pushing water out of the mineral crystals and into tiny pores between the grains.
The sediment sampled in this study is still dehydrating. By the time any of it reaches the plate boundary, Dugan says, it’ll be buried under kilometers of more sediment and will probably be completely dehydrated.

At first, the liberated water would have softened the material, actually decreasing the risk of a big earthquake by allowing it to absorb more force, Dugan says. As the sediment got closer to the fault over millions of years, though, the water flowed away, leaving it brittle and unstable — the perfect setup for a mega-quake.

The timing of this sediment dehydration process can make or break a quake. Had the sediment near the fault been in a softened state when the quake struck in 2004, the tremor might not have been as deadly, Dugan says. But since enough time had passed for it to become brittle again, the tectonic plates were able to rapidly slip past each other for a much greater distance during the quake. That massive motion displaced the seafloor itself, setting a tsunami into motion.
“It’s really the tsunamis from these earthquakes that prove to be the deadliest and most dangerous,” says Roland Bürgmann, a seismologist at the University of California, Berkeley who wasn’t part of the study. And quakes that displace the seafloor are far more likely to trigger tsunamis.

The findings could apply to other faults with similarly thick sediment, such as the Cascadia Subduction Zone in the Pacific Northwest, suggests study coauthor Andre Hüpers, a geophysicist at the University of Bremen in Germany.

But more evidence is needed before applying such analysis to faults beyond this one, says Bürgmann. The argument for what happened along the Sumatran fault is compelling, he says. “But nonetheless, it’s only one data point. It doesn’t yet make for a pattern.”

The first thing you’ll notice is the noise. Monitors beep steadily, relentlessly, ready to sound a car-alarm blare if a baby is in trouble.

The air has an astringent odor — not clean exactly, but reminiscent of an operating room (there’s one next door). Ceiling lights shine fluorescent white. Half are off, but glare from the monitors throws out extra light. It’s midday on a Friday, but it’ll be just as bright at midnight.

Here on the fourth floor of Yale New Haven Children’s Hospital, 10 tiny beds hold 10 tiny infants, each with Band-Aid–like patches stuck to their bodies to continuously monitor health. Between beds, nurses squeeze through narrow aisles crammed with folding chairs and plastic incubators. This space, one of five in the hospital’s neonatal intensive care unit, has the people and equipment needed to keep sick babies alive — heart rate monitors, oxygen tanks, IV poles to deliver medications.
Until recently, Yale’s NICU and hundreds like it across the country were considered the place to be for newborns withdrawing from opioid drugs. But now, as the number of drug-dependent babies surges, doctors here and elsewhere are searching for better options.

“We’re really focused on trying to get these kids out of the NICU,” says Yale pediatrician Matthew Grossman. “We’re looking at moms and the dads as the first line of treatment.”

The nationwide rate of babies withdrawing from opioids has soared — up nearly 400 percent from 2000 to 2012. The booming numbers are the bleak by-product of the United States’ ongoing battle with the drugs: Sales of prescription opioid pain relievers alone quadrupled from 1999 to 2010, and overdose deaths tripled from 2000 to 2014.
When pregnant women use opioids, the drugs pass from bloodstream to baby. After exposure in the womb to Vicodin, methadone or heroin, for example, babies can become dependent. At birth, when the drug flow stops, babies can go through agonizing withdrawal — body shakes, intestinal problems, constant crying. The condition is known as neonatal abstinence syndrome, or NAS.
But there’s no clear consensus on how to care for these struggling babies, Grossman says. Usually they’re whisked off to the NICU and treated with opioids. The drugs ease symptoms, but they prolong exposure to “really powerful and potentially dangerous medications,” he says.

At Yale, NAS babies used to spend weeks in the NICU — they still do in many U.S. hospitals. But in the last few years, Grossman and others have begun to question this method of care. Infants suffering from opioid withdrawal might actually do better back in parents’ arms, away from the high-tech hubbub. Comfort is key. Quiet, dark environments, swaddling, breastfeeding, rocking and holding, no unnecessary tests — it’s baby care 101.

