Rogue antibody linked to severe second dengue infections

The playground ditty “first the worst, second the best” isn’t always true when it comes to dengue fever. Some patients who contract the virus a second time can experience more severe symptoms. A rogue type of antibody may be to blame, researchers report in the Jan. 27 Science. Instead of protecting their host, the antibodies are commandeered by the dengue virus to help it spread, increasing the severity of the disease.

Four closely related viruses cause dengue, a mosquito-transmitted disease marked by fever, muscle pain and other flulike symptoms. When a previously infected person contracts a second type of dengue, leftover antibodies can react with the new virus.
Fewer than 15 percent of people with a second infection develop severe dengue disease. Those who do may produce a different type of antibody, says Taia Wang, an infectious diseases researcher with the Stanford University School of Medicine.

Wang and colleagues found that dengue patients with a dangerously low blood platelet count — a sign of severe dengue disease — had an abundance of these variant antibodies.

Tests in mice supported the connection. “We found that when we transferred the antibodies from patients with severe disease into mice, they triggered platelet loss,” Wang says.

Wang says it’s not known why some people have this alternate antibody. She and her team want to determine that, along with how these antibodies are regulated by the immune system. With further research, they may be able to screen people to identify those more susceptible to severe dengue disease, Wang says.

Anna Durbin, a dengue vaccine researcher at the Johns Hopkins Bloomberg School of Public Health, doesn’t see a strong connection between this type of antibody and the severity of dengue disease. But she says that the research was interesting in how it connected dengue to low platelet count, a condition known as thrombocytopenia.

“There’s a lot of different theories out there about the role of dengue antibodies and thrombocytopenia, and whether or not the virus itself can enter platelets,” Durbin says. “I think this paper may provide more insight into what is the pathogenic mechanism of thrombocytopenia and dengue, and raises some good avenues for further research.”

For calmer chickens, bathe eggs in light

Fearful, flighty chickens raised for eating can hurt themselves while trying to avoid human handlers. But there may be a simple way to hatch calmer chicks: Shine light on the eggs for at least 12 hours a day.

Researchers at the University of California, Davis bathed eggs daily in light for different time periods during their three-week incubation. When the chickens reached 3 to 6 weeks old, the scientists tested the birds’ fear responses. In one test, 120 chickens were randomly selected from the 1,006-bird sample and placed one by one in a box with a human “predator” sitting visibly nearby. The chickens incubated in light the longest — 12 hours — made an average of 179 distress calls in three minutes, compared with 211 from birds incubated in complete darkness, animal scientists Gregory Archer and Joy Mench report in January in Applied Animal Behaviour Science.

Chickens exposed to lots of light as eggs “would sit in the closest part of the box to me and just chill out,” Archer says. The others spent their time trying to get away. How light has its effect is unclear. On commercial chicken farms, eggs typically sit in warm, dark incubation rooms. The researchers are now testing light’s effects in large, commercial incubators. Using light exposure to raise less-fearful chickens could reduce broken bones during handling at processing plants, Archer says. It might also decrease harmful anxious behaviors, such as feather pecking of nearby chickens.

Birth may not be a major microbe delivery event for babies

Babies are born germy, and that’s a good thing. Our microbiomes — the microbes that live on and in us — are gaining cred as tiny but powerful keepers of our health.

As microbes gain scientific stature, some scientists are trying to answer questions about how and when those germs first show up on babies. Birth itself may be an important microbe-delivery event, some researchers suspect. A trip through the birth canal can coat a baby with bacteria from his mother. A C-section, some evidence suggests, might introduce different bacteria, at least right after birth.

That difference forms the basis of the practice of vaginal seeding, which involves wiping vaginal fluids onto a baby born by C-section to introduce microbes the baby would have encountered in a vaginal birth.

Even while some parents are asking for the procedure, there’s dissent in the ranks of research about its benefits. Scientists don’t agree yet on how — or even whether — type of birth affects the microbiome. “It’s murky,” says obstetrician and maternal-fetal medicine specialist Kjersti Aagaard of the Baylor College of Medicine in Houston. Existing studies don’t clearly distinguish the effects of the C-section itself from those of certain diseases or conditions that can make a C-section more likely, such as maternal diabetes or obesity, she says. Other issues, like whether a baby received antibiotics or is breastfed, also muddy the waters. “You are left saying, ‘Wait a minute. Is it the surgery or not the surgery? What’s going on here?’” Aagaard says.

In a search for clarity, Aagaard and her colleagues surveyed the microbiomes of 81 pregnant women. Later on, the researchers added a second group of 82 women, whose microbiomes were assessed at the birth of their children.

Just after birth, babies who had been delivered by C-section had different mouth, nose and skin microbiomes than babies born vaginally. One possible explanation is that these babies are handled differently just after birth, Aagaard says. The microbiomes of the babies’ meconium, or stool, appeared to be similar, regardless of how the babies were born.

