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.

A thick sphere of icy debris known as the Oort cloud shrouds the solar system. Other star systems may harbor similar icy reservoirs, and those clouds may be visible in the universe’s oldest light, researchers report.

Astronomer Eric Baxter of the University of Pennsylvania and colleagues looked for evidence of such exo-Oort clouds in maps of the cosmic microwave background, the cool cosmic glow of the first light released after the Big Bang, roughly 13.8 billion years ago. No exo-Oort clouds have been spotted yet, but the technique looks promising, the team reports November 2 in the Astronomical Journal. Finding exo-Oort clouds could help shed light on how other solar systems — and perhaps even our own — formed and evolved.
The Oort cloud is thought to be a planetary graveyard stretching between about 1,000 and 100,000 times as far from the sun as Earth. Scientist think that this reservoir of trillions of icy objects formed early in the solar system’s history, when violent movements of the giant planets as they took shape tossed smaller objects outward. Every so often, one of those frozen planetary fossils dives back in toward the sun and is visible as a comet (SN: 11/16/13, p. 14).

But it’s difficult to observe the Oort cloud directly from within it. Despite a lot of circumstantial evidence for the Oort cloud’s existence, no one has ever seen it.

Ironically, exo-Oort clouds might be easier to spot, Baxter and colleagues thought. The objects in an exo-Oort cloud wouldn’t reflect enough starlight to be seen directly, but they would absorb starlight and radiate it back out into space as heat. For the sun’s Oort cloud, that heat signal would be smeared evenly across the entire sky from Earth’s perspective. But an exo-Oort cloud’s warmth would be limited to a tiny region around its star.

Baxter and colleagues calculated that the expected temperature of an exo-Oort cloud should be about –265° Celsius, or 10 kelvins. That’s right in range for experiments that detect the cosmic microwave background, or CMB, which is about 3 kelvins.
The team used data from the CMB-mapping Planck satellite to search for areas across the sky with the right temperature (SN Online: 7/24/18). Then, the researchers compared the results with the Gaia space telescope’s ultraprecise stellar map to see if those regions surrounded stars (SN: 5/26/18, p. 5).

Although the astronomers found some intriguing signals around several bright, nearby stars, it wasn’t enough to declare victory. “That’s pretty interesting, but we can’t definitively say that it’s from an Oort cloud or not,” Baxter says.

Other ongoing CMB experiments with higher resolution, like those with the South Pole Telescope and the Atacama Cosmology Telescope in the Chilean Andes, could confirm if those hints of exo-Oort clouds are real.

“It’s a super clever observational idea,” says astronomer Nicolas Cowan of McGill University in Montreal who was not involved in the new work. “Looking for exo-Oort clouds is looking for a signature of these violent histories in other solar systems.”

Cowan has suggested that the cosmic microwave background could also be used to search for a hypothetical Planet Nine in the sun’s Oort cloud (SN: 7/23/16, p. 7). “The very coolest thing would be if we could get measurements of the exo-Oort clouds and find planets in those systems,” he says.

A newly designed airplane prototype does away with noisy propellers and turbines.

Instead, it’s powered by ionic wind: charged molecules, or ions, flowing in one direction and pushing the plane in the other. That setup makes the aircraft nearly silent. Such stealth planes could be useful for monitoring environmental conditions or capturing aerial imagery without disturbing natural habitats below.

The aircraft is the first of its kind to be propelled in this way, researchers report in the Nov. 22 Nature. In 10 indoor test flights the small plane, which weighs about as much as a Chihuahua, traveled 40 to 45 meters for almost 10 seconds at a steady height, even gaining about half a meter of altitude over the course of a flight.
Most planes rely on spinning parts to move forward. In some, an engine turns a propeller that pushes the plane forward. Or a turbine sucks in air with a spinning fan, and then shoots out jets of gas that propel the plane forward.

Ionic wind is instead generated by a high-voltage electric field around a positively charged wire, called an emitter. The electricity, often supplied by batteries, makes electrons in the air collide with atoms and molecules, which then release other electrons. That creates a swarm of positively charged air molecules around the emitter, which are drawn to a negatively charged wire. The movement of molecules between the two wires, the ionic wind, can push a plane forward. The current design uses four sets of these wires.
Moving ions have helped other things to fly through the air, such as tiny airborne robots. But conventional wisdom said that using the approach to move something through the air as big as an airplane wasn’t possible, because adding enough battery power to propel a plane this way would make it too heavy to stay aloft. (The ion thrusters that propel spacecraft through the vacuum of space work in a very different way and aren’t functional in air.) Attempts to build ion-propelled aircraft in the 1960s weren’t very successful.
MIT aeronautics researcher Steven Barrett thought differently. With the right aircraft design and light enough batteries, flight might be possible, his initial calculations suggested. So he and his team used mathematical equations to optimize various features of the airplane — its shape, materials, power supply — and to predict how each version would fly. Then the researchers built prototypes of promising designs and tested the planes at the MIT indoor track, launching them via a bungee system.
“The models and the reality of construction don’t always match up perfectly,” Barrett says, so finding the right design took a lot of tries. But in the new study, he and his collaborators report success: 10 flights of the aircraft, which has a 5-meter wingspan and weighs just under 2.5 kilograms.

Barrett’s team isn’t the only one who thought the ionic wind method might take off. Based on calculations done in his lab, “we were confident that this could be done,” says Franck Plouraboue of the Toulouse Fluid Mechanics Institute in France, who wasn’t part of the research. “Here they’ve done it — which is fantastic!”

