At first glance, the stories taking the top two spots in Science News’ review of 2016 have little in common. Scientists began searching decades ago for gravitational waves. Discussions of these subtle signals from dramatic and distant phenomena appear dozens of times in the SN archive starting as early as the 1950s. Their long-awaited discovery, our No. 1 story of the year, touched off celebration of a new era in astronomy.
Less expected, and far from subtle, was the sudden rise in Brazil of microcephaly cases, linked this year to Zika virus infections — our No. 2 story. Little was known about Zika before the outbreak, which delivered devastation and fear across the Americas. In fact, only a single previous mention of Zika exists in the SN archive, in a book review from the 1990s. But the stories have at least one thing in common: Both highlight the power of scientific discoveries to trigger our deepest human emotions. Pure elation as well as overwhelming dread can accompany research advances.
2016 brought many more sentiments, too. There was enthusiasm for the discovery of the exoplanet Proxima b, concern for the prospects of three-parent babies and feelings of potential but also impending peril in the openings of Arctic passageways.
The editors and writers at Science News also recognize that some of the best and most moving stories are those that are still unfolding. So, in addition to the discoveries of 2016, we review milestones, setbacks and other tales of unsteady progress. Sonia Shah writes about a new wave of infectious diseases; Tom Siegfried explores convergent failures in the field of particle physics; and Laurel Hamers covers key challenges for self-driving cars. Then, Science News writers share what science news they’re most excited about in the year to come. — Elizabeth Quill
Four proteins that can transform adult cells into embryonic-like ones can also turn back the aging clock, a new study in mice suggests.
Partial reprogramming of cells within prematurely aging mice’s bodies extended the rodents’ average life span from 18 weeks to 24 weeks, researchers report December 15 in Cell. Normal mice saw benefits, too: Muscles and pancreas cells healed better in middle-aged mice that got rejuvenation treatments than in mice that did not. The experiment could be evidence that epigenetic marks — chemical tags on DNA and proteins that change with age, experience, disease and environmental exposures — are a driving factor of aging. Some marks accumulate with age while others are lost. “It’s an inspiring paper,” says Jan van Deursen, a biologist at the Mayo Clinic in Rochester, Minn., who studies diseases of aging. He gives the paper an “A” for sparking imagination, but lower marks for practical applications to human aging because it would involve gene therapy and could be risky. “It’s all cool, but I don’t see that it could ever be applied in medicine,” he says. “We could be terribly wrong. Hopefully we are.”
Researchers reset the mice’s aging clock by genetically engineering the animals to make four proteins when the rodents were treated with the antibiotic doxycycline. Those four proteins — Oct4, Sox2, Klf4 and c-Myc — are known as “Yamanaka factors” after Shinya Yamanaka. The Nobel Prize‒winning scientist demonstrated in 2006 that the proteins could turn an adult cell into an embryonic-like cell known as an induced pluripotent stem cell, or iPS cell (SN: 11/3/12, p. 13; SN: 7/14/07, p. 29). The factors help strip away epigenetic marks that enable cells to know whether they are heart, brain, muscle or kidney cells, for example. As a result, stripped cells revert to the ultraflexible pluripotent state and are capable of becoming nearly any type of cell. Other researchers have used the Yamanaka factors to reprogram cells within living mice before, but those attempts resulted in the growth of tumors. (Cancer cells resemble stem cells in that they don’t have a specific identity and are “undifferentiated.”) Those tumors indicated to Alejandro Ocampo and colleagues that the proteins were rewriting epigenetic programming to take cells back to an undifferentiated state. But “you don’t need to go all the way back to pluripotency” to erase the marks associated with aging, says Ocampo, a stem cell biologist at the Salk Institute for Biological Studies in La Jolla, Calif. A milder reprogramming treatment might reverse aging without stripping away cells’ identity, leading to cancer, Ocampo and colleagues thought.