But between four and six weeks later, these C-section/vaginal birth differences on the mouth, nose and skin were largely gone, Aagaard says. The microbes living in and on the babies born by C-section and those born vaginally were nearly indistinguishable, the researchers reported online January 23 in Nature Medicine.
Depending on where they lived, the populations of microbes had already taken on distinct identities by about a month after birth, the researchers found. Communities of nose-dwelling microbes were easy to distinguish from those living in the gut, for instance. These regional differences are signs of surprising microbial maturity, Aagaard says. “Postnatal microbiomes start looking like adults a little sooner than we may have appreciated,” she says.

The results raise an interesting question: If the type of birth isn’t one of the main shapers of microbiomes, then how and when do microbes get into babies? It’s possible that microbes from mothers slip into fetuses during pregnancy — a plausible idea, given some earlier results. Genetically tagged bacteria fed to pregnant mice showed up in their fetuses’ guts a day before the predicted due date, a result that suggests the bacteria traveled from mother to fetus. And Aagaard and colleagues have found evidence of microbes in the placenta of human mothers. They are now studying whether microbes, or perhaps pieces of them, move through the placenta from mother to baby. If that turns out to be the case, then babies meet their microbes, for better or worse, well before their birthday.

Invasive species, climate change threaten Great Lakes

Every summer, people flock to the Great Lakes to swim and fish in the seemingly infinite waters and hike along the idyllic shores. But an ominous undercurrent flows just out of sight. Below the water’s surface rages an environmental catastrophe 200 years in the making.

In The Death and Life of the Great Lakes, journalist Dan Egan describes how the lakes’ natural history gave way to an unnatural one. From the effects of global trade and urbanization to climate change, the book offers an exhaustive (and sometimes exhausting) account of the abuses the lakes have endured.
Scars left by retreating glaciers and a failed continental rift, lakes Huron, Ontario, Michigan, Erie and Superior are more like inland seas, holding about 20 percent of Earth’s surface freshwater. The lakes were mostly isolated from international waters until a series of canals and seaways let in freighters from around the world. “These ships are like syringes,” as one biologist put it, injecting into the lakes living pollution.

Nearly 200 nonnative species now call the lakes home. The worst offenders — alewives, sea lampreys and zebra and quagga mussels — have ruined food webs. Egan dedicates a third of the book to these invaders and biologists’ best, and sometimes misguided, efforts to contain them.

But the lakes also face lesser-known problems. Egan deftly explains the science of these complex issues, including runoff-induced toxic algal blooms and extreme fluctuations in the lakes’ water levels attributed to climate change.

Despite all the bad news, there are glimmers of hope. After decades of living on the brink of collapse, native whitefish and trout are regaining a foothold — a boon for the ecosystem and local economies. Scientists are also experimenting in the lab with gene drives to stop invasive Asian carp and with new ways to rid ships of stowaways lurking in ballast water.

The lakes still face overwhelming challenges, but their biggest threat, Egan argues, is our own ignorance: “We are still treating the lakes … as liquid highways that promise a shortcut to unimaginable fortune.” With few easy solutions and numerous political roadblocks, future generations are “perhaps the best hope the lakes have to recover,” he writes. But if this book is any indication, there’s no time to wait.

How one enslaving wasp eats through another

Parasites can drive their hosts to do weird, dumb things. But in certain oak trees, the parasites themselves get played.

“Creepy and awesome,” says Kelly Weinersmith of Rice University in Houston, who has helped reveal a Russian doll of nested parasitisms.

The saga begins when two majestic live oak species in the southeastern United States send out new shoots, and female crypt gall wasps (Bassettia pallida) arrive to lay eggs. A wasp mom uses the delivery ­end of her reproductive tract to drill through tree bark, injecting each of her eggs into a separate spot in the oak.
Wasp biochemistry induces the tree to form a botanical womb with an edible lining largely free of oak defense chemicals. The tree is hijacked into nurturing each larva, and wasp life is good — until the unlucky ones get noticed by a second exploiter.

Another wasp species, a newly discovered Euderus, arrives, barely visible to the naked eye but “amazingly iridescent,” Weinersmith says. Her colleague at Rice, Scott Egan, named these jewel blue and green specks after Set, an Egyptian god of evil and chaos.
E. set wasps enslave the B. pallida as laborers and living baby food. E. set females sense their prey inside the gall and inject eggs that hatch and feed on the original occupant. When the invaders mature, they are typically too frail to dig themselves out of the tree.But that’s not a problem, Weinersmith, Egan and colleagues report in the Jan. 25 Proceedings of the Royal Society B. That’s because, despite having a gnawing parasite inside, B. pallida wasps dig a tunnel to freedom.

Almost. When infested with E. set, the tunnelers don’t manage a large enough hole for their own escape. They die with their heads plugging the tunnel exit, perfect for the E. set attackers, who chew an escape hole through the stuck noggins.

