The Neil Armstrong biopic, opening October 12, follows about eight years of the life of the first man on the moon, and spends about eight minutes depicting the lunar surface. Instead of the triumphant ticker tape parades that characterize many movies about the space race, First Man focuses on the terror, grief and heartache that led to that one small step.
“It’s a very different movie and storyline than people expect,” says James Hansen, author of the 2005 biography of Armstrong that shares the film’s name and a consultant on the film. The story opens shortly before Armstrong’s 2-year-old daughter, Karen, died of a brain tumor in January 1962. That loss hangs over the rest of the film, setting the movie’s surprisingly somber emotional tone. The cinematography is darker than most space movies. Colors are muted. Music is ominous or absent — a lot of scenes include only ambient sound, like a pen scratching on paper, a glass breaking or a phone clicking into the receiver. Karen’s death also seems to motivate the rest of Armstrong’s journey. Getting a fresh start may have been part of the reason why the grieving Armstrong (portrayed by Ryan Gosling) applied to the NASA Gemini astronaut program, although he never explicitly says so. And without giving too much away, a private moment Armstrong takes at the edge of Little West crater on the moon recalls his enduring bond with his daughter.
Hansen’s book also makes the case that Karen’s death motivated Armstrong’s astronaut career. Armstrong’s oldest son, Rick, who was 12 when his father landed on the moon, agrees that it’s plausible. “But it’s not something that he ever really definitively talked about,” Rick Armstrong says.
Armstrong’s reticence about Karen — and almost everything else — is true to life. That’s not all the film got right. Gosling captured Armstrong’s gravitas as well as his humor, and Claire Foy as his wife, Janet Armstrong, “is just amazing,” Rick Armstrong says.
Beyond the performances, the filmmakers, including director Damien Chazelle and screenwriter Josh Singer, went to great lengths to make the technical aspects of spaceflight historically accurate. The Gemini and Apollo cockpits Gosling sits in are replicas of the real spacecraft, and he flipped switches and hit buttons that would have controlled real flight. Much of the dialog during space scenes was taken verbatim from NASA’s control room logs, Hansen says.
The result is a visceral sense of how frightening and risky those early flights were. The spacecraft rattled and creaked like they were about to fall apart. The scene of Armstrong’s flight on the 1966 Gemini 8 mission, which ended early when the spacecraft started spinning out of control and almost killed its passengers, is terrifying. The 1967 fire inside the Apollo 1 spacecraft, which killed astronauts Ed White, Gus Grissom and Roger Chaffee, is gruesome.
“We wanted to treat that one with extreme care and love and get it exactly right,” Hansen says. “What we have in that scene, none of it’s made up.”
Even when the filmmakers took poetic license, they did it in a historical way. A vomit-inducing gyroscope that Gosling rides in during Gemini astronaut training was, in real life, used for the earlier Mercury astronauts, but not for Gemini, for instance. Since the Mercury astronauts never experienced the kind of dizzying rotation that the gyroscope mimicked, NASA dismantled it before the next group of astronauts arrived.
“They probably shouldn’t have dismantled it,” Hansen says — it did simulate what ended up happening in the Gemini 8 accident. So the filmmakers used the gyroscope experience as foreshadowing.
Meanwhile, present-day astronauts are not immune to harrowing brushes with death: a Russian Soyuz capsule carrying two astronauts malfunctioned October 11, and the astronauts had to evacuate in an alarming “ballistic descent.” NASA is currently talking about when and how to send astronauts back to the moon from American soil. The first commercial crew astronauts, who will test spacecraft built by Boeing and SpaceX, were announced in August.
First Man is a timely and sobering reminder of the risks involved in taking these giant leaps.
Animated characters can learn from online tutorials, too.
A new computer program teaches virtual avatars new skills, such as dances, acrobatic stunts and martial art moves, from YouTube videos. This kind of system, described in the November ACM Transactions on Graphics, could render more physically coordinated characters for movies and video games, or serve as a virtual training ground for robots.
“I was really impressed” by the program, says Daniel Holden, a machine-learning researcher at Ubisoft La Forge in Montreal not involved in the work. Rendering accurate, natural-looking movements based on everyday video clips “has always been a goal for researchers in this field.” Animated characters typically have learned full-body motions by studying motion capture data, collected by a camera that tracks special markers attached to actors’ bodies. But this technique requires special equipment and often works only indoors.
The new program leverages a type of computer code known as an artificial neural network, which roughly mimics how the human brain processes information. Trained on about 100,000 images of people in various poses, the program first estimates an actor’s pose in each frame of a video clip. Then, it teaches a virtual avatar to re-create the actor’s motion using reinforcement learning, giving the character a virtual “reward” when it matches the video actor’s pose in a frame.