It’s an example of distributed electric propulsion, says Plouraboue — spreading out the thrust-generating parts of the plane, instead of having one centralized source. That’s a hot area for aircraft research right now. NASA’s X-57 Maxwell plane, for example, bears 14 battery-operated motors along its wings. Increasing the number of propellers makes the plane go farther on the same amount of energy, says Plouraboue, but also increases the drag. With ionic wind propulsion, increasing the number of wires doesn’t increase drag very much.

The plane still needs some upgrades before it’s ready for the real world: Its longest flight was only 12 seconds. And while the aircraft can maintain steady flight for a short time once launched, it can’t actually get off the ground using ionic wind.

Even with improvements, ion-propelled aircraft won’t find their niche as passenger planes, predicts Daniel Drew, an aerodynamics researcher at the University of California, Berkeley, who was not involved in the work. (Drew has designed miniature flying bots that fly using ionic propulsion.) It’s probably not feasible to scale up to something the size of a 747 — there are efficiency trade-offs as planes get bigger, he says. But down the road, the approach might be useful for small, uncrewed planes or drones.

From tales about whales to enthralling scientific histories and the memoir of a frustrated astrophysicist, 2018 was a banner year for science books. Here are Science News’ picks for the titles that should be on any science lover’s bookshelf. Find detailed reviews of many of these books in the links below and in our Editor’s Pick: Favorite books of 2018.

The Truth About Animals
Lucy Cooke

A zoologist debunks myths about bats, pandas, Adélie penguins and many other misunderstood creatures, recounting surprising stories from the animal kingdom (SN: 4/14/18, p. 26). Basic Books, $28

Spying On Whales
Nick Pyenson

In this captivating look at whales, a paleontologist dives into the animals’ past, exploring how some of Earth’s most intelligent species came to be, and their uncertain future (SN: 7/7/18, p. 29). Viking, $27

Eager
Ben Goldfarb

Some people see beavers as pests. But a science writer explains how the dam-building rodents are actually vital ecosystem engineers that can create or expand habitats that benefit the entire wildlife community (SN: 8/4/18, p. 28). Chelsea Green Publishing, $24.95

The Rise and Fall of the Dinosaurs
Steve Brusatte

In this memoir, a paleontologist blends experiences from his career with evolutionary science to take readers on an engrossing journey through time, from the beginnings of the dinosaurs to their ultimate extinction. William Morrow, $29.99

The Big Ones
Lucy Jones

A seismologist examines past catastrophic natural disasters, including volcanic eruptions, earthquakes and floods, and their impact on culture, politics and society (SN: 3/31/18, p. 26). With the past as a guide, the author warns readers to be prepared for when the next disaster strikes. Doubleday, $26.95

Losing the Nobel Prize
Brian Keating

An astrophysicist’s dream of winning a Nobel Prize turned to dust after a promising experiment failed to find the first definitive evidence of cosmic inflation. The experience revealed how the prize can hamper scientific progress (SN: 4/14/18, p. 27). W.W. Norton & Co., $27.95

The Poisoned City
Anna Clark

Weaving together history, science and reporting, a journalist explores the public health crisis that began in Flint, Mich., when lead started leaching into residents’ drinking water (SN: 7/21/18, p. 28). Metropolitan Books, $30

The Poison Squad
Deborah Blum

A Pulitzer Prize–winning journalist tells the story of a government chemist at the turn of the 20th century and his mission to make food safe in the United States. Penguin Press, $28

Aroused
Randi Hutter Epstein

The history of endocrinology makes for a strange and fascinating read, from the scientists who discovered the effects of hormones to the people whose lives have been irrevocably changed by these powerful substances (SN: 7/7/18, p. 28). W.W. Norton & Co., $26.95

Nine Pints
Rose George

Blood, the feared as well as revered substance that flows throughout the human body, has a rich historical and scientific past (SN: 10/27/18, p. 28). Metropolitan Books, $30

She Has Her Mother’s Laugh
Carl Zimmer

This comprehensive history recounts how researchers have come to understand genetic inheritance. Looking to the future, the author considers risks of gene manipulation (SN: 6/9/18, p. 29). Dutton, $30

Genetics in the Madhouse
Theodore M. Porter

Using archival records, a science historian traces the origins of the study of human heredity to insane asylums in the 1800s (SN: 7/7/18, p. 29). Princeton Univ., $35

The Tangled Tree
David Quammen

In chronicling the lives of researchers who made important advances in molecular biology and genetics, this book shows how recent findings shake up our understanding of evolution and the tree of life. Simon & Schuster, $30

Poop contains a lot of valuable scientific information. Researchers can monitor microbes, track enzyme activity or hunt for DNA to gather clues about overall health.

There’s so much one can learn from the waste product that microbiologist Aadra Bhatt at the University of North Carolina at Chapel Hill decided there should be a word for that research — something in the same vein as “in vivo” (research done in living animals) and “in vitro” (research done in a petri dish).

After some linguistic digging, she and two colleagues settled on “in fimo.” The term comes from fimus, one of several Latin words for manure or excrement. Their choice won out over the more obvious option of “in feces” because the word feces doesn’t have the same rich scatological legacy — originally it referred to the dregs in a wine cask, Bhatt says.

She and her colleagues, while already using in fimo at meetings and seminars, published their argument online December 13 in Gastroenterology. Compared with the laborious process of pulling together a scientific paper, coming up with this term was “delightful — and it wasn’t particularly drawn out,” Bhatt says. She hopes the word catches on and gains a place in the lexicon for poopetuity.

A few months back, a new storefront appeared in my small Oregon town. Its shelves were packed with tinctures, jars of salve, coffee beans, bath bombs — even beard oil. This motley collection shared a single star ingredient: CBD.

