Possible source of high-energy neutrino reported

Scientists may have found the cosmic birthplace of an ultra-high energy neutrino. They point the finger at a blazar — a brilliantly luminous galaxy that shoots a jet of radiation in the direction of Earth — 9 billion light years away.

If the link between the blazar and neutrino is real, scientists would be closer to long-sought answers about where such power-packing particles come from. Violent astronomical accelerators boost some neutrinos to high energies, but scientists have never been able to convincingly identify their sources.
Neutrinos are aloof elementary particles that rarely interact with other matter — they can sail straight through the Earth, and trillions of them zip through your body every second without a trace. On December 4, 2012, the neutrino in question (which scientists have affectionately nicknamed Big Bird) slammed into the Antarctic ice with an energy of around 2 million billion electron volts. The neutrino observatory IceCube glimpsed the aftermath of the collision and measured its energy with sensitive detectors embedded deep in the ice (SN Online: 04/07/14), leaving scientists hustling to pinpoint its source.

The blazar flared up at just the right time and place to be a prime suspect, researchers report in a paper accepted for publication in a peer-reviewed journal. The result, now available online at arXiv.org, strengthens the case that blazars are the source of such high-energy neutrinos, but it is no smoking gun.

After the neutrino was detected, a team of astrophysicists scoured the heavens for energetic galaxies with TANAMI, short for Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry, a network of telescopes peering into space at a variety of wavelengths. That team reported one likely candidate blazar.

But the candidate is not a surefire match, says IceCube leader Francis Halzen of the University of Wisconsin–Madison, who was not involved with the analysis. IceCube could determine the neutrino’s direction within only about 15 degrees on the sky, and the blazar flare-up continued for several months. The probability of such a chance concurrence between an unrelated neutrino and blazar is about 5 percent, the researchers say — too big to rule out chance. “It’s a very intriguing result,” says Halzen “but it’s not a proof.”

The matchup between the blazar and neutrino is noteworthy, even though the researchers can’t fully rule out the possibility that the match is a fluke, says astrophysicist Xiang-Yu Wang of Nanjing University in China, who was not involved with the research. “Given that the two events are very unique … I think it’s convincing.” Wang and colleagues have expanded on the result: In a paper accepted for publication in Physical Review Letters, they use the difference in arrival time between the neutrino and light from the blazar’s outburst — assuming the two are related — to test Einstein’s special and general theories of relativity. Certain theories of quantum gravity predict a delay in the arrival of a neutrino. (Einstein came out unscathed.)
The authors of the blazar study declined to comment on the result, citing the embargo policy of the journal where the paper will be published.

To convincingly identify a blazar as the source of a neutrino, Halzen says, scientists will need a better measurement of the neutrino’s direction, connected to a short-lived blazar outburst. In the future, Halzen says, IceCube will send out “astronomical telegrams” when it detects a neutrino, directing telescopes to take a look, perhaps catching a blazar in the act.

EPA underestimates methane emissions

The U.S. Environmental Protection Agency has a methane problem — and that could misinform the country’s carbon-cutting plans. Recent studies suggest that the agency’s reports fail to capture the full scope of U.S. methane emissions, including “super emitters” that contribute a disproportionate share of methane release. Those EPA reports influence the country’s actions to combat climate change and the regulation of methane-producing industries such as agriculture and natural gas production.

With EPA’s next annual methane report due to be published by April 15, early signs suggest that the agency is taking steps to fix the methane mismatch. A preliminary draft of the report revises the agency’s methane calculations for 2013 — the most recent year reported — upward by about 27 percent for the natural gas and petroleum sectors, a difference of about 2 million metric tons.
Yet it’s unclear how that and other revisions will factor into final methane emission totals in the upcoming report. The draft estimates that U.S. methane emissions from all sources in 2014 were about 28 million metric tons, up slightly from the revised estimate for 2013 and well above the original 2013 estimate of 25.453 million metric tons. But the totals in the draft don’t include updates to emission estimates from the oil and gas industry.
“EPA is reviewing the substantial body of new studies that have become available in the past year on the natural gas and petroleum sector,” says EPA spokesperson Enesta Jones. The agency is also gathering feedback from scientists and industry experts to further improve their reporting.

Methane, which makes up the bulk of natural gas, originates from natural sources, such as wetlands, as well as from human activities such as landfills, cattle ranches (SN: 11/28/15, p. 22) and the oil and gas industry. Globally, human activities release about 60 percent of the 600 million metric tons of methane emitted into the atmosphere each year. Once in the air, methane prevents some of Earth’s heat from escaping into space, causing a warming effect. Methane emissions currently account for about a quarter of human-caused global warming.

The EPA’s underestimation of U.S. methane emissions comes down to accounting. EPA samples emissions from known methane sources, such as cows or natural gas pipelines, and works out an average. That average is then multiplied by the nation’s number of cows, lengths of pipe and other methane sources. Results from this method disagree with satellite and land-based observations that measure changes in the total amount of methane in the air. A 2013 report in the Proceedings of the National Academy of Sciences found that U.S. methane emissions based on atmospheric measurements are about 50 percent larger than EPA estimates (SN Online: 11/25/13).
EPA’s reports don’t just misjudge the scale of emissions, they also miss the long-term trend, recent work suggests. EPA reported that U.S. methane emissions remained largely unchanged from 2002 to 2014. But researchers report online March 2 in Geophysical Research Letters that emissions of the greenhouse gas rose more than 30 percent over that period. The United States could be responsible for as much as 30 to 60 percent of the global increase in methane emissions over the last decade, the study’s authors conclude. “We’re definitely not a small piece of that pie,” says Harvard University atmospheric scientist Alex Turner, who coauthored the study.
Correctly tracking methane is important, Turner says, because over a 100-year period, the warming impact of methane is more than 25 times that of the same amount of CO2. Methane levels have also risen faster: Since the start of the industrial revolution, methane concentrations have more than doubled while CO2 has risen more than 40 percent.