Computer scientist Jason Peng and colleagues at the University of California, Berkeley, fed YouTube videos into the system to teach characters to do somersaults, backflips, vaulting and other stunts. Even characters such as animated Atlas robots with bodies drastically different from those of their human video teachers mastered these motions (SN: 12/13/14, p. 16). Characters could also perform under conditions not seen in the training video, like cartwheeling while being pelted with blocks or moving across terrain riddled with holes. The work, also reported October 8 at arXiv.org, is a step “toward making motion capture easier, cheaper and more accessible,” Holden says. Videos could be used to render virtual versions of outdoor activities, since motion capture is difficult to do outdoors, or to create lifelike avatars of large animals that would be difficult to stick with motion capture markers.
This kind of program may also someday be used to teach robots new skills, Peng says. An animated version of a robot could master skills in a virtual environment before that learned computer code powered a machine in the physical world.
These animated characters still struggle with nimble dance steps, such as the “Gangnam Style” jig, and learn from short clips featuring only a single person. David Jacobs, a computer scientist at the University of Maryland in College Park not involved in the work, looks forward to future virtual avatars that can reenact longer, more complex actions, such as pairs of people dancing or soccer teams playing a game.
“That’s probably a much harder problem, because [each] person’s not as clearly visible, but it would be really cool,” Jacobs says. “This is only the beginning.”
SAN DIEGO — Mice yanked out of their community and held in solitary isolation show signs of brain damage.
After a month of being alone, the mice had smaller nerve cells in certain parts of the brain. Other brain changes followed, scientists reported at a news briefing November 4 at the annual meeting of the Society for Neuroscience.
It’s not known whether similar damage happens in the brains of isolated humans. If so, the results have implications for the health of people who spend much of their time alone, including the estimated tens of thousands of inmates in solitary confinement in the United States and elderly people in institutionalized care facilities.
The new results, along with other recent brain studies, clearly show that for social species, isolation is damaging, says neurobiologist Huda Akil of the University of Michigan in Ann Arbor. “There is no question that this is changing the basic architecture of the brain,” Akil says. Neurobiologist Richard Smeyne of Thomas Jefferson University in Philadelphia and his colleagues raised communities of multiple generations of mice in large enclosures packed with toys, mazes and things to climb. When some of the animals reached adulthood, they were taken out and put individually into “a typical shoebox cage,” Smeyne said.
This abrupt switch from a complex society to isolation induced changes in the brain, Smeyne and his colleagues later found. The overall size of nerve cells, or neurons, shrunk by about 20 percent after a month of isolation. That shrinkage held roughly steady over three months as mice remained in isolation. To the researchers’ surprise, after a month of isolation, the mice’s neurons had a higher density of spines — structures for making neural connections — on message-receiving dendrites. An increase in spines is a change that usually signals something positive. “It’s almost as though the brain is trying to save itself,” Smeyne said.
But by three months, the density of dendritic spines had decreased back to baseline levels, perhaps a sign that the brain couldn’t save itself when faced with continued isolation. “It’s tried to recover, it can’t, and we start to see these problems,” Smeyne said.
The researchers uncovered other worrisome signals, too, including reductions in a protein called BDNF, which spurs neural growth. Levels of the stress hormone cortisol changed, too. Compared with mice housed in groups, isolated mice also had more broken DNA in their neurons.
The researchers studied neurons in the sensory cortex, a brain area involved in taking in information, and the motor cortex, which helps control movement. It’s not known whether similar effects happen in other brain areas, Smeyne says.
It’s also not known how the neural changes relate to mice’s behavior. In people, long-term isolation can lead to depression, anxiety and psychosis. Brainpower is affected, too. Isolated people develop problems reasoning, remembering and navigating.
Smeyne is conducting longer-term studies aimed at figuring out the effects of neuron shrinkage on thinking skills and behavior. He and his colleagues also plan to return isolated mice to their groups to see if the brain changes can be reversed. Those types of studies get at an important issue, Akil says. “The question is, ‘When is it too far gone?’”
The cause of a rare polio-like disease continues to elude public health officials even as the number of U.S. cases grows.
Confirmed cases of acute flaccid myelitis cases have risen to 90 in 27 states, out of a possible 252 under investigation, the U.S. Centers for Disease Control and Prevention announced November 13. That’s up from 62 confirmed cases out of 127 suspected just a month ago (SN Online: 10/16/18). There were a record 149 cases in 2016. “I understand parents want answers,” Nancy Messonnier, director of the CDC’s National Center for Immunization and Respiratory Diseases in Atlanta, said at a news conference. The agency continues to investigate the disease, which causes weakness in one or more limbs and primarily affects children. But “right now the science doesn’t give us an answer,” she said.
A deep dive into 80 of the confirmed cases offered some details about the course of AFM. In most, fever or respiratory symptoms like coughing and congestion, or both, preceded limb weakness by three to 10 days. Most cases involved weakness in an upper limb, researchers report online November 13 in the Morbidity and Mortality Weekly Report.
