How Science Beat the Virus

1.

In fall of 2019, exactly zero scientists were studying COVID‑19, because no one knew the disease existed. The coronavirus that causes it, SARS‑CoV‑2, had only recently jumped into humans and had been neither identified nor named. But by the end of March 2020, it had spread to more than 170 countries, sickened more than 750,000 people, and triggered the biggest pivot in the history of modern science. Thousands of researchers dropped whatever intellectual puzzles had previously consumed their curiosity and began working on the pandemic instead. In mere months, science became thoroughly COVID-ized.

As of this writing, the biomedical library PubMed lists more than 74,000 COVID-related scientific papers—more than twice as many as there are about polio, measles, cholera, dengue, or other diseases that have plagued humanity for centuries. Only 9,700 Ebola-related papers have been published since its discovery in 1976; last year, at least one journal received more COVID‑19 papers than that for consideration. By September, the prestigious New England Journal of Medicine had received 30,000 submissions—16,000 more than in all of 2019. “All that difference is COVID‑19,” Eric Rubin, NEJM’s editor in chief, says. Francis Collins, the director of the National Institutes of Health, told me, “The way this has resulted in a shift in scientific priorities has been unprecedented.”

Much like famous initiatives such as the Manhattan Project and the Apollo program, epidemics focus the energies of large groups of scientists. In the U.S., the influenza pandemic of 1918, the threat of malaria in the tropical battlegrounds of World War II, and the rise of polio in the postwar years all triggered large pivots. Recent epidemics of Ebola and Zika each prompted a temporary burst of funding and publications. But “nothing in history was even close to the level of pivoting that’s happening right now,” Madhukar Pai of McGill University told me.

That’s partly because there are just more scientists: From 1960 to 2010, the number of biological or medical researchers in the U.S. increased sevenfold, from just 30,000 to more than 220,000. But SARS-CoV-2 has also spread farther and faster than any new virus in a century. For Western scientists, it wasn’t a faraway threat like Ebola. It threatened to inflame their lungs. It shut down their labs. “It hit us at home,” Pai said.

In a survey of 2,500 researchers in the U.S., Canada, and Europe, Kyle Myers from Harvard and his team found that 32 percent had shifted their focus toward the pandemic. Neuroscientists who study the sense of smell started investigating why COVID‑19 patients tend to lose theirs. Physicists who had previously experienced infectious diseases only by contracting them found themselves creating models to inform policy makers. Michael D. L. Johnson at the University of Arizona normally studies copper’s toxic effects on bacteria. But when he learned that SARS‑CoV‑2 persists for less time on copper surfaces than on other materials, he partially pivoted to see how the virus might be vulnerable to the metal. No other disease has been scrutinized so intensely, by so much combined intellect, in so brief a time.

These efforts have already paid off. New diagnostic tests can detect the virus within minutes. Massive open data sets of viral genomes and COVID‑19 cases have produced the most detailed picture yet of a new disease’s evolution. Vaccines are being developed with record-breaking speed. SARS‑CoV‑2 will be one of the most thoroughly characterized of all pathogens, and the secrets it yields will deepen our understanding of other viruses, leaving the world better prepared to face the next pandemic.

But the COVID‑19 pivot has also revealed the all-too-human frailties of the scientific enterprise. Flawed research made the pandemic more confusing, influencing misguided policies. Clinicians wasted millions of dollars on trials that were so sloppy as to be pointless. Overconfident poseurs published misleading work on topics in which they had no expertise. Racial and gender inequalities in the scientific field widened.

Amid a long winter of sickness, it’s hard not to focus on the political failures that led us to a third surge. But when people look back on this period, decades from now, they will also tell stories, both good and bad, about this extraordinary moment for science. At its best, science is a self-correcting march toward greater knowledge for the betterment of humanity. At its worst, it is a self-interested pursuit of greater prestige at the cost of truth and rigor. The pandemic brought both aspects to the fore. Humanity will benefit from the products of the COVID‑19 pivot. Science itself will too, if it learns from the experience.

