Monday morning, 8 am. Neal Browning walked into the waiting room. He took in the reception desk, the play area for kids, the table full of magazines that he was too cautious to touch. There was another patient waiting, a woman in her forties with brown, chin-length hair. Browning wasn’t sure whether she was here for the same historic reason that he was, so he decided to follow standard waiting-room procedure and sat quietly—no conversation, no eye contact. After a few minutes, a nurse called the woman back and he watched her disappear behind a door. Another few minutes passed and it was his turn.
First, there were questions: Still no fever? Still no contact with anyone who’s been sick? Then there was a round of blood draws. Browning, a 46-year-old network engineer, had taken the morning off from his job at Microsoft, where he’d been unusually busy for weeks: His team was following the spread of a deadly new virus around the world, preparing firewalls and VPNs to allow a global workforce to suddenly start working from home. The engineers trailed the virus from Wuhan to the rest of China, to Europe, and to his own doorstep in Washington state.
Eighteen days before he walked into the waiting room, a teenager who lived 10 miles from Browning’s house in Bothell, Washington, had tested positive for the new virus. The teen hadn’t traveled abroad or had known contact with anyone with a positive case. Browning wrote on Facebook that Pandora’s box had been opened. The next day, officials announced that the first person in the United States had died from the virus, at a hospital just 5 miles from Browning’s house. (Earlier deaths would later be uncovered.) A few days later, when a friend texted Browning with news that a group of researchers were looking for volunteers to test a possible new vaccine, he marveled at how quickly the vaccine had appeared but didn’t hesitate to sign up.
The researchers got in touch, asking to check his blood work and his medical background. (For the earliest phase of trials, they were looking for participants with a clean bill of health, so it would be simpler to trace any changes caused by the vaccine.) Browning started Googling. Viruses, vaccines, RNA, DNA—so many details of his own biology to which he hadn’t spared a thought since an introductory science class back in college. He talked with his fiancée and his mother, both of whom are registered nurses, about the risks of offering himself as a test subject. There was the chance he’d have a bad reaction to the shot; the theoretical possibility that the vaccine might make his body produce antibodies that actually made the virus worse; and simply the inherent risk of unknowability associated with the brand-new. Still, to Browning, the risks seemed low when compared with the known danger. On the news, he watched as deaths mounted at a nearby nursing home, as the governor shut down concerts and then schools and then businesses. Now the moment was here, and he had no doubts. Only hopes.
Browning watched as his veins filled vial after vial, each of them a viscous red record of what his body was like now, in its “before” state. Then it was time for the shot. It took a few awkward tugs for the pharmacist to get the sleeve of Browning’s blue collared shirt above his deltoid, but that was the only drama visible for anyone to see. The needle slid in, the needle slid out. A news camera clicked. Twenty-five micrograms of fluid, the first and fastest hope for stopping a pandemic that had been officially declared just five days before, diffused into the muscle of his right arm.
To Browning, it felt like “a big nothing.” That’s what it looked like too. He pulled his sleeve back down. The pharmacist disposed of the syringe. From this moment on, any action would be invisible, hidden away inside Browning’s body, where the dramatis personae were proteins and cytokines, T cells and B cells.
In the exam room, where he was asked to wait an hour to make sure there was no immediate adverse reaction, Browning sent some texts, messed around on his phone, and tried to imagine what might be going on inside him. Right now, as far as he could tell, the answer seemed to be not much out of the ordinary. It was entirely possible that this would prove true—that nothing much would happen. This very first human trial of a vaccine designed to fight SARS-CoV-2, the newly emerged coronavirus that was disrupting the world, could lead to disappointment, just like so many trials for so many other vaccines for so many other diseases. To make a successful vaccine, to test its safety and effectiveness, and to get it licensed for widespread use in healthy humans, is usually a long and arduous process. Development commonly takes a decade or more; historically, for any given attempt, the statistical chance of failure is 94 percent.
But Browning was an optimist. He knew that the vaccine candidate now in his arm had made it there in record time. Instead of years, the timescale was measured in days: Just 66 of them had passed since the genome of the virus had first been published. Maybe more records were possible. He lay on the exam table and hoped, fervently, that at the gates of his cells something big was beginning.
