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More than a year and a half into the pandemic, researchers are beginning to get a handle on how the coronavirus makes people sick and what to do about it. That includes some valuable lessons about what doesn’t work. Now the trick is to find drugs or therapies that do work, especially for people who aren’t sick enough to go to the hospital. Early treatment may limit transmission of the virus and keep people out of overburdened hospitals.

Finding those treatments is proving to be particularly tricky. While the race to create vaccines was astonishingly successful, effective treatments have proved elusive. But they are crucial, especially because the pandemic is far from over. After seemingly gaining ground on the virus in the United States, cases and hospitalizations are again on the rise as the more infectious delta variant sweeps across the country (SN: 7/2/21). The variant is driving a surge of new infections globally, too.

“We still have a lot of people who remain unvaccinated” and at risk of getting COVID-19, says Susanna Naggie, an infectious diseases physician at Duke University School of Medicine. “The need for a safe therapy that can be administered at home remains huge.”

A few drugs — including the antiviral medication remdesivir, immune system–calming antibody therapies such as baricitinib and tocilizumab and steroids such as dexamethasone — have been literal lifesavers for some of the sickest patients (SN: 4/29/20; SN: 10/30/20; SN: 9/2/20). For instance, real-world data from more than 98,000 people hospitalized with COVID-19 suggest that infusions of remdesivir cut the chance of dying by up to 23 percent, researchers from the drug’s maker Gilead Sciences, Inc., reported at the World Microbe Forum, held online in June. Still, those drugs don’t save everyone, and they are reserved for people who are hospitalized.

Some lab-made antibodies may help newly diagnosed people avoid hospitalization and severe illness (SN: 9/22/20). But relatively few people have gotten the treatment, which requires intravenous infusions.

While finding effective, easy-to-take treatments has been no easy task, it’s not for lack of trying. But it can seem like for every encouraging lead, there’s a hurdle. Here’s a look at some of the challenges that have stymied efforts to develop treatments for COVID-19 and some of the promising approaches, including some in pill form, that may still pan out.

A false lead

To speed the search for treatments, researchers first reached for drugs already approved by the U.S. Food and Drug Administration and in the medicine cabinet for treating other diseases. Most of the proven treatments for COVID-19 started this way, with the exception of remdesivir. That antiviral drug was developed to fight RNA viruses, but hadn’t been approved prior to the pandemic. It is now the only FDA-approved treatment for COVID-19.

Most repurposed drugs haven’t panned out as coronavirus treatments despite some tantalizing hints they might. Now, scientists have insight into one reason why drugs such as hydroxychloroquine, chloroquine and about 30 others don’t work in people even though they stop SARS-CoV-2 from infecting cells in lab dishes (SN: 8/2/2020). It’s all connected to a particular side effect of the drugs.

The route to this discovery began in 2020 when researchers identified proteins called sigma receptors in human and monkey cells that interact with some of the virus’s proteins. Researchers thought that might be important for infection. So they proposed that some common antidepressants, antipsychotics and antihistamines may disrupt those interactions and might stymie the coronavirus’s ability to infect people (SN: 4/30/20).  

But further investigation showed that for many of the compounds, there was no relationship between a drug’s ability to grab the sigma receptors and effectiveness against the virus when tested on cells grown in lab dishes, says medicinal chemist Brian Shoichet. The drugs either targeted the sigma receptors or they stopped the virus from growing. They didn’t do both.

“When you see something like that, it’s a real showstopper for someone like myself,” says Shoichet, of the University of California San Francisco School of Pharmacy. “It really makes you think, ‘Oh, we’re digging in the wrong place. There’s something fundamentally wrong with our hypothesis,’” he says. The evidence seems to indicate that targeting sigma receptors won’t improve COVID-19 symptoms, he says.

But of the drugs that did have potent antiviral effects, many were ones known to disrupt the way human cells build and use fats called lipids, he noticed. That disruption can lead to a potentially serious side effect called phospholipidosis. That side effect causes lipids to build up in cells, giving some cells a foamy appearance. That buildup can lead to inflammation, which can damage organs or interfere with their functions.

Shoichet and his colleagues wondered if that lipid disruption was causing the antiviral effect. Teaming with researchers from the Novartis Institutes for BioMedical Research in Basel, Switzerland, they first tested whether the drugs were causing the side effect in cells. Sure enough, the more phospholipidosis the drugs caused, the more potently they inhibited virus growth in those cells, the researchers reported June 22 in Science.

That’s because SARS-CoV-2 needs to build lipid bubbles inside cells where it can replicate. Phospholipidosis may interfere with that process, Shoichet says. That might be a useful property, except for one thing: The drugs that caused the side effect didn’t work in animal experiments. In mice, these drugs didn’t stop the coronavirus from replicating in lung cells, colleagues at the Pasteur Institute in Paris discovered.

This disconnect between a drug’s antiviral activity in lab dishes and its inability to protect animals may happen for two reasons, says François Pognan, an investigative toxicologist at Novartis. Either the drugs have to be given in very high doses to cause phospholipidosis — much higher than would be safe — or they need to build up over time. In lab dishes, “it’s a piece of cake,” Pognan says. But in the body, it’s very difficult to reach levels of the drug that would cause enough lipid disruption to be protective.

That finding could help researchers avoid dead-ends. If a drug stops the coronavirus from growing in cells in the lab, researchers should test for phospholipidosis. If the drug causes that side effect, it should be discarded as a COVID-19 therapy.

Following that advice could impact many ongoing clinical trials and save time and money. Currently, at least 33 drugs, including the antibiotic azithromycin, that cause phospholipidosis are being tested in 136 clinical trials.

One trial at the University of California, San Francisco tested whether azithromycin could clear up symptoms of COVID-19 in 263 newly diagnosed people. There was no difference between the drug and a placebo, researchers reported July 16 in JAMA. What’s more, people taking the antibiotic were much more likely than those getting a placebo to report side effects, such as abdominal pain, diarrhea and nausea. And five people taking azithromycin were hospitalized, while no one in the placebo group was. An independent monitoring committee recommended ending the trial for “futility.”

