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“My first and biggest wish is that we had known early that Covid-19 was airborne,”

, “Once you’ve realized that, it informs an entirely different strategy for protection.” Masking, ventilation and air cleaning become key, as well as avoiding high-risk encounters with strangers, he says.

Instead of washing our produce and wearing hand-sewn cloth masks, we could have made sure to avoid superspreader events and worn more-effective N95 masks or their equivalent. “We could have made more of an effort to develop and distribute N95s to everyone,” says Dr. Volckens. “We could have had an Operation Warp Speed for masks.”

We didn’t realize how important clear, straight talk would be to maintaining public trust. If we had, we could have explained the biological nature of a virus and warned that Covid-19 would change in unpredictable ways.  

In the face of a pandemic, he says, the public needs an early basic and blunt lesson in virology

“The science is really important, but if you don’t get the trust and communication right, it can only take you so far,”

and mutates, and since we’ve never seen this particular virus before, we will need to take unprecedented actions and we will make mistakes, he says.

Since the public wasn’t prepared, “people weren’t able to pivot when the knowledge changed,”

By the time the vaccines became available, public trust had been eroded by myriad contradictory messages—about the usefulness of masks, the ways in which the virus could be spread, and whether the virus would have an end date.

, the absence of a single, trusted source of clear information meant that many people gave up on trying to stay current or dismissed the different points of advice as partisan and untrustworthy.

We didn’t know how difficult it would be to get the basic data needed to make good public-health and medical decisions. If we’d had the data, we could have more effectively allocated scarce resources

For much of the pandemic, doctors, epidemiologists, and state and local governments had no way to find out in real time how many people were contracting Covid-19, getting hospitalized and dying

Doctors didn’t know what medicines worked. Governors and mayors didn’t have the information they needed to know whether to require masks. School officials lacked the information needed to know whether it was safe to open schools.

people didn’t know whether it was OK to visit elderly relatives or go to a dinner party.

just months before the outbreak of the pandemic, the Council of State and Territorial Epidemiologists released a white paper detailing the urgent need to modernize the nation’s public-health system still reliant on manual data collection methods—paper records, phone calls, spreadsheets and faxes.

While the U.K. and Israel were collecting and disseminating Covid case data promptly, in the U.S. the CDC couldn’t. It didn’t have a centralized health-data collection system like those countries did, but rather relied on voluntary reporting by underfunded state and local public-health systems and hospitals.

doctors and scientists say they had to depend on information from Israel, the U.K. and South Africa to understand the nature of new variants and the effectiveness of treatments and vaccines. They relied heavily on private data collection efforts such as a dashboard at Johns Hopkins University’s Coronavirus Resource Center that tallied cases, deaths and vaccine rates globally.

With good data, Dr. Ranney says, she could have better managed staffing and taken steps to alleviate the strain on doctors and nurses by arranging child care for them.

To solve the data problem, Dr. Ranney says, we need to build a public-health system that can collect and disseminate data and acts like an electrical grid. The power company sees a storm coming and lines up repair crews.

If we’d known how damaging lockdowns would be to mental health, physical health and the economy, we could have taken a more strategic approach to closing businesses and keeping people at home.

t many doctors say they were crucial at the start of the pandemic to give doctors and hospitals a chance to figure out how to accommodate and treat the avalanche of very sick patients.

The measures reduced deaths, according to many studies—but at a steep cost.

The lockdowns didn’t have to be so harmful, some scientists say. They could have been more carefully tailored to protect the most vulnerable, such as those in nursing homes and retirement communities, and to minimize widespread disruption.

Lockdowns could, during Covid-19 surges, close places such as bars and restaurants where the virus is most likely to spread, while allowing other businesses to stay open with safety precautions like masking and ventilation in place.  