Across a panicked world, anybody who saw the day’s news—that the first four human beings had been injected with a vaccine meant to fight a virus that seemed to be changing everything—had to hope the same. Please, we pleaded, as businesses shuttered and families stayed apart and ambulance sirens wailed. Please, as people risked their lives in ERs and grocery stores. Please, as we tried to imagine a future that could safely return to what we had once been so bold as to think of as normal life. Please, let us be lucky, and please, down in the microscopic battlefield of Neal Browning’s immune system, let some drama be starting.
For the great hope against a 21st-century virus, inoculation is a surprisingly old technology. As early as the 10th century, the Chinese were known to put material from the lesions of people infected with smallpox on the nostrils of the healthy, in an attempt to give them a less virulent course of the disease; by the 1600s, people in the Ottoman Empire were letting pus be grafted under the skin of their arms and legs. In the 1720s, an updated version of the practice was so accepted that Caroline of Ansbach, the Princess of Wales, had it performed on her two young daughters. (Still, the death rate for those inoculated was as high as 3 percent.) Edward Jenner, the English doctor who proved that exposure to a different virus, cowpox, protected people from getting smallpox at all, started shipping what are considered the very first vaccines (the word derives from the Latin word for “cow”) to his medical colleagues in the same decade in which Eli Whitney invented the cotton gin.
Since then, the process of vaccine creation has changed dramatically. In the 19th century, scientists discovered that they could teach people’s immune systems to fight off viruses by exposing them to versions inactivated with heat or chemicals. As methods advanced, they found they could breed less virulent versions of viruses in labs. They could also make effective vaccines by exposing human cells to only a small part of a virus, such as the protein structures that actually irritate the immune system, or even to synthetic structures, convincing enough to be thoroughly confused for the real thing. They could circulate those structures by attaching them to other, less dangerous viruses; they could even, theoretically, instruct human cells to make the structures themselves. What mattered was simply that the body could meet a convincing enough threat that it would prepare its own specially designed resistance in advance, before it ever encountered the real thing. The strategies changed, but their basic principle stayed the same: For all our technology, our best defense is still to activate the ancient protections that are already waiting inside us.
When something unfamiliar and possibly dangerous enters your body, the first response is from what’s known as your innate immune system. This is your fastest, oldest (evolutionarily speaking), and certainly bluntest response to invasion, with one basic arsenal of weapons to use against whatever it meets. For its signature move, the innate immune system leans heavily on inflammation—which can manifest as everything from redness around a small cut to classic cold and flu symptoms such as fever and coughs to swelling in and around vital organs—as a way of calling in white blood cells to attack invaders. What we perceive as symptoms are often our bodies’ own, cruder defenses, mobilizing to kill germs where they are and keep them from spreading through the body. “When this process works correctly,” says Angela Rasmussen, a virologist at Columbia University’s Mailman School of Public Health, “inflammation is very tightly controlled.”
That’s because the innate immune system is also responsible for calling in your next, and more sophisticated line of defense—your adaptive, or acquired, immune system. This is the smart system, the one that can change and adjust, build new defenses to deal with specific threats, and then hold those protections in reserve in case their corresponding threats return. It also regulates the innate immune system. Peptides called cytokines serve as messengers, letting your immune responses know when it’s time to accelerate or pull back.
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Benjamin Neuman, a virologist at Texas A&M who has been studying coronaviruses for more than two decades, compares the innate immune system to a baby having a tantrum. It doesn’t learn, and it can’t recognize what it’s actually mad at; it mostly just screams and shouts and throws things. (Because its tantrums can be dangerous, Neuman also compares it to Rambo, firing its ammunition indiscriminately in all directions.) Still, its reaction protects you, somewhat, while the adaptive immune system, the adult in the room, hears the yelling, tells the baby to calm down, and figures out what to do.
