Why taking medications during pregnancy is so confusing

Obstetrician Cynthia Gyamfi-Bannerman was treating patients in New York City when the COVID-19 pandemic swept in. Hospitals began filling up. Some of her pregnant patients were among the sick.

It was a terrifying time. Little was known about the virus called SARS-CoV-2 to begin with, much less how it might affect a pregnancy, so doctors had to make tough calls. Gyamfi-Bannerman remembers doctors getting waivers to administer the antiviral drug remdesivir to pregnant COVID-19 patients, for instance, even though the drug hadn’t been tested during pregnancy.

“Our goal is to help the mom,” she says. “If we had something that might save her life — or she might die — we were 100 percent using all of those medications.”

These life-or-death decisions were very familiar to obstetricians even before the pandemic. Pregnant women have long been excluded from most drug testing to avoid risk to the fetus. As a result, there’s little data on whether many medications are safe to take while pregnant. This means tough choices for the roughly 80 percent of women who will take at least one medication during pregnancy. Some have serious conditions that can be dangerous for both mother and fetus if left untreated, like high blood pressure or diabetes.

“Pregnant women are essentially like everybody else,” Gyamfi-Bannerman says. They have the same underlying conditions, requiring the same drugs. In a 2013 study, the top 20 prescriptions taken during the first trimester included antibiotics, asthma and allergy drugs, metformin for diabetes, and antidepressants. Yet even for common drugs, the only advice available if you’re pregnant is “talk to your doctor.” With no data, doctors don’t have the answers either.

What’s frustrating to many doctors and researchers is that this lack of information is by design. Even the later stages of most clinical trials, which test a new drug’s safety and efficacy in people, specifically exclude pregnant people to avoid risk to the fetus. But in the wake of a pandemic that disproportionately harmed the pregnant population, researchers are questioning more than ever whether this is the best approach.

Typically, researchers have to justify excluding certain groups, such as older adults, from clinical trials in which they might benefit. “You never have to justify why you’re excluding pregnant people,” says Gyamfi-Bannerman, who now heads the obstetrics, gynecology and reproductive science department at the University of California, San Diego. “You can just go ahead and exclude them.

“The exclusion of pregnant people in clinical trials is a huge, historic problem,” she says, “and it really came to light with COVID.”

Pregnant in a crisis
Teresa Mathews was 43 years old when she found out she was pregnant in June 2020, just as the pandemic was tearing across the United States. “I was really worried,” she says. In addition to her age as a risk factor, Mathews has sickle cell trait, meaning she carries one defective gene copy that makes her prone to anemia and shortness of breath. COVID-19 also causes shortness of breath, so Mathews feared her unborn child could starve for oxygen if she caught the virus.

What’s more, the baby would be her first. “I don’t want to say it melodramatically, but it was my last chance of having a baby, right? So I didn’t really want to take chances.” She went into full lockdown for the rest of her pregnancy.

For good reason. A study during the pandemic’s first year in England found that pregnant women who got the virus were about twice as likely to have a stillbirth or early birth. And the U.S. Centers for Disease Control and Prevention reported in November 2020 that pregnant women are about three times as likely as other women to land in intensive care with COVID-19, and 70 percent more likely to die from the infection (SN Online: 2/7/22).
So when the race for a vaccine began, many doctors and officials hoped that vaccines would be tested in pregnant women and shown to be safe. There were promising signs: The U.S. Food and Drug Administration encouraged vaccine developers to include pregnant women in their trials. A large body of previous research suggested that risks would be low for vaccines like those for COVID-19, which do not contain live viruses.

But ultimately the three vaccines that the FDA cleared for use in the United States, from Pfizer/BioNTech, Moderna and Johnson & Johnson, excluded pregnant people from their initial clinical trials. After its vaccine was authorized for emergency use in December 2020, Pfizer began enrolling pregnant women for a clinical trial but called it off when federal officials recommended that all pregnant women get vaccinated. The company cited challenges with enrolling enough women for the trial, as well as ethical considerations in giving a placebo to pregnant individuals once the vaccine was recommended.

When pregnant people were excluded from vaccine trials, doctors knew it would be difficult to convince pregnant patients to take a vaccine that hadn’t been tested during pregnancy.

Mathews says she would have been willing to get vaccinated while pregnant if there had been data to support the decision. But the choice was made for her. Her daughter, Eulalia, was born healthy in February 2021, shortly before the vaccines became available to all adults in Mathews’ hometown of Knoxville, Tenn. At that point, there was still no clear guidance on whether to get vaccinated while pregnant or nursing.
Officials at the National Institutes of Health in Bethesda, Md., were worried about that lack of direction. Diana Bianchi, director of the National Institute of Child Health and Human Development, called for more COVID-19 vaccine research in the pregnant population in a February 2021 commentary in JAMA. She wrote, “Pregnant people and their clinicians must make real-time decisions based on little or no scientific evidence.”

Meanwhile, social media and pregnancy websites filled the void with conspiracy theories and scary stories about vaccines causing infertility or miscarriages. Alarmed, the American College of Obstetricians and Gynecologists warned last October that “the spread of misinformation and mistrust in doctors and science is contributing to staggeringly low vaccination rates among pregnant people.”

Indeed, the CDC had issued an urgent health advisory the month before warning that only 31 percent of pregnant people were fully vaccinated, compared with about 56 percent of the general population. (CDC and many experts favor “pregnant people” as a general term. Science News is following the language used by sources, and refers to pregnant women when a study population was designated as such.)

“Every week, I look at the number of pregnant people who have died due to COVID. Right now, the most recent statistic is 257 deaths,” Bianchi said in January. “I look at that and I say, that was a preventable statistic.”

