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.”

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.

Parents’ presence promotes a child’s pluck

BOSTON — The bond between parent and child is powerful enough to override fear. New research shows that if a parent sits with a young child during a potentially scary situation, the child isn’t as afraid of it later.

The study is in line with research suggesting that during particular stages of development, a strong connection with a caregiver tamps down activity in the amygdala, the brain structure that helps process fear and spurs the fight-or-flight response.
“Fight or flight is pointless if you are tiny,” said developmental neuroscientist Nim Tottenham of Columbia University, who presented the work March 26 at a Cognitive Neuroscience Society meeting. For young kids, the bond with a caregiver not only helps ensure survival but also makes kids feel safe, enabling them to approach the world with confidence, Tottenham said. “Attachment is a strategy that has worked very well; it trumps everything.”

Kids from ages 3 to 5 were shown two shapes — a green triangle and a blue square. Just the square was accompanied by a loud, fingers-on-the-chalkboard kind of noise. Some kids had a parent sitting next to them while they saw the shapes; others sat with a researcher. After the parents left, kids chose which door to go through to get a present: one with the scary blue square on it, the other with the innocuous green triangle.

Kids paired with the experimenter avoided the door with the blue square. But kids who had sat next to a parent showed a slight preference for that door, even though they knew they would collect the same present from behind either door.

How physicists will remember Stephen Hawking

Stephen Hawking, a black hole whisperer who divined the secrets of the universe’s most inscrutable objects, left a legacy of cosmological puzzles sparked by his work, and inspired a generation of scientists who grew up reading his books.

Upon Hawking’s death on March 14 at age 76, his most famous discovery — that black holes aren’t entirely black, but emit faint radiation — was still fueling debate.

Hawking “really, really cared about the truth, and trying to find it,” says physicist Andrew Strominger of Harvard University, who collaborated with the famed scientist. Hawking “was deeply committed, his whole life, to this quest of understanding more about the physical universe around us.”

After earning his Ph.D. in 1965 at the University of Cambridge, Hawking continued studying cosmology there for the rest of his life. Due to a degenerative illness, amyotrophic lateral sclerosis, or ALS, Hawking gradually lost control of his body, requiring a wheelchair and eventually a voice synthesizer to speak. Yet his desire to uncover nature’s secrets remained boundless.
In one of the most significant realizations of his career, Hawking reported in 1974 that black holes emit a faint glow of particles. This effect arises from quantum mechanics, which states that a sea of transient particles and antiparticles pervades all of space. These “virtual” particles usually annihilate in an instant, but if one of those particles is lost inside a black hole’s boundary, or event horizon, its partner can escape, producing what’s now known as Hawking radiation (SN: 5/31/14, p. 16).

As a result, black holes can gradually evaporate and disappear. This led to a still unresolved paradox: Throw an encyclopedia into a black hole and the information will eventually be lost. But according to quantum mechanics, information can never be destroyed.

Many solutions have been proposed for this problem, but none has stuck. In 2016, Hawking and colleagues proposed a path toward a solution: Black holes might have “soft hair,” low-energy particles that would retain information about what fell inside (SN: 2/06/16, p. 16). Hawking’s collaborators, including Strominger, are still working on the research. Standing at the interface between two seemingly incompatible theories — quantum mechanics, which describes the very small, and the general theory of relativity, which describes gravity — the quandary and its resolution may eventually help reveal a unified theory of quantum gravity.

Hawking made many other contributions, including studies of spacetime curvature during the Big Bang and the possibility that mini black holes might have formed in the universe’s infancy. Despite their groundbreaking nature, Hawking’s ideas remained largely theoretical, says Harvard theoretical astrophysicist Avi Loeb. Hawking radiation, for example, has never been directly detected. “That’s, unfortunately, why he didn’t get the Nobel Prize,” Loeb says.
Yet Hawking achieved a level of fame uncommon among scientists. He excelled at making abstruse science digestible to the public. With his books, most notably the best-selling A Brief History of Time, first published in 1988, Hawking inspired countless future scientists and science lovers (including the author of this article). Theoretical cosmologist Katie Mack of North Carolina State University in Raleigh first opened the book when she was about 10 years old. “I found it so fascinating at the time,” she says. “I found out that Stephen Hawking was called a cosmologist and so I said I wanted to be a cosmologist.” Hawking similarly motivated dozens of her colleagues, Mack says.

Hawking remained active in research even in the last months of his life. A paper on which he is a coauthor, which was updated in the weeks before his death, considered the physics of multiverses, the possibility that a slew of other universes exist in addition to our own.

