The first volunteers are already waiting when Rosa G. gets to the lab. She’s worked as a technician on human trials before but never seen people so eager to be injected with an experimental vaccine. She meets the first subject, a young woman in a mauve tank top, in an examination room. She has her sit, then draws a few milliliters of clear fluid from a clear vial.
“Ready?” Rosa asks.
“Yup,” the woman answers.
Rosa jabs the sharp end of the needle into the soft flesh of her tricep and presses the plunger. The woman looks exactly as she did a moment before, but in an instant her body has become something profoundly different: a new front line in the battle between mankind and the novel coronavirus. Hundreds of thousands have died of COVID-19, and more than seven billion immunologically defenseless bodies await like dry chaparral at the height of fire season.
Rosa has dosed the volunteer with an experimental vaccine made up of a mishmash of microscopic particles of the SARS-CoV-2 virus that have been chemically chopped up and rendered harmless, like a pistol run over by a steamroller. Though incapable of causing infection, to the immune system they are antigens: foreign particles that are unfamiliar and presumed dangerous. In response to their presence, the body learns to create antibodies that will circulate and latch onto any identical antigens they may encounter in the future. In swarming an antigen, antibodies prevent it from carrying out infection, and they also mark it for destruction by hunter-killer cells.
The idea behind this kind of vaccine, called “whole killed” or “inactivated,” has been successfully used many times in the past, from the Salk polio vaccine to annual flu shots. But will this formulation stimulate the body’s immune defenses enough? Or, conversely, will it trigger dangerous adverse reactions, like the 1976 swine flu vaccine that left 450 with a crippling neurological disease?
Over the weeks that follow, Rosa and her team will administer shots to inoculate 500 healthy volunteers in what’s known as the Phase I clinical trial to make sure the vaccine isn’t dangerous. In a few months the research team will move straight on to Phase II trials, dosing several thousand volunteers and watching to see if their bodies start building defenses against the virus.
The usual timeline for the development of a new vaccine is 15 years. Researchers move methodically from test-tube experiments to animal trials and then on to humans. To move faster, Rosa and her colleagues are going to have to take shortcuts. And that could potentially endanger millions of people.
Rosa withdraws the needle and presses a Band-Aid onto the dot of blood.
“So am I immune now?”
“No, unfortunately. If the vaccine works, it will take your body a couple of weeks to build its defenses against the virus,” she says. “But since it’s experimental, you really can’t assume it will work. Keep staying safe. Sorry.”
The path to a post-COVID future passes through a single door: a safe, effective, and widely available vaccine. The Trump administration has claimed it can have hundreds of millions of doses ready by this fall, but experts view that timeline as all but impossible. The rapid development of a COVID-19 vaccine is a scientific undertaking on the scale of putting a man on the moon.
If anything, for the vaccine the stakes are higher, the time pressure more urgent, and the outcome more uncertain. A moon rocket is huge and must be built to exacting standards, but its physics are straightforward. While we have been making vaccines for decades, the COVID-19 vaccine is a blitz into unknown territory. No one knows in great detail exactly how the virus works, what effects it can have on the human body, and how it interacts with the immune system. The vaccine candidates are themselves complex systems whose interactions with human biology are not yet fully understood. So planning to develop a successful one is a bit like planning to win the lottery: Even if you’ve got the money to buy a whole ton of tickets, you’re going to need a certain amount of time and luck.
We’re definitely buying a lot of tickets. Around the world, more than a hundred candidates are currently under development. Many of pharma’s biggest names are pouring billions of dollars into research and manufacturing, including AstraZeneca, GlaxoSmithKline, Johnson & Johnson, Pfizer, Sanofi, and Merck. Some teams are moving quickly, hoping that they’ll get lucky and their efforts will pay off with a speedy solution. Others are laying the groundwork more methodically in order to improve their odds. Each project is a long shot; historically, fewer than 10 percent of candidate vaccines turn out to be safe enough and effective enough to use in human populations. That means that when the smoke has cleared, only a handful might wind up proving worthwhile. “If we can get two or three vaccines from this, I think we will be thrilled,” says South African medical researcher Helen Rees, who has worked for years on the development of an HIV vaccine and is currently evaluating COVID-19 drugs.
What follows is a speculative guess at how the months ahead might unfold, based on discussions with vaccinologists, physicians, and public health experts and on the latest published science about the coronavirus. It’s not intended as a prediction—if the history of vaccine development has taught us anything, it’s to expect the unexpected—but as a rough preview of the story arc ahead.
