As our first beach vacation with two little kids loomed, I had to do one of those chores that sounds easy but turns out to be anything but. I had to buy sunscreen. It seems like the task should take five minutes on Amazon. But as any parent with an internet connection knows, the choice is fraught.
You can pick from formulas that block rays with chemicals or minerals such as zinc oxide. SPFs can surpass 100. There are lotions and sprays, “organic” and “natural,” “sensitive” and “sport.” Some are marketed specifically for kids. Some are endorsed by various interest groups. And then there’s the cost. Highly rated sunscreens on Amazon vary in cost by 3,000 percent. Amid the chaos, I ended up picking an SPF 30 and being done with it.
With the beach vacation behind us, I’ve had the presence of mind to take a clear-eyed look at the sunscreen boondoggle. It seems that my trouble was in some ways a mess of my own making. I was distracted by zippy marketing words that obscured the core attributes of a good sunscreen. It turns out that the task can be pretty simple, if you keep a few key things in mind.
Look for SPF of 30 or higher. The sun protection factor is a measurement that tells you how long the sunscreen will protect your skin from sunburn-causing ultraviolet-B rays, as compared to no sunscreen at all. Sunscreens with an SPF of 30 will protect you from UV-B rays for 30 times longer than normal. Say you’d normally burn after 20 minutes in the sun without any sunscreen. After you correctly apply a sunscreen with SPF 30, you’d be able to go 10 hours. Sunscreens with an SPF of 30 will block 97 percent of UV-B rays. There may be diminishing returns as the SPF number goes up, though. There’s little evidence that SPFs over 50 offer increasing protection.
Make sure the sunscreen says “broad spectrum” on the label. That means the sunscreen will thwart both UV-A and UV-B rays. UV-A rays are thought to be responsible for deep skin damage, while UV-Bs are the ones that cause sunburns. Both flavors of the sun’s rays can increase the risk of skin cancer.
Choose one that’s water resistant. That doesn’t mean that water won’t wash it off. No sunscreen is completely waterproof, a fact that means sunscreens are no longer allowed to make that claim.
Don’t necessarily trust the ratings. Of the sunscreens in the top 1 percent on Amazon, a full 40 percent of them failed to meet the criteria set out by the American Academy of Dermatology — SPF of 30 or higher, broad spectrum and water resistant, a recent JAMA Dermatology paper found.
Use it. As study coauthor Steve Xu of Northwestern University says, “Picking the right product is only the first step. Using it correctly is just as important.” Put sunscreen on to your kids before they go outside, so the sunscreen can soak in. Make sure to cover all exposed skin, including the tops of ears and toes. And reapply every two hours, or immediately after your kids get out of water.
Those are the main points. Of course, you could choose to wade through a lot more weeds in the decision. Sunscreens based on physical blockers, such as zinc oxide or titanium dioxide, reflect the sun’s rays. Chemical blockers such as oxybenzone absorb the rays and get rid of the extra energy in harmless ways. Mineral-based sunscreens may be less likely to irritate babies’ and children’s skin than chemical blockers, for instance.
The jury is still out on spray sunscreen, which aerosolizes the particles and promises fewer child chase-downs. The FDA has called for more data to evaluate those. And then there’s the question of sunscreen for babies younger than six months. Most sources say that when possible, opt for shade and hats instead of sunscreen for the littlest babies.
So as you prepare for your time in the sun, stick to a few basic facts to help you choose a sunscreen. Instead, apply the time you save toward forcing cute sunhats on your squirmy kids.
Fractions of a second after food hits the mouth, a specialized group of energizing nerve cells in mice shuts down. After the eating stops, the nerve cells spring back into action, scientists report August 18 in Current Biology. This quick response to eating offers researchers new clues about how the brain drives appetite and may also provide insight into narcolepsy.
These nerve cells have intrigued scientists for years. They produce a molecule called orexin (also known as hypocretin), thought to have a role in appetite. But their bigger claim to fame came when scientists found that these cells were largely missing from the brains of people with narcolepsy. People with narcolepsy are more likely to be overweight than other people, and this new study may help explain why, says neuroscientist Jerome Siegel of UCLA. These cells may have more subtle roles in regulating food intake in people without narcolepsy, he adds.
Results from earlier studies hinted that orexin-producing nerve cells are appetite stimulators. But the new results suggest the opposite. These cells actually work to keep extra weight off. “Orexin cells are a natural obesity defense mechanism,” says study coauthor Denis Burdakov of the Francis Crick Institute in London. “If they are lost, animals and humans gain weight.”