Weinersmith and Egan may be the first to describe E. set’s manipulation, but what could be a much earlier example was collected by Alfred Kinsey — yes, that Kinsey. Before shocking mid-20th century America with explicit chronicles of human sexual behavior, he specialized in gall wasps.

Kinsey named more than 130 new species in just three years, collecting at least 5.5 million specimens, now at New York’s American Museum of Natural History. One of his Bassettia has its head stuck in a too-small exit hole in a stem, suggesting a chaos-and-death wasp lurks inside.

Gene editing of human embryos yields early results

Scientists have long sought a strategy for curing genetic diseases, but — with just a few notable exceptions — have succeeded only in their dreams. Now, though, researchers in China and Texas have taken a step toward making the fantasies a reality for all inherited diseases.

Using the gene-editing tool known as CRISPR/Cas9, the researchers have successfully edited disease-causing mutations out of viable human embryos. Other Chinese groups had previously reported editing human embryos that could not develop into a baby because they carried extra chromosomes, but this is the first report involving viable embryos (SN Online: 4/8/16; SN Online: 4/23/15).
In the new work, reported March 1 in Molecular Genetics and Genomics, Jianqiao Liu of Guangzhou Medical University in China and colleagues used embryos with a normal number of chromosomes. The embryos were created using eggs and sperm left over from in vitro fertilization treatments. In theory, the embryos could develop into a baby if implanted into a woman’s uterus.

Researchers in Sweden and England are also conducting gene-editing experiments on viable human embryos (SN: 10/29/16, p. 15), but those groups have not yet reported results.

Human germline editing wasn’t realistic until CRISPR/Cas9 and other new gene editors came along, says R. Alta Charo, a bioethicist at the University of Wisconsin Law School in Madison. “We’ve now gotten to the point where it’s possible to imagine a day when it would be safe enough” to be feasible. Charo was among the experts on a National Academies of Sciences and Medicine panel that in February issued an assessment of human gene editing. Altering human embryos, eggs, sperm or the cells that produce eggs and sperm would be permissible, provided there were no other alternatives and the experiments met other strict criteria, the panel concluded (SN: 3/18/17, p. 7).
Still, technical hurdles remain before CRISPR/Cas9 can cross into widespread use in treating patients.

CRISPR/Cas9 comes in two parts: a DNA-cutting enzyme called Cas9, and a “guide RNA” that directs Cas9 to cut at a specified location in DNA. Guide RNAs work a little like a GPS system, says David Edgell, a molecular biologist at Western University in London, Ontario. Given precise coordinates or a truly unique address, a good GPS should take you to the right place every time.

Scientists design guide RNAs so that they will carry Cas9 to only one stretch of about 20 bases (the information-carrying subunits of DNA) out of the entire 6 billion base pairs that make up the human genetic instruction book, or genome. But most 20-base locations in the human genome aren’t particularly distinctive. They are like Starbucks coffee shops: There are a lot of them and they are often similar enough that a GPS might get confused about which one you want to go to, says Edgell. Similarly, guide RNAs sometimes direct Cas9 to cut alternative, or “off-target,” sites that are a base or two different from the intended destination. Off-target cutting is a problem because such edits might damage or change genes in unexpected ways.

“It’s a major issue for sure,” says Bruce Korf, a geneticist at the University of Alabama at Birmingham and president of the American College of Medical Genetics and Genomics Foundation. Doctors trying to correct one genetic defect in a patient want to be sure they aren’t accidentally introducing another.

But CRISPR/Cas9’s propensity to cut undesired sites may be exaggerated, says Alasdair MacKenzie, a molecular biologist at the University of Aberdeen in Scotland. In experiments with mice, MacKenzie and colleagues limited how much Cas9 was produced in cells and made sure the enzyme didn’t stick around after it made an edit. No off-target cuts were detected in any of the mice resulting from successfully edited embryos, MacKenzie and colleagues reported in November in Neuropeptides.

Other researchers have experimented with assembling the Cas9 and guide RNAs outside of the cell and then putting the preassembled protein-RNA complex into cells. That’s the strategy the Chinese researchers took in the new human embryo–editing study. No off-target cuts were detected in that study either, although only one edited embryo was closely examined.

Other researchers have been tinkering with the genetic scissors to produce high-fidelity versions of Cas9 that are far less likely to cut at off-target sites in the first place.

When a guide RNA leads Cas9 to a site that isn’t a perfect match, the enzyme can latch onto DNA’s phosphate backbone and stabilize itself enough to make a cut, says Benjamin Kleinstiver, a biochemist in J. Keith Joung’s lab at Harvard Medical School. By tweaking Cas9, Kleinstiver and colleagues essentially eliminated the enzyme’s ability to hold on at off-target sites, without greatly harming its on-target cutting ability.

