We may be on the cusp of an era of astonishing innovation — the limits of which aren’t even clear yet.Hype springs eternal in medicine, but lately the horizon of new possibility seems almost blindingly bright. “I’ve been running my research lab for almost 30 years,” says Jennifer Doudna, a biochemist at the University of California, Berkeley. “And I can say that throughout that period of time, I’ve just never experienced what we’re seeing over just the last five years.”A Nobel laureate, Doudna is known primarily for Crispr, the gene-editing Swiss Army knife that has been called “a word processor” for the human genome and that she herself describes as “a technology that literally enables the rewriting of the code of life.” The work for which Doudna shared the Nobel Prize was published more than a decade ago, in 2012, opening up what seemed like an almost limitless horizon for Crispr-powered therapies and cures. But surveying the recent landscape of scientific breakthroughs, she says the last half-decade has been more remarkable still: “I think we’re at an extraordinary time of accelerating discoveries.” The pandemic has exhausted many Americans of medicine, and it has become common to process the last few years as a saga of defeat and failure. And yet these brutal years — which brought more than a million American deaths and probably 20 million deaths worldwide, and seemed to return even the hypermodern citadels of the wealthy West to something like the experience of premodern plague — might also represent an unprecedented watershed of medical innovation. Beyond Crispr and Covid vaccines, there are countless potential applications of mRNA tools for other diseases; a new frontier for immunotherapy and next-generation cancer treatment; a whole new world of weight-loss drugs; new insights and drug-development pathways to chase with the help of machine learning; and vaccines heralded as game-changing for some of the world’s most intractable infectious diseases.“It’s stunning,” says the immunologist Barney Graham, the former deputy director of the Vaccine Research Center and a central figure in the development of mRNA vaccines, who has lately been writing about a “new era for vaccinology.” “You cannot imagine what you’re going to see over the next 30 years. The pace of advancement is in an exponential phase right now.” ‘World-changing’ innovationsIt is sometimes hard to see the silver lining for the cloud, particularly when it’s as dark as the last three years have been. But at the very center of the American Covid experience, amid all the death and suffering and despite the dysfunction that midwifed it into being, sits what would have stood out, in any previous era, as an astonishing biomedical miracle: the coronavirus vaccines. Drug-development timelines in previous history had swallowed whole decades; experts warned not to expect a resolution for years. But the mRNA sequence of the first shot was designed in a weekend, and the finished vaccines arrived within months, an accelerated timeline that saved perhaps several million American lives and tens of millions worldwide — numbers that are probably larger than the cumulative global death toll of the disease. The miracle of the vaccines wasn’t just about lives saved from Covid. As the first of their kind to be approved by the Food and Drug Administration, they brought with them a very long list of potential future mRNA applications: H.I.V., tuberculosis, Zika, respiratory syncytial virus (R.S.V.), cancers of various and brutal kinds. And the vaccine innovations stretch beyond mRNA: A “world-changing” vaccine for malaria, which kills 600,000 globally each year, is being rolled out in Ghana and Nigeria, and early trials for next-generation dengue vaccines suggest they may reduce symptomatic infection by 80 percent or more. Not every innovation arriving now or soon to market comes from U.S. research or shares the same saga of development. But many of their back stories do rhyme, often stretching back several decades through the time of the Human Genome Project, which was completed in 2003, and the near-concurrent near-doubling of the National Institutes of Health’s budget, which helped unleash what Donna Shalala, President Bill Clinton’s secretary for health and human services, last year called “a golden age of biomedical research.” Illustration by Ibrahim RayintakathA couple of decades later, it looks like a golden age for new treatments. New trials of breast-cancer drugs have led to survival rates hailed in The Times as “unheard-of,” and a new treatment for postoperative lung-cancer patients may cut mortality by more than half. Another new treatment, for rectal cancer, turned every single member of a small group of cases into cancer-free survivors. Ozempic and Wegovy have already changed the landscape for obesity in America — a breakthrough that has been described and debated so much in terms of cosmetic benefits and medical moral hazard that it can be easy to forget that obesity is among the largest risk factors for preventable death in the United States. Next-generation alternatives may prove even more effective, and there are signs of huge off-label implications: At least anecdotally, in some patients the drugs appear to curb compulsive behavior across a range of hard-to-treat addictions. And although the very first person to receive Crispr gene therapy in the United States received it just four years ago, for sickle-cell