Two drugs already on the market for other purposes can halt Ebola virus in mice. The findings open the way for further testing of the drugs, clomiphene and toremifene, against the deadly virus.
Scientists screened more than 2,000 drugs against Ebola, a process that required the highest level of safety precautions because the virus is so lethal. Several drugs called selective estrogen receptor modulators showed promise, including clomiphene, marketed as Clomid and prescribed to treat infertility, and toremifene, used to treat advanced breast cancer. In the June 19 Science Translational Medicine, researchers report that each drug prevented Ebola virus from commandeering cells in lab-dish experiments. The researchers also injected mice with one form of the Ebola virus, and nine of 10 mice given clomiphene one hour after exposure survived a month-long observation period. Five of 10 mice getting toremifene died within 10 days, but the other five survived the month. All mice given the virus without the drugs died within a week.
The drugs bottled up Ebola in a cell compartment called an endosome, which the virus uses as a way station when it invades a cell. How the drugs thwart the virus there is unclear, says study coauthor Gene Olinger, a virologist at the U.S. Army Medical Research Institute of Infectious Diseases in Frederick, Md. But the results suggest that the drugs might stop other versions of the Ebola virus and the related Marburg virus, another deadly pathogen. In theory, the drugs would be given to patients and health care workers in an outbreak, he says.
“This is an interesting study, and it’s the way one wants to go with these viruses,” says Stephan Becker, a virologist at Philipps University in Marburg, Germany. Ebola burst on the scene in 1976 with deadly outbreaks in Zaire and Sudan. But it has been a sporadic menace, racking up about 2,300 victims worldwide. Despite a stunning mortality rate, Becker says, the small numbers suggest that the best strategy against Ebola is to repurpose drugs already cleared for other uses.
While testing an established drug for a new use is faster than starting from scratch, Olinger says, approval of these drugs for Ebola might still take five to 10 years. There is currently no cure for an Ebola infection.
An exotic subatomic particle could be the first amalgamation of more than three quarks — a fundamental building block of atoms — to be produced experimentally. If it is what physicists think it is, the particle could provide clues about the force that holds nuclei together and perhaps about the earliest moments of the universe.
“We have very solid evidence of an unconventional particle,” says Ronald Poling, a physicist at the University of Minnesota in Minneapolis. “But it’s the interpretation — the possibility that it has four quarks — that makes it very exciting.” The details of the particle, inelegantly named Zc(3900), appear June 17 in Physical Review Letters. Physicists have known since the 1960s that protons and neutrons are made up of quarks, as are hundreds of other particles. All of these particles can be divided into two categories: mesons, which contain two quarks, and baryons (including protons and neutrons), which contain three.
Over the last decade many physicists, including those at the Belle experiment in Japan and the BESIII experiment in China have fruitlessly searched for particles with more than three quarks. Probing a particle’s insides is tough because physicists can’t see quarks directly. Instead they have to measure all the properties they can for a given particle, such as its mass, charge and decay products, looking for unusual characteristics that can be explained only by a peculiar combination of quarks.
The Belle and BESIII teams were both studying an odd particle called Y(4260) when they realized that it decayed to make another interesting particle, Zc(3900). Its mass, says Poling, who is part of the BESIII team, suggests that it is an electrically neutral meson made up of two quarks with opposite charges, called charm and anticharm. But surprisingly, both teams found that Zc(3900) has an electrical charge.
In fact, Poling says no two-quark or three-quark combinations can explain Zc(3900)’s charge and mass. That is leading physicists to the more exotic and exciting conclusion that the particle consists of four quarks: a charm and an anticharm along with an up and an antidown, which are extremely light and create a net positive charge. “The particle’s charge makes it a smoking gun for a four-quark state,” says Tomasz Skwarnicki, a physicist at Syracuse University in New York.
Assuming the evidence for a four-quark arrangement holds up, the big question will be how those quarks are arranged. Zc(3900) could be a single entity of four quarks, Skwarnicki says, but it could also be a coupling of two mesons, analogous to two atoms linking up to form a molecule.
Poling says that understanding the particle’s internal structure could improve physicists’ understanding of the strong nuclear force, which dictates how quarks bond together to create protons, neutrons and other composite forms of matter.
In addition, physicists believe that just after the Big Bang, matter existed in the form of a hot soup of individual quarks and gluons, particles that carry the strong force. Perhaps, as the universe cooled, that soup solidified into exotic multiquark combinations such as Zc(3900) before breaking up into the particles observed today. “The more complete our picture of all the elementary particles and their interactions,” Poling says, “the better we’ll understand where we started out and how we got to where we are.”
The internet is rife with advice for keeping the brain sharp as we age, and much of it is focused on the foods we eat. Headlines promise that oatmeal will fight off dementia. Blueberries improve memory. Coffee can slash your risk of Alzheimer’s disease. Take fish oil. Eat more fiber. Drink red wine. Forgo alcohol. Snack on nuts. Don’t skip breakfast. But definitely don’t eat bacon.
One recent diet study got media attention, with one headline claiming, “Many people may be eating their way to dementia.” The study, published last December in Neurology, found that people who ate a diet rich in anti-inflammatory foods like fruits, vegetables, beans and tea or coffee had a lower risk of dementia than those who ate foods that boost inflammation, such as sugar, processed foods, unhealthy fats and red meat. But the study, like most research on diet and dementia, couldn’t prove a causal link. And that’s not good enough to make recommendations that people should follow. Why has it proved such a challenge to pin down whether the foods we eat can help stave off dementia?
First, dementia, like most chronic diseases, is the result of a complex interplay of genes, lifestyle and environment that researchers don’t fully understand. Diet is just one factor. Second, nutrition research is messy. People struggle to recall the foods they’ve eaten, their diets change over time, and modifying what people eat — even as part of a research study — is exceptionally difficult.
For decades, researchers devoted little effort to trying to prevent or delay Alzheimer’s disease and other types of dementia because they thought there was no way to change the trajectory of these diseases. Dementia seemed to be the result of aging and an unlucky roll of the genetic dice.
While scientists have identified genetic variants that boost risk for dementia, researchers now know that people can cut their risk by adopting a healthier lifestyle: avoiding smoking, keeping weight and blood sugar in check, exercising, managing blood pressure and avoiding too much alcohol — the same healthy behaviors that lower the risk of many chronic diseases.