After the vaccines received emergency use authorization, the CDC analyzed the outcomes for nearly 2,500 vaccinated pregnant people and found no safety concerns related to pregnancy. The agency recommended vaccination for anyone who is pregnant, lactating or considering becoming pregnant. But that recommendation arrived more than six months after the first vaccine became available.
Since then, the vaccines have also proved to be highly effective in pregnancy. More than 98 percent of COVID-19 critical care admissions in a group of more than 130,000 pregnant women in Scotland were unvaccinated, researchers reported in January in Nature Medicine. And all of the infants who died had unvaccinated moms.

“The story of COVID is yet another cautionary tale,” says Anne Lyerly, a bioethicist at the University of North Carolina at Chapel Hill who trained as an obstetrician and gynecologist. “It highlighted what we’re up against.” Researchers have an ethical duty, she says, not only to protect fetuses from the potential risks of research, but also to ensure that “the drugs that go on the market are safe and effective for all the people who will take them.”

Good intentions
Increasingly, scientists are questioning what Gyamfi-Bannerman calls a “knee-jerk” tendency to exclude pregnant individuals from clinical trials. In 2009, Lyerly and colleagues formed the Second Wave Initiative to promote ethical ways to include pregnant women in research. As their ideas have spread, more researchers — mostly women — have held conferences and spearheaded research. Collectively, they’re pushing back on the prevailing culture “that pregnant people need to be protected from research instead of protected through research,” Bianchi says.

“We got here with good intentions,” says Brookie Best, a clinical pharmacologist at UC San Diego who studies medication use among pregnant people. “There were some terrible, terrible tragedies of pregnant people taking a drug and having bad outcomes.”

The most famous of these was thalidomide. Starting in the late 1950s, the drug was prescribed for morning sickness, but it had never been tested in pregnant people. By the early 1960s, it became clear that it caused birth defects including missing or malformed limbs (SN: 7/14/62, p. 22). Afterward, drug companies were reluctant to take on the risk, or legal liability, of potential birth defects. While the FDA enacted new safety rules in response to the thalidomide disaster, the agency did not require testing during pregnancy before drugs went to market.

In 1977, the FDA recommended the exclusion of all women of childbearing age from the first two phases of clinical trials. When the U.S. Congress passed a bill in 1993 requiring that women and minorities be included in clinical research, the requirement did not extend to pregnant women.
Some scientists still see plenty of good reasons not to include pregnant women in clinical trials. For example, reproductive epidemiologist Shanna Swan has seen unexpected health effects crop up long after substances were deemed safe. With that in mind, Swan, of the Icahn School of Medicine at Mount Sinai in New York City, says that observational studies that follow women and their children after a drug has been approved remain the best approach. These studies are “expensive, and very slow,” she admits, but safer.

For decades, that level of precaution has extended to essentially all medications. As a result, the reproductive effects of a medicine aren’t usually discovered until long after a drug enters the market. Even then, such research is not required for most new drugs, so doctors and researchers must take the initiative. Typically, this happens through pregnancy registries, which enroll pregnant volunteers who are taking a particular drug and follow them throughout pregnancy or beyond.

But voluntary registries leave huge data gaps. A 2011 review of 172 drugs approved by the FDA in the preceding decade found that the risk of harm to fetal development was “undetermined” for 98 percent of them, and for 73 percent there was no safety data during pregnancy at all.

That doesn’t mean all those drugs are dangerous. Relatively few drugs cause major birth defects, and many of those fall into known classes. For example, ACE inhibitors used to control blood pressure have been linked to a range of issues, including kidney and cardiovascular problems in infants, when taken during pregnancy. But the potential for more subtle, long-term effects has been trickier to tease out.

For instance, several studies in the 2010s reported links between mothers taking antidepressants during pregnancy and their kids having developmental problems like attention-deficit/hyperactivity disorder and autism spectrum disorder. Some moms became afraid to treat their own depression. But in 2017, studies of siblings found no difference in these conditions among children who had been exposed to antidepressants in the womb and those who had not (SN: 5/13/17, p. 9). More likely, the problem was the depression the mom was experiencing, the studies suggested, not the drugs.

No legal requirement
How the contents of a pregnant woman’s medicine cabinet might affect her child depends on a host of factors, including how the drug works and whether it crosses the placenta. The main way to gauge whether a drug may harm a fetus is through animal studies called developmental and reproductive toxicology, or DART, studies. But drug companies often don’t begin these studies until they’ve already gotten clinical trials rolling.

This creates a catch-22, because clinical trials can’t include pregnant people until DART studies suggest it’s safe to do so. That’s why Lyerly and others pushing for change say that pharmaceutical companies should start doing these studies earlier, before clinical trials begin.

In 2018, the FDA issued draft guidance to help the pharmaceutical industry decide how and when to include pregnant people in clinical trials (SN Online: 5/30/18). That guidance is an encouraging first step, Lyerly says, but it didn’t change any of the stringent rules for when pregnant people could be included in research.

Plus, it’s all completely voluntary, says Leyla Sahin, acting deputy director for safety in FDA’s Division of Pediatric and Maternal Health. “We advise industry…. We tell them we recommend that you include pregnant women in your clinical trials,” Sahin says. “But there’s no requirement.”

In fact, the FDA doesn’t even have the legal authority to create a requirement. In that sense, Sahin says, “we’re where pediatrics was 20 years ago.” Until Congress passed the Pediatric Research Equity Act of 2003, children were routinely excluded from clinical trials just as pregnant women are now. The pediatric law required drug companies to gather data on the safety and effectiveness of medications in children and to provide FDA an appropriate plan for pediatric studies.

Congress could pass a similar law for pregnancy. And in 2020, a government task force recommended exactly that to the Department of Health and Human Services, which oversees FDA. But “it’s almost like it’s gone into this black hole,” Sahin says. “We haven’t heard from HHS. We haven’t heard from Congress.”
Stocking the medicine cabinet
Until clinical trials during pregnancy become more routine, pregnant people face an untenable choice — take a drug without knowing its safety, or leave their medical conditions untreated.