Produced by the cannabis plant, CBD is the straitlaced cousin of marijuana’s more famous component — the THC that delivers a mind-swirling high. CBD, or cannabidiol, has no such intoxicating effects on the mind. Yet the molecule has captured people’s attention in a profound way, sold as a remedy for pain, anxiety, insomnia and other ailments — all without the high.

That neighborhood shop, CBD Scientific, is far from alone in its efforts to sell people on the benefits of CBD, which is found in both marijuana and hemp, two versions of the Cannabis sativa plant. CBD is popping up in products in pet stores, coffee shops and the health and beauty sections of mainstream grocery stores. It’s even being brewed into beer. I left the shop with a $5 bottle of water infused with “5,000,000 nanograms” of CBD.

So far, messages of CBD’s purported health benefits come from people trying to sell CBD products — not from scientists, says Margaret Haney, a neurobiologist who directs the Marijuana Research Laboratory at Columbia University. A gaping chasm separates the surging CBD market and the scientific evidence backing it. While there are reasons to be excited about CBD, the science just isn’t there yet, Haney says.
Scientists still don’t know all of the targets CBD hits in the human body, nor what effects it may have, if any. With the exception of tests in people with rare forms of epilepsy, large studies that compare CBD with placebos in people are rare. Much of the existing research was done with cells in the lab or in lab animals, with results that don’t necessarily translate to people.

And there’s always the chance that for some people, CBD’s magic is made not by the compound itself but by a powerful placebo effect; people who expect good outcomes are more likely to see benefits.

Researchers are stepping into the void, lured by promising early data. Small trials are under way looking at the effect of CBD on anxiety, pain, opioid addiction, depression and other health problems. National Institutes of Health funding for CBD studies went from zero in 2014 to an estimated $16 million in 2018.
“We’re very interested in CBD,” says Susan Weiss, director of the Division of Extramural Research at the National Institute on Drug Abuse in Bethesda, Md. Still, she urges caution to people eager to try CBD. Because of lax oversight, there’s no telling what’s inside many of those tinctures, oils, rubs and foods for sale online and in stores. “A lot of the products that people are taking may not be what they think,” she says.

Despite the risks and warnings, it seems safe to say that the collective fascination with CBD isn’t going to wear off anytime soon. “People think it’s great for everything,” says cognitive neuroscientist Kent Hutchison of the University of Colorado Boulder. That can’t possibly be true, he says. “But I do think it’s going to be great for some things. We just need to figure out what those things are.”

Mystery molecule
Each morning, Samantha Montanaro of Portland, Ore., drops a CBD tincture under her tongue. “I’m kind of testing out my own body with this,” she says. “I’m finding that it really helps with anxiety and stress.”

Montanaro isn’t alone; CBD testimonials are increasingly easy to find. In 2016, Montanaro, now 35, cofounded Tokeativity, a global cannabis community for women. Back then, “CBD wasn’t even a thing,” she says. But the first sparks of the CBD movement caught fire fast. “It’s been pretty crazy to watch how things have evolved,” she says. Some bullish analysts predict that the CBD market in the United States will balloon from hundreds of millions of dollars in 2018 to almost $20 billion by 2022.

Ziva Cooper directs UCLA’s Cannabis Research Initiative and fields a lot of questions about CBD. Her answers invariably disappoint. “When I tell [people] we don’t have very much evidence in people, they’re actually surprised,” she says. When it comes to CBD’s benefits, “there’s actually very little out there to hang our hats on.”

The one exception is for rare forms of childhood epilepsy. Neurologist Elizabeth Thiele of Massachusetts General Hospital in Boston had a young patient who was having over 100 seizures a day. After other treatments had failed, the boy’s parents began searching for a source of CBD oil, which they desperately wanted to try after learning about promising early results in animals. The family flew to England, so the boy could try the CBD formulation made by GW Pharmaceuticals. The child’s results, Thiele says, were remarkable. After a week of CBD, his daily seizures had fallen to single digits.
That result ultimately led to clinical trials, one of which included 171 people, mostly children, with Lennox-Gastaut syndrome, a rare and severe seizure disorder. In addition to their normal medication, half of the participants got doses of CBD that were rigorously tested and standardized by the drug’s maker. The other half received their regular treatment plus a placebo. After 14 weeks, the people taking CBD saw a median drop in monthly seizure frequency of about 44 percent; seizures in people who took the placebo dropped almost 22 percent. Thiele and her colleagues published those results in March 2018 in the Lancet.

Side effects were manageable, the researchers found. Diarrhea, sleepiness, poor appetite and vomiting were more likely to occur in the people who took CBD than in those who got the placebo. Along with results from several other trials, those data were strong enough to prompt the U.S. Food and Drug Administration to approve the CBD drug, called Epidiolex, last June.
Despite rigorous testing of Epidiolex, big gaps in knowledge on how the drug works in epilepsy remain. Researchers don’t know how CBD tames seizures. Because the molecule comes from cannabis, the early assumption was that CBD latches onto the same chemical receptors that THC connects to, one primarily in the brain and one mainly on immune cells. It turns out, however, that CBD doesn’t seem to hit either of those receptors.

Instead, studies in rats and mice point to two different targets. One, called TRPV1, is known to play a role in pain sensation and maybe epilepsy, too. The other, called GPR55, might change the activity level of nerve cells in the brain, a feat that may be behind CBD’s antiseizure power.