This is where your B cells and T cells, the problem-solvers and soldiers of the adaptive immune system, come in. Each day, these cells are undergoing their own form of natural selection: developing and recombining at random to create billions of antibodies and receptors in different patterns, each of them a possible match for dangers your body has never actually encountered. (T and B cells, thanks to this random development, are some of the only cells that are different from one identical twin to the next.) All that variation creates a vast, always rotating repertoire of potential immune responses. When a new virus comes along, wielding a new shape of protein that it can use like a crowbar to break into your healthy cells, some of your B and T cells, simply because there are so many of them, will be able to neutralize it. (The name for the specific molecular structure that your immune system targets is “antigen.”) Immune cells are “circulating in your blood, all the time, just waiting to bind with their specific form,” Rasmussen says. “They’re out there, looking for their one. And for a very small percentage of those, that one is going to be SARS-CoV-2.”
Once the match is made, the cells that can make the right antibodies start replicating like mad. This, plus something called immunological memory, is why vaccines work: B and T cells, like a sports team learning the playbook of a rival, gradually become better and faster at counteracting the new intruder. When the adversary (or, in the case of a vaccine, the imitation of the adversary) is gone, the immune system hangs on to copies of the playbook, in the form of clones of those more “experienced” cells. If the antigen returns, they can skip the whole process; they already know how to win.
Every vaccine, explains Shane Crotty, a virologist in the Center for Infectious Disease and Vaccine Research at La Jolla Institute for Immunology, depends on this scattershot genius of the immune system: “Boy, are you glad that you have those rare cells that could actually recognize the rare germ.”
Inside your body, the arrival of a new virus starts the clock on a frantic race—but a strange one, where the runners are full of tricks and schemes to try to trip each other up. The virus, unable to survive on its own, wants to hijack your cells and use them to replicate itself. For your adaptive immune system, the challenge is to find and create enough of the right antibodies before the virus spreads too far—but also before the screaming baby Rambo that is your innate immune system does too much damage.
With SARS-CoV-2, the competition is a particularly difficult one. Some viruses are made up of only the bare minimum genetic material necessary to get inside a host cell and make copies of themselves. But coronaviruses, says Neuman, “are the biggest RNA viruses that we know, and so they’ve got more of these little bells and whistles”—by which he means clever tricks to bias the race, to confound and hobble and outrun the immune system. “They’ve got the gold package,” he says. The novel coronavirus is as much as 10 times better than the first SARS virus at binding to a cell. Once inside, it twists the structure of human cells, turning them into superefficient virus factories. It has a camouflage strategy that lets it sneak past cell receptors. And it has an enzyme that Neuman likens to a paper shredder: It destroys the messenger RNA that the cell uses to call for help once it does realize that something has gone wrong.
Scientists are still scrambling to understand the details of how the novel coronavirus affects us and why different people, once infected, have such different outcomes. But the patients who do best, Rasmussen says, seem to have ongoing, solid communication between the parts of their immune systems: a quick inflammatory response, but one that is turned off once it has served its purpose. When patients die, it appears to be because the virus has managed to spread widely by sneaking past or disabling the alarms. The body responds, belatedly, with “an immuno-pathological response”—so much unregulated inflammation that it damages its own cells and organs. Doctors are seeing what are called “cytokine storms,” surges of uncontrolled activity by the innate immune system, in the lungs but perhaps also in the liver and kidneys, the heart and the brain. “It’s chaos,” says Rasmussen. “Every cell is yelling these pro-inflammatory messages.” If no one comes to hush the angry Rambo baby, and it keeps screaming and shooting, the damage can be widespread. “The innate immune system buys you time,” says Neuman, “but it will also kill you if left to its own devices.”
Some hospitals have begun taking plasma from people who have recovered from the virus and transfusing it into people who are still fighting it. This is meant to give a struggling immune system a breather, a chance to catch up. But the break is only temporary; plasma can’t teach your body to actually beat the virus. It has to learn on its own. So for now, the outbreak is this: millions of infected people whose immune systems are running their own individual sprints, some of them desperate and dangerous, against an opponent trying to fill the course with potholes and trip wires. We’ve separated ourselves from each other in an attempt to keep our champions from ever getting on the track, so that most racers will at least have access to the doctors and nurses and medicines and ventilators that will give them the best chance of winning. But in the meantime, we’re stuck. We can’t relax our social distancing without sending more racers into a deadly arena.
