The most distant quasar yet spotted sends its light from the universe’s toddler years. The quasar, called J1342+0928, existed when the universe was only 690 million years old, right when the first stars and galaxies were forming.
Quasars are bright disks of gas and dust swirling around supermassive black holes. The black hole that powers J1342+0928 has a mass equivalent to 800 million suns, and it’s gobbling gas and dust so fast that its disk glows as bright as 40 trillion suns, Eduardo Bañados of the Carnegie Institution for Science in Pasadena, Calif., and his colleagues report December 6 in Nature. “The newly discovered quasar gives us a unique photo of the universe when it was 5 percent [of] its present age,” Bañados says. “If the universe was a 50-year-old person, we would be seeing a photo of that person when she/he was 2 1/2 years old.”
This quasar is only slightly smaller than the previous distance record-holder, which weighs as much as 2 billion suns and whose light is 12.9 billion years old, emitted when the universe was just 770 million years old (SN: 7/30/11, p. 12). Scientists still aren’t sure how supermassive black holes like these grew so big so early.
“They either have to grow faster than we thought, or they started as a bigger baby,” says study coauthor Xiaohui Fan of the Steward Observatory in Tucson.
The temperature of the gas surrounding the newfound quasar places it squarely in the epoch of reionization (SN: 4/1/17, p. 13), when the first stars stripped electrons from atoms of gas that filled interstellar space. That switched the universe’s gas from mostly cold and neutral to hot and ionized. When this particular black hole formed, the universe was about half hot and half cold, Fan says. “We’re very close to the epoch when the first-generation galaxies are appearing,” Fan says.
NEW ORLEANS — The New Horizons team may get more than it bargained for with its next target. Currently known as 2014 MU69, the object might, in fact, be two rocks orbiting each other — and those rocks may themselves host a small moon.
MU69 orbits the sun in the Kuiper Belt, a region more than 6.5 billion kilometers from Earth. That distance makes it difficult to get pictures of the object directly. But last summer, scientists positioned telescopes around the globe to catch sight of MU69’s shadow as it passed in front of a distant background star (SN Online: 7/20/17), a cosmic coincidence known as an occultation. Analyzing that flickering starlight raised the idea that MU69 might have two lobes, like a peanut, or might even be a pair of distinct objects. Whatever its shape, MU69 is not spherical and may not be alone, team members reported in a news conference on December 12 at the fall meeting of the American Geophysical Union.
Another stellar flicker sighting raised the prospect of a moon. On July 10, NASA’s airborne Stratospheric Observatory for Infrared Astronomy observed MU69 pass in front of a different star (SN: 3/19/16, p. 4). SOFIA saw what looked like a new, shorter dip in the star’s light. Comparing that data with orbit calculations from the European Space Agency’s Gaia spacecraft suggested that the blip could be another object around MU69.
A double object with a smaller moon could explain why MU69 sometimes shifts its position from where scientists expect it to be during occultations, said New Horizons team member Marc Buie of the Southwest Research Institute in Boulder, Colo.
The true shape will soon be revealed. The New Horizons spacecraft set its sights on the small space rock after flying past Pluto in 2015, and will fly past MU69 on January 1, 2019.
Our solar system is no longer the sole record-holder for most known planets circling a star.
An artificial intelligence algorithm sifted through data from the planet-hunting Kepler space telescope and discovered a previously overlooked planet orbiting Kepler 90 — making it the first star besides the sun known to host eight planets. This finding, announced in a NASA teleconference December 14, shows that the kinds of clever computer codes used to translate text and recognize voices can also help discover strange new worlds. The discovery, also reported in a paper accepted to the Astronomical Journal, can also help astronomers better understand the planetary population of our galaxy. “Finding systems like this that have lots of planets is a really neat way to test theories of planet formation and evolution,” says Jeff Coughlin, an astronomer at the SETI Institute in Mountain View, Calif., and NASA’s Ames Research Center in Moffett Field, Calif.
Kepler 90 is a sunlike star about 2,500 light-years from Earth in the constellation Draco. The latest addition to Kepler 90’s planetary family is a rocky planet about 30 percent larger than Earth called Kepler 90i. It, too, is the third planet from its sun — but with an estimated surface temperature higher than 400° Celsius, it’s probably not habitable.
Story continues below graphic The seven previously known planets in this system range from small, rocky worlds like Kepler 90i to gas giants, which are all packed closer to their star than Earth is to the sun. “It’s very possible that Kepler 90 has even more planets,” study coauthor Andrew Vanderburg, an astronomer at the University of Texas at Austin, said in the teleconference. “There’s a lot of unexplored real estate in the Kepler 90 system.” Astronomers have identified over 2,300 new planets in Kepler data by searching for tiny dips in a star’s brightness when a planet passes in front of it. Kepler has collected too much data for anyone to go through it all by hand, so humans or computer programs typically only verify the most promising signals of the bunch. That means that worlds that produce weaker light dips — like Kepler 90i — can get passed over. Vanderburg and Christopher Shallue, a software engineer at Google in Mountain View, Calif., designed a computer code called a neural network, which mimics the way the human brain processes information, to seek out such overlooked exoplanets. Researchers previously automated Kepler data analysis by hard-coding programs with rules about how to detect bona fide exoplanet signals, Coughlin explains. Here, Vanderburg and Shallue provided their code with more than 10,000 Kepler signals that had been labeled by human scientists as either exoplanet or non-exoplanet signals. By studying these examples, the neural network learned on its own what the light signal of an exoplanet looked like, and could then pick out the signatures of exoplanets in previously unseen signals.
