Swallow the wrong microbe, and you might end up in the hospital with a needle or two in your arm — and plenty of itty-bitty bacterial needles poking at you from the inside. That’s because many bacteria that make us sick use microscopic, syringelike structures to inject our cells with proteins that wreak havoc from the inside. Now, researchers have shown how these microbes load their nanoscale needles with proteins.
Tracking individual proteins as they jittered around inside living bacteria revealed the microbes use a shuttle bus–like system to load their syringes: shuttle proteins travel random paths within the microbes’ interiors, grabbing cargo destined for injection as they go and dropping it off at the syringes, scientists report January 3 in Nature Microbiology. Knowing how these bacterial needles work could help scientists learn how to disrupt them — or commandeer them for medical applications, like using bacterial needles to inject cancer cells with targeted drugs while leaving healthy tissue unscathed.
Shuttling proteins to the syringe is “a really novel molecular mechanism that was not known before,” says microbiologist Andreas Diepold of the Max Planck Institute for Terrestrial Microbiology in Marburg, Germany.
Under the microscope, the syringelike structures, called a type-III secretion system, look like hollow needles just wide enough for a single unfolded protein to slither through, Diepold says. A microbe’s entire surface might be covered in such needles, giving the bacterium the look of a sinister little pincushion. Scientists know the protein structure of these nanoscale needles quite well. But “we don’t know the basic question of how they recruit whatever is injected,” he says.
Imaged by a transmission electron microscope, these free-floating Type-III secretion systems look like tiny syringes, complete with a needle and wider grip at the base where they’d usually be attached to a bacterium’s inner membrane. The needles are just wide enough for a single, unfolded protein to slither through into a host cell.O. Schraidt et al/PLOS Pathogens 2010
Previous studies suggested that a ring of proteins at the base of the secretion system, where it attaches to the bacterial cell membrane, might act something like a sorting platform that grabs target proteins and loads them into the syringe. But that work wasn’t done in living cells, says microbial geneticist Kelly Hughes of the University of Utah in Salt Lake City, who was not involved in the new study.
Other studies in live cells, including recent work by Diepold and his colleagues, hinted that the components of the sorting platform might not stay put at the bases of the syringes. Instead, they might wander around the gel-like jumble of fluids, proteins and other biological bits enclosed within a bacterium’s cell membrane, picking up and dropping off target proteins as they go — like shuttle buses.
The new study put the shuttle-bus idea to the test by using fluorescence microscopy to track the movement of individual sorting platform proteins in Yersinia enterocolitica, a stomach bug that lurks in undercooked pork. Maps of the proteins’ paths show them wandering random, zigzag paths through the cells. And experiments with mutant Y.enterocolitica that lack injectable proteins revealed that the shuttle-bus proteins move more quickly in the mutants — without any injectable targets to bind to, the shuttle-bus proteins don’t get weighed down by cargo and can diffuse faster through the cells. This showed that the sorting platform proteins don’t just wander; they also pick up passengers along the way.
“What I loved about this paper was that it was all set in vivo,” in living cells, Hughes says. “You get these beautiful pictures. And you know, a picture’s worth a thousand words.”
Unraveling more of the outstanding mysteries surrounding these microscale needles will make it easier for scientists to throw a wrench in these machines, or to tinker with them. This type of secretion system, one of a handful of different types of needles bacteria have at their disposal, is widespread across different species of bacteria, Diepold says, so they’re good targets for new types of antibacterial drugs (SN: 3/30/22).
They’re also promising tools for medicine and biotech, Hughes says. But as much as they look like medical syringes, bacterial syringes work differently — and scientists still don’t know exactly how bacteria push proteins through their needles. It’s also unclear how the proteins that load up the needles recognize their targets. “We want to understand the riddle of how these systems work,” Diepold says. “We want to understand which solutions evolution came up with to allow bacteria to infect us.”
When it comes to tail wagging among dogs, some questions still hound researchers.
We know that domesticated dogs (Canis familiaris) use their tails to communicate — with other dogs as well as humans — and even what various types of wags mean, researchers note in a new review of the scientific literature. But we don’t know why dogs seem to wag more than other canines or even how much of it is under their control, ethologist Silvia Leonetti and colleagues report January 17 in Biology Letters.
“Among all possible animal behavior that humans experience in everyday life, domestic dog tail wagging is one of the most common,” says Leonetti, who is now at the University of Turin in Italy. “But a lot of dog behavior remains a scientific enigma.”
So Leonetti and her colleagues pored through previous studies to figure out what elements of tail wagging are understood and which remain mysterious. They also hypothesized about the behavior’s origins: Perhaps tail wagging placates some human need for rhythm, the researchers suggest, or maybe the behavior is a genetic tagalong, a trait tied to others that humans bred into domesticated dogs.
“People think wagging tail equals happy dog. But it’s actually a lot more complicated than that,” says Emily Bray, an expert in canine cognition at the University of Arizona in Tucson who was not involved with the work. Understanding why dogs wag their tails is important partly from an animal welfare perspective, she says, as it could help dog owners read their pups’ cues better.
One main thing that researchers know about tail wagging is that it’s used predominantly for communication instead of locomotion, like a whale, or swatting away bugs, like a horse. Wagging also means different things depending on how the tail is wagged, such as its height or side-to-side movement.
For example, when the tail wags more to the right, the researchers say, it typically means the dog is interested in a stimulus or wants to approach something. But when it wags more to the left, it signals uncertainty or wanting to withdraw. When wagged low and near the legs, it’s a sign of submission or insecurity. Dogs can interpret and react differently to these varied wags (SN: 11/1/13).
But for such a ubiquitous behavior, questions abound. One gap is how much tail wagging is under dogs’ conscious control, the team reports. Several studies have also observed that dogs wag their tails more than other canines, particularly compared with their closest relative, the wolf (C. lupus) — but scientists don’t yet know why.
One idea is the domesticated rhythmic wagging hypothesis, Leonetti and colleagues suggest. Scientists know that humans’ brains respond positively to rhythm, and because tail wagging is a rhythmic behavior, the authors suggest it could be that humans consciously or unconsciously preferred dogs that wag more.
Or the domestication syndrome hypothesis could be at work. It’s an existing theory that unintended, genetically linked traits can pop up when specific traits are bred for through domestication. Perhaps, the researchers propose, the canine characteristics that humans found desirable to breed for — such as temperament — might be genetically linked to tail wagging.
Evolutionary biologist Tom Reimchen isn’t so sure about either hypothesis. He’s skeptical that domestic dogs do wag their tails more than other canines. More research is needed to compare tail wagging between nondomestic canine species and the epigenetic influences behind canids’ tail wagging, says Reimchen, of the University of Victoria in British Columbia.
Leonetti, who did the work while at the Max Planck Institute for Psycholinguistics in Nijmegen, Netherlands, says a multidisciplinary approach would be helpful in future tail wagging research, for example combining neurology, cognition and physiology. Because the domestication process was also an evolutionary process — one humans were involved in — studying dog behavior and their wags could reveal something about us too, she says (SN: 9/7/22).
It “can shed light not only on our understanding of dog behavior, but also we’ll then understand something about human psychology.”
Each morning after breakfast, Scott Broadbent takes a plastic bottle from the refrigerator in his home in Alameda, Calif., pops the top, and drinks the contents, 2.5 ounces of milky liquid. “It has sort of a pineapple creamy flavor,” he says. “It’s really not bad.”
The bottle might contain ketone ester, a supplement meant to help the body burn fat instead of carbohydrates. Researchers are now testing whether it might also slow the aging process. Or Broadbent might instead be getting a placebo. He is part of a clinical trial at the nearby Buck Institute for Research on Aging to assess the supplement’s safety and side effects in older adults.
