For the first time in the United States, researchers have used gene editing to repair a mutation in human embryos.

Molecular scissors known as CRISPR/Cas9 corrected a gene defect that can lead to heart failure. The gene editor fixed the mutation in about 72 percent of tested embryos, researchers report August 2 in Nature. That repair rate is much higher than expected. Work with skin cells reprogrammed to mimic embryos had suggested the mutation would be repaired in fewer than 30 percent of cells.
In addition, the researchers discovered a technical advance that may limit the production of patchwork embryos that aren’t fully edited. That’s important if CRISPR/Cas9 will ever be used to prevent genetic diseases, says study coauthor Shoukhrat Mitalipov, a reproductive and developmental biologist at Oregon Health & Science University in Portland. If even one cell in an early embryo is unedited, “that’s going to screw up the whole process,” says Mitalipov. He worked with colleagues in Oregon, California, Korea and China to develop the embryo-editing methods.

Researchers in other countries have edited human embryos to learn more about early human development or to answer other basic research questions (SN: 4/15/17, p. 16). But Mitalipov and colleagues explicitly conducted the experiments to improve the safety and efficiency of gene editing for eventual clinical trials, which would involve implanting edited embryos into women’s uteruses to establish pregnancy.
In the United States, such clinical trials are effectively banned by a rule that prevents the Food and Drug Administration from reviewing applications for any procedure that would introduce heritable changes in human embryos. Such tinkering with embryo DNA, called germline editing, is controversial because of fears that the technology will be used to create so-called designer babies.

“This paper is not announcing the dawn of the designer baby era,” says R. Alta Charo, a lawyer and bioethicist at the University of Wisconsin Law School in Madison. The researchers have not attempted to add any new genes or change traits, only to correct a disease-causing version of a gene.

In the study, sperm from a man who carries a mutation in the MYBPC3 gene was injected into eggs from women with healthy copies of that gene. Carrying just one mutant copy of the gene causes an inherited heart problem called hypertrophic cardiomyopathy (SN: 9/17/16, p. 8). That condition, which strikes about one in every 500 people worldwide, can cause sudden heart failure. Mutations in the MYBPC3 gene are responsible for about 40 percent of cases. Doctors can treat symptoms of the condition, but there is no cure.

Along with the man’s sperm, researchers injected into the egg the DNA-cutting enzyme Cas9 and a piece of RNA to direct the enzyme to snip the mutant copy of the gene. Another piece of DNA was also injected into the egg. That hunk of DNA was supposed to be a template that the fertilized egg could use to repair the breach made by Cas9. Instead, embryos used the mother’s healthy copy of the gene to repair the cut.

Embryos’ self-healing DNA came as a surprise, because gene editing in other types of cells usually requires an external template, Mitalipov says. The discovery could mean that it will be difficult for researchers to fix mutations in embryos if neither parent has a healthy copy of the gene. But the finding could be good news for those concerned about designer babies, because embryos may reject attempts to add new traits.

Timing the addition of CRISPR/Cas9 is important, the researchers also discovered. In their first experiments, the team added the gene editor a day after fertilizing the eggs. Of 54 injected embryos, 13 were patchwork, or mosaic, embryos with some repaired and some unrepaired cells. Such mosaic embryos probably arise when the fertilized egg copies its DNA before researchers add Cas9, Mitalipov says.

Injecting Cas9 along with the sperm — before an egg had a chance to replicate its DNA — produced only one patchwork embryo. That embryo had repaired the mutation in all its cells, but some cells used the mother’s DNA for repair while others used the template supplied by the researchers.

None of the tested embryos showed any signs that Cas9 was cutting where it shouldn’t be. “Off-target” cutting has been a safety concern with the gene editor because of the possibility of creating new DNA errors.

The study makes progress toward using gene editing to prevent genetic diseases, but there’s still has a long way to go before clinical testing can begin, says Janet Rossant, a developmental biologist at the Hospital for Sick Children and the University of Toronto. “We need to be sure this can be done reproducibly and effectively.”

Famously sneaky particles have been caught behaving in a new way.

For the first time, scientists have detected neutrinos scattering off the nucleus of an atom. The process, predicted more than four decades ago, provides a new way to test fundamental physics. It will also help scientists to better characterize the neutrino, a misfit particle that has a tiny mass and interacts so feebly with matter that it can easily sail through the entire Earth.
The detection, reported online August 3 in Science, “has really big implications,” says physicist Janet Conrad of MIT, who was not involved with the research. It fills in a missing piece of the standard model, the theory that explains how particles behave: The model predicts that neutrinos interact with nuclei. And, says Conrad, the discovery “opens up a whole new area of measurements” to further test the standard model’s predictions.

Scientists typically spot neutrinos when they interact with a single proton or neutron. But the new study measures “coherent” scattering, in which a low-energy neutrino interacts with an entire atomic nucleus at once, ricocheting away and causing the nucleus to recoil slightly in response.

“It’s exciting to measure it for the first time,” says physicist Kate Scholberg of Duke University, spokesperson for the collaboration — named COHERENT — that made the new finding.

In the past, neutrino hunters have built enormous detectors to boost their chances of catching a glimpse of the particles — a necessity because the aloof particles interact so rarely. While still rare, coherent neutrino scattering occurs more often than previously detected types of neutrino interactions. That means detectors can be smaller and still catch enough interactions to detect the process. COHERENT’s detector, a crystal of cesium and iodine, weighs only about 15 kilograms. “It’s the first handheld neutrino detector; you can just carry it around,” says physicist Juan Collar of the University of Chicago.

Collar, Scholberg and colleagues installed their detector at the Spallation Neutron Source at Oak Ridge National Laboratory in Tennessee. The facility generates bursts of neutrons and, as a by-product, produces neutrinos at energies that COHERENT’s detector can spot. When a nucleus in the crystal recoils due to a scattering neutrino, a flash of light appears and is captured by a light sensor. The signal of the recoiling nucleus is incredibly subtle — like detecting the motion of a bowling ball when hit by a ping-pong ball — which is why the effect remained undetected until now.
The amount of scattering the researchers saw agreed with the standard model. But such tests are still in their early stages, says physicist Leo Stodolsky of the Max Planck Institute for Physics in Munich, who was not involved with the research. “We’re looking forward to more detailed studies to see if it really is accurately in agreement with the expectations.” Physicists hope to find a place where the standard model breaks down, which could reveal new secrets of the universe. More precise tests may reveal discrepancies, he says. “That would be extremely interesting.”