The fully trained neural network examined 670 star systems known to host multiple planets to see whether previous searches had missed anything. It spotted Kepler 90i, as well as a sixth, Earth-sized planet around the star Kepler 80. This feat marks the first time a neural network program has successfully identified new exoplanets in Kepler data, Jessie Dotson, an astrophysicist at NASA’s Ames Research Center said at the teleconference.
Vanderburg and Shallue now plan to apply their neural network to Kepler’s full cache of data on more than 150,000 stars, to see what other unrecognized exoplanets it might turn up.
Coughlin is also excited about the prospect of using artificial intelligence to assess data from future exoplanet search missions, like NASA’s TESS satellite set to launch next year. “The hits are going to keep on coming,” regarding potential exoplanet signals, he says. Having self-taught computer programs help humans slog through the data could significantly speed up the rate of scientific discovery.
Globs of an inflammation protein beckon an Alzheimer’s protein and cause it to accumulate in the brain, a study in mice finds. The results, described in the Dec. 21/28 Nature, add new details to the relationship between brain inflammation and Alzheimer’s disease.
Researchers suspect that this inflammatory cycle is an early step in the disease, which raises the prospect of being able to prevent the buildup of amyloid-beta, the sticky protein found in brains of people with Alzheimer’s disease. “It is a provocative paper,” says immunologist Marco Colonna of Washington University School of Medicine in St. Louis. Finding an inflammatory protein that can prompt A-beta to clump around it is “a big deal,” he says.
Researchers led by Michael Heneka of the University of Bonn in Germany started by studying specks made of a protein called ASC that’s produced as part of the inflammatory response. (A-beta itself is known to kick-start this inflammatory process.) Despite being called specks, these are large globs of protein that are created by and then ejected from brain immune cells called microglia when inflammation sets in. A-beta then accumulates around these ejected ASC specks in the space between cells, Haneke and colleagues now propose. A-beta can directly latch on to ASC specks, experiments in lab dishes revealed. The two proteins were also caught in close contact in brain tissue taken from people with Alzheimer’s disease. Researchers didn’t see any ASC specks mingling with A-beta in the brains of people without the disease. Mice engineered to produce lots of A-beta had telltale signs of its accumulation in their brains at 8 and 12 months of age, roughly comparable to middle age in people. But in mice that also lacked the ability to produce ASC specks, this A-beta brain load was much lighter, and these mice performed better on a memory test. Similar reductions in A-beta loads came when researchers used an antibody to prevent A-beta from sticking to ASC specks, results that suggest the specks are needed for A-beta to clump up.
The details show “a quite new and specific mechanism” that’s worth exploring for potential treatments, says Richard Ransohoff, a neuroinflammation biologist at Third Rock Ventures, a venture capital firm in Boston.
To be effective as a treatment, an antibody like the one in the study that kept A-beta from sticking to ASC would need to be able to enter the brain and persist at high levels — a big challenge, Ransohoff says. Still, the results are promising, he says. “I like the data. I like the line of experimentation.”
Many questions remain. The results are mainly from mice, and it’s not clear whether ASC specks and A-beta have similar interactions in human brains. Nor is it obvious how to stop the A-beta from accumulating around the specks without affecting the immune system more generally.
What’s more, the role of the microglia immune cells that release ASC specks is complex, Colonna says. In some cases, microglia serve as brain protectors by surrounding and sequestering sticky A-beta plaques in the brain (SN: 11/30/13, p. 22). But the current results suggest that by releasing ASC specks, the same cells can also make A-beta accumulation worse. The dueling roles of the cells — protective in some cases and potentially harmful in others — make it challenging to figure out how to tweak their behavior therapeutically, Colonna says.
Our Top 10 stories of 2017 cover the science that was earthshaking, field-advancing or otherwise important. But choosing our favorite stories requires some different metrics.
Here are some of our staff’s favorites from 2017, selected for their intrigue, their power, their element of surprise — or because they were just really, really fun.
Stories that moved us “The eclipse the eclipse the eclipse omg the eclipse.”
Astronomy writer Lisa Grossman didn’t hesitate in her e-mail reply when I asked for everyone’s personal favorites of the year. For the Great American Eclipse, Lisa wrote a 10-part preview of questions scientists would pursue during totality. She then traveled to Wyoming for the eclipse itself, reporting from a Baptist summer camp–turned-observatory. The whole experience was surprisingly emotional, Lisa says, and one that has stuck with her. “I keep looking at the sun now and thinking about how all that beautiful gossamer structure is there, all the time, and we just can’t see it. And how lucky we are that the moon is just the size and distance it is, so that we can experience this.” The Cassini spacecraft’s journey to Saturn also struck an emotional chord with the SN staff. “Cassini crashing into Saturn wins the award for ‘2017 science event that made me cry the most,’” says staff writer Laurel Hamers. After traveling 4.9 billion miles over nearly 20 years, the spacecraft dove into Saturn’s atmosphere and vaporized. “It was a very human drama about a machine,” says audience engagement editor Mike Denison. “It was the sort of science story even a layman like me can get very invested in.”