The researchers put genetically engineered mice with a premature aging disease called progeria on a regimen in which the animals were treated with doxycycline two days per week to turn on the Yamanaka factors. Mice that made the reprogramming proteins lived six weeks longer on average than mice that didn’t get the treatment. The mice didn’t get cancer, but still died prematurely (lab mice usually live two to three years on average). “We are far away from perfection,” Ocampo says.
Normally aging mice also got benefits from the treatment. When the animals were 1 year old (roughly middle-aged), the researchers treated them with doxycycline two days per week for three weeks. Treated mice were better able to repair muscles and replace insulin-producing cells in the pancreas than untreated mice. Not all organs fared as well, Ocampo says, citing preliminary evidence. Ongoing experiments will determine whether the epigenetic reprogramming can make the mice live any longer or healthier. People probably won’t be genetically engineered the way mice are. But chemicals and small molecules might also be able to wipe away epigenetic residue that builds up with aging and restore marks that were lost over time, returning to a pattern seen in youth, Ocampo suggests.
Researchers still don’t know whether all cells are rejuvenated by the treatment. Yamanaka factors may breathe new life into aging stem cells, allowing them to replenish damaged tissues. Or the factors may wake up senescent cells — cells that have shut down normal functions and cease to divide, but may send signals to neighboring cells that cause them to age (SN: 3/5/16, p. 8). Reviving senescent cells could be dangerous, says van Deursen; the body shuts cells down to prevent them from becoming cancerous.
Plenty of evidence indicates that resetting epigenetic programming can extend life, says Ocampo. He points to a recent report that Dolly the Sheep’s cloned sisters are aging normally (SN: 8/20/16, p. 6) as a hopeful sign that reprogramming probably isn’t dangerous, and might one day safely prevent many of the diseases associated with aging in people, if not lengthening life spans.
An experimental Ebola vaccine has triumphed in West Africa.
Of 5,837 people in Guinea who received a single shot of the vaccine, rVSV-ZEBOV, in the shoulder, none became infected with the virus 10 to 84 days after vaccination. That’s “100% protection,” researchers report December 22 in the Lancet.
World Health Organization researcher Ana Maria Henao-Restrepo and colleagues tested a “ring vaccination” approach, by immediately vaccinating family members and other contacts of people infected with Ebola. This strategy seemed to staunch the virus’s spread. Among 4,507 people never vaccinated or who got a delayed vaccine, 23 contracted Ebola.
The findings echo preliminary results reported in 2015, and offer a promising line of defense for future outbreaks. But scientists still do not know how long-lasting the vaccine’s protection would be.
In late 2013, West Africa saw the beginning of what would become the largest Ebola outbreak in history, with more than 11,300 deaths reported, and 28,616 cases in Guinea, Sierra Leone and Liberia. Since then, scientists have been racing to create a safe and effective vaccine.
A molecule originally proposed more than 40 years ago breaks the rules about how carbon connects to other atoms, scientists have confirmed. In this unusual instance, a carbon atom bonds to six other carbon atoms. That structure, mapped for the first time using X-rays, is an exception to carbon’s textbook four-friend limit, researchers report in the Jan. 2 Angewandte Chemie.
Although the idea for the structure isn’t new, “I think it has a larger impact when someone can see a picture of the molecule,” says Dean Tantillo, a chemist at the University of California, Davis who wasn’t part of the study. “It’s super important that people realize that although we’re taught carbon can only have four friends, carbon can be associated with more than four atoms.” Atoms bond by sharing electrons. In a typical bond two electrons are shared, one from each of the atoms involved. Carbon has four such sharable electrons of its own, so it tends to form four bonds to other atoms.
But that rule doesn’t always hold. In the 1970s, scientists made an unusual discovery about a molecule called hexamethylbenzene. This molecule has a flat hexagonal ring made of six carbon atoms. An extra carbon atom sticks off each vertex of the ring, like six tiny arms. Hydrogen atoms attach to the ring’s arms. And leftover electrons zip around the middle of the ring, strengthening the bonds and making the molecule more stable. When the scientists removed two electrons from the molecule, leaving it with a positive charge, some evidence suggested it might dramatically change its shape. It seemed to rearrange so that one carbon atom was bonded to six other carbons. But the researchers didn’t experimentally confirm that structure. Now, a different lab has revisited the question. Making this charged version of hexamethylbenzene is a challenge because it’s stable only in extremely strong acid, says study coauthor Moritz Malischewski, a chemist at the Free University of Berlin. And the experimental details in the old study were a bit fuzzy. But after a bit of tinkering, he managed to create the charged molecule. He and coauthor Konrad Seppelt crystallized it with some other molecules, and then used X-rays to get a three-dimensional map of the crystal structure.
