Biologists are one step closer to creating snake venom in the lab

SAN DIEGO — Labs growing replicas of snakes’ venom glands may one day replace snake farms.

Researchers in the Netherlands have succeeded in growing mimics of venom-producing glands from multiple species of snakes. Stem cell biologist Hans Clevers of the Hubrecht Institute in Utrecht, the Netherlands, reported the creation of these organoids on December 10 at a joint meeting of the American Society for Cell Biology and the European Molecular Biology Organization.

If scientists can extract venom from the lab-grown glands, that venom might be used to create new drugs and antidotes for bites including from snakes that aren’t currently raised on farms.

Up to 2.7 million people worldwide are estimated to be bitten by venomous snakes each year. Between about 81,000 to 138,000 people die as a result of the bite, and as many as roughly 400,000 may lose limbs or have other disabilities, according to the World Health Organization.
Antivenoms are made using venom collected from snakes usually raised on farms. Venom is injected into other animals that make antibodies to the toxins. Purified versions of those antibodies can help a bitten person recover, but must be specific to the species of snake that made the bite. “If it’s a fairly rare or local snake, chances are there would be no antidote,” Clevers says.

Three postdoctoral researchers in Clevers’ lab wanted to know if they could make organoids — tissues grown from stem cells to have properties of the organs they mimic — from snakes and other nonmammalian species. The researchers started with Cape coral snakes (Aspidelaps lubricus) that were dissected from eggs just before hatching. Stem cells taken from the unhatched snakes grew into several different types of organoids, including some that make venom closely resembling the snake’s normal venom, Clevers reported at the meeting.

His team has produced venom-gland organoids from at least seven species of snakes. The organoids have survived in the lab for up to two years so far.

Clevers and colleagues hope to harvest venom from the organoids, which produce more highly concentrated venom than snakes usually make. “It’s probably going to be easier than milking a snake,” he says.

Here’s what was surprising about Kilauea’s 3-month-long eruption

WASHINGTON — After a stunningly explosive summer, Kilauea, the world’s longest continuously erupting volcano, finally seems to have taken a break. But the scientists studying it haven’t. Reams of new data collected during an unprecedented opportunity to monitor an ongoing, accessible eruption are changing what’s known about how some volcanoes behave.

“It was hugely significant,” says Jessica Larsen, a petrologist at the University of Alaska Fairbanks, and “a departure from what Kilauea had been doing for more than 35 years.”
The latest eruption started in May. By the time it had ended three months later, over 825 million cubic meters of earth had collapsed at the summit. That’s the equivalent of 300,000 Olympic-sized swimming pools, Kyle Anderson, a geophysicist with the U.S. Geologic Survey in Menlo Park, Calif., said December 11 in a news conference at the annual meeting of the American Geophysical Union.

As the summit crater deflated, magma gushed through underground tunnels, draining out through fissures along an area called the lower eastern rift zone at a rate of roughly 50 meters per day. That lava eventually covered 35.5 square kilometers of land, Anderson and his colleagues reported in a study published December 11 in Science.

The volcano also taught scientists a thing or two.
Scientists previously believed that groundwater plays a big role in how a caldera collapses. When craters were drained of their magma, “cooling, cracking depressurized the caldera, allowing groundwater to seep in and create a series of explosive eruptions,” Anderson said. “But groundwater did not play a significant role in driving the explosions this summer.”

Instead, the destruction of Kilauea’s crater is what’s called a piston-style caldera collapse, he said. Sixty-two small collapse events rattled the volcano from mid-May to late August, with each collapse causing the crater to sink and pushing the surrounding land out and up. By the end, the center of the volcano sank by as much as 500 meters — more than the height of the Empire State Building.

That activity didn’t just destroy the crater. “We could see surges in the eruption rate 40 kilometers away whenever there was a collapse,” Anderson said.
Life finds a way
Under the sea, life moved in around the brand-new land surprisingly quickly. Using a remotely operated vehicle to explore the seafloor, researchers in September found evidence of hydrothermal activity along newly deposited lava flows about 650 meters deep. More surprising, bright yellow, potentially iron-oxidizing microbes had already moved in.