At its core, Cassini’s mission was basic exploration — the same drive that made the moon landing so captivating. “It’s amazing that there is still so much of our solar system we haven’t explored directly, and the goodies from that mission and the final dive will be reported for years to come,” writes acting editor in chief Beth Quill. “Plus, I love the narrative potential of a spacecraft that sacrifices itself.”
Physics writer Emily Conover’s personal favorite was also our No. 1 story, the detection of two neutron stars colliding — a finding that she had predicted. “I’m patting myself on the back a little bit for that,” she says.
“It was a lot of fun to think about how we’ve detected something completely new and confirmed that some of the tangible stuff around us, like the gold in my wedding ring, came from collisions like that,” she adds. “It’s one of those stories that if you think about it hard enough, it makes you feel like a very small part in a giant, wonderful, fascinating universe.”
Stories that surprised us We spend our days devouring science, combing scientific journals, interviewing scientists, attending meetings and reading science news in other publications. You’d think very little would surprise us. Not true. Maria Temming’s story on the discovery of a mysterious void in the Great Pyramid of Giza was one of our most-read stories of the year . By placing detectors throughout the pyramid to measure subatomic particles called muons, researchers discovered a previously unknown cavity inside the pyramid. “The topic was this beautiful juxtaposition of modern, cutting-edge technology — as in the muon detectors — with the ancient technology of pyramid construction,” says Maria, SN ’s technology writer. “It’s also kind of hilarious to think that the Great Mysterious Thing in this story is not the high-energy particles from outer space — that’s the thing we’ve got a handle on!” Science News for Students managing editor and Wild Things blogger Sarah Zielinski has a keen eye for amazing animal stories, so her pick for a favorite story surprised me: It was our May story and infographic on how an asteroid impact would kill you. “You assume that you know what an asteroid impact would do,” Sarah says, “but it turns out that your assumptions are completely wrong.”
Senior writer Tina Hesman Saey has been covering molecular and developmental biology for more than a decade, but was surprised when a new study overturned the idea that female is the default sex in developing mammals, and that only male tissues have to be actively built. A study she reported on this year found that male structures must be demolished to set off female development. “I was amazed that no one knew a basic of developmental biology: that development of female reproductive organs is an active process,” Tina says. A story about circulation in sea spiders takes the surprise prize for biology writer Susan Milius. “I had never written a story about them, so they were on my taxonomic bucket list,” she says. It turns out that oxygen-rich blood circulates up and down the animal’s legs as contractions move bits of food through the digestive tract in the legs. “It’s circulation by gut lump!” Susan says. “This still blows me away.” The story of how the house mouse came to live with people was a favorite for Science News for Students writer and Scicurious blogger Bethany Brookshire. “It was something I’d never thought of before and it was interesting to find how just how much we were affecting the species around us, even the littlest ones!”
Graphic designer Tracee Tibbitts highlighted two more, well, animalistic animal stories: One about a coconut crab attacking a bird, and one about gulls eating hookworms from seals’ feces — directly from the source. “We see a lot of cute animal stories online that give us warm fuzzies or a ‘they’re just like us!’ reaction,” Tracee says. “But both of these stories remind us that — NOPE. Animals are still wild and out there fighting each other for food and resources and survival.”
Stories that intrigued, for better or worse The gene-editing technology CRISPR/Cas9 caught Beth’s attention this year, “though I would say that last year and would say it again next year,” she says. “It is especially interesting to me to watch a technology from its infancy and understand the twists and turns it takes, all the ways it’s used and the ethical implications that arise.”
CRISPR made our Top 10 list this year as Tina had predicted in 2016. “I was right that CRISPR would still be a thing,” Tina says.
But Susan hadn’t expected CRISPR to creep into her beat as well. “What I missed by light-years was how fast CRISPR would cease to be just Tina’s business and become a matter that someone writing about conservation, ecology and real outdoor evolution has to watch,” Susan says. In an in-depth story on ticks, Susan described preliminary work to engineer mice using CRISPR gene editing to curb the spread of the Lyme disease parasite. “It might happen in six or seven years, and at the current speed, gene editing for wild, free-roaming organisms may, for better or worse — or both — be a real thing,” Susan says. “I certainly see the need for caution, but wow, are the possibilities changing fast.”
Stories scientists tell Part of the fun of many of the stories we cover is talking to the researchers who do the work. “I had so much fun interviewing scientists for [the neutron star collision] story,” Emily says. “Some of the members of LIGO were practically losing their minds about how amazing the detection was. It was so easy to get caught up in the excitement.” Tina got a chance to talk to planetary scientists and astrochemists — not her usual crowd — for a news story on a molecule on Saturn’s moon Titan that could be a key building block for any strange life-forms that might exist in the moon’s frigid methane lakes. In 2016, Tina had written a feature story on what alien life might look like , and in it described computer simulations of a molecule that could form bubblelike structures that resemble cell membranes. The new work showed that the molecule actually does exist on Titan. “It was a thrill to see that one prediction about truly alien life might come true,” Tina says. Laurel enjoyed talking to scientists trying to create better surgical adhesives inspired by slugs, worms and other critters. “People who study weird slime-making animals give the best interviews,” she says.