If England’s March 23, 2020, lockdown had begun one week earlier, the measure would have nearly halved the estimated 48,600 deaths in the first wave of England’s pandemic

If the lockdown had begun a week later, deaths in the same period would have more than doubled

The key isn’t to have the lockdowns last a long time, but that they are deployed earlier,

It is possible to avoid lockdowns altogether. Taiwan, South Korea and Hong Kong—all countries experienced at handling disease outbreaks such as SARS in 2003 and MERS—avoided lockdowns by widespread masking, tracking the spread of the virus through testing and contact tracing and quarantining infected individuals.

Had we known that even a mild case of Covid-19 could result in long Covid and other serious chronic health problems, we might have calculated our own personal risk differently and taken more care.

Early in the pandemic, public-health officials were clear: The people at increased risk for severe Covid-19 illness were older, immunocompromised, had chronic kidney disease, Type 2 diabetes or serious heart conditions

t had the unfortunate effect of giving a false sense of security to people who weren’t in those high-risk categories. Once case rates dropped, vaccines became available and fear of the virus wore off, many people let their guard down, ditching masks, spending time in crowded indoor places.

it has become clear that even people with mild cases of Covid-19 can develop long-term serious and debilitating diseases. Long Covid, whose symptoms include months of persistent fatigue, shortness of breath, muscle aches and brain fog, hasn’t been the virus’s only nasty surprise

In February 2022, a study found that, for at least a year, people who had Covid-19 had a substantially increased risk of heart disease—even people who were younger and had not been hospitalized

respiratory conditions.

Some scientists now suspect that Covid-19 might be capable of affecting nearly every organ system in the body. It may play a role in the activation of dormant viruses and latent autoimmune conditions people didn’t know they had

 A blood test, he says, would tell people if they are at higher risk of long Covid and whether they should have antivirals on hand to take right away should they contract Covid-19.

If the risks of long Covid had been known, would people have reacted differently, especially given the confusion over masks and lockdowns and variants? Perhaps. At the least, many people might not have assumed they were out of the woods just because they didn’t have any of the risk factors.

he started receiving death threats. People said they wished he and his family had been killed by drug lords, told him that “sooner or later your punishment will arrive” and proposed that he be nailed into a coffin or run over by a cement roller.

Mr. Moreno, who grew up in Colombia, began working as a researcher in a computer science and robotics lab in Paris in 1983; the career that followed involved creating a start-up, meeting the Dalai Lama and being named a knight of the Légion d’Honneur. His work has won several awards and spanned many fields — automotive, medical, nuclear, military, even home goods.

Many of the recent threats have been directed at scientists studying Covid-19. In a survey of 321 such scientists who had given media interviews, the journal Nature found that 22 percent had received threats of physical or sexual violence and 15 percent had received death threats

Last year, an Austrian doctor who was a vocal supporter of vaccines and a repeated target of threats died by suicide.

increasingly, even professors and researchers without much of a public persona have faced intimidation from extremists and conspiracy theorists.

Around 2010, he started thinking about how technology could help create sustainable cities. Eventually, he refined his ideas about “human smart cities” and “living cities” into his 2016 proposal for 15-minute cities.

The idea owes much to its many predecessors: “neighborhood units” and “garden cities” in the early 1900s, the community-focused urban planning pioneered by the activist Jane Jacobs in the 1960s, even support for “new urbanism” and walkable cities in the 1990s. So-called low-traffic neighborhoods, or LTNs, have been set up in several British cities over the past few decades.

Critics of 15-minute cities have been outspoken, arguing that a concept developed in Europe may not translate well to highly segregated American cities. A Harvard economist wrote in a blog post for the London School of Economics and Political Science in 2021 that the concept was a “dead end” that would exacerbate “enormous inequalities in cities” by subdividing without connecting them.

Jordan Peterson, a Canadian psychologist with four million Twitter followers, suggested that 15-minute cities were “perhaps the worst imaginable perversion” of the idea of walkable neighborhoods. He linked to a post about the “Great Reset,” an economic recovery plan proposed by the World Economic Forum that has spawned hordes of rumors about a pandemic-fueled plot to destroy capitalism.

A member of Britain’s Parliament said that 15-minute cities were “an international socialist concept” that would “cost us our personal freedoms.” QAnon supporters said the derailment of a train carrying hazardous chemicals in Ohio was an intentional move meant to push rural residents into 15-minute cities.