Scientists also don’t know whether CBD keeps working year after year. For some of Thiele’s patients, CBD seems to still be effective after five years of taking the drug, even allowing them to taper off some of their other medications, she says. But data from 92 other patients, presented in December at the American Epilepsy Society’s annual meeting, suggest that CBD’s benefits can start to fade after about seven months on the drug. About a third of the people in the study needed a dose increase after their CBD doses became less effective, researchers from Tel Aviv Sourasky Medical Center reported.

Research on CBD and other ailments lags way behind the epilepsy work. Early experiments, mostly on lab animals but some in small numbers of people, suggest that CBD might fight anxiety, ease schizophrenia symptoms and address pain.

One example: Healthy men who took CBD before a stressful public speaking task were calmer than those who took a placebo, researchers reported in October in the Brazilian Journal of Psychiatry. But only the 15 men who received doses of 300 milligrams were more relaxed. The 27 who took less or more CBD didn’t see benefits. Other types of studies with people, and studies of mice and rats, have turned up antianxiety effects, too. But most of these studies looked at single doses of CBD, not consistent use.

Early evidence of CBD’s promise against schizophrenia comes from a trial of 88 people with the disorder. After six weeks, people who had received a big daily dose of CBD (1,000 milligrams a day) in addition to their normal medication had more improvements in certain symptoms when compared with people who received a placebo. Those results hint that CBD might be a new type of drug for schizophrenia, researchers wrote in March 2018 in the American Journal of Psychiatry.

Studies in lab animals suggest that CBD may help relieve chronic pain. A study appearing in 2017 in Pain found that CBD could block osteoarthritis pain and nerve damage in rats. Hard data for humans are harder to find, but anecdotes abound. Pain clinician Kimberly Mauer of Oregon Health & Science University in Portland and colleagues at the OHSU Comprehensive Pain Center have seen an uptick in patients who say they’re taking CBD. Their experiences are mixed, she says: “About half the patients say they get some benefit, and about half say they didn’t notice anything.”

No easy access
To answer the many outstanding questions about CBD’s effects, scientists need access to the compound. But a complex web of U.S. regulations makes that difficult. CBD is subject to rules from both the FDA and the U.S. Drug Enforcement Administration. CBD produced by the marijuana plant remains on the DEA’s list of the most restrictive class of drugs, Schedule 1, alongside LSD, ecstasy and other drugs deemed to have no accepted medical use and high potential for abuse. Access restrictions on industrial hemp, and by extension, the CBD that comes from hemp, were eliminated in the 2018 Farm Bill, signed into law in December. However, regardless of its provenance, CBD is still subject to FDA regulations, as well as any regulations imposed by states.
“As easy as it’s gotten for the average person to go legally to buy recreational marijuana and consume it in many states, it’s gotten harder for scientists,” says Haney at Columbia. One of the few approved sources of CBD is a government-sanctioned cannabis facility at the University of Mississippi in Oxford. After she gets the CBD she needs for her studies, Haney is required to meticulously account for every milligram. “I have a gun safe in a locked room that I get into with my fingerprints to store both cannabidiol and marijuana.”

With those restrictions, many scientists just can’t do the studies they want, Hutchison says. “The whole thing is a little bit crazy. People can sell it everywhere, but it’s very difficult for scientists to study its effects in humans.”

Hutchison and colleagues have figured out a legal work-around that doesn’t require researchers to obtain supplies of CBD. The team is avoiding the government-grown cannabis, which can be quite different from the products in circulation, by testing the effects of the cannabis products that people are actually using. To do this, the researchers created a mobile pharmacology lab they call the CannaVan. The tricked-out Dodge contains equipment to study people after they’ve taken a product containing CBD (or THC) that they bought themselves. The researchers are currently collecting data on CBD’s effects on anxiety and pain.
Buyer beware
FDA rules say that CBD cannot be legally added to food and sold across state lines, sold as a dietary supplement or marketed with claims of treating diseases. But aside from sending some warning letters, the FDA has, so far, let the marketplace run uninhibited. (Some local health authorities, however, are beginning to flex their might, warning restaurants in New York City, for instance, to take CBD off the menu.)

Overall, no one really knows what’s inside the bottles, rubs and coffees for sale. A study published in 2017 in JAMA gives a sense of the problem. Researchers ordered and tested 84 products sold online in 2016 as CBD-containing products. Of those, only 26 were labeled accurately (containing CBD within 10 percent of the claimed amount); 36 of the products had more CBD than their labels said; and 22 products had less. The researchers also found THC in 18 of the 84 samples.
Sophie Cloyd is a 30-year-old manager for the CBD company Ablis of Bend, Ore. She is also pregnant. I met her recently at a ski lodge, where she was offering beverage tastes and describing tinctures, oils and lotions. CBD, she says, has helped her manage this pregnancy, her second. She was prescribed the anti-nausea drug Zofran early in her pregnancy, but “the research on Zofran scared me more than the lack of research on CBD,” she says.

Ablis, which makes CBD-infused fizzy drinks and other products, currently gets purified CBD from Colorado, Cloyd says. When the CBD arrives, the company sends it to an independent lab to confirm that it has the right amount of CBD, no pesticides and no THC. But not all CBD sellers test their products.

An unexpected THC dose might not be enough to get a user high, but it could still be a problem, as news reports have begun to point out. To ease his pain from psoriatic arthritis, a school bus driver in Beaverton, Ore., had been taking a daily dose of CBD oil. In early 2018, he failed a periodic drug test with high THC levels, which caused him to lose his job, Portland news channel KATU reported. Even seemingly small amounts of THC can build up in the body with repeated use.

A product might contain even worse surprises. Between December 2017 and January 2018, for example, 52 people fell ill in Utah, with symptoms such as hallucinations, vomiting and seizures, after taking what they thought was CBD. It turned out that the products, many labeled “Yolo CBD oil,” contained a synthetic cannabinoid, and it had poisoned them.