Regular versions of Cas9 cut between two and 25 off-target sites for seven guide RNAs the researchers tested. But the high-fidelity Cas9 worked nearly flawlessly for those guides. For instance, high-fidelity Cas9 reduced off-target cutting from 25 sites to just one for one of the guide RNAs, the researchers reported in January 2016 in Nature. That single stray snip, however, could be a problem if the technology were to be used in patients.
A group led by CRISPR/Cas9 pioneer Feng Zhang of the Broad Institute of MIT and Harvard tinkered with different parts of the Cas9 enzyme. That team also produced a cutter that rarely cleaved DNA at off-target sites, the team reported last year in Science.

Another problem for gene editing has been that it is good at disabling, or “knocking out,” genes that are causing a problem but not at replacing genes that have gone bad. Knocking out a gene is easy because all Cas9 has to do is cut the DNA. Cells generally respond by gluing the cut ends back together. But, like pieces of a broken vase, they rarely fit perfectly again. Small flaws introduced in the regluing can cause the problem gene to produce nonfunctional proteins. Knocking out genes may help fight Huntington’s disease and other genetic disorders caused by single, rogue versions of genes.

Many genetic diseases, such as cystic fibrosis or Tay-Sachs, are caused when people inherit two mutated, nonfunctional copies of the same gene. Knocking those genes out won’t help. Instead, researchers need to insert undamaged versions of the genes to restore health. Inserting a gene starts with cutting the DNA, but instead of gluing the cut ends together, cells use a matching piece of DNA as a template to repair the damage.

In the new human embryo work, Liu and colleagues, including Wei-Hua Wang of the Houston Fertility Institute in Texas, first tested this type of repair on embryos with an extra set of chromosomes. Efficiency was low; about 10 to 20 percent of embryos contained the desired edits. Researchers had previously argued that extra chromosomes could interfere with the editing process, so Liu’s group also made embryos with the normal two copies of each chromosome (one from the father and one from the mother). Sperm from men that have genetic diseases common in China were used to fertilize eggs. In one experiment, Liu’s group made 10 embryos, two of which carried a mutation in the G6PD gene. Mutations in that gene can lead to a type of anemia.

Then the team injected Cas9 protein already leashed to its guide RNA, along with a separate piece of DNA that embryos could use as a template for repairing the mutant gene. G6PD mutations were repaired in both embryos. Since both of the two embryos had the repair, the researchers say they achieved 100 percent efficiency. But one embryo was a mosaic: It carried the fix in some but not all of its cells. Another experiment to repair mutations in the HBB gene, linked to blood disorders, worked with 50 percent efficiency, but with some other technical glitches.

Scientists don’t know whether editing just some cells in an embryo will be enough to cure genetic diseases. For that reason, some researchers think it may be necessary to step back from embryos to edit the precursor cells that produce eggs and sperm, says Harvard University geneticist George Church. Precursor cells can produce many copies of themselves, so some could be tested to ensure that proper edits have been made with no off-target mutations. Properly edited cells would then be coaxed into forming sperm or eggs in lab dishes. Researchers have already succeeded in making viable sperm and eggs from reprogrammed mouse stem cells (SN: 11/12/16, p. 6). Precursors of human sperm and eggs have also been grown in lab dishes (SN Online: 12/24/14), but researchers have yet to report making viable human embryos from such cells.

The technology to reliably and safely edit human germline cells will probably require several more years of development, researchers say.

Germline editing — as altering embryos, eggs and sperm or their precursors is known — probably won’t be the first way CRISPR/Cas9 is used to tackle genetic diseases. Doctors are already planning experiments to edit genes in body cells of patients. Those experiments come with fewer ethical questions but have their own hurdles, researchers say.

“We still have a few years to go,” says MacKenzie, “but I’ve never been so hopeful as I am now of the capacity of this technology to change people’s lives.”

New rules for cellular entry may aid antibiotic development

Like entry to an exclusive nightclub, getting inside a gram-negative bacterial cell is no easy feat for chemical compounds. But now a secret handshake has been revealed: A new study lays out several rules to successfully cross the cells’ fortified exteriors, which could lead to the development of sorely needed antibiotics.

“It’s a breakthrough,” says microbiologist Kim Lewis of Northeastern University in Boston, who was not involved with the work. The traditional way to learn how compounds get across the bacterial barrier is to study the barrier, he says. “They decided to attack the problem from the other end: What are the properties of the molecules that may allow them to penetrate across the barrier?” The work describing these properties is published online in Nature on May 10.

Escherichia coli and other gram-negative bacteria — so described because of how they look when exposed to a violet dye called a gram stain — have two cellular membranes. The outer membrane is impermeable to most antibiotics, says Paul Hergenrother, a chemical biologist at the University of Illinois at Urbana-Champaign. “Even if a drug might be really good at killing that gram-negative pathogen, it may not be able to get in the bacteria,” he says.

Many antibiotics that have been effective against gram-negative bacteria are becoming unreliable, as the bugs have developed resistance (SN: 10/15/16, p. 11). To encourage drug development, in February the World Health Organization released a list of pathogens that are resistant to multiple drugs and threaten human health. All of the bacteria in the critical priority group are gram-negative.
The outer membrane of gram-negative cells is dotted with proteins called porins. These channel structures allow the bacteria to take up nutrients. Those antibiotics that can get inside gram-negative bacteria typically pass through porins, says Hergenrother.