A retired chemist who used to work for pharmaceutical companies, Broadbent is 70 and in excellent health today, but he worries about the future. He’s not necessarily afraid of dying, but he doesn’t want to be sick and in pain as he grows older. His dad had Parkinson’s disease. Broadbent survived prostate cancer and recently developed tinnitus, which spooked him and sparked anxiety attacks. “I thought if I had to live like this the rest of my life, I don’t know if I’d want to do it,” he says.
Some scientists think there’s a better way. These researchers — part of a burgeoning field called “geroscience” — aren’t seeking immortality. The focus is much more pragmatic: By addressing the root causes of aging, they hope to stave off the disability and diseases that can make old age so miserable. They want to help people feel healthy for longer, compressing the years of illness that often accompany old age into a much shorter time frame. “Let’s build a medicine that would be safe enough for someone in midlife to take almost like a supplement, like a daily vitamin, but with much more profound biological effects,” says James Peyer, CEO of Cambrian Bio in New York City.
Just don’t call these potential medicines antiaging therapies. “That term is associated with an industry that is trying to sell products to the public to separate people from their money,” says S. Jay Olshansky, a demographer and geroscientist at the University of Illinois Chicago. The antiaging market includes everything from face creams meant to zap wrinkles to pills that promise to turn back the clock. “It’s bogus,” he says. Geroscientists instead are doing legitimate research at respected research institutions to find medicines that can slow the aging process. Many of the compounds under study show promise in mice and even humans, and some are in clinical trials.
Better health in old age is not just about individual benefits. By 2030, 73 million baby boomers in the United States will be 65 or older. By the same year, experts project, there will be a billion people 65 and older globally. And though people are living longer, they are not necessarily living healthier than previous generations.
An aging population
Estimates suggest there will be a billion people age 65 and older globally by the year 2030, and the global figure could hit 2.5 billion by the end of the century.
World population by age group
C. ChangC. Chang
Source: World Population Prospects 2022, United Nations
“There’s this fear of what is this going to do to our health care system,” says Laura Niedernhofer, a geneticist and researcher studying aging at the University of Minnesota in Minneapolis. “And it goes well beyond just health care. We don’t have the nursing homes. We don’t have the personal care staff to deal with this at all.” Drugs to help keep older adults healthy, active and independent would be a societal boon.
But whether developing such drugs is even possible remains to be seen. Getting the medicines to market means securing more funding, overcoming stumbling blocks related to study design and combating near constant hype.
How did geroscience begin?
The advent of modern medicine and public health has more than doubled the average human life span — from about 30 in the early 1800s to more than 70 today. “This is perhaps one of the biggest things that has happened to humankind, period,” says Jamie Justice, a geroscientist who heads the health domain at the XPRIZE Foundation, which holds competitions to spur technological developments and announced a new prize related to aging in November. “We are a lot less dead than we used to be because of where public health and modern medicine has gotten us.”
There’s a downside, of course. We’re living long enough to see the frailty and illness that comes with old age. Cells stop dividing, DNA degrades, the immune system falters. We become increasingly vulnerable to disease. Many of us spend our last decades beset by medical maladies — broken bones, weakness, dementia, cancer, heart disease and more. Doctors can do little more than play whack-a-mole, beating back illnesses one at a time.
For decades, scientists thought the gradual decline that comes with old age was unavoidable. But experiments in the 1980s and ’90s suggested that the process might not be so fixed.
In one notable experiment, Cynthia Kenyon, a molecular biologist at the University of California, San Francisco, and colleagues found that mutations in a single gene in the roundworm C. eleganscould double its life span. Typical 13-day-old worms barely moved. “The animal is clearly in the nursing home,” Kenyon said in a 2011 TED Talk. The mutant worms moved as if they were much younger, and they lived longer too.
For researchers interested in human health, this and similar findings from other teams led to a profound realization: Perhaps the aging process is malleable. If so, scientists might be able to develop therapies to attack the root of aging rather than simply combating the pileup of diseases.
By the late 2000s, “the whole perspective of the scientific community changed,” says Felipe Sierra, who was then a program officer at the National Institute on Aging in Bethesda, Md. Aging biology moved from a phase of description into a phase of molecular investigation. Sierra wanted a name to bring the field together. He landed on geroscience, a word he had first seen in a grant proposal by another researcher studying aging, Gordon Lithgow. “Gero-” comes from the Greek word for old man. It wasn’t difficult to convince other researchers to get on board. “Everybody listened to me because I was in charge of the money,” says Sierra, now chief scientific officer at Hevolution Foundation, a nonprofit that funds geroscience research.
What compounds might fight aging?
Though there are no proven therapies for people yet, geroscientists are eyeing several compounds that can slow the aging process, at least in worms, fruit flies and mice. Some have already been tested in humans, and many more clinical trials are under way. Which will work? “Let me see. Let me look at the crystal ball,” Sierra jokes. “Who knows?”
Perhaps the best studied is rapamycin, a compound first discovered in a soil sample collected in 1964 from Rapa Nui, or Easter Island. Today, people who receive organ transplants take the drug to help keep their immune systems from rejecting the foreign tissue. But rapamycin also prolongs life in yeast, flies and mice. And it’s being tested in people in clinical trials. How it counters aging isn’t entirely clear. The drug inhibits a protein complex called mechanistic target of rapamycin, mTOR for short, which plays a role in cell growth and protein synthesis. This inhibition appears to have wide-ranging effects, including reducing inflammation, clearing old and damaged cells, and altering cellular metabolism — some of the key processes that researchers think are to blame for the aging process.
Rapamycin isn’t the only drug to impact mTOR. Researchers at the biotech company resTORbio tested other mTOR inhibitors in elderly adults to try and improve immune function. About 250 people participated in the clinical trial, which tested two mTOR inhibitors alone and in combination compared with a placebo. In 2018, the team reported that those who received the drugs had fewer infections and mounted a better response to the flu vaccine. The company tried one of those compounds in a subsequent study, though, and it failed to show an effect on self-reported respiratory illnesses. resTORbio no longer exists, but the company’s chief medical officer, Joan Mannick, hasn’t given up on mTOR inhibitors. She cofounded a new company called Tornado Therapeutics, based in New York City, that is working to develop new rapamycin analogs, or “rapalogs.”
Another promising class of drugs targets cells that have stopped dividing but don’t die. These senescent cells release chemical signals that can trigger inflammation, disrupt tissue repair and harm neighboring cells. In some cases, these signals even prod neighbors to become senescent too.
One of the most commonly tested senolytic regimens is a combination of two compounds: the anticancer drug dasatinib and quercetin, an antioxidant that occurs naturally in grapes, berries and other fruits and vegetables. Other research efforts plan to compare fisetin, a compound found in strawberries and apples, with a placebo to see if it has an impact on frailty and markers of inflammation in the blood.
Unity Biotechnology, based in San Francisco, is focused on senolytic therapies exclusively. The company’s most advanced compound, called UBX1325, targets a protein abundant in the blood vessels and retina that regulates cell death. Preliminary results from a trial in patients with diabetic macular edema, a thickening of the retina related to diabetes, suggest that the compound can improve eyesight.
12 hallmarks of aging
Researchers have identified a dozen hallmarks of aging that appear capable of nudging life span — and likely health span — one way or another across a range of animals. A network of interactions among genes and their products underlies these interconnected hallmarks, and it’s that network that drugs such as rapamycin and senolytics are targeting.
Genomic instability includes changes to DNA, chromosomal rearrangements and defects in nuclear architecture.
Telomere attrition is the cumulative damage or loss of DNA at the ends of chromosomes, called telomeres.
Epigenetic alterations can change how a gene is expressed without changing the DNA itself, such as methylation.