That’s hard to do in the busy, loud NICU, says Grossman. Plus, there’s no place for parents to stay. They can visit, perched on folding chairs wedged between beds, says Yale pediatrician Rachel Osborn, but moms and dads “often feel like they’re extraneous and in the way.”

Faced with these and other obstacles, Grossman, Osborn and others are radically redefining their methods. They’re examining traditional practices, testing new ideas and getting back to basics. The results have been dramatic.

“We’re treating the families with respect and the babies like babies,” Grossman says. The parents have everything the baby needs, he says. “It’s not a whole lot more complicated than that.”
State of alarm
Maine, Vermont and West Virginia reported the highest rates of neonatal abstinence syndrome, opioid withdrawal linked to maternal drug use. Maine, Maryland, Massachusetts and Rhode Island rates are from 2012; the rest are 2013.

Click or tap the map below to learn more.
Tough going
Families today are much more likely to deal with opioid use — and its consequences for newborns — than they were a decade ago.

In 2004, NAS rates were consistently low across the country: For every 1,000 babies born, roughly one was diagnosed with NAS. By 2013, when pediatrician Nicole Villapiano and colleagues examined rural versus urban data, rates were up across the board. But rural areas had been hit the hardest, with nearly 8 per 1,000 babies diagnosed with NAS, the researchers reported in February in JAMA Pediatrics.

In an urban hospital near Rhode Island’s Providence River, Villapiano witnessed infant opioid withdrawal firsthand. She was first assigned to the newborn nursery service at Women and Infants Hospital in Providence in 2011. “I imagined it’d be a joyful time, seeing babies going off with their families, having wonderful lives.”

Reality quickly dashed that hopeful picture. On any given day, she might see several babies at a time struggling with withdrawal. “These children were miserable,” says Villapiano, now at the University of Michigan in Ann Arbor. “Their cries were persistent and their irritability was profound.”

NAS isn’t easy to define. Babies suffer a wide range of symptoms. They’re sweating, shaking, stiff. Stools are loose, eating and sleeping are difficult, and crankiness is common. Babies with NAS can also have breathing problems, seizures and low birth weights.

The syndrome was first described in heroin-exposed infants. Scientists now know that all sorts of opioids used during pregnancy can trigger the condition, including “maintenance” drugs like methadone or buprenorphine used to treat opioid addiction, and even painkillers commonly prescribed during pregnancy, such as codeine and hydrocodone.

Not all infants exposed to opioids in utero go through withdrawal — and exactly what conditions lead to NAS is still unclear. The particular opioid and how much a pregnant woman uses, whether she takes certain antidepressants and even the number of cigarettes she smokes per day all seem to factor in, Stephen Patrick of Vanderbilt University in Nashville and colleagues reported in Pediatrics in 2015. A nonsmoking woman on oxycodone for a few weeks, for example, might have roughly a 1 percent chance of delivering a baby with NAS. For a pack-a-day smoker on antidepressants and buprenorphine for six months, the risk could be more than 30 percent.

Because opioids are such a broad family of addictive drugs, opioid-using moms don’t fit neatly into one category, says Ju Lee Oei, a neonatologist at the University of New South Wales in Sydney. “We need to be aware that Mrs. Smith down the road who’s getting a bit of codeine for her back pain could have a baby with NAS,” Oei says.
Some women give birth to NAS babies while recovering from opioid addiction — even though they’re doing everything doctors advise, says pediatrician Alison Holmes of Children’s Hospital at Dartmouth-Hitchcock in Lebanon, N.H.

“Sometimes people think, ‘Oh, these mothers are such horrible addicts,’ ” Holmes says. But a lot of the time, “they’re staying on their methadone, they’re staying on their buprenorphine, they’re keeping symptoms under control — but their babies are still going to withdraw.”

No one knows exactly what opioid exposure does to fetal brains, or how these kids will fare in the future. Certain brain regions may not grow correctly, previous studies have suggested. Children can also have vision trouble and may develop behavior and attention problems. One long-term Australian study published in February linked a diagnosis of NAS with poor academic performance — all the way up to age 12 or 13.