To uncover the dos and don’ts of porin passage, Hergenrother’s group synthesized 100 compounds that share characteristics with antimicrobials found in nature, such as those from plants. The researchers took each compound, incubated it with E. coli bacteria in a tube for 10 minutes and then measured how much got inside the cells.

One feature stood out among the dozen of those compounds that significantly accumulated inside the bacterial cells: They all contained an amine group, a chemical group that contains the element nitrogen.

Next, the team collected a larger set of compounds that have amine groups and again measured whether or not the compounds accumulated inside E. coli cells. The researchers used a computer program to predict what other attributes would be necessary to get through porins. This analysis revealed that a compound should be rigid, rather than flexible, and flat, as opposed to spherical. It’s much easier to put a ruler through a narrow opening than a basketball, notes Hergenrother.

To test the new rules, the researchers turned to an antimicrobial called deoxynybomycin. This compound is effective only against gram-positive bacteria, which has just one cellular membrane. Deoxynybomycin is flat and rigid, so it already has “the right geometrical parameters,” says Hergenrother. That makes it a good compound “to try to add an amine to, in a place that doesn’t disrupt how it interacts with the biological target.”

The team synthesized a derivative of deoxynybomycin with an amine group and tested the compound against a number of gram-negative pathogens that are resistant to many antibiotics. The altered deoxynybomycin successfully killed all but one of the types of pathogens tested.

It’s possible other antibiotics that specifically target gram-positive bacteria could be converted into drugs that kill gram-negative bugs too by following the new rules, says Hergenrother. And keeping these guidelines in mind when assembling compound collections could make screening for drug candidates more successful.

The research could also “revive the failed effort to rationally design antibiotics,” says Lewis. Knowing the rules, it may be possible to build a compound that both hits its bacterial target and has the features needed to penetrate the target’s barrier.

Drowned wildebeests can feed a river ecosystem for years

More than a million wildebeests migrate each year from Tanzania to Kenya and back again, following the rains and abundant grass that springs up afterward. Their path takes them across the Mara River, and some of the crossings are so dangerous that hundreds or thousands of wildebeests drown as they try to traverse the waterway.

Those animals provide a brief, free buffet for crocodiles and vultures. And, a new study finds, they’re feeding an aquatic ecosystem for years.

Ecologist Amanda Subalusky of the Cary Institute of Ecosystem Studies in Millbrook, N.Y., had been studying water quality in the Mara River when she and her colleagues noticed something odd. Commonly used indicators of water quality, such as dissolved oxygen and turbidity, were sometimes poorest where the river flowed through a protected area. They quickly realized that it was because of the animals that flourished there. Hippos, which eat grass at night and defecate in the water during the day, were one contributor. And dead wildebeests were another.

“Wildebeest are especially good at following the rains, and they’re willing to cross barriers to follow it,” says Subalusky. The animals tend to cross at the same spots year after year, and some are more dangerous than others. “Once they’ve started using a site, they continue, even if it’s bad,” she notes. And on average, more than 6,000 wildebeests drown each year. (That may sound like a lot, but it’s only about 0.5 percent of the herd.) Their carcasses add the equivalent of the mass of 10 blue whales into the river annually.

Subalusky and her colleagues set out to see how all that meat and bone affected the river ecosystem. When they heard about drownings, they would go to the river to count carcasses. They retrieved dead wildebeests from the water to test what happened to the various parts over time. And they measured nutrients up and downstream from river crossings to see what the wildebeest carcasses added to the water.

“There are some interesting challenges working in this system,” Subalusky says. For instance, in one experiment, she and her colleagues put pieces of wildebeest carcass into mesh bags that went into the river. The plan was that they would retrieve the bags over time and see how quickly or slowly the pieces decomposed. “We spent a couple of days putting the whole thing together and we came back the next day to collect our first set of samples,” she recalls. “At least half the bags with wildebeest meat were just gone. Crocodiles and Nile monitors had plucked them off the chain.”
The researchers determined that the wildebeests’ soft tissue decomposes in about two to 10 weeks. This provides a pulse of nutrients — carbon, nitrogen and phosphorus — to the aquatic food web as well as the nearby terrestrial system. Subalusky and her colleagues are still working out the succession of scavengers that feast on the wildebeests, but vultures, marabou storks, egg-laying bugs and things that eat bugs are all on the list.
Once the soft tissue is gone, the bones remain, sometimes piling up in bends in the river or other spots downstream. “They take years to decompose,” Subalusky says, slowly leaching out most of the phosphorus that had been in the animal. The bones can also become covered in a biofilm of algae, fungi and bacteria that provides food for fish.

What initially looks like a short-lived event actually provides resources for seven years or more, Subalusky and her colleagues report June 19 in the Proceedings of the National Academy of Sciences.