Loss of proteostasis refers to imbalances in proteins in the body, which can lead to the formation of protein aggregates, as in Alzheimer’s.
Disabled macroautophagy leaves cells unable to sequester and digest material in the cytoplasm, thus affecting the replacement of organelles.
Dysbiosis is the disruption of the body’s microbial communities, which play a role in nutrient digestion, disease protection and more.
Chronic inflammation increases with aging, both across the body and locally, and typically comes with a decline in immune function.
Altered intercellular communication brings more noise into the system, disrupting neural, neuroendocrine and hormonal signaling.
Stem cell exhaustion leads to a reduction in tissue renewal rates across the body and can limit tissue repair after injury.
Cellular senescence, when cells stop dividing but don’t die, has been linked to kidney disease, diabetes, Alzheimer’s, Parkinson’s and more.
Mitochondrial dysfunction can prevent a cell from producing the energy it needs, as well as contribute to inflammation and cell death.
Deregulated nutrient-sensing affects a whole series of pathways that shape cell activity, which makes diet a practical aging intervention.
Icons & source: C. LÓPEZ-OTÍN ET AL/CELL 2023
Diet is also known to profoundly affect the aging process. Studies have found that the low-carb ketogenic diet, for example, can help mice live longer. But restrictive diets can be hard to follow and have side effects. Broadbent followed the ketogenic diet for a month or so, but his cholesterol levels went dramatically up. Ketone ester, the compound Broadbent might be downing each morning for the Buck Institute’s clinical trial, may mimic the longevity benefits of such diets.
When the body runs out of glucose to use for energy, the liver creates another source by converting fat into molecules called ketone bodies. “If we don’t eat for a day or so, we’ll start to make ketone bodies,” says John Newman, a geriatrician at the Buck Institute who is leading the trial. “And we’ll make more and more the longer that we starve in order to fuel our bodies.” These compounds are more than just fuel. They help regulate inflammation and control other cellular processes, many of them involved in the aging process. Drinking ketone esters, which quickly break down, is a way to deliver the ketone bodies without the diet.
Among the dozens of clinical trials testing potential gerotherapies, very few are yet assessing their ability to prevent the onslaught of diseases that come with aging. Instead, the goal is establishing safety or seeing whether a compound can nudge some biomarker in the right direction. And many of the potential treatments under study are natural compounds or existing drugs that are already off patent, which might leave drug companies hesitant to invest in future trials or to seek approval from the U.S. Food and Drug Administration or other regulatory agencies.
What’s more, as James Kirkland, a geriatrician at the Mayo Clinic in Rochester, Minn., points out, many of the clinical trials happening now will fail. “In fact, most will,” he says. That’s just a part of drug development.
For now, some companies are bolstering their chances of success by pursuing many options. Cambrian Bio, the parent company of Tornado Therapeutics, for example, is “taking a number of different shots on goal,” Peyer says. “We don’t know which drug is going to really be the first multidisease preventative.”
Aging hallmarks link up
In one example of interconnections, several hallmarks can affect cellular senescence, which then drives inflammation and dysbiosis.
Icons: C. LÓPEZ-OTÍN ET AL/CELL 2023; Graphic: C. ChangIcons: C. LÓPEZ-OTÍN ET AL/CELL 2023; Graphic: C. Chang
What are the barriers to progress?
One of the big challenges for geroscience is to figure out how to show that a compound prevents age-related diseases in people. Scientists would have to give the drug to healthy people and then track their health as they age, an expensive and time-consuming endeavor. “In mice, it takes us four years. In humans, it would take decades and tens of thousands of people,” Niedernhofer says.
An easier path to the clinic would be to develop these therapies as a treatment for a single disease rather than a multidisease preventive. “That’s something that the FDA is very comfortable with,” says Nathan LeBrasseur, a researcher studying aging at the Mayo Clinic. Once the drug is approved for one indication, it would be much easier to seek approval for others — and potentially widen to a preventive. “The absolute irony of all of this is, to try and advance geroscience, we’re going right back to the old way of doing things, which is one disease at a time,” Niedernhofer says. For example, Unity is developing its lead antiaging candidates as therapies for a variety of eye diseases.
One group of researchers, however, has developed a clever work-around. Rather than treating healthy people and waiting for them to age, the team has devised a study that will recruit people who have one age-related disease and assess whether a drug reduces the time it takes to develop another. In this case, the researchers have chosen the diabetes drug metformin. Metformin has a long safety record, and studies suggest it can impact heart disease, cancer and cognitive decline. Metformin may even reduce the risk of long COVID. The precise mechanisms that underpin these effects aren’t entirely clear. The study, called Targeting Aging with Metformin, or TAME, will look at things such as cardiovascular events, cancer, cognitive decline, dementia and death.
But nearly eight years after investigators first announced the 3,000-person trial, they’re still trying to get together funding. Metformin is cheap and readily available, no longer protected by a patent, so drug companies have no incentive to develop it for aging. Nir Barzilai, director of the Institute for Aging Research at the Albert Einstein College of Medicine in New York City, who is leading the study, has started telling people the trial will start in January. “And as long as I don’t say which year, it will be true,” he jokes.
Part of what holds the field back is society’s approach to medicine, says Justice, of the XPRIZE Foundation. “We have a model of medicine that prioritizes treatment of diseases,” she says. “You get one disease. You treat one disease. You restore homeostasis.” But that approach isn’t relevant for aging. Geroscientists also have to fight society’s views of aging. The mind-set is “things get old. It just happens. There’s nothing you can do, just let it go,” Justice says. “I think that is actually a fundamentally ageist view, as if people who are older don’t have a right to health.”
Geroscientist Matt Kaeberlein of the University of Washington in Seattle agrees. No one would argue that we shouldn’t develop therapies for Alzheimer’s or cancer because these diseases are a natural part of getting older. So, he asks, why would this argument hold for aging? “I don’t really see what the field is trying to do as any different than trying to cure disease,” he says. “It’s just a much more efficient and effective approach, or it’s likely to be.”
Kaeberlein thinks dogs, because they age much faster than people, could bridge the gap between lab studies in mice and therapy approval. “You can do longevity clinical trials in dogs that you can’t do in people,” he says. And companion animal medications are regulated much like human medications. The Dog Aging Project, which Kaeberlein codirects, is testing rapamycin in 500 middle-aged dogs to assess its impact on the heart, the immune system, cancer incidence and cognition.
Kate Creevy (with dogs Poet and Sophie) is chief veterinary officer of the Dog Aging Project, an effort that seeks to identify factors contributing to dog longevity and may offer insights for humans too.TEXAS A&M COLLEGE OF VETERINARY MEDICINE & BIOMEDICAL SCIENCES
But even if geroscientists find compounds that treat the decline that comes with aging, it’s not clear whether they will compress the period of age-related illness — that’s the goal — or simply delay it. It’s also uncertain whether such therapies might add to the average life span and, if so, how many years. John Davis, an ethicist at California State University, Fullerton, worries about how such increases might affect demographics. If the average life span jumps to 120 years, the effects aren’t too pronounced, he says. If it goes far longer, there is the potential for “really spectacular increases in population on a planet that I personally feel is already overloaded.” And then there are concerns about how longer life might impact existing inequalities. “Billionaires who live longer have more time to accumulate even more wealth,” Davis adds.
Beware the antiaging hype
There’s another potential obstacle: hype.
No one can say with any certainty that there will be a pill to prevent aging. Yet that hasn’t stopped some companies and less scrupulous researchers from cashing in. The public’s interest in escaping aging makes overselling results enticing. In 2019, for example, the FDA warned consumers against receiving infusions of plasma from young donors, which some companies offered for $8,000 a liter. The treatment was based on promising mouse studies that gave older mice blood from younger mice, either via transfusions or by connecting the two animals’ circulatory systems. The young blood appeared to rejuvenate the older animals’ muscles, livers and brains, but the benefits haven’t been proved in human patients.