Diet is wrapped up in several of those healthy behaviors, and many studies suggest that diet may also directly play a role. But what makes for a brain-healthy diet? That’s where the research gets muddled.
Despite loads of studies aimed at dissecting the influence of nutrition on dementia, researchers can’t say much with certainty. “I don’t think there’s any question that diet influences dementia risk or a variety of other age-related diseases,” says Matt Kaeberlein, who studies aging at the University of Washington in Seattle. But “are there specific components of diet or specific nutritional strategies that are causal in that connection?” He doubts it will be that simple.
Worth trying In the United States, an estimated 6.5 million people, the vast majority of whom are over age 65, are living with Alzheimer’s disease and related dementias. Experts expect that by 2060, as the senior population grows, nearly 14 million residents over age 65 will have Alzheimer’s disease. Despite decades of research and more than 100 drug trials, scientists have yet to find a treatment for dementia that does more than curb symptoms temporarily (SN: 7/3/21 & 7/17/21, p. 8). “Really what we need to do is try and prevent it,” says Maria Fiatarone Singh, a geriatrician at the University of Sydney.
Forty percent of dementia cases could be prevented or delayed by modifying a dozen risk factors, according to a 2020 report commissioned by the Lancet. The report doesn’t explicitly call out diet, but some researchers think it plays an important role. After years of fixating on specific foods and dietary components — things like fish oil and vitamin E supplements — many researchers in the field have started looking at dietary patterns.
That shift makes sense. “We do not have vitamin E for breakfast, vitamin C for lunch. We eat foods in combination,” says Nikolaos Scarmeas, a neurologist at National and Kapodistrian University of Athens and Columbia University. He led the study on dementia and anti-inflammatory diets published in Neurology. But a shift from supplements to a whole diet of myriad foods complicates the research. A once-daily pill is easier to swallow than a new, healthier way of eating. Earning points Suspecting that inflammation plays a role in dementia, many researchers posit that an anti-inflammatory diet might benefit the brain. In Scarmeas’ study, more than 1,000 older adults in Greece completed a food frequency questionnaire and earned a score based on how “inflammatory” their diet was. The lower the score, the better. For example, fatty fish, which is rich in omega-3 fatty acids, was considered an anti-inflammatory food and earned negative points. Cheese and many other dairy products, high in saturated fat, earned positive points.
During the next three years, 62 people, or 6 percent of the study participants, developed dementia. People with the highest dietary inflammation scores were three times as likely to develop dementia as those with the lowest. Scores ranged from –5.83 to 6.01. Each point increase was linked to a 21 percent rise in dementia risk.
Such epidemiological studies make connections, but they can’t prove cause and effect. Perhaps people who eat the most anti-inflammatory diets also are those least likely to develop dementia for some other reason. Maybe they have more social interactions. Or it could be, Scarmeas says, that people who eat more inflammatory diets do so because they’re already experiencing changes in their brain that lead them to consume these foods and “what we really see is the reverse causality.”
To sort all this out, researchers rely on randomized controlled trials, the gold standard for providing proof of a causal effect. But in the arena of diet and dementia, these studies have challenges.
Dementia is a disease of aging that takes decades to play out, Kaeberlein says. To show that a particular diet could reduce the risk of dementia, “it would take two-, three-, four-decade studies, which just aren’t feasible.” Many clinical trials last less than two years.
As a work-around, researchers often rely on some intermediate outcome, like changes in cognition. But even that can be hard to observe. “If you’re already relatively healthy and don’t have many risks, you might not show much difference, especially if the duration of the study is relatively short,” says Sue Radd-Vagenas, a nutrition scientist at the University of Sydney. “The thinking is if you’re older and you have more risk factors, it’s more likely we might see something in a short period of time.” Yet older adults might already have some cognitive decline, so it might be more difficult to see an effect.
Many researchers now suspect that intervening earlier will have a bigger impact. “We now know that the brain is stressed from midlife and there’s a tipping point at 65 when things go sour,” says Hussein Yassine, an Alzheimer’s researcher at the Keck School of Medicine of the University of Southern California in Los Angeles. But intervene too early, and a trial might not show any effect. Offering a healthier diet to a 50- or 60-year-old might pay off in the long run but fail to make a difference in cognition that can be measured during the relatively short length of a study.
And it’s not only the timing of the intervention that matters, but also the duration. Do you have to eat a particular diet for two decades for it to have an impact? “We’ve got a problem of timescale,” says Kaarin Anstey, a dementia researcher at the University of New South Wales in Sydney.
And then there are all the complexities that come with studying diet. “You can’t isolate it in the way you can isolate some of the other factors,” Anstey says. “It’s something that you’re exposed to all the time and over decades.”
Food as medicine? In a clinical trial, researchers often test the effectiveness of a drug by offering half the study participants the medication and half a placebo pill. But when the treatment being tested is food, studies become much more difficult to control. First, food doesn’t come in a pill, so it’s tricky to hide whether participants are in the intervention group or the control group.
Imagine a trial designed to test whether the Mediterranean diet can help slow cognitive decline. The participants aren’t told which group they’re in, but the control group sees that they aren’t getting nuts or fish or olive oil. “What ends up happening is a lot of participants will start actively increasing the consumption of the Mediterranean diet despite being on the control arm, because that’s why they signed up,” Yassine says. “So at the end of the trial, the two groups are not very dissimilar.”
Second, we all need food to live, so a true placebo is out of the question. But what diet should the control group consume? Do you compare the diet intervention to people’s typical diets (which may differ from person to person and country to country)? Do you ask the comparison group to eat a healthy diet but avoid the food expected to provide brain benefits? (Offering them an unhealthy diet would be unethical.)
And tracking what people eat during a clinical trial can be a challenge. Many of these studies rely on food frequency questionnaires to tally up all the foods in an individual’s diet. An ongoing study is assessing the impact of the MIND diet (which combines part of the Mediterranean diet with elements of the low-salt DASH diet) on cognitive decline. Researchers track adherence to the diet by asking participants to fill out a food frequency questionnaire every six to 12 months. But many of us struggle to remember what we ate a day or two ago. So some researchers also rely on more objective measures to assess compliance. For the MIND diet assessment, researchers are also tracking biomarkers in the blood and urine — vitamins such as folate, B12 and vitamin E, plus levels of certain antioxidants. Another difficulty is that these surveys often don’t account for variables that could be really important, like how the food was prepared and where it came from. Was the fish grilled? Fried? Slathered in butter? “Those things can matter,” says dementia researcher Nathaniel Chin of the University of Wisconsin–Madison.