Whether that’s caused by NAS is hard to say, says Oei, a coauthor of the study. Poverty, poor childhood nutrition and prenatal exposure to alcohol or other drugs could also come into play. But the results are a red flag for all those newly diagnosed babies. “You expect your baby to go to school and get good grades,” Oei says. But from as early as third grade, “these kids don’t seem to be able to do that.”

Still, research on NAS outcomes and potential treatments remains full of gaps, a 2015 report from the U.S. Government Accountability Office found. And there’s no nationally accepted treatment protocol for NAS. “Everyone’s doing it their own way,” says Scott Wexelblatt, a pediatrician at Cincinnati Children’s Hospital Medical Center.

Time for a change
The traditional way to assess NAS was published more than 40 years ago by neonatologist Loretta Finnegan, now at the College on Problems of Drug Dependence in Philadelphia. Every four to eight hours, sometimes more frequently, nurses evaluate symptoms using a detailed scoring list: the Finnegan Neonatal Abstinence Scoring System. Hit a certain score, and doctors will start up the withdrawal-easing opioids, typically morphine or methadone.
But there’s a push and pull between managing withdrawal and dosing babies with more drugs, Wexelblatt says. “We don’t want to expose babies to opioids unless we really need to.”

Care of NAS babies varies widely in hospitals across the United States, according to a study in the May–June Academic Pediatrics. Some newborns may be getting too much opioids. To see if standardizing care could help infants get off the drugs faster, Wexelblatt and colleagues trained nurses on Finnegan scoring and outlined a detailed protocol for weaning.

That simple step made a big difference. Hospitals that adopted the protocol cut infant stays from an average of 31.6 days before the intervention to 23.7 days afterward, Wexelblatt’s team reported in 2015 in Pediatrics. Duration of opioid treatment dropped as well. By 2016, hospital stays were down to 20 days, he says.

Now, 54 hospitals — almost all delivery hospitals in Ohio — use the weaning protocol, Wexelblatt says. The team has since refined its methods, focusing on family support and nonmedication options for care, like swaddling and breastfeeding. And as of 2013, every delivering mom in the Cincinnati region gets urine-tested for opioids upon admission so that care can start early, if needed. Ohio’s strategy is paying off: Doctors are using fewer opioids to treat NAS babies and the infants are getting out of the hospital faster too, early results suggest.

Researchers at Yale and Dartmouth-Hitchcock have also taken a hard look at the hospitals’ methods, starting with the Finnegan scoring system. Some aspects just didn’t make sense, Holmes and colleagues reported last June in Pediatrics. Nurses sometimes woke sleeping babies or removed them from family members’ arms for scoring, and they gave hungry babies points for crying.

“We said, ‘This is crazy,’ ” Holmes remembers. It makes more sense to just score the babies after they eat and while they’re being held. That way, she says, nurses might be able to sift the actual signs of withdrawal from the normal whines and wails of a hungry or tired baby.

Grossman and colleagues at Yale were skeptical too. Finnegan’s system looks for warning signs like vomiting and fever, but also gives points for sneezing and yawning. The final score guides doctors’ decision to dial meds up or down. “Is it truly best to give morphine to an infant who yawned 4 times instead of 3, as the [scoring system] guides us to do?” they asked in a Hospital Pediatrics commentary in February.

Grossman scoured the scientific literature, searching for clues to improve treatment. But research results bounced all over the place. “We ended up questioning everything,” he says. “It turned out there wasn’t really a good answer for anything we were doing.”
Family first
Around the same time Grossman was digging into research on opioid withdrawal in newborns, he had his first child, who screamed constantly. “I’m pacing in the middle of the night, thinking, if this was an NAS baby, he’d be on medication
immediately.”

Instead, Grossman paced and rocked and held his son — all of the tricks parents use to soothe a cranky newborn. As he found ways to settle the baby, he thought, what if NAS babies needed something similar?