While methane is more potent than CO2, there is about 200 times less methane in the atmosphere than CO2. Furthermore, methane stays in the atmosphere for only around 12 years before being absorbed by soil or breaking apart in chemical reactions. “If we reduce methane emissions, the climate responds very quickly and global warming would slow down almost immediately,” says Cornell University earth systems scientist Robert Howarth. “CO2, on the other hand, has an influence that will go hundreds to even thousands of years into the future.”

Turner and colleagues tracked methane across the continental United States using land stations that measure methane in the air and satellite observations that record dips in the infrared radiation frequencies absorbed and reemitted by methane. The researchers compared these methane measurements with those taken over Bermuda and the North Pacific Ocean — places upwind of the United States and far from major methane sources.

From 2002 through 2014, methane concentrations over the continental United States grew faster than those over the oceans, the researchers found. The difference was most pronounced over the central United States, where methane concentrations rose nearly twice as fast as in the rest of the country. Natural gas drilling and production boomed in in the central United States during the period studied, though the researchers could not precisely trace the source of the additional methane.

Turner and colleagues say they’re now working with EPA to reconcile the methane estimates. EPA will provide small-scale estimates of methane emissions down to a 10-kilometer-wide grid. By combining that grid with space and land observations, scientists should be able to isolate where methane mismatches are the most pronounced.

While Turner’s research can’t pinpoint the exact origins of the additional methane, other studies point to the oil and gas industry. The numbers that the EPA uses to tabulate methane emissions assume that equipment is functioning as intended, says Stanford University sustainability engineer Adam Brandt. Malfunctioning equipment can spew huge amounts of methane. That became abundantly – and visibly – clear last October when the largest U.S. methane leak in history began in an underground storage facility near Los Angeles. The leak released 97,100 metric tons of methane, equivalent to the annual greenhouse gas emissions of 572,000 cars, before being permanently sealed in February, researchers estimated in the March 18 Science.

Super methane emitters are a big problem elsewhere, too, albeit typically much smaller than the California leak, researchers report in the June 2016 Environmental Pollution. Surveying emissions from 100 natural gas leaks around Boston, the researchers found that 7 percent of leaks contributed half of the total methane released. In 2014, a different research team reported in Environmental Science & Technology that 19 percent of pneumatic controllers used at natural gas production sites accounted for 95 percent of all controller emissions.

Monitoring and quick repairs can stamp out rogue methane sources quickly, Brandt says. “This is a problem that’s easier to fix than it is to understand,” he says.

Nightshade plants bleed sugar as a call to ants for backup

Herbivores beware: Take a bite out of bittersweet nightshade (Solanum dulcamara), and you might have an ant problem on your hands. The plants produce a sugary goo that serves as an indirect defense, attracting ants that eat herbivores, Tobias Lortzing of Berlin’s Free University and colleagues write April 25 in Nature Plants.

Observations of wild nightshade plants in Germany suggest that plants that ooze goo attract more ants (mostly European fire ants, or Myrmica rubra) than undamaged plants. In greenhouse experiments, those ants fed on both the goo and roving slugs and flea beetle larvae, substantially reducing leaf damage. Leaf-munching adult flea beetles and, to a lesser degree, slugs prompted the goo production. The ants didn’t attack the beetles but did protect the plant from slugs and beetle larvae.

Plenty of other plants produce defensive nectars via organs called nectaries, and nightshades’ bleeding may be a unique, primitive version of that protective strategy, the scientists report.

Why Labrador retrievers are obsessed with food

Labrador retrievers tend to be more overweight and keen to scarf down their kibble than other dog breeds. Eleanor Raffan of the University of Cambridge and her colleagues chalk this trend up — least in part — to a suspect gene.

The team found that, among a small group of assistance dogs, a form of a gene called POMC that was missing a chunk of DNA was more common in obese Labs than in lean ones. This held true on a larger scale, too: Out of 411 Labs in the United Kingdom and United States, 22 percent carried the deletion mutation. Looking across other breeds, only Labradors and flat coat retrievers, a close relative, carried the gene variant, which also correlated with greater weight and food begging tendencies, the team reports May 3 in Cell Metabolism.

POMC plays a role in a metabolism pathway, and the deletion may inhibit the production of proteins that regulate hunger, the researchers suspect. (That might explain why the variant turned up in about 75 percent of assistance dogs, which are trained using food motivation.)

Here are a few more things for the childproofing list

There’s nothing like having kids to open your eyes to the world’s dangers. With two little rascals in tow, grocery stores, dentists’ offices and even grandparents’ homes morph into death traps full of sharp, poisonous and heavy things. Short of keeping a tight grip on little hands, there’s not much you can do to childproof absolutely everything when you’re out and about. At home, it’s easier to make rooms safe for kids: Cover electrical outlets, keep drugs and potentially poisonous stuff out of reach, bolt dressers to the wall, and so on.