“There’s no reason why we should have expected there would be hydrothermal activity that would be alive within the first 100 days,” Chris German, a geologist at Woods Hole Oceanographic Institution in Falmouth, Mass., said at the news conference. “This is actually life here!”

The discovery suggests “how volcanism can give rise to the chemical energy that can drive primitive microbial organisms and flower a whole ecosystem,” he said.

Studying these ecosystems can provide insight into how life may form in places like Enceladus, an icy moon of Saturn. Hydrothermal activity is common where Earth’s tectonic plates meet. But alien worlds don’t show evidence of plate tectonics, though they can be volcanically active, German says. Studying how hydrothermal life forms near volcanoes that aren’t along tectonic boundaries on Earth could reveal a lot about other celestial bodies.

“This is a better analog of what we expect to them to be like,” says German, but “it is what’s least studied.”

What comes next
As of December 5, Kilauea had not erupted for three months, suggesting it’s in what’s called a pause – still active but not spewing lava. Observations from previous eruptions suggest that the next phase of Kilauea’s volcanic cycle may be a quieter one. But the volcano likely won’t stay quiet forever, says Christina Neal, the head scientist at the USGS Hawaiian Volcano Observatory and a coauthor of the Science paper. “We’re in this lull and we just don’t know what is going to happen next,” she says.Life finds a way
Under the sea, life moved in around the brand-new land surprisingly quickly. Using a remotely operated vehicle to explore the seafloor, researchers in September found evidence of hydrothermal activity along newly deposited lava flows about 650 meters deep. More surprising, bright yellow, potentially iron-oxidizing microbes had already moved in.

“There’s no reason why we should have expected there would be hydrothermal activity that would be alive within the first 100 days,” Chris German, a geologist at Woods Hole Oceanographic Institution in Falmouth, Mass., said at the news conference. “This is actually life here!”

The discovery suggests “how volcanism can give rise to the chemical energy that can drive primitive microbial organisms and flower a whole ecosystem,” he said.

Studying these ecosystems can provide insight into how life may form in places like Enceladus, an icy moon of Saturn. Hydrothermal activity is common where Earth’s tectonic plates meet. But alien worlds don’t show evidence of plate tectonics, though they can be volcanically active, German says. Studying how hydrothermal life forms near volcanoes that aren’t along tectonic boundaries on Earth could reveal a lot about other celestial bodies.
Scientists are tracking ground swelling near the Puu Oo vent, where much of Kilauea’s lava has flowed from during the volcano’s 35-year eruption history. That inflation is an indication that magma may still be on the move deep below.

The terrain surrounding this remote region is dense with vegetation, making it a difficult area to study. But new methods tested during the 2018 eruption, such as the use of uncrewed aerial vehicles, for example, could aid in tracking the recent deformation.

Scientists are also watching the volcano next door: Mauna Loa. History has shown that Mauna Loa can act up during periods when Kilauea sleeps. For the past several years, volcanologists have kept an eye on Kilauea’s larger sister volcano, which went silent last fall, after a period with few earthquakes and intermittent deformation. “We’re seeing a little bit of inflation at Mauna Loa and some earthquake swarms where it had been active, Neal says. “So that’s another issue of concern for us going into the future.”

DNA tests of Lassa virus mid-outbreak helped Nigeria target its response

When an outbreak of a viral hemorrhagic fever hit Nigeria in 2018, scientists were ready: They were already in the country testing new disease-tracking technology, and within weeks managed to steer health workers toward the most appropriate response.