disease, it has since been rolled out for testing on congenital blindness, heart disease, diabetes, cancer and H.I.V. So far only two applications for such treatments have been submitted to the F.D.A., but all told, some 400 million people worldwide are afflicted by one or more diseases arising from single-gene mutations that would be theoretically simple for Crispr to fix. And when Doudna allows herself to imagine applications a decade or two down the line, the possibilities sound almost intoxicating: offering single-gene protection against high cholesterol and therefore coronary artery disease, for instance, or, in theory, inserting a kind of genetic prophylaxis against Alzheimer’s or dementia. ‘Can we actually do it?’In January, a much-talked-about paper in Nature suggested that the rate of what the authors called disruptive scientific breakthroughs was steadily declining over time — that, partly as a result of dysfunctional academic pressures, researchers are more narrowly specialized than in the past and often tinkering around the margins of well-understood science. But when it comes to the arrival of new vaccines and treatments, the opposite story seems more true: whole branches of research, cultivated across decades, finally bearing real fruit. Does this mean we are riding an exponential curve upward toward radical life extension and the total elimination of cancer? No. The advances are more piecemeal and scattered than that, and indeed there are those who believe that progress should be moving faster still. In the midst of the pandemic, a number of calls for greater acceleration have been issued, some emphasizing the need to reduce costs for drug development, which have doubled every decade since the 1970s, perhaps by redesigning clinical trials or employing what are called human-challenge trials, or by streamlining the drug-approval process. Graham, who is now a senior adviser for global health equity at the Morehouse School of Medicine, emphasizes questions of global distribution and access: Will the new technologies actually get where they are needed most? “The biology and the science that we need is already in place,” he says. “The question now to me is: Can we actually do it?”In 1987, the economist Robert Solow commented that you could see the computer revolution everywhere but the productivity statistics — that despite intuitions about how fully information technology had transformed all forms of work in America, the step-change hadn’t really made a mark on the country’s economy in any obvious statistical way. Until a few years ago, perhaps, you might have said the same about billions of dollars spent researching potential H.I.V. vaccines or the decoding of the human genome, which unleashed a venture-capital-like boom-and-bust biotech hype cycle that sputtered out before most Americans had seen any real gains from it. Sometimes these things just take a little time. David Wallace-Wells is a staff writer at the magazine and the author of “The Uninhabitable Earth: Life After Warming.”

More than one in six people on the planet live in China. That’s 1.4 billion people who have spent the last three years in the world’s most intrusive pandemic surveillance state, designed to limit the spread of Covid-19 at almost any cost.Americans, particularly on the right, have spent an awful lot of time and political energy complaining about pandemic overreach for the last two years. But our restrictions had nothing on China’s. In the United States, many statewide stay-at-home orders lasted just a few weeks. None exceeded three months, and most were only sporadically enforced. As protests erupted across China last month, one-third of the country was in partial or total lockdown — workers stuck in quarantine facilities, neighborhoods sealed, businesses and schools closed.It is too soon to say whether the protests will mark the beginning of a true phase shift in China’s pandemic policy — so far, they have produced both a dramatic police crackdown and the relaxation of restrictions in some cities. But to a worldwide audience watching China with a mix of fascination and horror, mass public protest in the world’s last large “zero Covid” holdout seems to mark a global turning point. For several years now, many public health experts have acknowledged privately that the opportunity to contain and eradicate Covid-19 might have been lost as early as the winter of 2020. And for several years now China has tried to beat the disease back at the border anyway.Remarkably, it has basically succeeded, almost entirely suppressing disease spread within the country’s borders for three years now, an effort that has put it on an entirely different pandemic timeline from most of the rest of the world. It has also made reflexive efforts to analogize the situation in China a bit suspect. Some Americans who believed our pandemic response was excessive have treated the protests as a tacit endorsement of the more laissez-faire approach we’ve embraced post-vaccines; others who might’ve argued for doing more here are also taking the protests as a sign that, in the end, compared with China, the United States got things right.But however it may look from outside, China’s leaders are not operating in a risk landscape like the one Americans are in today, where more than 90 percent of the country has probably gotten Covid at least once and more than 90 percent of people over age 65 are vaccinated. They are looking at