Unless, that is, one of the candidate vaccines that researchers are developing is successful in giving our adaptive immune systems a major head start against the virus. Neuman described vaccines as a fitting rejoinder to a sneaky opponent, a way to re-bias the rules of the race in the other direction—tilting them, decisively, in our own favor. Crotty used the same metaphor but continued it a little differently. “That’s the brilliant thing about a vaccination,” he says. “You get rid of the race.”
The record for the fastest path to a licensed vaccine, depending on how you clock it, is held by the mumps vaccine—developed in just four years in the 1960s—but the process is usually far slower. In February, years after an outbreak that caused more than 11,000 deaths, four African countries finally licensed an Ebola vaccine that had been in development since at least 2003. “The international response was too late,” Norway’s prime minister, Erna Solberg, said in 2017, as the vaccine inched forward. “But now we know how to respond faster the next time.”
Solberg was announcing the formation of a new international organization with a goal of underwriting and coordinating accelerated development for vaccines when they were most needed, during outbreaks. The Coalition for Epidemic Preparedness Innovations, or CEPI, would focus on a short list of priority diseases. One was Middle East respiratory syndrome, or MERS, a disease caused by a coronavirus that emerged in Saudi Arabia in 2012. (It wasn’t easily spread, but of those who got sick, about a third died.) The coalition would also start planning to respond to a theoretical disease, which the World Health Organization referred to as “Disease X.” It was likely to emerge suddenly, just as MERS and its predecessor, a coronavirus that caused severe acute respiratory syndrome, had. And it might be deadlier or more easily transmissible. Disease X might belong to any number of virus families, says Melanie Saville, CEPI’s director of vaccine development, but coronaviruses were “one of the ones that we thought was a prime candidate.” Whatever it turned out to be, a deeply interconnected planet could find itself desperate for the fastest possible vaccine. “What happens in Lagos will affect Davos tomorrow,” Jeremy Farrar, director of the Wellcome Trust in the UK, said when CEPI was announced. “The world is incredibly vulnerable.”
Some of the slowest parts of the vaccine development process are the necessary rounds of safety and efficacy testing: Because vaccines are given to people who aren’t already sick, their rewards must be proven to dramatically outweigh their risks. And clinical testing depends on waiting long enough for human bodies to reveal success or problems; for that part, Saville says, “there’s no shortcut.” So CEPI officials, as they began investigating other ways to speed things up, started investing in what they called “rapid-response platforms,” new and experimental methods of vaccine development that they hoped could move to clinical trials in record time.
In the US, Barney Graham and John Mascola, leaders at the Vaccine Research Center, and their boss, Anthony Fauci, the director of the National Institute of Allergy and Infectious Diseases, were thinking along similar lines. In 2018 they wrote that traditional vaccine development methods, using whole viruses or even proteins, were hindered by their need to be uniquely designed to fit different viruses. Newer technologies, including those that used either DNA or messenger RNA to move through the body, could potentially work for multiple viruses, with only parts of their designs swapped out. With more research, these platforms might herald a new era of far quicker vaccine deployment. Since 2003, they noted, the institute had developed candidate DNA vaccines to target SARS, two influenza outbreaks, and Zika, and had seen the time it took to go from a sequence of a new virus to the first phase of human trials shorten from 20 months to just over three.
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Rather than introduce killed or weakened viruses as the antigens to activate the immune system, DNA vaccines are meant to work by convincing the body to become its own antigen factory. The vaccine delivers a carefully designed DNA sequence, which enters a cell and instructs it to create a protein that imitates part of the virus. If all goes as planned, the body starts producing both an ersatz attacker and the defenses it needs to stop it. Crucially, if a new virus comes along, the same platform can be used to target a different antigen.