Another 180 trials were devoted to hydroxychloroquine or chloroquine, which also lead to the lipid foaming side effect. (Hydroxychloroquine and chloroquine have other issues, too: Both fail to block the coronavirus’s preferred route of entry and don’t help patients, researchers discovered last year (SN: 8/2/20).)

Together, those 316 trials cost an estimated $6 billion. That money, time and effort would be better spent on drug candidates that don’t cause the side effect, Shoichet, Pognan and colleagues say.

Helping too few

Even drugs that work as they are supposed to might not be worth giving to everyone who gets COVID-19. Take interferons. These immune system chemicals are among the first to do battle with viruses (SN: 8/6/20). Before the pandemic, researchers at the drug company Synairgen, a spinoff company from the University of Southampton in England, developed an inhaled form of interferon beta and were testing it in people with other respiratory problems, including MERS coronavirus infections. The company quickly began clinical trials to see if interferon beta could help COVID-19 patients, too.

In a trial in 101 hospitalized patients and 120 people who were ill but still at home, participants were randomly assigned to get either inhaled interferon or a placebo. Only two people in the home-care group needed hospitalization, the company said in a preliminary report. Both were in the placebo group. That’s a low percentage of people — about 3 percent — much lower than researchers expected, says Richard Marsden, Synairgen’s CEO. That’s too few to figure out how to target the drug to those who might benefit the most.

The vast majority of people, even people who have health conditions that put them at high risk of complications, don’t get sick enough to need hospitalization. “They have very mild symptoms,” Marsden says. “They need little more than [acetaminophen], a hot water bottle and some sympathy, and they recover very well.”

About 10 percent of people will develop concerning breathlessness and some may end up in the hospital. But it’s so relatively few that you would need to treat a huge number of people just to stop one or two from landing in the hospital, Marsden says. “That’s the quirk of this virus,” he says.

For viruses such as the original SARS or the MERS coronaviruses, which have much higher mortality rates, it makes sense to treat everyone who gets sick right away. But with SARS-CoV-2, the severe breathlessness that sends people to the hospital usually doesn’t show up until the second week of infection. That may be how long it takes for the virus to move down into the lungs and start causing damage there that interferon beta may be able to counter, Marsden hypothesizes (SN: 7/22/2021). So treating people at home earlier might not help anyway.

Results of a Phase III trial for efficacy of interferon beta for hospitalized patients are expected later this year. In the earlier trial, hospitalized people who got the drug were more than twice as likely as those that got a placebo to recover fully to a point where they had no restrictions on their activities, the company reported.

“It’s not worth giving our drug to everybody. Wait until they develop lower respiratory tract illness and then give it to them,” when it may do more good, Marsden says. “It’s a huge ask of a drug that it be so safe and so efficacious that you can give it to everybody.”

Trial troubles

Keeping people out of the hospital in the first place would help relieve the burden on health systems and perhaps prevent people from developing long-term consequences from severe illness. But it’s no surprise that early in the pandemic researchers weren’t focused on at-home treatments.  

“A lot of the scientific community was just trying to save lives, particularly for patients who were in the hospital,” says Esther Krofah, executive director of FasterCures, part of the Milken Institute think tank based in Washington, D.C. “But there was not a full concerted effort on repurposed drugs that could be helpful for mild to moderate cases.”

One reason for that is that hospitalized patients are easier to recruit into studies, says Naggie of the Duke Clinical Research Institute. “You don’t have to convince them to come in and communicate with the team.”

Outpatient studies often have to advertise, set up hotlines, send letters or call people on the phone to find volunteers willing to take part in the trial. And that can set up situations in which multiple trials are competing for participants. As a result, many trials conducted over the past year didn’t enroll enough people to get definitive answers about whether their treatments worked.

“We need to create a much more cohesive clinical trial system in this country,” Krofah says.

That’s beginning to happen. The National Institutes of Health have launched a large trial called ACTIV-6, expected to enroll 13,500 people. It is similar to earlier trials of hospitalized patients that determined that remdesivir, steroids and other treatments can reduce death rates or shave days off hospital stays.

ACTIV-6 will test a battery of existing drugs against a placebo to see if any of them can reduce the chance of people needing hospitalization. The goal is to have five or six, and potentially up to eight “arms” of the trial with all of the drugs being tested at the same time, each in about 600 people, says Naggie, who is one of the study’s principal investigators. People getting the placebo will serve as the comparison group for all of the drugs. First up is the antiparasitic drug ivermectin.

Ivermectin has been used globally for a long time in various forms for treating intestinal parasitic worms, head lice and skin conditions such as rosacea. It’s given to animals to prevent heartworm disease and to treat infections with other parasites. Generally, it is a safe drug, Naggie says.

And there are hints it could work against SARS-CoV-2. The drug had already been shown to limit infections caused by HIV and other RNA viruses, including West Nile, dengue and influenza viruses in lab studies. Researchers in Australia tested ivermectin against SARS-CoV-2 in green monkey cells growing in lab dishes and found that the drug could quickly shut down production of viral RNA, the group reported last year in Antiviral Research.

Clinical trials have pitted ivermectin against COVID-19. But the studies measured success by different standards, with some tracking viral loads or symptom severity, and others tracking time to recovery or death. Some were randomized and placebo-controlled; others didn’t have control groups. Some trials were done in hospitalized people, others in outpatient settings. Some mixed ivermectin with other drugs.

The results varied. Some showed a benefit of the drug; others showed no difference between ivermectin and a placebo or standard care. Those trials did have one thing in common, says Naggie. “None of them are yet definitive. The quality is not as high as we would like it to be.” 

To date, health officials have recommended against taking ivermectin for COVID-19 outside of clinical trials. Even the pharmaceutical company Merck, which makes ivermectin, has said there is no evidence to support the drug as a COVID-19 treatment.