Lassa fever, which is transmitted from rodents to humans, pops up every year in West Africa. But 2018 was the worst season on record for Nigeria. By mid-March, there were 376 confirmed cases — more than three times as many as by that point in 2017 — and another 1,495 suspected. Health officials weren’t sure if the bad year was being caused by the strains that usually circulate, or by a new strain that might be more transmissible between humans and warrant a stronger response.
New technology for analyzing DNA in the field helped answer that question mid-outbreak, confirming the outbreak was being caused by pretty much the same strains transmitted from rodents to humans in past years. That rapid finding helped Nigeria shape its response, allowing health officials to focus efforts on rodent control and safe food storage, rather than sinking time and money into measures aimed at stopping unlikely human-to-human transmission, researchers report in the Jan. 4 Science.

While the scientists were reporting their results to the Nigeria Centre for Disease Control, they were also discussing the data with other virologists and epidemiologists in online forums. This kind of real-time collaboration can help scientists and public health workers “see the bigger picture about pathogen spread,” says Nicholas Loman, a microbial genomicist at the University of Birmingham in England who was not involved in the research.

Portable DNA sequencers, some as small as a cell phone, have allowed scientists to read the genetic information of viruses emerging in places without extensive lab infrastructure. Looking for genetic differences between patient samples can give clues to how a virus is being transmitted and how quickly it’s changing over time — key information for getting outbreaks under control. If viral DNA from several patients is very similar, that suggests the virus may be transmitted between people; if the DNA is more distinct, people might be picking up the virus independently from other animals.

The technology has also been used amid recent Ebola and Zika outbreaks. But the Lassa virus presents a unique challenge, says study coauthor Stephan Günther, a virologist at the Bernhard-Nocht-Institute for Tropical Medicine in Hamburg, Germany. Unlike Ebola or Zika, Lassa has a lot of genetic variation between strains. So while the same small regions of DNA from various strains of Ebola or Zika can be identified for analysis, it’s hard to accurately target similar regions for comparison among Lassa strains.
Instead, Günther and his team used a tactic called metagenomics: They collected breast milk, plasma and cerebrospinal fluid from patients and sequenced all the DNA within — human, viral and anything else lurking. Then, the team picked out the Lassa virus DNA from that dataset.

All told, the scientists analyzed Lassa virus DNA from 120 patients, far more than initially intended. “We went to the field to do a pilot study,” Günther says. “Then the outbreak came. And we quickly scaled up.” Preexisting relationships in Nigeria helped make that happen: The team had been collaborating for a decade with researchers at the Irrua Specialist Teaching Hospital and working alongside the World Health Organization and the Nigeria Centre for Disease Control.

Analyzing and interpreting the massive amounts of data generated by the metagenomics approach was a challenge, especially with limited internet connection, Günther says. Researchers analyzed 36 samples during the outbreak — less than a third of their total dataset, but still enough to guide the response. The full analysis, completed after the outbreak, confirmed the initial findings.

A metagenomics approach could be useful in disease surveillance more broadly. Currently, “we look for things that we know about and expect to find. Yet evidence from Ebola in West Africa and Zika in the Americas is that emerging pathogens can pop up in unexpected places, and take too long to be recognized,” Loman says. Sequencing all DNA in a sample, he says, could allow scientists to detect problem pathogens before they cause outbreaks.Instead, Günther and his team used a tactic called metagenomics: They collected breast milk, plasma and cerebrospinal fluid from patients and sequenced all the DNA within — human, viral and anything else lurking. Then, the team picked out the Lassa virus DNA from that dataset.

All told, the scientists analyzed Lassa virus DNA from 120 patients, far more than initially intended. “We went to the field to do a pilot study,” Günther says. “Then the outbreak came. And we quickly scaled up.” Preexisting relationships in Nigeria helped make that happen: The team had been collaborating for a decade with researchers at the Irrua Specialist Teaching Hospital and working alongside the World Health Organization and the Nigeria Centre for Disease Control.

Analyzing and interpreting the massive amounts of data generated by the metagenomics approach was a challenge, especially with limited internet connection, Günther says. Researchers analyzed 36 samples during the outbreak — less than a third of their total dataset, but still enough to guide the response. The full analysis, completed after the outbreak, confirmed the initial findings.