Mice were allowed to eat normally while researchers eavesdropped on the behavior of their orexin nerve cells. Within milliseconds of eating, orexin nerve cells shut down and stopped sending signals. This cellular quieting was consistent across foods. Peanut butter, mouse chow, a strawberry milkshake and a calorie-free drink all prompted the same response. “Foods with different flavors and textures had a similar effect, implying that it is to do with the act of eating or drinking, rather than with what is being eaten,” Burdakov says. When the eating ended, the cells once again resumed their activity. When Burdakov and colleagues used a genetic technique to kill orexin nerve cells, mice ate more food than normal, behavior that led to weight gain, the team found. But a reduced-calorie diet slimmed these mice down. The results suggest that giving orexin to people who lack it may reduce obesity. But that might not be a good idea. An overactive orexin system has been tied to stress and anxiety, Burdakov says. Orexin’s link to stress raises a different possibility —that anxiety can be reduced by curbing orexin nerve cell activity. “And our study suggests that the act of eating can do just that,” Burdakov says. “This provides a candidate explanation for why people turn to eating at times of anxiety.”
WASHINGTON — Vocally warming up puts more dazzle into a bird’s singing for the day, a new test shows, perhaps helping to explain widespread outbursts of birdsong at dawn.
Males of Puerto Rico’s Adelaide’s warblers (Setophaga adelaidae) start trilling through their repertoires of 30 or so songs while it’s still pitch black. Tracking the songs of individual males showed that the order of performance had a strong effect on performance quality, behavioral ecologist David Logue said August 17 at the North American Ornithological Conference. In the early versions of particular songs, males didn’t quickly change pitch as well as they did later, Logue, of the University of Lethbridge in Canada, and colleagues found.
This was the first test for a warm-up effect for daily singing among birds, Logue said. To catch the full stretch of repetitions of songs, Orlando J. Medina (now with the U.S. Fish and Wildlife Service) had to beat the warblers at getting out of the nest in the morning. His recordings of each of nine males’ morning performance for four days allowed computer analysis of how fast a male swept through his trills.
Time of day alone didn’t explain the improvement in singing. So Logue and study coauthor Hannes Schraft, now at San Diego State University, don’t think that factors like increasing light or rising temperatures could explain the improvements. The robust effect of repetition leads Logue to propose what may be a new explanation for big dawn choruses: Males warming up sooner would fare better in competing for mates. Over time, a melodious arms race could have broken out as earlier warm-ups were beaten by even earlier ones.
Thirsty zebra finches “drink” their body fat. The songbirds are the first birds shown to get through a day without water by breaking down adipose tissue to stay hydrated, says evolutionary physiologist Ulf Bauchinger.
Two earlier tests of deprived birds summoning water from their tissues report that birds rely on protein. But zebra finches (Taeniopygia guttata) coped with one-day droughts in the lab not by breaking down such tissues as muscle but with the safer choice of metabolizing fat, say Bauchinger, Joanna Rutkowska and their colleagues at Jagiellonian University in Kraków, Poland. In comfortable temperatures and humidity, the little birds (averaging 13.5 grams in weight) produced about 0.444 grams of water metabolically. That boost would have taken large amounts of fleshy moist protein, equivalent to one-third the mass of their flight muscles or three times the mass of their hearts, the researchers say online August 31 in the Journal of Experimental Biology. “Exciting,” says Alexander Gerson of the University of Massachusetts Amherst, whose own work has shown birds taking the protein route. Gerson’s interest in animals deriving water by metabolizing body parts traces to research on migratory birds surviving several thousand kilometers of flight across the Sahara. His wind-tunnel tests of five-hour flights in dry air suggested that birds were fueling their flight with energy from fat reserves but were supplementing with water produced by breaking down protein.
What deprived birds do when they’re not migrating, however, might involve different trade-offs. But Gerson’s work with house sparrows kept from water still showed evidence of metabolizing proteins.
Unlike house sparrows, zebra finches have an evolutionary history of life in dry places, such as arid Australia. To see their water-management techniques, the researchers in Poland created total food and/or water shortages for lab birds just doing mundane finch things in cages instead of crossing a desert.
All the birds reached the end of their bad day without signs of dehydration, the researchers found. But 12 birds deprived of food and water showed more total fat loss than another 12 birds allowed to drink but not eat. Parched finches had 42 percent less fat than birds that had access to drinking water. Measures of lost lean tissue, including protein-rich muscle, barely differed.
Other bird species might respond to water shortages in the same way, Rutkowska speculates. Her test method differs a bit from the sparrow work. Gerson muses that zebra finches, with arid lands in their native range, might have different thresholds for metabolizing fat versus protein than house sparrows do.