Plus there are the things researchers can’t control. For example, how does the food interact with an individual’s medications and microbiome? “We know all of those factors have an interplay,” Chin says.
The few clinical trials looking at dementia and diet seem to measure different things, so it’s hard to make comparisons. In 2018, Radd-Vagenas and her colleagues looked at all the trials that had studied the impact of the Mediterranean diet on cognition. There were five at the time. “What struck me even then was how variable the interventions were,” she says. “Some of the studies didn’t even mention olive oil in their intervention. Now, how can you run a Mediterranean diet study and not mention olive oil?”
Another tricky aspect is recruitment. The kind of people who sign up for clinical trials tend to be more educated, more motivated and have healthier lifestyles. That can make differences between the intervention group and the control group difficult to spot. And if the study shows an effect, whether it will apply to the broader, more diverse population comes into question. To sum up, these studies are difficult to design, difficult to conduct and often difficult to interpret.
Kaeberlein studies aging, not dementia specifically, but he follows the research closely and acknowledges that the lack of clear answers can be frustrating. “I get the feeling of wanting to throw up your hands,” he says. But he points out that there may not be a single answer. Many diets can help people maintain a healthy weight and avoid diabetes, and thus reduce the risk of dementia. Beyond that obvious fact, he says, “it’s hard to get definitive answers.”
A better way In July 2021, Yassine gathered with more than 30 other dementia and nutrition experts for a virtual symposium to discuss the myriad challenges and map out a path forward. The speakers noted several changes that might improve the research.
One idea is to focus on populations at high risk. For example, one clinical trial is looking at the impact of low- and high-fat diets on short-term changes in the brain in people who carry the genetic variant APOE4, a risk factor for Alzheimer’s. One small study suggested that a high-fat Western diet actually improved cognition in some individuals. Researchers hope to get clarity on that surprising result. Another possible fix is redefining how researchers measure success. Hypertension and diabetes are both well-known risk factors for dementia. So rather than running a clinical trial that looks at whether a particular diet can affect dementia, researchers could look at the impact of diet on one of these risk factors. Plenty of studies have assessed the impact of diet on hypertension and diabetes, but Yassine knows of none launched with dementia prevention as the ultimate goal.
Yassine envisions a study that recruits participants at risk of developing dementia because of genetics or cardiovascular disease and then looks at intermediate outcomes. “For example, a high-salt diet can be associated with hypertension, and hypertension can be associated with dementia,” he says. If the study shows that the diet lowers hypertension, “we achieved our aim.” Then the study could enter a legacy period during which researchers track these individuals for another decade to determine whether the intervention influences cognition and dementia.
One way to amplify the signal in a clinical trial is to combine diet with other interventions likely to reduce the risk of dementia. The Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability, or FINGER, trial, which began in 2009, did just that. Researchers enrolled more than 1,200 individuals ages 60 to 77 who were at an elevated risk of developing dementia and had average or slightly impaired performance on cognition tests. Half received nutritional guidance, worked out at a gym, engaged in online brain-training games and had routine visits with a nurse to talk about managing dementia risk factors like high blood pressure and diabetes. The other half received only general health advice.
After two years, the control group had a 25 percent greater cognitive decline than the intervention group. It was the first trial, reported in the Lancet in 2015, to show that targeting multiple risk factors could slow the pace of cognitive decline.
Now researchers are testing this approach in more than 30 countries. Christy Tangney, a nutrition researcher at Rush University in Chicago, is one of the investigators on the U.S. arm of the study, enrolling 2,000 people ages 60 to 79 who have at least one dementia risk factor. The study is called POINTER, or U.S. Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk. The COVID-19 pandemic has delayed the research — organizers had to pause the trial briefly — but Tangney expects to have results in the next few years.
This kind of multi-intervention study makes sense, Chin says. “One of the reasons why things are so slow in our field is we’re trying to address a heterogeneous disease with one intervention at a time. And that’s just not going to work.” A trial that tests multiple interventions “allows for people to not be perfect,” he adds. Maybe they can’t follow the diet exactly, but they can stick to the workout program, which might have an effect on its own. The drawback in these kinds of studies, however, is that it’s impossible to tease out the contribution of each individual intervention. Preemptive guidelines Two major reports came out in recent years addressing dementia prevention. The first, from the World Health Organization in 2019, recommends a healthy, balanced diet for all adults, and notes that the Mediterranean diet may help people who have normal to mildly impaired cognition.
The 2020 Lancet Commission report, however, does not include diet in its list of modifiable risk factors, at least not yet. “Nutrition and dietary components are challenging to research with controversies still raging around the role of many micronutrients and health outcomes in dementia,” the report notes. The authors point out that a Mediterranean or the similar Scandinavian diet might help prevent cognitive decline in people with intact cognition, but “how long the exposure has to be or during which ages is unclear.” Neither report recommends any supplements.
Plenty of people are waiting for some kind of advice to follow. Improving how these studies are done might enable scientists to finally sort out what kinds of diets can help hold back the heartbreaking damage that comes with Alzheimer’s disease. For some people, that knowledge might be enough to create change. “Inevitably, if you’ve had Alzheimer’s in your family, you want to know, ‘What can I do today to potentially reduce my risk?’ ” says molecular biologist Heather Snyder, vice president of medical and scientific relations at the Alzheimer’s Association.
But changing long-term dietary habits can be hard. The foods we eat aren’t just fuel; our diets represent culture and comfort and more. “Food means so much to us,” Chin says.
“Even if you found the perfect diet,” he adds, “how do you get people to agree to and actually change their habits to follow that diet?” The MIND diet, for example, suggests people eat less than one serving of cheese a week. In Wisconsin, where Chin is based, that’s a nonstarter, he says.
But it’s not just about changing individual behaviors. Radd-Vagenas and other researchers hope that if they can show the brain benefits of some of these diets in rigorous studies, policy changes might follow. For example, research shows that lifestyle changes can have a big impact on type 2 diabetes. As a result, many insurance providers now pay for coaching programs that help participants maintain healthy diet and exercise habits.