Case in point: A group of 91 doctors and scientists published a consensus statement in September 2021 in Nature Reviews Endocrinology warning that acetaminophen, the most commonly used drug during pregnancy, may harm fetal development. Research suggests the drug disrupts hormones, with effects ranging from undescended testicles in male infants to an increased risk of ADHD and autism spectrum disorder in boys and girls.

But as is often the case with drugs and pregnancy, there’s not exactly a consensus among doctors about what pregnant people should do. In response to the new paper, the American College of Obstetricians and Gynecologists issued a statement saying the evidence wasn’t strong enough to suggest doctors should change their standard practice, which is to recommend acetaminophen be taken as needed and in moderation.

Acetaminophen is an active ingredient in more than 600 medications, including Tylenol, and is estimated to be used by up to 65 percent of pregnant people in the United States. It has long been the preferred pain medication and fever reducer during pregnancy because the FDA recommends against the anti-inflammatory drugs known as NSAIDs — such as ibuprofen and aspirin — in the second half of pregnancy. Those drugs have been linked to rare fetal kidney problems and low amniotic fluid levels.

While at the University of Copenhagen, clinical pharmacologist David Kristensen began studying acetaminophen’s effects on fetal development after noticing that the drug is structurally similar to chemicals that disrupt hormones. In 2011, he and colleagues published animal and human studies linking acetaminophen use during pregnancy with concerning effects in infants, including undescended testicles.

“My ears perked up when I heard that,” says Swan, the Mount Sinai reproductive epidemiologist and coauthor of the 2021 acetaminophen review. She had seen similar effects with maternal exposure to phthalates, chemicals used in plastics that are known to alter the activity of hormones needed to regulate fetal development.

She and colleagues surveyed 25 years of acetaminophen studies. The group found that five out of 11 relevant studies linked prenatal acetaminophen use to urogenital and reproductive tract abnormalities in children, and 26 out of 29 epidemiological studies linked fetal exposure to acetaminophen with neurodevelopmental and behavioral problems. The strength of these links varied, but were “generally modest,” the authors wrote.

“We’re looking at subtle effects here,” Swan says, “but that doesn’t mean that they’re not important.” With such widespread use, “there’s a good chance that a fair number of offspring are affected.”

Although Swan is wary of testing new drugs in pregnant women, she would like to see better research on medications during pregnancy. “There’s a whole range of options short of doing human study,” she says.

To start with, Swan says, scientists need better data on what medications pregnant women are taking, and how much. That means more studies should ask women to keep daily logs of every pill they take. Researchers can also do more studies of drugs’ reproductive effects in animals, she notes, and even transplant human tissues such as brain, liver or gonads into animals to learn how they respond to drugs.

Not the same vulnerability
The cultural shift around pregnancy research may be gaining momentum.

Government-funded research is one key area for change. In 2016, the 21st Century Cures Act established an interagency task force on research specific to pregnant and lactating women. It included officials from NIH, CDC and FDA, as well as medical societies and industry. One of the task force’s recommendations was acted upon in 2018: removing pregnant women as a “vulnerable” group in a federal regulation called the Common Rule, which governs federally funded research. Pregnant women had been listed along with children, prisoners and people with intellectual disabilities as vulnerable and thus requiring special protections if included in research.

Unlike the other groups in that list, pregnant people “don’t have a diminished capacity to provide informed consent,” says Lyerly, the bioethicist at the University of North Carolina. That rule change alone could help “change the culture of research.”

Meanwhile, researchers are forging ahead with studies on many drugs used during pregnancy. HIV drugs are among the most studied, says Best of UC San Diego, in part because the virus can pass from pregnant women to their fetuses. “So right off the bat, everybody knew that we needed to treat these [pregnant] patients with medication,” she says. Yet data on HIV drugs during pregnancy lagged as much as 12 years after FDA approval.
Many pregnant women appear to be willing to participate in research. More than 18,000 pregnant people had enrolled in the COVID-19 vaccine pregnancy registry as of March, and every year many volunteer for other pregnancy registries.

Gyamfi-Bannerman says that in her experience, plenty of pregnant patients are willing to volunteer, even for experimental drugs, if there’s potential to benefit from the drug and they will be monitored closely. At Columbia University, she helped lead a clinical trials network called the Maternal Fetal Medicine Units Network that specifically studies complications during pregnancy. “It’s a very safe and protective environment,” she says.

As for next steps, a few policy changes could make a big difference, Best says, like “getting those preclinical studies done earlier and allowing people who accidentally get pregnant while participating in a clinical trial to make the choice of whether or not to stay.” Right now, “if you get pregnant, you’re out. Boom, that’s it,” she says. “But they were already exposed to the risk, and now they’re not getting the benefit. And so we don’t think that’s actually ethical.”

Thalidomide was prescribed to pregnant women to treat morning sickness, without ever having been tested in pregnant women. “We took the wrong lesson from thalidomide,” Lyerly says. “The first lesson of thalidomide is that we should do research, not that we shouldn’t.”

Gravitational waves gave a new black hole a high-speed ‘kick’

This black hole really knows how to kick back.

Scientists recently observed two black holes that united into one, and in the process got a “kick” that flung the newly formed black hole away at high speed. That black hole zoomed off at about 5 million kilometers per hour, give or take a few million, researchers report in a paper in press in Physical Review Letters. That’s blazingly quick: The speed of light is just 200 times as fast.

Ripples in spacetime, called gravitational waves, launched the black hole on its breakneck exit. As any two paired-up black holes spiral inward and coalesce, they emit these ripples, which stretch and squeeze space. If those gravitational waves are shot off into the cosmos in one direction preferentially, the black hole will recoil in response.
It’s akin to a gun kicking back after shooting a bullet, says astrophysicist Vijay Varma of the Max Planck Institute for Gravitational Physics in Potsdam, Germany.