The internet is likewise rife with supplements and even prescription medications with purported antiaging benefits. Many of the pills being touted as age-reversing miracle drugs are the same compounds geroscientists are currently testing in trials. “[Companies] start trying to sell it to the public before it’s been tested for safety and efficacy,” Olshansky says. That can make it especially difficult for consumers trying to sort fiction from fact.
LeBrasseur is concerned that if scientists oversell their progress, they run the risk of losing public trust. And a rush to clinical trials might lead to safety problems. “If something bad happens, that’s going to set the entire field back,” he says. “I just think we have to be patient and humble.”
A student of Newman’s, at the Buck Institute, asked him recently how geroscience has changed clinical practice. “The honest answer is it hasn’t at all,” he says. “We’re still building the data. We’re still running the clinical trials waiting for it to come in. And this all takes time.”
But Broadbent, and many others, aren’t satisfied waiting for settled science. He likes to do his own research, and ketone ester seems like a good bet. The particular product he may be drinking as part of the clinical trial is now being sold as a supplement, and he plans to continue taking it after the trial ends. “I’ll sign up right away,” he says. “I’ll be on an annual subscription.”
Many scientists are convinced that the geroscience revolution is coming. Until then, there’s a tried-and-true method for improving your health span. It’s the advice any doctor will give you: Eat a balanced diet, exercise, get vaccinated and avoid tobacco and alcohol.
In the hunt for new materials, scientists have traditionally relied on tinkering in the lab, guided by intuition, with a hefty serving of trial and error.
But now a new battery material has been discovered by combining two computing superpowers: artificial intelligence and supercomputing. It’s a discovery that highlights the potential for using computers to help scientists discover materials suited to specific needs, from batteries to carbon capture technologies to catalysts.
Calculations winnowed down more than 32 million candidate materials to just 23 promising options, researchers from Microsoft and Pacific Northwest National Laboratory, or PNNL, report in a paper submitted January 8 to arXiv.org. The team then synthesized and tested one of those materials and created a working battery prototype.
While scientists have used AI to predict materials’ properties before, previous studies typically haven’t seen that process through to producing the new material. “The nice thing about this paper is that it goes all the way from start to finish,” says computational materials scientist Shyue Ping Ong of the University of California, San Diego, who was not involved with the research.
The researchers targeted a coveted type of battery material: a solid electrolyte. An electrolyte is a material that transfers ions — electrically charged atoms — back and forth between a battery’s electrodes. In standard lithium-ion batteries, the electrolyte is a liquid. But that comes with hazards, like batteries leaking or causing fires. Developing batteries with solid electrolytes is a major aim of materials scientists.
The original 32 million candidates were generated via a game of mix-and-match, substituting different elements in crystal structures of known materials. Sorting through a list this large with traditional physics calculations would have taken decades, says computational chemist Nathan Baker of Microsoft. But with machine learning techniques, which can make quick predictions based on patterns learned from known materials, the calculation produced results in just 80 hours.
First, the researchers used AI to filter the materials based on stability, namely, whether they could actually exist in the real world. That pared the list down to fewer than 600,000 candidates. Further AI analysis selected candidates likely to have the electrical and chemical properties necessary for batteries. Because AI models are approximate, the researchers filtered this smaller list using tried-and-tested, computationally intensive methods based on physics. They also weeded out rare, toxic or expensive materials.
That left the researchers with 23 candidates, five of which were already known. Researchers at PNNL picked a material that looked promising — it was related to other materials that the researchers knew how to make in the lab, and it had suitable stability and conductivity. Then they set to work synthesizing it, eventually fashioning it into a prototype battery. And it worked.
“That’s when we got very excited,” says materials scientist Vijay Murugesan of PNNL in Richland, Wash. Going from the synthesis stage to the functional battery took about six months. “That is superfast.”
The new electrolyte is similar to a known material containing lithium, yttrium and chlorine, but swaps some lithium for sodium — an advantage as lithium is costly and in high demand (SN: 5/7/19).
Combining lithium and sodium is unconventional. “In a usual approach … we would not mix these two together,” says materials scientist Yan Zeng of Florida State University in Tallahassee, who was not involved in the research. The typical practice is to use either lithium or sodium ions as a conductor, not both. The two types of ions might be expected to compete with one another, resulting in worse performance. The unorthodox material highlights one hope for AI in research, Zeng says: “AI can sort of step out of the box.”
In the new work, the researchers created a series of AI models that could predict different properties of a material, based on training data from known materials. The AI architecture is a type known as a graph neural network, in which a system is represented as a graph, a mathematical structure composed of “edges” and “nodes.” This type of model is particularly suited for describing materials, as the nodes can represent atoms, and the edges can represent bonds between the elements.
To perform both the AI and physics-based calculations, the team used Microsoft’s Azure Quantum Elements, which provides access to a cloud-based supercomputer tailored for chemistry and materials science research.
The project, Baker says, is an example of a practice known in tech circles as “eating your own dog food,” in which a company uses its own product to confirm that it works. In the future, he says he hopes others will pick up the tool and use it for a variety of scientific endeavors.
The study is one of many efforts to use AI to discover new materials. In November, researchers from Google DeepMind used graph neural networks to predict the existence of hundreds of thousands of stable materials, they reported in the Dec. 7 Nature. And in the same issue of Nature, Zeng and colleagues reported on a laboratory operated by AI, designed to produce new materials autonomously.
A sledgehammer dealt the final blow to New York City’s dream of a paleontology museum.
On May 3, 1871, workers broke into the workshop of famed British artist Benjamin Waterhouse Hawkins. Inside, they came upon a plaster skeleton of a towering duck-billed dinosaur — modeled after the first dinosaur fossil unearthed in New Jersey 13 years earlier — alongside a statue of the beast as it would have appeared in life.
These were the first 3-D renderings of any North American dinosaur, a testament to the continent’s geologic past that scientists were only just beginning to understand. But the public would never see the skeleton or the statute.
The workers wrecked the workshop. Plans and drawings were torn to pieces. Sledgehammers shattered the dinosaurs.
In the more than 150 years since, this vandalism has remained one of the most infamous events in paleontology. The story passed down through the years is that the workshop was destroyed on the orders of New York political boss William Tweed in a malicious act of political and religious vengeance.
Tweed viewed dinosaurs as “inconsistent with the doctrines of received religion,” a paleontologist noted later in 1940. The destruction is cited as one of the early battles between a traditional Christian worldview and a growing scientific understanding of Earth’s deep past.
The loss of Hawkins’ dinosaurs has “always been a shock to the paleontological community,” says Vicky Coules, an art historian at the University of Bristol in England. It’s been thought that Tweed “was basically against the whole concept of dinosaurs,” she says.
But the story might be due for a rewrite. Recent historical sleuthing by Coules and her Ph.D. adviser Michael Benton, a paleontologist at the University of Bristol, suggests that the demise of Hawkins’ dinosaurs was not religiously motivated, or even ordered by Tweed.
Instead, the story that paleontologists tell about this affair may say more about the history of anti-evolution sentiment during the 20th century than in the 1800s.
Who was Benjamin Waterhouse Hawkins?
Today, dinosaurs are everywhere, the most iconic creatures of the prehistoric past. Their place in the public imagination is in no small part due to Hawkins.
Hawkins dedicated his career to depicting the natural world, even helping Charles Darwin illustrate the 1839 book The Voyage of the Beagle (SN: 1/16/09). In 1854, Hawkins’ most famous artwork went on display when the Crystal Palace reopened in London. Thousands flocked to this showcase of (sometimes looted) wonders from across the British Empire. A natural history section featured life-size statues of dinosaurs made by Hawkins.