one somewhat more like the one we faced years ago, when immunity from vaccines and infections was substantially lower. And Hong Kong’s deadly brush with the Omicron variant this year — death rates were about twice as bad there as in Britain or the United States — may prove to be the closest harbinger of what’s to come.Ninety percent of people in China are now vaccinated. But many fewer infections there and a low uptake of vaccines among older people — only 65.8 percent of those over 80 are fully vaccinated — means an enormous population of vulnerable, immunologically naïve people. Considerably more could still be done to protect the population going forward, such as more fully embracing imported mRNA vaccines, which seem to offer greater protection than the vaccines produced in China, and pushing even harder to vaccinate vulnerable older people. In the meantime, the risks of reopening are still large. A true reopening, however unlikely, could lead to millions of deaths.There is no easy or obvious resolution to that dilemma, no matter how intuitive a return to normalcy may seem to those of us living in pandemic-battered parts of the world. Here a new normal was won through vaccination, to a large degree, but also through near-universal infection and mass death. So far, American Covid mortality in 2022 is below the levels of 2020 and 2021, but not that far below, with deaths this year two-thirds of those in 2020 and half as high as those in 2021. Covid-19 is on track to be the country’s third leading cause of death for the third straight year, behind only heart disease and cancer.Something like that could well lie ahead for China, given a vaccine rollout that prioritized uptake by the young and healthy and discouraged it by the older and more vulnerable. (At first, vaccination was only approved for the young and healthy.) Exactly why they did this is still not clear, at least to international observers, many of whom may have wondered why it is so much harder for an outwardly authoritarian regime to mandate vaccination for the old, or even very aggressively promote it, than it has been to lock down entire cities for weeks at a time.Perhaps it is a sign, like the protests themselves, that the party’s grip is less strong than we imagine it to be; perhaps that the government missed its good-will window for pushing more aggressively for shots; or perhaps it’s an indication that bodily autonomy is a different and more deeply held kind of liberty than political autonomy. Perhaps the regime distrusted its vaccines even more than the rest of the world did, or worried more about their side effects. Perhaps it was more concerned about the accumulating effect of reinfections and was waiting for nasal spray vaccines more capable not just of limiting disease severity but of stopping transmission. (Such vaccines, stuck in bureaucratic and developmental bottlenecks here, have been approved in China, though they haven’t been rolled out at scale yet.) Perhaps it was just more confident that zero Covid could work indefinitely, or so invested in the political narrative of the country’s exceptional pandemic success that a change of course was, to Xi, unthinkable.Is it thinkable now? This week, my colleague Paul Krugman wrote that the protests were a sign that “China lost the Covid war,” emphasizing that, despite appearances early in the pandemic, democracies now seem to have definitely outperformed autocracies, and calling on Chinese leaders to recognize the error of their ways and change course. In The Guardian, Yu Jie wrote that “zero Covid can’t continue,” with reopening “the only way to quell public anger.” But personally, I would bet only on much smaller-scale adjustments, of the kind that had already been floated by Beijing in the weeks before the protests began.That’s because the best model of what might transpire in a truly opened-up China is Hong Kong’s experience with Omicron. By mid-February 2022, there had been a reported total of just over 200 deaths in the city since the beginning of the pandemic. By mid-April, it was over 9,000. And while a much more aggressive mainland campaign to deliver mRNA vaccines to older people could lessen the death toll, the experience of other countries largely credited with doing everything right suggests that even best-case exits from the emergency phase of the pandemic can be quite messy.Consider the experience in Japan, one of the world’s most celebrated pandemic success stories. Covid deaths there are 70 percent higher this calendar year than they were in the first two years of the pandemic combined. In Iceland, another often-cited success story, five times as many people have died from Covid in 2022 as in the first two years of the pandemic. In Australia, it is six times as many. This past January, Taiwan had registered under 1,000 deaths; today that figure is over 14,000. According to The Economist’s gold standard tracker, New Zealand is now the only nation in the world with negative excess mortality across the whole span of the pandemic — meaning that the country has had fewer deaths since 2020 than would have been expected in a world without SARS-CoV-2. And yet even there, the last year has upended some narratives: As recently as January 2022, only 52 New Zealanders had died from Covid; today the figure is above 2,000, more than 40 times as high.In each of these countries, rapid increases in Covid mortality this year come from very low and