Gravitational wave observatories LIGO and Virgo, located in the United States and Italy, detected the black holes’ spacetime ripples when they reached Earth on January 29, 2020. Those waves revealed details of how the black holes merged, hinting that a large kick was probable. As the black holes orbited one another, the plane in which they orbited rotated, or precessed, similar to how a top wobbles as it spins. Precessing black holes are expected to get bigger kicks when they merge.

So Varma and colleagues delved deeper into the data, gauging whether the black hole got the boot. To estimate the kick velocity, the researchers compared the data with various predicted versions of black hole mergers, created based on computer simulations that solve the equations of general relativity, Einstein’s theory of gravity (SN: 2/3/21). The recoil was so large, the researchers found, that the black hole was probably ejected from its home and kicked to the cosmic curb.

Dense groups of stars and black holes called globular clusters are one locale where black holes are thought to partner up and merge. The probability that the kicked black hole would stay within a globular cluster home is only about 0.5 percent, the team calculated. For a black hole in another type of dense environment, called a nuclear star cluster, the probability of sticking around was about 8 percent.

The black hole’s great escape could have big implications. LIGO and Virgo detect mergers of stellar-mass black holes, which form when a star explodes in a supernova and collapses into a black hole. Scientists want to understand if black holes that partner up in crowded clusters could partner up again, going through multiple rounds of melding. If they do, that could help explain some surprisingly bulky black holes previously seen in mergers (SN: 9/2/20). But if merged black holes commonly get rocketed away from home, that would make multiple mergers less likely.

“Kicks are very important in understanding how heavy stellar-mass black holes form,” Varma says.

Previously, astronomers have gleaned evidence of gravitational waves giving big kicks to supermassive black holes, the much larger beasts found at the centers of galaxies (SN: 3/28/17). But that conclusion hinges on observations of light, rather than gravitational waves. “Gravitational waves, in a way, are cleaner and easier to interpret,” says astrophysicist Manuela Campanelli of the Rochester Institute of Technology in New York, who was not involved in the new study.

LIGO and Virgo data had already revealed some evidence of black holes getting small kicks. The new study is the first to report using gravitational waves to spot a black hole on the receiving end of a large kick.

That big kick isn’t a surprise, Campanelli says. Earlier theoretical predictions by Campanelli and colleagues suggested that such powerful kicks were possible. “It’s always exciting when someone can measure from observations what you predicted from calculations.”

Glowing spider fossils may exist thanks to tiny algae’s goo 

The secret ingredient for fossil preservation at a famous French site wouldn’t be found in a Julia Child cookbook. It was a sticky goo made by microalgae, researchers suggest.

An analysis of roughly 22-million-year-old spider fossils from a fossil-rich rock formation in Aix-en-Provence, France, reveals that the arachnids’ bodies were coated with a tarry black substance. That substance, a kind of biopolymer, was probably secreted by tiny algae called diatoms that lived in the lake or lagoon waters at the ancient site, scientists report April 21 in Communications Earth & Environment.

The biopolymer didn’t just coat the spiders’ bodies — it pickled them. By chemically reacting with the spiders’ carbon-rich exoskeletons, the goo helped preserve the bodies from decomposition, allowing them to more easily become fossils, the team hypothesizes.
A clue that this coating might play a role in fossilization came when the researchers, on a whim, placed a spider fossil under a fluorescence microscope. To their surprise, the substance glowed a bright yellow-orange. “It was amazing!” says geologist Alison Olcott of the University of Kansas in Lawrence.

The fluorescent imaging painted a bright, colorful palette onto what was otherwise a fairly faint spider fossil, Olcott says. In the original, she could barely tell the spider apart from the background rock. But under fluorescence, she says, the spider fossil glowed in one color, the background in another and the biopolymer in a third.

That discovery — along with an abrupt halt in early 2020 to any additional fossil-collecting plans due to the COVID-19 pandemic — swiftly shifted the focus of the team’s work. “Had it been normal times, this would have been a side note in a taxonomy study” classifying ancient spiders, Olcott says. Instead, “I really had to explore what I had,” she adds. “It was me and these images.”

The researchers next sought to identify the chemical makeup of the mysterious substance. The orange-yellow glow, the team found, comes from abundant carbon and sulfur in the coating. “That got me thinking about sulfurization,” Olcott says.
Sulfurization is the reaction of organic carbon with sulfur, which forms sturdy chemical bonds with the carbon, making it more resistant to degradation and breakdown — similar to how tire manufacturers harden rubber to make it more durable. The process requires a ready supply of sulfur available for bonding.

In modern times, such a supply comes from the sulfur-rich gooey secretions of diatoms, microalgae found floating in many waters around the world. When these secretions meet carbon-laden marine particles headed for the bottom of the ocean, this sulfurization process helps lock the carbon in place and possibly keep it buried in the seafloor.

Similarly, sulfurization might help to preserve delicate carbon-rich fossils, helping them to withstand the test of millions of years of geologic time, Olcott says. Scientists have often noted diatoms in the fossil-bearing rock formations of Aix-en-Provence, as well as at many similar fossil-rich sites, she adds. “Everyone’s seeing diatoms everywhere. Thinking about that and the chemistry, I was like, ‘Wait a minute. All the pieces are here to make this chemistry happen.’”

The arachnids’ preservation might have gone like this: A dead spider, floating in the water column, became covered in the diatoms’ sticky goo. The goo chemically reacted with the spider’s chitin exoskeleton, more or less pickling it and keeping the exoskeleton largely intact and ready for fossilization.

That scenario “makes sense based on what we know about organic sulfur cycling in modern environments so far,” says Morgan Raven, an organic geochemist at the University of California, Santa Barbara. Scientists still have a lot to learn about the conditions that allow materials like chitin to sulfurize, Raven says. “But this study highlights why that matters.”

For example, if sulfurization selectively helps preserve some types of organic matter — such as soft-bodied fossils — that “could be a crucial filter on our fossil record, influencing what we do and don’t know about plant and animal evolution,” she adds.