The X-ray experiment confirmed what other scientists had suggested in the 1970s: When hexamethylbenzene lost two electrons, it reordered itself. One carbon atom jumped out of the ring and took a new position on top, turning the flat hexagonal ring into a five-sided carbon pyramid. And the carbon on top of the pyramid was indeed bonded to six other carbons — five in the ring below, and one above.
“This molecule is very exceptional,” says Malischewski. Though scientists have found other exceptions to carbon’s four-bond limit, this is the first time carbon has been shown associating with this many other carbon atoms.
When Malischewski measured the length of the molecule’s chemical bonds, the top carbon’s six bonds were each a bit longer than an ordinary carbon-carbon bond. A longer bond is generally less strong. So by picking more partners, that carbon has a slightly weaker connection to each one.
“The carbon isn’t making six bonds in the sense that we usually think of a carbon-carbon bond as a two-electron bond,” Tantillo says. That’s because the carbon atom still has only four electrons to share. As a result, it spreads itself a bit thin by sharing electrons among the six bonds.
This class of ancient marine invertebrates has now been firmly pegged as lophophorates, a group whose living members include horseshoe worms and lamp shells, concludes an analysis of more than 1,500 fossils, including preserved soft tissue.
The soft-bodied creatures, encased in conical shells, concealed U-shaped guts and rings of tentacles called lophophores that surrounded their mouths. Fossil analysis suggests that hyoliths used those tentacles and spines, called helens, to trawl the seafloor more than 500 million years ago, researchers report online January 11 in Nature.
For years, paleontologists have argued over where on the tree of life these bottom-feeders belonged. Some scientists thought hyoliths were closely related to mollusks, while others thought the odd-looking creatures deserved a branch all their own. This new insight into hyolith anatomy “settles a long-standing paleontological debate,” the researchers write.
Dinosaur fashion, like that of humans, is subject to interpretation. Bony cranial crests, horns or bumps may have served to woo mates or help members of the same species identify one another. While the exact purpose of this skull decor is debated, the standout structures tended to come with an even more conspicuous trait: bigger bodies.
Terry Gates, a paleontologist at North Carolina State University in Raleigh, and colleagues noticed an interesting trend in the fossil record of theropods, a group of dinosaurs that includes Tyrannosaurus rex and the ancestors of birds. Bigger beasts often sported skeletal headgear. Across the family tree, Gates and his team analyzed 111 fossils dating from 65 million to 210 million years ago, and the trend held true. It makes sense: “Dinosaur size matters in terms of how they will be visually talking to one another,” says Gates. “When you’re smaller, your means of visual communication would be different than when you’re giant.”
The researchers also calculated that over time, theropod lineages with head ornaments evolved giant bodies (larger than 1,000 kilograms) 20 times faster on average than those without. Ornaments might have supersized some dinos, but researchers aren’t sure. The analysis, which appeared September 27 in Nature Communications, suggests theropods had to reach at least 55 kilograms to grow the headgear.
But among big-boned relatives of modern birds, skull toppers weren’t in vogue. Many of these dinos grew heavier than 55 kilograms, but they instead sported feathers that resembled those used by modern birds for flight. That might be because bigger, bolder feathers and showy headwear served similar ends. Gates speculates: “Once you have a signaling device in the form of a feather, why grow a bony cranial crest?” For these plumed dinosaurs, feathers were in and bony ornaments were out.