presumably unsustainable baselines, but even so, they tell a striking story. Mitigation measures mattered, particularly until the arrival of vaccines, when vaccination mattered even more. But in any particular country the dream of actually defeating the pandemic outright — or even holding it at bay long enough to fully protect the population through universal vaccination — was no match for the disease itself. Eventually, every country got it.Or almost every country. Throughout the pandemic, many international observers questioned the reliability of official Chinese data about the toll of the pandemic. But given the global context, that data remains pretty astonishing, even correcting for its unreliability: In January, China reported just under 5,000 total Covid deaths. Today that figure is just over 5,000. A nation of 1.4 billion registered barely 500 official deaths over the course of the year in which their pandemic policy began to crumble. In total, over three years, the country has reported only 1.6 million official infections, and while that is surely a gross underestimate, it suggests that only about one-tenth of 1 percent of the country has ever gotten sick with Covid. In the United States, a larger share of our population has died from it — nearing 1.1 million deaths in total.That isn’t at all to suggest that China’s permanent lockdowns are a better model, or that any of the world’s major countries would or should want to trade places with China. But the binary contrast between the approaches is not as illuminating as it may seem.In the United States, where people sometimes say “lockdowns” and mean “mask mandates” and “school closures” or sometimes just “widespread testing,” even relatively mild mitigation measures have grown politically and socially toxic. But the most obvious tools to limit ongoing spread are not especially obtrusive: investments in air quality and better workplace safety standards, paid sick leave, aggressive rollout of those nasal vaccines and an emphasis on the vulnerability of the country’s older people, who make up about 90 percent of its distressingly high ongoing deaths. In China, pandemic policy only became significantly more restrictive than it was in the United States and Britain in the summer of 2021, according to a “stringency index” calculated by the University of Oxford’s government response tracker, and the country faces tough choices now not because of how effective those restrictions have been but because of unrelated problems in vaccine rollout and efficacy.When most of the world, armed with vaccines, pulled back from aggressive mitigation, it was in part an act of resignation — an acknowledgment that the cat was out of the bag, that the virus was irretrievably in circulation and had conferred considerable natural immunity already, and that while continuing infections were regrettable, vaccination and treatments could blunt the impact. In China, where there has been much less infection and much less death, the protests appear to express something more like pure pandemic exhaustion. By its own standards, China’s zero Covid policy didn’t really fail. But the country is running out of patience for it anyway.David Wallace-Wells (@dwallacewells), a writer for Opinion and a columnist for The New York Times Magazine, is the author of “The Uninhabitable Earth.”

What is the panic about pandemic learning loss actually about?There are some legitimate reasons for concern. The testing declines are real and significant, returning national performance in math and reading to levels last seen a couple of decades ago, and imposing the largest and more worrying setbacks on the most vulnerable students. At the nationwide level, educational gains are exceedingly hard to come by, which means even modest setbacks are worrying, too. There are, as always, good reasons to ask what can be done to address learning shortfalls, and how to best support teachers and schools in addressing them — particularly as billions in federal funding to counter learning loss awaits distribution.But when I look at the data in detail, I just don’t see the signs of catastrophe that so many others seem to. I’m inclined to see that data as, at least, a glass half full, if not quite a best-case scenario. That’s because the declines, all told, strike me as relatively small, given the context: a brutal pandemic that terrified the country and killed more than a million of its citizens, upending nearly every aspect of our lives along the way.The panic of parents and policymakers is both unsurprising and, to a degree, productive: As we approach the three-year anniversary of the beginning of the pandemic, we should be thinking about what went right and what went wrong, with school closures and other mitigation policies. But in doing so let’s try not to forget the scale of the impact or the context in which it happened.As a country, prompted in part by midterm elections, we are now doing some of that reckoning — mostly in a one-sided way, with Republicans running on the Covid excesses of liberals and Democrats mostly trying to avoid the subject. But it isn’t just partisanship skewing things. We are talking a lot more about possible policy overreach — on school closures, on mask mandates — than we are about how brutal and disorienting the pandemic actually was. And we aren’t doing that in a world in which the whole thing turned out to be no big deal, or some false alarm panic that made