Measuring coherent neutrino scattering could help scientists understand the processes that occur within exploding stars, or supernovas, which emit huge numbers of neutrinos (SN: 02/18/17, p. 24). The process could be used to detect supernovas as well — if a supernova explodes nearby, scientists could spot its neutrinos scattering off nuclei in their detectors.

Similar scattering might also help scientists detect dark matter, an invisible source of mass that pervades the universe. Dark matter particles could scatter off atomic nuclei just as neutrinos do, causing a recoil. The study indicates that such recoils are detectable — good news since several dark matter experiments are currently attempting to measure recoils of nuclei (SN: 11/12/16, p. 14). But it also suggests a looming problem: As dark matter detectors become more sensitive, neutrinos bouncing off the nuclei will swamp any signs of dark matter.

Coherent neutrino scattering detectors could lead to practical applications as well: Small-scale neutrino detectors could eventually detect neutrinos produced in nuclear reactors to monitor for attempts to develop nuclear weapons, for example.

Physicist Daniel Freedman of MIT, who predicted in 1974 that neutrinos would scatter off nuclei, is pleased that his prediction has finally been confirmed. “It’s a thrill.”

I heard it for the first time a few days ago: “She’s copying me!” my 4-year-old wailed in a righteous complaint about her little sister. And she most certainly was copying, repeating the same nonsense word over and over. While it was distressing to my older kid, I thought it was funny that it took her so long to realize her sister copies almost everything she does.

This egregious violation occurred just after I had read about an experiment that pitted young kids against bonobos in a test to see who might copy other individuals more. I’ll get right to the punch line: Kids won, by a long shot. The results, published online July 24 in Child Development, show that despite imitation annoying older siblings everywhere, it’s actually really important.

“Imitation is one of the most essential skills for being human,” says study coauthor Zanna Clay, a comparative psychologist at the University of Birmingham and Durham University, both in England. Learning how to talk, operating the latest iPhone and figuring out how to buy bulk goods at the local co-op — these skills all rely on imitation. Not only that, but imitation is also important for cementing social relationships. My daughter notwithstanding, “Humans like to be imitated, and we like those who imitate us,” Clay says.
Clay and her colleague Claudio Tennie tested just how strong the urge to imitate is in 77 children ages 3 to 5 and a group of 46 bonobos ages 3 to 29. In one-on-one trials, the researchers sat next to the kids and bonobos with a small wooden box about the size of a hand. Inside was a treat: a sticker for the kids and a bit of apple for the bonobos.

Before opening the box, the researcher performed nonsensical actions over it, either rubbing the box with the back of the hand and doing a wrist twist in the air or tracing a cross into the top of the box and then tracing the edges.

These hand motions were totally irrelevant to the actual opening of the box. Nonetheless, after seeing the gestures, the vast majority of the kids made the same motions before trying to open their own box. Not a single bonobo, though, copied the irrelevant actions.
What the bonobos did — not copying the meaningless gestures — “is the rational thing to do,” says Clay. “Yet the irrational thing that the kids did is part of the reason why human cultures have evolved so rapidly and so diversely.”

Such excessive imitation, called overimitation, is a special form of copying in which people perform actions that clearly serve no purpose. It may be behind rituals, social norms and language that keep our societies running smoothly.

And it may be unique to humans: Other studies have failed to spot overimitation among chimpanzees and orangutans. These findings hint that our powerful urge to imitate even nonsensical gestures may be one of the things that separate humans from other apes.

The 2011 tsunami that devastated Japan’s coast cast an enormous amount of debris out to sea — way out. Japanese marine life took advantage of the new floating real estate and booked a one-way trip to America. From 2012 to 2017, at least 289 living Japanese marine species washed up on the shores of North America and Hawaii, hitching rides on fishing boats, docks, buoys, crates and other nonbiodegradable objects, a team of U.S. researchers report in the Sept. 29 Science.

Organisms that surprisingly survived the harsh 7,000-kilometer journey across the Pacific Ocean on 634 items of tsunami debris ranged from 52-centimeter-long fish (a Western Pacific yellowtail amberjack) to microscopic single-celled protists. About 65 percent of the species have never been seen in North America’s Pacific waters. If these newcomers become established, they have the potential to become invasive, disrupting native marine habitats, says study coauthor James Carlton, a marine scientist at Williams College in Mystic, Conn.
Meet some of the slimiest, strangest and potentially most invasive marine castaways that took this incredible journey:

The Northern Pacific sea star (Asterias amurensis) is among the world’s most invasive species. Though this purple and yellow sea star is normally found in shallow habitats, it can live as deep as 200 meters.

Skeleton shrimp (Caprella cristibrachium and C. mutica (shown)) grasp onto algae with their strong rear claws, earning them the nickname “praying mantis of the sea.” These lanky amphipods can grow up to about 5 centimeters long and are found in the Sea of Japan.
A white, brittle Bryozoan (Biflustra grandicella) that can grow as big as a basketball is already invasive in Australia. The tiny swimming larvae of these sea creatures, also known as moss animals, may live up to a week, long enough to settle in to a new habitat.

Most of the wooden Japanese debris items collected carried at least one of seven species of large wormlike mollusks called Japanese shipworms (Psiloteredo sp.). Some of the more monstrous shipworms found, which bore into everything from wooden pilings to docks, had grown to about 50 centimeters long.
Five Japanese barred knifejaw fish (Oplegnathus fasciatus), also known as striped beakfish, were found trapped in the stern well of a Japanese fishing boat found beached in 2013 in Washington. These black-and-white striped fish are native to the Northwest Pacific Ocean and Hawaii. The well acted as a tide pool of sorts, sustaining the fish during their two-year journey.

The wavy-shelled slipper snail (Crepidula onyx), also known as a slipper limpet, has essentially come full circle in its journey around the Pacific Ocean. Native to the U.S. West Coast, the well-traveled snail became an invasive species in Japan, and now has returned to America on Japanese debris.