For humans, Rutkowska says she gets asked about implications for dieting. Her answer: Sorry, no evidence of miracle shortcuts here.
Few people today could recite the scientific accomplishments of 19th century physician Julius Petri. But almost everybody has heard of his dish.
For more than a century, microbiologists have studied bacteria by isolating, growing and observing them in a petri dish. That palm-sized plate has revealed the microbial universe — but only a fraction, the easy stuff, the scientific equivalent of looking for keys under the lamppost.
But in the light — that is, the greenhouse-like conditions of a laboratory — most bacteria won’t grow. By one estimate, a staggering 99 percent of all microbial species on Earth have yet to be discovered, remaining in the shadows. They’re known as “microbial dark matter,” a reference to astronomers’ description of the vast invisible matter in space that makes up most of the mass in the cosmos. In the last decade or so, though, scientists have developed new tools for growing bacteria and collecting genetic data, allowing faster and better identifications of microbes without ever removing them from natural conditions. A device called the iChip, for instance, encourages bacteria to grow in their home turf. (That device led to the discovery of a potential new antibiotic, in a time when infections are fast outwitting all the old drugs.) Recent genetic explorations of land, water and the human body have raised the prospect of finding hundreds of thousands of new bacterial species.
Already, the detection of these newfound organisms is challenging what scientists thought they knew about the chemical processes of biology, the tree of life and the manner in which microbes live and grow. The secrets of microbial dark matter may redefine how life evolved and exists, and even improve the understanding of, and treatments, for many diseases.
“Everything is changing,” says Kelly Wrighton, a microbiologist at Ohio State University in Columbus. “The whole field is full of enthusiasm and discovery.” Counter culture Microbiologists have in the past discovered new organisms without petri dishes, but those experiments were slow going. In one of her first projects, Tanja Woyke analyzed the bacterial community huddled inside a worm that lives in the Mediterranean Sea. Woyke, a microbiologist at the U.S. Department of Energy’s Joint Genome Institute in Walnut Creek, Calif., and colleagues published the report in Nature in 2006. It was two years in the making.
They relied on metagenomics, which involves gathering a sample of DNA from the environment — in soil, water or, in this case, worm insides. After extracting the genetic material of every microbe the worm contained, Woyke and colleagues determined the order, or sequences, of all the DNA units, or bases. Analyzing that sequence data allowed the researchers to infer the existence of four previously unknown microbes. It was a bit like obtaining boxes of jigsaw puzzle pieces that need assembly without knowing what the pictures look like or how many different puzzles they belong to, she says. The project involved 300 million bases and cost more than $100,000, using the time-consuming methods available at the time. Just as Woyke was wrapping up the worm endeavor, new technology came online that gave genetic analysis a turbo boost. Sequencing a genome — the entirety of an organism’s DNA — became faster and cheaper than most scientists ever predicted. With next-generation sequencing, Woyke can analyze more than 100 billion bases in the time it takes to turn around an Amazon order, she says, and for just a few thousand dollars. By scooping up random environmental samples and searching for DNA with next-generation sequencing, scientists have turned up entirely new phyla of bacteria in practically every place they look. In 2013 in Nature, Woyke and her colleagues described more than 200 members of almost 30 previously unknown phyla. Finding so many phyla, the first big groupings within a kingdom, tells biologists that there’s a mind-boggling amount of uncharted diversity.
Woyke has shifted from these broad genetic fishing expeditions to working on individual bacterial cells. Gently breaking them open, she catalogs the DNA inside. Many of the organisms she has found defy previous rules of biological chemistry. Two genomes taken from a hydrothermal vent in the Pacific Ocean, for example, contained the code UGA, which stands for the bases uracil, guanine and adenine in a strand of RNA. UGA normally separates the genes that code for different proteins, acting like a period at the end of a sentence. In most other known species of animal or microbe, UGA means “stop.” But in these organisms, and one found about the same time in a human mouth, instead of “stop,” the sequence codes for the amino acid glycine. “That was something we had never seen before,” Woyke says. “The genetic code is not as rigid as we thought.”
Other recent finds also defy long-held notions of how life works. This year in the ISME Journal, Ohio State’s Wrighton reported a study of the enzyme RubisCO taken from a new microbial species that had never been grown in a laboratory. RubisCO, considered the most abundant protein on Earth, is key to photosynthesis; it helps convert carbon from the atmosphere into a form useful to living things. Because the majority of life on the planet would not exist without it, RubisCO is a familiar molecule — so familiar that most scientists thought they had found all the forms it could take. Yet, Wrighton says, “we found so many new versions of this protein that were entirely different from anything we had seen before.”
