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Mysterious deaths of bald eagles, mallards and other lake life in the southeastern United States have puzzled scientists for more than 20 years. After a long slog exploring the quirks of cyanobacteria gluing themselves to an invasive water weed, a research team has found a toxin that could be the culprit.

And it’s an odd one, the team reports March 26 in Science.

Nicknamed AETX, the toxin has an unusual chemical structure requiring building blocks rich in the element bromine, says Susan Wilde, an aquatic ecologist at the University of Georgia in Athens. Yet those bromide building blocks are not routinely abundant in southern lake water. That’s where the life story of a particular water weed comes in.

The mystery of the unknown toxin began at an Arkansas lake during the winter of 1994–95 with the nation’s largest unexplained die-off of bald eagles. The eagles, coots and some other birds lost their motor coordination, struggled to fly or even walk, and had seizures. Checking the ill animals’ brains revealed swathes of unnatural microscopic holes, or vacuoles. By 1998, six states had confirmed bird die-offs with the same disease, now called VM, short for vacuolar myelinopathy.

Wilde noticed that lakes with die-offs grew dense expanses of the green bottlebrush-shaped invasive water plant called Hydrilla verticillata. In 2001, she and several generations of students and international collaborators began a long journey of exploring whether the plants and their ride-along cyanobacteria might sometimes destroy brains.

“It’s not a safe topic for a dissertation,” she warned prospective grad students. There wasn’t much money or any certainty of success. But “it’s so cool,” she remembers them saying.

One clue came from looking at this Hydrilla under microscope lighting that can make certain substances fluoresce. That revealed splats of cyanobacteria gripping the undersides of leaves and protecting their colonies with goo. Some other cyanobacteria, which slosh around as soup in water, release great flushes of toxins that kill fish and threaten human swimmers, but leaf-clingers weren’t typically menaces.

This cyanobacterium turned out to be a new species (Aetokthonos hydrillicola). It also turned out to be hard to grow in the lab. It took two years after collecting the stuff from a reservoir before the team raised enough cyanobacteria for their first trial feeding a watery solution of it to test animals.

This cyanobacteria soup didn’t seem to bother the test chickens at all, however. Microscopic analysis found no tiny holes in their brains.

The researchers then wondered if something weird was going on with the lab culture setup. They collected wild weeds glopped with cyanobacteria from lakes with confirmed VM outbreaks. Using an elaborate lab setup to detect what chemical compounds the bacteria were making, the team hunted for unusual suspects. And there, lurking in the splotches marking the bacterial colonies, was a previously unknown compound, with abundant bromide molecules. These colonies did yield substances that killed test animals. And providing bromide compounds to lab colonies made them turn toxin too.

Bromine can get into lakes from various sources, some natural and not, such as power plants. Researchers discovered that the invasive Hydrilla builds up extreme concentrations of bromine compounds, 20 times greater than the concentrations in the lake bottom mud and 500 to 1,000 times greater than in lake water. In late summer, the warm water stays at the top of the lake trapping chilly, dark, low-oxygen water below. The weedy Hydrilla stops flourishing and starts leaking bromine-rich compounds. That’s when the cyanobacteria have the ingredients to make their deadly toxin.

The newly discovered exotic chemistry of these toxin-makers doesn’t surprise Jason Stajich of University of California, Riverside, who studies other cyanobacteria in his genetic explorations of microbial evolution. Free-floating cyanobacteria cause toxic blooms in both marine and fresh water (SN: 8/28/18). But this green bacterial group also includes species that create the world we love. The desert crusts Stajich studies (like “bread crust” but on desert surfaces, he says) take years to form and depend on networks of cyanobacteria (SN: 12/10/19).

In this case, now that the suspect has been nabbed, there’s even more reason to get rid of the Hydrilla invaders that facilitate the toxin making. Water birds gorge on the Hydrilla and its ride-along bacteria and thus get a deadly dose of toxin. Predators such as eagles and owls that feast on those water birds also get poisoned. In the lab, the toxin affects other vertebrates, such as amphibians and snakes. Knowing the makeup of the toxin will now let the lab check for effects on mammals. With such a wide range of potentially susceptible creatures, solving the mystery couldn’t have come soon enough.

Wearing waders and work gloves, three dozen employees from the U.S. Department of Agriculture’s Natural Resources Conservation Service stood at a small creek amid the dry sagebrush of southeastern Idaho. The group was eager to learn how to repair a stream the old­-fashioned way.

Tipping back his white cowboy hat, 73-year-old rancher Jay Wilde told the group that he grew up swimming and fishing at this place, Birch Creek, all summer long. But when he took over the family farm from his parents in 1995, the stream was dry by mid-June.

Wilde realized this was partly because his family and neighbors, like generations of American settlers before them, had trapped and removed most of the dam-building beavers. The settlers also built roads, cut trees, mined streams, overgrazed livestock and created flood-control and irrigation structures, all of which changed the plumbing of watersheds like Birch Creek’s.

Many of the wetlands in the western United States have disappeared since the 1700s. California has lost an astonishing 90 percent of its wetlands, which includes streamsides, wet meadows and ponds. In Nevada, Idaho and Colorado, more than 50 percent of wetlands have vanished. Precious wet habitats now make up just 2 percent of the arid West — and those remaining wet places are struggling.

Nearly half of U.S. streams are in poor condition, unable to fully sustain wildlife and people, says Jeremy Maestas, a sagebrush ecosystem specialist with the NRCS who organized that workshop on Wilde’s ranch in 2016. As communities in the American West face increasing water shortages, more frequent and larger wildfires (SN: 9/26/20, p. 12) and unpredictable floods, restoring ailing waterways is becoming a necessity.

Landowners and conservation groups are bringing in teams of volunteers and workers, like the NRCS group, to build low-cost solutions from sticks and stones. And the work is making a difference. Streams are running longer into the summer, beavers and other animals are returning, and a study last December confirmed that landscapes irrigated by beaver activity can resist wildfires.

Filling the sponge

Think of a floodplain as a sponge: Each spring, floodplains in the West soak up snow melting from the mountains. The sponge is then wrung out during summer and fall, when the snow is gone and rainfall is scarce. The more water that stays in the sponge, the longer streams can flow and plants can thrive. A full sponge makes the landscape better equipped to handle natural disasters, since wet places full of green vegetation can slow floods, tolerate droughts or stall flames.

Typical modern-day stream and river restoration methods can cost about $500,000 per mile, says Joseph Wheaton, a geomorphologist at Utah State University in Logan. Projects are often complex, and involve excavators and bulldozers to shore up streambanks using giant boulders or to construct brand-new channels.