A metagenomics approach could be useful in disease surveillance more broadly. Currently, “we look for things that we know about and expect to find. Yet evidence from Ebola in West Africa and Zika in the Americas is that emerging pathogens can pop up in unexpected places, and take too long to be recognized,” Loman says. Sequencing all DNA in a sample, he says, could allow scientists to detect problem pathogens before they cause outbreaks.

Satellites make mapping hot spots of ammonia pollution easier

Satellites may be a more accurate way to track smog-producing ammonia.

It’s notoriously tricky to pinpoint accurate numbers for ammonia gas emissions from sources such as animal feedlots and fertilizer plants. But new maps, generated from infrared radiation measurements gathered by satellites, reveal global ammonia hot spots in greater detail than before. The new data suggest that previous estimates underestimate the magnitude of these emissions, researchers report December 5 in Nature.

In the atmosphere, ammonia, which contains nitrogen, can help form tiny particles that worsen air quality and harm human health. The research could help keep tabs on who’s emitting how much, to make sure that factories and farms are meeting environmental standards.
Emissions are usually estimated by adding up output from individual known sources of activity, but those calculations are only as good as the data that go into them. Ammonia sticks around only hours to a few days in the atmosphere, so on-the-ground measurements vary a lot even in the same place, says coauthor Martin Van Damme, an atmospheric scientist at the Université Libre de Bruxelles in Belgium.

“There’s so much uncertainty in ammonia emissions,” says Daven Henze, a mechanical engineer at the University of Colorado Boulder who wasn’t part of the research. Other scientists, including his research group, have estimated ammonia releases using satellite data before. But these new maps rely on a more detailed dataset and have substantially better resolution, Henze says — fine enough that the study authors were able to link areas of high emissions to specific factories or farms.
The new maps show 248 nitrogen emission hot spots across the globe at a resolution of about a kilometer. Eighty-three of those hot spots arose from agricultural activity that involved high numbers of cows, pigs and chickens, such as a site in Colorado that overlapped on satellite imagery maps with two big cattle feedlots. Ammonia emissions from feedlots come largely from livestock waste. Another 158 sites were affected by industrial emissions — mostly from sites that produced ammonia-based fertilizer, such as in Marvdasht, Iran. Six hot spots couldn’t be pinned to specific activity.
Ammonia is also emitted naturally, from volcanoes or seabird colonies. But most of those sources were too weak or not concentrated enough to show up as hot spots in the data. Lake Natron in Tanzania is the one exception — its mud flats show up as an ammonia-releasing hot spot, perhaps due to decaying algae. But it’s not clear why other lakes with similar mud flats didn’t. Some natural sources may have gone undetected because of where they were located — in places with heavy cloud cover that obscured the data, or where turbulent air dissipated ammonia especially quickly, Van Damme suggests.

Some areas with particularly high overall ammonia emissions from biomass burning or fertilizer, such as West Africa and the Indus Valley in Pakistan and northern India, didn’t reveal specific hot spots, either, the researchers report.

U.S. fentanyl deaths are rising fastest among African-Americans

Since people in the United States began dying in the fentanyl-related drug overdose epidemic, whites have been hit the hardest. But new data released March 21 by the Centers for Disease Control and Prevention show that African-Americans and Hispanics are catching up.

Non-Hispanic whites still experience the majority of deaths involving fentanyl, a synthetic opioid. But among African-Americans and Hispanics, death rates rose faster from 2011 to 2016. Whites experienced a 61 percent annual increase, on average, while the rate rose 140.6 percent annually for blacks and 118.3 percent per year for Hispanics. No reliable data were available for other racial groups.
Overall, the number of U.S. fentanyl-related deaths in 2011 and 2012 hovered just above 1,600. A sharp increase began in 2013, reaching 18,335 deaths in 2016. That’s up from 0.5 deaths per 100,000 people in 2011 to 5.9 per 100,000 in 2016.