“Conspiracy-mongers have built a complete story: climate denialism, Covid-19, anti-vax, 5G controlling the brains of citizens, and the 15-minute city for introducing a perimeter for day-to-day life,” Mr. Moreno said. “This storytelling is totally insane, totally irrational for us, but it makes sense for them.”

The multipronged conspiracy theory quickly became “turbocharged” after the Oxford protest, said Jennie King, head of climate research and policy at the Institute for Strategic Dialogue, a think tank that studies online platforms.

“You have this snowball effect of a policy, which in principle was only going to affect a small urban population, getting extrapolated and becoming this crucible where far-right groups, industry-sponsored lobbying groups, conspiracist movements, anti-lockdown groups and more saw an opportunity to insert their worldview into the mainstream and to piggyback on the news cycle,”

The vitriol currently directed at Mr. Moreno and researchers like him mirrors “the broader erosion of trust in experts and institutions,”

Modern conspiracy theorists and extremists turn the people they disagree with into scapegoats for a vast array of societal ills, blaming them personally for causing the high cost of living or various health crises and creating an “us-versus-them” environment, she said.

“I am not a politician, I am not a candidate for anything — as a researcher, my duty is to explore and deepen my ideas with scientific methodology,” he said. “It is totally unbelievable that we could receive a death threat just for working as scientists.”

But to understand why Republicans have died at higher rates, you can’t look at vaccine status alone. Congressional districts controlled by a trifecta of Republican leaders—state governor, Senate, and House—had an 11 percent higher death rate, according to the Lancet study. A likely explanation, the authors write, could be that in the post-vaccine era, those leaders chose policies and conveyed public-health messages that made their constituents more likely to die. Although we still can’t say these decisions led to higher death rates, the association alone is jarring.

One of the most compelling studies comes from researchers at Yale, who published their findings as a working paper in November. They link political party and excess-death rate—the percent increase in deaths above pre-COVID levels—among those registered as either Democrats or Republicans, providing a more granular view. They chose to analyze data from Florida and Ohio from before and after vaccines were available. Looking at the period before the vaccine,  researchers found a 1.6 percentage-point difference in excess death rate among Republicans and Democrats, with a higher rate among Republicans. But after vaccines became available, that gap widened dramatically to 10.4 percentage points, again with a higher Republican excess death rate. “When we compare individuals who are of the same age, who live in the same county in the same month of the pandemic, there are differences correlated with your political-party affiliation that emerge after vaccines are available,”

What’s most concerning about all of this is that partisan disparities in death rates were also apparent before COVID. People living in Republican jurisdictions have been at a health disadvantage for more than 20 years. From 2001 to 2019, the death rate in Democratic counties decreased by 22 percent, according to a recent study; in Republican counties, it declined by only 11 percent. In the same time period, the political gap in death rates increased sixfold.

over the decades, state policy decisions on health issues such as Medicaid, gun legislation, tobacco taxes, and, indeed, vaccines have likely had a stronger impact on state health trajectories than other factors

the long-term decline of health in red states indicates that there is an ongoing problem at a high level in Republican-led places, and that something has gone awry. “If you happen to live in certain states, your chances for living a long life are going to be much higher than if you’re an American living in a different state,”

o acknowledge how many Republicans didn’t have to die would mean giving credence to scientific and medical expertise. So long as America remains locked in a poisonous partisan battle in which science is wrongly dismissed as being associated with the left, the death toll will only rise.

During the 20th century, the list got much longer. In came existential crises, midlife crises, energy crises and environmental crises. When Koselleck was writing about the subject in the 1970s, he counted up more than 200 kinds of crisis we could then face

Waking up each morning to hear about the latest crisis is dispiriting for some, but throughout history it has been a bracing experience for others. In 1857, Friedrich Engels wrote in a letter that “the crisis will make me feel as good as a swim in the ocean”. A hundred years later, John F Kennedy (wrongly) pointed out that in the Chinese language, the word “crisis” is composed of two characters, “one representing danger, and the other, opportunity”. More recently, Elon Musk has argued “if things are not failing, you are not innovating enough”.