A growing band of digital characters that converse, read faces and track body language is helping humans to communicate better with one another. While virtual helpers that perform practical tasks, such as dealing with customer service issues, are becoming ubiquitous, computer scientist M. Ehsan Hoque is at the forefront of a more emotionally savvy movement. He and his team at the University of Rochester in New York create software for digital agents that recognize when a person is succeeding or failing in specific types of social interactions. Data from face-to-face conversations and feedback from professional counselors and interviewers with relevant expertise inform this breed of computer advisers.

One of Hoque’s digital helpers grooms people to be better public speakers. With words on a screen, this attentive app notes, for example, how many times in a practice talk a person says “um,” gestures inappropriately or awkwardly shifts vocal tone. With the help of Google Glass, the app even offers useful reminders during actual speeches. Another computerized helper, this one in the form of an avatar, helps people hone their job interviewing skills, flagging long-winded responses or inconsistent eye contact in practice interviews. In the works are computerized conversation coaches that can improve speech and communication skills among people with developmental conditions such as autism and mediate business meetings in ways that encourage everyone to participate in decision making.

“There has been some progress in artificial intelligence, but not much in developing emotional aspects of AI,” Hoque says. “We’re just cracking through the surface at this point.”
The U.S. Department of Defense and the U.S. Army have taken notice. With their financial support, Hoque is developing avatars that collaborate with humans to solve complex problems, and digital observers that monitor body language to detect when people are lying.
This is heady stuff for a 35-year-old who earned a doctoral degree just four years ago. Hoque, who was born in Bangladesh and immigrated to the United States as a teenager, did his graduate work with the MIT Media Lab’s Affective Computing research group. The group’s director, Rosalind Picard, helped launch the field of “affective computing” in the 1990s, which focuses on the study and development of computers and robots that recognize, interpret and simulate human emotions.

Hoque’s approach puts a service spin on affective computing. As a grad student, he developed software he dubbed MACH, short for My Automated Conversation coacH. This system simulates face-to-face conversations with a computer-generated, 3-D man or woman that sees, hears and makes decisions while conversing with a real-life partner. Digital analyses of a human partner’s speech and nonverbal behavior inform the avatar’s responses during a session. A simulated coach may, for instance, let a user know if smiles during an interview look forced or are mistimed. After a session, users see a video of the interaction accompanied by displays of how well or poorly they did on various interaction skills, such as keeping eye contact and nodding at appropriate times.

MACH got its start in trials that trained MIT undergraduates how to conduct themselves during interviews with career counselors. First, Hoque analyzed smiles and other behaviors that either helped or hurt the impressions job candidates left on experienced counselors in mock interviews. In a series of follow-up studies, his team developed an automated system that recognized impression-enhancing behaviors during simulated interviews. That pilot version of MACH was then put to the test. Women, but not men, who received MACH training and got feedback from their digital coach while watching videos of their initial interviews with a counselor displayed substantial improvement in follow-up interviews. MACH trainees who watched interview videos but got no feedback showed minimal improvement. Testing with larger groups of men and women is under way.
As he developed MACH, Hoque consulted MIT sociologist and clinical psychologist Sherry Turkle. That was a bold move, since Turkle has warned for 30 years that, despite its pluses, digital culture discourages person-to-person connections. Social robots, in particular, represent a way for people to escape the challenges of forging authentic relationships, Turkle contends.

But she came away impressed with Hoque, whose goals she calls refreshingly modest and transparent. “His avatars will be helpers and facilitators,” she says, “not companions, friends, therapists and pretend people.”

Hoque’s approach grew out of personal experience. He is the primary caregiver for his 16-year-old brother, Eshteher, who has Down syndrome and does not speak. Eshteher can make sounds to refer to certain things, such as food, and has limited use of sign language. “I’ve spent a lot of time with him and can read what he’s experiencing, like when he’s frustrated or repentant,” Hoque says.
So it’s not surprising that Hoque’s next-generation MACH, dubbed LISSA for Live Interactive Social Skill Assistance, is an avatar that conducts flexible, “getting acquainted” conversations while providing feedback on users’ eye contact, speaking volume, smiling and body movements via flashing icons.

LISSA has shown promise in preliminary tests aimed at improving the conversational chops of college students attending speed-dating sessions and individuals with autism spectrum disorders. Hoque plans to expand this technology for use with people suffering from social phobia and post-traumatic stress disorder. He’s also working on an avatar that trains doctors to communicate clearly and compassionately with patients being treated for life-threatening cancers.

Hoque’s work on emotionally perceptive avatars may eventually transform the young industry of digital assistants, currently limited to voices-in-a-box such as Apple’s Siri and Microsoft’s Cortana, says cognitive scientist Mary Czerwinski, a principal researcher at Microsoft Research Lab in Redmond, Wash. Avatar research “could lead to more natural, personable digital assistants,” Czerwinski predicts. Hoque agrees.

“In the future, we’ll all have digital, personalized assistants,” he says. If he gets his way, emotionally attuned helpers will make us more social and less isolated. That’s something to applaud — if we can manage to put down our smartphones.

One of the planet’s deadliest viruses makes an annual pass through the United States with little fanfare. It rarely generates flashy headlines or news footage of health workers in hazmat suits. There’s no sudden panic when a sick person shows up coughing and feverish in an emergency room. Yet before next spring, this season’s lethal germ will probably have infected millions of Americans, killing tens of thousands. Still, it’s often referred to as just the flu.

The influenza virus seems so normal to most Americans that only about half of us will heed those “time for your flu shot” banners that pop up at pharmacies and worksites every autumn. Those annual shots remain the best means of protection, but they must be manufactured months before flu season starts, based on a best educated guess of what strains of the virus will be circulating. That means even in a successful year, vaccine performance may not be impressive. During the 2015–2016 season, only about half of those immunized were protected, according to a study in the Aug. 10 New England Journal of Medicine. Some years’ vaccines are duds: For the 2014–2015 season, the vaccine protected only 19 percent of people who received it, based on U.S. Centers for Disease Control and Prevention data.
Scientists have long worked to develop a flu shot that works better and lasts longer. But, unlike the very stable measles virus, influenza is a moving target. While only a few strains of flu virus circulate worldwide in a typical year, dozens more may exist. Each one is highly likely to mutate from year to year, with just enough shape-shifting to be unrecognizable to the body’s defenses.