“You need to establish policies. You need to change cities, change urban design. You need to do a lot of things to enable healthier choices to become easier choices,” Radd-Vagenas says. But that takes meatier data than exist now.
During winter in India’s mountainous Ladakh region, some farmers use pipes and sprinklers to construct building-sized cones of ice. These towering, humanmade glaciers, called ice stupas, slowly release water as they melt during the dry spring months for communities to drink or irrigate crops. But the pipes often freeze when conditions get too cold, stifling construction.
Now, preliminary results show that an automated system can erect an ice stupa while avoiding frozen pipes, using local weather data to control when and how much water is spouted. What’s more, the new system uses roughly a tenth the amount of water that the conventional method uses, researchers reported June 23 at the Frontiers in Hydrology meeting in San Juan, Puerto Rico. “This is one of the technological steps forward that we need to get this innovative idea to the point where it’s realistic as a solution,” says glaciologist Duncan Quincey of the University of Leeds in England who was not involved in the research. Automation could help communities build larger, longer-lasting ice stupas that provide more water during dry periods, he says.
Ice stupas emerged in 2014 as a means for communities to cope with shrinking alpine glaciers due to human-caused climate change (SN: 5/29/19). Typically, high-mountain communities in India, Kyrgyzstan and Chile pipe glacial meltwater into gravity-driven fountains that sprinkle continuously in the winter. Cold air freezes the drizzle, creating frozen cones that can store millions of liters of water.
The process is simple, though inefficient. More than 70 percent of the spouted water may flow away instead of freezing, says glaciologist Suryanarayanan Balasubramanian of the University of Fribourg in Switzerland.
So Balasubramanian and his team outfitted an ice stupa’s fountain with a computer that automatically adjusted the spout’s flow rate based on local temperatures, humidity and wind speed. Then the scientists tested the system by building two ice stupas in Guttannen, Switzerland — one using a continuously spraying fountain and one using the automated system.
After four months, the team found that the continuously sprinkling fountain had spouted about 1,100 cubic meters of water and amassed 53 cubic meters of ice, with pipes freezing once. The automated system sprayed only around 150 cubic meters of water but formed 61 cubic meters of ice, without any frozen pipes.
The researchers are now trying to simplify their prototype to make it more affordable for high-mountain communities around the world. “We eventually want to reduce the cost so that it is within two months of salary of the farmers in Ladakh,” Balasubramanian says. “Around $200 to $400.”
A man with a hole in his forehead, who was interred in what’s now northwest Alabama between around 3,000 and 5,000 years ago, represents North America’s oldest known case of skull surgery.
Damage around the man’s oval skull opening indicates that someone scraped out that piece of bone, probably to reduce brain swelling caused by a violent attack or a serious fall, said bioarchaeologist Diana Simpson of the University of Nevada, Las Vegas. Either scenario could explain fractures and other injuries above the man’s left eye and to his left arm, leg and collarbone.
Bone regrowth on the edges of the skull opening indicates that the man lived for up to one year after surgery, Simpson estimated. She presented her analysis of the man’s remains on March 28 at a virtual session of the annual meeting of the American Association of Biological Anthropologists. Skull surgery occurred as early as 13,000 years ago in North Africa (SN: 8/17/11). Until now, the oldest evidence of this practice in North America dated to no more than roughly 1,000 years ago.
In his prime, the new record holder likely served as a ritual practitioner or shaman. His grave included items like those found in shamans’ graves at nearby North American hunter-gatherer sites dating to between about 3,000 and 5,000 years ago. Ritual objects buried with him included sharpened bone pins and modified deer and turkey bones that may have been tattooing tools (SN: 5/25/21).
Investigators excavated the man’s grave and 162 others at the Little Bear Creek Site, a seashell covered burial mound, in the 1940s. Simpson studied the man’s museum-held skeleton and grave items in 2018, shortly before the discoveries were returned to local Native American communities for reburial.
Science, some would say, is an enterprise that should concern itself solely with cold, hard facts. Flights of imagination should be the province of philosophers and poets.
On the other hand, as Albert Einstein so astutely observed, “Imagination is more important than knowledge.” Knowledge, he said, is limited to what we know now, while “imagination embraces the entire world, stimulating progress.”
So with science, imagination has often been the prelude to transformative advances in knowledge, remaking humankind’s understanding of the world and enabling powerful new technologies. And yet while sometimes spectacularly successful, imagination has also frequently failed in ways that retard the revealing of nature’s secrets. Some minds, it seems, are simply incapable of imagining that there’s more to reality than what they already know.
On many occasions scientists have failed to foresee ways of testing novel ideas, ridiculing them as unverifiable and therefore unscientific. Consequently it is not too challenging to come up with enough failures of scientific imagination to compile a Top 10 list, beginning with:
Atoms By the middle of the 19th century, most scientists believed in atoms. Chemists especially. John Dalton had shown that the simple ratios of different elements making up chemical compounds strongly implied that each element consisted of identical tiny particles. Subsequent research on the weights of those atoms made their reality pretty hard to dispute. But that didn’t deter physicist-philosopher Ernst Mach. Even as late as the beginning of the 20th century, he and a number of others insisted that atoms could not be real, as they were not accessible to the senses. Mach believed that atoms were a “mental artifice,” convenient fictions that helped in calculating the outcomes of chemical reactions. “Have you ever seen one?” he would ask.
Apart from the fallacy of defining reality as “observable,” Mach’s main failure was his inability to imagine a way that atoms could be observed. Even after Einstein proved the existence of atoms by indirect means in 1905, Mach stood his ground. He was unaware, of course, of the 20th century technologies that quantum mechanics would enable, and so did not foresee powerful new microscopes that could show actual images of atoms (and allow a certain computing company to drag them around to spell out IBM).
Composition of stars Mach’s views were similar to those of Auguste Comte, a French philosopher who originated the idea of positivism, which denies reality to anything other than objects of sensory experience. Comte’s philosophy led (and in some cases still leads) many scientists astray. His greatest failure of imagination was an example he offered for what science could never know: the chemical composition of the stars.
Unable to imagine anybody affording a ticket on some entrepreneur’s space rocket, Comte argued in 1835 that the identity of the stars’ components would forever remain beyond human knowledge. We could study their size, shapes and movements, he said, “whereas we would never know how to study by any means their chemical composition, or their mineralogical structure,” or for that matter, their temperature, which “will necessarily always be concealed from us.”