Size matters Many large theropods, a group of dinosaurs that includes Tyrannosaurus rex and the ancestors of birds, had bony head ornaments such as crests, horns and bumps. New research suggests theropods had to reach at least 55.2 kilograms to grow the cranial decor. But big-boned dinos related to modern birds lacked the ornaments. Instead, they were decked out in feathers resembling those used by modern birds for flight.
An enduring source of magma on Mars fueled volcanic eruptions for billions of years, clues inside a rock flung from the Red Planet reveal.
The newfound rock belongs to a batch of meteorites called shergottites that originated from the same Martian volcanic system, researchers report February 1 in Science Advances. But the new rock is considerably older than its counterparts. While previously discovered shergottites solidified from Martian magma between 427 million and 574 million years ago, the new rock formed around 2.4 billion years ago, chemical analyses show. Such a wide range of ages means that a volcanic system on Mars churned out hot rocks from a stable source of magma for nearly half of the planet’s history, says study coauthor Thomas Lapen, a geologist at the University of Houston. That endurance could help scientists better understand Mars’ interior. “These are some of the longest-lived volcanoes in the solar system,” Lapen says.
Lapen and colleagues studied elements inside a Martian meteorite discovered in Algerian desert in 2012. Some of those elements serve as stopwatches that record the history of the rock. Isotopes of beryllium and aluminum, formed during exposure to cosmic rays, reveal that the rock zipped through space for around 1 million years. The steady decay of carbon 14 — left behind after cosmic ray collisions — suggests that the rock landed on Earth roughly 2,300 years ago. By combining these two measurements, the researchers found that the meteorite probably blasted off Mars alongside other shergottites a little over a million years ago. This exodus probably followed a massive impact in Mars’ volcano-filled Tharsis region. The rocks share more than their exit route, the researchers found. Chemical similarities between the meteorites suggest that they all originate from the same source of hot rock deep within the Red Planet. That’s surprising given that the mix of radioactive elements inside the newfound meteorite suggests it solidified 1.8 billion years earlier than the next oldest shergottite, Lapen says.
Mars is known to have many volcanic systems across its surface, all fed by magma upwelling from the planet’s depths. Studies have previously suggested that some of these systems operated for billions of years. Though little is known about the Martian interior, many scientists had assumed that the magma feeding this volcanism changed over time as the Martian interior mixed. The absence of any difference in composition of the shergottites suggests Mars’ interior is relatively stagnant. That may result from Mars’ lack of plate tectonics, a process that helps blend Earth’s innards, Lapen proposes. Understanding the differences between Earth and Mars could help reveal why the two planets took such different trajectories, with Earth so much more life-friendly than Mars (SN: 5/2/15, p. 24). Similarities between the shergottites could have another explanation, says planetary scientist Stephanie Werner of the University of Oslo. Large impacts can melt rocks, resetting their age. The shergottites may have formed around the same time billions of years ago before some had their ages altered by impacts over time, she proposes.
Upcoming missions will help illuminate what’s going on beneath the Martian surface, says James Head, a planetary scientist at Brown University in Providence, R.I. NASA’s InSight lander, currently slated for launch in 2018, will use seismic activity to map the Red Planet’s interior.
In A.D. 185, Chinese records note the appearance of a “guest star” that then faded away over the span of several months. In 1572, astronomer Tycho Brahe and many others watched as a previously unknown star in the constellation Cassiopeia blasted out gobs of light and then eventually disappeared. And 30 years ago, the world witnessed a similar blaze of light from a small galaxy that orbits the Milky Way. In each case, humankind stood witness to a supernova — an exploding star — within or relatively close to our galaxy (representative border in gray, below).
Here’s a map of six supernovas directly seen by human eyes throughout history, and one nearby explosion that went unnoticed. Some were type 1a supernovas, the detonation of a stellar core left behind after a star releases its gas into space. Others were triggered when a star at least eight times as massive as the sun blows itself apart.
BOSTON — A fungus among us may tip the body toward developing asthma.
There’s mounting evidence that early exposure to microbes can protect against allergies and asthma (SN Online: 7/20/16). But “lo and behold, some fungi seem to put kids at risk for asthma,” microbiologist Brett Finlay said February 17 at a news conference during the annual meeting of the American Association for the Advancement of Science.