Only two samples of cerebrospinal fluid — the clear fluid that bathes the brain and spinal cord — tested positive for a pathogen, each for a different enterovirus. Since 2014, when the first big outbreak of AFM occurred, most AFM spinal fluid samples haven’t produced a culprit, Messonnier said. The body may clear the pathogen or it hides in tissues, she said, or the body’s own immune response to a pathogen may lead to spinal cord damage.
“This time of year, many children have fever and respiratory symptoms [and] most of them do not go on to develop AFM,” Messonnier said. “We’re trying to figure out what the triggers are that would cause someone to develop AFM later.”
A proton’s mass is more than just the sum of its parts. And now scientists know just what accounts for the subatomic particle’s heft.
Protons are made up of even smaller particles called quarks, so you might expect that simply adding up the quarks’ masses should give you the proton’s mass. However, that sum is much too small to explain the proton’s bulk. And new, detailed calculations show that only 9 percent of the proton’s heft comes from the mass of constituent quarks. The rest of the proton’s mass comes from complicated effects occurring inside the particle, researchers report in the Nov. 23 Physical Review Letters.
Quarks get their masses from a process connected to the Higgs boson, an elementary particle first detected in 2012 (SN: 7/28/12, p. 5). But “the quark masses are tiny,” says study coauthor and theoretical physicist Keh-Fei Liu of the University of Kentucky in Lexington. So, for protons, the Higgs explanation falls short.
Instead, most of the proton’s 938 million electron volts of mass is due to complexities of quantum chromodynamics, or QCD, the theory which accounts for the churning of particles within the proton. Making calculations with QCD is extremely difficult, so to study the proton’s properties theoretically, scientists rely on a technique called lattice QCD, in which space and time are broken up into a grid, upon which the quarks reside. Using this technique, physicists had previously calculated the proton’s mass (SN: 12/20/08, p. 13). But scientists hadn’t divvied up where that mass comes from until now, says theoretical physicist André Walker-Loud of Lawrence Berkeley National Laboratory in California. “It’s exciting because it’s a sign that … we’ve really hit this new era” in which lattice QCD can be used to better understand nuclear physics.
In addition to the 9 percent of the proton’s mass that comes from quarks’ heft, 32 percent comes from the energy of the quarks zipping around inside the proton, Liu and colleagues found. (That’s because energy and mass are two sides of the same coin, thanks to Einstein’s famous equation, E=mc2.) Other occupants of the proton, massless particles called gluons that help hold quarks together, contribute another 36 percent via their energy.
The remaining 23 percent arises due to quantum effects that occur when quarks and gluons interact in complicated ways within the proton. Those interactions cause QCD to flout a principle called scale invariance. In scale invariant theories, stretching or shrinking space and time makes no difference to the theories’ results. Massive particles provide the theory with a scale, so when QCD defies scale invariance, protons also gain mass.
The results of the study aren’t surprising, says theoretical physicist Andreas Kronfeld of Fermilab in Batavia, Ill. Scientists have long suspected that the proton’s mass was made up in this way. But, he says, “this kind of calculation replaces a belief with scientific knowledge.”
Locust: The Opera finds a novel way to doom a soprano: species extinction.
The libretto, written by entomologist Jeff Lockwood of the University of Wyoming in Laramie, features a scientist, a rancher and a dead insect. The scientist tenor agonizes over why the Rocky Mountain locust went extinct at the dawn of the 20th century. He comes up with hypotheses, three of which unravel to music and frustration.
The project hatched in 2014. “Jeff got in his head, ‘Oh, opera is a good way to tell science stories,’ which takes a creative mind to think that,” says Anne Guzzo, who composed the music. Guzzo teaches music theory and composition at the University of Wyoming. locust brought famine and ruin to farms across the western United States. “This was a devastating pest that caused enormous human suffering,” Lockwood says. Epic swarms would suddenly descend on and eat vast swaths of cropland. “On the other hand, it was an iconic species that defined and shaped the continent.” Lockwood had written about the locust’s mysterious and sudden extinction in the 2004 book Locust , but the topic “begged in my mind for the grandeur of opera.” He spent several years mulling how to create a one-hour opera for three singers about the swarming grasshopper species. Then the ghost of Hamlet’s father, in the opera “Amleto,” based on Shakespeare’s play, inspired a breakthrough. Lockwood imagined a spectral soprano locust, who haunted a scientist until he figured out what killed her kind.
To make one locust soprano represent trillions, Guzzo challenged her music theory class to find ways of evoking the sound of a swarm. They tried snapping fingers, rattling cardstock and crinkling cellophane. But “the simplest answer was the most elegant,” Guzzo says — tasking the audience with shivering sheets of tissue paper in sequence, so that a great wave of rustling swept through the auditorium.