This process of diatom-assisted sulfurization may have been at work in other fossil-rich sites during the Cenozoic Era, Olcott says. That span of time began 66 million years ago, after an asteroid ended the Age of Dinosaurs, and continues to the present day. Before that era, diatoms were not widespread. That didn’t happen until silica-bearing grasses sprouted around the world during the Cenozoic, offering a ready source of silica for the tiny creatures to build their delicate bodies (SN: 5/1/19).

It’s unknown if other biopolymer-producing algae might have helped fossilize soft-bodied creatures from even earlier, such as during the flourishing of Cambrian Period life-forms beginning around 541 million years ago, Olcott says (SN: 4/24/19). “But it would be really interesting to expand this further out.”

The Large Hadron Collider has restarted with upgraded proton-smashing potential

After a hiatus of more than three years, the Large Hadron Collider is back.

Scientists shut down the particle accelerator in 2018 to allow for upgrades (SN: 12/3/18). On April 22, protons once again careened around the 27-kilometer-long ring of the Large Hadron Collider, or LHC, located at the particle physics laboratory CERN in Geneva.

The LHC is coming out of hibernation gradually. Researchers started the accelerator’s proton beams out at relatively low energy, but will ramp up to slam protons together at a planned record-high energy of 13.6 trillion electron volts. Previously, LHC collisions reached 13 trillion electron volts. Likewise, the beams are starting out wimpy, with relatively few protons, but will build to higher intensity. And when fully up to speed, the upgraded accelerator will pump out proton collisions more quickly than in previous runs. Experiments at the LHC will start taking data this summer.

Physicists will use this data to further characterize the Higgs boson, the particle discovered at the LHC in 2012 that reveals the source of mass for elementary particles (SN: 7/4/12). And researchers will be keeping an eye out for new particles or anything else that clashes with the standard model, the theory of the known particles and their interactions. For example, researchers will continue the hunt for dark matter, a mysterious substance that so far can be observed only by its gravitational effects on the cosmos (SN: 10/25/16).

After several years of operations, the LHC will shut down again to prepare the High-Luminosity LHC (SN: 6/15/18), which will further boost the rate of proton collisions and allow for even more detailed studies of the fundamental constituents of matter.

Muons spill secrets about Earth’s hidden structures

Inside Egypt’s Great Pyramid of Giza lies a mysterious cavity, its void unseen by any living human, its surface untouched by modern hands. But luckily, scientists are no longer limited by human senses.

To feel out the contours of the pyramid’s unexplored interior, scientists followed the paths of tiny subatomic particles called muons. Those particles, born high in Earth’s atmosphere, hurtled toward the surface and burrowed through the pyramid. Some of the particles imprinted hints of what they encountered on sensitive detectors in and around the pyramid. The particles’ paths revealed the surprising presence of the hidden chamber, announced in 2017 (SN: 11/25/17, p. 6).

That stunning discovery sparked plans among physicists to use muons to explore other archaeological structures. And some researchers are using the technique, called muography, to map out volcanoes’ plumbing. “You can see inside the volcano, really,” says geophysicist Giovanni Leone of Universidad de Atacama in Copiapó, Chile. That internal view could give scientists more information about how and when a volcano is likely to erupt.
Muons are everywhere on Earth’s surface. They’re produced when high-energy particles from space, known as cosmic rays, crash into Earth’s atmosphere. Muons continuously shower down through the atmosphere at various angles. When they reach Earth’s surface, the particles tickle the insides of large structures like pyramids. They penetrate smaller stuff too: Your thumbnail is pierced by a muon about once a minute. Measuring how many of the particles are absorbed as they pass through a structure can reveal the density of an object, and expose any hidden gaps within.

The technique is reminiscent of taking an enormous X-ray image, says Mariaelena D’Errico, a particle physicist at the National Institute for Nuclear Physics in Naples, Italy, who studies Mount Vesuvius with muons. But “instead of X-rays, we use … a natural source of particles,” the Earth’s very own, never-ending supply of muons.

Physicists have typically studied cosmic rays to better understand the universe from whence they came. But muography turns this tradition on its head, using these cosmic particles to learn more about previously unknowable parts of our world. For the most part, says particle physicist Hiroyuki Tanaka of the University of Tokyo, “particles arriving from the universe have not been applied to our regular lives.” Tanaka and others are trying to change that.
No particle like it
Awkward cousins of electrons, muons may seem like an unnecessary oddity of physics. When the particle’s identity was first revealed, physicists wondered why the strange particle existed at all. While electrons play a crucial role in atoms, the heavier muons serve no such purpose.

But muons turn out to be ideal for making images of the interiors of large objects. A muon’s mass is about 207 times as large as an electron’s. That extra bulk means muons can traverse hundreds of meters of rock or more. The difference between an electron and a muon passing through matter is like the difference between a bullet and a cannonball, says particle physicist Cristina Cârloganu. A wall may stop a bullet, while a cannonball passes through.

Muons are plentiful, so there’s no need to create artificial beams of radiation, as required for taking X-ray images of broken bones in the doctor’s office, for example. Muons “are for free,” says Cârloganu, of CNRS and the National Institute of Nuclear and Particle Physics in Aubière, France.
Another crucial upside of muons: “They’re also very easy to detect,” says nuclear physicist Richard Kouzes of the Pacific Northwest National Laboratory in Richland, Wash. A simple detector made of strips of plastic and light sensors will do the trick. Other muon detectors require little more than a specialized version of photographic film. There’s no other particle like it, Kouzes says.

Muons have a negative electric charge, like an electron. Their antiparticles, antimuons, which also shower down on Earth, have a positive charge. Muon detectors capture tracks of both negatively and positively charged varieties. When these particles pass through material, they lose energy in various ways, for example, by colliding with electrons and knocking them loose from their atoms.