But every so often, I come across a study that points out an unexpectedly dangerous object. Clearly, none of these things rise to Bag O’Glass danger levels. But in the spirit of The More You Know, here are five objects that carry hidden risks to children:

Laundry pods
These cute, candy-colored packets can be irresistible to children — and toxic when eaten. Since 2012, when single-load pods for laundry detergent became popular, poison control centers have been fielding calls about toddlers who got ahold of pods. From 2013 to 2014, over 22,000 U.S. children under age 6 were exposed to these pods, mostly by eating them, data from the National Poison Data System show. And in just that two-year period, cases of laundry pod exposure rose 17 percent, scientists reported in the May Pediatrics.

Those numbers are particularly worrisome because laundry pods appeared to be more dangerous than regular laundry detergent (liquid or powder) and dishwasher detergent in any form (pod, liquid or powder). In a small number of kids, eating laundry pods caused serious trouble, including coma, respiratory arrest and cardiac arrest. Two children died, scientists wrote in the Pediatrics paper.

Tiny turtles
Oh, they’re adorable, but turtles can carry salmonella, bacteria that come with diarrhea, fever and cramps. Kids are particularly susceptible, and infections can be severe for them. Recognizing this risk, the FDA banned the sale of small turtles (shell less than 4 inches long) in 1975.
Yet in recent years, small turtles have slowly crawled back into children’s grubby little hands, carrying salmonella with them, scientists reported in January in Pediatrics. From 2011 to 2013, turtles were implicated in eight multistate Salmonella outbreaks, hitting hard in children younger than 5. Of the 473 people affected by the outbreaks, the median age was 4.

Big TVs
I’m not talking about the dangers of screen time here. I mean the television itself. Today’s flat screen TVs are more wobbly than the older, heavier tube-based TVs. Every 30 minutes, a kid is treated in the emergency room for a TV-related injury — that’s more than 17,000 children in the United States per year and increasing. And little heads and necks are the most frequently injured body parts.

Liquid nicotine
Along with the rise of e-cigarettes come refill cartridges, most of which contain concentrated liquid nicotine in flavors such as cherry crush, vanilla and mint. These appealing flavors mask nicotine that can be dangerous to kids. In 2015, poison control centers reported over 3,000 incidents of unintentional nicotine exposure, many of them in children. In comparison, just 271 exposures were reported in 2011.

That worrisome increase prompted the Child Nicotine Poisoning Prevention Act of 2015, signed into law by President Obama on January 28, requiring nicotine cartridges to be packaged in child-proof containers — a no-brainer.

Trampolines
Maniacal bouncing is clearly exhilarating for children, but also risky. I say this as a childhood-double-bounce survivor, so I understand the appeal. But just a note of caution: These springy injury machines come with a constellation of scary medical stats. Concussions, broken bones, sprains and neck injuries are signature trampoline troubles. A survey of a national injury database showed that broken bones accounted for 29 percent of all trampoline injuries reported to emergency departments, scientists reported in 2014 in the Journal of Pediatrics Orthopedics. The vast majority (93 percent) of those fractures belonged to children 16 and under.

Attempts to make trampolines safer — by putting a net around the perimeter, for instance — don’t seem to lower injury rates, an Australian study found. That’s why the American Academy of Pediatrics, the Canadian Paediatric Society, the American Academy of Orthopaedic Surgeons and other groups all urge caution, or an outright ban.

Space experts say sending humans to Mars worth the risk

WASHINGTON — There’s a long-standing joke that NASA is always 20 years from putting astronauts on Mars. Mission details shared at a recent summit shows that the space agency is right on schedule. A to-do list from 2015 looks remarkably similar to one compiled in 1990. One difference: NASA is now building a rocket and test-driving technologies needed to get a crew to Mars. But the specifics for the longest road trip in history — and what astronauts will do once they arrive — remain an open question.

“Are we going to just send them there to explore and do things that we could do robotically though slower, or can we raise the bar?” asked planetary scientist Jim Bell during the Humans to Mars summit. “We need to make sure that what these folks are being asked to do is worthy of the risk to their lives,” said Bell, of Arizona State University in Tempe.
The three-day symposium, which ended May 19, was organized by Explore Mars Inc., a nonprofit dedicated to putting astronauts on Mars by the 2030s.

While the summit didn’t break new scientific ground, it did bring together planetary scientists , space enthusiasts and representatives from both NASA and the aerospace industry to talk about the challenges facing a crewed mission to Mars and rough ideas for how to get there.

Part of the appeal in sending humans is the pace of discovery. Drilling just one hole with the Curiosity rover, which has been exploring Gale Crater on Mars since August 2012 (SN: 5/2/2015, p. 24), currently takes about a week. “It’s a laborious, frustrating, wonderful — frustrating — multiday process,” said Bell.

Humans also can react to novel situations, make quick decisions and see things in a way robotic eyes cannot. “A robot explorer is nowhere near as good as what a human geologist can do,” says Ramses Ramirez, a planetary scientist at Cornell University. “There’s just a lot more freedom.”