For the libretto, Lockwood took an unusually data-driven approach. After surveying opera lengths and word counts, he paced his work at 25 to 30 words per minute, policing himself sternly. If a scene was long by two words, he’d find two to cut. He wrote the dialogue not in verse, but as conversation, some of it a bit professorial. Guzzo asked for a few line changes. “I just couldn’t get ‘manic expressions of fecundity’ to fit where I wanted it to,” she says. Eventually, the scientist solves the mystery, but takes no joy in telling the beautiful locust ghost that humans had unwittingly doomed her kind by destroying vital locust habitat. For tragedy, Lockwood says, “there has to be a loss tinged with a kind of remorse.”
The opera, performed twice in Jackson, Wyo., will next be staged in March in Agadir, Morocco.
Editor’s note: This story will be periodically updated as new images are released.
NASA’s InSight lander touched down on Mars on November 26 for a study of the Red Planet’s insides.
“Touchdown confirmed, InSight is on the surface of Mars!” said Christine Szalai, a spacecraft engineer at NASA’s Jet Propulsion Laboratory in Pasadena, Calif., in a live broadcast from mission control. The lander sent its first picture — which mostly showed the inside of the dust cover on its camera lens — shortly after landing. The landing of InSight, short for Interior Exploration using Seismic Investigations, Geodesy and Heat Transport, brings the total number of successful NASA Mars landings to eight. InSight touched down at about 2:55 p.m. Eastern time in a wide, flat plain called Elysium Planitia, near Mars’ equator. News of the landing was relayed by a pair of tiny satellites called MarCO that travelled to Mars with InSight as an in-house communications team (SN Online: 11/18/18).
Over the next Martian year (about two Earth years), InSight will use a seismometer to listen for “Marsquakes” and other seismic waves rippling through the planet (SN: 5/26/18, p. 13). The lander will also drill five meters into Mars’ surface to measure the planet’s internal heat flow, a sign of how geologically active Mars is today. Update, November 27, 2018: InSight has opened its solar panels and is charging its batteries. In the next few days, the Mars lander will stretch out its robotic arm and take photos of the ground so the InSight team can decide where to place its scientific instruments. The first image from the Instrument Deployment Camera, taken shortly after landing November 26 and beamed back at 8:30 p.m. Eastern Standard Time, shows the spacecraft’s body, the folded-up robotic arm and the wide flat expanse of Elysium Planitia.
The U.S.S. Leviathan set sail from Hoboken, N.J., on September 29, 1918, carrying roughly 10,000 troops and 2,000 crewmen. The ship, bound for the battlefields in France, had been at sea less than 24 hours when the first passengers fell ill. By the end of the day, 700 people had developed signs of the flu.
The medical staff tried to separate the sick from the healthy, but that soon proved impossible. The poorly ventilated bunkrooms filled with the stench of illness. The floor grew slippery with blood from many nosebleeds, and the wails of the sick and dying echoed below deck. Bodies piled up and began decomposing, until finally the crew was forced to heave them into the sea. It was the stuff of nightmares. This is just one of the grisly scenes in Pandemic 1918 by historian Catharine Arnold. The book details how the movement of troops during World War I helped drive the spread of a deadly strain of influenza around the globe — from the American Midwest to Cape Town, South Africa, to New Zealand and beyond.
Scientists have yet to conclusively determine where that flu originated; Arnold suggests it was on a massive military base in Étaples, France. But all agree that the pandemic that became known as the Spanish flu didn’t begin in Spain. And the disease, which ultimately killed more than 50 million people, wasn’t caused by any ordinary influenza strain. Grim eyewitness accounts chronicle the gory details of how this virus differed. Victims often bled from the nose or mouth, writhed in pain and grew delirious with fever. Their faces turned dusky blue as their lungs filled with pus. Healthy men and women in their prime were dying, sometimes within days of falling ill. And there was a smell associated with the sick, “like very musty straw,” recalled one survivor. Arnold’s graphic depictions of the carnage make for some gripping scenes, but the book is perhaps too ambitious. She zigzags between so many people and places that only the most careful reader will be able to keep track of who fell ill where.
Another book tied to the 100th anniversary of the Spanish flu, Influenza, by long-time emergency room doctor Jeremy Brown, covers some of the same ground. Both Arnold and Brown, for instance, chronicle the hunt for the 1918 virus in bodies buried in Arctic permafrost and efforts to reconstruct the virus’s genetic code. But while Arnold’s book is rooted primarily in the past, Brown spends more time on recent research. He provides an in-depth look at what scientists now know about the 1918 strain, an H1N1 virus that originated in birds and spent time in an unknown mammalian host before infecting humans. In 2005, researchers managed to re-create the virus and test it in mice. The experiment provided insight into how the virus might have wrought so much damage in the lungs, but it also renewed a debate over the ethics of reconstructing deadly viruses. These kinds of experiments can help scientists better understand the inner workings of pathogens, but might also help people build biological weapons.