Associate editor Cassie Martin had a challenging time getting in touch with a scientist for a piece on the cholera epidemic in Yemen. “Finding a scientist and health worker in the war-torn country without actually traveling there took a lot of time and determination,” Cassie says. Once she did, though, she learned more than she expected. “I learned so much about what was happening not only with the epidemic, but about how war affects the scientific enterprise.”
For a video story on the anniversary of the detection of supernova 1987A, web producer Helen Thompson talked to Ian Shelton, who discovered the stellar explosion. The video told the story of the night of the discovery and reviewed all the insights the explosion has given to astronomy. The video also featured Shelton’s voice — and his likeness, in Claymation form. “I got to do a video that combined Claymation and glitter, which are my two favorite things,” Helen says.
Story continues below video The story of the moment You know when someone asks you what your favorite TV show is, and the show that springs to mind is the one you’re binge-watching right now? That often happens with our favorite science stories. Behavioral sciences writer Bruce Bower is putting the finishing touches on a feature story, due out early next year, on fantasy and reality in children’s play. Today, it’s his favorite. “It brings together psychology, anthropology/ethnography and archaeology, an interdisciplinary service that journalists can provide because scientists rarely do,” Bruce says.
For biomedical writer Aimee Cunningham, it’s all of the stories. “The majority of the stories I’ve written this year have met my criteria for why I do this work: to talk to interesting people, learn cool science and share what I find out.”
And that’s what we love about the work that we do. Here’s to 2018 and all the moving, surprising, intriguing, fascinating stories it will bring.
A new version of the periodic table showcases the predicted properties of 2-D metals, an obscure class of synthetic materials.
Arrayed in 1-atom-thick sheets, most of these 2-D metals have yet to be seen in the real world. So Janne Nevalaita and Pekka Koskinen, physicists at the University of Jyväskylä in Finland, simulated 2-D materials of 45 metallic elements, ranging from lithium to bismuth. For each sheet, the researchers measured the average chemical bond length, bond strength and the material’s compressibility, how difficult it is to squeeze the atoms closer together. The team then charted those features in the new periodic table. The new work, described in the Jan. 15 Physical Review B, could help researchers identify which 2-D metals are most promising for various applications, like spurring chemical reactions or sensing gases.
These metals are similar to previously studied 2-D materials, such as the supermaterial graphene (SN: 10/3/15, p. 7) and its cousin diamondene (SN: 9/2/17, p. 12). But whereas those materials were made up of covalent bonds — in which pairs of atoms share electrons — these 2-D metals are composed of metallic bonds, where electrons flow more freely among atoms. “It’s a whole new type of family of nanostructures,” Koskinen says. “Sky’s the limit, for what the applications could be.”
Like other superflat materials, some potential 2-D metals might exhibit exotic quantum qualities, such as 2-D magnetism or superconductivity, the ability to transmit electricity without resistance. Such properties may make those materials useful for quantum computing, says Joshua Robinson, a materials scientist at Penn State not involved in the work.
Nevalaita and Koskinen created three periodic tables that chart the properties of 2-D metals with atoms in triangular, square or honeycomb configurations. Using their trio of tables, the researchers discovered that the properties of 2-D metals were related to those of their 3-D counterparts. For instance, atoms of any given metal arranged in a triangular lattice typically had about 70 percent the bond strength of atoms in the 3-D version of that metal. Square and honeycomb lattices generally showed about 66 percent and 54 percent the bond strength of 3-D metals, respectively. The periodic tables revealed similar relationships between 2-D and 3-D metals in bond length and compressibility. These findings could allow researchers to get a quick profile of a 2-D metal that has never been created in the lab or in a computer simulation, just based on the well-known characteristics of its 3-D analog.
Nevalaita and Koskinen also compared the stability of 2-D metals whose atoms were arranged in the three different configurations. The researchers found that many 2-D metals were stable in triangular and honeycomb patterns, but not in squares. Future computer simulations could examine the electric and magnetic properties of these materials, Koskinen says. Knowing the stability and property profiles of 2-D metals could inform which materials scientists fabricate in the lab.
“This is the tip of the iceberg in the area of 2-D metals,” says Mauricio Terrones, a chemical physicist at Penn State not involved in the work.
Closing out a series in the NBA Playoffs is never easy, but the task may have gotten more difficult for the Lakers.
In the fourth quarter of a potential closeout game against the Warriors, Anthony Davis was forced to exit the game after taking an inadvertent shot to the head from Warriors center Kevon Looney.
What does this mean for Davis and the Lakers? Here is what we know about his injury and status moving forward. Anthony Davis injury update While battling for position on the inside, Davis took an inadvertent elbow from Looney to the side of his head. Davis was taken out of the game, brought back for evaluation, and eventually ruled out for Game 5 with what the Lakers ruled as a head injury.