This was several years before Darwin published his theory of evolution and only about a decade after the term “dinosaur” had entered the lexicon. For many people, seeing Hawkins’ statues was the first time they had come face-to-face with the concept of deep time (SN: 6/4/19).
Displaying dinosaurs in the flesh was “enormously innovative,” Benton says. “No one had attempted anything like this before.”
Some of Benjamin Waterhouse Hawkins’ Crystal Palace dinosaur statues are still on display in London.Ian Wright/Wikimedia Commons (CC BY-SA 2.0 DEED)
The exhibit made Hawkins the de facto expert on depicting prehistoric life, and in 1868, the Board of Commissioners of Central Park — the group in charge of developing New York’s new green space — asked Hawkins to build similar statues. They were to be the centerpiece for the park’s planned Paleozoic Museum, dedicated to American paleontology.
At this time, most of the major dinosaur discoveries were happening in Europe or its colonies. American scientists had yet to dig into the ample bone grounds of western North America, and most of the continent’s major paleontological finds — including Tyrannosaurs rex— were still at least a decade away (SN: 3/30/23).
But a small number of fossils were starting to come out of the East Coast, including a dinosaur with a flat, beaklike snout named Hadrosaurus found in New Jersey. The Paleozoic Museum, the Central Park commission thought, would give Americans a chance to prove that they too had a prehistory worth remembering. Hawkins’ Crystal Palace statutes “hit [the public] between the eyes,” Benton says. Now, “New York wanted that.”
Hawkins accepted the job. He would dedicate the next few years to a museum that would never open its doors.
The story that paleontologists tell
In the 1860s, New York was a city on the rise. One of the men riding that high was William Tweed, a state senator who dominated the city’s political scene. Tweed stripped power from all who opposed him. In May 1870, for instance, he dissolved Central Park’s board of commissioners and created a new group filled with his cronies.
By year’s end, the new commissioners canceled the Paleozoic Museum and moved to discontinue their relationship with Hawkins — without paying him.
The museum’s demise had been simmering in the background for months. Already, Hawkins’ workshop had been relocated from a government building to a shed in the park. The move made room for the growing collection of the upcoming American Museum of Natural History, which, unlike the publicly funded Paleozoic Museum, had the private financial backing of New York’s wealthiest citizens, including the banker J.P. Morgan.
Plans for the two museums coexisted for a while. But eventually, the park commissioners decided that a museum dedicated solely to paleontology and funded by the public was just too big a burden to take on. It didn’t help that at least one member of the park commission was also on the committee for the American Museum of Natural History.
Before being nixed, the Paleozoic Museum in Central Park was intended to be a showcase of North America’s prehistoric past (as seen in this sketch of what the museum might have looked like).Public domain
In March 1871, the New York Times — which frequently ran stories critical of Tweed — reported on the loss of the Paleozoic Museum, which Hawkins had lamented at a public meeting.
Two months later, the artist’s dino models lay in pieces.
“Hawkins was distraught,” Coules says. The destruction sent ripples through the scientific community, eventually becoming one of the foundational stories in the history of American paleontology, she says.
And the villain in the story: Tweed.
The Times article allegedly sent Tweed into a rage, and he ordered one of his cronies to descend “upon the Paleozoic Museum with vengeance in his soul,” paleontologists later wrote.
But it wasn’t just the bad press that supposedly angered Tweed. “There was always a rumor that there was some sort of creationist angle to it,” says paleontologist Carl Mehling of the American Museum of Natural History.
This version of the story, which paleontologists have repeated since at least the 1940s, rests on Tweed and his men referring to Hawkins’ dinosaurs as “pre-Adamite” animals and an incident in which one of Tweed’s followers told Hawkins he should focus on living animals. The argument fits into a common perception that emerged during the mid-20th century that religion and prehistory were often at odds in the late 19th century.
This is where the Central Park story begins to unravel.
Rethinking the Central Park dinosaur scandal
Last year while Coules was working on her Ph.D., she read up on Hawkins and things weren’t adding up.
For one, the timing of events didn’t make sense. Why would Tweed wait two months after the Times article to retaliate against Hawkins? When Coules dug up the newspaper story, she found it on Page 5, with no mention of Tweed in the article.
“My first question was, why on Earth would you be upset about that?” Coules recalls.
Tweed had bigger things to worry about. At the time, he had been accused of everything from bribery to money laundering. (Tweed was eventually arrested in late 1871 and died in prison several years later.) So it seemed odd that Tweed, who was fighting for his political life, would take such offense to a story buried so deep in the paper.
In the 19th century, the artist Benjamin Waterhouse Hawkins (left) was a well-known paleoartist while William Tweed (right) was infamous in New York City’s political scene.From left: Wikimedia Commons; Mathew Brady/National Archives and Records Administration/Wikimedia Commons
Coules started to suspect another culprit: Henry Hilton. Tweed appointed Hilton, a top lawyer to New York’s wealthiest men, to the new board in charge of Central Park in 1870. Hilton took to the role immediately, regularly visiting the park to search for areas of improvement.
Some of these “improvements” were head-scratchers. Hilton had workers paint a bronze statue of the biblical Eve entirely white, permanently damaging the metal. His penchant for destructive whitewashing — he ordered a similar treatment for a whale skeleton destined for a museum — became a joke in the press.
One day while going through her notes at a café, Coules came across park commission meeting minutes from the day before the models were destroyed. In that meeting, the committee resolved to remove Hawkins’ workshop “under the direction of the Treasurer” — Henry Hilton.
“I was like, wow! Look at this!” Coules says. Hawkins himself blamed Hilton for the vandalism. Coules found New York Times articles from the period in which Hawkins implicated Hilton.
But why did Hilton want the dinosaurs destroyed? Coules’ research didn’t pick up any hint that religion was a major motivation. Rather, she argues, Hilton “had a strange relationship with artifacts,” as demonstrated by his whitewashing habits.
Hilton would also go on to harbor other destructive tendencies — swindling a wealthy widow out of her fortune and running her late husband’s business into the ground.
Hilton had “quite strange ideas [that managed] basically to piss off everybody,” says Coules, who published her findings with Benton last year in the Proceedings of the Geologist’s Association.
That Hilton’s “strange ideas” would be behind the Hawkins incident makes sense to Ellinor Mitchel, an evolutionary biologist at the Natural History Museum in London and coauthor of a book on Hawkins’ Crystal Palace dinosaurs. “I think that’s the way of much of history, that it turns it’s sort of out human strengths and weaknesses that pivot the direction of things,” she says.
But not everyone is so sure. “It seemed quite convincing to me that Hilton played an important role,” says Lukas Rieppel, a science historian at Brown University in Providence, R.I., and author of a book on dinosaurs during America’s Gilded Age. But “it’s very hard for historians to know the private motivations of people who died over 100 years ago.”
Still, Coules’ work convincingly shows religion wasn’t a motivating factor.
For one thing, “pre-Adamite” was simply a way to refer to deep time, Benton says. So even if Tweed and Hilton did refer to Hawkins’ models in this way, it would have been more descriptive than derisive. What’s more, natural history — including paleontology — was seen as a respectable, middle-class occupation in the 19th century. “Natural history was seen as an expression of piety,” Rieppel says. “So a way that one could express one’s devotion to God [was] by learning about God’s works in the natural world.”
In fact, the idea that the world was ancient was widely accepted at the time, Benton adds. A more inflexible view of creationism, in which evolution is false and the world is only a few thousand years old, really started to gain steam only in the 20th century, he says.
Religion’s supposed role in the Hawkins’ saga may have been introduced by paleontologists writing about this incident in the mid-20th century, who may have been projecting their experiences with creationist movements into the past, Rieppel says. From there, the story stuck.