Within a few decades, though, a newfangled technology called spectroscopy enabled astronomers to analyze the colors of light emitted by stars. And since each chemical element emits (or absorbs) precise colors (or frequencies) of light, each set of colors is like a chemical fingerprint, an infallible indicator for an element’s identity. Using a spectroscope to observe starlight therefore can reveal the chemistry of the stars, exactly what Comte thought impossible.
Canals on Mars Sometimes imagination fails because of its overabundance rather than absence. In the case of the never-ending drama over the possibility of life on Mars, that planet’s famous canals turned out to be figments of overactive scientific imagination.
First “observed” in the late 19th century, the Martian canals showed up as streaks on the planet’s surface, described as canali by Italian astronomer Giovanni Schiaparelli. Canali is, however, Italian for channels, not canals. So in this case something was gained (rather than lost) in translation — the idea that Mars was inhabited. “Canals are dug,” remarked British astronomer Norman Lockyer in 1901, “ergo there were diggers.” Soon astronomers imagined an elaborate system of canals transporting water from Martian poles to thirsty metropolitan areas and agricultural centers. (Some observers even imagined seeing canals on Venus and Mercury.) With more constrained imaginations, aided by better telescopes and translations, belief in the Martian canals eventually faded. It was merely the Martian winds blowing dust (bright) and sand (dark) around the surface in ways that occasionally made bright and dark streaks line up in a deceptive manner — to eyes attached to overly imaginative brains.
Nuclear fission In 1934, Italian physicist Enrico Fermi bombarded uranium (atomic number 92) and other elements with neutrons, the particle discovered just two years earlier by James Chadwick. Fermi found that among the products was an unidentifiable new element. He thought he had created element 93, heavier than uranium. He could not imagine any other explanation. In 1938 Fermi was awarded the Nobel Prize in physics for demonstrating “the existence of new radioactive elements produced by neutron irradiation.”
It turned out, however, that Fermi had unwittingly demonstrated nuclear fission. His bombardment products were actually lighter, previously known elements — fragments split from the heavy uranium nucleus. Of course, the scientists later credited with discovering fission, Otto Hahn and Fritz Strassmann, didn’t understand their results either. Hahn’s former collaborator Lise Meitner was the one who explained what they’d done. Another woman, chemist Ida Noddack, had imagined the possibility of fission to explain Fermi’s results, but for some reason nobody listened to her.
Detecting neutrinos In the 1920s, most physicists had convinced themselves that nature was built from just two basic particles: positively charged protons and negatively charged electrons. Some had, however, imagined the possibility of a particle with no electric charge. One specific proposal for such a particle came in 1930 from Austrian physicist Wolfgang Pauli. He suggested that a no-charge particle could explain a suspicious loss of energy observed in beta-particle radioactivity. Pauli’s idea was worked out mathematically by Fermi, who named the neutral particle the neutrino. Fermi’s math was then examined by physicists Hans Bethe and Rudolf Peierls, who deduced that the neutrino would zip through matter so easily that there was no imaginable way of detecting its existence (short of building a tank of liquid hydrogen 6 million billion miles wide). “There is no practically possible way of observing the neutrino,” Bethe and Peierls concluded.
But they had failed to imagine the possibility of finding a source of huge numbers of high-energy neutrinos, so that a few could be captured even if almost all escaped. No such source was known until nuclear fission reactors were invented. In the 1950s, Frederick Reines and Clyde Cowan used reactors to definitely establish the neutrino’s existence. Reines later said he sought a way to detect the neutrino precisely because everybody had told him it wasn’t possible to detect the neutrino.
Nuclear energy Ernest Rutherford, one of the 20th century’s greatest experimental physicists, was not exactly unimaginative. He imagined the existence of the neutron a dozen years before it was discovered, and he figured out that a weird experiment conducted by his assistants had revealed that atoms contained a dense central nucleus. It was clear that the atomic nucleus packed an enormous quantity of energy, but Rutherford could imagine no way to extract that energy for practical purposes. In 1933, at a meeting of the British Association for the Advancement of Science, he noted that although the nucleus contained a lot of energy, it would also require energy to release it. Anyone saying we can exploit atomic energy “is talking moonshine,” Rutherford declared. To be fair, Rutherford qualified the moonshine remark by saying “with our present knowledge,” so in a way he perhaps was anticipating the discovery of nuclear fission a few years later. (And some historians have suggested that Rutherford did imagine the powerful release of nuclear energy, but thought it was a bad idea and wanted to discourage people from attempting it.)
Age of the Earth Rutherford’s reputation for imagination was bolstered by his inference that radioactive matter deep underground could solve the mystery of the age of the Earth. In the mid-19th century, William Thomson (later known as Lord Kelvin) calculated the Earth’s age to be something a little more than 100 million years, and possibly much less. Geologists insisted that the Earth must be much older — perhaps billions of years — to account for the planet’s geological features.
Kelvin calculated his estimate assuming the Earth was born as a molten rocky mass that then cooled to its present temperature. But following the discovery of radioactivity at the end of the 19th century, Rutherford pointed out that it provided a new source of heat in the Earth’s interior. While giving a talk (in Kelvin’s presence), Rutherford suggested that Kelvin had basically prophesized a new source of planetary heat.
While Kelvin’s neglect of radioactivity is the standard story, a more thorough analysis shows that adding that heat to his math would not have changed his estimate very much. Rather, Kelvin’s mistake was assuming the interior to be rigid. John Perry (one of Kelvin’s former assistants) showed in 1895 that the flow of heat deep within the Earth’s interior would alter Kelvin’s calculations considerably — enough to allow the Earth to be billions of years old. It turned out that the Earth’s mantle is fluid on long time scales, which not only explains the age of the Earth, but also plate tectonics.
Charge-parity violation Before the mid-1950s, nobody imagined that the laws of physics gave a hoot about handedness. The same laws should govern matter in action when viewed straight-on or in a mirror, just as the rules of baseball applied equally to Ted Williams and Willie Mays, not to mention Mickey Mantle. But in 1956 physicists Tsung-Dao Lee and Chen Ning Yang suggested that perfect right-left symmetry (or “parity”) might be violated by the weak nuclear force, and experiments soon confirmed their suspicion.