With that energy loss, muons slow down, sometimes enough to stop. The denser the material, the fewer muons will make it through to a detector placed underneath or to the side of the material. So large, dense objects such as volcanoes or pyramids cast a muon shadow. And any gaps within those structures will appear as bright spots within that shadow, because more muons can slip through. Interpreting such dappled shadows can open a vista into hidden worlds.

Probing pyramids
Muography proved itself in a pyramid. One of the first uses of the technique was in the 1960s, when physicist Luis Alvarez and colleagues looked for hidden chambers in Khafre’s pyramid in Giza, a slightly smaller neighbor of the Great Pyramid. Detectors found no hint of unexpected rooms, but proved that the technique worked.

Still, the idea took time to take off, because muon detectors of the era tended to be bulky and worked best in well-controlled laboratory conditions. To spot the muons, Alvarez’s team used detectors called spark chambers. Spark chambers are filled with gas and metal plates under high voltage, so that charged particles passing through create trails of sparks.

Now, thanks to advances in particle physics technologies, spark chambers have largely been replaced. “We can make very compact, very sturdy detectors,” says nuclear physicist Edmundo Garcia-Solis of Chicago State University. Those detectors can be designed to work outside a carefully controlled lab.

One type of resilient detector is built with plastic containing a chemical called scintillator, which releases light when a muon or other charged particle passes through (SN Online: 8/5/21). The light is then captured and measured by electronics. Later this year, physicists will use these detectors to take another look at Khafre’s pyramid, Kouzes and colleagues reported February 23 in the Journal for Advanced Instrumentation in Science. Compact enough to fit within two large carrying cases, the detector “can be carried into the pyramid and then operated with a laptop and that’s all,” Kouzes says.
A different but particularly low-maintenance type of detector, called a nuclear emulsion film, was crucial to uncovering the Great Pyramid’s hidden void in 2017. Nuclear emulsions record particle tracks in a special type of photographic film. The detectors are left in place for a period of time, then brought back to a lab for analysis of the tracks imprinted in them.

Particle physicist Kunihiro Morishima of Nagoya University in Japan helped discover the secret chamber through work on an international project called ScanPyramids. “Nuclear emulsions are lightweight, compact and do not require a power supply,” he explains. That meant that multiple detectors could be placed in prime viewing locations in one of the pyramid’s rooms, the Queen’s Chamber, and a small niche next to it. The detectors’ measurements were supplemented with plastic scintillator detectors inside the Queen’s Chamber, and gas-based detectors outside the pyramid.
Since the discovery of the void, Morishima and colleagues have been taking additional measurements to better sketch out its properties. The team placed emulsion detectors in 20 locations in the pyramid, as well as gas detectors in several different spots. Using their new array of instruments, the researchers determined that the void is over 40 meters long. Its purpose is still unknown.

A more extensive survey of the Great Pyramid, placing much larger detectors outside the pyramid, is being planned by another team of researchers. The detectors will be periodically moved to measure muons from multiple angles, the team reported March 6 in the Journal for Advanced Instrumentation in Science. The result, says co­author and particle physicist Alan Bross of Fermilab in Batavia, Ill., will offer a 3-D view of what’s inside (SN: 12/18/21 & 1/1/22, p. 44).

Pyramids in other parts of the world are also getting closer scrutiny. Garcia-Solis and colleagues are now planning muography of the Maya pyramid known as El Castillo at Chichén Itzá in Mexico. Morishima and colleagues, as well, are planning work on Maya pyramids.

Scientists hope such studies might reveal new chambers, or features not visible with other techniques for peering inside of objects. Ultrasound, ground-penetrating radar or X-rays, for example, can only penetrate a short distance from the surface, Bross explains. Muons, on the other hand, give an in-depth picture. For studying pyramids, Bross says, “muons really are ideal.”

Peering inside a volcano
Vesuvius is a known menace in Naples and the surrounding municipalities that snuggle up against the volcano’s flanks. Infamous for destroying the ancient city of Pompeii in A.D. 79, the volcano has been quiescent since 1944, when a major eruption destroyed several nearby villages (SN: 2/29/20, p. 5). But if it erupted, it would endanger the lives of roughly 600,000 people who live closest to it, and many others in the vicinity.

“Vesuvius always scared me,” D’Errico says. “I was born and I live under this volcano.” Now, as part of the Muon Radiography of Vesuvius experiment, or MURAVES, she seeks to better understand the volcano and its dangers.
Using muon detectors 1.5 kilometers from the volcano’s crater, the team is mapping out muon densities — and thus rock densities — at the top of Vesuvius’ cone. In a paper posted February 24 at arXiv.org, the researchers presented preliminary hints of density differences between the volcano’s northwestern and southeastern halves. MURAVES is still collecting data; future observations should help scientists understand finer details of the volcano’s internal structure, which is thought to be layered due to repeated eruptions.

Information about a volcano’s structure can help scientists predict what hazards to expect in an eventual eruption, such as where landslides might occur. And that could help scientists know what steps to take to reduce risks to people living nearby, says Cârloganu, who studied the dormant volcano Puy de Dôme near Clermont-Ferrand, France, with muography and is now working to image the aptly named island of Vulcano in Italy.

When Mount St. Helens in Washington erupted in 1980, for example, an entire flank of the volcano collapsed. The disaster killed 57 people and caused widespread damage. Knowing where a volcano’s structural weaknesses lie could help scientists better predict how an eruption might play out, and what areas sit inside the danger zone, Cârloganu says.

Cârloganu thinks muons will be useful for pointing out structural weaknesses, but not for giving a warning when the volcano is going to blow. Other researchers are more optimistic about muons’ capability for giving timely forewarnings.

Muography is ripe for inclusion in volcano early-warning systems, Leone, Tanaka and colleagues wrote last November in Proceedings of the Royal Society A. But more work needs to be done to integrate muography with other established methods that help warn of an upcoming eruption, Leone says. These methods include seismic measurements, as well as observations of ground deformation and volcanic gas emissions.