2.

In February, Jennifer Doudna, one of America’s most prominent scientists, was still focused on CRISPR—the gene-editing tool that she’d co-discovered and that won her a Nobel Prize in October. But when her son’s high school shut down and UC Berkeley, her university, closed its campus, the severity of the impending pandemic became clear. “In three weeks, I went from thinking we’re still okay to thinking that my whole life is going to change,” she told me. On March 13, she and dozens of colleagues at the Innovative Genomics Institute, which she leads, agreed to pause most of their ongoing projects and redirect their skills to addressing COVID‑19. They worked on CRISPR-based diagnostic tests. Because existing tests were in short supply, they converted lab space into a pop-up testing facility to serve the local community. “We need to make our expertise relevant to whatever is happening right now,” she said.

Scientists who’d already been studying other emerging diseases were even quicker off the mark. Lauren Gardner, an engineering professor at Johns Hopkins University who has studied dengue and Zika, knew that new epidemics are accompanied by a dearth of real-time data. So she and one of her students created an online global dashboard to map and tally all publicly reported COVID‑19 cases and deaths. After one night of work, they released it, on January 22. The dashboard has since been accessed daily by governments, public-health agencies, news organizations, and anxious citizens.

Studying deadly viruses is challenging at the best of times, and was especially so this past year. To handle SARS‑CoV‑2, scientists must work in “biosafety level 3” labs, fitted with special airflow systems and other extreme measures; although the actual number is not known, an estimated 200 such facilities exist in the U.S. Researchers often test new drugs and vaccines on monkeys before proceeding to human trials, but the U.S. is facing a monkey shortage after China stopped exporting the animals, possibly because it needed them for research. And other biomedical research is now more difficult because of physical-distancing requirements. “Usually we had people packed in, but with COVID, we do shift work,” Akiko Iwasaki, a Yale immunologist, told me. “People are coming in at ridiculous hours” to protect themselves from the very virus they are trying to study.

Experts on emerging diseases are scarce: These threats go neglected by the public in the lulls between epidemics. “Just a year ago I had to explain to people why I was studying coronaviruses,” says Lisa Gralinski of the University of North Carolina at Chapel Hill. “That’s never going to be a concern again.” Stressed and stretched, she and other emerging-disease researchers were also conscripted into unfamiliar roles. They’re acting as makeshift advisers to businesses, schools, and local governments. They’re barraged by interview requests from journalists. They’re explaining the nuances of the pandemic on Twitter, to huge new follower counts. “It’s often the same person who’s helping the Namibian government to manage malaria outbreaks and is now being pulled into helping Maryland manage COVID‑19,” Gardner told me.

But the newfound global interest in viruses also means “you have a lot more people you can talk through problems with,” Pardis Sabeti, a computational geneticist at the Broad Institute of MIT and Harvard, told me. Indeed, COVID‑19 papers are more likely than typical biomedical studies to have authors who had never published together before, according to a team led by Ying Ding, who works at the University of Texas at Austin.

Fast-forming alliances could work at breakneck speed because many researchers had spent the past few decades transforming science from a plodding, cloistered endeavor into something nimbler and more transparent. Traditionally, a scientist submits her paper to a journal, which sends it to a (surprisingly small) group of peers for (several rounds of usually anonymous) comments; if the paper passes this (typically months-long) peer-review gantlet, it is published (often behind an expensive paywall). Languid and opaque, this system is ill-suited to a fast-moving outbreak. But biomedical scientists can now upload preliminary versions of their papers, or “preprints,” to freely accessible websites, allowing others to immediately dissect and build upon their results. This practice had been slowly gaining popularity before 2020, but proved so vital for sharing information about COVID‑19 that it will likely become a mainstay of modern biomedical research. Preprints accelerate science, and the pandemic accelerated the use of preprints. At the start of the year, one repository, medRxiv (pronounced “med archive”), held about 1,000 preprints. By the end of October, it had more than 12,000.