“What that means is please don’t go take your dog’s ivermectin or your horse’s ivermectin. It has not been proven to be an effective remedy for COVID-19,” Naggie says.

Her study will test ivermectin’s effect in people 30 and older who have been sick for 10 days or less. And people don’t have to leave their homes to participate. Study participants will be mailed the pills and will be asked to fill out daily surveys about their symptoms. Perhaps the trial will show once and for all whether ivermectin works as well in people as it does in lab dishes.

A quick-fix pill?

Meanwhile, other treatment trials are already well under way, some of which may announce results before the end of this year. Of particular interest are orally administered drugs, some of which are “looming on the horizon quite quickly,” says Yasmeen Long, director of FasterCures.

Among the most promising is an antiviral drug called molnupiravir (formerly EIDD-2801), The drug mimics a building block of RNA and interferes with the virus’s replication, much like remdesivir does (SN: 8/24/2020). Unlike remdesivir, the new drug is in pill form and can be easily be given to newly diagnosed people.

Merck and Miami-based Ridgeback Biotherapeutics are testing the antiviral in a Phase III trial, which will measure the drug’s efficacy in non-hospitalized people who have at least one risk factor for serious complications from COVID-19. Already the U.S. government has agreed to buy 1.7 million courses of the drug, if the FDA grants it emergency use authorization, Merck announced in a news release. 

Early results of a Phase II trial of safety, dosing and efficacy found that people who took 800 milligrams of molnupiravir twice daily for five days had less virus in their noses than people who got a placebo, researchers reported June 17 at medRxiv.org. Within three days of starting treatment, only 1.9 percent of the 202 people taking 800 mg of molnupiravir had detectable virus in nasal swabs. That compares with 16.7 percent of those taking the placebo.

By day five of treatment, researchers detected no virus in people taking molnupiravir, while 11.1 percent of people on the placebo still had detectable virus in their swabs. If those preliminary results, which have not been reviewed by other scientists yet, hold up, it may mean that the drug could shorten the course of illness, keep people out of the hospital and reduce the chance of spreading the virus to others. 

Other studies, including one testing the antidepressant pill fluvoxamine (SN: 2/1/21) and a large study of other repurposed drugs may also yield easy, early and effective treatments. “Which is great,” Naggie says, because “whether or not one trial is going to change all of clinical practice is questionable.” Having multiple studies of people who are sick at home might “help move the needle on what might be useful,” she says.

Wild Souls
Emma Marris
Bloomsbury, $28

On the Arctic Ocean’s fringe, polar bears stand on ice thinning from human-caused climate change. Without thick ice from which to powerfully pounce on seals, many of these symbols of the wild north can’t eat. Should we feed polar bears to right our wrongs? Or should we leave them alone, even if that means they starve to extinction?

Emma Marris’ Wild Souls prompts readers to grapple with this question and more. An absorbing and nuanced blend of philosophy and science, the book explores what we owe the nonhuman world. Like her 2011 book Rambunctious Garden, which challenged the notion of “pristine wilderness” in a world where humans touch everything (SN: 9/23/11), Wild Souls questions the very concepts of wildness and nature. The result challenges readers to reconsider how they relate to nonhuman animals, from caged creatures to polar bears in the warming north.

Marris guides readers through a series of case studies, from Indigenous hunting practices to municipal zoos, all brought to life through attentive on-the-ground reporting. Running through these examples is a central ethical tension: How do we weigh the tangible moral value of an individual sentient creature who can suffer against the more abstract value of species or ecosystems, which are of course unfeeling but rouse such depths of emotion in us when they are threatened or lost?

Islands are a front line of this conflict, where life that’s blossomed in isolation is threatened by species we’ve introduced. Marris examines efforts, from the Galápagos to New Zealand, to kill (often painfully with poison) millions of individual mice, rats and other creatures in the name of preserving species deemed more important. 

Marris is frank on where she stands on certain issues, arguing, for example, that zoos are immoral. She also asks whether it’s ever right to save a species like the California condor — which once soared above most of North America but dwindled to just a handful of individuals in the 1980s — by caging them for captive breeding.

The book makes a clear case for the moral value of individual sentient creatures, providing a rundown of the latest science that dissolves the distinct line often drawn between humans and nonhumans. These include studies that suggest fish feel pain and that rats help fellow rats in need because they experience emotions (SN: 1/12/21).

Defining the objective, inherent value of species proves trickier. “There’s something precious in what we call ‘nature,’ in the flow of energy, in the will to survive,” she writes. “But I cannot present overwhelming arguments that this is true. I can only passionately assert it.”

In the end, Marris finds no set formula for making ethical choices about animals’ fates. Instead, readers may realize something profound: There are no perfect ways to act ethically toward all animals and all species when incommensurable values collide. As we try to mend the mess we’ve made of nature, all we can do is act with thoughtful humility.

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We know quite a lot about stars. After centuries of pointing telescopes at the night sky, astronomers and amateurs alike can figure out key attributes of any star, like its mass or its composition.

To calculate a star’s mass, just look it its orbital period and do a bit of algebra. To determine what it’s made of, look to the spectrum of light the star emits. But the one variable scientists haven’t quite cracked yet is time.

“The sun is the only star we know the age of,” says astronomer David Soderblom of the Space Telescope Science Institute in Baltimore. “Everything else is bootstrapped up from there.”

Even well-studied stars surprise scientists every now and then. In 2019 when the red supergiant star Betelgeuse dimmed, astronomers weren’t sure if it was just going through a phase or if a supernova explosion was imminent. (Turns out it was just a phase.) The sun also shook things up when scientists noticed that it wasn’t behaving like other middle-aged stars. It’s not as magnetically active compared with other stars of the same age and mass. That suggests that astronomers might not fully understand the timeline of middle age.

Calculations based on physics and indirect measurements of a star’s age can give astronomers ballpark estimates. And some methods work better for different types of stars. Here are three ways astronomers calculate the age of a star.