Here's the play where Davis was injured as well as the aftermath that includes him receiving attention on the bench before being taken to the locker room. Turner Sports' Chris Haynes reported that Davis was being evaluated at Chase Center, with the possibility of a concussion looming as a potential diagnosis. Haynes added that Davis was brought to the locker room in a wheelchair following his evaluation.
In a later report, Haynes added that Davis "appears to have avoided a concussion and is doing better now," a positive sign for Davis and the Lakers.
Lakers head coach Darvin Ham told reporters that he spoke with Davis, who he said "seems to be doing really good already." Davis exited Game 5 with 21 points (on 10-of-18 shooting), nine rebounds and three assists in 32 minutes.
Will Anthony Davis play in Game 6? Davis' availability largely depends on the diagnosis of his injury and whether or not he is dealing with a concussion. If Davis is not diagnosed with a concussion, there is a clear path for him to return to the floor for Game 6.
Here is an excerpt from the NBA's Concussion Policy: There is just a one-day layoff between Games 5 and 6 of the Western Conference Semifinals series between the Lakers and Warriors.
Lakers vs. Warriors schedule Here is the schedule for the second-round series between Los Angeles and Golden State, with the final two games airing on the ESPN family of networks.
Fans in the U.S. can watch the NBA Playoffs on Sling TV, which is now offering HALF OFF your first month! Stream Sling Orange for $20 in your first month to catch all the games on TNT, ESPN & ABC. For games on NBA TV, subscribe to Sling Orange & Sports Extra for $27.50 in your first month. Local regional blackout restrictions apply. SIGN UP FOR SLING: English | Spanish
Date Game Time (ET) TV channel May 2 Lakers 117, Warriors 112 10 p.m. TNT May 4 Warriors 127, Lakers 100 9 p.m. ESPN May 6 Lakers 127, Warriors 97 8:30 p.m. ABC May 8 Lakers 104, Warriors 101 10 p.m. TNT May 10 Warriors 121, Lakers 106 10 p.m. TNT May 12 Game 6 TBD ESPN May 14 Game 7* TBD ABC
On July 31, 2012, Maggie de Grauw looked out the window of her flight back to New Zealand after a holiday in Samoa and glimpsed a mysterious mass floating below. That mass turned out to be a raft of lightweight pumice rock, the product of an erupting underwater volcano called Havre. The 2012 eruption turned out to be the largest of its kind in the last 100 years. And now, the pumice raft has become a crucial clue in revealing the eruption’s surprisingly complex nature. Although underwater eruptions happen all the time, scientists have only recorded such events since the 1990s, and pumice rafts can often float under the radar. Typically, researchers use depth sensors aboard ships to examine the crime scene of an underwater eruption.
But “what we found on the seafloor was almost entirely different from what we expected,” says Rebecca Carey, a volcanologist at the University of Tasmania in Australia. Havre challenges the reliability of the geologic record when it comes to big deep-sea eruptions.
In 2015, Carey and her colleagues set out to get a more detailed view of Havre’s big outburst than what ship-based sensors could reveal. The researchers deployed a robot to measure the depth of the 4-kilometer-wide caldera. Another robot, operated remotely from a ship, allowed the team to get a closer look at specific features in and around the caldera, and to take rock and water samples. A bit of satellite-image detective work revealed the size and path of the pumice raft, which formed no more than 21 1/2 hours after the eruption ended.
The robotic diving duo provided a high-resolution topographic map of the underwater posteruption landscape. The map shows a massive rupture, lava from 14 different vents ranging from 900 to 1,220 meters below the surface, chunks of pumice, landslide deposits and a blanket of ash. This diversity of volcanic material was unexpected, the researchers write January 10 in Science Advances. Although the Havre event was larger than the 1980 eruption of Mount St. Helens, a similar type of volcano that shot a huge column of debris into the air, the seafloor data weren’t indicative of such a large eruption. “When you shoot a lot of material up into water, there’s resistance,” Carey says. “So you expect to see a lot of it deposited on the seafloor.” But using an old seafloor map of Havre and satellite data, Carey and her colleagues calculated that more than 75 percent of the material produced by Havre ended up in the 400-square-kilometer pumice raft. That raft eventually broke apart and washed up on Australian and other South Pacific beaches. Volcanic gases might have pushed debris to the surface, Carey speculates, but it’s impossible to pinpoint a cause.
Many submarine eruptions go unnoticed, and few have been mapped in this manner. Frequently, researchers rely only on clues on the seafloor surface to determine an eruption’s size. And, if Carey’s team had just done that, the researchers would have never known the true size and nature of the eruption.
“That is a real eye-opener from this study,” says Bill Chadwick, a volcanologist at the National Oceanic and Atmospheric Administration’s Pacific Marine Environmental Laboratory in Newport, Ore. “What they found tells us a lot about how submarine eruptions behave differently than those on land.”
And if the Havre data are any guide, previous estimates of underwater eruption size may be off. “Now we know that the geological rock record is unfaithful to these very large magnitude powerful events,” Carey says.
In a white lab coat and blue latex gloves, Neda Vishlaghi peers through a light microscope at six milky-white blobs. Each is about the size of a couscous grain, bathed in the pale orange broth of a petri dish. With tweezers in one hand and surgical scissors in the other, she deftly snips one tiny clump in half.
When growing human brains, sometimes you need to do some pruning.