In the first three years of the data, men and women died from fentanyl-related overdoses at similar rates, around 0.5 per 100,000. But in 2013, those paths diverged, and by 2016, the death rate among men was 8.6 per 100,000; for women it was 3.1 per 100,000. Overdose death rates rose most sharply along the East Coast, including in New England and the middle Atlantic, and in the Great Lakes region.

One of the most powerful opioids, fentanyl has been around for decades and is still prescribed to fight pain. But it has emerged as a street drug that is cheap to make and is found mixed into other drugs. In 2013, fentanyl was the ninth most common drug involved in overdose deaths, according to the CDC report; in 2016, it was number one. Just a little bit can do a lot of damage: The drug can quickly kill a person by overwhelming several systems in the body (SN: 9/3/2016, p. 14).

Women have a new weapon against postpartum depression, but it’s costly

Approval of the first and only treatment in the United States specifically targeting postpartum depression offers hope for millions of women each year who suffer from the debilitating mental health disorder after giving birth.

The new drug brexanolone — marketed under the name Zulresso and approved on March 19 by the U.S. Food and Drug Administration — is expected to become available to the public in late June. Developed by Sage Therapeutics, based in Cambridge, Mass., the drug is costly and treatment is intensive: It’s administered in the hospital as a 60-hour intravenous drip, and a treatment runs between $20,000 and $35,000. But researchers say that it could help many of the estimated 11.5 percent of U.S. new moms each year who experience postpartum depression, which can interfere with normal bonding between mothers and infants and lead to feeling hopeless, sad or overly anxious.
Here’s a closer look at the drug, its benefits and some potential drawbacks.

How does the new drug work?
How exactly brexanolone works is not known. But because the drug’s chemical structure is nearly identical to the natural hormone allopregnanolone, it’s thought that brexanolone operates in a similar way.

Allopregnanolone enhances the effects of a neurochemical called gamma-aminobutyric acid, or GABA, which stops nerve cells in the brain from firing. Ultimately this action helps quell a person’s anxiety or stress.
During pregnancy, the concentration of allopregnanolone in a woman’s brain spikes. This leads some neurons to compensate by temporarily tuning out GABA so that the nerve cells don’t become too inactive. Levels of the steroid typically return to normal quickly after a baby is born, and the neurons once again responding to GABA shortly thereafter. But for some women, this process can take longer, possibly resulting in postpartum depression.

Brexanolone temporarily elevates the brain’s allopregnanolone levels again, which results in a patient’s mood improving. But it’s still not clear exactly why the drug has this effect, says Samantha Meltzer-Brody, a reproductive psychiatrist at the University of North Carolina School of Medicine in Chapel Hill and the lead scientist of the drug’s clinical trials. Nor is it clear whether allopregnanolone’s, and thus possible brexanolone’s, influence on GABA is affecting only postpartum depression. But the drug clearly “has this incredibly robust response,” she says, “unlike anything currently available.”

How effective was the drug in clinical trials?
Brexanolone went through three separate clinical trials in which patients were randomly given either the drug or a placebo: one Phase II trial, which tests the drug’s effectiveness and proper dosage, and two Phase III trials, which tested the drug’s effects on moderate or severe postpartum depression and were necessary to gain approval for the drug’s commercial use in people.

Of 234 people who completed the trials, 94 received the suggested dosage of brexanolone. About 70 of those patients, or 75 percent, had what Meltzer-Brody described as a “robust response” to just one course of treatment. And of those patients with positive responses, 94 percent continued to feel well 30 days after the treatment. The results suggest that the drug may be most effective for those with severe postpartum depression; among those with moderate symptoms, the drug and the placebo had a fairly similar impact.

Can people take the drug again?
“There’s nothing prohibiting” a second course of brexanolone, but the effects of a repeat course have not been studied, Meltzer-Brody says. The drug was designed to be taken in tandem with the start of antidepressants, which take effect after about two to four weeks. So by the time the brexanolone wears off, the antidepressants would have kicked in.

It’s not clear yet if some patients could need a second dose. The clinical trials compared a group of women taking both antidepressants and brexanolone with another group taking only brexanolone and found no difference in the two group’s response 30 days after tests ended, Meltzer-Brody says. Because the study ended at 30 days, it’s unclear if the effects of brexanolone on its own last longer.