Hertzsprung-Russell diagrams

Scientists do have a pretty good handle on how stars are born, how they live and how they die. For instance, stars burn through their hydrogen fuel, puff up and eventually expel their gases into space, whether with a bang or a whimper. But when exactly each stage of a star’s life cycle happens is where things get complicated. Depending on their mass, certain stars hit those points after a different number of years. More massive stars die young, while less massive stars can burn for billions of years.

At the turn of the 20th century, two astronomers — Ejnar Hertzsprung and Henry Norris Russell — independently came up with the idea to plot stars’ temperature against their brightness. The patterns on these Hertzsprung-Russell, or H-R, diagrams corresponded to where different stars were in that life cycle. Today, scientists use these patterns to determine the age of star clusters, whose stars are thought to have all formed at the same time.

The caveat is that, unless you do a lot of math and modeling, this method can be used only for stars in clusters, or by comparing a single star’s color and brightness with theoretical H-R diagrams. “It’s not very precise,” says astronomer Travis Metcalfe of the Space Science Institute in Boulder, Colo. “Nevertheless, it’s the best thing we’ve got.”

Tell us what you think of this video in a short survey.

Rotation rate

By the 1970s, astrophysicists had noticed a trend: Stars in younger clusters spin faster than stars in older clusters. In 1972, astronomer Andrew Skumanich used a star’s rotation rate and surface activity to propose a simple equation to estimate a star’s age: Rotation rate = (Age) ^-½.

This was the go-to method for individual stars for decades, but new data have poked holes in its utility. It turns out that some stars don’t slow down when they hit a certain age. Instead they keep the same rotation speed for the rest of their lives.

“Rotation is the best thing to use for stars younger than the sun,” Metcalfe says. For stars older than the sun, other methods are better.

Stellar seismology

The new data that confirmed rotation rate wasn’t the best way to estimate an individual star’s age came from an unlikely source: the exoplanet-hunting Kepler space telescope. Not just a boon for exoplanet research, Kepler pushed stellar seismology to the forefront by simply staring at the same stars for a really long time.

Watching a star flicker can give clues to its age. Scientists look at changes in a star’s brightness as an indicator of what’s happening beneath the surface and, through modeling, roughly calculate the star’s age. To do this, one needs a really big dataset on the star’s brightness — which the Kepler telescope could provide.

“Everybody thinks it was all about finding planets, which was true,” Soderblom says. “But I like to say that the Kepler mission was a stealth stellar physics mission.”

This approach helped reveal the sun’s magnetic midlife crisis and recently provided some clues about the evolution of the Milky Way. Around 10 billion years ago, our galaxy collided with a dwarf galaxy. Scientists have found that stars left behind by that dwarf galaxy are younger or about the same age as stars original to the Milky Way. Thus, the Milky Way may have evolved more quickly than previously thought.

As space telescopes like NASA’s TESS and the European Space Agency’s CHEOPS survey new patches of sky, astrophysicists will be able to learn more about the stellar life cycle and come up with new estimates for more stars.

Aside from curiosity about the stars in our own backyard, star ages have implications beyond our solar system, from planet formation to galaxy evolution — and even the search for extraterrestrial life.

“One of these days — it’ll probably be a while — somebody’s going to claim they see signs of life on a planet around another star. The first question people will ask is, ‘How old is that star?’” Soderblom says. “That’s going to be a tough question to answer.”

A century ago, the Milky Way galaxy was the entirety of the known universe. We had no idea what made the stars shine, and only one star — our own sun — was known to harbor any planets. Of those planets, humans had explored only one: Earth.

“The stellar universe, as we know it … is a flattened, watch-shaped organization of stars and nebulae,” astronomer Harlow Shapley wrote in Science News Bulletin, the earliest version of Science News, in August 1921 (SN: 8/8/1921, p. 3). That sparkling pocket watch was the Milky Way, and at the time Shapley wrote this, astronomers were just beginning to conceive that anything at all might lie beyond it.

Today, spacecraft have flown by every one of the solar system’s planets, taking close-ups of their wildly alien faces. The solar system, it turns out, contains a cornucopia of small rocky and icy bodies that have challenged the very definition of a planet. Thousands of planets have been spotted orbiting other stars, some of which may have the right conditions for life to thrive. And the Milky Way, we now know, is just one of billions of galaxies.

The last 100 years have brought a series of revolutions in astronomy, each one kicking Earth a bit farther from the center of things. Along the way, people have not exactly been receptive to these blows to our home planet’s centrality. In 1920, the question of whether there could be other “island universes” — galaxies — was the subject of the Great Debate between two astronomers. In the 1970s, when Mars was shown to have a pink sky, not blue, reporters booed. Their reaction “reflects our wish for Mars to be just like the Earth,” said astronomer Carl Sagan afterward. And in the 1990s, astronomers almost missed extrasolar planets hiding in their data because they had tailored their search techniques to find planets more like those in our own solar system.

But turning our focus from Earth has opened our minds to new possibilities, new universes, new places where life might exist. The next century of astronomy could bring better views of our cosmic origins and new strategies for finding worlds that other creatures call home.

The misperceptions of decades past suggest scientists should be careful when predicting just what we’ll find in the future.

“You learn a lot of humility in this business,” says planetary scientist Candice Hansen of the Planetary Science Institute, based in Tucson. “You always learn a lot more when you’re wrong than when you’re right.”

More than the Milky Way

At the turn of the 20th century, conventional wisdom held that the Milky Way stood alone. It contained stars, sometimes organized in clusters, and fuzzy patches of light known as nebulae. That was about it.

Some nebulae had spiral structures, “appearing in the telescope like vast Fourth-of-July pinwheels,” as Science News Letter, the predecessor of Science News, described them in 1924. In the 18th century, German philosopher Immanuel Kant had described nebulae as “higher universes,” or, “so to speak, Milky Ways.” But by the early 1900s, most astronomers thought that drawing that parallel was ridiculous.

“No competent thinker,” wrote historian of astronomy Agnes Clerke in 1890, can “maintain any single nebula to be a star system of coordinate rank with the Milky Way.”