A funeral was held for Hawking on March 31. Later this year, his ashes will be interred in Westminster Abbey in London, where they will rest alongside the remains of other famous British scientists, including Isaac Newton and Charles Darwin.

How ravens caused a LIGO data glitch

While the data was amassing, suddenly there came a tapping,
As of something gently rapping, rapping at LIGO’s door.

The source of a mysterious glitch in data from a gravitational wave detector has been unmasked: rap-tap-tapping ravens with a thirst for shaved ice. At the Advanced Laser Interferometer Gravitational-Wave Observatory, or LIGO, in the desert of Hanford, Wash., scientists noticed a signal that didn’t look like gravitational waves, physicist Beverly Berger said on April 16 at a meeting of the American Physical Society.

A microphone sensor that monitors LIGO’s surroundings caught the sounds of pecking birds on tape in July 2017, Berger, of the LIGO Laboratory at Caltech, said. So the crew went out to the end of one of the detector’s 4-kilometer-long arms to check for evidence of the ebony birds at the scene.

Sure enough, frost covering a pipe connected to the cooling system was covered in telltale peck marks from the thirsty birds. One raven, presumably seeking relief from the desert heat, was caught in the act. Altering the setup to prevent ice buildup now keeps the ravens from tapping, evermore.

NASA’s TESS spacecraft launches to begin its exoplanet search

After a two-day delay, the planet-hunting TESS telescope successfully launched into a clear blue sky at Cape Canaveral, Fla., at 6:51 p.m. EDT on April 18.

TESS, the Transiting Exoplanet Survey Satellite, is headed to an orbit between the Earth and the moon, a journey that will take about two months. In its first two years, the telescope will seek planets orbiting 200,000 nearby, bright stars, and identify the best planets for further study. TESS’ cameras will survey 85 percent of the sky by splitting it up into 26 zones and focusing on each zone for 27 days apiece.

TESS launched on a SpaceX Falcon 9 rocket. A previous launch attempt on April 16 was scrubbed so that SpaceX could run more tests on the rocket’s guidance, navigation and control system. SpaceX recovered the rocket’s first stage booster on an autonomous drone ship and hopes to reuse the rocket on a future launch.

Spooky quantum entanglement goes big in new experiments

Quantum entanglement has left the realm of the utterly minuscule, and crossed over to the just plain small. Two teams of researchers report that they have generated ethereal quantum linkages, or entanglement, between pairs of jiggling objects visible with a magnifying glass or even the naked eye — if you have keen vision.

Physicist Mika Sillanpää and colleagues entangled the motion of two vibrating aluminum sheets, each 15 micrometers in diameter — a few times the thickness of spider silk. And physicist Sungkun Hong and colleagues performed a similar feat with 15-micrometer-long beams made of silicon, which expand and contract in width in a section of the beam. Both teams report their results in the April 26 Nature.
“It’s a first demonstration of entanglement over these artificial mechanical systems,” says Hong, of the University of Vienna. Previously, scientists had entangled vibrations in two diamonds that were macroscopic, meaning they were visible (or nearly visible) to the naked eye. But this is the first time entanglement has been seen in macroscopic structures constructed by humans, which can be designed to meet particular technological requirements.

Entanglement is a strange feature of quantum mechanics, through which two objects’ properties become intertwined. Measuring the properties of one object immediately reveals the state of the other, even though the duo may be separated by a large distance (SN: 8/5/17, p. 14).

Quantum mechanics’ weird rules typically apply to small fry — atoms, electrons and other tiny particles — and not to larger things such as cats, chairs or buildings. But that division leads to a confounding puzzle. “Atoms behave like atoms, and cats behave like cats, and so where is that transition in between?” says physicist Ben Sussman of the National Research Council of Canada in Ottawa, who was not involved in the research.

Now, scientists are extending the dividing line to larger and larger objects. “One of our motivations is to keep on testing how far we can push quantum mechanics,” says Sillanpää, of Aalto University in Finland. “There might be some fundamental limit for how big objects can be” and still be quantum.
In Sillanpää’s experiment, two tiny aluminum sheets — consisting of about a trillion atoms and just barely visible with the naked eye — vibrate like drumheads and interact with microwaves bouncing back and forth in a cavity. Those microwaves play the role of drum major, causing the two drumheads to sync up their motions. In many previous demonstrations of entanglement, the delicate quantum link is transient. But this one was long-lived, persisting as long as half an hour in experiments, Sillanpää says, and, in theory, even longer. “Our entanglement lasts forever, basically.”
Taking a different tactic, Hong and colleagues demonstrated entanglement with two silicon beams, big enough to be seen with a magnifying glass. Within a region of each beam, in a 1-micrometer-long section composed of about 10 billion atoms, the structure expanded and contracted — as if taking deep breaths in and out — in response to being hit with light. Instead of microwaves, Hong and colleagues’ work used infrared light of the wavelength typically transmitted in telecommunications networks made of optical fibers, which means it could be incorporated into a future quantum internet. “From a technology standpoint, that really is crucial,” says physicist John Teufel of the National Institute of Standards and Technology in Boulder, Colo., who was not involved with the work.