Brown also provides a fascinating look at the factors that make the more common seasonal flu so challenging to predict and prevent. Because data collection relies on the generosity of health care workers and because doctors rarely test for influenza, researchers can’t get a full picture of the scope of the disease. And because the virus mutates easily, scientists struggle to accurately predict what next year’s outbreak might look like. The strains circulating when pharmaceutical companies begin making vaccines might not be the strains that are circulating when the vaccines reach clinics and pharmacies. That’s why the flu shot’s efficacy varies from about 10 to 60 percent each year (SN: 10/28/17, p. 18).
Both books provide fresh perspectives on the 1918 pandemic and the influenza virus that caused it. Readers interested in a deep dive into the harrowing details and eyewitness accounts from that dark time should pick up Arnold’s book. For those who want more science with a frank discussion of the challenges influenza still poses, Brown delivers a clear and captivating overview. Together the books offer an unsettling picture of the damage influenza inflicted on the world 100 years ago and the misery that this virus might yet bring again.
Martha Carlin married the love of her life in 1995. She and John Carlin had dated briefly in college in Kentucky, then lost touch until a chance meeting years later at a Dallas pub. They wed soon after and had two children. John worked as an entrepreneur and stay-at-home dad. In his free time, he ran marathons.
Almost eight years into their marriage, the pinky finger on John’s right hand began to quiver. So did his tongue. Most disturbing for Martha was how he looked at her. For as long as she’d known him, he’d had a joy in his eyes. But then, she says, he had a stony stare, “like he was looking through me.” In November 2002, a doctor diagnosed John with Parkinson’s disease. He was 44 years old.
Carlin made it her mission to understand how her seemingly fit husband had developed such a debilitating disease. “The minute we got home from the neurologist, I was on the internet looking for answers,” she recalls. She began consuming all of the medical literature she could find.
With her training in accounting and corporate consulting, Carlin was used to thinking about how the many parts of large companies came together as a whole. That kind of wide-angle perspective made her skeptical that Parkinson’s, which affects half a million people in the United States, was just a malfunction in the brain.Martha Carlin married the love of her life in 1995. She and John Carlin had dated briefly in college in Kentucky, then lost touch until a chance meeting years later at a Dallas pub. They wed soon after and had two children. John worked as an entrepreneur and stay-at-home dad. In his free time, he ran marathons.
Almost eight years into their marriage, the pinky finger on John’s right hand began to quiver. So did his tongue. Most disturbing for Martha was how he looked at her. For as long as she’d known him, he’d had a joy in his eyes. But then, she says, he had a stony stare, “like he was looking through me.” In November 2002, a doctor diagnosed John with Parkinson’s disease. He was 44 years old.
Carlin made it her mission to understand how her seemingly fit husband had developed such a debilitating disease. “The minute we got home from the neurologist, I was on the internet looking for answers,” she recalls. She began consuming all of the medical literature she could find.
With her training in accounting and corporate consulting, Carlin was used to thinking about how the many parts of large companies came together as a whole. That kind of wide-angle perspective made her skeptical that Parkinson’s, which affects half a million people in the United States, was just a malfunction in the brain. “I had an initial hunch that food and food quality was part of the issue,” she says. If something in the environment triggered Parkinson’s, as some theories suggest, it made sense to her that the disease would involve the digestive system. Every time we eat and drink, our insides encounter the outside world.
John’s disease progressed slowly and Carlin kept up her research. In 2015, she found a paper titled, “Gut microbiota are related to Parkinson’s disease and clinical phenotype.” The study, by neurologist Filip Scheperjans of the University of Helsinki, asked two simple questions: Are the microorganisms that populate the guts of Parkinson’s patients different than those of healthy people? And if so, does that difference correlate with the stooped posture and difficulty walking that people with the disorder experience? Scheperjans’ answer to both questions was yes.
Carlin had picked up on a thread from one of the newest areas of Parkinson’s research: the relationship between Parkinson’s and the gut. Other than a small fraction of cases that are inherited, the cause of Parkinson’s disease is unknown. What is known is that something kills certain nerve cells, or neurons, in the brain. Abnormally misfolded and clumped proteins are the prime suspect. Some theories suggest a possible role for head trauma or exposure to heavy metals, pesticides or air pollution. People with Parkinson’s often have digestive issues, such as constipation, long before the disease appears. Since the early 2000s, scientists have been gathering evidence that the malformed proteins in the brains of Parkinson’s patients might actually first appear in the gut or nose (people with Parkinson’s also commonly lose their sense of smell). From there, the theory goes, these proteins work their way into the nervous system. Scientists don’t know exactly where in the gut the misfolded proteins come from, or why they form, but some early evidence points to the body’s internal microbial ecosystem. In the latest salvo, scientists from Sweden reported in October that people who had their appendix removed had a lower risk of Parkinson’s years later (SN: 11/24/18, p. 7). The job of the appendix, which is attached to the colon, is a bit of a mystery. But the organ may play an important role in intestinal health.