Even if product labels were always accurate, people have no idea of the correct dose of CBD (assuming the right dose would be effective). “You see it marketed in doses like 10 milligrams,” Hutchison says. “Well, 10 milligrams probably does nothing.” For comparison, people who participated in one Epidiolex study took 20 milligrams per kilogram of body weight. To reach that daily dose, I’d need to chug 254 bottles of that 5 million nanogram CBD water I bought — at a cost of $1,270.

Haney makes the same point: “You’re not getting anything resembling an effective dose when you get CBD added to your coffee, or you buy a mint with a little bit of CBD in it,” she says.

There’s even less known about CBD products that you rub on your skin. Scientists don’t know that CBD in creams, oils and ointments actually makes it into the body. “I’m not convinced that anything you’re rubbing on your body with CBD is even getting through,” Haney says.
At its heart, the trouble is that most CBD use isn’t backed up by science, Haney says. “I am not against CBD,” she says. In fact, she is about to start a study looking at CBD to treat nerve pain due to chemotherapy in cancer patients. “But I don’t like marketers determining what it’s good for and what it’s not.”

Hype run amok isn’t anything new, says Mauer, the OHSU pain doctor. Consumers try lots of things before the science is definitive — keto diets, for instance, or vitamin D supplements (SN: 2/2/19, p. 16). And even if it turns out that the chemical doesn’t work, the placebo effect might be enough to help reduce symptoms.

So far, the science on CBD isn’t mature enough to weigh in, one way or another. But judging by the number of studies and clinical trials under way, this nascent research field is growing up fast, seeking to quickly fill the space between the science and what people want to know.

This research boom heartens Montanaro. Her message to the scientific community: “I would encourage curiosity,” she says. “I’m not a doctor, and I’m not a scientist, but I certainly know my own body,” and she says that CBD helps her. From her perspective, science has got some catching up to do.

This story appears in the March 30, 2019 issue of Science News with the headline, “The Allure of CBD: People seek health benefits despite lack of evidence.”

For 40 years, they’ve held the front line in Florida’s fight against mosquito-borne diseases. And it turns out that the chickens standing sentinel in cities, marshes, woodlands and residential backyards are clucking good at their job.

Last year, chickens in 268 coops in over a third of Florida’s counties provided scientists weekly blood samples that revealed whether the birds had been bitten by mosquitoes carrying West Nile virus or the Eastern equine encephalitis or St. Louis encephalitis viruses.
If a chicken’s blood tests positive for antibodies to one of those viruses, authorities know that the pathogen is circulating. And if enough birds have the antibodies, state officials can ratchet up mosquito-killing measures such as pesticide spraying to help halt disease spread.

The sentinel chicken surveillance programs are “a really good way of monitoring” for certain virus activity, says Thomas Unnasch, a biologist who studies vector-borne diseases at the University of South Florida in Tampa. The birds “are sampling literally hundreds or thousands of mosquitoes every day,” he says. (The chickens can’t keep tabs on dengue or Zika; the mosquitoes carrying those viruses prefer to bite people rather than birds.)
In 2018, 833 chickens tested positive for West Nile virus antibodies in Florida, but only 39 people did, according to data from the state’s health department. For Eastern equine encephalitis virus, 154 chickens tested positive in 2018, compared with only three people.
Chickens that test positive for the viruses being surveyed don’t transmit them, and people don’t either. Both are considered “dead-end hosts,” meaning that the viral concentration in the blood doesn’t get high enough to infect another mosquito after it bites. Infected cardinals, robins and other backyard birds are the animal reservoirs that help keep the three viruses spreading in the area.
Sentinel chickens, by detecting where and when disease-carrying mosquitoes are buzzing, are also providing valuable data on how a virus can spread. Data from 2005 to 2016 revealed that Eastern equine encephalitis virus is active year-round in the Florida panhandle, making the area a source from which the virus moves elsewhere in the state and along the eastern United States, Unnasch and his colleagues report online March 11 in the American Journal of Tropical Medicine and Hygiene.

In people, the viral diseases monitored by the chickens are relatively rare, but can be deadly. The chickens don’t get especially sick, though. “You don’t usually see any symptoms at all,” Unnasch says.

Any chicken whose blood tests positive for the antibodies is removed from the coops since that bird can no longer alert authorities to a new infection. For these chickens, retirement may be spent on a farm, with school or 4-H clubs, or in a backyard coop, depending on the county. The sentinel chicken programs are ready with replacements, raising chicks to supply new birds to signal “where we have a threat to human health,” Unnasch says.

It took just a 9-volt battery and a little brain zapping to turn science writer Sally Adee into a stone-cold sharpshooter.

She had flown out to California to test an experimental DARPA technology that used electric jolts to speed soldiers’ sniper training. When the juice was flowing, Adee could tell. In a desert simulation that pit her against virtual bad guys, she hit every one.

“Getting my neurons slapped around by an electric field instantly sharpened my ability to focus,” Adee writes in her new book, We Are Electric. That brain-stimulating experience ignited her 10-year quest to understand how electricity and biology intertwine. And she’s not just talking neurons.
Bioelectricity, Adee makes the case, is a shockingly under­explored area of science that spans all parts of the body. Its story is one of missed opportunity, scientific threads exposed and abandoned, tantalizing clues and claims, “electroquacks” and unproven medical devices — and frogs. Oh so many frogs.

Adee takes us back to the 18th century lab of Luigi Galvani, an Italian scientist hunting for what gives animals the spark of life. His gruesome experiments on twitching frog legs offered proof that animal bodies generate their own electricity, an idea that was hotly debated at the time. (So many scientists repeated Galvani’s experiments, in fact, that Europe began to run out of frogs.)