Restoring sanity to nature, many physicists thought, required antimatter. If you just switched left with right (mirror image), some subatomic processes exhibited a preferred handedness. But if you also replaced matter with antimatter (switching electric charge), left-right balance would be restored. In other words, reversing both charge (C) and parity (P) left nature’s behavior unchanged, a principle known as CP symmetry. CP symmetry had to be perfectly exact; otherwise nature’s laws would change if you went backward (instead of forward) in time, and nobody could imagine that.
In the early 1960s, James Cronin and Val Fitch tested CP symmetry’s perfection by studying subatomic particles called kaons and their antimatter counterparts. Kaons and antikaons both have zero charge but are not identical, because they are made from different quarks. Thanks to the quirky rules of quantum mechanics, kaons can turn into antikaons and vice versa. If CP symmetry is exact, each should turn into the other equally often. But Cronin and Fitch found that antikaons turn into kaons more often than the other way around. And that implied that nature’s laws allowed a preferred direction of time. “People didn’t want to believe it,” Cronin said in a 1999 interview. Most physicists do believe it today, but the implications of CP violation for the nature of time and other cosmic questions remain mysterious.
Behaviorism versus the brain In the early 20th century, the dogma of behaviorism, initiated by John Watson and championed a little later by B.F. Skinner, ensnared psychologists in a paradigm that literally excised imagination from science. The brain — site of all imagination — is a “black box,” the behaviorists insisted. Rules of human psychology (mostly inferred from experiments with rats and pigeons) could be scientifically established only by observing behavior. It was scientifically meaningless to inquire into the inner workings of the brain that directed such behavior, as those workings were in principle inaccessible to human observation. In other words, activity inside the brain was deemed scientifically irrelevant because it could not be observed. “When what a person does [is] attributed to what is going on inside him,” Skinner proclaimed, “investigation is brought to an end.”
Skinner’s behaviorist BS brainwashed a generation or two of followers into thinking the brain was beyond study. But fortunately for neuroscience, some physicists foresaw methods for observing neural activity in the brain without splitting the skull open, exhibiting imagination that the behaviorists lacked. In the 1970s Michel Ter-Pogossian, Michael Phelps and colleagues developed PET (positron emission tomography) scanning technology, which uses radioactive tracers to monitor brain activity. PET scanning is now complemented by magnetic resonance imaging, based on ideas developed in the 1930s and 1940s by physicists I.I. Rabi, Edward Purcell and Felix Bloch.
Gravitational waves Nowadays astrophysicists are all agog about gravitational waves, which can reveal all sorts of secrets about what goes on in the distant universe. All hail Einstein, whose theory of gravity — general relativity — explains the waves’ existence. But Einstein was not the first to propose the idea. In the 19th century, James Clerk Maxwell devised the math explaining electromagnetic waves, and speculated that gravity might similarly induce waves in a gravitational field. He couldn’t figure out how, though. Later other scientists, including Oliver Heaviside and Henri Poincaré, speculated about gravity waves. So the possibility of their existence certainly had been imagined.
But many physicists doubted that the waves existed, or if they did, could not imagine any way of proving it. Shortly before Einstein completed his general relativity theory, German physicist Gustav Mie declared that “the gravitational radiation emitted … by any oscillating mass particle is so extraordinarily weak that it is unthinkable ever to detect it by any means whatsoever.” Even Einstein had no idea how to detect gravitational waves, although he worked out the math describing them in a 1918 paper. In 1936 he decided that general relativity did not predict gravitational waves at all. But the paper rejecting them was simply wrong. As it turned out, of course, gravitational waves are real and can be detected. At first they were verified indirectly, by the diminishing distance between mutually orbiting pulsars. And more recently they were directly detected by huge experiments relying on lasers. Nobody had been able to imagine detecting gravitational waves a century ago because nobody had imagined the existence of pulsars or lasers.
All these failures show how prejudice can sometimes dull the imagination. But they also show how an imagination failure can inspire the quest for a new success. And that’s why science, so often detoured by dogma, still manages somehow, on long enough time scales, to provide technological wonders and cosmic insights beyond philosophers’ and poets’ wildest imagination.
Buried within the Las Pinturas pyramid in San Bartolo, Guatemala, thousands of painted plaster mural fragments offer a window into ancient Maya civilization. Two of those fragments form the earliest known record of a Maya calendar, created between 300 and 200 B.C.
The fragments depict the date of “7 Deer” from the 260-day sacred calendar common across ancient Mesoamerica and still used today by indigenous communities in Guatemala and southern Mexico, archaeologist David Stuart and colleagues report April 13 in Science Advances. The calendar system’s longevity attests to the persistence of Maya intellectual culture, says Stuart, of the University of Texas at Austin.
From 400 B.C. to 100 A.D., Mayas razed and rebuilt the pyramid seven times, creating a series of discrete time capsules stacked on top of each other, says study coauthor Heather Hurst, project director of the San Bartolo-Xultun Regional Archaeological Project. By radiocarbon dating both the material in the layer where the calendar fragments were found and the material used to bury that layer, researchers determined a narrow time window in which the 7 Deer day record would have been produced. After two decades of excavation, the site continues to be an important source of ancient Maya artifacts. The earliest known Maya writing, also dated to between 300 and 200 B.C., was found in the same time capsule as the 7 Deer day record (SN: 1/17/06).
The 260-day calendar system “survived not only close to 1,800 years in the Maya world before the Spanish showed up, but it persisted even more recently, since conquests . . . in some of the most oppressed areas,” Stuart says. “I find that an incredible thing.”
In fact, the intricacy of the depiction suggests that the calendar system had already existed for centuries by the time it was drawn, says Stephen Houston, an archaeologist at Brown University in Providence, R.I., who was not involved in the study. The characters are “very well practiced. This isn’t a stumbling baby step.”
Ten other fragments described in the study feature different styles of handwriting that indicate multiple scribes worked on the murals. This suggests that the Maya literary tradition was already robust by this time, Houston says. “There’s a density of knowledge here.”
The windy and chaotic remains surrounding recently exploded stars may be launching the fastest particles in the universe.