Researchers saw the human advantage firsthand in 1997 when they sent a rover called Nomad on a 45-day trek across the Atacama Desert in Chile. Nomad was controlled by operators in the United States to simulate operating a robot on another planet. Humans at the rover site provided a reality check on the data Nomad sent back. “There was a qualitative difference,” says Edwin Kite, a planetary scientist at the University of Chicago. And it wasn’t just that the geologists could do things faster. “The robots were driving past evidence of life that humans were finding very obvious.”
To get astronauts ready to explore Mars, the Apollo program is a good template, said Jim Head, a geologist at Brown University who helped train the Apollo astronauts. “Our strategy was called t-cubed: train them, trust them and turn them loose.” While each of the moon expeditions had a plan, the astronauts were trusted to use their judgment. Apollo 15 astronaut David Scott, for example, came across a chunk of deep lunar crust that researchers hoped to find although it wasn’t at a planned stop. “He spotted it three meters away,” said Head. “He saw it shining and recognized it immediately. That’s exploration.”

Despite a lack of clear goals for a jaunt to Mars, NASA is forging ahead. The Orion crew capsule has already been to space once; a 2014 launch atop a Delta IV Heavy rocket sent an uncrewed Orion 5,800 kilometers into space before it splashed down in the Pacific Ocean (SN Online: 12/5/2014). And construction of the Space Launch System, a rocket intended to hurl humans at the moon and Mars, is under way. The first test flight, scheduled for October 2018, will send Orion on a multiday uncrewed trip around the moon. NASA hopes to put astronauts onboard for a lunar orbit in 2021.

Meanwhile, the crew aboard the International Space Station is testing technologies that will keep humans healthy and happy during an interplanetary cruise. Astronaut Scott Kelly recently completed a nearly yearlong visit to the station intended to reveal the effects of long-duration space travel on the human body (SN Online: 2/29/2016). And on April 10, a prototype inflatable habitat — the Bigelow Expandable Activity Module — arrived at the station and was attached to a docking port six days later. The station crew will inflate the module for the first time on May 26. No one will live in it, but over the next two years, astronauts will collect data on how well the habitat handles radiation, temperature extremes and run-ins with space debris.
Beyond that, the plans get fuzzy. The general idea is to construct an outpost in orbit around the moon as a testing and staging ground starting in the late 2020s. The first crew to Mars might land on the planet — or might not. One idea is to set up camp in Mars orbit; from there, astronauts could operate robots on the surface without long communication delays. Another idea has humans touching down on one of Mars’ two moons, Phobos or Deimos. When crews do land on the Martian surface, NASA envisions establishing a base from which astronauts could plan expeditions.

With so few details, it’s difficult for the space agency to identify specific technologies to invest in. “There have been lots of studies — we get a lot of grief that it’s nothing but studies,” said Bret Drake, an engineer at the Aerospace Corp. in El Segundo, Calif. “But out of the studies, there are a lot of common things that come to the top no matter what path you take.”

Any mission to Mars has to support astronauts for roughly 500 to 1,000 days. The mission has to deal with round-trip communication delays of up to 42 minutes. It will need the ability to land roughly 40-ton payloads on the surface of Mars (current robotic missions drop about a ton). Living off the land is also key, making use of local water and minerals. And astronauts need the ability to not just survive, but drive around and explore. “We want to land in a safe place, which is going to be geologically boring, but we want to go to exciting locations,” said Drake.

The technical and logistical challenges might be the easiest part. “We do know enough to pull this off,” Ramirez says. “The biggest problem is political will.” Congress has yet to sign off on funding this adventure (nor has NASA presented a budget — expected to be in the hundreds of billions of dollars), and future administrations could decide to kill it.

Multiple summit speakers stressed the importance of using technology that is proven or under development — no exotic engines or rotating artificial gravity habitats for now. And a series of small missions —baby steps to the moon and an asteroid before committing to Mars — could show progress that might help keep momentum (and public interest) alive.

“We thought going to the moon was impossible, but we got there,” says Ramirez. “If we dedicate ourselves as a nation to do something crazy, we’ll do it. I have no doubt.”

Jumping gene turned peppered moths the color of soot

Peppered moths and copycat butterflies owe their wing color-changing abilities to a single gene, two independent studies suggest.

A genetic tweak in a portion of the cortex gene that doesn’t make protein painted the speckled gray wings of peppered moths black, researchers report online June 1 in Nature. Genetic variants in DNA interspersed with and surrounding the cortex gene also help some tasty species of Heliconius butterflies mimic unpalatable species and avoid getting eaten by predators, a second team of scientists reports, also June 1 in Nature.
In the often-told evolutionary tale, the color shift in moths began as factories in Britain started to darken the skies with coal smoke during the Industrial Revolution in the 1800s. Victorian naturalists took note as a newly discovered, all-black carbonaria form of peppered moths (Biston betularia) blended into soot-covered backgrounds; the light-colored typica moths, which lacked the mutation, were easily picked off by birds. By 1970, nearly 99 percent of peppered moths were black in some localities. As air pollution decreased in the late 20th century, black moths became more visible to birds. As a result, carbonaria moths are now rare.

“This begins to unravel exactly what the original mutation was that produced the black … moths that were favored by natural selection” during much of the last century, says evolutionary biologist Paul Brakefield of the University of Cambridge in England. “It adds a new and exciting element to the story.”