Now, after years of searching, scientists believe they have better strategies to attack the parts of the virus that stay the same from year to year, offering the hope of protection across multiple seasons. The vaccines being developed in laboratories around the world “offer more promise than we’ve ever had,” says Walter Orenstein, associate director of the Emory Vaccine Center in Atlanta. And there are new creative approaches: One research group is trying to make a kind of super shot by anticipating every possible mutation a circulating virus might undergo.

“I’m optimistic we are going to get to a vaccine,” says Anthony Fauci, head of the National Institute of Allergy and Infectious Diseases, or NIAID, in Bethesda, Md. Then, you may need to heed those “time for your flu shot” messages only once.
Researchers often describe the flu virus as looking like a ball with lollipops sticking out. Tucked inside the ball is RNA, which the virus needs to make copies of itself. The lollipops on the outside are proteins: hemagglutinin and neuraminidase. There are 18 different kinds of hemagglutinin and 11 kinds of neuraminidase. Each kind of flu virus is named for its particular combination of these proteins; the current forms circulating around the world are H1N1 and H3N2. Hemagglutinin attaches to human cells to launch an infection; neuraminidase is more important for spreading the virus once infection has occurred.

Flu viruses involved in human epidemics are divided into types A and B, and A viruses are sliced even further into group 1 and group 2. Influenza A, the most troublesome for vaccine scientists, travels the world among birds, pigs and humans. The bird and pig versions don’t easily infect people, but the virus is constantly mutating and even swapping genes with other influenza viruses it meets along the way. Sometimes these genetic changes create a version that allows a bird or pig flu to move directly into humans. In 2013, one called H7N9 moved into people in China (SN Online: 3/11/15). The virus has since infected more than 1,500 people. Mostly, though, the genetic changes are more subtle, with just enough alterations to evade the human immune system.
Like kids with a sweet tooth, the immune system gets most excited about the top part of the hemagglutinin lollipop, and makes antibodies against it. The top is, after all, the first thing the immune system notices once the virus slips inside the nose, mouth and lungs. Every year, genetic mutations in the virus slightly change the chemical flavor of the lollipop, making it more sweet or sour than last season’s — just different enough so the immune system doesn’t recognize it. That’s why most years there’s a new flu shot.

Sometimes, in the gene shuffling with viruses in birds and pigs, the changes are so great that the flavor changes completely. Those are pandemic years, when there is so little residual immunity that a large portion of the global population falls ill from the new virus. The devastating 1918 flu, which killed an estimated 50 million people globally, was caused by such a drastic genetic shift (SN Online: 4/29/14). The most recent pandemic occurred in 2009, with the appearance of the “swine flu,” so named because the virus was first found in pigs. By one analysis, it caused between 148,000 and 249,000 deaths around the world.

Attack the stem
The 2009 disaster helped provide a blueprint for some of the latest experimental vaccines. Researchers noticed that when people with swine flu developed antibodies to the virus, those antibodies did something odd: They favored the hemagglutinin stem — the stick of the lollipop. And, more important, they appeared to react broadly against two kinds of flu virus. Scientists had known that the hemagglutinin stem, or stalk, isn’t as apt to change as the lollipop top, which theoretically makes the stem a good target for a universal vaccine. But in a usual flu season, the human body isn’t inclined to make infection-fighting antibodies against the stem.

“Unfortunately, the immune system preferentially recognizes the head, and we don’t know why it does that,” says Adrian McDermott, an immunologist at NIAID. So after infection, the biggest share of antibodies flocks to the hemagglutinin head. (Neuraminidase, the bigger player in disease after infection, is a target for influenza treatments but not a major focus for vaccine development.)

But in a study reported in the Journal of Experimental Medicine in 2011, a team of scientists from Emory and elsewhere found that antibodies to the so-called swine flu behaved unexpectedly. “If you have a head that the immune system hasn’t seen, you potentially redirect to a stalk response,” McDermott says. “That was an aha! moment.”
Researchers investigated further. For one study in 2012 in Frontiers in Immunology, scientists from Canada injected these stem-recognizing antibodies into mice to see if the mice were shielded from a different strain of flu. Not only were the mice protected from lethal doses of flu virus, but the protection was also in large part due to the absence of familiar antibodies against the head, the researchers found. Without the distraction of a head it recognized, the immune system seemed to rally against the stem.

Then came the what ifs: What if a vaccine produced just antibodies to the stem? Would that be enough protection? For the last few years, McDermott and others have been trying to develop vaccines made of “headless stalks” — just the sticks of the lollipops. With no head in place to hoard the immune response, the vaccine might coax the body to make enough stem-focused antibodies to protect against flu, the researchers hoped, regardless of the seasonal mutations occurring at the top.

Several groups soon found that headless stalks are difficult to make. Without the top to stabilize it, the molecular assembly tended to break apart. Two teams working independently reported in 2015 their success in keeping the stalk in one piece. NIAID scientists and their partners held the stalks together by anchoring them to the protein ferritin, which can assemble itself into nanoparticles. In a study in Nature Medicine, the team reported that vaccinated mice and ferrets appeared to be protected from dying of the H5N1 bird flu after receiving the vaccine, even when they developed symptoms. Unvaccinated mice and ferrets died.

The second team, from the Janssen Center of Excellence for Immunoprophylaxis in Leiden, the Netherlands, and the Scripps Research Institute in La Jolla, Calif., glued the stalk together by creating a series of genetic mutations at its top. In Science, the researchers reported that the vaccine reduced the symptoms of flu in vaccinated monkeys.

“We realized that the stem has much less variability than the head, and then we developed the capability to use it for a possible vaccine,” says Fauci, commenting on both efforts. “These were two important things that came together.”

Despite progress, these stalk-focused vaccines haven’t yet been put to human tests that would show whether they could protect broadly against many mutations of flu circulating annually, which is the ultimate test. And some stalk-directed antibodies might be better than others. In July in Science Immunology, McDermott and colleagues reported that the stalk antibodies against group 2 of the A viruses appear to be more broadly effective than those against group 1 viruses.