But around the same time, Galvani critic Alessandro Volta, another Italian scientist, invented the electric battery. It was the kind of razzle-dazzle, history-shaking device that stole the spotlight from animal electricity, and the fledgling field fizzled. “The idea had been set,” Adee writes. “Electricity was not for biology. It was for machines, and telegraphs, and chemical reactions.”
It took decades for scientists to pick up Galvani’s experimental threads and get the study of bioelectricity back on track. Since then, we’ve learned just how much electricity orchestrates our lives, and how much more remains to be discovered. Electricity zips through our neurons, makes our hearts tick and flows in every cell of the body. We’re made up of 40 trillion tiny rechargeable batteries, Adee writes.

She describes how cells use ion channels to usher charged molecules in and out. One thing readers might not expect from a book that illustrates the intricacies of ion channels: It’s surprisingly funny.
Chloride ions, for example, are “perpetually low-key ashamed” because they carry a measly -1 charge. Bogus medical contraptions (here’s looking at you, electric penis belts) were “electro-foolery.” In her acknowledgements, Adee jokes about the “life-saving powers of Voltron” and thanks people for enduring her caffeine jitters. That energy thrums through the book, charging her storytelling like a staticky balloon.

Adee is especially electrifying in a chapter about spinal nerve regeneration and why initial experiments juddered to a halt. Decades ago, scientists tried coaxing severed nerves to link up again by applying an electric field. The controversial technique sparked scientific drama, but the idea of using electricity to heal may have been ahead of its time. Fast-forward to 2020, and DARPA has awarded $16 million to researchers with a similar concept: a bio­electric bandage that speeds wound healing.

Along with zingy Band-Aids of the future, Adee describes other sci-fi–sounding devices in the works. One day, for example, surgeons may sprinkle your brain with neurograins, neural lace or neural dust, tiny electronic implants that could help scientists monitor brain activity or even help people control robotic arms or other devices (SN: 9/3/16, p. 10).

Such implants bring many challenges — like how to marry electronics to living tissue — but Adee’s book leaves readers with a sense of excitement. Not only could bioelectricity inspire new and improved medical devices, it could also reveal a current of unexpected truths about the body.

As Adee writes: “We are electrical machines whose full dimensions we have not even yet dreamed of.”

The April 25 Nepal earthquake killed more than 8,000 people and caused several billion dollars in damage, but new research suggests the toll could have been a lot worse.

GPS readings taken during the quake indicate that most of the tremors vibrated through the ground as long shakes rather than quick pulses. That largely spared the low-lying buildings that make up much of Nepal’s capital, Kathmandu, geophysicists report online August 6 in Science. Those same low-frequency rumbles, though, toppled Kathmandu’s handful of larger buildings, such as the historic 62-meter tall Dharahara Tower.

Understanding why the fault produced a quake at such low frequencies could help seismologists better identify future seismic hazards, says Jean-Philippe Avouac of the University of Cambridge. “This could be some good news not only for this major fault, but also potentially for similar faults around the world.”

Nepal sits over a tectonic boundary where the Indian Plate slips under the Eurasian Plate. At places, the two plates snag together, building stress that abruptly releases as an earthquake (SN: 5/16/15, p. 12).
Earthquakes stronger than April’s magnitude 7.8 shakedown have hit Nepal before, including a magnitude 8.0 quake in 1934. Despite the recent quake’s feebler intensity, its trembles somehow destroyed large buildings that had previously endured mightier earthquakes.

Avouac and colleagues monitored April’s quake using a network of 35 solar-powered GPS stations, the first time such an accurate system was in place during a major quake on this type of fault. The stations measured ground movements five times each second. The earthquake shook most intensely at 0.25 hertz, or one full wave every four seconds, with only moderate shaking above 1 hertz, or one or more complete waves each second.

A building is most vulnerable when shook near its resonance frequency, a range where even small outside forces can result in big vibrations in the structure. Because taller structures have lower resonance frequencies, the April quake’s low-frequency rumbles caused larger buildings to sway and crumble while largely sparing smaller dwellings, the researchers found.

The low frequencies resulted from the smooth and relatively long duration of the tectonic slipping that initiated the quake, the researchers propose. The low-frequency waves then echoed across the region and produced protracted violent shaking.

Determining where future low-frequency quakes will strike could save lives by identifying which building types are most vulnerable to collapse, says geologist Kristin Morell of the University of Victoria in Canada. “These are things that should be built into building codes.”

You’d be forgiven for thinking that depression has a simple explanation.

The same mantra — that the mood disorder comes from a chemical imbalance in the brain — is repeated in doctors’ offices, medical textbooks and pharmaceutical advertisements. Those ads tell us that depression can be eased by tweaking the chemicals that are off-kilter in the brain. The only problem — and it’s a big one — is that this explanation isn’t true.

The phrase “chemical imbalance” is too vague to be true or false; it doesn’t mean much of anything when it comes to the brain and all its complexity. Serotonin, the chemical messenger often tied to depression, is not the one key thing that explains depression. The same goes for other brain chemicals.
The hard truth is that despite decades of sophisticated research, we still don’t understand what depression is. There are no clear descriptions of it, and no obvious signs of it in the brain or blood.

The reasons we’re in this position are as complex as the disease itself. Commonly used measures of depression, created decades ago, neglect some important symptoms and overemphasize others, particularly among certain groups of people. Even if depression could be measured perfectly, the disorder exists amid myriad levels of complexity, from biological confluences of minuscule molecules in the brain all the way out to the influences of the world at large. Countless combinations of genetics, personality, history and life circumstances may all conspire to create the disorder in any one person. No wonder the science is stuck.