The list of oddities goes on. Some newly discovered organisms are so small that they barely qualify as bacteria at all. Jillian Banfield, a microbiologist at the University of California, Berkeley, has long studied the microorganisms in the groundwater pumped out of an aquifer in Rifle, Colo. To filter this water, she and her colleagues used a mesh with openings 0.2 micrometers wide — tiny enough that the water coming out the other side is considered bacteria-free. Out of curiosity, Banfield’s team decided to use next-generation sequencing to identify cells that might have slipped through. Sure enough, the water contained extremely minuscule sets of genes. “We realized these genomes were really, really tiny,” Banfield says. “So we speculated if something has a tiny genome, the cells are probably pretty tiny, too.” And she has pictures to prove it. Last year in Nature Communications, she and her team published the first images (taken with an electron microscope) and detailed description of these ultrasmall microbes (see, right). They are probably difficult to isolate in a petri dish, Banfield says, because they are slow-growing and must scavenge many of the essential nutrients they need from the environment around them. Part of the price of a minigenome is that you don’t have room for the DNA to make everything you need to live.
Relationship status: It’s complicated Banfield predicts that an “unimaginably large number” of species await in every cranny of the globe — soil, rocks, air, water, plants and animals. The human microbiome alone is probably teeming with unfamiliar microbial swarms. As a collection of organisms that live on and in the body, the human microbiome affects health in ways that science is just beginning to comprehend (SN: 2/6/16, p. 6).
Scientists from UCLA, the University of Washington in Seattle and colleagues recently offered the most detailed descriptions yet of a human mouth bacterium belonging to a new phylum: TM7. (TM stands for “Torf, mittlere Schicht,” German for a middle layer of peat; organisms in this phylum were first detected in the mid-1990s in a bog in northern Germany.) German scientists found TM7 by sifting through soil samples, using a test that’s specific for the genetic information in bacteria. In the last decade, TM7 species have been found throughout the human body. An overabundance of TM7 appears to be correlated with inflammatory bowel disease and gum disease, plus other conditions.
Until recently, members of TM7 have stubbornly resisted scientists’ efforts to study them. In 2015, Jeff McLean, a microbiologist at the University of Washington, and his collaborators finally isolated a TM7 species in a lab and deciphered its full genome. To do so, the team combined the best of old and new technology: First the researchers figured out how to grow most known oral bacteria together, and then they gradually thinned down the population until only two species remained: TM7 and a larger organism.
“The really remarkable thing is we finally found out how it lives,” McLean says, and why it wouldn’t grow in the lab. They discovered that this species of TM7, like the miniature bacteria in Colorado groundwater, doesn’t have the cellular machinery to get by on its own. Even more unusual, these bacteria pilfer missing amino acids and whatever else they need by latching on, like parasites, to a larger bacterium. Eventually they can kill their host. “We think this is the first example of a bacterium that lives in this manner,” McLean says.
He expects to see more unusual relationships among microbes as the dark matter comes to light. Many have evaded detection, he suspects, because of their small size (sometimes perhaps mistaken for bacterial debris) and dependence on other organisms for survival. In 2013 in the Proceedings of the National Academy of Sciences, McLean and colleagues were the first to describe a member of another uncultivated phylum, TM6. They found this group growing in the slime in a hospital sink drain. Later studies determined that the organism lives by tucking itself inside an amoeba. One of the greatest hopes for microbial dark matter exploration is that newly found microbes might provide desperately needed antibiotics. From the 1940s to the 1960s, scientists discovered 10 new classes of drugs by testing chemicals found in soil and elsewhere for action against common infections. But only two classes of medically important antibiotics have been discovered in the last 30 years, and none since 1997. Some major infections are at the brink of being unstoppable because they’ve become resistant to most existing drugs (SN Online: 5/27/16). Many experts think that natural sources of antibiotics have been exhausted.
Maybe not. In 2015, a research team led by scientists from Northeastern University in Boston captured headlines after describing in Nature a new chemical extracted from a ground-dwelling bacterium in Maine. The scientists isolated the organism using the iChip, a thumb-sized tool that contains almost 400 separate wells, each large enough to hold only an individual bacterial cell plus a smidgen of its home dirt. The bacteria grow on this scaffold in part because they never leave their natural surroundings. In lauding the discovery, Francis Collins, director of the National Institutes of Health, called the iChip “an ingenious approach that enhances our ability to search one of nature’s richest sources of potential antibiotics: soil.” So far, the research team has discovered about 50,000 new strains of bacteria.