If the gut connection theory proves true — still a big if — it could open up new avenues to one day treat or at least slow the disease.
“It really changes the concept of what we consider Parkinson’s,” Scheperjans says. Maybe Parkinson’s isn’t a brain disease that affects the gut. Perhaps, for many people, it’s a gut disease that affects the brain.
Gut feeling London physician James Parkinson wrote “An essay on the shaking palsy” in 1817, describing six patients with unexplained tremors. Some also had digestive problems. (“Action of the bowels had been very much retarded,” he reported of one man.) He treated two people with calomel — a toxic, mercury-based laxative of the time — and noted that their tremors subsided.
But the digestive idiosyncrasies of the disease that later bore Parkinson’s name largely faded into the background for the next two centuries, until neuroanatomists Heiko Braak and Kelly Del Tredici, now at the University of Ulm in Germany, proposed that Parkinson’s disease might arise from the intestine. Writing in Neurobiology of Aging in 2003, they and their colleagues based their theory on autopsies of Parkinson’s patients. The researchers were looking for Lewy bodies, which contain clumps of a protein called alpha-synuclein. The presence of Lewy bodies in the brain is a hallmark of Parkinson’s, though their exact role in the disease is still under investigation.
Lewy bodies form when alpha-synuclein, which is produced by neurons and other cells, starts curdling into unusual strands. The body encapsulates the abnormal alpha-synuclein and other proteins into the round Lewy body bundles. In the brain, Lewy bodies collect in the cells of the substantia nigra, a structure that helps orchestrate movement. By the time symptoms appear, much of the substantia nigra is already damaged.
Substantia nigra cells produce the chemical dopamine, which is important for movement. Levodopa, the main drug prescribed for Parkinson’s, is a synthetic replacement for dopamine. The drug has been around for a half-century, and while it can alleviate symptoms for a while, it does not slow the destruction of brain cells.
In patient autopsies, Braak and his team tested for the presence of Lewy bodies, as well as abnormal alpha-synuclein that had not yet become bundled together. Based on comparisons with people without Parkinson’s, the researchers found signs that Lewy bodies start to form in the nasal passages and intestine before they show up in the brain. Braak’s group proposed that Parkinson’s disease develops in stages, migrating from the gut and nose into the nerves to reach the brain.
Neural highway Today, the idea that Parkinson’s might arise from the intestine, not the brain, “is one of the most exciting things in Parkinson’s disease,” says Heinz Reichmann, a neurologist at the University of Dresden in Germany. The Braak theory couldn’t explain how the Lewy bodies reach the brain, but Braak speculated that some sort of pathogen, perhaps a virus, might travel along the body’s nervous system, leaving a trail of Lewy bodies.
There is no shortage of passageways: The intestine contains so many nerves that it’s sometimes called the body’s second brain. And the vagus nerve offers a direct connection between those nerves in the gut and the brain (SN: 11/28/15, p. 18).
In mice, alpha-synuclein can indeed migrate from the intestine to the brain, using the vagus nerve like a kind of intercontinental highway, as Caltech researchers demonstrated in 2016 (SN: 12/10/16, p. 12). And Reichmann’s experiments have shown that mice that eat the pesticide rotenone develop symptoms of Parkinson’s. Other teams have shown similar reactions in mice that inhale the chemical. “What you sniff, you swallow,” he says.
To look at this idea another way, researchers have examined what happens to Parkinson’s risk when people have a weak or missing vagus nerve connection. There was a time when doctors thought that an overly eager vagus nerve had something to do with stomach ulcers. Starting around the 1970s, many patients had the nerve clipped as an experimental means of treatment, a procedure called a vagotomy. In one of the latest studies on vagotomy and Parkinson’s, researchers examined more than 9,000 patients with vagotomies, using data from a nationwide patient registry in Sweden. Among people who had the nerve cut down low, just above the stomach, the risk of Parkinson’s began dropping five years after surgery, eventually reaching a difference of about 50 percent compared with people who hadn’t had a vagotomy, the researchers reported in 2017 in Neurology. The studies are suggestive, but by no means definitive. And the vagus nerve may not be the only possible link the gut and brain share. The body’s immune system might also connect the two, as one study published in January in Science Translational Medicine found. Study leader Inga Peter, a genetic epidemiologist at the Icahn School of Medicine at Mount Sinai in New York City, was looking for genetic contributors to Crohn’s disease, an inflammatory bowel condition that affects close to 1 million people in the United States.