Other researchers have stabilized the stalk by attaching a new hemagglutinin head — a lollipop flavor that the human immune system has never tasted. In this case, researchers from the Icahn School of Medicine at Mount Sinai in New York City took tops from two flu strains that circulate only in birds, and connected each one to a human hemagglutinin stalk. This experimental vaccine consists of two doses. The first dose prompts the immune system to make antibodies against the stalk with the first top, and a second dose produces a second round of antibodies against the stalk with the second top. The idea is that the abundance of stem-focused antibodies — amplified from the two shots of vaccine — will come to the rescue during a natural infection from a virus that possesses a third, totally different head.
“The human immune system will try to find something it has seen before,” says Peter Palese, chairman of microbiology at Mount Sinai. In theory, the only antibodies in play will be the ones responding to the parts of the stalk that the immune system recognizes, known as the “conserved domains.”

“The $64,000 question,” according to Palese: “Will the immune response to these conserved domains be enough to elicit a broad immune system reaction?”

In 2016, Palese and colleagues described a test of the vaccine in the Journal of Virology. Six ferrets given the two doses were housed with six ferrets infected with H1N1 flu. Within 10 days, the vaccinated animals had become infected but had no symptoms or signs of being able to easily spread virus to others. A report in June in the same journal described tests of the vaccine in mice against influenza B viruses; the animals were protected from normally lethal doses of flu.

What’s not known is whether the stem-focused antibodies are enough to protect people from all virus variants. The vaccine from the Mount Sinai researchers is entering the first human safety trials with drugmaker GlaxoSmithKline.

Unhide and seek
Another approach incorporates proteins that don’t tend to mutate like the hemagglutinin head but are hidden from the immune system under normal circumstances. When these proteins are made visible to types of white blood cells called T cells, the immune system wakes up. T cells don’t make antibodies, but certain T cells hold on to a memory of foreign molecules seen before. When these pre-programmed T cells recognize an infection, they destroy the invader.

This work began in the 1990s, when researchers at the Weizmann Institute of Science in Rehovot, Israel, set out to find parts of the virus that remain unchanged from year to year. The team identified stable regions in three proteins — hemagglutinin, plus one from the virus membrane and one from the virus core. In 2003, a company called BiondVax Pharmaceuticals formed to develop and test, in humans, an experimental vaccine that takes these proteins and packages them in a way that the immune system can recognize them.

So far, almost 700 volunteers have participated in six small trials, all of which showed signs of a lasting immune response among most volunteers. Writing in February in Vaccine, the researchers reported that the stored serum of elderly volunteers who received the vaccine in 2011 showed an immune response to new strains of flu that were circulating three years later. The company is starting larger trials to see if the vaccine can actually protect people from getting sick.
Out of many, one
Other experimental vaccines take a different approach. Rather than relying on precision to hit a narrow target, microbiologist Ted Ross and colleagues at the University of Georgia in Athens are attempting to cast a wide net. The researchers are taking hemagglutinin mutations from every flu strain that has ever circulated, dumping them into a kind of scientific blender and attaching them to particles that can form the basis of a vaccine.

“The question we asked is, how can we make a vaccine against a strain we don’t even know exists?” Ross says. The technique he uses is called COBRA for computationally optimized broadly reactive antigen. A computer compiles all seemingly possible genetic iterations of a particular flu type — in this case H1N1 — and then bundles them into one molecule. It’s kind of like taking every novel in your local library and combining them into one giant book.

Last year in the Journal of Virology, Ross and colleagues described a COBRA-derived vaccine that represented almost all forms of H1N1 that have been around for the last 100 years. The vaccine protected mice against infection from strains of H1N1 that the mice had never been exposed to. “We took a bunch of different hemagglutinins and mixed them into one hemagglutinin molecule,” Ross says. “It protected against any strain of H1N1 we could throw at it.”

The study caught the attention of vaccine maker Sanofi Pasteur, which plans to test the vaccine in clinical trials. Ross’ lab is now using the same strategy to develop a vaccine against H3N2 strains, the other dominant kind of flu circulating around the world. Same approach, different library.

Meanwhile, the virus isn’t waiting around. Based on the heavy flu season in the Southern Hemisphere, some experts are predicting this year’s epidemic could be severe. It’s still too early to know whether the current vaccine will provide good protection, but someday, a super shot may remove the guesswork altogether.

Campfire legends of massive, shaggy bipeds called yetis are grounded in a less mysterious truth: bears.

Eight samples of remains such as fur, bones and teeth purportedly from mountain-dwelling yetis actually come from three different kinds of bears that live in the Himalayas, researchers report November 29 in the Proceedings of the Royal Society B. A ninth sample turned out to come from a dog.

Previous analyses of smaller fragments of “yeti” DNA yielded controversial results. The new study looks at bigger chunks of DNA, analyzing the complete mitochondrial genomes from alleged yetis and comparing them with the mitochondrial genomes of various bears, including polar bears and Tibetan brown bears.
The results also give new insight into the genetic relationships between the different bears that call the Tibetan Plateau home, which could guide efforts to protect these rare subspecies. During a period of glaciation about 660,000 years ago, Himalayan brown bears were one of the first groups to branch off and become distinct from other brown bears, the data suggest.

Tibetan brown bears, on the other hand, share a more recent common ancestor with their relatives in Eurasia and North America. They might have migrated to the area around 340,000 years ago, but were probably kept geographically isolated from Himalayan brown bears by the rugged mountain terrain.

COLLEGE PARK, Md. — Campus life typically challenges students with new opportunities for learning, discovery — and intimacy with germs. Lots of germs.

That makes dormitories and their residents an ideal natural experiment to trace the germs’ paths. “You pack a bunch of college kids into a very small environment … we’re not known as being the cleanliest of people,” says sophomore Parker Kleb at the University of Maryland in College Park. Kleb is a research assistant for an ongoing study tracking the spread of respiratory viruses through a student population. The study’s goal is to better understand how these viruses move around, in order to help keep illness at bay — all the more pressing, as the current flu season is on track to be among the worst recorded in the United States.
Called “C.A.T.C.H. the Virus,” which stands for Characterizing and Tracking College Health, the study traces the trajectory of viral infections using blood samples, nasal swabs and breath samples from ailing freshmen and their closest contacts. (Tagline: It’s snot your average research study.)