Hawkins’ lasting influence
Benjamin Waterhouse Hawkins mounted the skeleton of a duck-billed dinosaur for a public showing, setting a precedent for how dinosaur fossils are displayed.V. Coules and M.J. Benton/Proceedings of the Geologists’ Association 2023
The loss of the Paleozoic Museum might have been for the best. It would have been “obsolete almost immediately and I fear almost comical,” Mehling says — soon overshadowed by bigger discoveries from the American West.
But that doesn’t mean that Hawkins’ models didn’t have value, Mehling says. Dinosaur statues may now be the stuff of tacky roadside attractions and miniature golf courses. But in the 19th century, Hawkins’ statues were key to opening the public’s imagination to an ancient world that was quite different from the present.
Hawkins’ display was so awe-inspiring that in 1905, when the American Museum of Natural History unveiled its 20-meter-long Brontosaurus, it displayed the skeleton upright (SN: 4/7/15).
And Hawkins’ work continues to influence how people think of dinosaurs. While doing research for the Paleozoic Museum, Hawkins strung together the fossil pieces of Hadrosaurus into a standing skeleton and displayed it in Philadelphia. Before this, fossils had only ever been displayed flat on a table or kept in drawers. Visitors flocked to see the strung-together skeleton, overwhelming staff at the institution where it was housed.
The tradition stuck. And today, most museums display their fossils using Hawkins’ method.
Neutron tomography can help scientists capture 3-D images of the insides of fossils and artifacts without damaging them. The technique can uncover hidden features within dense material that X-ray scanning can’t detect, James R. Riordon reported in “Seeing into the past” (SN: 11/4/23, p. 18).
Reader Rob Janes asked how the 3-D images are captured.
In neutron tomography, scientists blast beams of neutrons at an object they want to study, Riordon says. Detectors on the other side of the object record the proportion of neutrons that make it through without being reflected or absorbed along the way. Using that data, computer algorithms create virtual slices of the object, which can then be assembled to provide 3-D views of the object’s interior, he says.
Reader Heidi Wilson asked whether neutron tomography has been used on ancient manuscripts that can’t be unfolded.
X-ray computed tomography has been the go-to method for analyzing ancient manuscripts, Riordon says. The artifacts are generally made of low-density material, such as papyrus or parchment, that X-rays can effectively image.
One recent exception, reported in 2021 in Archaeometry, is a medieval amulet made of a folded lead scroll that contains inscriptions. Since X-rays cannot easily penetrate particularly dense materials like lead, the researchers turned to neutron tomography to virtually unfold the sheet and reveal the inscribed runes. “Although ancient metal manuscripts are comparatively rare, neutrons offer a way to read them without risking the damage that opening them up would cause,” Riordon says.
Thinking about loneliness
Social scientists are learning more about how feeling detached from animals, places and routines — not just people — can cause loneliness. These revelations may lead to new interventions, Sujata Gupta reported in “What is loneliness?” (SN: 11/4/23, p. 24).
“While reading [this story], I found myself once again thinking about the demise of the front porch in our communities…. Having grown up in a small town in western New York that came into its own in the mid-1800s, front porches are to be found on most of the older homes,” reader Jim Sobek wrote. “A few years ago, while in town for a week of bicycling, I spent an evening with cousins on their front porch. As we whiled away the evening in conversation, neighbors out for their evening walks stopped by to talk for a while and then went on their way, only to be replaced by other neighbors also taking their evening constitutionals. Warm greetings and friendly conversation were exchanged between neighbors who knew each other well.”
Many modern homes “have large backyards, large decks, some pools and always-spacious air-conditioned interiors, but at best only a small covered concrete front stoop,” Sobek continued. “The residents often do not speak with neighbors, and sometimes don’t even know who their neighbors are.” While these homes are more comfortable, Sobek wonders whether they have also contributed to the loneliness and loss of community that some people now feel.
Correction
In “Clear the air,” the unit of the x-axis in the graph titled “Methane emissions in 2022, by source” was labeled incorrectly (SN: 11/18/23, p. 18). It should have been million metric tons, not metric tons.
Ask thousands of teens whether frequent use of certain substances brings a high risk of harm, and they mostly nail it: a majority say yes for cigarettes, alcohol, cocaine and heroin. But there’s one substance that many skip over — cannabis.
It’s a sentiment that some of their parents may share. Parents often don’t understand that the products used today “are not what they knew when they were in high school,” says Kelly Young-Wolff, a licensed clinical psychologist and research scientist at Kaiser Permanente Northern California Division of Research in Oakland. If their children are using cannabis, parents may think, “‘it’s not that bad, at least they’re not using this other drug that’s worse.’”
Cannabis is legal for adults to use recreationally in 24 states and Washington, D.C., and is allowed for medical use in 38 states and D.C. The widespread availability of cannabis “promotes the idea that it’s safe,” says pediatrician Beth Ebel of the University of Washington School of Medicine and Seattle Children’s Hospital. But that “is an incorrect assumption.” THC can impact brain chemistry “in a way that wasn’t intended,” Ebel says. “Some of the worst effects can have lifelong health consequences, especially for a young person.”
Concentrated cannabis products can be so extremely potent, and so different from what’s been known as cannabis, that “we need to start calling them something else,” says neuroscientist Yasmin Hurd of the Icahn School of Medicine at Mount Sinai in New York City. “These are new drugs.”
How does THC affect the adolescent brain?
As is true for other drugs, adolescence is an especially risky time to use cannabis. “The adolescent brain is still developing into early adulthood,” Hurd says. During this period, connections within adolescents’ brains are forming, getting reinforced or being pruned. “Your brain is trying to figure out, ‘what is important that I need to learn, and what is important that I need to retain,’” Ebel says, and this process is “negatively affected by THC.”
Studies in animals have found that exposure to THC in adolescence can reduce CB1 receptors in the brain and lead to long-lasting problems with memory and learning. One of the areas the psychoactive chemical alters is the prefrontal cortex, which matures during adolescence and is integral to problem-solving and emotional regulation. In adolescent rats injected with THC, nerve cell protrusions that connect with other nerve cells were prematurely cut back, disrupting the circuitry of the prefrontal cortex, Hurd and colleagues reported in Molecular Psychiatry in 2019.
There’s also evidence in people that THC changes teens’ brains. Researchers analyzed close to 1,600 magnetic resonance images of the brains of nearly 800 adolescents, taken at 14 and 19 years of age, on average. There was an association between cannabis use over the five years and an accelerated thinning of the prefrontal cortex, the researchers reported in JAMA Psychiatry in 2021. Cortical thinning is expected in adolescence and is likely tied to the pruning of underused connections. But accelerated thinning means that process isn’t following the normal developmental plan. The researchers hypothesize that the accelerated thinning might be connected to the premature loss of nerve cell protrusions that was described in the rat study.
Marijuana use is linked to mental health harms
Using cannabis puts teens’ mental health at risk. That’s true even for someone using cannabis recreationally. Adolescents ages 12 to 17 whose cannabis use did not meet the threshold for a substance use disorder were about twice as likely to develop depression or have suicidal ideation as those who didn’t use cannabis, according to a study of more than 68,000 adolescents published in May in JAMA Network Open.
The risks increase for those with cannabis use disorder, which is diagnosed when someone’s use interferes with daily life, but they aren’t able to stop using, among other symptoms. The JAMA Network Open study reported that adolescents with cannabis use disorder were 2.5 and 3 times as likely to have depression or suicidal ideation, respectively, as those who didn’t use cannabis.
Cannabis and mental health
Adolescents who met the diagnosis for cannabis use disorder or who used the drug recreationally had a higher prevalence of depression and suicidal ideation than those who didn’t use cannabis.