Highly magnetic neutron stars known as pulsars whip up a fast and strong magnetic wind. When charged particles, specifically electrons, get caught in those turbulent conditions, they can be boosted to extreme energies, astrophysicists report April 28 in the Astrophysical Journal Letters. What’s more, those zippy electrons can then go on to boost some ambient light to equally extreme energies, possibly creating the very high-energy gamma-ray photons that led astronomers to detect these particle launchers in the first place.
“This is the first step in exploring the connection between the pulsars and the ultrahigh-energy emissions,” says astrophysicist Ke Fang of the University of Wisconsin, Madison, who was not involved in this new work.
Last year, researchers with the Large High Altitude Air Shower Observatory, or LHAASO, in China announced the discovery of the highest-energy gamma rays ever detected, up to 1.4 quadrillion electron volts (SN: 2/2/21). That’s roughly 100 times as energetic as the highest energies achievable with the world’s premier particle accelerator, the Large Hadron Collider near Geneva. Identifying what’s causing these and other extremely high-energy gamma rays could point, literally, to the locations of cosmic rays — the zippy protons, heavier atomic nuclei and electrons that bombard Earth from locales beyond our solar system. Some gamma rays are thought to originate in the same environs as cosmic rays. One way they’re produced is that cosmic rays, shortly after being launched, can slam into relatively low-energy ambient photons, boosting them to high-energy gamma rays. But the electrically charged cosmic rays are buffeted by galactic magnetic fields, which means they don’t travel in a straight line, thus complicating efforts to trace the zippy particles back to their source. Gamma rays, however, are impervious to magnetic fields, so astrophysicists can trace their unwavering paths back to their origins — and figure out where cosmic rays are created.
To that end, the LHAASO team traced the hundreds of gamma-ray photons that it detected to 12 spots on the sky. While the team identified one spot as the Crab Nebula, the remnant of a supernova about 6,500 light-years from Earth, the researchers suggested that the rest could be associated with other sites of stellar explosions or even young massive star clusters (SN: 6/24/19).
In the new study, astrophysicist Emma de Oña Wilhelmi and colleagues zeroed in one of those possible points of origin: pulsar wind nebulas, the clouds of turbulence and charged particles surrounding a pulsar. The researchers weren’t convinced such locales could create such high-energy particles and light, so they set out to show through calculations that pulsar wind nebulas weren’t the sources of extreme gamma rays. “But to our surprise, we saw at the very extreme conditions, you can explain all the sources [that LHAASO saw],” says de Oña Wilhelmi, of the German Electron Synchrotron in Hamburg.
The young pulsars at the heart of these nebulas — no more than 200,000 years old — can provide all that oomph because of their ultrastrong magnetic fields, which create a turbulent magnetic bubble called a magnetosphere.
Any charged particles moving in an intense magnetic field get accelerated, says de Oña Wilhelmi. That’s how the Large Hadron Collider boosts particles to extreme energies (SN: 4/22/22). A pulsar-powered accelerator, though, can boost particles to even higher energies, the team calculates. That’s because the electrons escape the pulsar’s magnetosphere and meet up with the material and magnetic fields from the stellar explosion that created the pulsar. These magnetic fields can further accelerate the electrons to even higher energies, the team finds, and if those electrons slam into ambient photons, they can boost those particles of light to ultrahigh energies, turning them into gamma rays.
“Pulsars are definitely very powerful accelerators,” Fang says, with “several places where particle acceleration can happen.”
And that could lead to a bit of confusion. Gamma-ray telescopes have pretty fuzzy vision. For example, LHASSO can make out details only as small as about half the size of the full moon. So the gamma-ray sources that the telescope detected look like blobs or bubbles, says de Oña Wilhelmi. There could be multiple energetic sources within those blobs, unresolved to current observatories.
“With better angular resolution and better sensitivity, we should be able to identify what [and] where the accelerator is,” she says. A few future observatories — such as the Cherenkov Telescope Array and the Southern Wide-field Gamma-ray Observatory — could help, but they’re several years out.
The U.S. defense and intelligence communities are taking unidentified flying objects, officially known as unidentified aerial phenomena, seriously. And some researchers think the scientific community should too.
On May 17, the U.S. Congress held its first public hearing about these objects in decades (SN: 6/26/71). Two Pentagon officials described efforts to catalog and analyze sightings, many by military personnel such as pilots, of the unexplained phenomena because of their potential threat to national security.
Scott Bray, the deputy director of naval intelligence, shared new details on a database of images and videos that now includes about 400 reports of sightings of unidentified phenomena from 2004 to 2021. While officials were able to attribute some of the sightings to artifacts of certain sensors or other mundane explanations, there were others the officials “can’t explain,” Bray said.
Bray stressed that nothing in the database or studied by a task force set up to investigate the sightings “would suggest it’s anything nonterrestrial in origin.” Both Bray and Ronald Moultrie, the undersecretary of defense for intelligence and security, identified “insufficient data” as a barrier to understanding what the unidentified phenomena are. “That’s one of the challenges we have,” Moultrie said.
That’s something that other scientists can help with, say astrobiologists Jacob Haqq Misra and Ravi Kopparapu.
Science News spoke with Haqq Misra, of Blue Marble Space Institute of Science in Seattle, and Kopparapu, of NASA’s Goddard Space Flight Center in Greenbelt, Md., to learn more about how and why. Their answers have been edited for brevity and clarity.
What are unidentified aerial phenomena? Haqq Misra: “What are they” is the billion-dollar question. We don’t know what they are, and that’s what makes them interesting.
Unidentified aerial phenomena, or UAP, is the term that the military has been using. It’s a little different from the term UFO in the sense that a phenomenon could be something that’s not necessarily a physical solid object. So UAP is maybe a more all-encompassing term.
Should we scientifically study them? Why? Kopparapu: Yes. We conduct scientific studies of unknown phenomena all the time. This should not be any different. The most critical point to remember is that when conducting those studies, we should not let our speculations drive the conclusions. The collected data should do it.
Haqq Misra: As scientists, what we should do is study things that we don’t understand.
With UAP, there seem to be some anomalous observations that are difficult to explain. Maybe they’re a sign of something like new physics, or maybe it’s just instrumental artifacts that we don’t understand or things that birds are doing.
It could be anything, but any of those possibilities, anything from the most extreme to the most mundane, would teach us something.
So there’s the scientific curiosity. And it’s also about safety for pilots too, especially if there’s something in the sky that pilots are seeing that they consider a flight safety risk.