The wildebeest migration is the largest terrestrial migration on the planet, and others of its kind have largely disappeared as humans have killed off animals or cut off their migration routes.

Only a few hundred years ago, for instance, millions of bison roamed the western United States. There are accounts in which thousands of bison drowned in rivers, similar to what happens with wildebeests. Those rivers may have fundamentally changed after bison were nearly wiped out, Subalusky and her colleagues contend.

We’ll never know if that was the case, but there are still some places where scientists may be able to study the effects of mass drownings on rivers. A large herd of caribou reportedly drowned in Canada in the 1980s, and there are still some huge migrations of animals, such as reindeer. Like the wildebeests, these animals might be feeding an underwater food web that no one has ever noticed.

How earthquake scientists eavesdrop on North Korea’s nuclear blasts

On September 9 of last year, in the middle of the morning, seismometers began lighting up around East Asia. From South Korea to Russia to Japan, geophysical instruments recorded squiggles as seismic waves passed through and shook the ground. It looked as if an earthquake with a magnitude of 5.2 had just happened. But the ground shaking had originated at North Korea’s nuclear weapons test site.

It was the fifth confirmed nuclear test in North Korea, and it opened the latest chapter in a long-running geologic detective story. Like a police examiner scrutinizing skid marks to figure out who was at fault in a car crash, researchers analyze seismic waves to determine if they come from a natural earthquake or an artificial explosion. If the latter, then scientists can also tease out details such as whether the blast was nuclear and how big it was. Test after test, seismologists are improving their understanding of North Korea’s nuclear weapons program.
The work feeds into international efforts to monitor the Comprehensive Nuclear-Test-Ban Treaty, which since 1996 has banned nuclear weapons testing. More than 180 countries have signed the treaty. But 44 countries that hold nuclear technology must both sign and ratify the treaty for it to have the force of law. Eight, including the United States and North Korea, have not.

To track potential violations, the treaty calls for a four-pronged international monitoring system, which is currently about 90 percent complete. Hydroacoustic stations can detect sound waves from underwater explosions. Infrasound stations listen for low-frequency sound waves rumbling through the atmosphere. Radio­nuclide stations sniff the air for the radioactive by-products of an atmospheric test. And seismic stations pick up the ground shaking, which is usually the fastest and most reliable method for confirming an underground explosion.

Seismic waves offer extra information about an explosion, new studies show. One research group is exploring how local topography, like the rugged mountain where the North Korean government conducts its tests, puts its imprint on the seismic signals. Knowing that, scientists can better pinpoint where the explosions are happening within the mountain — thus improving understanding of how deep and powerful the blasts are. A deep explosion is more likely to mask the power of the bomb.
Separately, physicists have conducted an unprecedented set of six explosions at the U.S. nuclear test site in Nevada. The aim was to mimic the physics of a nuclear explosion by detonating chemical explosives and watching how the seismic waves radiate outward. It’s like a miniature, nonnuclear version of a nuclear weapons test. Already, the scientists have made some key discoveries, such as understanding how a deeply buried blast shows up in the seismic detectors.
The more researchers can learn about the seismic calling card of each blast, the more they can understand international developments. That’s particularly true for North Korea, where leaders have been ramping up the pace of military testing since the first nuclear detonation in 2006. On July 4, the country launched its first confirmed ballistic missile — with no nuclear payload — that could reach as far as Alaska.

“There’s this building of knowledge that helps you understand the capabilities of a country like North Korea,” says Delaine Reiter, a geophysicist with Weston Geophysical Corp. in Lexington, Mass. “They’re not shy about broadcasting their testing, but they claim things Western scientists aren’t sure about. Was it as big as they claimed? We’re really interested in understanding that.”

Natural or not
Seismometers detect ground shaking from all sorts of events. In a typical year, anywhere from 1,200 to 2,200 earthquakes of magnitude 5 and greater set off the machines worldwide. On top of that is the unnatural shaking: from quarry blasts, mine collapses and other causes. The art of using seismic waves to tell one type of event from the others is known as forensic seismology.

Forensic seismologists work to distinguish a natural earthquake from what could be a clandestine nuclear test. In March 2003, for instance, seismometers detected a disturbance coming from near Lop Nor, a dried-up lake in western China that the Chinese government, which signed but hasn’t ratified the test ban treaty, has used for nuclear tests. Seismologists needed to figure out immediately what had happened.

One test for telling the difference between an earthquake and an explosion is how deep it is. Anything deeper than about 10 kilometers is almost certain to be natural. In the case of Lop Nor, the source of the waves seemed to be located about six kilometers down — difficult to tunnel to, but not impossible. Researchers also used a second test, which compares the amplitudes of two different kinds of seismic waves.