Can women breastfeed while taking brexanolone?
As a precaution, treated women did not breastfeed until six days after taking the drug. But in tests of breastmilk from 12 treated, lactating women, concentrations of brexanolone in breastmilk were negligible — less than 10 nanograms per millileter — in most of the women 36 hours after they received the infusion, according to Sage’s briefing document for the FDA. The FDA has yet to issue guidance on breast feeding.

Are there side effects?
About a third of the trial patients experienced sleepiness, sedation or headaches. The possibility of drowsiness led to the FDA’s requirement that the drug be administered by IV drip in a supervised setting. “If someone isn’t supervised, then there would be the risk that someone could get sleepy and pass out,” Meltzer-Brody says.

Are there plans for different versions of the drug?
Sage Therapeutics is developing a pill version of a drug called SAGE-217. It’s chemically similar to brexanolone and has similar antidepressant effects. Early results from a Phase III trial reported by the company in January show that, of 78 women treated with the pill, 72 percent responded favorably within two weeks, and 53 percent had not experienced a recurrence of symptoms four weeks later.

Is it worth the price and time?
Setting aside 60 hours to be hospitalized for an expensive drug could be discouraging for some. “It’s going to be very important for insurance to cover it in order for it be accessible,” Meltzer-Brody says. “I’m hoping that will be the case.” But based on the reaction of women with severe postpartum depression who participated in the trials, “two-and-a-half days seems like nothing if your debilitating, depressive symptoms will be gone.”

The delight of discovering an asteroid that spits

These are wondrous times for space exploration. Just when you think exploring the cosmos couldn’t possibly get more fun, another discovery delivers a new “oh wow” moment.

Consider the asteroid Bennu. It’s an unprepossessing space rock that drew scientists’ curiosity because it is among the most pristine objects in our solar system, and it might provide clues to the origins of life. But checking out Bennu is no trip to Paris; it’s about 130 million kilometers from Earth. NASA launched its OSIRIS-REx probe to Bennu in 2016, and it didn’t arrive until last December. The spacecraft is currently orbiting its quarry in preparation for an attempt at gathering samples from the asteroid’s surface in 2020 and then toting them back to Earth. Estimated delivery date: September 24, 2023. Clearly, asteroid science is not a discipline for those with short attention spans.
So imagine scientists’ delight when OSIRIS-REx already had news to share: Bennu is squirting jets of dust into space. It’s an asteroid behavior no one had ever seen before. Astronomy writer Lisa Grossman learned all about Bennu’s surprise jets while attending the Lunar and Planetary Science Conference in March. She reports that the dusty fountains may be the work of volatile gases beneath Bennu’s surface. The presence of volatiles would suggest that the rock wandered into the inner solar system relatively recently. But astronomers still have a lot to figure out about Bennu’s history, and they couldn’t be happier.

In other surprising space rock news from the conference, astronomers analyzing the much-more-distant object dubbed Ultima Thule now think it’s an agglomeration of mini-worlds that stuck together in the early days of the solar system — as Grossman terms it, a “Frankenworld.” That’s just the latest unexpected news from this Kuiper Belt denizen. If you’re as space rock obsessed as we are, you may recall that the first fuzzy images from NASA’s New Horizons spacecraft, which flew by Ultima Thule on January 1, suggested that the rock looked like a bowling pin or a snowman spinning in space. More recent images reveal not a snowman, but instead two pancakes or hamburger patties glued end to end (SN: 3/16/19, p. 15). That has scientists scrambling to figure out what forces could create such an oddly shaped object.

We’ll be hearing more about Bennu, Ultima Thule and other residents of our solar system in the months to come. I’m particularly looking forward to news from the Parker Solar Probe, which is tightening its orbit around the sun. I’m the one who is going to have to be patient in this case, though that’s not an attribute typically associated with journalists. The spacecraft won’t make its closest encounter with the sun until 2024, before ending its mission the following year. But the probe will be reporting in, and we’ll be reporting, too, as it makes this historic journey (SN: 1/19/19, p. 7).