Infants whose guts harbored a particular kind of fungus — a yeast called Pichia — were more likely to develop asthma than babies whose guts didn’t have the fungus, Finlay reported. Studies in mice and people suggest that exposure to some fungi can both trigger and exacerbate asthma, but this is the first work linking asthma to a fungus in the gut microbiome of infants. Finlay, of the University of British Columbia in Vancouver, and his colleagues had recently identified four gut bacteria in Canadian infants that seem to provide asthma protection. To see if infants elsewhere were similarly protected by such gut microbes, he decided to look at another population of children with an asthma rate similar to Canada’s (about 10 percent). He and his colleagues sampled the gut microbes of 100 infants in rural Ecuador and followed up five years later.
The researchers identified several factors that might influence risk of developing asthma, such as exposure to antibiotics, having respiratory infections, and whether or not the infants were breastfed. Of the 29 infants in the high-risk asthma group, more than 50 percent had asthma by age 5, Finlay said.
Surprisingly, the strongest predictor of whether a child developed asthma wasn’t bacterial. It was the presence of Pichia. And the yeast wasn’t protective; it tipped the scales toward asthma.
Finlay speculated that molecules made by the fungi interact with the infants’ developing immune systems in a way that somehow increases asthma risk. It isn’t clear how the infants’ guts acquire the fungus; some species of Pichia are found in soil, others in raw milk and cheese. Finlay and his colleagues are now going to look for the fungus in Canadian children’s gut microbes..
The researchers also looked at other gut microbe‒related factors that upped the Ecuadorean children’s asthma risk. Children with access to clean water had higher asthma rates, Finlay said. While drinking clean water helps people avoid several ills such as cholera, the link to asthma highlights how some dirt can be protective, he said. “We’ve cleaned up our world too much.” This research underscores that caution should be used when generalizing about our intestinal flora. “What’s emerging is that it is very personalized,” gastroenterologist Eran Elinav of the Weizmann Institute of Science in Rehovot, Israel, said at the news conference. For example, evidence implicates some fungi in the development of inflammatory bowel disease, Elinav said, but it depends on the individual.
For a scientist, conducting a scientific study is walking into a minefield of potential biases that could detonate all over the results. Are the mice in the study randomly distributed among treatment groups? Does the person evaluating an animal’s behavior know what treatment the mouse got — and thus have an expectation for the outcome? Are there enough subjects in each group to reduce the odds that the results are due to chance?
“I think we’re getting increasingly better at identifying these risks and identifying clever and practical solutions,” says Hanno Würbel, an applied ethologist at the University of Bern in Switzerland. “But it’s not all obvious, and if you look back at the history of science you find that these methods have accumulated through a learning process.”
In theory, every time scientists design an experiment, they keep an eye out for these and other potential sources of bias. Then, when scientists submit the study design for approval or write journal articles about the work, they share that research design with their colleagues.
But scientists may be leaving some rather key bits out of their reports. Few animal research applications and published research reports include specific mentions of key factors used to eliminate bias in research studies, Würbel and colleagues Lucile Vogt, Thomas Reichlin and Christina Nathues report December 2 in PLOS Biology. The results suggest that the officials who approve animal research studies — and the scientists who peer review studies before publication — are trusting that researchers have accounted for potential biases, whether or not there is evidence to support that trust.
The team gained access to 1,277 applications for animal experiments submitted to the Swiss government in 2008, 2010 and 2012. The researchers examined the applications for seven common measures used to prevent bias: Randomization, calculations to make sure sample sizes were large enough, not telling the experimenter what treatment will be administered to the next animal, blinding the experimenter during testing to which animals received which treatment, criteria used to include or exclude subjects (say, the animal’s age or sex), explicitly stating the primary outcome to be measured and plans for statistical analysis of the data.
Most of the time, the applications didn’t mention how or whether any of those measures were considered. Scientists included statistical plans 2.4 percent of the time and sample size calculations only 8 percent of the time. Even the primary outcome variable — the main objective measured in the study — was mentioned in only 18.5 percent of the applications.