She and a worldwide team studied about 2,000 people from an Ashkenazi Jewish population, which has an elevated risk of Crohn’s, and compared them with people without the disease. The research led Peter and colleagues to suspect the role of a gene called LRRK2. That gene is involved in the immune system — which mistakenly attacks the intestine in people who have Crohn’s. So it made sense for a variant of that gene to be involved in inflammatory disease. The researchers were thrown, however, when they discovered that versions of the gene also appeared to increase the risk for Parkinson’s disease.
“We refused to believe it,” Peter says. The finding, although just a correlation, suggested that whatever the gene was doing to the intestine might have something to do with Parkinson’s. So the team investigated the link further, reporting results in the August JAMA Neurology.
In their analysis of a large database of health insurance claims and prescriptions, the scientists found more evidence of inflammation’s role. People with inflammatory bowel disease were about 30 percent more likely to develop Parkinson’s than people without it. But among those who had filled prescriptions for an anti-inflammatory medication called antitumor necrosis factor, which the researchers used as a marker for reduced inflammation, Parkinson’s risk was 78 percent lower than in people who had not filled prescriptions for the drug.
Belly bacteria Like Inga Peter, microbiologist Sarkis Mazmanian of Caltech came upon Parkinson’s disease almost by accident. He had long studied how the body’s internal bacteria interact with the immune system. At lunch one day with a colleague who was studying autism using a mouse version of the disease, Mazmanian asked if he could take a look at the animals’ intestines. Because of the high density of nerves in the intestine, he wanted to see if the brain and gut were connected in autism.
Neurons in the gut “are literally one cell layer away from the microbes,” he says. “That made me feel that at least the physical path or conduit was there.” He began to study autism, but wanted to switch to a brain disease with more obvious physical symptoms. When he learned that people with Parkinson’s disease often have a long history of digestive problems, he had his subject.
Mazmanian’s group examined mice that were genetically engineered to overproduce alpha-synuclein. He wanted to know whether the presence or absence of gut bacteria influenced symptoms that developed in the mice.
The results, reported in Cell in 2016, showed that when the mice were raised germ free — meaning their insides had no microorganisms — they showed no signs of Parkinson’s. The animals had no telltale gait or balance problems and no constipation, even though their bodies made alpha-synuclein (SN: 12/24/16 & 1/7/17, p. 10). “All the features of Parkinson’s in the animals were gone when the animals had no microbiome,” he says.
However, when gut microbes from people diagnosed with Parkinson’s were transplanted into the germ-free mice, the mice developed symptoms of the disease — symptoms that were much more severe than those in mice transplanted with microbes from healthy people.
Mazmanian suspects that something in the microbiome triggers the misfolding of alpha-synuclein. But this has not been tested in humans, and he is quick to say that this is just one possible explanation for the disease. “There’s likely no one smoking gun,” he says.
Microbial forces If the microbiome is involved, what exactly is it doing to promote Parkinson’s? Microbiologist Matthew Chapman of the University of Michigan in Ann Arbor thinks it may have something to do with chemical signals that bacteria send to the body. Chapman studies biofilms, which occur when bacteria form resilient colonies. (Think of the slime on the inside a drain pipe.)
Part of what makes biofilms so hard to break apart is that fibers called amyloids run through them. Amyloids are tight stacks of proteins, like columns of Legos. Scientists have long suspected that amyloids are involved in degenerative diseases of the brain, including Alzheimer’s. In Parkinson’s, amyloid forms of alpha-synuclein are found in Lewy bodies.
Despite amyloids’ bad reputation, the fibers themselves aren’t always undesirable, Chapman says. Sometimes they may provide a good way of storing proteins for future use, to be snapped off brick by brick as needed. Perhaps it’s only when amyloids form in the wrong place, like the brain, that they contribute to disease. Chapman’s lab group has found that E. coli bacteria, part of the body’s normal microbial population, produce amyloid forms of some proteins when they are under stress.
When gut bacteria produce amyloids, the body’s own cells could also be affected, wrote Chapman in 2017 in PLOS Pathogens with an unlikely partner: neurologist Robert Friedland of the University of Louisville School of Medicine in Kentucky. “This is a difficult field to study because it’s on the border of several fields,” Friedland says. “I’m a neurologist who has little experience in gastroenterology. When I talked about this to my colleagues who are gastroenterologists, they’ve never heard that bacteria make amyloid.” Friedland and collaborators reported in 2016 in Scientific Reports that when E. coli in the intestines of rats started to produce amyloid, alpha-synuclein in the rats’ brains also congealed into the amyloid form. In their 2017 paper, Chapman and Friedland suggested that the immune system’s reaction to the amyloid in the gut might have something to do with triggering amyloid formation in the brain.
In other words, when gut bacteria get stressed and start to produce their own amyloids, those microbes may be sending cues to nearby neurons in the intestine to follow suit. “The question is, and it’s still an outstanding question, what is it that these bacteria are producing that is, at least in animals, causing alpha-synuclein to form amyloids?” Chapman says.