One strain held an antibiotic, named teixobactin (SN: 2/7/15, p. 10). In laboratory experiments, it killed two major pathogens in a way that did not appear easily vulnerable to the development of resistance. Most antibiotics work by disrupting a microbe’s survival mechanism. Over time, the bacteria genetically adapt, find a work-around and overcome the threat. This new antibiotic, however, prevents a microbe from assembling the molecules it needs to form an outer wall. Since the antibiotic interrupts a mechanical process and not just a specific chemical reaction, “there’s no obvious molecular target” for resistance, says Kim Lewis, a microbiologist at Northeastern. Everything is illuminated Some microbiologists feel like astronomers who, after years of staring up into the dark, were just handed the Hubble Space Telescope. Billions of galaxies are coming into view. Banfield expects this new microbial universe to be mapped over the next few years. Then, she says, an even more exciting era begins, as science explores how these dark matter bacteria make a living. “They are doing a lot of things, and we have no idea what,” she says.
Part of the excitement comes from knowing that microbes have a history of granting unexpected solutions to problems that scientists never expected to solve. Consider that the enzyme that makes the laboratory technique PCR possible came from organisms that live inside the thermal vents at Yellowstone National Park. PCR, which works like a photocopier to make multiple copies of DNA segments, is now used across a range of situations, from diagnosing cancer to paternity testing. CRISPR, a powerful gene-editing technology, relies on “molecular scissors” that were found in bacteria (SN: 9/3/16, p. 22).
Banfield estimates that 30 to 50 percent of newly discovered organisms contain proteins that never met a petri dish. Their function in the chemistry of life is an obscure mystery. Since microbes are the world’s most abundant organism, Banfield says, “the vast majority of life consists of biochemistry we don’t understand.” But once we do, the future could be very bright.
For chickens, a dip in the sandbox is good hygiene.
Cage-free flocks that “bathe” by flapping around in diatomaceous earth (a fine dust of fossilized algae) and sand prevent serious mite infections, researchers report September 14 in the Journal of Economic Entomology. Major infections of more than 100 mites per bird make hens lay 2 to 4 percent fewer eggs on average. So access to boxes filled with dust, which look like tiny sandboxes, makes sense for birds’ health and for farmers’ wallets.
Dust baths damage mites’ waxy outer coating and kill the pests by drying them out. Scientists already knew dust can help manage mites in badly infested birds but weren’t sure if it could also be preventative.
Researchers from the University of California, Riverside kept cage-free chickens in poultry houses with dust boxes. The scientists infected clean chickens with 20 to 30 mites each, for two consecutive weeks, and then monitored the size of each bird’s infestation. Over six to 10 weeks, each dust-bathing hen carried 100 or fewer mites, on average. When the dust baths were removed, mite populations skyrocketed. The new results point to dust boxes as an alternative to pesticides for cage-free and organic farms, the researchers say.
A star that mysteriously disappeared might be the first confirmed case of a failed supernova, a star that tried to explode but couldn’t finish the job. A newborn black hole appears to have been left behind to snack on the star’s remains.
In 2009, a star in the galaxy NGC 6946 flared up over several months to become over 1 million times as bright as the sun. Then, it seemed to vanish. While the star could just be hiding behind a wall of dust, new observations with the Hubble Space Telescope, reported online September 6 at arXiv.org, strongly suggest that the star did not survive. A faint trickle of infrared light, however, emanates from where the star used to be. The remnant glow probably comes from debris falling onto a black hole that formed when the star died, write Caltech astronomer Scott Adams and colleagues. Black holes are typically thought to form in the aftermath of a supernova, the explosive death of a massive star. But multiple lines of evidence have recently hinted that not all heavyweights go out with a bang. Some stars might skip the supernova and collapse into a black hole. Until now, though, evidence that this happens has been either spotty or indirect.
“This is the first really solid observational evidence for a failed supernova,” says Elizabeth Lovegrove, an astronomer at the University of California, Santa Cruz. “Some supernovas really do fail and this is what they look like.”
This attempt at a supernova, first observed with the Large Binocular Telescope in Arizona, occurred about 19 million light-years away in the constellation Cygnus. Only one other known star — a yellow supergiant that faded away in 2010 — is suspected to be a failed supernova, though there’s not enough data to say for certain.
When a star at least eight times as heavy as the sun runs out of thermonuclear fuel, it can no longer support its own weight. Gas crashes down on the star’s core, bounces and sends a shock wave racing back toward the surface that tears the star apart. Some stars might be so massive that the shock wave doesn’t have enough oomph to push against the onrush of collapsing star stuff. The shock fizzles, the supernova fails and the core gathers enough mass to collapse into a black hole, possibly taking the rest of the star down with it.