It’s not enough to find a vaccine; once one is found, billions of doses are going to have to be manufactured. At a weekly staff meeting, Rosa watches video updates from an engineer at a large pharmaceutical company that is retrofitting its manufacturing facility in Indiana to make their vaccine, tearing out old equipment that was used to grow virus particles in chicken eggs and replacing it with stainless steel brewing vats that will grow the virus inside human cells. Around the world, dozens of production facilities are being renovated and repurposed, and dozens more are under construction. Billions of dollars are being poured into the work, yet it’s almost a certainty that most of that investment will wind up getting thrown out, because each kind of vaccine requires a different kind of production facility. Those built to produce failed candidates will wind up getting torn down without producing a single vial: an insane approach, under normal circumstances, but one that makes sense if it can free the world economy from rolling lockdowns.
Rosa’s team works for a nonprofit research organization that is also tackling diseases like HIV and tuberculosis. This isn’t their first rodeo, and compared to players like AstraZeneca and Moderna, which announced that its vaccine produced antibodies in patients earlier that summer, they’re moving at a tortoise pace. But they also understand the importance of getting details right. As her boss likes to say, “The product is the process.” Moving too fast and fumbling could scotch what otherwise might have been a successful candidate.
As she’s doing the dishes one night, her cell phone buzzes with a text alert: The U.S. Department of Health and Human Services has abruptly canceled its funding for her project. She feels numb, then a flash of panic as she realizes what must have happened. Among the vaccine’s other backers is CEPI, the Coalition for Epidemic Preparedness Innovations, whose members include the World Health Organization and the Bill & Melinda Gates Foundation. At a press conference the day before President Trump said he’d heard that Bill Gates is an agent of the Chinese secret police and that he was plotting to use COVID-19 vaccinations to implant behavior-control chips.
Lightheaded, Rosa hurries to the sofa to sit down. She can’t believe that one of the leading vaccine candidates in the world, in the midst of a global pandemic, could just be cut loose.
In the end, it isn’t. After a week of frantic scrambling, CEPI patches together a deal in which the governments of France and Germany step in to make up the difference. The project is back on track.
Rosa’s team has barely finished inoculating the last of the Phase II subjects when they shift their focus to recruiting and inoculating Phase III subjects. The pressure’s on—Moderna and AstraZeneca have been in Phase III for months already, and are preparing to release their results. In this stage of the process, the goal is to see whether the vaccine candidate offers demonstrable protection against infection out in the real world. To do that, the researchers will need to find subjects who are at high risk of infection, give them the vaccine, and then watch to see how they do compared to subjects who didn’t get it. If the difference is stark, they’ll have the proof they need before they distribute the vaccine to the general public.
Every night on her subway ride home, Rosa pulls out her iPad and catches up on developments in the field. Toward the end of the month, rumors start to circulate that Phase III data is in on one of the candidates, and it’s strong enough to support the release of the vaccine to the general public. If this is true, it would be a breathtaking development. The candidate is based on a new and unproven technology: snippets of mRNA genetic material injected directly into a patient’s body, where they are taken up by cells and translated into viral spike protein, which the host’s immune system can learn to recognize. In the past the developer has been cagey about its results, preferring to issue press releases rather than let other scientists review their raw data, so it’s hard to know how seriously to take these claims.
Finally, a week before the election, President Trump himself makes the announcement: The results are in, and they show that the vaccine is “perfect.” Hundreds of millions of doses will be ready for distribution by the end of the week. He says that the coronavirus is a “bad hombre” but that “we kicked its ass.” Public reaction is surprisingly muted. The developer still refuses to release its Phase III data, and when pressed Dr. Anthony Fauci declines to endorse Trump’s characterization of the vaccine’s efficacy, saying only that he believes that “the vaccine will help reduce the severity of the disease in many patients, and thereby save lives.”
Rosa’s team and the other developers around the world continue to work on their vaccine candidates.
By New Year’s more than 40 percent of the U.S. population has been vaccinated against COVID-19. Schools, shops, and businesses have reopened. Life starts to feel like it did before the pandemic. But the feeling of relief is short-lived. It becomes clear that something has gone wrong. Not only do coronavirus cases begin to rise again, but some who’ve received the jab are showing up in emergency rooms with especially severe cases of COVID-19. It turns out that for some recipients the vaccine actually makes the disease worse, spurring the development of antibodies that, instead of blocking the virus from attacking human cells, work as a kind of gate pass to get them inside. On her phone Rosa watches a viral video of a nurse mopping the forehead of an unconscious child hooked up to a ventilator, his lungs and liver ravaged almost to the point of shutdown. When the child dies, public outrage spawns furious street protests across the country. Reluctantly, the NIH is forced to cancel the vaccine’s emergency authorization. All remaining doses are destroyed.
The methodical approach is paying off for Rosa’s team. The data from the three trial phases is coming in thick and fast now. Every morning Rosa sits at her cubicle with a cup of black Peet’s coffee and reviews the previous day’s data. Each batch adds to a slowly emerging picture, like the image in a newly snapped Polaroid. Unfortunately, the picture that’s emerging isn’t great. The volunteers who got the shots aren’t falling sick as often as the control group, and when they do fall sick their symptoms aren’t as bad. But they’re still getting sick. The vaccine appears to be only weakly effective.