The blobs are 8-week-old bits of brainlike tissue. While they wouldn’t be mistaken for Lilliputian-sized brains, some of their fine-grained features bear a remarkable resemblance to the human cerebral cortex, home to our memories, decision making and other high-level cognitive powers.
Vishlaghi created these “minibrains” at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, where she’s a research assistant. First she immersed batches of human pluripotent stem cells — which can morph into any cell type in the body — in a special mix of chemicals. The free-floating cells multiplied and coalesced into itty-bitty balls of neural tissue. Nurtured with meticulously timed doses of growth-supporting ingredients, the cell clumps were eventually transferred to petri dishes of broth laced with Matrigel, a gelatin-like matrix of proteins.
On day 56, the blobs display shadowy clusters of neural “rosettes.” Under a laser scanning microscope, razor-thin slices of those rosettes reveal loose-knit layers of a variety of dividing neural stem cells and the nerve cells, or neurons, they give rise to. The layered structures look similar to the architecture of a human fetal brain at 14 weeks of gestation. Across the globe, labs such as this one, led by UCLA developmental biologist and neuroscientist Bennett Novitch, are cultivating thousands of these brainy clumps for research. Less than five years ago, a team of biologists in Austria and the United Kingdom and one in Japan wowed the world when they announced they had made rudimentary bits of 3-D human cerebral cortex in a dish. Since then, researchers have been eagerly tinkering with techniques for producing these miniature brain models, like chefs obsessively refining their favorite recipes.
“It’s like making a cake: You have many different ways in which you can do it,” says Novitch, who prefers using the Japanese method with a few tweaks. “There are all sorts of little tricks that people have come up with to overcome some of the common challenges.”
For instance, because the brain blobs lack a built-in blood supply, they must absorb enough oxygen and nutrients from the tissue-culture broth to remain healthy. To help, some labs circulate the broth around the tissue clumps. The UCLA researchers choose instead to grow theirs at higher oxygen levels and chop the blobs at the 35-day mark, when they are as wide as three millimeters, and then about every two weeks after. Sounds radical, but the slicing gives cells on the inside — some of which start dying — exposure to much-needed oxygen and nutrients. Those divided bits then continue growing separately. But cutting can be done only so many times before the expanding rosette structures inside are damaged.
With all the experimenting, researchers have cooked up a lot of innovations, including some nifty progress reported in just the last year. Scientists have concocted tiny versions of several brain regions ranging from the hypothalamus, which regulates body temperature, thirst and hunger, to the movement-controlling basal ganglia. Electrical chatter among neurons, reflecting active brain circuits, has been detected. And research groups have recently begun linking bits of specific regions like Legos. Scientists have even observed some early developmental processes as they happen within the human brain blobs. Stem cell payoff The work is part of a broader scientific bonanza that comes from coaxing human stem cells to self-assemble into balls of organlike tissue, known as organoids, that are usually no bigger than a lentil. Although the organoids don’t grow enough to replicate entire human organs, these mini-versions can mimic the 3-D cellular infrastructure of everything from our guts to our lungs. That’s something you can’t get from studies of rodents, which have different biology than humans do.
Mini-organ models promise enormous advantages for understanding basic human biology, teasing apart human disease processes, and offering an accurate testing ground for finding or vetting drug therapies. And by creating personalized organoids from the reprogrammed cells of patients, scientists could study disease in a very individualized way — or maybe even use organoid structures to replace certain damaged tissues, such as in the liver or spinal cord.
“Organoids offer an unprecedented level of access into the inner workings of the human brain,” Novitch says, noting that our brains are largely off-limits to poking and cutting into for research. If scientists can study accurate models of working neural circuits in these brain bits, he and others say, researchers might finally get a handle on uniquely human neurological conditions. Such disorders, which include epilepsy and, experts theorize, schizophrenia and autism (SN Online: 7/17/15), can arise when the brain’s communication networks develop off-kilter. But the research is still in its early days. Although there’s been exciting headway, studies sometimes overstate the extent to which human brain organoids reproduce features of actual developing brain tissue, says stem cell biologist Arnold Kriegstein of the University of California, San Francisco. The minimodels still lack many basic components, including certain cell types, a blood-vessel network and inputs from other neural regions.
Another stumbling block is that brain organoids can vary a lot from protocol to protocol, or even batch to batch within the same lab. “The major focus now needs to be on reproducibility, and being able to get an approach that you can rely on to give you the same outcome each time,” Kriegstein says.
DIY organs For decades, biology research has relied on cell lines grown in flat sheets in petri dishes, but those sheets lack the structural complexity of living tissue. Then came pioneering work that unveiled the do-it-yourself magic of stem cells raised free-floating in broth.
Organlike tissue bits can be generated from pluripotent stem cells that are either plucked from embryos or created by taking a person’s adult skin or blood cells and chemically inducing them to revert to an embryonic-like state. Starting in the mid-2000s, Yoshiki Sasai’s team at the RIKEN Center for Developmental Biology in Kobe, Japan, demonstrated how to grow brainlike structures using embryonic stem cells, first from mice and then humans. In their groundbreaking study in 2013 in Proceedings of the National Academy of Sciences, the researchers used chemical cues to direct human embryonic stem cells to form a specific region of the human cortex. (Tragically, Sasai committed suicide the next year, after two stem cell studies that he coauthored were retracted amid scientific misconduct charges against a research colleague [SN: 12/27/14, p. 25]. Before his death, Sasai was cleared of any direct involvement. The discredited studies were not related to the organoid research.)