Prevalence of mental health events in adolescents by cannabis use
R.S. Sultan et al./JAMA Network Open 2023R.S. Sultan et al./JAMA Network Open 2023
Beginning cannabis use as a teen is more likely to lead to dependence than starting as an adult, just like alcohol, cocaine and nicotine. Compared with young adults, adolescents are more susceptible to dependence within a year of taking up marijuana. Eleven percent of those ages 12 to 17 progressed to cannabis use disorder by 12 months, but only 6 percent of those ages 18 to 25 did, researchers reported in 2021 in JAMA Pediatrics. After three years, the prevalence was 20 percent of adolescents versus 11 percent of young adults.
Yet many teens are turning to marijuana as a coping mechanism. A study of what motivated high school seniors to use cannabis found that reasons related to coping — such as to escape problems, relieve tension or deal with anger — approximately doubled in prevalence during the last four decades, researchers reported in 2019 the Journal of Studies on Alcohol and Drugs. For a project on how cannabis legalization for adults in California has impacted adolescent health, Young-Wolff has talked to clinicians who care for adolescents. They’ve told her that many of their patients who use cannabis are doing so to self-medicate, to try to relieve symptoms of depression or anxiety.
Ebel has seen this too. But as the drug wears off, users are more anxious than they were before, she says. “It drives a cycle that drives increased use.”
When marijuana is a part of a teen’s everyday life, it can change their future trajectory. A study of young people in Australia and New Zealand compared the frequency of cannabis use before the age of 17 with how participants had fared by age 30. Those who used cannabis daily were more likely to become dependent on cannabis, use other drugs and attempt suicide, and less likely to finish high school, compared with teens who had never used, researchers reported in 2014 in the Lancet Psychiatry.
Cannabis addiction is also tied to the development of the psychiatric disorder schizophrenia. A study of nearly 7 million Danish people ages 16 to 49 found an association between cannabis use disorder and schizophrenia, researchers reported in May in Psychological Medicine. The association was stronger for males overall and especially at the ages of 16 to 25 years old. The researchers estimate that in 2021, without cannabis use disorder, around 15 percent of cases of schizophrenia in males and 4 percent in females would not have occurred.
The risks of using concentrated cannabis products
Although smoking the marijuana plant is still the most common way teens use cannabis, vaping cannabis concentrates is on the rise. A study of high school seniors reported that from 2015 to 2018, among past-year cannabis users, smoking decreased from 95 percent to 90 percent, while vaping increased from 26 percent to 34 percent. Daily use was also more common among those who vaped, at 29 percent, verses those who smoked, at 18 percent, researchers reported in JAMA Pediatrics in 2020.
There is early evidence that high-potency products are associated with an increased risk of psychosis, a symptom of schizophrenia. In a study of adults, daily use of high-potency cannabis products led to nearly five times the risk of psychosis compared with people who didn’t use cannabis, researchers reported in 2019 in Lancet Psychiatry. For the purposes of the study, high potency was defined as having 10 percent THC or higher.
There are also reports of a rise in cannabis hyperemesis syndrome, a complication of high potency cannabis use that leads to abdominal pain, nausea and repeated vomiting. A Canadian study found that emergency department visits for the syndrome increased 13-fold from 2014 to 2021.
Ebel says concentrated cannabis products are largely unstudied and “pose new and alarming health risks.” Hurd says that because we don’t know the full impact on health from high potency products, users are essentially the test subjects.
So as with other substances, public health officials recommend that parents talk with their kids about the risks of cannabis use. Especially with indications that teens are turning to cannabis to self-medicate, “if you notice a change in your child’s behavior, try to find out what’s going on,” Young-Wolff says. It’s also important for parents to consider the messages they send about marijuana, she says. The clinicians Young-Wolff has talked to have noticed that parents are using cannabis more and that they’ve become more permissive about teen cannabis use. “That can really make it hard to get this message to the kids to not use,” she says.
So, for adults who are taking part in the new legality of marijuana: “If you are going to use cannabis,” Young-Wolff says, “don’t use in front of your children.”
Soft fruits may have been the main dish on some ancient primate menus.
An analysis of hundreds of fossilized primate teeth from the Fayum Depression, a desert basin in Egypt, shows just a handful were fractured, researchers report December 13 in the American Journal of Biological Anthropology. So few chipped teeth suggests the animals more often feasted on easy-to-chew foods like fruits rather than hard objects like seeds or nuts that might inflict tooth damage.
The more than 400 analyzed teeth belonged to five primate genera — including Propliopithecus, Apidium and Aegyptopithecus — and are around 29 million to 35 million years old. Fossils that old date to a time when the last common ancestor of apes, including humans, and African and Asian monkeys still existed, says Ian Towle, a dental anthropologist at Centro Nacional de Investigación sobre la Evolución Humana in Burgos, Spain.
By examining dental damage from millions of years ago that might have been caused by food, “it gives insight into our own evolution, our own dietary changes through time,” he says.
While at the University of Otago in New Zealand, Towle and colleagues counted fractures that could be seen with the naked eye, noting each fracture’s severity and position on the tooth. Just 21 teeth, about 5 percent, were chipped.
“That’s right at the low end of what we see in living primates,” for which 4 to 40 percent of teeth show food damage, Towle says. Species like the sooty mangabey, a forest-dwelling monkey, that regularly eat hard food might have fractures on as many as half of their teeth. For species like chimpanzees that consume mostly soft food such as insects as well as fruit, less than 10 percent may be chipped.
What’s more, two Propliopithecus individuals had cavities, the researchers found. The presence of tooth decay suggests that the soft food of choice may have been sweet fruits. Primate diets might not have diversified to include nuts and seeds until later.
Teeth from two Propliopithecus chirobates individuals had cavities (shown with white arrows), a sign the animals ate sweet fruit as part of their diet.I. Towle et al/American Journal of Biological Anthropology 2023
That some individuals had cavities fits with other studies suggesting that fruit was part of diets early on in monkey and ape evolutionary history, says dental anthropologist Debra Guatelli-Steinberg of the Ohio State University in Columbus. But, she notes, whether teeth have chips or not doesn’t always perfectly match what primates eat, so it’s hard to say how much of the diet was soft food.
Similarly, there is some murkiness over what the species analyzed in the new study ate. Previous work analyzing tooth shape and wear has suggested that Apidium and Aegyptopithecus ate hard items instead of soft ones, Towle says. Tooth shape can differentiate between leaf- and fruit-based diets, and microscopic damage can show only what an animal ate in its last few weeks or months of life. Chipping, on the other hand, can last years or decades before it’s visibly worn away, providing a longer dietary record.
“At the moment, we really don’t know why [different methods] are coming up with different results,” Towle says, but using multiple techniques to piece things together is key. It’s possible that ancient primates ate fruit and their teeth — seemingly well-suited for chowing down on nuts or seeds — served an unknown purpose. Or choppers of old may have had features that made them less likely to chip.
“It’s definitely something that’s going to be interesting for researchers to look into,” Towle says, “to see why there is this potential disparity.”
Ancient tiny fossils from Australia may carry evidence of great power: the ability to make oxygen through photosynthesis.
The fossilized bacteria, dating from 1.73 billion to 1.78 billion years ago, are chock-full of structures that resemble those where oxygen-producing photosynthesis takes place in most modern cyanobacteria and in plants. Called thylakoid membranes, the structures are the oldest ever found, researchers report January 3 in Nature. The finding pushes back the evidence of thylakoids in cyanobacteria by 1.2 billion years.
Cyanobacteria’s invention of photosynthesis is responsible for the oxygen in Earth’s atmosphere. “So they’re a big deal,” says Woodward Fischer, a geobiologist at Caltech who was not involved finding the thylakoid membranes. And “this is the kind of information that I thought we were not going to be able to pull out of fossils,” he says.