The institute was also working, in collaboration with Moderna, a relatively small biotech company based in Massachusetts, on a new vaccine to prevent MERS. This vaccine would essentially skip a step and directly inject messenger RNA encoded with the genetic blueprint that instructs a cell to build a version of the spike protein that MERS uses to penetrate cells. Like a DNA vaccine, this platform could be rapidly repurposed and redeployed, without waiting for a lab to modify and grow a bunch of viruses. (More traditional vaccines rely on cells grown in giant bioreactors; the machines that Moderna uses “look more like little beermaking kits,” says Ray Jordan, Moderna’s head of corporate affairs.) All that was needed to get started was a genetic sequence. And then, Jordan says, “instead of the bioreactor, you use the human body.”
Saville says these mRNA vaccines are “an early but very promising platform.” Still, there are lots of ways trial vaccines can fail; in the worst cases, they can actually make the immune response more unregulated, the disease’s damage worse. With RNA vaccines, though, a common concern has been the opposite: There’s no actual virus replicating in the body, which means that these vaccines are believed to be safe, but they might not trigger the complex chain of immune responses. Even if the vaccine works as planned, and the immune system creates antibodies that target the chosen antigen, those antibodies may not be sufficient to actually make the recipient immune. But the technology has been rapidly improving. Moderna’s first crack at a Zika vaccine, for example, didn’t create much of an immune response. A second try was at least 20 times more potent, according to an article in Nature.
By the winter of 2019, Moderna had eight mRNA vaccines, for a variety of viruses, in some stage of development: Six were in Phase 1 trials, which primarily test the safety, not the effectiveness, of a vaccine candidate, while one was just preparing to enter a Phase 2 efficacy trial. According to the company, all had shown some form of immune response—not proven effectiveness, yet, but signs that are correlated with it. Still, Moderna had not yet brought a single vaccine all the way through human trials and into the market. Nor had any other company created a DNA or mRNA vaccine of any kind that had been approved for use in humans. It was still a hope waiting to be verified.
Late last December, fewer than three months before Neal Browning and the three other first vaccine trial participants offered their arms for injection, Jason McLellan, who runs a molecular biosciences laboratory at the University of Texas at Austin, started hearing about a new respiratory pathogen that had just emerged in Wuhan, China. Given the symptoms, he wondered if it might be a coronavirus.
McLellan had done his postdoc at the Vaccine Research Center, working with Barney Graham. When he finished in 2013, shortly after the emergence of MERS, he talked to Graham about what he should do next. They agreed there was a family of viruses calling out for further study: “We thought it was clear that there would be additional coronavirus outbreaks.”
McLellan started his own lab, which focused on understanding the protein structures of just two families of RNA viruses: Pneumoviridae, such as respiratory syncytial virus, which widely infects infants and children, and Coronaviridae, whose spike-shaped proteins are now infamous. The spike, his team found, operated similarly across all the coronaviruses they studied. The lab members began to create three-dimensional maps of the spikes, so detailed that they showed the location of each atom. (They used a technique called cryo-electron microscopy: essentially using liquid nitrogen to freeze molecules in place, and then using a bombardment of electrons to capture their structure.) They knew that blueprints of the structures that the adaptive immune system would have to learn to neutralize could be invaluable for future efforts to make vaccines.
But there was a complication: The spikes kept transforming. It was their nature. They needed to be one shape to bind to a cell and then another to enter it; once this fusion began, what started out looking like a mushroom changed—losing its cap, elongating, and twisting into something new. It might do little good for the immune system to learn to recognize this post-fusion structure, so McLellan’s lab started researching ways to stabilize the protein, locking it into the shape that it actually used to break into cells. They mapped which parts of the structure changed and which didn’t, and they found that they could use carefully engineered genetic mutations as if they were staples, locking down regions of the spike that wanted to move around by binding them to regions that did not.
In early January, McLellan was snowboarding with his family in Utah when he got a call from Graham. He was calling about the disease circulating in Wuhan: “It looks like this is a coronavirus,” Graham said. “Are you ready to put everything together and race on this?”
“Yes,” McLellan replied. “We’re ready.”