“Even though we spend at least $15 billion per year repairing waterways in the U.S., we’re hardly scratching the surface of what needs fixing,” Wheaton says.

Big yellow machines are certainly necessary for restoring big rivers. But 90 percent of all U.S. waterways are small streams, the kind you can hop over or wade across.

For smaller streams, hand-built restoration solutions work well, often at one-tenth the cost, Wheaton says, and can be self-sustaining once nature takes over. These low-tech approaches include building beaver dam analogs to entice beavers to stay and get to work, erecting small rock dams or strategically mounding mud and branches in a stream. The goal of these simple structures is to slow the flow of water and spread it across the floodplain to help plants grow and to fill the underground sponge.

Fixes like these help cure a common ailment that afflicts most streams out West, including Birch Creek, Wheaton says: Human activities have altered these waterways into straightened channels largely devoid of debris. As a result, most riverscapes flow too straight and too fast.

“They should be messy and inefficient,” he says. “They need more structure, whether it’s wood, rock, roots or dirt. That’s what slows down the water.” Wheaton prefers the term “riverscape” over stream or river because he “can’t imagine a healthy river without including the land around it.”

Natural structures “feed the stream a healthy diet” of natural materials, allowing soil and water to accumulate again in the floodplain, he says.

Since as much as 75 percent of water resources in the West are on private land, conservation groups and government agencies like the NRCS are helping ranchers and farmers improve the streams, springs or wet meadows on their property.

“In the West, water is life,” Maestas says. “But it’s a very time-limited resource. We’re trying to keep what we have on the landscape as long as possible.”

Beaver benefits

In watersheds across the West, beavers can be a big part of filling the floodplain’s sponge. The rodents gnaw down trees to create lodges and dams, and dig channels for transporting their logs to the dams. All this work slows down and spreads out the water.

On two creeks in northeastern Nevada, streamsides near beaver dams were up to 88 percent greener than undammed stream sections when measured from 2013 to 2016. Even better, beaver ponds helped maintain lush vegetation during the hottest summer months, even during a multiyear drought, Emily Fairfax, an ecohydrologist at California State University Channel Islands, and geologist Eric Small of University of Colorado Boulder reported in 2018 in Ecohydrology.

“Bringing beavers back just makes good common sense when you get down to the science of it,” Wilde says. He did it on his ranch.

Using beavers to restore watersheds is not a new idea. In 1948, for instance, Idaho Fish and Game biologists parachuted beavers out of airplanes, partly to improve trout habitat on public lands.

Wilde used trucks instead of parachutes. In 2015 and 2016, he partnered with the U.S. Forest Service and Idaho Fish and Game to livetrap and relocate nine beavers to Birch Creek from public lands about 120 kilometers away. To ensure the released rodents had a few initial ponds where they could escape from predators, Wilde worked with Anabranch Solutions, a riverscape restoration company cofounded by Wheaton and colleagues, to construct 26 beaver dam analogs. Would these simple branch-and-post structures entice the beavers to stay in Birch Creek?

It worked like a charm. In just three years, those beavers built 149 dams, transforming the once-narrow strip of green along the stream into a wide, vibrant floodplain. Birch Creek flowed 42 days longer, through the hottest part of the summer. Fish rebounded quickly too: Native Bonneville cutthroat trout populations were up to 50 times as abundant in the ponded sections in 2019 as they were when surveyed by the U.S. Forest Service in 2000, before beavers went to work.

“When you see the results, it’s almost like magic,” Wilde says. Even more magical, the transformation cost Wilde only “a couple hundred bucks in fence posts” and a few days of sweat equity, thanks in part to those NRCS staffers who came in 2016 and a host of volunteers.

Rock dams in the desert

Beaver-powered restoration isn’t the answer everywhere, especially in the desert where creeks are ephemeral, flowing only intermittently. In Colorado’s Gunnison River basin, ranchers were looking for ways to boost water availability to ensure their cattle had enough drinking water and green grass in the face of climate change. Meanwhile, the area’s public land managers wanted to restore streams to help at-risk wildlife species like the Gunnison sage grouse, once prolific across sagebrush country.

In 2012, a group of private landowners, public agencies and nonprofit organizations launched the Gunnison Basin Wet Meadow and Riparian Restoration and Resilience-building Project to revive streams and keep meadows green. The group hired Bill Zeedyk to instruct on how to build simple, low-profile dams by stacking rocks, known widely as Zeedyk structures, to slow down the water.

Zeedyk, now 85, runs his own wetland and stream restoration firm in New Mexico, after 34 years as a wildlife biologist at the U.S. Forest Service. His 2014 book Let the Water Do the Work has inspired people across the West — including Maestas and Wheaton — to turn to simple, nature-based stream restoration solutions.

Over the last nine years, Zeedyk has helped the Gunnison collaborative build nearly 2,000 rock structures throughout the roughly 10,000-square-kilometer upper Gunnison watershed. The group has restored 43 kilometers of stream and improved nearly 500 hectares of wet habitat for people and wildlife. A typical project involves a dozen volunteers working for a day or two in one creek bottom where they build dozens of rock structures.

In 2017, Maestas asked Zeedyk to show more than 100 people involved in the NRCS-led Sage Grouse Initiative how to install rock structures. The white-bearded Zeedyk led them along an eroding gully near Gunnison that June.

Lifting his wooden walking staff, Zeedyk pointed out how the adjacent dirt road originally created by horses and wagons cut off the creek from its historic floodplain. The road made the channel shorter, straighter and steeper over time. “There’s less growing space, and the whole system is less productive,” he explained.

As participants decided where to stack rocks to spread water across the dusty sagebrush flat, Zeedyk encouraged them to “read the landscape” and “think like water.” After three hours of work, participants could already see ponds forming behind their rock creations.

Watching the teams work and laugh together, Maestas called it the aha moment for the crew. “When you get your hands dirty, there’s a degree of buy-in that can’t come from sitting in a classroom or reading about it.”

The grass is greener

The hope is that, like the beaver dam analogs, these hand-built rock structures will halt erosion, capture sediment, fill the floodplain sponge and grow more water-loving plants.

Patience, Zeedyk says, is crucial. “After we put natural processes into play in a positive direction, we have to wait for the water to do its work.”

The wait isn’t necessarily long. At four of the sites in the Gunnison basin restored with Zeedyk structures, wetland plant cover (including sedges, rushes, willows and wetland forbs) increased an average of 160 percent four years post-treatment, compared with a 15 percent average increase at untreated areas near each study site, according to a 2017 report by The Nature Conservancy.