By now a dozen vaccine candidates have been dropped, five appear to offer minimal protection, and the rest are still in too early a stage of testing to tell. Regardless of how they ultimately turn out, it’s looking less and less likely that a vaccine will be ready by the end of 2021.
To add to the frustration, COVID-19 maintains a tenacious grip on the United States. While countries like Germany, France, Japan, and New Zealand have successfully suppressed the pandemic and gotten back to life as usual, in the U.S. outbreaks keep popping up, getting beaten back, and popping up somewhere else. Amazingly, it’s still hard to get enough testing kits and even PPE.
Rosa and the rest of her team start a new trial, this time with a combination of vaccines: their own inactivated vaccine and another candidate that also proved only weakly effective in trials. This one is a so-called “viral vector” vaccine that implants spike-protein mRNA into a virus that normally infects chimpanzees. The chimp virus can’t replicate in humans, but it gets the mRNA into the human cells, where it can be translated into spike protein. When registration begins for Phase III volunteers, Rosa adds her name to the list.
A particularly severe wave of the pandemic swells and retreats, leaving the U.S. death toll at north of half a million. The shared trauma has not unified Americans behind the science that could save them, but fractured it. As she’s arriving at work one morning, Rosa finds a picket line of shouting, unmasked protesters. One carries a sign that reads: “Vaccine = Mind Pollution.” Rosa has no idea what that’s supposed to mean. As she pushes through, one of the protesters screams, “Bill Gates lies!” and deliberately coughs on her.
Her mask filters out two-thirds of the virus-laden particles, but thousands get through and settle inside her mouth and throat. That evening the first generation of infected cells is bursting, seeding millions of virions up and down her respiratory tract. The next morning, she wakes up feeling meh. She checks her temperature: 99 degrees. Not enough to stay home from work. Only weeks later, when she goes to have her blood drawn as part of the trial, will she learn that her inoculation helped her beat a case of COVID-19.
Rosa’s case isn’t statistically significant. But taken together with what is happening to the hundreds of other volunteers, it is a point in a compelling picture. Taken in combination, these two vaccines work.
A series of conference calls between CEPI, WHO officials, and government regulators turns into a flurry of Zoom meetings and group chats with pharmaceutical companies, manufacturers, logistics specialists, and NGOs. With growing excitement, the community realizes that a consensus has emerged. The time has come.
The groundwork has been well laid out. For months factories filled with giant tanks of growth medium, the solution used to grow microorganisms, have been running flat out. The regulatory playbook has been torn up and patched back together a third of the time. Officials have reviewed the study data, checked plant blueprints, assessed production standards. The chance that things could go terribly wrong is much higher than normally would be deemed acceptable. But the upside is too huge to pass up.
Calls go out. The next morning, Rosa is standing in Times Square when the alert scrolls across the news crawl:
EFFECTIVE NEW COVID-19 VACCINE APPROVED WORLDWIDE.
Although hundreds of millions of doses have already been manufactured in anticipation of this moment and stockpiled around the globe, that still only covers a tiny fraction of those who need to be protected. So it will be administered in tranches: first to front-line health care workers, then the elderly and ill, then essential-industry workers, then children, then adults with compromising medical conditions, and finally healthy adults.
Around the world, church bells ring, car horns blare, and strangers hug. But in the United States, the jubilation is short-lived, as the government announces that a monopoly in the country has been granted to a company owned by the husband of the secretary of Health and Human Services. Elsewhere in the world, the shots will cost $5; here they will cost $500. In Times Square, protesters turn over a police car and set it on fire.
Rosa is staring out the plane window when the whiteness of the clouds gives way to the choppy gray waters of the harbor and the skyscrapers beyond. She’s surprised at the surge of emotion she feels at the sight, a mixture she can’t quite name. It’s been nearly a year since she moved to Amsterdam to lead an influenza research team, and she’d thought she was done with America for good.
She walks around her old neighborhood in New York, past the place she used to live, her favorite bar, the park. She’s jetlagged and plane-weary, and it all feels like a dream. Shops are boarded up and her friends have moved away. The people on the sidewalks now are different people. They walk around without masks, strolling hand in hand, standing close to each other and talking and laughing without care.
There’s a coffee shop now where the old pupusa place used to be, with tables out on the sidewalk. Rosa takes a seat under a linden that is still unfurling its buds. At the next table a couple sit with their chairs pressed together. They’re probably the same age Rosa was when she came to the city. She can imagine how they feel, the exciting sense of possibility, and is happy for them. Her city is gone, but theirs is just beginning.
This article originally ran in GQ on July 16, 2020.