On January 10, one day before China announced its first death from the new disease—at that point it was known to have sickened just 41 people—a consortium of researchers published a draft sequence of the genome of the new virus. Labs across the world got to work. In Texas, it was Friday night, but McLellan and his team didn’t wait. SARS-CoV-2 was a new version of a familiar problem; they could apply the stabilizing mutations they’d been developing right away. McLellan messaged Daniel Wrapp, a grad student, on WhatsApp. The next morning, Wrapp and Kizzmekia Corbett, the scientific lead of the Vaccine Research Center team that studies coronaviruses, got to work using mutations their colleague Nianshuang Wang had already identified. Within an hour or two, they had a genetic sequence for a stabilized version of the new virus’s spike protein.
As their MERS collaboration continued, scientists at the Vaccine Research Center and Moderna had been exploring whether it would be possible, if a viral epidemic were to break out, to work together and use Moderna’s mRNA platform to make a rapid vaccine. Within a day of getting the sequence of the new virus, they decided to try. In those early days, the outbreak was still widely expected to be contained. Rather than a world-changing pathogen, says Moderna’s president, Stephen Hoge, the virus at first seemed like an interesting opportunity to test the potential of their collaboration and their technology.
The scientists adapted their previous work to target the specific spike of SARS-CoV-2. “Plug and play,” Corbett calls it. First, they had to choose which protein to express. The teams considered whether to use the wild form of the new virus’s spike protein or the stabilized, pre-fusion one, but they agreed that the latter was more likely to make the best antigen. (“The point of a vaccine is to do better than natural infection,” Corbett would later explain on CNN. “The point of a vaccine is to create an immune response that is very potent, so, high-level immunity for an extended period of time.”)
Then it was up to Moderna to decide how to encode that protein in mRNA—a problem with an overwhelming number of possible solutions, but one that the company had prepared for, by using machine learning to train algorithms to pick sequences best able to express a given protein. From those possibilities, they manually selected the most promising. (They also planned backups, in case their selection wasn’t supported by new data, but the alternatives didn’t prove necessary.) By January 13, the scientists had finalized the genetic sequence of a vaccine they called mRNA-1273, which would enter Neal Browning’s arm two months later. The process was incredibly fast, says Jordan, but only if you ignored all the work that came before. “You’re able to do this in a few weeks, but it’s a few weeks plus 10 years.”
Even with the head start, beginning the trials so quickly required a sprint. The news about the virus’s spread, and its effects on those it infected, kept getting scarier. It was soon clear that more was riding on the vaccine than anyone had initially realized. Within two weeks, scientists at Moderna, without being asked, were staying late, working weekends. Corbett’s team started growing spike proteins and stocking freezers with vials. They immunized mice with the vaccine, then tested their blood for antibodies. A clinical batch was ready by February 7, tested and shipped by February 24, and green-lit for human testing by March 4. (It was a coincidence that the human trials began in what had, by March, become the first hot spot in the US; Kaiser Permanente Washington Health Research Institute had been selected to conduct them in late January.) There was never a singular moment, says Hoge, when he realized the researchers had begun an 18-month marathon. Instead, “it felt like every day, can you run faster, can you run faster, can you run faster?”
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Even after trials began in record time, that remained a key question. Were there other ways to speed up development? Usually, a vaccine moves through phases sequentially, proving itself before its producers are willing to invest in the next step. By the end of January, CEPI selected mRNA-1273, along with three other vaccine candidates, for emergency funding, allowing the researchers to start preparing extra vaccine material for future phases of testing. In April the US government approved nearly half a billion dollars for Moderna from the Biomedical Advanced Research and Development Authority (Barda)—money that would allow for more staff, more equipment, and more space to produce large quantities of a vaccine that was still months from being proven (or disproven) to work. (Barda also supported other companies, including Johnson & Johnson and Sanofi.) Instead of the normal sequential process, Jordan says, Moderna was “shingling”: preparing everything it could, as soon as it could, in the hope that all the work wouldn’t turn out to be wasted. “This is not normal times,” explained Hoge. The company is now preparing to produce a million doses a month by the end of this year, and tens of millions of doses a month in early 2021. All of a vaccine that has not yet entered an efficacy trial.