“As of 2019, we had increased the wetland species cover by 200 percent in six years,” says Renee Rondeau, an ecologist at the Colorado Natural Heritage Program, based in Hesperus. “So great to see this success.”

Animals seem to enjoy all that fresh green growth too. Colorado Parks and Wildlife set up remote cameras to monitor whether wildlife use the restored floodplain. Since 2016, the cameras have captured more than 1.5 million images, most of which show a host of animals — from cattle and elk to sage grouse and voles — munching away in the now-lush meadows. A graduate student at Western Colorado University is classifying photos to determine whether there’s a significant difference in the number of Gunnison sage grouse at the restored sites compared with adjacent untreated areas.

“Sage grouse chicks chase the green line as the desert dries up,” Maestas explains. After hatching in June, hens and their broods seek out wet areas where chicks stock up on protein-rich insects and wildflowers to grow and survive the winter.

Water in the bank

The Gunnison basin is not the only place where sticks-and-stones restoration is paying dividends for people and wildlife. Nick Silverman, a hydroclimatologist and geospatial data scientist, and his colleagues at the University of Montana in Missoula used satellite imagery to evaluate changes in “greenness” at three sites that used different simple stream restoration treatments: Zeedyk’s rock structures in Gunnison, beaver dam analogs in Oregon’s Bridge Creek and fencing projects that kept livestock away from streambanks in northeastern Nevada’s Maggie Creek.

Late summer greenness increased up to 25 percent after streams were restored compared with before, the researchers reported in 2018 in Restoration Ecology. Plus, the streams showed greater resilience to climate variability as time went on: Along Maggie Creek, restored more than two decades before the study, the plants stayed green even when rainfall was low, and the area had substantial increases in plant production during late summer, when vegetation usually dries out.

“It’s like putting water in a piggy bank when it’s wet, so plants and animals can withdraw it later when it’s dry,” Silverman says. Even more exciting, he adds, is that the impact of the low-cost options is large enough to see from space.

Water doesn’t burn

The Sharps Fire that scorched south-central Idaho in July 2018 burned a wide swath of a watershed where Idaho Fish and Game had relocated beavers to restore a floodplain. A strip of wet, green vegetation stood untouched along the beavers’ ponds. Wheaton sent a drone to take photos, tweeting out an image on September 5, 2018: “Why is there an impressive patch of green in the middle of 65,000 acres of charcoal? Turns out water doesn’t burn. Thank you beaver!”

Fairfax, the ecohydrologist who reported that beaver dams increase streamside greenness, had been searching for evidence that beavers could help keep flames at bay. Wheaton’s tweet was a “kick in the pants to push my own research on beavers and fire forward,” she says.

With undergraduate student Andrew Whittle, now at the Colorado School of Mines, Fairfax got to work analyzing satellite imagery from recent wildfires. The two mapped thousands of beaver dams within wildfire-burned areas in several western states. Choosing five fires of varying severity in both shrubland and forested areas, the pair analyzed the data to see if creeks with beaver activity stayed greener than creeks without beavers during wildfires.

“Across the board, beaver-dammed areas didn’t burn,” Fairfax says. The study was published last December in Ecological Applications during one of the West’s worst fire seasons. It garnered plenty of attention from land managers asking for more specifics, like how many beavers are needed to buffer a fire.

Fairfax plans to study several more burned sites with beaver ponds. She hopes to eventually create a statistical model that can help people plan nature-powered stream restoration projects.

“When we’re seeing hotter, more unpredictable fires that are breaking all the rules we know of,” Fairfax says, “we have to figure out how to preserve critical wet habitats.”

Organics on Mars — Science News, March 27, 1971

[Researchers] have exposed a mixture of gases simulating conditions believed to exist on the surface of Mars to ultraviolet radiation. The reaction produced organic compounds. They conclude that the ultraviolet radiation bombarding the surface of Mars could be producing organic matter on that planet.… The fact that such organic compounds may be produced on the Martian surface increases the possibility of life on Mars.

Update

In 1976, a few years after those experiments, NASA took its search for organic molecules to the Red Planet’s surface. That year, the Viking landers became the first U.S. mission to land on Mars. Though the landers failed to turn up evidence in the soil, NASA has continued the hunt. In 2018, the Curiosity rover found hints of life: organic molecules in rocks and seasonal shifts in atmospheric methane. A new phase of the hunt began in February when the Perseverance rover landed on Mars (SN Online: 2/17/21). It will find and store rocks that might preserve signs of past life for eventual return to Earth.

First of two parts

In mystery stories, the chief suspect almost always gets exonerated before the end of the book. Typically because a key piece of evidence turned out to be wrong.

In science, key evidence is supposed to be right. But sometimes it’s not. In the mystery of the invisible “dark matter” in space, evidence implicating one chief suspect has now been directly debunked. WIMPs, tiny particles widely regarded as prime dark matter candidates, have failed to appear in an experiment designed specifically to test the lone previous study claiming to detect them.

For decades, physicists have realized that most of the universe’s matter is nothing like earthly matter, which is made mostly from protons and neutrons. Gravitational influences on visible matter (stars and galaxies) indicate that some dark stuff of unknown identity pervades the cosmos. Ordinary matter accounts for less than 20 percent of the cosmic matter abundance.

For unrelated reasons, theorists have also long suggested that nature possesses mysterious types of tiny particles predicted by a theoretical mathematical framework known as supersymmetry, or SUSY for short. Those particles would be massive by subatomic standards but would interact only weakly with other matter, and so are known as Weakly Interacting Massive particles, hence WIMPs.

Of the many possible species of WIMPs, one (presumably the lightest one) should have the properties necessary to explain the dark matter messing with the motion of stars and galaxies (SN: 12/27/12). Way back in the last century, searches began for WIMPs in an effort to demonstrate their existence and identify which species made up the dark matter.

In1998, one research team announced apparent success. An experiment called DAMA (for DArk MAtter, get it?), consisting of a particle detector buried under the Italian Alps, seemingly did detect particles with properties matching some physicists’ expectations for a dark matter signal.

It was a tricky experiment to perform, relying on the premise that space is full of swarms of WIMPs. A detector containing chunks of sodium iodide should give off a flash of light when hit by a WIMP. But other particles from natural radioactive substances would also produce flashes of light even if WIMPs are a myth.