Open data sets and sophisticated new tools to manipulate them have likewise made today’s researchers more flexible. SARS‑CoV‑2’s genome was decoded and shared by Chinese scientists just 10 days after the first cases were reported. By November, more than 197,000 SARS‑CoV‑2 genomes had been sequenced. About 90 years ago, no one had even seen an individual virus; today, scientists have reconstructed the shape of SARS‑CoV‑2 down to the position of individual atoms. Researchers have begun to uncover how SARS‑CoV‑2 compares with other coronaviruses in wild bats, the likely reservoir; how it infiltrates and co-opts our cells; how the immune system overreacts to it, creating the symptoms of COVID‑19. “We’re learning about this virus faster than we’ve ever learned about any virus in history,” Sabeti said.

3.

By March, the odds of quickly eradicating the new coronavirus looked slim. A vaccine became the likeliest endgame, and the race to create one was a resounding success. The process normally takes years, but as I write this, 54 different vaccines are being tested for safety and efficacy, and 12 have entered Phase 3 clinical trials: the final checkpoint. As of this writing, Pfizer/BioNTech and Moderna have announced that, based on preliminary results from these trials, their respective vaccines are roughly 95 percent effective at preventing COVID‑19. “We went from a virus whose sequence was only known in January, and now in the fall, we’re finishing—finishing—a Phase 3 trial,” Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases and a member of the White House’s coronavirus task force, told me. “Holy mackerel.”

Most vaccines comprise dead, weakened, or fragmented pathogens, and must be made from scratch whenever a new threat emerges. But over the past decade, the U.S. and other countries have moved away from this slow “one bug, one drug” approach. Instead, they’ve invested in so-called platform technologies, in which a standard chassis can be easily customized with different payloads that target new viruses. For example, the Pfizer/BioNTech and Moderna vaccines both consist of nanoparticles that contain pieces of SARS‑CoV‑2’s genetic material—its mRNA. When volunteers are injected with these particles, their cells use the mRNA to reconstruct a noninfectious fragment of the virus, allowing their immune system to prepare antibodies that neutralize it. No company has ever brought an mRNA vaccine to market before, but because the basic platform had already been refined, researchers could quickly repurpose it with SARS‑CoV‑2’s mRNA. Moderna got its vaccine into Phase 1 clinical trials on March 16, just 66 days after the new virus’s genome was first uploaded—far faster than any pre-COVID vaccine.

Meanwhile, companies compressed the process of vaccine development by running what would normally be sequential steps in parallel, while still checking for safety and efficacy. The federal government’s Operation Warp Speed, an effort to accelerate vaccine distribution, funded several companies at once—an unusual move. It preordered doses and invested in manufacturing facilities before trials were complete, reducing the risk for pharmaceutical companies looking to participate. Ironically, federal ineptitude at containing SARS‑CoV‑2 helped too. In the U.S., “the fact that the virus is everywhere makes it easier to gauge the performance of a vaccine,” says Natalie Dean of the University of Florida, who studies vaccine trials. “You can’t do a [Phase 3] vaccine trial in South Korea,” because the outbreak there is under control.

Vaccines will not immediately end the pandemic. Millions of doses will have to be manufactured, allocated, and distributed; large numbers of Americans could refuse the vaccine; and how long vaccine-induced immunity will last is still unclear. In the rosiest scenario, the Pfizer/BioNTech and Moderna vaccines are approved and smoothly rolled out over the next 12 months. By the end of the year, the U.S. achieves herd immunity, after which the virus struggles to find susceptible hosts. It still circulates, but outbreaks are sporadic and short-lived. Schools and businesses reopen. Families hug tightly and celebrate joyously over Thanksgiving and Christmas.

And the next time a mystery pathogen emerges, scientists hope to quickly slot its genetic material into proven platforms, and move the resulting vaccines through the same speedy pipelines that were developed during this pandemic. “I don’t think the world of vaccine development will ever be the same again,” says Nicole Lurie of the Coalition for Epidemic Preparedness Innovations.