The idea jibed with his experiences at the hospital. Sometimes withdrawing infants would do great for days—their moms were there, and Finnegan scores stayed low. But if moms had to leave, babies would backslide, and scores would rocket up again. “Do these kids need more mom or more meds?” Grossman and colleagues wondered. “We started to think, ‘Well, maybe it’s more mom.’ ”

At Dartmouth-Hitchcock, Holmes and her crew were coming up with their own ideas. The team stopped interpreting Finnegan scores so rigidly, for one. But their biggest change was keeping mothers and babies together, 24-7. It’s called “rooming-in,” and previous studies in Canada and other countries had suggested it might ease babies’ transition from the womb to the world.
“What withdrawing babies need is a calm, quiet, dark place where they can be held by a caring individual,” Holmes says. Her team focused on involving moms and families (and even volunteer cuddlers), and the hunch paid off. From 2012 to 2015, the average length of stay for morphine-treated NAS babies dropped from 16.9 days to 12.3 days. The fraction of babies given morphine plummeted too, from 46 percent to 27 percent. Now, two years later, that number has fallen even further — to just 20 percent, she says.

Holmes says her own kids joke about her work: “Babies like their mothers—surprise, surprise! What a discovery!” She laughs, and then adds, “They’re kind of right.”

Grossman’s team at Yale has pushed the family-focused approach even further. “Our mind-set is rooming-in on steroids,” he says. For NAS, parental care is considered more important—and more effective—than medication. Doctors ask parents: “How do we get you here or dad here or grandma here?” Grossman says. “Because that’s what your baby needs.”

His team rolled in other ideas too, like fortifying formula and pumped breast milk with extra calories. And hospital personnel stopped using Finnegan scores to guide medication dosing. Today, they base assessments on three simple parameters: whether an infant can eat, sleep and be consoled.

The patient rooms where parents can bunk with their babies are a world apart from the NICU. One room at Yale has a couch that converts into a bed and ceiling tiles with pictures of Elmo and Tweety Bird. Monitors are muted, nothing beeps incessantly and natural light pours in from the window. There’s plenty of space for parents to walk around and tend to their baby. In these rooms, “it feels like the parent is a necessary part of the care team,” Yale’s Osborn says.

In 2016, babies with NAS stayed in the Yale hospital just 5.9 days — a cliff dive compared with the 2008–2010 average of 22.4 days, Grossman, Osborn and colleagues reported online May 18 in Pediatrics. Even more staggering is the fraction of these babies treated with morphine: just 14 percent in 2016, down from 98 percent in 2008–2010.
Taking the plunge
From 2008 to 2016, the proportion of opioid-withdrawing infants treated with morphine at Yale New Haven Children’s Hospital dropped from 98 percent to 14 percent, a drastic reduction in the number of babies given the medication.

Click or tap the graph below to learn more.

Yale’s approach basically comes down to common sense, Grossman says: a quiet room, lots of holding, feeding when hungry and simply keeping babies with mom and dad. “It’s not rocket science,” he says. Medication became more of a plan B.

Still, other doctors looking to transform NAS treatment may run into barriers. Not all U.S. hospitals are set up like Dartmouth-Hitchcock or Yale New Haven, Wexelblatt says. There’s not always room for mom to stay with her baby once she’s released. And universal drug testing of moms won’t work everywhere, he warns. In Tennessee, a law passed in 2014 allowed new mothers to be prosecuted for using illegal drugs while pregnant if the newborn was harmed. The law expired last July, but such legislation drives women away from medical care, Wexelblatt says.

It could be that the best care for babies begins with care and compassion for moms. Rather than blame mothers, Holmes says, “We need to do as much as we can to support them in being good parents.”

Fossil DNA may be rewriting the history of elephant evolution.

The first genetic analysis of DNA from fossils of straight-tusked elephants reveals that the extinct animals most closely resembled modern African forest elephants. This suggests that straight-tusked elephants were part of the African, not Asian, elephant lineage, scientists report online June 6 in eLife.