It’s easy to see why a simple “chemical imbalance” explanation holds appeal, even if it’s false, says Awais Aftab, a psychiatrist at Case Western Reserve University in Cleveland. What causes depression is nuanced, he says — “not something that can easily be captured in a slogan or buzzword.”

So here, up front, is your fair warning: There will be no satisfying wrap-up at the end of this story. You will not come away with a scientific explanation for depression, because one does not exist. But there is a way forward for depression researchers, Aftab says. It requires grappling with nuances, complexity and imperfect data.

Those hard examinations are under way. “There’s been some really interesting and exciting scientific and philosophical work,” Aftab says. That forward motion, however slow, gives him hope and may ultimately benefit the millions of people around the world weighed down by depression.

How is depression measured?
Many people who feel depressed go into a doctor’s office and get assessed with a checklist. “Yes” to trouble sleeping, “yes” to weight loss and “yes” to a depressed mood would all yield points that get tallied into a cumulative score. A high enough score may get someone a diagnosis. The process seems straightforward. But it’s not. “Even basic issues regarding measurement of depression are actually still quite open for debate,” Aftab says.

That’s why there are dozens of methods to assess depression, including the standard description set by the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders, or DSM-5. This manual is meant to standardize categories of illness.

Variety in measurement is a real problem for the field and points to the lack of understanding of the disease itself, says Eiko Fried, a clinical psychologist at Leiden University in the Netherlands. Current ways of measuring depression “leave you with a really impoverished, tiny look,” Fried says.

Scales can miss important symptoms, leaving people out. “Mental pain,” for instance, was described by patients with depression and their caregivers as an important feature of the illness, researchers reported in 2020 in Lancet Psychiatry. Yet the term doesn’t show up on standard depression measurements.

One reason for the trouble is that the experience of depression is, by its nature, deeply personal, says clinical psychologist Ioana Alina Cristea of the University of Pavia in Italy. Individual patient complaints are often the best tool for diagnosing the disorder, she says. “We can never let these elements of subjectivity go.”

In the middle of the 20th century, depression was diagnosed through subjective conversation and psychoanalysis, and considered by some to be an illness of the soul. In 1960, psychiatrist Max Hamilton attempted to course-correct toward objectivity. Working at the University of Leeds in England, he published a depression scale. Today, that scale, known by its acronyms HAM-D or HRSD, is one of the most widely used depression screening tools, often used in studies measuring depression and evaluating the promise of possible treatments.
“It’s a great scheme for a scale that was made in 1960,” Fried says. Since the HRSD was published, “we have put a man on the moon, invented the internet and created powerful computers small enough to fit in people’s pockets,” Fried and his colleagues wrote in April in Nature Reviews Psychology. Yet this 60-year-old tool remains a gold standard.

Hamilton developed his scale by observing patients who had already been diagnosed with depression. They exhibited symptoms such as weight loss and slowed speech. But those mixtures of symptoms don’t apply to everyone with depression, nor do they capture nuance in symptoms.

To spot these nuances, Fried looked at 52 depression symptoms across seven different scales for depression, including Hamilton’s scale. On average, each symptom appeared in three of the seven scales. A whopping 40 percent of the symptoms appeared in only one scale, Fried reported in 2017 in the Journal of Affective Disorders. The only specific symptom common to all seven scales? “Sad mood.”

In a study that examined depression symptoms reported by 3,703 people, Fried and Randolph Nesse, an evolutionary psychiatrist at the University of Michigan Medical School in Ann Arbor, found 1,030 unique symptom profiles. Roughly 14 percent of participants had combinations of symptoms that were not shared with anyone else, the researchers reported in 2015 in the Journal of Affective Disorders.

Before reliable thermometers, the concept of temperature was murky. How do you understand the science of hot and cold without the tools to measure it? “You don’t,” Fried says. “You make a terrible measurement, and you have a terrible theory of what it is.” Depression presents a similar challenge, he says. Without good measurements, how can you possibly diagnose depression, determine whether symptoms get better with treatments or even prevent it in the first place?

Depression differs by gender, race and culture
The story gets murkier when considering who these depression scales were made for. Symptoms differ among groups of people, making the diagnosis even less relevant for certain groups.
Behavioral researcher Leslie Adams of Johns Hopkins Bloomberg School of Public Health studies depression in Black men. “It’s clear that [depression] is negatively impacting their work lives, social lives and relationships. But they’re not being diagnosed at the same rate” as other groups, she says. For instance, white people have a lifetime risk of major depression disorder of almost 18 percent; Black people’s lifetime risk is 10.4 percent, researchers reported in 2007 in JAMA Psychiatry. This discrepancy led Adams to ask: “Could there be a problem with diagnostic tools?”

Turns out, there is. Black men with depression have several characteristics that common scales miss, such as feelings of internal conflict, not communicating with others and feeling the burdens of societal pressure, Adams and colleagues reported in 2021 in BMC Public Health. A lot of depression measurements are based on questions that don’t capture these symptoms, Adams says. “ ‘Are you very sad?’ ‘Are you crying?’ Some people do not emote in the same way,” she says. “You may be missing things.”

American Indian women living in the Southeast United States also experience symptoms that aren’t adequately caught by the scales, Adams and her team found in a separate study. These women also reported experiences that do not necessarily signal depression for them but generally do for wider populations.