Wing pattern changes in butterflies and peppered moths are textbook examples of natural selection, but the molecular details behind the adaptation have eluded scientists for decades. In 2011, researchers tracked the traits to a region of a chromosome all the species have in common (SN: 5/7/11, p. 11; SN: 9/24/11, p. 16). Which of the many genes in that region might be responsible remained a mystery.
In peppered moths, the region of interest stretches over about 400,000 DNA bases and contains 13 genes and two microRNAs. “There aren’t really any genes that scream out to you, ‘I’m involved in wing patterning,’” says evolutionary geneticist Ilik Saccheri at the University of Liverpool in England.
Saccheri and colleagues compared that region in one black moth and three typical moths. The researchers found 87 places where the black moth differed from the light-colored moths. Most of the differences were changes in single DNA bases — the information-carrying chemicals in DNA. Such genetic variants are known as SNPs for single nucleotide polymorphisms. One difference was the insertion of a 21,925-base-long stretch of DNA into the region. This big chunk of DNA contained multiple copies of a transposable element, or jumping gene. Transposable elements are viruslike pieces of DNA that copy and insert themselves into a host’s DNA.

By examining the DNA of hundreds more typica moths and ruling out mutations one by one, the team ended up with one candidate: the large transposable element that had landed in the cortex gene. But the jumping gene didn’t land in the DNA that encodes the protein. Instead it landed in an intron — a stretch of DNA that gets chopped out after the gene is copied into RNA and before a protein is made.

The jumping gene first landed in the cortex intron in about 1819, the researchers calculated from historical measurements of how common the trait was throughout history. That timing gave the mutation about 20 to 30 moth generations to spread through the population before people first reported sightings of the black moths in 1848. Saccheri and colleagues found the transposable element in 105 of 110 wild-caught carbonaria moths and none of the 283 typica moths tested. The remaining five moths are black because of another, unknown, genetic variation.

Similarly, Nicola Nadeau, an evolutionary geneticist at the University of Sheffield in England, and colleagues combed through more than 1 million DNA bases in each of five species of Heliconius butterflies. The researchers were looking for genetic variants associated with the presence or absence of yellow bands on the wings.

Nadeau’s team found 108 SNPs in all H. erato favorinus butterflies that have a yellow band on their hind wings. Most of those SNPs were in introns of the cortex gene or outside of the gene. Butterflies that lack the yellow band don’t have those SNPs.

Other DNA changes were found to draw yellow bars on the wings of different species of Heliconius butterflies, suggesting that evolution acted multiple times on the cortex gene with similar results.

The finding that the same gene influences wing patterns in butterflies and moths supports an idea that some genes are hot spots of natural selection, says Robert Reed, an evolutionary biologist at Cornell University.

None of the genetic differences in the butterflies or peppered moths change the cortex gene itself. That leaves open the possibility that the transposable element and SNPs aren’t doing anything to cortex, but may be regulating a different gene. But the evidence that cortex really is the gene upon which natural selection has acted is strong, says Reed. “I’d be surprised if they were wrong.”

Still, it’s not obvious how cortex changes wing patterns, says Saccheri. “We’re both equally puzzled about how it is doing what it appears to be doing.” The teams have evidence that cortex helps determine when certain wing scales grow. In butterflies and moths, the timing of wing scale development affects the color of the wings, says Reed. “You see colors popping up almost like a paint-by-numbers.”

Yellow, white and red scales develop first. Black scales come later. Cortex is known to be involved in cell growth. So varying levels of the protein may speed up development of wing scales, causing them to become colored, or slow their growth, allowing them to turn black, the researchers speculate.

Vaccines could counter addictive opioids

By age 25, Patrick Schnur had cycled through a series of treatment programs, trying different medications to kick his heroin habit. But the drugs posed problems too: Vivitrol injections were painful and created intense heroin cravings as the drug wore off. Suboxone left him drowsy, depressed and unable to study or go running like he wanted to. Determined to resume the life he had before his addiction, Schnur decided to hunker down and get clean on his own.

In December 2015, he had been sober for two years and had just finished his first semester of college, with a 4.0 grade point average. Yet, just before the holidays, he gave in to the cravings. Settling into his dorm room he stuck a needle in his vein. It was his last shot.
Scientists are searching for a different kind of shot to prevent such tragedies: a vaccine to counter addiction to heroin and other opioids, such as the prescription painkiller fentanyl and similar knockoff drugs. In some ways, the vaccines work like traditional vaccines for infectious diseases such as measles, priming the immune system to attack foreign molecules. But instead of targeting viruses, the vaccines zero in on addictive chemicals, training the immune system to usher the drugs out of the body before they can reach the brain.

Such a vaccine may have helped Schnur, a onetime computer whiz who grew up in the Midwest, far removed from the hard edges of the drug world. His overdose death reflects a growing heroin epidemic and alarming trend. In the 1960s, heroin was seen as a hard-core street drug abused mostly in inner cities. Now heroin is a problem in many suburban and rural towns across America, where it is used primarily by young, white adults — male and female, according to research published by psychiatrist Theodore Cicero of Washington University in St. Louis and colleagues in 2014 in JAMA Psychiatry.
His team’s surveys of nearly 2,800 patients in substance abuse treatment programs suggest a shift in the demographics of heroin users in recent years. In the 1960s, more than 80 percent of users took heroin as their first opioid. From 2000 to 2010, 75 percent of heroin users came to the drug because it was easier to get and less expensive than the prescription opioids they had been taking.