Victor H Mair, a professor of Chinese literature at the University of Pennsylvania, points out that in fact the Chinese word for crisis, wēijī, refers to a perilous situation in which you should be particularly cautious

“Those who purvey the doctrine that the Chinese word for ‘crisis’ is composed of elements meaning ‘danger’ and ‘opportunity’ are engaging in a type of muddled thinking that is a danger to society,” he writes. “It lulls people into welcoming crises as unstable situations from which they can benefit.” Revolutionaries, billionaires and politicians may relish the chance to profit from a crisis, but most people world prefer not to have a crisis at all.

A 2019 study which involved observing participants using bricks, found that those who had been threatened before the task tended to come up with more harmful uses of the bricks (such as using them as weapons) than people who did not feel threatened

The first world war sparked the growth of modernism in painting and literature. The second fuelled innovations in science and technology. The economic crises of the 1970s and 80s are supposed to have inspired the spread of punk and the creation of hip-hop

psychologists have also found that when we are threatened by a crisis, we become more rigid and locked into our beliefs. The creativity researcher Dean Simonton has spent his career looking at breakthroughs in music, philosophy, science and literature. He has found that during periods of crisis, we actually tend to become less creative.

When he looked at 5,000 creative individuals over 127 generations in European history, he found that significant creative breakthroughs were less likely during periods of political crisis and instability.

psychologists have found that it is what they call “malevolent creativity” that flourishes when we feel threatened by crisis.

These are innovations that tend to be harmful – such as new weapons, torture devices and ingenious scams.

A common folk theory is that times of great crisis also lead to great bursts of creativity.

Students presented with information about a threatening situation tended to become increasingly wary of outsiders, and even begin to adopt positions such as an unwillingness to support LGBT people afterwards.

during moments of crisis – when change is really needed – we tend to become less able to change.

When we suffer significant traumatic events, we tend to have worse wellbeing and life outcomes.

, other studies have shown that in moderate doses, crises can help to build our sense of resilience.

we tend to be more resilient if a crisis is shared with others. As Bruce Daisley, the ex-Twitter vice-president, notes: “True resilience lies in a feeling of togetherness, that we’re united with those around us in a shared endeavour.”

Crises are like many things in life – only good in moderation, and best shared with others

The challenge our leaders face during times of overwhelming crisis is to avoid letting us plunge into the bracing ocean of change alone, to see if we sink or swim. Nor should they tell us things are fine, encouraging us to hide our heads in the san

during moments of significant crisis, the best leaders are able to create some sense of certainty and a shared fate amid the seas of change.

This means people won’t feel an overwhelming sense of threat. It also means people do not feel alone. When we feel some certainty and common identity, we are more likely to be able to summon the creativity, ingenuity and energy needed to change things.

Dr. Longo, who is also a professor of gerontology and director of the U.S.C. Longevity Institute in California, has long advocated longer and better living through eating Lite Italian, one of a global explosion of Road to Perpetual Wellville theories about how to stay young in a field that is itself still in its adolescence.

In addition to identifying genes that regulate aging, he has created a plant and nut-based diet with supplements and kale crackers that mimics fasting to, he argues, allow cells to shed harmful baggage and rejuvenate, without the down side of actually starving.

He has patented and sold his ProLon diet kits; published best-selling books (“The Longevity Diet”); and been called an influential “Fasting Evangelist” by Time magazine.

Last month, he published a new study based on clinical trials of hundreds of older people — including in the Calabria town from which his family hails — that he said suggests that periodic cycles of his own faux-fasting approach could reduce biological age and stave off illnesses associated with aging.