Most fossils preserve mineralized tissues such as bone or shells, but bacteria don’t contain such mineral structures. These fossils are “just compressions of carbon” squished into mud, Fischer says. To find the bacteria preserved is impressive enough, but the new fossils reveal complex structures inside the microscopic bacteria. “It suggests this kind of future where we might be able to pull more information, more cell biology and morphological detail out of these minuscule fossils,” he says.
Researchers already had indirect evidence from genetics and chemical studies that cyanobacteria had developed thylakoids by the time these fossilized bacteria lived, says Patricia Sanchez-Baracaldo, an evolutionary microbiologist at the University of Bristol in England (SN: 9/8/15). Still, exactly when the structures evolved is hotly debated (SN: 3/2/17). So it’s exciting to see fossil evidence of such old thylakoids, says Sanchez-Baracaldo, who was not involved in the work. “Any evidence that you have from that time period is important because the fossil record is really very sparse.”
Some researchers think that thylakoids may have evolved before the Great Oxidation Event around 2.4 billion years ago (SN: 12/11/19). Prior to that event, there were whiffs of oxygen here and there in the atmosphere, but it took the concentrated action of photosynthetic bacteria to send Earth’s oxygen levels skyrocketing. Stacks of thylakoids within cyanobacteria may have multiplied the bacteria’s oxygen production.
During the period when the now-fossilized cyanobacteria lived, oxygen levels in Earth’s atmosphere had plummeted again to a fraction of today’s levels, Sanchez-Baracaldo says. The fossils hint that there may have been small pockets where oxygen was abundant and could have fostered the evolution of the ancestors of plants and animals.
Many rocks that might harbor such fossils have been compressed and “cooked” destroying delicate intracellular structures like thylakoids, says Emmanuelle Javaux, an astrobiologist at the University of Liège in Belgium.
“We didn’t know that they could be preserved in such old microfossils,” she says. But she has no doubt that the dark lines stacked through tiny sausage-shaped cells represent thylakoids. “It cannot be something else, actually. This arrangement is very unique to cyanobacteria with thylakoids,” she says.
Researchers found microscopic fossils of cyanobacteria dubbed Navifusa majensis (left) in 1.73 billion- to 1.78 billion-year-old shale from Australia). A peek inside the fossils revealed black horizontal lines indicating the bacterium contained stacks of membranes known as thylakoids (right) like those in modern bacteria and plants where oxygen-producing photosynthesis takes place.C.F. Demoulin, et al./Nature 2024Researchers found microscopic fossils of cyanobacteria dubbed Navifusa majensis (left) in 1.73 billion- to 1.78 billion-year-old shale from Australia). A peek inside the fossils revealed black horizontal lines indicating the bacterium contained stacks of membranes known as thylakoids (right) like those in modern bacteria and plants where oxygen-producing photosynthesis takes place.C.F. Demoulin, et al./Nature 2024
Javaux and colleagues found the oldest thylakoid-like structures in microfossils in shale from Australia. The structures were also present in about 1 billion-year-old fossils from Canada, but not in 1 billion-year-old ones from Congo. The rocks from Congo experienced slightly higher temperatures than the others, which may have destroyed fossil evidence of thylakoids. Or maybe those fossils are cyanobacteria that never evolved the structures or are another type of microbe entirely.
The researchers can’t tell from the fossils whether the Australian and Canadian cyanobacteria are direct ancestors of living species, Javaux says, but they are almost certainly cousins. The team hopes to investigate even older rocks from before the Great Oxidation Event for even more ancient evidence of thylakoids.
A surge of a hormone made by fetuses triggers the stomach-turning nausea and vomiting of morning sickness, a new study suggests.
People who have naturally low levels of the protein in their blood before pregnancy are more susceptible to a severe form of morning sickness called hyperemesis gravidarum when hit with the rush of protein, researchers report December 13 in Nature. The findings could help identify people at risk of the severe illness and lead to treatments.
Up to 80 percent of pregnant people get nauseous in the early stages of pregnancy, and about half vomit — a combo of symptoms often called (misleadingly) morning sickness. A small percentage of pregnant people — up to 3 percent — will develop hyperemesis gravidarum, vomiting so severe and frequent it can lead to weight loss, dehydration and even hospitalization and death of the fetus or mother.
Previously, researchers speculated morning sickness is caused by estrogen or other hormones that are elevated early in pregnancy, says gynecologist and obstetrician Jone Trovik, who was not involved in the study. For severe sickness, she says, studies implicated elevated thyroid hormone, infections and other causes.
“Most problematic has been that it has been considered to be a psychological cause, which has been widely refuted,” says Trovik, of Haukeland University hospital and the University of Bergen in Norway. “Women have been told, ‘Maybe you don’t want this pregnancy. Maybe you’re angry with your husband.’”
The new findings, Trovik says, provide “evidence that this is a real disease.”
Patients who had nausea and vomiting during pregnancy had higher levels of a protein called GDF15 in their blood than pregnant people without the symptoms, endocrinologist Stephen O’Rahilly of Cambridge University and colleagues report. That protein, which is made throughout the body and helps cells respond to stress, was previously found to act on a part of the brain involved in producing nausea and vomiting.
Study coauthor Marlena Fejzo and colleagues had already shown that people with a certain genetic variant in the GDF15 gene have up to 10 times the risk of developing hyperemesis gravidarum than people without the variant. But those with the variant produce less GDF15 than is typical, those researchers discovered.
That finding was a conundrum, says Fejzo, a geneticist and hyperemesis gravidarum researcher at the Keck School of Medicine of USC in Los Angeles. If people with the variant produce low levels of GDF15, but high levels are associated with nausea and vomiting, why is the variant a risk for severe morning sickness?
Turns out that people with the risk variant make less of the protein before pregnancy, but have elevated levels of GDF15 in their blood when pregnant. The twist is that most of the GDF15 produced in pregnancy comes from the fetus and placenta, the study’s researchers found. People with the risk variant aren’t used to GDF15’s sick-making effects. “So when you’re met with those high levels in early pregnancy, you’re highly sensitive to them, more than the average person,” Fejzo says.
Conversely, people with a rare blood disorder called beta thalassemia have high levels of GDF15. Those people rarely get queasy during pregnancy, the researchers found. That finding suggested that exposure to the protein before pregnancy might desensitize people so they don’t become so sick.
The team tested the idea in mice. Rodents that got a big dose of the protein cut back on eating, something the animals typically do when nauseous. But if the mice got prepped for the surge with a lesser dose of long-acting GDF15 three days beforehand, they weren’t bothered as much. The result suggests that small amounts of the protein can blunt the effect of a bigger dose later.
All the findings together also suggest avenues for treatment. The diabetes drug metformin raises GDF15 levels and might be given to people at risk of hyperemesis gravidarum before pregnancy, O’Rahilly says. Or, future drugs may be developed to block the action of GDF15 on the brain.
Fejzo notes one caveat, though: Most of the genetic studies were done with people of European descent, so it’s not certain that GDF15 is a major player for all ethnic groups.
Also, gastroenterologist Sumona Saha says that before any treatment can be given, researchers will need plenty of safety data from animal studies (SN: 4/21/22). No one really knows what effect blocking GDF15 may have on fetal development or if raising levels of the protein before pregnancy could affect conception, says Saha, of the University of Wisconsin School of Medicine and Public Health in Madison.
Currently, doctors try a variety of antinausea medications, neurological drugs and other therapies, sometimes including intravenous fluids and nutrition to treat people with severe nausea and vomiting. Having therapies focused on GDF15 may improve treatment, Saha says.
“We’ve got, potentially, a very targeted therapy versus a lot of other treatments, which are like taking a hammer to a problem. Now, we potentially will have an X-Acto knife that we can use.”