Straight-tusked elephants roamed Europe and Asia until about 30,000 years ago. Much like modern Asian elephants, they sported high foreheads and double-domed skulls. These features convinced scientists for decades that straight-tusked and Asian elephants were sister species, says Adrian Lister, a paleobiologist at the Natural History Museum in London who was not involved in the study.
For the new study, researchers extracted and decoded DNA from the bones of four straight-tusked elephants found in Germany. The fossils ranged from around 120,000 to 240,000 years old. The genetic material in most fossils more than 100,000 years old is too decayed to analyze. But the elephant fossils were unearthed in a lake basin and a quarry, where the bones would have been quickly covered with sediment that preserved them, says study author Michael Hofreiter of the University of Potsdam in Germany.

Hofreiter’s team compared the ancient animals’ DNA with the genomes of the three living elephant species — Asian, African savanna and African forest — and found that straight-tusked genetics were most similar to African forest elephants.

When the researchers told elephant experts what they’d found, “Everybody was like, ‘This can’t possibly be true!’” says study coauthor Beth Shapiro of the University of California, Santa Cruz. “Then it gradually became, ‘Oh yeah, I see.… The way we’ve been thinking about this is wrong.’”

If straight-tusked elephants were closely related to African forest elephants, then the African lineage wasn’t confined to Africa — where all elephant species originated — as paleontologists previously thought. It also raises questions about why straight-tusked elephants bore so little resemblance to today’s African elephants, which have low foreheads and single-domed skulls.
Accounting for this new finding may not be as simple as moving one branch on the elephant family tree, Lister says. It’s possible that straight-tusked elephants really were a sister species of Asian elephants, but they exhibit genetic similarities to African forest elephants from interbreeding before the straight-tusked species left Africa.

It’s also possible that a common ancestor of Asian, African and straight-tusked elephants had particular genetic traits that were, for some reason, only retained by African and straight-tusked elephants, he says.

Lister and colleagues are now reexamining data on straight-tusked skeletons to reconcile the species’ skeletal features with the new information on their DNA. “I will feel most comfortable if we can understand these genetic relationships in terms of the [physical] differences between all these species,” he says. “Then we’ll have a complete story.”

BOSTON — Some aspects of speech are as Southern as pecan pie. Consider the vowel shift that makes the word pie sound more like “pah.” While that pronunciation is found from Florida to Texas, a new study reveals a surprising diversity in Southern vowel pronunciation that’s linked to a speaker’s age, social class, gender, race and geography.

The research, presented June 29 at a meeting of the Acoustical Society of America, could help software developers create better speech recognition tools for smartphones and other devices.
To understand the medley of southern vowel sounds, linguist Margaret Renwick of the University of Georgia in Athens dove into the Digital Archive of Southern Speech. The archive comprises almost 400 hours of interviews with 64 native Southerners representing a mix of ethnicities, social classes, education levels and ages.

Renwick’s analysis of more than 300,000 vowel sounds finds, for example, that Southern upper middle class women are often at the extreme end of variation in pronunciation. While Southern men and women are equally likely to shift the vowel in bet to “bay-ut,” upper middle class Southern women are more likely to stretch the vowel sound in bit to “bee-ut.” They are also most likely to pronounce bait as bite. The finding that women are more inclined to draw a sound out into two syllables — or change it entirely — is in line with other research suggesting that women are linguistic innovators, and less likely to adhere to the norms of standard American English, Renwick said.

For a glue that holds up inside the body, turn to the humble slug, Arion subfuscus. A new super-sticky material mimics slug slime’s ability to stick on slick wet surfaces and could lead to more effective medical adhesives.

The material has two parts: a sticky layer that attaches to a surface, and a shock-absorbing layer that reduces strain. That makes the adhesive less likely to snap off.

Researchers tested the material as a surgical adhesive in a number of different scenarios: It stuck to pig skin and liver. It latched on to a beating pig’s heart, even when the surface was coated in blood. It sealed up a heart defect, preventing liquid from leaking even when the organ was inflated and deflated tens of thousands of times. And it was less toxic in the body than a commonly used commercialized tissue adhesive, researchers report July 28 in Science.

The researchers hope the material could someday be used in surgical procedures in place of invasive sutures and staples.