“It’s very similar to the original Mediterranean diet, not the present one,” she said, pointing at photographs on the wall of a bowl of ancient legumes similar to the chickpe

“Almost nobody in Italy eats the Mediterranean diet,”

He added that many Italian children, especially in the country’s south, are obese, bloated on what he calls the poisonous five Ps — pizza, pasta, protein, potatoes and pane (or bread).

in recent years, Silicon Valley billionaires who hope to be forever young have funded secretive labs. Wellness articles have conquered newspaper home pages and Fountains-of-Youth workout and diet ads featuring insanely fit middle-aged people teem on the social media feeds of not insanely fit middle-aged people.

he said Italy’s lack of investment in research was a disgrace.

even as concepts like longevity, intermittent fasting and biological age — you’re only as old as your cells feel! — have gained momentum, governments like Italy’s are fretting over a creakier future in which booming populations of old people drain resources from the dwindling young.

many scientists, nutritionists and longevity fanatics the world over continue to stare longingly toward Italy, seeking in its deep pockets of centenarians a secret ingredient to long life.

“Probably they kept breeding between cousins and relatives,” Dr. Longo offered, referring to the sometimes close relations in little Italian hill towns. “At some point, we suspect it sort of generated the super-longevity genome.”

The genetic drawbacks of incest, he hypothesized, slowly vanished because those mutations either killed their carriers before they could reproduce or because the town noticed a monstrous ailment — like early onset Alzheimer’s — in a particular family line and steered clear.

Dr. Longo wonders whether Italy’s centenarians had been protected from later disease by a starvation period and old-fashioned Mediterranean diet early in life, during rural Italy’s abject war-era poverty. Then a boost of proteins and fats and modern medicine after Italy’s postwar economic miracle protected them from frailty as they got older and kept them alive.

At age 16, he moved to Chicago to live with relatives and couldn’t help notice that his middle-aged aunts and uncles fed on the “Chicago diet” of sausages and sugary drinks suffered diabetes and cardiovascular disease that their relatives back in Calabria did not.

He eventually earned his Ph.D in biochemistry at U.C.L.A. and did his postdoctoral training in the neurobiology of aging at U.S.C. He overcame early skepticism about the field to publish in top journals and became a zealous evangelizer for the age-reversing effects of his diet. About 10 years ago, eager to be closer to his aging parents in Genoa, he took a second job at the IFOM oncology institute in Milan.

He found a fount of inspiration in the pescatarian-heavy diet around Genoa and all the legumes down in Calabria.

he also found the modern Italian diet — the cured meats, layers of lasagna and fried vegetables the world hungered for — horrendous and a source of disease.

His private foundation, also based in Milan, tailors diets for cancer patients, but also consults for Italian companies and schools, promoting a Mediterranean diet that is actually foreign to most Italians today.

“Italy’s got such incredible history and a wealth of information about aging,” he said. “But spends virtually nothing.”

He talked about how he and others had identified an important regulator of aging in yeast, and how he has investigated whether the same pathway was at work in all organisms.

Dr. Longo said he thinks of his mission as extending youth and health, not simply putting more years on the clock, a goal he said could lead to a “scary world,” in which only the rich could afford to live for centuries, potentially forcing caps on having children

A more likely short-term scenario, he said, was division between two populations. The first would live as we do now and reach about 80 or longer through medical advancements. But Italians would be saddled with long — and, given the drop in the birthrate, potentially lonely — years burdened by horrible diseases.

The other population would follow fasting diets and scientific breakthroughs and live to 100 and perhaps 110 in relative good health.

But only a handful of cancers—of the breast, lung, colon and cervix—have screening tests recommended by the U.S. Preventive Services Task Force

Many companies are developing blood tests that can detect cancer signals before symptoms occur, and Grail’s is the most advanced. A study found it can identify more than 50 types of cancer 52% of the time and the 12 deadliest cancers in Stages I through III 68% of the time.

There’s a hitch. The test costs $949 and isn’t covered by Medicare or most private insurance.

The trouble is that this cancer is almost never caught early. There’s no routine screening for it, and symptoms don’t develop until it is advanced. Mr. Royse, 64, had no idea he was sick until he took a blood test called Galleri, produced by the Menlo Park, Calif., startup Grail. He had surgery and chemotherapy and is now cancer-free.