Würbel’s group also looked at 50 publications that came out of some of those animal research applications that were ultimately approved. Here, scientists were better about reporting their effort to stave off bias in their studies. If scientists mentioned one of the seven efforts to combat bias in their animal experiment applications, they were more likely to mention it when their final papers were published. But they still only reported the statistical plan 34 percent of the time, and none of the 50 papers reported sample size calculations. Switzerland’s animal research application process didn’t actually require that any of these measures of bias be disclosed, Würbel notes. But “unless [the licensing officials] know the studies have been designed rigorously, they can’t assess the benefit.” The implication, the researchers suggest, is that authorities approving the studies trusted that the scientists knew what they were doing, and that peer reviewers and editors trusted that the authors of journal articles took those forms of bias into account.
Was that trust well placed? To find out, Reichlin, Vogt and Würbel surveyed 302 Swiss scientists who do experiments on living organisms, asking about the efforts they made to combat bias, and how often they reported those efforts. When asked directly, scientists said that of course they control their studies for certain risks of bias. The vast majority — 90 percent — reported that they included the primary outcome variable, and 82 percent included a statistical analysis plan. A full 69 percent reported that they calculated their sample sizes. Most also reported that they wrote these antibias efforts into their latest published research article.
But when the team probed deeper, asking scientists specific questions about what methods they used to combat bias, “you find out they don’t know much about methods,” Würbel notes. Only about 44 percent of the researchers knew about the guidelines for how to report animal experiments, even though 51 percent of them had published in a journal that endorsed those guidelines, the researchers report December 2 in PLOS ONE.
“This is a type of empirical work that we need, to see how people think and what they do,” says John Ioannidis, a methods researcher at Stanford University in California.
Just because scientists aren’t reporting certain calculations or plans doesn’t mean that their research will be subject to those biases. But without efforts to rigorously prevent bias, it can sneak in — subjects that aren’t randomly assigned properly, or an experimenter who unconsciously leans toward one result or another. Too small of a sample size and a researcher could detect a difference that disappears in a larger group. If a researcher knows which animals got which treatment, they may unconsciously focus more carefully on some aspects of the treated animals’ behavior — ignoring similar behavior in the control. And that can result in studies that are tougher to replicate — or that can’t be replicated at all.
None of this means that scientists are ill-educated or performing science badly, notes Malcolm Macleod, a neurologist at the University of Edinburgh. “I think there’s a temptation to make this binary, [to say] people don’t know so we need to train them,” he says. “The fact is most scientists know a bit … [but] everyone has something they can do better.”
How do you make scientists take more actions against bias, and then report what they’ve done? Journals, funding bodies and agencies approving animal research projects could require more information of scientists. Journals could require checklists for reporting methods, for example. Journals or funding bodies could also require full preregistration of animal studies, where a scientist gives all the details of a study and how it will be analyzed before the experiments are ever performed. (Such pre-registration became mandatory for clinical studies in humans in the United States in 2000.) Detailed reporting isn’t complete insurance against an irreproducible result, but “the more information you have, the easier it is to reproduce,” says Vogt, who studies animal welfare at the University of Bern.
Some scientists might worry that preregistration is too onerous, or that it could straitjacket researchers into unproductive studies. It would be frustrating, after all, to be stuck with a hypothesis that is clearly not bearing out, when the data provide tantalizing hints of another path to pursue. But it’s possible to provide the flexibility to pursue interesting questions, while still making sure the studies are rigorous, Ioannidis says.
But when scientists don’t know sources of bias in the first place, more education might be a good place to start. “When I first came into the lab for my master’s thesis, I had a lot of information [about research design] but I wasn’t ready to apply it,” Vogt explains. “I needed guidance through the steps of how to plan an experiment, and how to plan to report the experiment afterward.” Education doesn’t stop when graduate students leave the classroom, and more continuing education might help scientists — students and emeriti alike — recognize unfamiliar sources of bias and provide tools to combat it.