Tanaka and colleagues are studying Sakurajima, one of the most active volcanoes in the world, near Kagoshima, Japan. One of the volcano’s craters, the Showa crater, erupted frequently until 2017 when the activity abruptly shifted to another crater, Minamidake. Comparing muography data taken before and after this shift revealed that a new, dense region had formed below the Showa crater, Tanaka and colleagues reported in 2019 in Geophysical Research Letters. That hints at the reason Showa’s eruptions stopped: It was clogged with a dense plug of solidified magma, Tanaka says.
These results suggest that scientists can use muography to help predict volcanic eruptions, Tanaka says. In fact, using deep learning techniques on the muography data from Sakurajima, Tanaka and colleagues reported in Scientific Reports in 2020 that they were able to predict whether the volcano would erupt the next day, by analyzing the previous week’s data. The technique correctly predicted eruption days of the volcano more than 72 percent of the time, and correctly predicted non-eruption days more than 85 percent of the time.

Just as the discovery of X-rays unveiled a whole new way of seeing the world, harnessing muons could change our perspective on our surroundings. Attitudes toward a particle once thought to be unnecessary — unwanted and unloved by physicists — have been transformed. One day, perhaps, muons could save lives.

NFL tickets 2022: Breaking down the hottest games & cheapest prices on sale for football season

The NFL schedule release isn't the most interesting event on the league's offseason calendar, but it still serves an important purpose for fans. It helps them to plan which NFL games they might like to attend during the season.

Once the schedule is announced, the NFL's most eager fans tend to circle the matchups they most want to see in the upcoming season. The 2022 campaign will be no different, and there are plenty of marquee matchups on this year's game slate.

Cowboys vs. Buccaneers; Chiefs vs. Bills; Seahawks vs. Broncos; there are plenty of high-end matchups at which NFL fans will want to be. But just how expensive will those top-tier games get? The prices can get a little bit out of control, even for bargain hunters.

Which of this year's 256 games are the most expensive, and which are the cheapest? The Sporting News breaks down the NFL's hottest (and coldest) tickets using the price from TicketSmarter.com.

MORE: Buy 2022 NFL season tickets with TicketSmarter

Most expensive NFL tickets for 2022 season
There are currently 17 games during the NFL season that have an average ticket price of $800 or higher. The most expensive of the bunch is the Packers vs. Giants game, which is commanding an average price of $2,136 per ticket. That contest is set to be played in London at the Tottenham Hotspur's stadium.

The Seahawks vs. Buccaneers game is also set to have an average price of greater than $1,000 per ticket. That contest is the first in NFL history to be played in Germany, so Munich residents will relish a chance to play in the game.

Another notably expensive game is Russell Wilson's return to Seattle, which will be the most expensive game played on American soil this year. The Broncos are participants in two of the games that feature average ticket prices over $1,000 while the Buccaneers lead the pack with four appearances in such games.

Below is a look at the most expensive games of the 2022 NFL season. This includes the high and low prices to get into the stadium thanks to TicketSmarter.

Cheapest NFL tickets for 2022 season
If you're looking for a cheap way to get to an NFL game this season, you're in luck. There are about a dozen and a half games at which it shouldn't be too hard to land favorably priced tickets.

There are 19 games in the NFL where the average ticket price is less than $220, and 10 of them have a price tag of $200 or lower. Unsurprisingly, many of the teams that are coming off down seasons or are projected to have rough 2022 campaigns are on the list.

The Lions, Panthers, Falcons, Jaguars and Texans are frequently on the list of teams with the lowest average price. The Jaguars and Texans both have tickets available at as low as $32, and the Colts have discounted their game against the Jaguars to a minimum price of $32.
The cheapest overall game right now is set to take place on Oct. 2 when the Seahawks travel to Detroit to take on the Lions. The average ticket price for that contest is $158 while the highest-priced ticket for the game is just $804. Only two other games on the schedule — Panthers at Ravens and Dolphins at Lions — have maximum ticket prices in the $800 range.

Below is a look at the least expensive games of the 2022 NFL season. This includes the high and low prices to get into the stadium thanks to TicketSmarter.
MORE: LeSean McCoy rips Chiefs OC Eric Bieniemy, explains why he isn't a head coach

How much do NFL tickets cost by team?
Unsurprisingly, the Buccaneers ($757.26) have the highest average ticket price for any NFL team in 2022. That makes sense given that Tom Brady is in what could be his last NFL season, so fans are willing to pay a premium to see him play once again.

Beyond the Bucs, only three other teams have tickets that cost an average of more than $600. They are the Cowboys ($690), the Raiders ($674) and the Patriots ($643).

The Lions have the NFL's cheapest ticket, as their games cost, on average, about $224. The Jaguars ($258), Jets ($265), Cardinals ($276) and Browns ($282) are the league's other four teams that have an average ticket cost of under $300.

Below is a full look at the list of average ticket prices, via TicketSmarter. Please note that this average includes events at all venues, including away games.

Missing COVID-19 data leave us in the dark about the current surge

As science journalists, we’re accustomed to data. We sift through it and talk it over with experts. We pay close attention to the stories that numbers can tell. But at this point in the pandemic, many of us are having a hard time finding the story. That’s because the numbers aren’t there.

Data on coronavirus infections in the United States have become less reliable, many experts say. Fewer people are getting tested, local governments have stopped reporting results, and home test results rarely make it into official counts (SN: 4/22/22).
To be sure, there are still official numbers to be found. They don’t look great. Hospitalizations are low compared with earlier in the pandemic, but they’re rising again, and the case counts that do exist are ticking up, too. After dipping in March, the tally in the United States is back up to more than 100,000 known cases a day. A third of Americans now live in places with “medium to high” levels of virus spread.