Open your Web browser or your trusty print magazine and join us for the adventure. We hope you’ll enjoy the journey as much as we do.

50 years ago, scientists were unlocking the secrets of bacteria-infecting viruses

Unusual virus is valuable tool —

Viruses, which cannot reproduce on their own, infect cells and usurp their genetic machinery for use in making new viruses…. But just how viruses use the cell machinery is unknown.… Some answers may come from work with an unusual virus, called M13, that has a particularly compatible relationship with … [E. coli] bacteria. — Science News, April 5, 1969

Update
M13 did help unlock secrets of viral replication. Some bacteria-infecting viruses, called bacteriophages or simply phages, kill the host cell after hijacking the cell’s machinery to make copies of themselves. Other phages, including M13, leave the cell intact. Scientists are using phage replication to develop drugs and technologies, such as virus-powered batteries (SN: 4/25/09, p. 12). Adding genetic instructions to phage DNA for making certain molecules lets some phages produce antibodies against diseases such as lupus and cancer. The technique, called phage display, garnered an American-British duo the 2018 Nobel Prize in chemistry (SN: 10/27/18, p. 16).

Toddlers tend to opt for the last thing in a set, so craft your questions carefully

My youngest child, now just over a year old, has started to talk. Even though I’ve experienced this process with my older two, it’s absolutely thrilling. He is putting words to the thoughts that swirl around in his sweet little head, making his mind a little less mysterious to the rest of us.

But these early words may not mean what we think they mean, a new study hints. Unsurprisingly, when 2-year-olds were asked a series of “this or that” questions, the toddlers showed strong preferences — but not for the reasons you’d think. Overwhelmingly, the toddlers answered the questions with the last choice given.
That bias, described in PLOS ONE on June 12, suggests that young children’s answers to these sorts of questions don’t actually reflect their desires. Instead, kids may simply be echoing the last thing they heard.

This verbal quirk can be used by parents to great effect, as the researchers point out in the title of their paper: “Cake or broccoli?” More fundamentally, the results raise questions about what sort of information a verbal answer actually pulls out of a young child’s mind. This murkiness is especially troublesome when it comes to questions whose answers call for adult action, such as: “Did you hit your sister on purpose or on accident?”

In the first series of experiments, researchers led by Emily Sumner at the University of California, Irvine, asked 24 1- and 2-year-olds a bunch of two-choice questions, some of which involved a polar bear named Rori or a grizzly bear named Quinn. One question, for example, was, “Does Rori live in an igloo or a tepee?” Later, the researchers switched the bear and the order of the options, asking, for example, “Does Quinn live in a tepee or an igloo?”

The toddlers could answer either verbally or, for reluctant speakers, by pointing at one of two stickers that showed the choices. When the children answered the questions by pointing, they chose the second option about half the time, right around chance. But when the toddlers spoke their answers, they chose the second option 85 percent of the time, regardless of the bear.
SECOND BEST A toddler taking part in a study selects the second option in three either-or questions. This tendency, called the recency bias, may reflect kids’ inability to juggle several choices in their minds simultaneously. Credit: E. Sumner et al/PLOS ONE 2019

This abundance of second options selected — a habit known as the recency bias — might be due to the fact that young children have trouble holding the first option in mind, the researchers suspect. Other experiments showed that children’s tendency toward the second option got stronger when the words got longer.

Adults actually have the opposite tendency: We’re more inclined to choose the first option we’re given (the primacy bias). To see when this shift from last to first occurs, the researchers studied transcripts of conversations held between adults and children ages 1.5 to 4. In these natural conversations, 2-year-olds were more likely to choose the second option. But 3- and 4-year-olds didn’t show this bias, suggesting that the window closes around then.