By the 1920s, though, that view was already being challenged. As early as 1914, astronomer Heber Curtis of Lick Observatory in California argued that spiral nebulae are not part of the Milky Way, but rather “inconceivably distant galaxies of stars or separate stellar universes so remote that an entire galaxy becomes but an unresolved haze of light.”

Around the same time, Shapley, of Mount Wilson Observatory in California, began to prove that the Milky Way itself was inconceivably vast.

Shapley built on work by Henrietta Leavitt, one of a group of women “computers” at Harvard University who pored over photographic plates capturing the night sky. In studying photographs of the Magellanic Clouds, which we now know are two small galaxies that orbit the Milky Way, Leavitt noticed that certain stars varied in brightness over time, some of them in a peculiar way. “It is worthy of notice,” she wrote in 1908, that “the brighter variables have the longer periods.” In other words, brighter stars twinkled more slowly.

That meant that these variable stars, called Cepheids, could be used to estimate cosmic distances. It’s hard to tell how far away a cosmic object truly is — bright-looking stars could be intrinsically dim but close, while faint-looking stars could be intrinsically bright but distant. But all the Cepheids within the same cloud should be roughly the same distance from Earth. That meant “their periods are apparently associated with their actual emission of light,” Leavitt wrote in 1912. To figure out any Cepheid’s true brightness, all an astronomer had to do was measure its twinkling speed. It was a short step from there to figuring out its distance.

Shapley put this fact to use just a few years later, measuring distances to Cepheids within globular clusters of stars to figure out the sun’s position in the Milky Way. To his surprise, the sun was not in the center of the galaxy but off to one side. The Milky Way’s starry disk was also about 10 times wider than previous astronomers had assumed: about 300,000 light-years across, according to his calculations. (He overshot a bit; modern astronomers think it’s somewhere between 120,000 and 200,000 light-years.)

He and Curtis took their opposing views to the public at a meeting of the National Academy of Sciences in Washington, D.C., in April 1920, in an event that became known as the Great Debate. Each had 40 minutes to present their views on whether there is only one or several universes — what we now think of as galaxies.

Shapley, who was in his 30s and considered a rising star in the field, went first. A former journalist who reportedly was uncomfortable speaking to crowds, he read his argument from a typewritten script. He barely touched on the question of other universes, focusing instead on his new measurements of the Milky Way’s size. The implication was that the Milky Way was too large for other galaxies to make sense.

Curtis was an older, well-respected authority on spiral nebulae, as well as a gifted speaker. He argued for the then-standard view that the Milky Way was much smaller than Shapley supposed. But even a large Milky Way shouldn’t negate the possibility of other, equally large galaxies, he argued. The spectra of light coming from spiral nebulae was similar enough to that of the Milky Way that they could be similar objects, he maintained.

Both astronomers were partly right, and partly wrong.

Galaxies come into view

The Great Debate was resolved by a young astronomer named Edwin Hubble working at Mount Wilson. Hubble also used Leavitt’s Cepheid variable technique to measure cosmic distances, this time by finding the variable stars in the spiral nebulae themselves.

Hubble started observing the Andromeda nebula, one of the brightest nebulae on the sky, in the fall of 1923. He used Mount Wilson’s 60-inch telescope and its 100-inch telescope, then the world’s largest. Over the next year or so, he studied 35 Cepheids in Andromeda and a different nebula called Triangulum. Their periods were long enough that the nebulae had to be on the order of a million light-years away for the stars to appear so faint. (We now know it’s more like 2.5 million light-years to Andromeda and 2.7 million to Triangulum.)

“Measuring the distance to Andromeda was a big deal because it was the first evidence that there are galaxies beyond our own,” says astronomer Emily Levesque of the University of Washington in Seattle. “It changed what we thought of as the shape of our universe.”

A few hints that the Milky Way was not alone had cropped up before that, but Hubble’s finding clinched it. Even if the Milky Way was as big as Shapley claimed, Andromeda lay outside its borders. When Shapley received Hubble’s paper, he reportedly said, “Here is the letter that destroyed my universe.”

Science News Letter reported Hubble’s finding under the headline “Sky Pinwheels Are Stellar Universes 6,000,000,000,000,000,000 Miles Away” in December 1924 (SN: 12/6/24, p. 2).

“It seems probable that many of the smaller spiral nebulae are still more remote and appear smaller on this account,” the story quotes Hubble as saying. “The portion of the universe within the range of our investigation consists of vast numbers of stellar galaxies comparable to our own, scattered about through nearly empty space and separated from one another by distances of inconceivable magnitude.” Here at last was the modern view of the universe.

By the end of the decade, Hubble had not only shown that the spiral nebulae were “island universes,” he also had begun to classify different galaxy types and think about how they evolved over time. What’s more, he showed that galaxies were flying away from each other at speeds proportional to their distance. In other words, the universe was expanding.

By the end of the century, astronomers knew that the universe was dotted with billions of galaxies of all shapes and sizes. In April 1990, NASA launched the first optical space telescope into Earth’s orbit, giving the world a new perspective on space.

“Instead of these blurry blobs from even the best mountaintop observatories on our planet,” says planetary scientist Jim Bell of Arizona State University in Tempe, “all of a sudden the entire realm of solar system, galaxy, extragalactic … was opened up by getting above the atmosphere.”

NASA named the telescope after the scientist who opened astronomers’ minds to the existence of such a universe: the Hubble Space Telescope.

The images it has captured over 30 years of operations — star clusters, galaxies and nebulae — are so iconic they are printed on everything from socks and coffee mugs to high fashion runway designs. The telescope itself was recently immortalized in Lego form.

“It’s the one that literally everyone has heard of,” says Levesque. Most people today think Hubble was “the guy who built the telescope.”

One image from early on in the space telescope’s tenure stands out. In December 1995, the telescope’s director, Robert Williams, decided to train the observatory on a tiny, dark patch of sky near the handle of the Big Dipper for 10 consecutive days. The resulting portrait of this featureless bit of sky revealed thousands of previously unknown galaxies sending their light from farther away than astronomers had ever seen before (SN: 1/20/96, p. 36). The universe as Edwin Hubble had imagined it, chock-full of island universes, was captured in one hard look.