How can we study these phenomena? Haqq Misra: The problem with studying UAP so far is that all of the data are held by the government. From the hearing, there does seem to be a plan to declassify some data, once it’s been vetted for possible security risks, but I’m not holding my breath for that to happen soon. It was nice to hear, though.
The reality is if you want to understand a particular set of data, you need to know something about the instrument that collected the data. Military instruments are probably classified for good reason, for our safety. I think we’re not going to get the kind of data from the government that we need to scientifically answer the question. Even if you had that data, from the government or commercial pilots or others, it has not been intentionally collected. These have been accidental, sporadic observations.
So what you would need is to set up a network of detectors all around the world. Ideally, you’d have ground-based sensors and you’d have satellite coverage. It’s not enough for someone to just see something. You need to measure a detection with multiple sensors and multiple wavelengths.
Kopparapu: Some of these are transient events. We need, for example, fast-tracking cameras and optical, infrared and radar observations to collect more data to find patterns in the events’ behaviors.
And we need to share such data with scientists so that independent groups can reach a consensus. This is how science progresses. There are some initiatives from academics in this direction, so that is a good sign.
What are some possible next steps for the scientific community for studying them? Haqq Misra: There are some groups that are trying to build detectors now. Fundraising is the hardest part. [The nonprofit] UAPx is one, and the Galileo Project [at Harvard University] is another.
And this was underscored in the hearing, but stigma has been a big problem. It seems like the military is trying to not only streamline the reporting process but also destigmatize it. That’s important for science too. If that starts to change more in the culture, that would go a long way.
Kopparapu: I think the scientific study of UAP should not be stigmatized. There should be open discussions, comments and constructive criticisms that can help further the study of UAP.
There should be discussions about how and which kinds of instruments are needed to collect data. The focus should be on collecting and sharing the data and then commenting on the topic.
How did you get interested in this topic? Kopparapu: Over a couple of years, I read several articles either dismissing or advocating for a particular explanation regarding UAP. Then I started digging into it, and I found physicist James McDonald’s “Science in Default” report from 1969. That one particular report about UFOs changed my perspective. It was written similar to how we write our scientific articles. That resonated with me as a scientist, and I started to think that a science investigation is the only way we can understand UAP.
Haqq Misra: I got interested in this subject because I’m an astrobiologist and other people asked me about UFOs. UFOs are not necessarily an astrobiology topic, because we don’t know what they are. But lots of people think that they’re extraterrestrials. And I felt a little silly, being an astrobiologist and having nothing to say.
So I went to Carl Sagan’s files, and I realized that even though he lived decades before me, there are things in his files that we’re talking about now, that are related to airborne anomalies seen by pilots.
Ultimately, I realized for a scientist who wants to understand what’s going on with this UFO thing, there’s a lot of noise to sift through. There’s a lot of public discourse about other topics like crop circles, alien abductions and paranormal stories that muddy the waters, and the more we can be clear about the specific aerial anomalies that we’re talking about, the more we can actually solve the problem.
Deep in the human brain, a very specific kind of cell dies during Parkinson’s disease.
For the first time, researchers have sorted large numbers of human brain cells in the substantia nigra into 10 distinct types. Just one is especially vulnerable in Parkinson’s disease, the team reports May 5 in Nature Neuroscience. The result could lead to a clearer view of how Parkinson’s takes hold, and perhaps even ways to stop it.
The new research “goes right to the core of the matter,” says neuroscientist Raj Awatramani of Northwestern University Feinberg School of Medicine in Chicago. Pinpointing the brain cells that seem to be especially susceptible to the devastating disease is “the strength of this paper,” says Awatramani, who was not involved in the study.
Parkinson’s disease steals people’s ability to move smoothly, leaving balance problems, tremors and rigidity. In the United States, nearly 1 million people are estimated to have Parkinson’s. Scientists have known for decades that these symptoms come with the death of nerve cells in the substantia nigra. Neurons there churn out dopamine, a chemical signal involved in movement, among other jobs (SN: 9/7/17).
But those dopamine-making neurons are not all equally vulnerable in Parkinson’s, it turns out.
“This seemed like an opportunity to … really clarify which kinds of cells are actually dying in Parkinson’s disease,” says Evan Macosko, a psychiatrist and neuroscientist at Massachusetts General Hospital in Boston and the Broad Institute of MIT and Harvard. The tricky part was that dopamine-making neurons in the substantia nigra are rare. In samples of postmortem brains, “we couldn’t survey enough of [the cells] to really get an answer,” Macosko says. But Abdulraouf Abdulraouf, a researcher in Macosko’s laboratory, led experiments that sorted these cells, figuring out a way to selectively pull the cells’ nuclei out from the rest of the cells present in the substantia nigra. That enrichment ultimately led to an abundance of nuclei to analyze.
By studying over 15,000 nuclei from the brains of eight formerly healthy people, the researchers further sorted dopamine-making cells in the substantia nigra into 10 distinct groups. Each of these cell groups was defined by a specific brain location and certain combinations of genes that were active.
When the researchers looked at substantia nigra neurons in the brains of people who died with either Parkinson’s disease or the related Lewy body dementia, the team noticed something curious: One of these 10 cell types was drastically diminished.
These missing neurons were identified by their location in the lower part of the substantia nigra and an active AGTR1 gene, lab member Tushar Kamath and colleagues found. That gene was thought to serve simply as a good way to identify these cells, Macosko says; researchers don’t know whether the gene has a role in these dopamine-making cells’ fate in people.
The new finding points to ways to perhaps counter the debilitating diseases. Scientists have been keen to replace the missing dopamine-making neurons in the brains of people with Parkinson’s. The new study shows what those cells would need to look like, Awatramani says. “If a particular subtype is more vulnerable in Parkinson’s disease, maybe that’s the one we should be trying to replace,” he says.
In fact, Macosko says that stem cell scientists have already been in contact, eager to make these specific cells. “We hope this is a guidepost,” Macosko says.
The new study involved only a small number of human brains. Going forward, Macosko and his colleagues hope to study more brains, and more parts of those brains. “We were able to get some pretty interesting insights with a relatively small number of people,” he says. “When we get to larger numbers of people with other kinds of diseases, I think we’re going to learn a lot.”