So the experimenters adopted a clever suggestion proposed earlier by physicists Katherine Freese, David Spergel and Andrzej Drukier, known formally as an annual modulation test. But let’s just call it the June-December approach.

As the Earth orbits the sun, the sun also moves, traveling around the Milky Way galaxy, carried by a spiral arm in the direction of the constellation Cygnus. If the galaxy really is full of WIMPs, the sun should be constantly plowing through them, generating a “WIMP wind.” (It’s like the wind you feel if you stick your head out of the window of a moving car.) In June, the Earth’s orbit moves it in the same direction as the sun’s motion around the galaxy — into the wind. But in December, the Earth moves the opposite direction, away from the wind. So more WIMPs should be striking the Earth in June than in December. It’s just like the way your car windshield smashes into more raindrops when driving forward than when going in reverse.

At an astrophysics conference in Paris in December 1998, Pierluigi Belli of the DAMA team reported a clear signal (or at least a strong hint) that more particles arrived in June than December. (More precisely, the results showed an annual modulation in frequency of light flashes, peaking around June with a minimum in December.) The DAMA data indicated a WIMP weighing in at 59 billion electron volts, roughly 60 times the mass of a proton.

But some experts had concerns about the DAMA team’s data analysis. And other searches for WIMPs, with different detectors and strategies, should have found WIMPs if DAMA was right — but didn’t. Still, DAMA persisted. An advanced version of the experiment, DAMA/LIBRA, continued to find the June-December disparity.

Perhaps DAMA was more sensitive to WIMPs than other experiments. After all, the other searches did not duplicate DAMA’s methods. Some used substances other than sodium iodide as a detecting material, or watched for slight temperature increases as a sign of a WIMP collision rather than flashes of light.

For that matter, WIMPs might not be what theorists originally thought. DAMA initially reported 60 proton-mass WIMPs based on the belief that the WIMPs collided with iodine atoms. But later data suggested that perhaps the WIMPs were hitting sodium atoms, implying a much lighter WIMP mass — lighter than other experiments had been optimally designed to detect. Yet another possibility: Maybe trace amounts of the metallic element thallium (much heavier atoms than either iodine or sodium) had been the WIMP targets. But a recent review of that proposal found once again that the DAMA results could not be reconciled with the absence of a signal in other experiments.

And now DAMA’s hope for vindication has been further dashed by a new underground experiment, this one in Spain. Scientists with the ANAIS collaboration have repeated the June-December method with sodium iodide, in an effort to reproduce DAMA’s results with the same method and materials. After three years of operation, the ANAIS team reports no sign of WIMPs.

To be fair, the no-WIMP conclusion relies on a lot of seriously sophisticated technical analysis. It’s not just a matter of counting light flashes. You have to collect rigorous data on the behavior of nine different sodium iodide modules. You have to correct for the presence of rare radioactive isotopes generated by cosmic ray collisions while the modules were still under construction. And then the statistical analysis needed to discern a winter-summer signal difference is not something you should try at home (unless you’re fully versed in things like the least-square periodogram or the Lomb-Scargle technique). Plus, ANAIS it still going, with plans to collect two more years of data before issuing a final analysis. So the judgment on DAMA’s WIMPs is not necessarily final.

Nevertheless, it doesn’t look good for WIMPs, at least for the WIMPs motivated by belief in supersymmetry.   

Sadly for SUSY fans, searches for WIMPs from space are not the only bad news. Attempts to produce WIMPs in particle accelerators have also so far failed. Dark matter might just turn out to consist of some other kind of subatomic particle.

If so, it would be a plot twist worthy of Agatha Christie, kind of like Poirot turning out to be the killer. For symmetry has long been physicists’ most reliable friend, guiding many great successes, from Einstein’s relativity theory to the standard model of particles and forces.

Still, failure to find SUSY particles so far does not necessarily mean they don’t exist. Supersymmetry just might be not as simple as it first seemed. And SUSY particles might just be harder to detect than scientists originally surmised. But if supersymmetry does turn out not to be so super, scientists might need to reflect on the ways that faith in symmetry can lead them astray.

Marine science has its own crop circle mysteries. Sea turtles, sharks, penguins and even whales sometimes just go circular, swimming around and around in a loop or spiral. The puzzles are not whodunits so much as whydoits.

“I doubted my eyes when I first saw the data,” says marine biologist Tomoko Narazaki of the University of Tokyo. A green sea turtle (Chelonia mydas) she and colleagues tagged near an African island with good places for laying eggs made a total of 26 circles. The turtle turning and turning underwater swam “like a machine,” Narazaki says.

When Narazaki got home and enthused to her institute colleagues, she found that they had recorded circling or spiraling bouts now and then in other marine animals.  Going back more than a decade, 3-D data-logging devices fastened on 10 sea species as diverse as king penguins and a Cuvier’s beaked whale had picked up enough detail to reconstruct the animals’ circles and squiggles, Narazaki and colleagues report March 18 in iScience.

It’s easy to imagine what’s going on with some of the swimmers: Tiger sharks (Galeocerdo cuvier) looping around during the deep phase of their plunges to depths near the Hawaiian Islands are probably circling in search of prey.  Other researchers have found humpback whales whooshing around creating circular death traps of bubbles that keep prey in a dense, gulpable mass (SN: 11/9/19). But some acrobatics get more mysterious.

The green sea turtle that amazed Narazaki was circling steadily — no lunges or exploratory side-loopings —so the researchers doubt the animal was looking for food. Narazaki saw this behavior while tracking a turtle that researchers had moved off-course on its way to lay eggs. The turtle didn’t swim bouts of repeated circles until near the inviting island. That circling may have had something to do with getting a good read on an important location, perhaps checking the geomagnetic field, the researchers propose. They note that submarines also circle as they take geomagnetic data.

“This might be similar to what humans often do when hiking through wilderness,” says Kenneth Lohmann, at the University of North Carolina at Chapel Hill. When turning off a path, we often take a special look around the crucial spot so we can retrace our steps. Lohmann has studied direction finding in hatchling sea turtles, and can imagine the adult green turtles checking not just the magnetic field, but a variety of location clues including chemical traces and sounds.

One of the new paper’s more puzzling curled paths followed a Cuvier’s beaked whale (Ziphius cavirostris) coming up from a deep dive. Its route angled up in a relatively straight line from around the depths until roughly 640 meters from the surface. Then the whale started spiraling upward in wide curlicues.

Several possible explanations come to mind, says Sascha Kate Hooker, from the University of St. Andrews in Scotland, who studies dive physiology in marine mammals. In theory, deep-plunging whales could risk getting the bends if they swim upward too fast, she has calculated. A slower ascent, with loops, might reduce that risk.