Earthquakes and explosions generate several types of seismic waves, starting with P, or primary, waves. These waves are the first to arrive at a distant station. Next come S, or secondary, waves, which travel through the ground in a shearing motion, taking longer to arrive. Finally come waves that ripple across the surface, including those called Rayleigh waves.
In an explosion as compared with an earthquake, the amplitudes of Rayleigh waves are smaller than those of the P waves. By looking at those two types of waves, scientists determined the Lop Nor incident was a natural earthquake, not a secretive explosion. (Seismology cannot reveal the entire picture. Had the Lop Nor event actually been an explosion, researchers would have needed data from the radionuclide monitoring network to confirm the blast came from nuclear and not chemical explosives.)

For North Korea, the question is not so much whether the government is setting off nuclear tests, but how powerful and destructive those blasts might be. In 2003, the country withdrew from the Treaty on the Nonproliferation of Nuclear Weapons, an international agreement distinct from the testing ban that aims to prevent the spread of nuclear weapons and related technology. Three years later, North Korea announced it had conducted an underground nuclear test in Mount Mantap at a site called Punggye-ri, in the northeastern part of the country. It was the first nuclear weapons test since India and Pakistan each set one off in 1998.

By analyzing seismic wave data from monitoring stations around the region, seismologists concluded the North Korean blast had come from shallow depths, no more than a few kilometers within the mountain. That supported the North Korean government’s claim of an intentional test. Two weeks later, a radionuclide monitoring station in Yellowknife, Canada, detected increases in radioactive xenon, which presumably had leaked out of the underground test site and drifted eastward. The blast was nuclear.

But the 2006 test raised fresh questions for seismologists. The ratio of amplitudes of the Rayleigh and P waves was not as distinctive as it usually is for an explosion. And other aspects of the seismic signature were also not as clear-cut as scientists had expected.

Researchers got some answers as North Korea’s testing continued. In 2009, 2013 and twice in 2016, the government set off more underground nuclear explosions at Punggye-ri. Each time, researchers outside the country compared the seismic data with the record of past nuclear blasts. Automated computer programs “compare the wiggles you see on the screen ripple for ripple,” says Steven Gibbons, a seismologist with the NORSAR monitoring organization in Kjeller, Norway. When the patterns match, scientists know it is another test. “A seismic signal generated by an explosion is like a fingerprint for that particular region,” he says.

With each test, researchers learned more about North Korea’s capabilities. By analyzing the magnitude of the ground shaking, experts could roughly calculate the power of each test. The 2006 explosion was relatively small, releasing energy equivalent to about 1,000 tons of TNT — a fraction of the 15-kiloton bomb dropped by the United States on Hiroshima, Japan, in 1945. But the yield of North Korea’s nuclear tests crept up each time, and the most recent test, in September 2016, may have exceeded the size of the Hiroshima bomb.
Digging deep
For an event of a particular seismic magnitude, the deeper the explosion, the more energetic the blast. A shallow, less energetic test can look a lot like a deeply buried, powerful blast. Scientists need to figure out precisely where each explosion occurred.

Mount Mantap is a rugged granite mountain with geology that complicates the physics of how seismic waves spread. Western experts do not know exactly how the nuclear bombs are placed inside the mountain before being detonated. But satellite imagery shows activity that looks like tunnels being dug into the mountainside. The tunnels could be dug two ways: straight into the granite or spiraled around in a fishhook pattern to collapse and seal the site after a test, Frank Pabian, a nonproliferation expert at Los Alamos National Laboratory in New Mexico, said in April in Denver at a meeting of the Seismological Society of America.

Researchers have been trying to figure out the relative locations of each of the five tests. By comparing the amplitudes of the P, S and Rayleigh waves, and calculating how long each would have taken to travel through the ground, researchers can plot the likely sites of the five blasts. That allows them to better tie the explosions to the infrastructure on the surface, like the tunnels spotted in satellite imagery.

One big puzzle arose after the 2009 test. Analyzing the times that seismic waves arrived at various measuring stations, one group calculated that the test occurred 2.2 kilometers west of the first blast. Another scientist found it only 1.8 kilometers away. The difference may not sound like a lot, Gibbons says, but it “is huge if you’re trying to place these relative locations within the terrain.” Move a couple of hundred meters to the east or west, and the explosion could have happened beneath a valley as opposed to a ridge — radically changing the depth estimates, along with estimates of the blast’s power.

Gibbons and colleagues think they may be able to reconcile these different location estimates. The answer lies in which station the seismic data come from. Studies that rely on data from stations within about 1,500 kilometers of Punggye-ri — as in eastern China — tend to estimate bigger distances between the locations of the five tests when compared with studies that use data from more distant seismic stations in Europe and elsewhere. Seismic waves must be leaving the test site in a more complicated way than scientists had thought, or else all the measurements would agree.
When Gibbons’ team corrected for the varying distances of the seismic data, the scientists came up with a distance of 1.9 kilometers between the 2006 and 2009 blasts. The team also pinpointed the other explosions as well. The September 2016 test turned out to be almost directly beneath the 2,205-meter summit of Mount Mantap, the group reported in January in Geophysical Journal International. That means the blast was, indeed, deeply buried and hence probably at least as powerful as the Hiroshima bomb for it to register as a magnitude 5.2 earthquake.