As for Henrietta Leavitt, she missed out on the recognition she deserved for helping knock the Milky Way from its central perch. A Swedish mathematician wrote to her in 1925 saying that her work “has impressed me so deeply that I feel seriously inclined to nominate you to the Nobel Prize in physics for 1926.” He received a reply from Shapley, by then director of the Harvard College Observatory: Leavitt had died four years earlier.

Steps to Mars

The first liquid-fueled rockets, precursors to the ones that later carried robots and people into space, launched in the 1920s. A century later, robots have flown past, orbited or landed on every planetary body that was known in 1920, and a few that weren’t. People have walked on the moon and have lived in space for more than a year at a time. And serious talks about sending people to Mars are in the works.

NASA used to explore other worlds in a clear order, first observing with telescopes and then carrying out increasingly complex missions: flybys, orbiters, landers, rovers, then people and sample returns. “We’ve taken that entire progression on the moon, in [the last] century,” Bell says. “Sometime in this new century, we’ll add Mars to that list. All the rest of the solar system, we’ve got large chunks of that matrix checked off.”

After the Soviet Union launched the first artificial satellite, Sputnik 1, in 1957, space launches came fast and furious. Many were demonstrations of political and military might. But a lot of them had scientific merit, too. The Soviet Luna 3 spacecraft photographed the farside of the moon in 1959 — shortly after NASA’s founding. Spacecraft flew past Venus and Mars in the 1960s, sending back the first closeup data on their alien atmospheres and surfaces.

That same decade, humans landed on the moon and brought back rocks, opening a wide and detailed window into the history of the solar system. The lunar samples from the Apollo missions gave scientists a way to figure out how old planetary surfaces are around the solar system, taught us that the entire inner solar system was bombarded with impacts in its youth and gave us an origin story for the moon (SN: 7/6/19 & 7/20/19, p. 18).

“Until we started the space program, we really had no idea what the geology was on other places,” says Hansen of the Planetary Science Institute. “Early in the century, they were still debating whether the craters on the moon were impact craters or volcanic calderas. Even right there in our own backyard, we didn’t know what was going on.”

And extraterrestrial geology was surprising. Without meaning to, planetary scientists had based a lot of their expectations for other worlds on the Earth. The cover of Science News from June 1976, the month before NASA’s Viking 1 lander became the first long-lived spacecraft to land softly on Mars, showed Mars with a Cheez Whiz–colored desert under a clear blue sky. In the sleep-deprived rush to release the first color images sent back by Viking 1, scientists processed the image to produce a blue sky there, too.

But the day after the landing, James Pollack of the imaging team told reporters that the Martian sky was actually pink, probably thanks to scattered light from dust particles suspended in the air.

“When we found the sky of Mars to be a kind of pinkish-yellow rather than the blue which had erroneously first been reported, the announcement was greeted by a chorus of good-natured boos from the assembled reporters,” Sagan later wrote in the introduction to his popular book Cosmos. “They wanted Mars to be, even in this respect, like the Earth.”

Still, the Viking 1 and 2 landings brought Mars down to Earth, so to speak. “Mars had become a place,” Viking project scientist Gerald Soffen said in an interview for a NASA historical project published in 1984. “It went from a word, an abstract thought, to a real place.”

In some ways, the Viking landers’ views of Mars were disappointing. The mission’s central goal was explicitly to search for microbial life. It was “a long shot,” journalist Janet L. Hopson wrote in Science News in June 1976 (SN: 6/5/76, p. 374). But “even if no signs of life appear, [biologists] stand to gain their first real perspective on terrestrial biochemistry, life origins and evolution.”

The results of the Viking mission’s life-detection experiments were inconclusive, a finding almost worse than a true negative.

NASA subsequently pulled back from seeking life directly. The next 45 years of Mars missions searched for signs of past water, potentially habitable environments and organic molecules, instead of living organisms. All of those features turned up in data from the Spirit, Opportunity and Curiosity rovers in the 2000s and 2010s.

Now, NASA’s Perseverance rover, which landed in February 2021, is hunting for signs of ancient microbial life. The rover will cache rock samples that a future mission will bring back to Earth. And the joint Russian and European space agencies’ ExoMars rover — named Rosalind Franklin, after the chemist whose work was central to discovering DNA’s structure — aims to seek molecular signatures of life on Mars and just below the surface after it launches in 2022.

Sagan predicted in 1973 that if he had been born 50 years in the future, the search for life on Mars would have already been completed. Today, 48 years later, we’re still looking.

Exotic moons

The year after the Vikings landed on Mars, another pair of spacecraft launched to check almost the entire rest of the solar system off scientists’ must-see list. Astronomers realized that in 1977, the planets would line up in such a way that a spacecraft launched that year could reach Jupiter, Saturn, Uranus and Neptune one by one, stealing a little angular momentum from each world as it went along. The mission was dubbed Voyager (SN: 8/27/77, p. 132).

“There’s never been anything like it, and there never will be again,” says Bell, of Arizona State. “It was comparable to the voyages of Magellan or Darwin or Lewis and Clark. Just an absolutely profound mission of discovery that completely changed the landscape of planetary science in this century.”

Voyager’s views of the outer solar system forced scientists to think outside of the “Earth box,” says Hansen, who worked on the mission. “The Voyager imaging team, bless their hearts, they would make predictions and then they’d be wrong,” she says. “And we would learn something.”

Hansen recalls chatting with a member of the imaging team when the spacecraft was approaching Jupiter and its dozens of moons. “He said, ‘Candy, we will see craters on [moons] Io and Europa, because we know from the density that those are rocky worlds. But not on Ganymede and Callisto, because those are ice,’ ” she recalls. Instead, the images showed Ganymede and Callisto were covered in craters. “That was an aha moment — ice is going to act like rock at those temperatures.” Meanwhile, ocean-swathed Europa and molten Io had almost no craters.