Yet speeds vary so much in rising beaked whales there must be more than basic physiology in play, Hooker says. She’s convinced by other researchers that evading the killer whales matters a lot on these upward trips. A straight path can take the beaked whale a kilometer (horizontally) away from its starting point in the depths. So spirals might let the animal cover the distance upward and start looking for its companions without moving so far off. ‘I wonder if this relatively passive second half of the ascent, staying in the same spot, would help animals regroup,” she says.

King penguins (Aptenodytes patagonicus) don’t forage as deeply as beaked whales but do swim circles near the surface, Narazaki reports. If they’re circling rather slowly, they might just be preening their feathers, a vital task for maintaining insulation in Antarctic waters, says Manfred Enstipp of Hubert CURIEN Multidisciplinary Institute in Strasbourg, France, who also has studied these birds. If the penguins are circling fast though, the muscle activity might help them get blood flowing and warm up. So that’s another possible comparison with humans outdoors, stamping our feet to warm up on a winter’s day, maybe even turning in little mystery circles ourselves.

Barely a year after the World Health Organization declared the coronavirus outbreak a pandemic, 11 vaccines worldwide have been granted emergency use authorization or given full approval. Millions of shots are going into arms every day: As of March 19, 410 million people around the world have gotten the jabs.

As mind-boggling as that is, it still falls far short of the need.  

Those 11 vaccines “will not be enough to fulfill the global need in the short term,” says Esther Krofah, executive director of FasterCures, part of the Milken Institute think tank in Washington, D.C. Of the more than 7 billion people on Earth, only about 1.2 percent of the world’s population is now fully vaccinated against the coronavirus. “We need as many vaccines over the finish line as can get through the scientific process,” she says.

Help may be on the way. Another 251 COVID-19 vaccines are at some stage of development with 60 far enough along to be tested in people, says Carly Gasca, senior associate at FasterCures.

Some vaccines are close to the finish line. For example, one made by Novavax of Gaithersburg, Md., may soon request emergency use authorization in the United States and other countries. But vaccines in the pipeline can fail at any stage. Already at least four vaccine candidates have been abandoned, including two from pharmaceutical giant Merck that failed to generate immune responses as strong as those from natural infections. That company is now helping produce Johnson & Johnson’s one-dose vaccine (SN: 2/27/21).

Among the hurdles: The already-in-use vaccines have set a high bar. For instance, mRNA vaccines from Moderna and Pfizer have proven to have about 94 to 95 percent efficacy in clinical trials and in real-world situations and may protect against infection and disease after just one shot (SN: 2/26/21). And finding people willing to participate in gold-standard clinical trials in which they might get a placebo instead of a vaccine could be tough, especially in countries where other authorized vaccines are available.

“You have to have something super über-duper special about your product to survive in this environment,” says Onyema Ogbuagu, a virologist who heads COVID-19 clinical trials at Yale School of Medicine.

That edge could come from logistics. To be effective, vaccines have to get into people’s bodies. So unlike the Pfizer and Moderna shots, vaccines that don’t have to be frozen have a better chance of being used in rural or remote areas and places that don’t have resources to buy and maintain freezers, Gasca says.  

Or an edge could come from an ability to handle emerging variants of the coronavirus that may be more infectious, more deadly or both (SN: 2/5/21). “The variants emerging are changing the landscape of the kind of virus we’re fighting now versus the virus that we were fighting in the fall and in the summer,” Krofah says. New vaccines may need to combat even more variants.

Here’s a closer look at some of the novel ways vaccine makers are approaching these challenges.  

COVAXX

How it works: COVAXX designed small pieces of protein, called peptides, from several of the proteins from SARS-CoV-2, the coronavirus that causes COVID-19. Peptides mimic important structures within the coronavirus proteins, including a part of the spike protein used to break into cells. When injected into the body, the lab-made peptides prod the immune system to build antibodies and gear up other immune cells to attack the coronavirus should the vaccinated person encounter it later. (The Dallas-based company is not connected to the similarly named World Health Organization’s COVAX program that distributes vaccines to low-income countries.)

How it’s different: While other vaccines, including Novavax’s candidate, use the entire spike protein, COVAXX has homed in on portions of coronavirus proteins that are important for function and are likely to provoke a reaction from the immune system. The vaccine is stable at refrigerator temperature.

Clinical trial status: The company completed Phase I testing for safety and the ability to rev up the immune system in 60 adults. All of the volunteers made antibodies and had immune cells known as T cells and B cells trained to recognize the coronavirus in the event of future encounters. Participants had only mild side effects, with few people reporting symptoms such as fever and fatigue.

COVAXX is doing Phase II testing in Taiwan to learn more about the immune response and side effects. Phase II and III testing will begin soon in Brazil to determine the vaccine’s efficacy.

Combating variants: The company is already working a second generation of the vaccine that could work against multiple variants, says COVAXX cofounder Mei Mei Hu.   

Thoughts on being behind: “I never thought this was winner takes all,” Hu says. “The demand is still incredible, and even when it is met, there will continue to be unmet needs,” including vaccines that can tackle variants, vaccines that work well for people with suppressed immune systems, vaccines for children and vaccines that can mix and match with others in case booster shots are needed.

Vaxart

How it works: The San Francisco–based company engineered a common cold virus called an adenovirus to carry instructions for making two coronavirus proteins into human cells.  There, the proteins can be made to prime the immune system to later fend off the coronavirus.

How it’s different: Vaxart’s vaccine is a pill: It can be swallowed instead of injected. The tablets can be stored at room temperature and don’t need trained medical workers or equipment to administer. That could make the pill ideal for sending booster doses through the mail or using in hard-to-reach places where keeping vaccines cold is difficult. And people who are afraid of needles might like a tablet alternative.

Taking the vaccine orally also may produce more of an immune response in the mucous membranes that line the nose, mouth, throat and digestive tract than injected vaccines do, says Sean Tucker, Vaxart’s founder and chief scientific officer.

Other vaccines already in use, including the Johnson & Johnson, AstraZeneca, Sputnik V and CanSino vaccines, also contain engineered adenoviruses. But those vaccines have instructions for making just one coronavirus protein, the famous spike protein. Vaxart’s vaccine contains instructions for making the spike protein, and also for the nucleocapsid, or N protein. The N protein is important for replication and assembly of the coronavirus. It provides another target for antibodies that can shut the virus down.