Other seismologists have been squeezing information out of the seismic data in a different way — not in how far the signals are from the test blast, but what they traveled through before being detected. Reiter and Seung-Hoon Yoo, also of Weston Geophysical, recently analyzed data from two seismic stations, one 370 kilometers to the north in China and the other 306 kilometers to the south in South Korea.

The scientists scrutinized the moments when the seismic waves arrived at the stations, in the first second of the initial P waves, and found slight differences between the wiggles recorded in China and South Korea, Reiter reported at the Denver conference. Those in the north showed a more energetic pulse rising from the wiggles in the first second; the southern seismic records did not. Reiter and Yoo think this pattern represents an imprint of the topography at Mount Mantap.

“One side of the mountain is much steeper,” Reiter explains. “The station in China was sampling the signal coming through the steep side of the mountain, while the southern station was seeing the more shallowly dipping face.” This difference may also help explain why data from seismic stations spanning the breadth of Japan show a slight difference from north to south. Those differences may reflect the changing topography as the seismic waves exited Mount Mantap during the test.

Learning from simulations
But there is only so much scientists can do to understand explosions they can’t get near. That’s where the test blasts in Nevada come in.

The tests were part of phase one of the Source Physics Experiment, a $40-million project run by the U.S. Department of Energy’s National Nuclear Security Administration. The goal was to set off a series of chemical explosions of different sizes and at different depths in the same borehole and then record the seismic signals on a battery of instruments. The detonations took place at the nuclear test site in southern Nevada, where between 1951 and 1992 the U.S. government set off 828 underground nuclear tests and 100 atmospheric ones, whose mushroom clouds were seen from Las Vegas, 100 kilometers away.

For the Source Physics Experiment, six chemical explosions were set off between 2011 and 2016, ranging up to 5,000 kilograms of TNT equivalent and down to 87 meters deep. The biggest required high-energy–density explosives packed into a cylinder nearly a meter across and 6.7 meters long, says Beth Dzenitis, an engineer at Lawrence Livermore National Laboratory in California who oversaw part of the field campaign. Yet for all that firepower, the detonation barely registered on anything other than the instruments peppering the ground. “I wish I could tell you all these cool fireworks go off, but you don’t even know it’s happening,” she says.

The explosives were set inside granite rock, a material very similar to the granite at Mount Mantap. So the seismic waves racing outward behaved very much as they might at the North Korean nuclear test site, says William Walter, head of geophysical monitoring at Livermore. The underlying physics, describing how seismic energy travels through the ground, is virtually the same for both chemical and nuclear blasts.
The results revealed flaws in the models that researchers have been using for decades to describe how seismic waves travel outward from explosions. These models were developed to describe how the P waves compress rock as they propagate from large nuclear blasts like those set off starting in the 1950s by the United States and the Soviet Union. “That worked very well in the days when the tests were large,” Walter says. But for much smaller blasts, like those North Korea has been detonating, “the models didn’t work that well at all.”
Walter and Livermore colleague Sean Ford have started to develop new models that better capture the physics involved in small explosions. Those models should be able to describe the depth and energy release of North Korea’s tests more accurately, Walter reported at the Denver meeting.

A second phase of the Source Physics Experiment is set to begin next year at the test site, in a much more rubbly type of rock called alluvium. Scientists will use that series of tests to see how seismic waves are affected when they travel through fragmented rock as opposed to more coherent granite. That information could be useful if North Korea begins testing in another location, or if another country detonates an atomic bomb in fragmented rock.

For now, the world’s seismologists continue to watch and wait, to see what the North Korean government might do next. Some experts think the next nuclear test will come at a different location within Mount Mantap, to the south of the most recent tests. If so, that will provide a fresh challenge to the researchers waiting to unravel the story the seismic waves will tell.

“It’s a little creepy what we do,” Reiter admits. “We wait for these explosions to happen, and then we race each other to find the location, see how big it was, that kind of thing. But it has really given us a good look as to how [North Korea’s] nuclear program is progressing.” Useful information as the world’s nations decide what to do about North Korea’s rogue testing.

Body clock mechanics wins U.S. trio the Nobel Prize in physiology or medicine

Discoveries about the clocklike ups and downs of daily life have won Jeffery C. Hall, Michael Rosbash and Michael W. Young the Nobel Prize in physiology or medicine.

Circadian rhythms are daily cycles of hormones, gene activity and other biological processes that govern sleep, body temperature and metabolism. When thrown out of whack, there can be serious health consequences, including increased risk of diabetes, heart and Alzheimer’s diseases.

Hall and Rosbash discovered the first molecular gear of the circadian clockworks: A protein called Period increases and decreases in abundance on a regular cycle during the day. Young discovered that another protein called Timeless works with Period to drive the clock. Young also discovered other circadian clockworks.