Donald Milton, an environmental and occupational health physician-scientist, heads the project. On a recent day, he described the study to a classroom of freshmen he hopes to recruit. He ticked off questions this research seeks to answer: What is it that makes people susceptible to getting sick? What makes them contagious? And how do they transmit a virus to others? “Maybe your house, your room has something to do with whether you’re at risk of getting infected,” Milton said.

He had a receptive audience: members of the College Park Scholars’ Global Public Health program. Infection control is right up their alley. “How sick do we have to be?” one student asked. It’s the culprit that matters, she’s told. The study covers acute respiratory infections due to influenza viruses, adenoviruses, coronaviruses or respiratory syncytial virus, known as RSV.

Of most interest, however, is influenza. “Flu is important to everybody,” says Milton. Influenza is thought to spread among humans three ways — touch; coughing and sneezing, which launches droplets containing virus from the lungs onto surfaces; and aerosols, smaller droplets suspended in the air that could be inhaled (SN: 6/29/13, p. 9).
How much each of these modes of transmission contributes to the spread of viruses is a point of fierce debate, Milton says. And that makes infection control difficult, especially in hospitals. “If we don’t understand how [viruses] are transmitted, it’s hard to come up with policies that are really going to work.”
Milton and his colleagues recently reported that people with the flu can shed infectious virus particles just by breathing. Of 134 fine-aerosol samples taken when patients were breathing normally, 52 contained infectious influenza virus — or 39 percent, according to the study, published online January 18 in the Proceedings of the National Academy of Sciences . Those fine-aerosol particles of respiratory tract fluid are 5 microns in diameter or less, small enough to stay suspended in the air and potentially contribute to airborne transmission of the flu, the researchers say.
“This could mean that just having good cough and sneeze etiquette — sneezing or coughing into tissues — may not be enough to limit the spread of influenza,” says virologist Andrew Pekosz at Johns Hopkins University, who was not involved with the study. “Just sitting in your office and breathing could fill the air with infectious influenza.”

The C.A.T.C.H. study aims to find out if what’s in the air is catching. In two University of Maryland dorms, carbon dioxide sensors measure how much of the air comes from people’s exhalations. In addition, laboratory tests measure how much virus sick students are shedding into the air. To get those samples, students sit in a ticket booth‒sized contraption called the Gesundheit-II and breathe into a giant cone. These data can help researchers estimate students’ airborne exposure to viruses, Milton says.

Another key dataset comes from DNA testing of the viruses infecting the students. “The virus mutates reasonably fast,” Milton says, so the more people it’s moved through, the more changes it will have. By combining this molecular chain of transmission with the social chain of transmission, the researchers will try to “establish who infected whom, and where, and how,” Milton says.

The goal is to enroll 130 students in C.A.T.C.H. It’s doubtful they’ll all get sick, but not that many students from this initial group are needed to start the ball rolling, says Jennifer German, a virologist and C.A.T.C.H. student engagement coordinator. “For every index case that has an infection we’re interested in, we’re following four additional contacts,” she says. “And then if any of those contacts becomes sick, we’ll get their contacts and so on.”

The study began in November 2017. As of the end of January, German says, researchers have collected samples from five sick students, but only one was infected with a target virus, influenza. The researchers now are following three contacts from that case.

But timing and the size of the current flu outbreak may be on the researchers’ side. Kleb, the research assistant, says that students are still waiting for this season’s flu to sweep through the dorms. “Once one person gets sick, it goes around to everyone on the floor,” he says. “I’m very interested to see what happens in the next few weeks, and how the study will hopefully benefit.”

The ghost catfish transforms from glassy to glam when white light passes through its mostly transparent body. Now, scientists know why.

The fish’s iridescence comes from light bending as it travels through microscopic striped structures in the animal’s muscles, researchers report March 13 in the Proceedings of the National Academy of Sciences.

Many fishes with iridescent flair have tiny crystals in their skin or scales that reflect light (SN: 4/6/21). But the ghost catfish (Kryptopterus vitreolus) and other transparent aquatic species, like eel larvae and icefishes, lack such structures to explain their luster.

The ghost catfish’s see-through body caught the eye of physicist Qibin Zhao when he was in an aquarium store. The roughly 5-centimeter-long freshwater fish is a popular ornamental species. “I was standing in front of the tank and staring at the fish,” says Zhao, of Shanghai Jiao Tong University. “And then I saw the iridescence.”

To investigate the fish’s colorful properties, Zhao and colleagues first examined the fish under different lighting conditions. The researchers determined its iridescence arose from light passing through the fish rather than reflecting off it. By using a white light laser to illuminate the animal’s muscles and skin separately, the team found that the muscles generated the multicolored sheen.
The researchers then characterized the muscles’ properties by analyzing how X-rays scatter when traveling through the tissue and by looking at it with an electron microscope. The team identified sarcomeres — regularly spaced, banded structures, each roughly 2 micrometers long, that run along the length of muscle fibers — as the source of the iridescence.

The sarcomeres’ repeating bands, comprised of proteins that overlap by varying amounts, bend white light in a way that separates and enhances its different wavelengths. The collective diffraction of light produces an array of colors. When the fish contracts and relaxes its muscles to swim, the sarcomeres slightly change in length, causing a shifting rainbow effect.
The purpose of the ghost catfish’s iridescence is a little unclear, says Heok Hee Ng, an independent ichthyologist in Singapore who was not involved in the new study. Ghost catfish live in murky water and seldom rely on sight, he says. But the iridescence might help them visually coordinate movements when traveling in schools, or it could help them blend in with shimmering water to hide from land predators, like some birds, he adds.

Regardless of function, Ng is excited to see scientists exploring the ghost catfish’s unusual characteristics.

“Fishes actually have quite a number of these interesting structures that serve them in many ways,” he says. “And a lot of these structures are very poorly studied.”

Tiny particles of plastic have been found everywhere — from the deepest place on the planet, the Mariana Trench, to the top of Mount Everest. And now more and more studies are finding that microplastics, defined as plastic pieces less than 5 millimeters across, are also in our bodies.