Scientists could use such vibrating structures within a quantum network to convert quantum information from one type to another, transitioning from particles of light to vibrations, for example. Once constructed, a quantum internet could allow quantum computers to communicate and provide unhackable communication across the globe (SN: 10/15/16, p. 13).

The ability to entangle these specially designed structures moves scientists a step closer to that vision. “You can really start to think about building real devices with these things,” Sussman says.

New ideas about how stars die help solve a decades-old mystery

New insights into how stars like the sun die might help explain why astronomers find bright planetary nebulae where they’re least expected. Simulations of how these stellar remnants form suggest that smaller stars have cores that heat up fast enough to produce bright nebulae upon their demise, researchers report online May 7 in Nature Astronomy.

A planetary nebula is what’s left over when a sunlike star sheds its outer envelope of gas. Radiation from the stellar core, now exposed, sets the expanding shell of gas aglow, creating the kind of candy-colored clouds seen in spectacular Hubble Space Telescope images, like that of the Cat’s Eye Nebula and the butterfly-shaped NGC 6302 (SN Online: 9/5/13).
Astronomers had thought a star’s mass dictated what sort of nebula it produced, with more massive stars creating the brightest nebulae and stars with lower masses, like the sun, making nebulae too faint to see from another galaxy.

But that idea didn’t match observations: The brightest planetary nebulae in older elliptical galaxies — thought to be home to only low-mass stars — are just as luminous as those in younger, spiral galaxies, where massive stars abound. The puzzle vexed astronomers for decades.

Now, astrophysicist Albert Zijlstra at the University of Manchester in England, and colleagues have simulated planetary nebulae formation based on a new theory of stellar evolution. This theory says that after smaller stars shed their outer envelopes, their bare cores heat up more quickly than previously thought. That allows the cinderlike stellar core to pump more energetic radiation into the surrounding nebula before the gas expands too far out into space, ultimately making for a brighter nebula, explains Christophe Morisset, an astronomer at the National Autonomous University of Mexico in Mexico City not involved in the work.

Simulations showed that stars ranging from 1.1 to three times the mass of the sun produce nebulae with similar brightness. That result could explain why nebulae found in galaxies with stars that are 7 billion years old can be just as bright as those found in galaxies chock-full of 1-billion-year-old stars.
This finding marks “an important step forward” in understanding the universe’s population of planetary nebulae, says Penn State astronomer Robin Ciardullo, who was not involved in the work.

But some mystery still remains: For the most ancient elliptical galaxies with very small stars over 7 billion years old, the simulations didn’t produce planetary nebulae bright enough to match what astronomers see in the sky. So there’s still “a little ways to go” before astronomers can explain why bright nebulae are so ubiquitous, he says.

Globetrotting tourists are leaving a giant carbon footprint on the Earth

Going green may mean staying at home.

Global tourism contributes about 8 percent of total greenhouse gas emissions to the atmosphere, researchers report May 7 in Nature Climate Change. That carbon footprint is about three times as large as tourism-related emissions estimated by previous studies.

The jump is largely because the new study doesn’t just tally up emissions from the traveling itself, like hopping a flight, going on a road trip or taking a cruise. It also looks at the impact of the goods and services that tourists enjoy, from food to shopping to hotel stays.
Who has the biggest carbon footprint? The United States topped the list, as both a top destination for tourists and a source of tourists. Other prosperous nations, such as Canada and Germany, also have a big footprint, and increasingly wealthy nations, such as China and Mexico, are catching up in this amazing race.

Take a look at global tourism by the numbers:

4.5 gigatons
The amount of carbon dioxide and other greenhouse gases that came from tourism in 2013.

2.7 percent
The share of the global total of emissions that comes just from Canadians and Mexicans traveling to the United States for tourism.

300 kilograms
Increase, from 2009 to 2013, in the yearly carbon footprint for each inhabitant of the tiny island nation of the Maldives as a result of international tourism.

$4.7 trillion
The amount of money, in U.S. dollars, spent on global tourism in 2013. That’s up from $2.5 trillion in 2009.

3 percent
Current annual growth in money spent on global tourism, which translates to tourism-related emissions of 6.5 gigatons of carbon dioxide and other greenhouse gases by 2025.