A few months before the 2013 Sasai team paper, Madeline Lancaster and Juergen Knoblich of the Institute of Molecular Biotechnology in Vienna and U.K. colleagues demonstrated their more freewheeling, landmark approach to growing brain organoids (SN: 9/21/13, p. 5). The recipe, described in Nature, allows human pluripotent stem cells to spontaneously attempt to assemble into a tiny approximation of a whole brain by making whatever brain structures the stem cells choose.
Meanwhile, biologists elsewhere were whipping up other types of organoids, starting instead with adult stem cells. These rare, damage-repairing cells are found in many organs (including the brain), but the cells can transform into only a limited range of cell types. In 2009, Hans Clevers of the Hubrecht Institute in Utrecht, the Netherlands, announced that his lab unexpectedly created a miniature version of a gut while cultivating adult stem cells that the team had discovered in mouse intestinal tissue. Grown in a drop of Matrigel with a trio of growth-inducing factors, these cells coalesced into little spheres containing tiny projections that resembled the fingerlike villi that absorb nutrients in the gut.
Scientists soon were concocting tiny facsimiles of human stomachs, livers, kidneys, lungs and more (SN: 12/28/13, p. 20). “We essentially are discovering the vitality of what the stem cells actually do,” says Clevers, who is president of the International Society for Stem Cell Research. “We give [the cells] a little push, and they do whatever they’re good at.”
The trick is knowing exactly which ingredients to use to make different organs. For pluripotent stem cells, that means exposing them to just the right growth factors or inhibitors at just the right times, over about a month, says James Wells of the Center for Stem Cell and Organoid Medicine at Cincinnati Children’s Hospital Medical Center. Some of those essential instructions are well-known from decades of research on embryo development in fish, chickens and rodents; the same chemical cues generally work for all animals with spinal cords, including people. However, for many body parts, organoid makers must suss out recipe instructions from scratch. Working with Jorge Múnera and other colleagues, Wells recently produced a minimodel of a human colon using human induced pluripotent stem cells. But first, the team conducted months of experiments on frog and mouse embryos to identify the signals for forming a colon. “It took a while to figure out what the special sauce was,” Wells says.
Some scientists have distant dreams of using organoid methods to grow full-size livers or kidneys in the lab for transplantation. A more attainable goal may be regenerative tissue transplants, for example, replacing dying liver cells in someone with early-stage liver disease with chunks of healthy stem cells from a personalized liver organoid. Or, in patients who’ve had part of the small intestine removed, tiny pieces of gut organoid tissue could be implanted and, after growing larger, connected to the intestine.
Head games The human brain, meanwhile, is vastly more complicated than any other organ. It’s unlikely that scientists will ever be able to build a full replica. While the initial brain-making recipes were stunning for what they could achieve, they left much room for improvement. In the years since the 2013 debut of human brain organoids, research groups have worked to grow bigger brain tissue clumps and more uniform structures.
The Austrian method for making whole-brain organoids, in particular, produced a random mix of neural regions laid out in a topsy-turvy manner. But bioengineering tricks may help. In a study last year, Lancaster, now at the MRC Laboratory of Molecular Biology in Cambridge, England, and Knoblich got more consistent results by adding polymer filaments as scaffolding to guide the organization of the minibrain models. Other scientists, following the Japanese approach, which generally gives more predictable results, have concentrated on coaxing out specific cell types or structural features of the real brain. For instance, one constraint is that the organoids form slowly, more or less sticking to the same timeline of development as does a human brain during gestation. But without a blood supply, growth is limited; the brain bits reach only a few millimeters in size. That means organoid models are often short on cell types from later development stages, such as cells called astrocytes. These star-shaped cells are crucial for creating and curating the connections between neurons, and also may help with forming memories (SN Online: 11/15/17).
Astrocytes don’t fully mature in a baby’s brain until after birth. But Stanford University neuroscientist Sergiu Paşca has crafted a method for making and maintaining 4-millimeter-wide balls of human cortex–like tissue (he calls them spheroids) in 3-D culture for an extended time. Last August in Neuron, his team described organoids that survived for more than 20 months — long enough, analyses showed, for astrocytes to mature and function in ways that mimic their real-brain counterparts.
Of great interest, also, are the outer radial glial (oRG) cells, neural stem cells that are pivotal for constructing the unusually big cortex that’s unique to humans; oRG cells are scarce in mouse brains. When Novitch’s lab group at UCLA tried the original Japanese and Austrian organoid-making recipes, the output of oRG cells was underwhelming. So Novitch worked with Vishlaghi and postdoctoral researcher Momoko Watanabe to refine the protocol to pump up the cells’ production and reliably generate better cerebral blobs.