“What we are looking at is the biggest oil spill ever,” says Maria Westerbos, founder of the Plastic Soup Foundation, an Amsterdam-based nonprofit advocacy organization that works to reduce plastic pollution around the world. Nearly all plastics are made from fossil fuel sources. And microplastics are “everywhere,” she adds, “even in our bodies.”
In recent years, microplastics have been documented in all parts of the human lung, in maternal and fetal placental tissues, in human breast milk and in human blood. Microplastics scientist Heather Leslie, formerly of Vrije Universiteit Amsterdam, and colleagues found microplastics in blood samples from 17 of 22 healthy adult volunteers in the Netherlands. The finding, published last year in Environment International, confirms what many scientists have long suspected: These tiny bits can get absorbed into the human bloodstream.

“We went from expecting plastic particles to be absorbable and present in the human bloodstream to knowing that they are,” Leslie says.
The findings aren’t entirely surprising; plastics are all around us. Durable, versatile and cheap to manufacture, they are in our clothes, cosmetics, electronics, tires, packaging and so many more items of daily use. And the types of plastic materials on the market continues to increase. “There were around 3,000 [plastic materials] when I started researching microplastics over a decade ago,” Leslie says. “Now there are over 9,600. That’s a huge number, each with its own chemical makeup and potential toxicity.”

Though durable, plastics do degrade, by weathering from water, wind, sunlight or heat — as in ocean environments or in landfills — or by friction, in the case of car tires, which releases plastic particles along roadways during motion and braking.

In addition to studying microplastic particles, researchers are also trying to get a handle on nanoplastics, particles which are less than 1 micrometer in length. “The large plastic objects in the environment will break down into micro- and nanoplastics, constantly raising particle numbers,” says toxicologist Dick Vethaak of the Institute for Risk Assessment Sciences at Utrecht University in the Netherlands, who collaborated with Leslie on the study finding microplastics in human blood.

Nearly two decades ago, marine biologists began drawing attention to the accumulation of microplastics in the ocean and their potential to interfere with organism and ecosystem health (SN: 2/20/16, p. 20). But only in recent years have scientists started focusing on microplastics in people’s food and drinking water — as well as in indoor air.

Plastic particles are also intentionally added to cosmetics like lipstick, lip gloss and eye makeup to improve their feel and finish, and to personal care products, such as face scrubs, toothpastes and shower gels, for the cleansing and exfoliating properties. When washed off, these microplastics enter the sewage system. They can end up in the sewage sludge from wastewater treatment plants, which is used to fertilize agricultural lands, or even in treated water released into waterways.

What if any damage microplastics may do when they get into our bodies is not clear, but a growing community of researchers investigating these questions thinks there is reason for concern. Inhaled particles might irritate and damage the lungs, akin to the damage caused by other particulate matter. And although the composition of plastic particles varies, some contain chemicals that are known to interfere with the body’s hormones.

Currently there are huge knowledge gaps in our understanding of how these particles are processed by the human body.

How do microplastics get into our bodies?
Research points to two main entry routes into the human body: We swallow them and we breathe them in.

Evidence is growing that our food and water is contaminated with microplastics. A study in Italy, reported in 2020, found microplastics in everyday fruits and vegetables. Wheat and lettuce plants have been observed taking up microplastic particles in the lab; uptake from soil containing the particles is probably how they get into our produce in the first place.

Sewage sludge can contain microplastics not only from personal care products, but also from washing machines. One study looking at sludge from a wastewater treatment plant in southwest England found that if all the treated sludge produced there were used to fertilize soils, a volume of microplastic particles equivalent to what is found in more than 20,000 plastic credit cards could potentially be released into the environment each month.

On top of that, fertilizers are coated with plastic for controlled release, plastic mulch film is used as a protective layer for crops and water containing microplastics is used for irrigation, says Sophie Vonk, a researcher at the Plastic Soup Foundation.

“Agricultural fields in Europe and North America are estimated to receive far higher quantities of microplastics than global oceans,” Vonk says.
A recent pilot study commissioned by the Plastic Soup Foundation found microplastics in all blood samples collected from pigs and cows on Dutch farms, showing livestock are capable of absorbing some of the plastic particles from their feed, water or air. Of the beef and pork samples collected from farms and supermarkets as part of the same study, 75 percent showed the presence of microplastics. Multiple studies document that microplastic particles are also in fish muscle, not just the gut, and so are likely to be consumed when people eat seafood.

Microplastics are in our drinking water, whether it’s from the tap or bottled. The particles may enter the water at the source, during treatment and distribution, or, in the case of bottled water, from its packaging.

Results from studies attempting to quantify levels of human ingestion vary dramatically, but they suggest people might be consuming on the order of tens of thousands of microplastic particles per person per year. These estimates may change as more data come in, and they will likely vary depending on people’s diets and where they live. Plus, it is not yet clear how these particles are absorbed, distributed, metabolized and excreted by the human body, and if not excreted immediately, how long they might stick around.

Babies might face particularly high exposures. A small study of six infants and 10 adults found that the infants had more microplastic particles in their feces than the adults did. Research suggests microplastics can enter the fetus via the placenta, and babies could also ingest the particles via breast milk. The use of plastic feeding bottles and teething toys adds to children’s microplastics exposure.

Microplastic particles are also floating in the air. Research conducted in Paris to document microplastic levels in indoor air found concentrations ranging from three to 15 particles per cubic meter of air. Outdoor concentrations were much lower.

Airborne particles may turn out to be more of a concern than those in food. One study reported in 2018 compared the amount of microplastics present within mussels harvested off Scotland’s coasts with the amount of microplastics present in indoor air. Exposure to microplastic fibers from the air during the meal was far higher than the risk of ingesting microplastics from the mussels themselves.

Extrapolating from this research, immunologist Nienke Vrisekoop of the University Medical Center Utrecht says, “If I keep a piece of fish on the table for an hour, it has probably gathered more microplastics from the ambient air than it has from the ocean.”
What’s more, a study of human lung tissue reported last year offers solid evidence that we are breathing in plastic particles. Microplastics showed up in 11 of 13 samples, including those from the upper, middle and lower lobes, researchers in England reported.

Perhaps good news: Microplastics seem unable to penetrate the skin. “The epidermis holds off quite a lot of stuff from the outside world, including [nano]particles,” Leslie says. “Particles can go deep into your skin, but so far we haven’t observed them passing the barrier, unless the skin is damaged.”