In recent decades, overdoses of both illicit and prescription drugs have surged. In 2014, overdose deaths surpassed deaths from motor vehicle accidents, the U.S. Centers for Disease Control and Prevention reported in January. In that year, 28,647 people died of opioid-related overdoses, primarily from prescription pain relievers and heroin.

“The opioid epidemic is devastating and the number of people dying demands an urgent intervention,” says Nora Volkow, director of the U.S. National Institute on Drug Abuse.

A family of drugs
The term opioid refers to a host of painkillers derived from the opium poppy as well as synthetic versions of its active compounds. Heroin is processed from morphine, which is extracted from the plant. Prescription medications such as Vicodin, Percocet, OxyContin and fentanyl are made from synthetic morphine, altered to produce different effects.

Currently, three medications, sold under various brand names, are available to help people with heroin or opioid addiction get clean and stay drug-free: methadone, buprenorphine and naltrexone. The treatments work, Volkow says, but not perfectly. Some addicted patients, such as Schnur, experience unwanted side effects from the daily or monthly treatments and stop using them. Others lack access to treatments due to high costs and strict federal limits on dispensing the drugs.

“Unfortunately, only a small percentage — about 25 percent — of people who could benefit from treatment actually get these medications,” Volkow says.
Round two for vaccines
Vaccines could offer an alternative to patients who have kicked their habit and want to stay clean, scientists say. The vaccines aim to make an addict immune to a drug’s effects, decreasing the motivation to seek more of the drug. That’s important, Volkow says, because over time the treatment may allow recovery of the overactive circuitry in the brain that pushes drug users to keep using.

The idea of antidrug vaccines isn’t new. Scientists began working on formulations in the 1970s, but those efforts were eclipsed by the availability of methadone. Methadone, a synthetic opioid, relieves withdrawal symptoms and cravings for heroin or prescription painkillers by acting on the same brain targets as the drugs, but in a slow, controlled manner, so patients can function normally without feeling high. But the treatment is a method for harm reduction, not a cure for addiction, and must be taken daily to be effective.

In the late 1990s, scientists resumed antidrug vaccine efforts, focusing on vaccines for everything from cocaine to nicotine to heroin (SN: 2/10/07, p. 90). Vaccines for nicotine and cocaine were tested in people, but worked for only a small percentage.

Now, to help combat the growing opioid addiction crisis, two vaccines for heroin users are advancing toward human trials and other antiopioid vaccines are in the pipeline, including one for fentanyl, now a popular street drug.

Among the antiheroin vaccines being tested, one — developed at the Scripps Research Institute in La Jolla, Calif. — spurs the immune system to attack heroin and helps eliminate it from the body so effectively that it can neutralize even lethal levels of the drug in animals. A second anti­heroin vaccine, developed at the Walter Reed Army Institute of Research in Silver Spring, Md., goes after two closely linked problems: It keeps heroin from reaching the brain while preventing HIV infection.

Addiction’s grip
Once a person is addicted, the fight to stay clean never ends, Volkow says. That’s because heroin and other addictive substances alter the brain’s pleasure circuits, producing changes that persist long after users stop taking the drug. Volkow, who has studied these effects for more than two decades, says addiction is a brain disease because of the structural and functional changes that occur.
Drugs of abuse produce their high by interacting with cells located in brain areas that govern reward, including the nucleus accumbens, a key region in the pleasure circuit. Though each type of drug works in a slightly different way, all addictive drugs increase the amount of the chemical dopamine in this area. Dopamine is a neurotransmitter, carrying signals between nerve cells, or neurons.

Opioids boost dopamine levels by stimulating molecules called mu receptors that sit on the surface of certain neurons. Normally, these receptors are activated by hormones and brain chemicals made in the body, such as endorphins, to reinforce pleasurable behavior such as eating, having sex or listening to music. A single dose of heroin, however, releases many times the amount of dopamine produced by a favorite food or song.

Dopamine fuels the high that people feel from taking an addictive drug, but other molecules help to get people hooked. Glutamate, a neurotransmitter that increases the chatter among cells in areas that govern learning and boost motivation, helps engrave the experience of a drug’s high into the brain. Memories of the high become so enduring that years later they can be reawakened. This long-lasting pull is why more than 60 percent of people with addiction experience relapse within the first year after they are discharged from treatment.

Taken over time, drugs of abuse can change signaling in a number of the brain’s circuits. Last year in Cell, Volkow and NIDA biochemist Marisela Morales outlined two common features of the addicted brain: a decreased sensitivity in the brain’s reward centers and disruption of circuits involved in self-control.

With repeated drug use, the number of dopamine receptors declines as the brain attempts to calm down, Volkow says. With fewer receptors available to take up dopamine molecules, it takes more stimulation to produce feelings of pleasure. Addicts soon find that they are no longer motivated by everyday activities that had been enjoyable or exciting, and they need higher doses of the drug to get the euphoric feelings once provided by smaller doses.

“The brain rapidly learns that the only thing that’s going to stimulate these pleasure circuits is the drug,” Volkow says. “That’s one of the components that drives drug-seeking behavior.” Eventually, the drug no longer produces a high. Instead, it becomes a necessity to stave off feelings of anxiety and despair.