For the first time in the United States, researchers have used gene editing to repair a mutation in human embryos.

Molecular scissors known as CRISPR/Cas9 corrected a gene defect that can lead to heart failure. The gene editor fixed the mutation in about 72 percent of tested embryos, researchers report August 2 in Nature. That repair rate is much higher than expected. Work with skin cells reprogrammed to mimic embryos had suggested the mutation would be repaired in fewer than 30 percent of cells.
In addition, the researchers discovered a technical advance that may limit the production of patchwork embryos that aren’t fully edited. That’s important if CRISPR/Cas9 will ever be used to prevent genetic diseases, says study coauthor Shoukhrat Mitalipov, a reproductive and developmental biologist at Oregon Health & Science University in Portland. If even one cell in an early embryo is unedited, “that’s going to screw up the whole process,” says Mitalipov. He worked with colleagues in Oregon, California, Korea and China to develop the embryo-editing methods.

Researchers in other countries have edited human embryos to learn more about early human development or to answer other basic research questions (SN: 4/15/17, p. 16). But Mitalipov and colleagues explicitly conducted the experiments to improve the safety and efficiency of gene editing for eventual clinical trials, which would involve implanting edited embryos into women’s uteruses to establish pregnancy.
In the United States, such clinical trials are effectively banned by a rule that prevents the Food and Drug Administration from reviewing applications for any procedure that would introduce heritable changes in human embryos. Such tinkering with embryo DNA, called germline editing, is controversial because of fears that the technology will be used to create so-called designer babies.

“This paper is not announcing the dawn of the designer baby era,” says R. Alta Charo, a lawyer and bioethicist at the University of Wisconsin Law School in Madison. The researchers have not attempted to add any new genes or change traits, only to correct a disease-causing version of a gene.

In the study, sperm from a man who carries a mutation in the MYBPC3 gene was injected into eggs from women with healthy copies of that gene. Carrying just one mutant copy of the gene causes an inherited heart problem called hypertrophic cardiomyopathy (SN: 9/17/16, p. 8). That condition, which strikes about one in every 500 people worldwide, can cause sudden heart failure. Mutations in the MYBPC3 gene are responsible for about 40 percent of cases. Doctors can treat symptoms of the condition, but there is no cure.

Along with the man’s sperm, researchers injected into the egg the DNA-cutting enzyme Cas9 and a piece of RNA to direct the enzyme to snip the mutant copy of the gene. Another piece of DNA was also injected into the egg. That hunk of DNA was supposed to be a template that the fertilized egg could use to repair the breach made by Cas9. Instead, embryos used the mother’s healthy copy of the gene to repair the cut.

Embryos’ self-healing DNA came as a surprise, because gene editing in other types of cells usually requires an external template, Mitalipov says. The discovery could mean that it will be difficult for researchers to fix mutations in embryos if neither parent has a healthy copy of the gene. But the finding could be good news for those concerned about designer babies, because embryos may reject attempts to add new traits.

Timing the addition of CRISPR/Cas9 is important, the researchers also discovered. In their first experiments, the team added the gene editor a day after fertilizing the eggs. Of 54 injected embryos, 13 were patchwork, or mosaic, embryos with some repaired and some unrepaired cells. Such mosaic embryos probably arise when the fertilized egg copies its DNA before researchers add Cas9, Mitalipov says.

Injecting Cas9 along with the sperm — before an egg had a chance to replicate its DNA — produced only one patchwork embryo. That embryo had repaired the mutation in all its cells, but some cells used the mother’s DNA for repair while others used the template supplied by the researchers.

None of the tested embryos showed any signs that Cas9 was cutting where it shouldn’t be. “Off-target” cutting has been a safety concern with the gene editor because of the possibility of creating new DNA errors.

The study makes progress toward using gene editing to prevent genetic diseases, but there’s still has a long way to go before clinical testing can begin, says Janet Rossant, a developmental biologist at the Hospital for Sick Children and the University of Toronto. “We need to be sure this can be done reproducibly and effectively.”