Head for a cure There is, in fact, a long list of questions about the microbiome, says Scheperjans, the neurologist whose paper Martha Carlin first spotted. So far, studies of the microbiomes of human patients are largely limited to simple observations like his, and the potential for a microbiome connection has yet to reach deeply into the neurology community. But in October, for the second year in a row, Scheperjans says, the International Congress of Parkinson’s Disease and Movement Disorders held a panel discussing connections to the microbiome.
“I got interested in the gastrointestinal aspects because the patients complained so much about it,” he says. While his study found definite differences in the bacteria of people with Parkinson’s, it’s still too early to know how that might matter. But Scheperjans hopes that one day doctors may be able to test for microbiome changes that put people at higher risk for Parkinson’s, and restore a healthy microbe population through diet or some other means to delay or prevent the disease. One way to slow the disease might be shutting down the mobility of misfolded alpha-synuclein before it has even reached the brain. In Science in 2016, neuroscientist Valina Dawson and colleagues at Johns Hopkins University School of Medicine and elsewhere described using an antibody to halt the spread of bad alpha-synuclein from cell to cell. The researchers are working now to develop a drug that could do the same thing.
The goal is to one day test for the early development of Parkinson’s and then be able to tell a patient, “Take this drug and we’re going to try to slow and prevent progression of disease,” she says.
For her part, Carlin is doing what she can to speed research into connections between the microbiome and Parkinson’s. She quit her job, sold her house and drained her retirement account to pour money into the cause. She donated to the University of Chicago to study her husband’s microbiome. And she founded a company called the BioCollective to aid in microbiome research, providing free collection kits to people with Parkinson’s. The 15,000 microbiome samples she has collected so far are available to researchers.
Carlin admits that the possibility of a gut connection to Parkinson’s can be a hard sell. “It’s a difficult concept for people to wrap their head around when you are taking a broad view,” she says. As she searches for answers, her husband, John, keeps going. “He drives, he runs biking programs in Denver for people with Parkinson’s,” she says. Anything to keep the wheels turning toward the future.One way to slow the disease might be shutting down the mobility of misfolded alpha-synuclein before it has even reached the brain. In Science in 2016, neuroscientist Valina Dawson and colleagues at Johns Hopkins University School of Medicine and elsewhere described using an antibody to halt the spread of bad alpha-synuclein from cell to cell. The researchers are working now to develop a drug that could do the same thing.
The goal is to one day test for the early development of Parkinson’s and then be able to tell a patient, “Take this drug and we’re going to try to slow and prevent progression of disease,” she says.
For her part, Carlin is doing what she can to speed research into connections between the microbiome and Parkinson’s. She quit her job, sold her house and drained her retirement account to pour money into the cause. She donated to the University of Chicago to study her husband’s microbiome. And she founded a company called the BioCollective to aid in microbiome research, providing free collection kits to people with Parkinson’s. The 15,000 microbiome samples she has collected so far are available to researchers.
Carlin admits that the possibility of a gut connection to Parkinson’s can be a hard sell. “It’s a difficult concept for people to wrap their head around when you are taking a broad view,” she says. As she searches for answers, her husband, John, keeps going. “He drives, he runs biking programs in Denver for people with Parkinson’s,” she says. Anything to keep the wheels turning toward the future.
Magnetism transforms a weird new material from soft to rigid in a split second.
This metamaterial — a synthetic structure designed to behave in ways that natural materials don’t — comprises a gridlike network of plastic tubes filled with fluid that becomes more viscous in a magnetic field, causing the tubes to firm up. The material could help make more adaptable robots or body armor, researchers report online December 7 in Science Advances.
Christopher Spadaccini, a materials engineer at Lawrence Livermore National Laboratory in California, and colleagues 3-D printed lattices composed of plastic struts 5 millimeters long and injected them with a mixture of tiny iron particles and oil. In the absence of a magnetic field, the iron microparticles remain scattered randomly throughout the oil, so the liquid is runny. But close to a magnet, these iron microparticles align into chains along the magnetic field lines, making the fluid viscous and the lattices stiffer. A solid hunk of iron microparticle–filled material would be heavy and expensive to make. Building tubular structures that are mostly open space makes this tunable material more lightweight, says coauthor Julie Jackson, an engineer at Lawrence Livermore. The researchers tested individual “unit cells” of the new material — hollow, die-shaped structures that can collectively form the larger lattices. Moving one unit cell from about eight centimeters to one centimeter away from a magnet increased its stiffness by about 62 percent.
In future technologies, this material could be paired with devices that use electricity to generate magnetic fields, called electromagnets. Material that becomes softer or stiffer on demand could be used to make next-generation sports pads or helmets with tunable impact absorption, Jackson says. Robots with changeable stiffness could squeeze into small spaces, but then be sturdy enough to carry or move other objects.