Clinical trial status: Because the vaccine works in airways and the digestive tract, it is difficult to directly compare with injected vaccines, Tucker says. But the vaccine appears to generate antibodies against both the spike and N proteins and revs up T cells to combat the virus, according to preliminary results from a small Phase I trial to test safety and immune responses. Full results are expected soon.

Side effects were generally mild. Some who took a high dose experienced diarrhea and nausea. Those symptoms are not usually seen with injected vaccines. A lower dose of the tablet vaccine didn’t produce those symptoms.

The company will soon begin a Phase IIa study to determine the optimal dose of the vaccine, and Tucker says the team hopes to start an efficacy study later this year.

Combating variants: Even though the spike protein has undergone many changes, the N protein hasn’t altered much. The difference between the N proteins in the B.1.351 variant first described in South Africa and the original SARS-CoV-2 is just one amino acid. Hopefully that will mean antibodies and T cells against the N protein can neutralize variants as well as they do the original virus, Tucker says. Meanwhile, he says, “we are looking at new versions of the vaccines in research and will test preclinically [in animals or cells] to see if there are advantages to making new matched vaccines.” 

Thoughts on being behind: The coronavirus may never go away entirely. If it behaves like coronaviruses that cause the common cold, people may get reinfected every two to five years. “I think our vaccine could be a great second-generation solution,” Tucker says. The pill vaccine might be an easy way to deliver boosters to people who have gotten other COVID-19 vaccines, he says.

Valneva

How it works: Valneva’s vaccine is an inactivated, or “killed,” version of SARS-CoV-2. The virus used in the vaccine was isolated from a patient in Italy. Then, Valneva’s scientists engineered it to lack a protein necessary for the virus to replicate. The vaccine virus has to be grown in monkey cells, which have been engineered to make the missing viral protein. Human cells don’t normally produce that protein, so the vaccine virus can’t replicate and cause disease, but can still stimulate immune responses.

Although inactivated vaccines have been used for decades, “our vaccine is not any less modern than any of the others,” says Thomas Lingelbach, the Saint-Herblain, France-based company’s president and chief executive officer.

How it’s different: Its engineering is different. Several inactivated COVID-19 vaccines, including ones made by the Chinese companies Sinopharm and Sinovac and by Bharat Biotech in India, are in use around the world. But those viruses are killed by dousing them in chemicals instead of engineering the virus the way Valneva has.

Clinical trial status: Results from a Phase I/II study are expected in April.

Combating variants: Because the vaccine contains the whole virus (minus one protein), variants that have tweaks in their spike protein may not be as big a problem for Valneva’s vaccines as for other vaccines. There are a lot of other parts of the virus for the immune system to recognize. The company is also working on creating versions of the vaccine based on strains circulating in people.

Thoughts on being behind: “We’re not entirely unhappy to be a bit slower,” Lingelbach says. The company may be able to build on other vaccines’ successes and learn from their failures. By comparing immune responses from its vaccine with already established vaccines, the company may be able to get hints of its vaccine’s efficacy early on in its development rather than having to wait for a Phase III trial. Regulators eventually may allow head-to-head comparisons of efficacy — as is commonly done with new flu vaccines — rather than testing each vaccine against a placebo.

INOVIO

How it works: DNA instructions for building the coronavirus spike protein are zapped into the skin with a split-second pulse of electricity. From there, cells in the body produce the spike protein and cue the immune defenses.

How it’s different: No other vaccine has this delivery method. Electrical pulses that push the DNA into cells are made by a handheld device that resembles an electric toothbrush. Some people report that the zap is less painful than a needle stick.

The vaccine may produce fewer side effects than some already in use.  “We haven’t seen fatigue and fever and other systemic effects,” says Joseph Kim, INOVIO’s chief executive officer. Kim speculates it may be because the vaccine contains only DNA and saline, or because different types of cells may take up the DNA than are affected by injected vaccines. Only five of 40 people tested in a Phase I study reported any side effects, and all of those were mild, researchers reported December 23 in EClinicalMedicine.

Additionally, the vaccine can be stored for a year at room temperature and for five years in a refrigerator.

Clinical trial status: Results from the Phase I study indicate that people make antibodies against the coronavirus at higher levels, on average, than those given the Johnson & Johnson and Sinovac vaccines, which use adenoviruses to deliver DNA instructions for building the spike protein to human cells, Kim says. It’s unclear why. And while antibody levels were lower than those produced by the mRNA vaccines, the DNA vaccine does a good job of revving up T cells to fight the coronavirus.  

INOVIO has started Phase II testing of its vaccine, with early results expected soon. A Phase III trial will start once the U.S. Food and Drug Administration clears a commercial version of the DNA delivery device to be used in the trial.

Combating variants: The company is testing whether antibodies made against the vaccine can still fight off the variants. In addition, INOVIO, headquartered in Plymouth Meeting, Pa., hopes to engineer a universal COVID vaccine that could fight off known and unknown versions of SARS-CoV-2.

Thoughts on being behind: The company isn’t worried about standing out against other vaccines, Kim says. “We have several advantages as a vaccine,” he says. “We are extremely motivated to get to our efficacy trial.… We’re working very eagerly and passionately to make sure that INO-4800 is one of the arsenals that global health will have to fight this infection around the world.

Complex carbon-bearing molecules that could help explain how life got started have been identified in space for the first time.

These molecules, called polycyclic aromatic hydrocarbons, or PAHs, consist of several linked hexagonal rings of carbon with hydrogen atoms at the edges. Astronomers have suspected for decades that these molecules are abundant in space, but none had been directly spotted before.

Simpler molecules with a single ring of carbon have been seen before. But “we’re now excited to see that we’re able to detect these larger PAHs for the first time in space,” says astrochemist Brett McGuire of MIT, whose team reports the discovery in the March 19 Science.

Studying these molecules and others like them could help scientists understand how the chemical precursors to life might get started in space. “Carbon is such a fundamental part of chemical reactions, especially reactions leading to life’s essential molecules,” McGuire says. “This is our window into a huge reservoir of them.”

Since the 1980s, astronomers have seen a mysterious infrared glow coming from spots within our galaxy and others. Many suspected that the glow comes from PAHs, but could not identify a specific source. The signals from several different PAHs overlap too much to tease any one of them apart, like a choir blending so well, the ear can’t pick out individual voices.

Instead of searching the infrared signals for a single voice, McGuire and colleagues turned to radio waves, where different PAHs sing different songs. The team trained the powerful Green Bank Telescope in West Virginia on TMC-1, a dark cloud about 430 light-years from Earth near the constellation Taurus.