initial precautions seem absurd and retrospective policy questions abstract. We’re doing it in a world in which a million Americans died — and we’re judging choices made before vaccines and Paxlovid and widespread natural immunity, when the risk of death was 10 times higher, by the much more laissez-faire standards we settled on much later.Could we have managed the first year of the pandemic more strategically, doing more to protect the vulnerable and prioritize essential functions like schools? Almost certainly. (Personally, I would’ve liked to have seen schools open nationwide in fall 2020, with additional focus on rapid testing and improved ventilation.) Do we know how well each mitigation measure suppressed spread and saved lives? Not as clearly as we might like if we were trying to strategize a plan for future pandemics, and we may well be less universally restrictive if given another chance. But however open these questions may seem to you today, they were first asked not in the context of endemic Covid but of mass death and illness, uncertainty and anxiety and social disarray.In that context, how did the kids fare? Last month, I wrote about early learning loss data from the National Assessment for Educational Progress tests, which showed, that for the country’s 9-year-olds, average test scores for math fell to 234 (out of 500) in 2022, down from 241 in 2020. For reading the scores fell to 215 in 2022 from 220 in 2020. These declines represented a setback of a couple of decades, since the average math score had been 232 in 1999 and the average reading score had been 216 in 2004. The scores varied from student to student and district to district, but nationally the effect did not resemble the cancellation of school. It was the equivalent of taking the nation’s schoolchildren, putting them in a time machine, and sending them off to be educated sometime around the year 2000.This week, N.A.E.P. released new data covering 450,000 fourth and eighth graders, generating a new round of hand-wringing. (The Washington Post called it “a generational emergency.”) But the new data only confirms the same story.For fourth graders, national performance in math fell from 241 in 2019 to an average of 236 in 2022 (close to what it had been in 2005). In reading, average scores by fourth graders fell to 217 in 2022 from 220 in 2019, more or less matching the average performance of 219 by fourth graders from 2005. For eighth graders, the average reading score in 2022 was 260, down from 263 in 2019. In math, the decline was a bit bigger, falling to an average of 274 in 2022 from 282 in 2019, erasing a couple of decades of gains and matching the scores achieved in 2000, when the national average was 273.All told, at least as judged by test scores, the effect of extensive and perhaps excessive disruption to schooling was to return the country as a whole to the levels of educational achievement of the No Child Left Behind years.State by state, it is hard to draw a line between school closures and learning loss, since some states that stayed closed longest fared best, and vice versa. Earlier research showed a clearer relationship between school closures and learning loss at the district level, but at a news conference announcing the latest N.A.E.P. report, the commissioner of the National Center for Education Statistics said, “There’s nothing in this data that tells us there is a measurable difference in the performance between states and districts based solely on how long schools were closed.”In New York City, the nation’s largest school district, schools reopened in September 2020. There, average scores for reading fell by about a point for fourth graders and improved by about a point for eighth graders; in math, fourth-grade scores fell by nine points (statewide scores fell by 12) and eighth-grade scores fell by four points (statewide scores fell by six). In Los Angeles, the second-largest district, schools stayed closed through January 2021. There, average scores actually improved in fourth-grade reading, eighth-grade math and eighth-grade reading, where they improved by a robust nine points (to 257 from 248). Scores fell only in fourth-grade math (to 220 from 224).In a vacuum, the pandemic declines look like bad news, if at a relatively small scale. But none of this happened in a vacuum. I’ve mentioned the million deaths not to fearmonger about how much higher those numbers might have been without school closures — the scale of that impact is, I believe, an open question — but just to point out the enormous and widespread human impact of the disease itself. And that impact was much larger than measured simply by mortality. More than 3.5 million Americans were hospitalized, according to one estimate, and probably at least as many suffered from long Covid. In the spring of 2020, the country’s unemployment rate exploded, jumping to nearly 15 percent from about 4 percent; for a brief period in April, six million new jobless claims were filed each week. In a single quarter, U.S. GDP fell by 9 percent. Murder rates grew by 30 percent; deadly car crashes spiked, too. Overdose deaths rose 30 percent in 2020 and 15 percent in 2021. According to some research, rates of depression tripled in the United States when the pandemic first hit. Some 600,000 teachers left the profession.This is the world in which American students — most of them learning remotely for many months, many of them for close to a year, and some for longer — fell off by a handful of points, on their reading and math exams, compared with their prepandemic peers.