If the dying star is a red supergiant — a ruddy orb that can be over 1,000 times as wide as the sun — it might give a signal before vanishing. As the core collapses, it releases an enormous amount of gravitational energy. A second shock wave ripples up through the star — not powerful enough for an explosion, but enough to burp off the loosely held outer layers of the supergiant and expose the feeding black hole. That’s exactly what Adams and colleagues think they saw. Hubble images from before 2009 reveal a star about 25 to 30 times as massive as the sun sitting where the flash of light came from. The star doesn’t show up in images taken since the eruption. Neither the brightness of the flash, the rate at which the brightness evolved nor the amount of light coming from there now fully matches other types of stellar incidents, such as a collision between a pair of stars or the violent outbursts that accompany some aging supermassive stars.
If the star did give birth to a black hole, X-rays may be radiating from debris spiraling down its gravitational throat. Adams and collaborators are waiting on observations from the space-based Chandra X-ray Observatory to check that idea. They also continue to monitor what’s left of the star. The star might still be there, hiding within a shell of dust expelled during the 2009 eruption. If that’s the case, it should become visible again in the coming years as the cloak dissipates.
In a recent poll, more than four-fifths of U.S. adults could not name a living scientist. Of those who could, the plurality (40 percent) named Stephen Hawking. (The next highest response was Neil deGrasse Tyson, followed by Jane Goodall.) No offense to the rightfully famous Hawking, but at Science News we would like to change these results. Why aren’t more scientists, particularly those who are young and accomplished, household names? Where, we want to know, are the Taylor Swifts of science?
You’ll find some of them below. For the second year in a row, Science News is highlighting 10 early- and mid-career scientists on their way to widespread acclaim. The SN 10: Scientists to Watch includes a laser physicist with laserlike focus, a materials scientist challenging what it means to be alive and a computational biologist willing to get personal with his microbiome, among many others who are making important advances in their chosen fields.
Though none of these scientists have recorded hit singles — at least not that our reporting uncovered — all were nominated by a Nobel laureate or recently elected member of the National Academy of Sciences. And all were age 40 or younger at the time of nomination.
These remarkable individuals have diverse personalities and talents: They are tenacious and creative, practical-minded and dreamers. They are lab animals and data heads. Some seek simplicity, others complexity. If there is one unifying trait, though, it would have to be their passion — a quality so cliché among successful scientists that it has to be true. As Marie Curie famously wrote in a letter to her sister, “Sometimes my courage fails me and I think I ought to stop working…. But I am held by a thousand bonds.” She did not know, she confessed, whether she could live without the laboratory.
After a year caring for patients at the heart of Brazil’s Zika epidemic, pediatric neurologist Vanessa van der Linden has seen some of the worst cases.
She was one of the first researchers to link Zika virus to microcephaly, a now well-known birth defect marked by a small, misshapen head and, sometimes, a forehead that slopes backward. Babies with the defect can have other symptoms, too: Van der Linden has seen 24-hour crying bouts, spasms, extreme irritability and difficulty swallowing. But microcephaly is just the tip of the Zika iceberg, she said September 22 at a workshop hosted by the National Institutes of Health in North Bethesda, Md. That’s something public health officials have been warning about for months. Now, scientists have begun to describe a head-to-toe assortment of health problems linked to Zika virus infection in utero; they’re calling it congenital Zika syndrome.
Still, the full scope of the problem, including the threat of more subtle neurologic disorders such as learning disabilities or developmental delays, remains murky, says Peter Hotez, a pediatrician and microbiologist at Baylor College of Medicine in Houston.
“That’s the big unknown: There’s probably a spectrum of illness,” similar to autism, he says. And it could take years for scientists to sort it all out.
It’s a problem that Brazil is facing now, and one that Puerto Rico has just begun grappling with.
As of September 23, the U.S. territory had reported 22,358 confirmed cases of Zika infection. Of these cases, 1,871 are pregnant women. Carmen Zorrilla, an obstetrician-gynecologist at the University of Puerto Rico’s Maternal-Infant Studies Center who has examined some of these women and their babies, emphasizes the importance of following up on all babies exposed to Zika in the womb — even those without apparent birth defects. “Even if they are born normal,” she said, “it doesn’t mean they’ll be OK.”