The moons of Jupiter presented “a whole, previously unimagined family of exotic worlds, each radically different not only from its companions, but also from everything else in the planet-watcher’s experience,” journalist Jonathan Eberhart wrote in Science News in April 1980 (SN: 4/19/80, p. 251).

Before 1979, Earth was the only geologically active, rocky world scientists knew about. But Voyager changed that view, too. A member of Voyager’s optical navigation team, Linda Morabito, spotted an odd, mushroom-shaped feature extending off the edge of Io while she was trying to plot the spacecraft’s position on March 9, 1979. She consulted with the science team, and they soon realized they were looking at a gigantic volcanic plume. Io was erupting in real time.

Three planetary scientists had predicted Io’s fire before the plumes were discovered. The three suggested the moon was heated by a gravitational tug-of-war between Jupiter and one or two of its other moons, Europa and Ganymede.

But most of the planetary science community was stunned. “We take gravity for granted here. It keeps our feet on the ground,” Hansen says. “But gravity molds and shapes so many things in so many unexpected ways.”

Voyager and subsequent missions to the outer planets, like Galileo at Jupiter in the 1990s and Cassini at Saturn in the 2000s, transformed our view of the solar system in another profound way. They revealed several surprising parts of the solar system where life might exist today.

Voyager hinted that Europa might have a liquid water ocean beneath an icy shell. Galileo strengthened that idea, and suggested the ocean might be salty and have contact with the moon’s rocky core, which could provide chemical nutrients for microbial life. NASA is now developing a mission to fly past Europa. “I will not be surprised if life is somehow discovered on Europa in my lifetime, or in this century,” Bell says.

Shortly after the Cassini spacecraft arrived at Saturn in 2004, scientists realized that the tiny moon Enceladus vents dramatic plumes of water vapor, dust and ice crystals into space from a hidden subsurface sea. That moon also looks like a good place for life.

If the last century of exploring the solar system was about coming to grips with alien geology, Hansen says, this coming century is going to be about oceanography — getting a grip on the strange seas in our own solar system.

“I think that’s going to shape a lot of the research going forward,” Hansen says. Now that it’s clear these moons have oceans, researchers will ask if they are habitable, and eventually, if they are inhabited.

Exoplanets detected

The first planet spotted outside our solar system — an exoplanet — was so different from anything in our solar system that astronomers weren’t hunting for anything like it.

“Knowing that there are actually planets around other stars now seems so trivial to say,” says exoplanet observer Debra Fischer of Yale University. “But we had arguments in 1995 about whether other stars have planets.”

So when astronomer Michel Mayor of the Geneva Observatory turned his spectrograph on the sky in April 1994, he kept quiet about his hopes of finding true exoplanets. He was more likely to find brown dwarfs, failed stars that never grew massive enough to burn hydrogen.

His instrument used a clever new way to hunt for other worlds, called the radial velocity technique. Previous exoplanet hunters had looked directly for a star’s motion in response to the gravity of an orbiting planet, watching to see if the star would move back and forth in the sky. That technique had led to several planetary claims, even dating back to 1855, but none of them had held up. Those motions are tiny; Jupiter’s influence moves the sun by just 12 meters per second.

Instead, Mayor and others studied a shift in the wavelength of starlight as a star moved to and fro. As a star approaches us, the light shifts to shorter, or bluer, wavelengths; as it moves away, the light grows redder. Calculating the velocity of a star’s back-and-forth motion, astronomers could figure out the minimum mass and length of the year of whatever was tugging that star.

The shifts Mayor was looking for were still minuscule. The search was considered futile, and fringe — like looking for little green men. So astronomers who explicitly claimed to be searching for planets had a hard time scheduling observations at telescopes. Brown dwarfs, on the other hand, were considered legitimate science, and would be easier to detect.

So the world was astounded when, in October 1995, Mayor and his student Didier Queloz reported strong evidence not of a brown dwarf, but of a true planet orbiting the sunlike star 51 Pegasi, about 50 light-years from our solar system.

The new planet was weird. It seemed to be about half the mass of Jupiter, too puny to be a brown dwarf. But it orbited the star once every 4.23 Earth days, putting it incredibly close to its star. There’s nothing like that in our solar system, and astronomers had no idea how it could exist.

“The news flashed through the astronomical community like a lightning bolt,” wrote journalist Ron Cowen in Science News, in the first of three stories on the new planet he would write within a month (SN: 10/21/95, p. 260).

51 Peg b, as it came to be known, launched a new era. “It means planets exist around other sunlike stars, we can find them, and they might be the exciting ones,” says Yale anthropologist Lisa Messeri, who has studied how astronomers create worlds out of pixels and spectra. “Firsts are exciting because they promise there will be seconds and thirds and fourths.”

The search was on. A group from San Francisco quickly found two more planets hiding in data the researchers hadn’t finished analyzing yet. Those next two planets, 70 Vir b and 47 UMa b, were also more massive and closer to their stars than expected.

The existence of these three worlds, which were named hot Jupiters because their close-in orbits should make them sizzle, upended the paradigm for what a planet could be like. Clearly, our solar system was not the template for the universe.

Yet for a few years after 51 Peg b was announced, astronomers debated whether the planet was really there. Maybe the star’s apparent back-and-forth was just its outer atmosphere breathing in and out. Those debates waned as more planets were discovered, but it took a new technique to really convince everyone.

Astronomers had predicted at least back to the 1850s that some planets would pass in front of their stars from the perspective of Earth. As it crossed, or transited, the face of its star, a planet could reveal its presence by blocking a little bit of the star’s light.

But if other solar systems are like ours, transits would be incredibly difficult to detect. Our planets are too small and too far from the sun to cast a large shadow. Hot Jupiters, on the other hand, should block way more of a star’s light than any planets in our solar system. With the discovery of 51 Peg b, transits seemed not only possible to detect, but almost easy.