With these not-so-great numbers in mind, it’s not a stretch to assume that the missing data probably wouldn’t tell us a cheery story either. We are almost certainly undercounting cases in the United States. And we’re not alone. Amid worldwide declines in testing and sequencing to see where coronavirus is spreading and how it’s changing, “we are blinding ourselves to the evolution of the virus,” Tedros Adhanom Ghebreyesus, the head of the World Health Organization, said May 22.

We’ve never had a perfect count of COVID-19 cases, of course. Early on in the pandemic, before testing ramped up in some places, scientists found clues about COVID-19’s transmission in odd places. Wastewater testing, for instance, spotted signs of the virus getting flushed down the toilet (SN: 5/28/20). That dirty water continues to be an indirect, but helpful, measure of viral loads in a community. Here in Oregon, where I live, some wastewater spots again show increases in coronavirus, suggesting a surge.

Even more indirect measurements can give us additional hints. Early on in the pandemic, “smart” thermometers connected to the internet generated fever data used to map risk of getting sick by region. Internet searches for words and phrases, such as “chills,” “fever” and “I can’t smell,” also pointed to virus hot spots.

My favorite digital sign of illness comes from online reviews of Yankee Candles. One-star reviews (“No scent.” “Embarrassed as this was a gift.”) tracked neatly with a rise in COVID-19 cases in 2020 and the subsequent loss of smell. Just last week, more one-star reviews showed up, notes Twitter user @drewtoothpaste, who compiled the latest complaints. “No smell.” “Absolutely no scent.” “Very disappointing!!!”
These one-star reviews are not airtight evidence of COVID-19 rates — not by any stretch. But they add to the broader picture that we are not yet done with this pandemic, as much as we would all love to be. We are still experiencing disruptions to our lives, illness, suffering and sadness. Very disappointing indeed.

To better understand this particular moment in the pandemic, I talked with data expert Beth Blauer of Johns Hopkins University. She’s been tracking metrics of the pandemic since it started. In the earliest days, she helped build databases, including a widely used COVID-19 tracker, that ultimately became the Coronavirus Resource Center at Hopkins. Those tools get data out to other scientists, health experts, government leaders, journalists and people who want to keep up with the latest numbers. The interview has been edited for length and clarity.

SN: How solid is the testing data right now in the United States?

Blauer: The testing data in this country is crumbling…. We’re barely getting data out of the application-based resources that come with home tests. And the home tests are running 10 bucks apiece. That’s cost prohibitive for people who live below the poverty line. Even middle-income people are not spending $20 for a pack of two. [Free tests are available in the United States, but it’s not known how many of those tests are reaching people who need them.]

We are flying blind. Completely. We are in a surge right now, but we don’t even appreciate fully how big of a surge this is.

SN: Any guesses?

Blauer: I have no idea. Anecdotally, I’m sure you and I both know a ton of people who have COVID-19 or who just got over it. All the mitigation strategies are not being spun up to meet the rising demand that a surge, like we’re in right now, calls for, which means we’re just going to be getting a lot more COVID-19. People are going on vacations, they’re traveling, graduations, all of these things are just going forward. So yes, we’re seeing some increase in hospitalization, but I don’t think we have any idea how much disease there is in the community.
SN: I’ve had trouble gauging my risk from COVID-19 in everyday life. Is that typical?

Blauer: It’s a mess. I think a lot of people are sensing that. And it dilutes our capacity to have faith in science and in all the things that have happened over time. It is confusing. It’s like, “Oh, we have just as much COVID, but we can go to parties? And school is in?” Everything all of a sudden gets called into question.

[That uncertainty highlights a] need to really think critically about our public health infrastructure in this country.

SN: How should we be living with this virus right now?

Blauer: We all acknowledge that we need social anchoring in our communities. We need to see people. We can’t hide away in our houses forever. But that means we have to think about what it means to live with a pathogen like COVID-19 out there. And we’re not giving ourselves all the best tools to be able to do that.

I work in a building where right down the hall, people are getting chemotherapy. I feel a responsibility to the community that I’m not giving them a disease that could potentially kill them. That’s not happening in a lot of places. For me, it’s sad. It’s like a loss of collective empathy, and I don’t think we should not talk about that.

I think I would feel the very same way even if I wasn’t leading this effort here at Hopkins. But I don’t know. Maybe it’s because I feel the toll of a million Americans who have died. I’ve experienced loss in my life. I do have a lot of empathy. But I don’t think I’m overdoing it.

SN: But you’re not saying we should all hunker down and stay away from people.

Blauer: No. We’re done with that. But we have to start integrating and really putting into place these habits [masking, testing and adjusting behavior when needed]. Because I think it’s the only way we get out of this.

Scientists made a Möbius strip out of a tiny carbon nanobelt

From cylindrical nanotubes to the hollow spheres known as buckyballs, carbon is famous for forming tiny, complex nanostructures (SN: 8/15/19). Now, scientists have added a new geometry to the list: a twisted strip called a Möbius carbon nanobelt.

Möbius strips are twisted bands that are famous in mathematics for their weird properties. A rubber band, for example, has an inside and an outside. But if you cut the rubber band crosswise, twist one end and glue it back together, you get a Möbius strip, which has only one face (SN: 7/24/07).

In 2017, researchers created carbon nanobelts, thin loops of carbon that are like tiny slices of a carbon nanotube. That feat suggested it might be possible to create a nanobelt with a twist, a Möbius carbon nanobelt. To make the itsy-bitsy twisty carbon, some of the same researchers stitched together individual smaller molecules using a series of 14 chemical reactions, chemist Yasutomo Segawa of the Institute for Molecular Science in Okazaki, Japan, and colleagues report May 19 in Nature Synthesis.

While carbon nanotubes can be used to make new types of computer chips and added to textiles to create fabric with unusual properties, scientists don’t yet know of any practical applications for the twisty nanobelts (SN: 8/28/19; SN: 2/8/19). But, Segawa says, the work improves scientists’ ability to make tiny carbon structures, especially complicated ones.