Previously, McGuire had discovered that the cloud contains benzonitrile, a molecule made of a single carbon ring (SN: 10/2/19). So he thought it was a good place to look for more complicated molecules.

The team detected 1- and 2-cyanonaphthalene, two-ringed molecules with 10 carbons, eight hydrogens and a nitrogen atom. The concentration is fairly diffuse, McGuire says: “If you filled the inside of your average compact car with [gas from] TMC-1, you’d have less than 10 molecules of each PAH we detected.”

But it was a lot more than the team expected. The cloud contains between 100,000 and one million times more PAHs than theoretical models predict it should. “It’s insane, that’s way too much,” McGuire says.

There are two ways that PAHs are thought to form in space: out of the ashes of dead stars or by direct chemical reactions in interstellar space. Since TMC-1 is just beginning to form stars, McGuire expected that any PAHs it contains ought to have been built by direct chemical reactions in space. But that scenario can’t account for all the PAH molecules the team found. There’s too much to be explained easily by stellar ash, too. That means something is probably missing from astrochemists’ theories of how PAHs can form in space.

“We’re working in uncharted territory here,” he says, “which is exciting.”

Identifying PAHs in space is “a big thing,” says astrochemist Alessandra Ricca of the SETI Institute in Mountain View, Calif., who was not involved in the new study. The work “is the first one that has shown that these PAH molecules actually do exist in space,” she says. “Before, it was just a hypothesis.”

Ricca’s group is working on a database of infrared PAH signals that the James Webb Space Telescope, slated to launch in October, can look for. “All this is going to be very helpful for JWST and the research on carbon in the universe,” she says.

Hayley Gudgin of Sammamish, Wash., got her first migraine in 1991 when she was a 19-year-old nursing student.

“I was convinced I was having a brain hemorrhage,” she says. “There was no way anything could be that painful and not be really serious.”

She retreated to her bed and woke up feeling better the next day. But it wasn’t long until another migraine hit. And another. Taking a pill that combines caffeine with the pain relievers acetaminophen and codeine made life manageable until she got pregnant and had to stop taking her medication. After her son was born, the migraines came back. She started taking the drugs again, but they didn’t work and actually made her attacks worse.

By the time Gudgin gave birth to her second son in 1997, she was having about 15 attacks a month. Her symptoms worsened over time and included severe pain, nausea, sensitivity to light, swollen hands, difficulty speaking, vomiting and diarrhea so intense she often wound up dehydrated in the emergency room.

“It hit me [that] I had to do something when I was vomiting in the toilet, and my 3-year-old came and pulled my hair back,” she says. “It was no way to live — and not just because of the pain. You go to sleep every night not knowing how you’re going to wake up. You make plans knowing you might have to cancel them.”

A headache specialist prescribed several preventive medicines, but each caused side effects for Gudgin, including weight gain and kidney stones. Then, in 2018, Gudgin read about a new type of treatment for frequent migraine sufferers. Her neurologist agreed it was worth a try. After much wrangling with her insurance company — the drug is costly, and she had to prove that two other drugs had failed to help her — she got approval to take it.

In August 2018, Gudgin received her first monthly injection of erenumab, sold as Aimovig. By the end of September, she was down to one or two attacks a month. “And the migraines I do get are usually gone within six hours. I don’t have to go to the ER or lie in a dark room all day,” she says. “It’s just been life changing.”

Gudgin injects the drug into her leg once a month using a device similar to an EpiPen. Erenumab is one of four monoclonal antibodies, manufactured proteins that can bind to substances in the body, that have been approved since 2018 by the U.S. Food and Drug Administration to prevent migraines. The antibodies inhibit the action of a neurotransmitter called calcitonin gene-related peptide, or CGRP, either by changing the peptide’s shape or attaching to its receptors in the brain.

The drugs have changed the game for some migraine sufferers. Roughly half of people who took one of the four drugs in clinical trials saw at least a 50 percent reduction in monthly migraines, says neurologist David Dodick of the Mayo Clinic in Phoenix, who reported the findings at a Migraine Trust International Symposium in October. About a third of patients had a 75 percent drop in migraine days.

The CGRP-blockers appear to be an improvement over existing preventive treatments, which were developed for other disorders. The newer drugs were designed specifically to target one of the mechanisms that researchers think leads to the painful episodes.

Doctors are embracing the new drugs because they can work better and generally have much fewer side effects than other options. “It’s really beneficial for improving quality of life in our patients with migraines. [The new drugs] don’t cause weight gain, sleepiness, brain fog,” says neurologist Nina Riggins, a headache specialist at the University of California, San Francisco.

And the options for blocking CGRP are expanding. Rimegepant, or Nurtec, is one of several drugs known as gepants that bind to the CGRP receptor. The drug, an oral tablet rather than a shot, was approved as a treatment for acute migraine in February 2020. When taken every other day, rimegepant appears to also offer some benefit as a preventive, as reported January 2 in the Lancet.

Nothing typical

Migraine is the third most common disorder in the world, according to the World Health Organization. Migraines or severe headaches affect more than 15 percent of U.S. adults, striking women twice as often as men, the U.S. Centers for Disease Control and Prevention reports. In all, more than 39 million Americans get migraine attacks, which can last four to 72 hours.

Along with the most common symptom — severe throbbing pain in the head — patients can experience sensitivity to light, smells and sound; dizziness; vomiting; numbness; and visual disturbances such as blind spots and tunnel vision.

“Migraine is probably more than one disease,” says neurologist Richard Lipton of Albert Einstein College of Medicine in the Bronx, N.Y. “There are more than 40 identified genes that contribute to the risk of migraine. What that means is that there are multiple pathways that lead to migraine, and as a consequence of that, migraine is not a one-size-fits-all condition.”

Although many genes have been identified as playing a role, researchers have not pinpointed the exact mechanisms involved with migraine. The long-held notion of blood vessel dilation being to blame has even fallen out of favor, says Amaal Starling, a neurologist at the Mayo Clinic in Scottsdale, Ariz.

“We know pain is caused by … abnormal activity in multiple parts of the brain, including the trigeminal nerve, trigeminal nucleus caudalis in the brain stem, and the pain networks,” Starling says. This leads to migraine-related pain in the head, face and neck.

Some theories suggest that migraine occurs — and a cascade starts — when nerve cells in the brain get overexcited and stimulate the trigeminal nerve, which controls movement of the jaw muscle and sensations of touch, pain and temperature in the face. The trigger can be hormonal changes, stress, food, smells, sounds, a visual stimulus or some combination. The first step in the cascade releases CGRP in the brain, which causes transmission of pain signals.