The results hold a multitude of delightful parenting hacks: “Would you like to jump on the bed all night, or go to sleep?” But more importantly, the study serves as a reminder that the utterances of small children, while fascinating, may not carry the same meanings as those that come from more mature speakers. If you really want a straight answer, consider showing the two options to the toddler. But if you go that route, be prepared to hand over the cake.

A gel cocktail uses the body’s sugars to ‘grow’ electrodes in living fish

For the first time, researchers have harnessed the body’s own chemistry to “grow” electrodes inside the tissues of living fish, blurring the boundary between biology and machines.

The technique uses the body’s sugars to turn an injected gel into a flexible electrode without damaging tissues, experiments show. Zebrafish with these electrodes grown in their brains, hearts and tail fins showed no signs of ill effects, and ones tested in leeches successfully stimulated a nerve, researchers report in the Feb. 24 Science.
Someday, these electrodes could be useful for applications ranging from studying how biological systems work to improving human-machine interfaces. They also could be used in “bioelectronic medicine,” such as brain stimulation therapies for depression, Parkinson’s disease and other conditions (SN: 2/10/19).

Soft electronics aim to bridge the gap between soft, curvy biology and electronic hardware. But these electronics typically still must carry certain parts that can be prone to cracks and other issues, and inserting these devices inevitably causes damage to tissues.

“All the devices we have made, even though we have made them flexible, to make them more soft, when we introduce them, there will still be a scar. It’s like sticking a knife into the organ,” says Magnus Berggren, a materials scientist at Linköping University in Sweden. That scarring and inflammation can degrade electrode performance over time.

Previous efforts to grow soft electronics inside tissues have drawbacks. One approach uses electrical or chemical signals to power the transformation from chemical soup to conducting electrodes, but these zaps also cause damage. A 2020 study got around this problem by genetically modifying cells in worms to produce an engineered enzyme that does the job, but the new method achieves its results without genetic alterations.

Berggren and colleagues’ electrodes instead exploit a natural energy source already present in the body: sugars. The gel cocktail contains molecules called oxidases that react with the sugars — glucose or lactate — to produce hydrogen peroxide. That then activates another ingredient in the cocktail, an enzyme called hydrogen peroxidase, which is the catalyst needed to transform the gel into a conducting electrode.

“The approach leverages elegant chemistry to overcome many of the technical challenges,” says biomedical engineer Christopher Bettinger of Carnegie Mellon University in Pittsburgh, who was not involved in the study.

To test the technique, the researchers injected the cocktail into the brains, hearts and tail fins of transparent zebrafish. The gel turns blue when it becomes conductive, giving a visual readout of its success.
“The beautiful thing is you can see it: The zebrafishes’ tail changes color, and we know that blue indicates a conducting polymer,” says materials scientist Xenofon Strakosas, also of Linköping University. “The first time I saw it, I thought ‘Wow, it’s really working!’”

The fish appeared to suffer no ill effects, and the researchers saw no evidence of tissue damage. In partially dissected leeches, the team showed that delivering a current to a nerve via a soft electrode could induce muscle contractions. Ultimately, devices like this could be paired with various wireless technologies in development.

Long-term implant performance remains to be determined, however. “The demonstrations are impressive,” Bettinger says. “What remains to be seen is the stability of the electrode.” Over time, substances in the body could react with the electrode materials, degrading it or even producing toxic substances.

The team still needs to refine how precisely the electrodes can stimulate nerves, says chemical engineer Zhenan Bao of Stanford University, who was not involved in the work. She and colleagues developed the way to “grow” electrical components using genetic modifications. Ensuring stimulation is concentrated where it’s needed for a treatment, while preventing the leakage of current to unwanted regions will be important, she says.

In the new study, the relative abundance of different sugars in different tissues determines exactly where electrodes form. But in the future, a component of the main ingredient could be swapped out for elements that attach to specific bits of biology to make targeting much more precise, Berggren says. “We’re conducting experiments right now where we’re trying to bind these materials directly on individual cells.” Notes Strakosas: “There are some applications where precision is really important; that’s where we have to invest effort.”