“The sudden onset of the pandemic has been the most catastrophic event in recent American history, making the expectation that there would not be something called ‘learning loss’ bizarre,” Keeanga-Yamahtta Taylor wrote recently in The New Yorker. “The idea that life would simply churn on in the same way it always has only underscores the extent to which there have been two distinct experiences of the pandemic,” she went on, emphasizing how much harder the pandemic was for the poor and marginalized to navigate, compared with those for whom its secondary effects were buffeted by wealth.International comparisons offer another bit of context for test score declines. In England, schools closed in the spring of 2020, opening again in some places in early summer and across the country in the fall (with an Omicron interruption of about a month that winter of 2021). In retrospect, that would have been a plausible but relatively aggressive school reopening approach in the United States, where many schools stayed remote well into the 2020-2021 school year. It also resulted in a drop of six percentage points in proficiency scores, roughly comparable to the American experience. In other words, in England, with a close-to-optimal school reopening, they fared no better.In the Netherlands, where schools were even less disrupted than in Britain, student performance fell by three percentage points — a bit better, but still below the standards set in prepandemic years. At the most extreme end of the spectrum, there is Sweden, which did not close schools at all, and which, some reporting has suggested, experienced no such declines. But the country also suspended its testing program, which means the data on which such claims might be based is pretty shaky.The American data, by contrast, is quite strong, and the picture is clear: Almost everywhere, there have been declines, generally modest. And yet rhetoric about the costs of school closure appears to be only intensifying — with the secretary of education calling the test scores “appalling and unacceptable,” for instance, adding that our response to the declines will determine “our nation’s standing in the world.”Perhaps it makes sense that in this period of reflection, schools would become such a hotly debated pandemic touchstone. Schools are hugely important, educational gains exceedingly hard to come by, and the setbacks are both real and large enough to justify plenty of genuine concern. Schools are also among the civic institutions Americans are most engaged with and involved in, which means that — unlike the running of hospitals, say, or pandemic policy in the military — the question of school closure felt much more immediate to many more people, including those whose lives were otherwise relatively untouched by pandemic disruption.School closures also had costs that went well beyond test scores — the social and emotional costs of isolation for children and the additional impact on many parents — and those scores are perhaps one way of talking generally about that larger burden. Like crime, school performance is a perennial and widespread source of American anxiety, and earlier conflicts — between reformers and teachers’ unions, between parents and local bureaucracies — offered a kind of road map for fights over pandemic policy. Those concerned about social inequalities could see easily and clearly, beginning in the fall of 2020, just how differently the matter of reopening was being handled by private schools, public schools in wealthy places and public schools in poor places — and be rightfully outraged by divergence.But I think, alongside those explanations, there’s something else: Americans as a whole are not exactly happy with how those two years went, and the pandemic has left almost all of us with some excess of rage and frustration. Early on, that was channeled into partisanship, with liberals blaming President Donald Trump for the pandemic itself and conservatives blaming liberals for pandemic restrictions. But the lines of Covid partisanship are much muddier now — a few years on, there’s a Democrat in the White House, and a growing recognition that, while policy matters and political leadership have surely failed the country, the virus was going to wreak some amount of havoc regardless.But that idea remains uncomfortable for many, that the pandemic was not just a policy failure or political choice but a generational and global public-health trauma against which very few of our peer countries fared very well either. And yet even as it grows harder to pin responsibility on one party or one president, we want to pin it somewhere, on some human or humans or human institution, if only to tell ourselves that if we make the right choices we will never have to live through all that again. As a country, we burden our schools with an almost impossible set of responsibilities — undoing racial disparities, for instance, or closing yawning income gaps. It makes sense that we’ve piled additional frustration and rage on them, wanting to believe schools could have navigated the pandemic smoothly, too. But to judge by the test scores, at least, they came remarkably close.David Wallace-Wells (@dwallacewells), a writer for Opinion and a columnist for The New York Times Magazine, is the author of “The Uninhabitable Earth.”