Insidious problems At the workshop, Zorrilla described the case of one of the first Puerto Rican babies born to a mother diagnosed with Zika. The baby didn’t have microcephaly, but she did have another unusual problem: She couldn’t open her eyes. A bad case of conjunctivitis (pinkeye) left her needing help opening her eyelids every morning — even 27 days after birth. Zorrilla can’t say for sure whether the problem was related to Zika, but “it really concerned me,” she said. “This is the first baby I’ve seen with conjunctivitis that lasted for so long.”
The case may be another clue that Zika’s assaults on the body are widespread. And Zorrilla can expect to see more cases soon. Ultrasound examinations of 228 women in Puerto Rico with confirmed Zika infection have spotted brain abnormalities in 13 fetuses, including one with microcephaly.
Another observation could hint at problems yet to come: Most of the Zika-exposed fetuses tended to have slightly smaller heads than average, although “still within the normal limits,” Zorrilla said. But measurements of leg bones and stomach size indicate that the rest of the body is growing normally. Implications remain unclear, but the findings — preliminary results from Alberto de la Vega, also an obstetrician-gynecologist at the University of Puerto Rico — are the latest in a litany of anomalies linked to Zika.
Long-term problems aren’t unusual in babies infected with a different kind of virus that causes microcephaly. Like Zika, cytomegalovirus can infect babies in the womb. Most CMV-infected babies don’t have any obvious symptoms, but asymptomatic kids may have problems as they grow, including intellectual disabilities, hearing loss or cerebral palsy, researchers suggested in the October Brain and Development.
Beyond microcephaly, scientists have recently described other symptoms linked to Zika infection. In some babies, for example, Zika seems to damage hearing. Of 70 Zika-exposed infants born with microcephaly, 10 percent had some hearing loss, researchers noted in a Sept. 2 report published by the U.S. Centers for Disease Control and Prevention. Zika can leave a mark on the eyes, too. More than a third of 29 babies with microcephaly had some sort of eye oddity, including mottled pigmenting and withered tissue, researchers reported in May in JAMA Ophthalmology.
Van der Linden has also observed a link between Zika and a deformity called arthrogryposis, where a child’s joints can be stuck in contorted positions — even in babies without microcephaly. The condition might stem from problems with infected babies’ motor neurons, the nerve cells that relay messages from the brain to the muscles, van der Linden and colleagues suggested August 9 in BMJ.
She has even seen babies born with normal head circumferences who later develop microcephaly or other brain defects. One mother, she says, came in five months after giving birth because she thought her baby wasn’t developing normally. Like children with congenital Zika syndrome, the baby’s head scans revealed “the same pattern of brain damage,” van der Linden says. This pattern includes a malformed cerebral cortex, the wrinkled outer layer of the brain, and calcifications, strange lumps of calcium deposited within the tissue.
Infiltrating the brain Scientists still don’t know exactly how Zika damages the brain, but they have some ideas.
One recent report found that the virus can infiltrate and kill both neuroepithelial stem cells, which give rise to all sorts of brain cells, and radial glial cells, which can generate newborn neurons and help guide them to their proper place in the brain.
Zika also hinders these cells’ ability to split into new cells, Yale University neuroscientist Marco Onorati and colleagues reported September 6 in Cell Reports. Stem cells at work in the fetal brain eventually give rise to structures responsible for thought and memory and learning, raising concerns of a cascade of problems down the road. “This is a virus that blocks the development of the fetal brain,” Hotez says. “That’s about the worst thing you can possibly imagine.”
And fetuses might not be the only ones at risk, he points out. “Kids in the first years of life also have growing, developing brains,” he says. “What if they get infected with Zika?”
It’s not an easy question to answer. But another disease could offer clues.
Malaria, for example, can cause severe neurological problems. In children, a condition called cerebral malaria may be linked to mental health disorders such as attention-deficit/hyperactivity disorder, antisocial behavior and depression, researchers reported in March in Malaria Journal.
Researchers will also need to watch out for long-term troubles in Zika-exposed babies born with no obvious symptoms, says the CDC’s Sonja Rasmussen. “We don’t want to make families too scared,” she says. “But we do recognize the possibility of later-on seizures or developmental delay.”
Since most people don’t show signs of Zika infection, pinpointing the total number of pregnant women (and babies) exposed to the virus may be impossible.
In the Americas, at least, the number is probably enormous. Tens of thousands of children may eventually suffer some sort of neurologic or psychiatric illness triggered by Zika, Hotez predicted in a paper published in JAMA Pediatrics in August.
Van der Linden can’t say whether the babies she has seen have learning disabilities or psychiatric illnesses, or other more subtle cognitive problems — most of her patients are between 9 months and 1 year old.