Among other tweaks, Novitch’s team added a dash of a molecule dubbed LIF, which recent studies by others had suggested can spur the oRGs to multiply. It worked, leading to a threefold increase in the oRG populations and enhanced growth of upper neuron layers. The researchers shared their revised protocol last October in Cell Reports. On a different front, labs have begun assembling more complex minibrain models, like playing with self-directed Legos. For two months, Paşca’s team at Stanford grew spheroids in separate sets of dishes that mimicked either cortex tissue or an adjacent underlying region known as the subpallium. Then the researchers put the different bits side-by-side and left them overnight in a culture tube. Similar to how the two regions normally connect in the developing brain, the little pieces knew what to do. “By the next day they are essentially fused to each other,” says Paşca, who announced the results in May in Nature.
During the fusion process, the researchers took time-lapse videos of long, spaghetti-like cells called interneurons migrating from a spheroid of the subpallium into a cortexlike spheroid.
“They don’t crawl, they actually jump,” Paşca says. The images capture aspects of a hallmark phenomenon that normally unfolds during the second and third trimester of fetal gestation.
Testing ground Once on the other side, interneurons form a circuit with — and quell the activity of — excitatory neurons in the cortexlike tissue, electrophysiological tests suggest. If not quieted, excitatory neurons will trigger neighboring cells to fire. In the real brain, maintaining a proper balance in neural network activity is important; disruptions in it appear to foster disorders such as epilepsy, and perhaps schizophrenia and autism.
Indeed, in the same paper, the Stanford team reported new discoveries using personalized brain spheroids derived from induced pluripotent stem cells of patients with Timothy syndrome — a rare condition caused by an overactive calcium channel found mainly in the brain and heart. Patients with the disorder have epilepsy, autism and heart problems. In the patients’ spheroids, interneurons migrated inefficiently but, by adding drugs that blocked the dysfunctional calcium channel, the researchers could reverse the problem. The brain organoids made these intriguing observations possible, Paşca says. “We couldn’t have done this in any other way.” Organoid experiments by others have, meanwhile, helped confirm that the Zika virus targets and kills oRG cells and other neural precursor cells, contributing to small brain size in infected infants.
In a 2016 study, Johns Hopkins University neuroscientists Guo-li Ming and Hongjun Song reported on their own techniques for creating brain bits that have a well-defined zone of oRG cells. After infecting these organoids with the Zika virus, the researchers observed a collapse of cortexlike tissue that may partly explain the stunted brain growth (SN: 4/2/16, p. 26). 2-D cell-culture and mouse experiments also provided key evidence of the virus’s modus operandi; although the rodent brain doesn’t harbor the full contingent of human neural stem cells, it has blood vessels and immune-system components that organoids lack.
In search of Zika-fighting treatments, Ming and Song, both now at University of Pennsylvania, and their colleagues have been screening thousands of compounds in 2-D cell cultures, and then validating the most promising candidates with tests in 3-D brain organoids. The team has found several potential antiviral and neuron-protecting agents to pursue. Novitch’s UCLA lab group has likewise used its brain organoids to pinpoint additional receptors by which the virus may gain entry into neural stem cells, and identified a few other drug leads for blocking infection.
Organoids may also prove valuable for tailoring treatments for patients, says David Panchision, chief of the developmental neurobiology program at the National Institute of Mental Health in Bethesda, Md. Researchers might generate personalized brain organoids from the reprogrammed skin cells of individuals with, say, schizophrenia and test which medications work best for patients with particular genetic profiles of the illness.
In the Netherlands, based on research reported in 2016 in Science Translational Medicine, Clevers and colleagues are already using personalized gut organoids, derived from rectal biopsies, to test whether cystic fibrosis patients will benefit from available drugs. Tailored regenerative therapies with 3-D substructures of neural tissue may also be possible, Panchision adds, for conditions like Parkinson’s disease or spinal cord injury. Growing pains For now, though, scientists have hefty challenges to overcome. Much work remains in optimizing how faithfully the bits of tissue reproduce normal brain function and architecture, Panchision says. For one thing, the organoids are developmentally young and don’t reflect a mature brain. And researchers must figure out how to build in some core features: the necessary blood vessels, immune-system cells called microglia and connections from other brain regions, such as the thalamus and cerebellum. Not to mention steroid and thyroid hormones, which also shape brain growth.
However, scientists don’t necessarily need or want to create a comprehensive replica of the human brain in a dish, Panchision and others point out. Rather, the goal is to build robust and reliable models for studying specific aspects of brain function.
Thus the pressing need for standardized, reproducible organoid-making recipes. Novitch’s group and many other labs are still trying to figure out why the brain bits can vary so much in size, composition and structure. Part of the trouble is the ingredients: Subtle variations in tissue-culture chemicals and Matrigel, or in different stem cell lines and how they are grown first in 2-D culture, can have a big impact on how the organoids turn out, Novitch says.
At the same time, researchers need to do a more thorough job of analyzing brain organoids to know what’s actually in them at different developmental time points, compared with actual human fetal brain tissue, says UCSF’s Kriegstein. It’s otherwise hard to say whether a brain blob truly recapitulates the neural tissue that scientists claim it does. Labs have started tackling the problem with a tool called single-cell transcriptome analysis, which gives readouts of all the genes that are active in individual cells.
“Greater rigor is needed,” Kriegstein says. “And I am sure we will eventually get there.”