The pain signals trigger an additional release of CGRP and other peptides. These molecules tell the brain to increase the dilation of blood vessels, releasing toxic chemicals. This is why, at least for some people, CGRP may be a big part of the problem.

No easy fix

Treating chronic migraine is often a two-pronged approach: Try to prevent migraine attacks by managing the underlying cause, and stop attacks when they strike.

Part of a long-lasting problem with chronic migraine is that drugs available for prevention were developed for other diseases, such as hypertension, depression and epilepsy. For example, doctors realized that patients with high blood pressure who also had migraines reported fewer migraines after taking beta-blockers. The medicine slows down the heart by blocking the effect of adrenaline, a hormone that speeds up circulation. Similar stories led to the use of anticonvulsants, antidepressants, antianxiety medications, narcotics and antihistamines.

None of these drugs are without side effects, and they are ineffective for 40 to 50 percent of chronic migraine patients, according to a 2017 analysis of insurance claims data by Dodick and colleagues in Cephalalgia. Within six months of starting four commonly used migraine prevention drugs, 75 percent of patients had stopped using them. The researchers assume, based on other studies, that the main reasons for stopping were side effects and lack of efficacy.

Side effects include weight gain, nausea, brain fog, drowsiness, speech disturbance and lack of concentration. And sometimes the treatments themselves can bring on headaches. “Most of the acute treatments that we use for migraine, if they’re taken too often, cause medication overuse headaches,” Lipton says.

Focus on one pathway

Researchers realized about 20 years ago that CGRP plays a role in migraine. The peptide helps nerve cells communicate with each other. “[CGRP] is very heavily represented in the pathways that are involved in migraine,” Lipton says.

In one study, researchers measured CGRP levels in the blood and found higher levels in people who had migraines than in people who did not. And among those who experienced migraines, CGRP blood levels went up as migraines came on. In a separate study, when an induced migraine attack was effectively treated, CGRP blood levels came down, says Deborah Friedman, a neuro-ophthalmologist at University of Texas Southwestern Medical Center in Dallas.

The work led to the creation of the four monoclonal antibodies approved for preventing migraines. One of them, erenumab, the drug that’s helping Gudgin, mimics the shape of CGRP, binding to the CGRP nerve receptor so the CGRP has no place to attach when it arrives at a nerve cell. The other three drugs — galcanezumab (Emgality), fremanezumab (Ajovy) and eptinezumab (Vyepti) — attach to CGRP itself, changing its shape so it can’t fit into the receptor. All four drugs are given as monthly or quarterly injections or intravenous infusions.

These monoclonal antibodies help some patients and produce fewer side effects than existing treatments. In a 2019 survey of nearly 600 people taking galcanezumab to prevent migraines, conducted by the drug’s maker, Indianapolis-based Eli Lilly, nearly 80 percent reported their migraine as “better” overall since starting the medication. In a study funded by eptinezumab’s manufacturer, H. Lundbeck A/S in Copenhagen, more than 80 percent of about 700 patients reported they had a 50 percent or greater drop in migraine days in at least one four-week interval, and about one-third of patients taking intravenous eptinezumab saw that same drop over the entire 24-week study.

Only 20.5 percent of patients taking a placebo saw the same drop in migraine days, as reported last October in the Journal of Headache and Pain.

“Most of the acute treatments that we use for migraine, if they’re taken too often, cause medication overuse headaches.”

Richard Lipton

The gepants go after the same pathway, but can be taken orally because they are small molecules. Gepants are prescribed on an as-needed basis to stop acute migraines. Recent studies suggest they may have preventive benefits too, according to an April 2020 report in Headache.

Gepants have been studied since 2004, but earlier versions caused liver problems, so they never made it to market. In 2019 and 2020, the FDA approved two formulations — ubrogepant, or Ubrelvy, and rimegepant, or Nurtec. Overall, the gepants appear to stop migraine pain within two hours in about 20 percent of patients and do not bring on the overuse headaches that are common with other acute treatments.

Two additional gepants, atogepant and zavegepant, are still in patient trials. Atogepant is being evaluated as a preventive, while zavegepant is being looked at as an acute medication.

Lipton and colleagues reported in the Lancet on January 2 the results of a Phase II/III prevention study of rimegepant, funded by Biohaven Pharmaceuticals of New Haven, Conn. Of 348 participants who took the drug every day, 49 percent experienced a 50 percent or greater reduction in moderate to severe migraine days each month. But the placebo group did almost as well, with a 41 percent reduction.

The need for new ideas

Clearly, this variety of CGRP inhibitors don’t work for everyone. And they cause side effects for some people, including constipation, increased risk for upper respiratory tract infections and injection-site pain.

Amy Chesney, a retired software engineer who lives in Bossier City, La., started getting migraines in 1992, tried three different CGRP drugs and found that they made her depressed and didn’t do anything for her migraines.

There’s also some concern about long-term effects from CGRP monoclonal antibodies, since CGRP exists in the peripheral nervous system as well as the brain. For instance, CGRP causes blood vessels to dilate in a variety of systems including the intestines.

Doctors say this is why constipation is one of the drugs’ most common side effects. CGRP is also involved in hair follicles, and some patients have reported hair loss. And CGRP is important to blood vessel health, which is why researchers say it will be important to complete long-term studies to look for cardiac issues, although so far none have surfaced.

Finally, the drugs are expensive and, as Gudgin discovered, insurance companies can make patients and doctors jump through hoops before covering the cost, says Matthew Robbins, a neurologist at Weill Cornell Medicine and New York-Presbyterian Hospital in New York City.

When erenumab received FDA approval, its manufacturers, Novartis of Basel, Switzerland, and Amgen of Thousand Oaks, Calif., set a price of $6,900 per year for the drug. “Generally, you can’t just prescribe them straight away. [Patients] have to either not tolerate established medications or [show] that they do not work first,” Robbins says.

It took two denials and three months before Gudgin’s insurance company would approve payment. First, she had to prove that she had tried cheaper preventive medications. Then she had to confirm that she got migraines frequently enough to classify her disease as chronic.

Gudgin says that although her insurance company finally paid for her treatment, she does have a rough time at the beginning of the year when her $4,000 deductible has not yet been met. However, it’s worth it for her, she says, and she would pay out of pocket if she had to. “I’m not stuck in a darkened room. I have a life again. You can’t put a price on that.”