The first transiting extrasolar planet revealed itself in 1999, when then-Harvard graduate student David Charbonneau drove to Colorado to do his thesis work with astronomer Tim Brown. Brown had built a tiny telescope on a friend’s farm north of Boulder, setting up the computers in a repurposed turkey coop, to search for transiting planets. By the time Charbonneau arrived, however, the farm had been sold and the telescope relocated to a lab site.

To practice the technique, Charbonneau aimed Brown’s telescope at a star, called HD 209458, that already had a suspected planet. The star’s light dimmed by about 1 percent, and then it shone bright again. That was a clear sign of a planet about 32 percent wider than Jupiter.

That discovery ended all doubts about the existence of exoplanets, says Fischer, who had worked with the exoplanet-hunting group in San Francisco. “It happened like that,” Fischer says, with a finger snap. The combined size and mass of the planet unambiguously ruled out brown dwarfs or other exotic explanations. “It walks like a Jupiter, talks like a Jupiter, it’s a Jupiter.”

There was another advantage to the transit method: It can show the composition of a planet’s atmosphere. Planets detected by the wobble technique were “little more than phantoms,” Cowen wrote in Science News in 2007. They were too small to be seen, and too close to the star to be photographed directly.

“Everyone had assumed that if you wanted to [detect] the atmosphere of an extrasolar planet, you’d have to image it,” Charbonneau told Science News. But starlight filtering through a transiting planet’s sky could reveal what gases surround the alien world without the need for a snapshot.

Hunt for habitable planets

Transits soon overtook wobbles as the most fruitful planet-finding strategy. That was mostly thanks to the launch of NASA’s Kepler space telescope in March 2009.

Kepler’s mission was explicitly about finding other Earths. For nearly four years, the telescope stared at 170,000 stars in a single patch of sky to catch as many transiting planets as it could. In particular, its operators were hoping for Earth-sized planets in Earthlike orbits around sunlike stars — places where life could conceivably exist.

The years that followed were a boom time for planet finders. By the end of its nearly 10-year run, Kepler had confirmed almost 2,700 planets and thousands more potential planets. Findings went beyond the hot Jupiters to worlds the size of Earth and planets in the “habitable zone,” where temperatures could be right for liquid water.

Discoveries came so quickly that a single new world stopped being a news story. Kepler’s data shifted from revealing new worlds one by one to taking an exoplanet census. It showed that hot Jupiters are not actually the most common type of planet; they were just the easiest ones to spot. The most common type makes no appearance in our solar system: worlds between the size of Earth and Neptune, which may be rocky super-Earths or gaseous mini-Neptunes.

And Kepler revealed that there are more planets in the galaxy than stars. Every one of the billions and billions of stars in the Milky Way should have at least one world in its orbit.

But the telescope never really achieved the goal of finding another Earth. Kepler required three transits to confirm a world’s existence. That means the telescope had to stare for at least three years to find a planet orbiting at Earth’s exact distance.

By 2013, after four years of observing, half of Kepler’s stabilizing reaction wheels had failed. The telescope couldn’t maintain its unblinking view of the same part of the sky. Mission scientists cleverly reprogrammed the telescope to look at other stars for shorter spans of time. But most of the planets found there orbited closer to their stars than Earth does, meaning they couldn’t be Earth twins.

Finally, Kepler ran out of fuel in 2018, with no true Earth analog in sight.

Messeri recalls an exoplanet conference at MIT in 2011 where a lot of the conversation was about finding a twin of Earth.

“It was a peak of excitement — maybe we’re going to find this planet in the next three years, or five years. It felt close,” she says. “What’s interesting is, in the 10 years since then, it still feels that close.”

But astronomers had already realized they might not need a true Earth analog to find a planet where life could exist. Rocky worlds orbiting smaller, dimmer stars than the sun are easier to find, and might be just as friendly to life.

Charbonneau again was ahead of the curve, having started a program called MEarth in 2008 to hunt for habitable planets around puny M dwarf stars using eight small telescopes in Arizona (plus another eight in Chile that were added in 2014). Within six months, Charbonneau and colleagues had found a super-Earth dubbed GJ 1214b that is probably a water world — maybe a bit too wet for life.

The European Southern Observatory started the TRAPPIST, for TRAnsiting Planets and PlanetesImals Small Telescope, survey from La Silla, Chile, in 2010. Another telescope, at Oukaïmeden Observatory in Morocco, came online to search for planets orbiting Northern Hemisphere stars in 2016. Among that survey’s discoveries is the TRAPPIST-1 system of seven Earth-sized planets orbiting a single M dwarf star, three of which might be in the habitable zone (SN: 3/18/17, p. 6).

NASA’s successor to Kepler, TESS, or Transiting Exoplanet Survey Satellite, has been scanning the entire sky since April 2018 for small planets orbiting bright nearby stars, including M dwarfs. It spotted more than 2,200 potential planets in its first full-sky scan, scientists announced in March 2021.

These days, astronomers are joining up with scientists across disciplines, from planetary scientists who study hypothetical exoplanet geology to microbiologists and chemists who think about what kinds of aliens could live on those planets and how to detect those life-forms. That’s a big shift from even 10 years ago, Messeri says. In the early 2010s, no one was talking about life.

“You weren’t allowed to say that,” she says. “Astronomers would whisper it to me during fieldwork, but this was not a search for aliens.”

Exoplanet astronomy is on firmer ground now. Its leading figures have won MacArthur “genius” grants. Pioneer planet finders Mayor and Queloz won the 2019 Nobel Prize in physics. The work is no longer hidden away in conferences that are actually about stars. “It doesn’t have to legitimize itself anymore,” Messeri says. “It’s a real science.”

The promise that transiting planets can reveal the contents of their alien atmospheres may soon be fulfilled. NASA’s James Webb Space Telescope may launch this year, after many years of delays. One of its first tasks will be to probe the atmospheres of transiting planets, including those of TRAPPIST-1.

If anything is alive on those absolutely alien, unearthly worlds, maybe the next century will bring it to light.