Addiction also impairs dopamine functioning in the prefrontal cortex, an area of the brain that includes regions involved in analysis, decision making and self-control. “Taking drugs interferes with one’s capacity to make good decisions” and follow through, Volkow says. “An addict might say ‘I don’t want to take that drug.’ But they don’t have the capacity to easily change their behavior.”

Protect the brain
Vaccines, potentially, offer a “transformative” way to treat addiction, Volkow says, because the treatments can train the immune system to attack drug molecules before they reach the brain. Vaccines typically contain an agent that resembles a disease-causing virus, teaching the immune system to respond quickly when it encounters the invader. In designing vaccines, scientists try to provoke at least one of the human body’s primary immune responders: T cells, which attack infected cells, or B cells, which release antibodies that recognize hostile molecules and attach to them, targeting them for destruction.

Easier said than done. For starters, drug molecules are tiny, much smaller than a bacterium or virus, and are not easily detected by the immune system. In addition, the body’s immune system is set up to fight invaders that arrive in small groups. When an influenza virus makes its way into a body, the initial levels of virus in the blood are very low, Volkow says. But when people inject heroin, for example, many millions of drug molecules and their breakdown products quickly rush into the bloodstream. In recent years, researchers have found new ways to help call the immune system’s attention to such surges of “invading” drugs.

While developing one heroin vaccine, chemist Kim Janda of Scripps and colleagues noticed that antibodies to heroin molecules alone didn’t stop animals from getting high. That’s because once heroin gets into the body — whether it’s injected, snorted or smoked — it is broken down into its active components, 6-acetylmorphine, or 6-AM, and morphine. “Those two metabolites are the real drugs in heroin,” Janda says.

Typically, vaccines lead to production of antibodies that target a single invader. To get the immune system to notice both heroin and its metabolites, Janda joined forces with neurobiologist George Koob, director of the National Institute on Alcohol Abuse and Alcoholism, to design a multitarget vaccine. The vaccine “cocktail,” as Janda calls it, has three components: a large protein that carries the druglike molecules into the body; a molecule called a hapten, chemically designed to induce an immune response to heroin and its metabolites 6-AM and morphine; and finally, alum, an agent commonly added to vaccines to stimulate release of cytokines, proteins that help rally the immune cells to fight invaders.

Over the last six years, Janda’s group has tinkered with the hapten to help the antibodies get a tight grip on heroin, 6-AM and morphine. The hapten, along with the protein carrier, draws attention from the immune system’s T cells, which learn to recognize the drug molecules as invaders. Later, if heroin or its metabolites are detected in the blood, the T cells will “remember” the invaders and remove them.
In rats, the three-pronged vaccine generated high numbers of antibodies against the drug and its metabolites, blocking heroin’s action on the brain. Once vaccinated, the formerly addicted rats were unable to get high, even when injected with extremely high doses of the drug, Janda’s group reported in 2013 in the Proceedings of the National Academy of Sciences. The result was decreased drug-seeking behavior in the vaccinated rats. By contrast, control rats, and those vaccinated only against morphine, continued to seek higher doses of the drug.

The vaccine showed similar effectiveness in nonhuman primates, Janda reported in May at the American Psychiatric Association’s annual meeting in Atlanta. In addition, the vaccine is specific to heroin metabolites, not other opiates. A vaccine that’s too broad could potentially make patients immune to the effects of all prescription opioids, leaving them vulnerable if they become injured and need pain relief.

Janda’s team recently tested another antiopioid vaccine in animals, one that arms the body against fentanyl. When given to mice, the vaccine trained the animals’ immune systems to generate antibodies that bind to fentanyl and prevent it from traveling to the brain from the bloodstream. The results, published March 7 in Angewandte Chemie, showed that in mice, the antibodies neutralized high levels of the drug — more than 30 times a normal dose — for months after a series of three shots. By blocking the effects of the drug and its high, the vaccine could potentially curb drug-seeking behavior.

Another group is going after heroin and its strong tie to high HIV infection rates worldwide. Scientists at the Walter Reed Army Institute of Research are developing a dual-purpose vaccine, called H2, to treat heroin addiction while preventing HIV infection.

Biochemist Gary Matyas and his group at Walter Reed first designed a vaccine to stimulate antibodies against heroin. Similar to Janda’s antiheroin vaccine, haptens are bound to a protein carrier, spurring the immune system to create high levels of antibody to bind heroin and its metabolites in the blood and prevent it from crossing the blood-brain barrier. Users will then experience no euphoria or addictive reactions.

The researchers plan to combine the heroin vaccine with an HIV vaccine, a combination that’s much trickier to develop. Scientists have long been frustrated by the ability of the AIDS virus to mutate and evade the immune system. The virus constantly changes the makeup of the proteins on its surface so that antibodies have difficulty recognizing and attacking it. But researchers have found that targeting a region called V2 on the surface of the virus decreased the risk of HIV infection.

The vaccine, tested in volunteers in Thailand by the country’s Ministry of Public Health and Walter Reed scientists, protected about a third of participants against HIV infection, according to a 2009 report.

There’s no timeline for moving the H2 vaccine into human trials, Matyas says. His hope is that the vaccine will concurrently address the entwined epidemics. “If you can reduce heroin use, you can reduce the spread of HIV,” he says. “That’s why we’re focusing on both heroin and HIV in one vaccine.”