On the same day Neal Browning got his shot of Moderna’s first-out-of-the-gate vaccine, another candidate from the company CanSino Biologics in China became the second SARS-CoV-2 vaccine to officially move into human trials. Within a few weeks, three other vaccines—two from Chinese labs and a DNA-based one pioneered by the Pennsylvania-based company Inovio—also got the green light. The list of projects for vaccines targeting SARS-CoV-2 expanded and expanded and then expanded some more; as of mid-April, the WHO listed 78 active efforts and 37 others for which statuses weren’t public. CanSino announced that one of its vaccines was ready to move onto efficacy testing.
The candidates could be used to teach a course on the history of vaccine strategies—on the growing diversity of methods, on their different strengths and drawbacks, on our continued reliance, no matter what, on our own immune response. Including Moderna’s and Inovio’s, there were some 20 vaccines using nucleic acids, split almost evenly between RNA and DNA platforms. Some vaccines used the real virus, either attenuated or inactivated; some used viruslike particles, or recombinant protein, or peptides, or replicating or nonreplicating viral vectors. When asked which approach she found most promising, Rasmussen replies that it’s still much too early to make more than a pure guess about which of the vaccines, if any of them, might be the one the world is waiting for. “I’m most interested,” she says, “in the vaccine that works.”
Still, the flowering of options reminded her of something. The growing list was a bit like a bunch of B cells, each floating around with a possible solution locked inside, each one part of a system that works simply by throwing answer after possible answer at a vexing new problem. In trying to help the ancient, adaptive defense system inside us prepare for a brand-new challenge, our scientific response had come to resemble it.
On March 23, seven days after his injection, Neal Browning returned to the office to have his blood drawn again: the first record of his immune system’s “after” state, though it was likely still too soon for any antibodies his body might be creating to be detectable. (The researchers didn’t expect to have results about immune response to share until late June.) In the waiting room, he saw the same brown-haired woman he’d noticed the week before. This time, they smiled and, from a safe distance, greeted each other. “You’re Neal,” she said. “You’re Jennifer!” he answered—Jennifer Haller, the world’s very first coronavirus vaccine recipient. Browning was the second. They recognized each other from being interviewed on TV.
Haller reported that she’d experienced no problems with the vaccine, and Browning agreed: “a feeling of underwhelming normalcy,” he called it.
In a few weeks, they’d return for another injection—a booster to juice their immune systems. By then, to calibrate the body’s response, two other cohorts of volunteers would have received their doses: injections of four and 10 times more vaccine that Haller and Browning received. The trial would have expanded to include volunteers considered both “older” and “elderly,” the ones who would need a vaccine the most.
Later, there would be more volunteers, more trials. If everything perfectly followed the desperate hopes of a watching world, a vaccine might really be ready for widespread deployment 12 to 18 months after Anthony Fauci, standing next to the president, had proposed that record-setting timeline. Under emergency protocols, it might be ready for higher-risk groups, such as health care workers, even sooner.
But all that waited somewhere in the deeply uncertain future. For now, almost three weeks after getting his first shot, Browning sat on the deck behind his house, watching a parade of hummingbirds come and go from his feeders, their wings beating so fast he couldn’t see them but still holding them aloft. He thought, yet again, about what his cells might be invisibly up to. There were a lot of possibilities. His B and T cells might be getting more efficient at fighting SARS-CoV-2 all the time; Crotty’s research has shown that, after a month, new generations of immune cells might be 1,000 or even 10,000 times better at binding to a pathogen than they were on the day of the shot. Or, it was possible that even now, all that carefully constructed RNA could be degrading away, leaving behind no real sign that it had ever been introduced.
Browning continued to be an optimist. When he pictured his immune system, he imagined a cadre of his own personal armed guards, sentries out on patrol. Maybe their training against their newest adversary had gone exactly as the whole world hoped. “Maybe,” he says, “my body saw it, and fought it off, and it’s done.”
BROOKE JARVIS lives in Seattle. Her most recent feature for WIRED, in issue 28.04, was about the natural world and carbon sequestration.
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