Mr. Royse visited Grail’s website, which referred him to a telemedicine provider who ordered a test. Another telemedicine doctor walked him through his results, which showed a cancer signal likely emanating from the pancreas, gallbladder, stomach or esophagus.

An MRI revealed a suspicious mass on his pancreas, which a biopsy confirmed was cancerous. Mr. Royse had three months of chemotherapy, surgery and another three months of chemotherapy, which ended last February. Because pancreatic cancer often recurs, he gets CT and MRI scans every three months. In addition, he has signed up for startup Natera’s Signatera customized blood test, which checks DNA specific to the patient’s cancer and can signal its return before signs are visible on the scans

Grail’s test likewise looks for DNA shed by cancer cells, which is tagged by molecules called methyl groups that are specific to a cancer’s origin. Grail uses genetic sequencing and machine learning to recognize links between DNA methyl groups and particular cancers

The test “is based on how much DNA is being shed by tumor,” Grail’s president, Josh Ofman, says. “Some tumors shed a lot of DNA. Some shed almost none.

ut slow-growing tumors typically aren’t shedding a lot of DNA.” That reduces the probability that Grail’s test will identify indolent cancers that pose no immediate danger.

Grail’s test has a roughly 0.5% false-positive rate, meaning 1 in 200 patients who don’t have cancer will get a positive signal

Its positive predictive value is 43%, so that of every 100 patients with a positive signal, 43 actually have cancer

the legislation’s price tag could reduce political support. According to one private company’s estimate, the test could cost the government $39 billion to $145 billion over a decade. Mr. Goldman counters that analysts usually overestimate the costs and underestimate the benefits of medical interventions.

Because Grail uses machine learning to detect DNA-methylation cancer linkages, the Grail test’s accuracy should improve as more tests and patient data are collected

regulators may balk at approving the test, and insurers at covering it, until it becomes cheaper and more reliable.

How would the FDA weigh the risk that a false positive on a test like Grail’s could require invasive follow-up testing against the dire but hard-to-quantify risk that a deadly cancer wouldn’t be caught until it’s much harder to treat? It’s unclear.

some experts urge the FDA to require large randomized controlled trials before approving blood cancer tests. “Multicancer screening would entail tremendous costs and potentially substantial harms,” H. Gilbert Welch and Tanujit Dey of Brigham and Women’s Hospital wrote

Dr. Welch and Mr. Dey also suggested that companies should be required to prove their tests reduce overall mortality, even though the FDA doesn’t require drugmakers to prove their products reduce deaths or extend life. Clinical trials for the mRNA Covid vaccines didn’t show they reduced deaths.

One alternative is to rely on real-world studies, which Grail is already doing. One study of patients 50 and older without signs of cancer showed that the test doubled the number of cancers detected.

One recurring problem he has seen: “Epidemiologists are always getting cancer wrong,” he says. “Epidemiologists a decade ago said U.S. overtreats cancers. Well, no, the EU undertreats cancer.”

A 2012 study that he co-authored found that the higher U.S. spending on cancer care relative to Europe between 1983 and 1999 resulted in significantly higher survival rates for American patients than for those in Europe

By his study’s calculation, U.S. spending on cancer treatments during that period resulted in $556 billion in net benefits owing to reduced mortality.

He expects Galleri and other multicancer early-detection tests to reduce deaths and produce public-health and economic benefits that exceed their monetary costs

Expanding access to multicancer early-detection tests could also help solve the chicken-and-egg problem of drug development. Because few patients are diagnosed at early stages of some cancers, it’s hard to develop treatments for them

the positive predictive value for some recommended cancer screenings is far lower. Fewer than 1 in 10 women with an abnormal finding on a mammogram are diagnosed with breast cancer.

Mr. Royse makes the same point with personal force. “I would be dead right now if not for multicancer early-detection testing,” Mr. Royse told an FDA advisory committee last fall. “The longer the FDA waits, the more people are going to die. It’s that simple.”