Extra help
While vaccines can’t be the only treatment for the opioid epidemic, they could offer users who want to abstain an additional and much needed option to deal with addiction. It’s not unusual for people to relapse, or to require more than one type of treatment, before finding a course of recovery that suits them, Volkow says.
Treating addiction like a disease that needs to be managed, such as diabetes or high blood pressure, with a multiplicity of treatment options would help addicts find a treatment that works well for them over the long haul, she says.

“Addiction is an extremely serious disease, with a high mortality rate and devastating consequences,” Volkow says. “We need to treat it very aggressively, and we need to have a variety of interventions so if one doesn’t work we have something else to offer the patient.”

Because relapse is common in addiction, Janda says he thinks that the antidrug vaccines’ value will come in helping people who want to abstain, but might falter in a weak moment. “Even if they try to do the drug, they’re not going to get the reward effects of the drug,” he says. “That means that they won’t spiral out of control and have to start all over again.”

Kathy Schnur, Patrick’s mother, remembers how, years into her son’s treatment, when the conversation turned to heroin — its euphoric high and mysterious spell — her son would confess to a desire to taste the drug “one more time.” A heroin vaccine would have taken a relapse off the table, she says. He would no longer have needed to make a daily decision to stay clean.

“If he knew he couldn’t get what he expected from the drug, it would remain a nonevent,” Schnur says. “Or, if he slipped up and tried it just one more time, the vaccine would prevent an overdose.”

Mars once had many moons

Mars’ misshapen moons, Phobos and Deimos, might be all that’s left of a larger family that arose in the wake of a giant impact with the Red Planet billions of years ago, researchers report online July 4 in Nature Geoscience.

The origin of the two moons has never been clear; they could be captured asteroids or homegrown satellites. But their orbits are hard to explain if they were snagged during a flyby, and previous calculations have had trouble reproducing locally sourced satellites. The new study finds that a ring of rocks blown off of the planet by a collision with an asteroid could have been a breeding ground for a set of larger satellites relatively close to the planet. Those moons, long since reclaimed by Mars, could have herded remaining debris in the sparsely populated outer part of the ring to form Phobos and Deimos.
Pascal Rosenblatt, a planetary scientist at the Royal Observatory of Belgium in Brussels, and colleagues ran computer simulations to show how the helper moons formed, did their duty and then fell to Mars, leaving behind a pair of moons similar to Phobos and Deimos.

The rain of moons is not over. While Deimos is in a stable orbit, Phobos is developing stress fractures as it slowly inches toward the Red Planet (SN: 12/12/15, p. 11).

Earliest evidence of monkeys’ use of stone tools found

Using tools is very old monkey business.

Capuchins in northeast Brazil have wielded stones to crack open cashew nuts for 600 to 700 years, researchers report July 11 in Current Biology. Unearthed “hammers” and “anvils” are the earliest evidence of monkey tool use to date.

Today, Brazilian bearded capuchin monkeys (Sapajus libidinosus) still open cashews by placing them on the flat surfaces of anvil rocks and pounding the nuts with large stones. Unlike pebbles and other rocks, the tool stones are distinctively heavy, blemished with wear marks, greased with cashew residue and clustered under cashew trees, Michael Haslam of the University of Oxford and colleagues found.
The team mapped where the monkeys left these modern tools scattered under cashew trees. When the researchers dug beneath dense, ancient cashew groves, they found 69 more stone tools — clustered in similar arrangements to modern tools, of similar heft and with the same distinctive wear marks — buried in three sequentially deeper layers of sediment. Radiocarbon dating of charcoal shows that the deepest tools rest in a layer of excavated soil dating back as early as 1266, suggesting that capuchins have been using stone tools to crack nuts for hundreds of years.
The new findings are “incredibly important,” says archaeologist Huw Barton of the University of Leicester in England. They “will help us reassess the earliest evidence of tool use by our own ancestors.”

Capuchins are the only monkeys in South America that frequently use tools. It’s a habit they evolved independently from other inventive primates, such as humans and chimps. (The three species last shared a common ancestor some 35 million years ago.) Understanding why capuchins picked up the skill could point to situations that inspired the rise of tool use across species, says primatologist and study coauthor Tiago Falótico of the University of Sao Paulo.

Elisabetta Visalberghi, a primatologist at the Institute of Cognitive Sciences and Technologies in Rome, agrees that it’s likely that the monkeys “used tools in the past as they do now.” But she doubts that wear-and-tear scratches — which Haslam’s team used to identify buried stones as tools — were indeed produced by cracking cashews. The nuts are relatively soft; so are the stones, she says. While Haslam’s team compared markings on modern and ancient tools, they didn’t test if new marks appear on modern stones after they are used by capuchins. Visalberghi says those experiments are “fundamental to evaluate the relevance of the results.”
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While this is not the first archaeological evidence of monkey tool use, it is the oldest by far. Haslam, Falótico and colleagues reported the first evidence last month in the Journal of Human Evolution: 10- to 50-year-old buried tools used by long-tailed macaques in Thailand. Before that, chimpanzees were the only primates other than humans with an ancient track record of tool use, dating back thousands of years (SN: 02/17/07, p. 99).

Compared with that of chimps, the record of capuchin tools is relatively young. But 600 to 700 years isn’t a final estimate, the researchers say. Even older monkey tools could rest in deeper soil under the cashew trees.