But she plans to follow these patients, and the babies who appeared normal at birth, for years. “We need time to better understand the disease,” she says.
Hotez agrees: “It’s going to take a generation of pediatric neurologists and infectious disease experts to figure this out.”
Figuring out the nuts and bolts of the cell’s recycling machinery has earned the 2016 Nobel Prize in physiology or medicine. Cell biologist Yoshinori Ohsumi of the Tokyo Institute of Technology has received the prize for his work on autophagy, a method for breaking down and recycling large pieces of cellular junk, such as clusters of damaged proteins or worn-out organelles.
Keeping this recycling machinery in good working condition is crucial for cells’ health (SN: 3/26/11, p. 18). Not enough recycling can cause cellular trash to build up and lead to neurological diseases such as Alzheimer’s and Parkinson’s. Too much recycling, on the other hand, has been linked to cancer. “It’s so exciting that Ohsumi has received the Nobel Prize, which he no question deserved,” says biologist Jennifer Lippincott-Schwartz of Howard Hughes Medical Institute’s Janelia Research Campus in Ashburn, Va. “He set the framework for an entire new field in cell biology.”
Ohsumi‘s discoveries helped reveal the mechanism and significance of a fundamental physiological process, biologist Maria Masucci of the Karolinska Institute in Sweden said in a news briefing October 3. “There is growing hope that this knowledge will lead to the development of new strategies for the treatment of many human diseases.”
Scientists got their first glimpse of autophagy in the 1960s, not long after the discovery of the lysosome, a pouch within cells that acts as a garbage disposal, grinding fats and proteins and sugars into their basic building blocks. (That discovery won Belgian scientist Christian de Duve a share of the Nobel Prize in 1974.) Researchers had observed lysosomes stuffed with big chunks of cellular material — like the bulk waste of the cellular world — as well as another, mysterious pouch that carried the waste to the lysosome.
Somehow, the cell had devised a way to consume large parts of itself. De Duve dubbed the process autophagy, from the Greek words for “self” and “to eat.” But over the next 30 years, little more became known about the process. “The machinery was unknown, and how the system was working was unknown, and whether or not it was involved in disease was also unknown,” said physiologist Juleen Zierath, also of the Karolinska Institute, in an interview after the prize’s announcement.
That all changed in the 1990s when Ohsumi decided to study autophagy in a single-celled organism called baker’s yeast, microbes known for making bread rise. The process was tricky to catch in action, partly because it happened so fast. So Ohsumi bred special strains of yeast that couldn’t break down proteins in their cellular garbage disposals (called vacuoles in yeast).
“He reasoned that if he could stop the degradation process, he could see an accumulation of the autophagy machinery in these cells,” Zierath said.
And that’s just what Ohsumi saw. When he starved the yeast cells, the “self-eating” machinery kicked into gear (presumably to scrounge up food for the cells). But because the garbage disposals were defective, the machinery piled up in the vacuoles, which swelled like balloons stuffed with sand. Ohsumi could see the bulging, packed bags clearly under a light microscope. He published the work in a 1992 paper in the Journal of Cell Biology. Finding the autophagy machinery let Ohsumi study it in detail. A year later, he discovered as many as 15 genes needed for the machinery to work. In the following years, Ohsumi and other scientists examined the proteins encoded by these genes and began to figure out how the components of the “bulk waste” bag, or autophagosome, came together, and then fused with the lysosome.
The work revealed something new about the cell’s garbage centers, Zierath said. “Before Ohsumi came on the scene, people understood that the waste dump was in the cell,” she said. “But what he showed was that it wasn’t a waste dump. It was a recycling plant.”
Later, Ohsumi and his colleagues studied autophagy in mammalian cells and realized that the process played a key maintenance role in all kinds of cells, breaking down materials for reuse. Ohsumi “found a pathway that has its counterparts in all cells that have a nucleus,” says 2013 Nobel laureate Randy Schekman, a cell biologist at the University of California, Berkeley. “Virtually every corner of the cell is touched by the autophagic process.”
Since Ohsumi’s discoveries, research on autophagy has exploded, says Lippincott-Schwartz. “It’s an amazing system that every year becomes more and more fascinating.”
Ohsumi, 71, remains an active researcher today. He received the call from the Nobel committee at his lab in Japan. The prize includes an award of 8 million Swedish kronor (equivalent to about $934,000). About his work, he said: “It was lucky. Yeast was a very good system, and autophagy was a very good topic.”
Still, he added in an interview with a Nobel representative, “we have so many questions. Even now we have more questions than when I started.”