What do we know about the potential health risks?
Studies in mice suggest microplastics are not benign. Research in these test animals shows that lab exposure to microplastics can disrupt the gut microbiome, lead to inflammation, lower sperm quality and testosterone levels, and negatively affect learning and memory.

But some of these studies used concentrations that may not be relevant to real-world scenarios. Studies on the health effects of exposure in humans are just getting under way, so it could be years before scientists understand the actual impact in people.

Immunologist Barbro Melgert of the University of Groningen in the Netherlands has studied the effects of nylon microfibers on human tissue grown to resemble lungs. Exposure to nylon fibers reduced both the number and size of airways that formed in these tissues by 67 percent and 50 percent, respectively. “We found that the cause was not the microfibers themselves but rather the chemicals released from them,” Melgert says.

“Microplastics could be considered a form of air pollution,” she says. “We know air pollution particles tend to induce stress in our lungs, and it will probably be the same for microplastics.”

Vrisekoop is studying how the human immune system responds to microplastics. Her unpublished lab experiments suggest immune cells don’t recognize microplastic particles unless they have blood proteins, viruses, bacteria or other contaminants attached. But it is likely that such bits will attach to microplastic particles out in the environment and inside the body.

“If the microplastics are not clean … the immune cells [engulf] the particle and die faster because of it,” Vrisekoop says. “More immune cells then rush in.” This marks the start of an immune response to the particle, which could potentially trigger a strong inflammatory reaction or possibly aggravate existing inflammatory diseases of the lungs or gastrointestinal tract.
Some of the chemicals added to make plastic suitable for particular uses are also known to cause problems for humans: Bisphenol A, or BPA, is used to harden plastic and is a known endocrine disruptor that has been linked to developmental effects in children and problems with reproductive systems and metabolism in adults (SN: 7/18/09, p. 5). Phthalates, used to make plastic soft and flexible, are associated with adverse effects on fetal development and reproductive problems in adults along with insulin resistance and obesity. And flame retardants that make electronics less flammable are associated with endocrine, reproductive and behavioral effects.

“Some of these chemical products that I worked on in the past [like the polybrominated diphenyl ethers used as flame retardants] have been phased out or are prohibited to use in new products now [in the European Union and the United States] because of their neurotoxic or disrupting effects,” Leslie says.
What are the open questions?
The first step in determining the risk of microplastics to human health is to better understand and quantify human exposure. Polyrisk — one of five large-scale research projects under CUSP, a multidisciplinary group of researchers and experts from 75 organizations across 21 European countries studying micro- and nanoplastics — is doing exactly that.

Immunotoxicologist Raymond Pieters, of the Institute for Risk Assessment Sciences at Utrecht University and coordinator of Polyrisk, and colleagues are studying people’s inhalation exposure in a number of real-life scenarios: near a traffic light, for example, where cars are likely to be braking, versus a highway, where vehicles are continuously moving. Other scenarios under study include an indoor sports stadium, as well as occupational scenarios like the textile and rubber industry.

Melgert wants to know how much microplastic is in our houses, what the particle sizes are and how much we breathe in. “There are very few studies looking at indoor levels [of microplastics],” she says. “We all have stuff in our houses — carpets, insulation made of plastic materials, curtains, clothes — that all give off fibers.”

Vethaak, who co-coordinates MOMENTUM, a consortium of 27 research and industry partners from the Netherlands and seven other countries studying microplastics’ potential effects on human health, is quick to point out that “any measurement of the degree of exposure to plastic particles is likely an underestimation.” In addition to research on the impact of microplastics, the group is also looking at nanoplastics. Studying and analyzing these smallest of plastics in the environment and in our bodies is extremely challenging. “The analytical tools and techniques required for this are still being developed,” Vethaak says.

Vethaak also wants to understand whether microplastic particles coated with bacteria and viruses found in the environment could spread these pathogens and increase infection rates in people. Studies have suggested that microplastics in the ocean can serve as safe havens for germs.

Alongside knowing people’s level of exposure to microplastics, the second big question scientists want to understand is what if any level of real-world exposure is harmful. “This work is confounded by the multitude of different plastic particle types, given their variations in size, shape and chemical composition, which can affect uptake and toxicity,” Leslie says. “In the case of microplastics, it will take several more years to determine what the threshold dose for toxicity is.”

Several countries have banned the use of microbeads in specific categories of products, including rinse-off cosmetics and toothpastes. But there are no regulations or policies anywhere in the world that address the release or concentrations of other microplastics — and there are very few consistent monitoring efforts. California has recently taken a step toward monitoring by approving the world’s first requirements for testing microplastics in drinking water sources. The testing will happen over the next several years.

Pieters is very pragmatic in his outlook: “We know ‘a’ and ‘b,’” he says. “So we can expect ‘c,’ and ‘c’ would [imply] a risk for human health.”

He is inclined to find ways to protect people now even if there is limited or uncertain scientific knowledge. “Why not take a stand for the precautionary principle?” he asks.

For people who want to follow Pieters’ lead, there are ways to reduce exposure.

“Ventilate, ventilate, ventilate,” Melgert says. She recommends not only proper ventilation, including opening your windows at home, but also regular vacuum cleaning and air purification. That can remove dust, which often contains microplastics, from surfaces and the air.

Consumers can also choose to avoid cosmetics and personal care products containing microbeads. Buying clothes made from natural fabrics like cotton, linen and hemp, instead of from synthetic materials like acrylic and polyester, helps reduce the shedding of microplastics during wear and during the washing process.

Specialized microplastics-removal devices, including laundry balls, laundry bags and filters that attach to washing machines, are designed to reduce the number of microfibers making it into waterways.

Vethaak recommends not heating plastic containers in the microwave, even if they claim to be food grade, and not leaving plastic water bottles in the sun.

Perhaps the biggest thing people can do is rely on plastics less. Reducing overall consumption will reduce plastic pollution, and so reduce microplastics sloughing into the air and water.

Leslie recommends functional substitution: “Before you purchase something, think if you really need it, and if it needs to be plastic.”

Westerbos remains hopeful that researchers and scientists from around the world can come together to find a solution. “We need all the brainpower we have to connect and work together to find a substitute to plastic that is not toxic and doesn’t last [in the environment] as long as plastic does,” she says.