On common scales, “there are some items that really do not capture the experience of depression for these groups,” Adams says. For instance, a common question asks how well someone agrees with the sentence: “I felt everything I did was an effort.” That “can mean a lot of things, and it’s not necessarily tied to depression,” Adams says. The same goes for items such as, “People dislike me.” A person of color faced with racism and marginalization might agree with that, regardless of depression, she says.

Our ways to measure depression capture only a tiny slice of the big picture. The same can be said about our understanding of what’s happening in the brain.

The flawed serotonin hypothesis
Serotonin came into the spotlight in part because of the serendipitous discovery of drugs that affected serotonin receptors, called selective serotonin re­uptake inhibitors, or SSRIs. After getting its start in the late 1960s, the “serotonin hypothesis” flourished in the late ’90s, as advertisers ran commercials that told viewers that SSRIs fixed the serotonin deficit that can accompany depression. These messages changed the way people talked and thought about depression. Having a simple biological explanation helped some people and their doctors, in part by easing the shame some people felt for not being able to snap out of it on their own. It gave doctors ways to talk with people about the mood disorder.

But it was a simplified picture. A recent review of evidence, published in July in Molecular Psychiatry, finds no consistent data supporting the idea that low serotonin causes depression. Some headlines declared that the study was a grand takedown of the serotonin hypothesis. To depression researchers, the findings weren’t a surprise. Many had already realized this simple description wasn’t helpful.

There’s plenty of data suggesting that serotonin, and other chemical messengers such as dopamine and norepinephrine, are somehow involved in depression, including a study by neuropharmacologist Gitte Moos Knudsen of the University of Copenhagen. She and colleagues recently found that 17 people who were in the midst of a depressive episode released, on average, less serotonin in certain brain areas than 20 people who weren’t depressed. The study is small, but it’s one of the first to look at serotonin release in living human brains of people with depression.

But Knudsen cautions that those results, published in October in Biological Psychiatry, don’t mean that depression is fully caused by low serotonin levels. “It’s easy to defer to simple explanations,” she says.

SSRIs essentially form a molecular blockade, stopping serotonin from being reabsorbed into nerve cells and keeping the levels high between the cells. Those high levels are thought to influence nerve cell activity in ways that help people feel better.

Because the drugs can ease symptoms in about half of people with depression, it seemed to make sense that depression was caused by problems with serotonin. But just because a treatment works by doing something doesn’t mean the disease works in the opposite way. That’s backward logic, psychiatrist Nassir Ghaemi of Tufts University School of Medicine in Boston wrote in October in a Psychology Today essay. Aspirin can ease a headache, but a headache isn’t caused by low aspirin.

“We think we have a much more nuanced picture of what depression is today,” Knudsen says. The trouble is figuring out the many details. “We need to be honest with patients, to say that we don’t know everything about this,” she says.

The brain contains seven distinct classes of receptors that sense serotonin. That’s not even accounting for sensors for other messengers such as dopamine and norepinephrine. And these receptors sit on a wide variety of nerve cells, some that send signals when they sense serotonin, some that dampen signals. And serotonin, dopamine and norepinephrine are just a few of dozens of chemicals that carry information throughout a multitude of interconnected brain circuits. This complexity is so great that it renders the phrase “chemical imbalance” meaningless.

Overly simple claims — low serotonin causes depression, or low serotonin isn’t involved — serve only to keep us stymied, Aftab says. “[It] just keeps up that unhelpful binary.”
Depression research can’t ignore the world
In the 1990s, Aftab says, depression researchers got intensely focused on the brain. “They were trying to find the broken part of the brain that causes depression.” That limited view “really hurt depression research,” Aftab says. In the last 10 years or so, “there’s a general recognition that that sort of mind-set is not going to give us the answers.”

Reducing depression to specific problems of biology in the brain didn’t work, Cristea says. “If you were a doctor 10 years ago, the dream was that the neuroscience would give us the markers. We would look at the markers and say, ‘OK. You [get] this drug. You, this kind of therapy.’ But it hasn’t happened.” Part of that, she says, is because depression is an “existentially complicated disorder” that’s tough to simplify, quantify and study in a lab.

Our friendships, our loves, our setbacks and our stress can all influence our health. Take a recent study of first-year doctors in the United States. The more these doctors worked, the higher the rate of depression, scientists reported in October in the New England Journal of Medicine. Similar trends exist for caregivers of people with dementia and health care workers who kept emergency departments open during the COVID-19 pandemic. Their high-stress experiences may have prompted depression in some way.

“Depression is linked to the state of the world — and there is no denying it,” Aftab says.
Today’s research on depression ought to be more pluralistic, Adams says. “There are so many factors at play that we can’t just rest on one solution,” she says. Research from neuroscience and genetics has helped identify brain circuits, chemical messengers, cell types, molecules and genes that all may be involved in the disorder. But researchers aren’t satisfied with that. “There is other evidence that remains unexplored,” Adams says. “With our neuro­science advances, there should be similar advances in public health and psychiatric work.”

That’s happening. For her part, Adams and colleagues have just begun a study looking at moment-to-moment stressors in the lives of Black adolescents, ages 12 to 18, as measured by cell phone questionnaires. Responses, she hopes, will yield clues about depression and risk of suicide.

Other researchers are trying to fit together all of these different ways of seeing the problem. Fried, for example, is developing new concepts of depression that acknowledge the interacting systems. You tug on one aspect of it — using an antidepressant for instance, or changing sleep patterns — and see how the rest of the system reacts.

Approaches like these recognize the complexity of the problem and aim to figure out ways to handle it. We will never have a simple explanation for depression; we are now learning that one cannot possibly exist. That may sound like cold comfort to people in depression’s grip. But seeing the challenge with clear eyes may be the thing that moves us forward.