text: In April, Cecie Elnicki agreed to participate in two possible upcoming COVID-19 vaccine trials. She'd previously volunteered with the same company conducting the trials, Manna Research, for a potential vaccine against the dangerous, hospital-acquired Clostridioides difficile, or C. difficile, bacteria, and also, a few years before that, for both a shingle vaccine and a flu vaccine. The media attention that followed her decision seemed to surprise her. One of her daughters was a frontline health worker during SARS, and the same daughter's husband was now working in a critical care unit. They were doing their bit during the pandemic. This was her way of doing hers. She didn't see herself as a hero, and despite some interviewers' attempts to push her to say otherwise, she didn't see her decision as dangerous, either. She saw it as a sign of hope—and as a way to further medical progress. She thought back to her C. difficile trial and how it could save lives. She was only too glad to say yes again, but also, she stressed, it wasn't that big of a deal. Elnicki joked that she only shared a single concern when contacted: after hearing that one of the candidates came from the U.S., she quipped, "It doesn't have any disinfectant in it, does it?"
  
  For all her modesty, people like Elnicki are a vital part of vaccine development, and especially so when that development is unlike anything previously attempted. Public health experts and virologists both widely agree the pandemic won't end until we have a vaccine. But what that means is more complex than many might realize. Under non-pandemic circumstances, vaccine development takes years, or even decades, making it an expensive, painstaking process. Attrition is high, and multiple candidates are often discarded before a vaccine is licensed for use in humans. Because of this, developers usually obey a set of established steps, checks, and balances, all in the same precise order. After animal trials are complete, human ones begin, following three distinct phases. The first vaccinates a small group of healthy people, who are monitored for adverse reactions. If the vaccine passes the first phase, it will next be administered to hundreds of subjects, where it will be evaluated for efficacy. The final phase stretches the net out to thousands, tracking participants to find out what happens when they naturally come into contact with the pathogen and determining whether it works at a group level. And not only does the vaccine have to work, it has to have the ability to be mass manufactured, all without losing quality or pushing the price point too high.
  
  The slow and patient progress of these tried-and-tested steps, however, makes little sense in a pandemic. That's why researchers worldwide developed a new paradigm under SARS-CoV-2. They wouldn't dare skip steps—a certain disaster—but they decided they could do them all at once, without waiting to see if the traditional first step was successful. For example, in some cases, animal trials and phase 1 clinical trials have been happening in parallel. Kelvin, for instance, has continued her animal testing to determine the various candidates' safety and efficacy, even as her colleagues have sought government approval to begin human trials on some of those platforms, or have already started on others. In certain instances, developers also began early manufacturing scale-up and commercial scale processes before ascertaining whether the vaccine had concrete clinical proof of concept. Such concurrent work is undertaken at considerable financial risk; if a vaccine fails a step, the sunk cost may be much, much higher than usual. Complicating it all further, most of the next-generation platforms have never been licensed for use against any pathogen and, therefore, have never been manufactured at a large scale. Meaning, not only are vaccine developers taking a chance on whether the platform is viable, they're also taking a chance on whether it can be made on a significant scale. And even after all these problems are solved, countries still have to convince enough people to get the vaccine.
  
  Though they've saved lives and helped control, and even eradicate, disease for centuries, vaccines have never had an easy or straight narrative. In 1717, Lady Mary Wortley Montagu, the wife of the British ambassador to Turkey, witnessed her first variolation in Constantinople. A precursor to vaccination, the process involved inserting a thread into the pustule of a person infected with a mild case of smallpox, and then inserting that saturated thread into a small cut in the arm of a healthy person, where it was left to soak for twenty-four hours. The motivation behind the experimental procedure was simple: everyone seemed to know that if a person survived smallpox, they never became infected with it again. So why not try to induce a mild, survivable case to ward off a more serious one? At the time, this method of protecting against smallpox—a disease that could both kill and permanently disfigure—was common in the Middle East and Asia, but not in Lady Montagu's home continent of Europe. As someone who'd survived but been gravely scarred by the disease, she vowed to have her children undergo variolation. When it worked, she spread the gospel upon her return to England. The apparently miraculous procedure was, however, met with plenty of skepticism, and it was initially carried out only on prisoners, who were offered freedom if they survived. Eventually, the method gained advocates across the Western world. George Washington used it to inoculate his entire army. Catherine the Great tried it, and the Princess of Wales inoculated her daughters. The controversy stuck, though: variolation was expensive, and it risked both killing its recipients and further spreading the disease.
  
  Still, the process undoubtedly inspired Edward Jenner, who is frequently dubbed the "father of vaccination." Working as a rural doctor in England, Jenner noticed that milkmaids infected with cowpox, a mild illness, also seemed to gain immunity to smallpox. Though he wasn't the first to notice the seeming coincidence, he was the first to document it and to gather data to confirm it. And, in 1796 he convinced his gardener to let him experiment on the man's eight-year-old son. (Eighteenth-century England may have been the peak of new science, but it was evidently not so great on the ethics front.) Jenner first gave the boy the cowpox virus, and then smallpox. He called his new process a "vaccination," drawing from the Latin word vaccinus, meaning "from cows," and thus naming the method after the black-and-white spotted animals that had made it possible. The smallpox vaccine came with less risk than variolation, and Jenner quickly gained high-profile converts, including Pope Pius VII and Napoleon, as well as high-profile controversy.
  
  Indeed, the birth of vaccines arrived with a twin: the birth of the anti-vaccination movement. In part, Jenner did some of the damage himself. He refused, even in the face of good evidence, to admit his vaccine did not offer lifelong immunity. (Today, it's believed the smallpox vaccine lasts up to twenty years before a person has to be revaccinated.) But opposition also came in the form of libertarianism: people resented the apparent intruding powers of the state, under what they saw as the guise of public health measures—call it, perhaps, the great, great, great, great grandparent to the current anti-mask movement. Others feared it violated God and nature to put something from a cow inside a human. As Frank M. Snowden wrote in Epidemics and Society, cartoons depicting vaccine recipients as hapless horn-sprouting monsters began to rise in popularity. One doctor stoked the hysteria, added Snowden, by saying women who took the vaccine would wander into fields and embark on sexual relations with bulls. Nonetheless, Jenner's smallpox vaccine marched on over the next two centuries and, in 1980, the WHO declared victory over the virus. Thanks to a concerted public health effort and vaccines themselves, naturally occurring smallpox was wiped from the earth.
  
  But the anti-vaccination movement persisted. Less than two decades after smallpox was eliminated, British surgeon Andrew Wakefield published a since-debunked article in the Lancet that linked the measles, mumps, and rubella vaccine to autism-spectrum disorders. It didn't seem to matter that biological signs of autism are readily visible in utero, or that it was later discovered that he'd knowingly fabricated the medical histories of his subjects, or even that he accepted six hundred thousand dollars from a law firm planning to sue vaccine manufacturers. As Joshua S. Loomis sharply noted in Epidemics, "Suddenly, everyone was an infectious disease expert because they had read a secondhand account of a study on a blog or website." It was, as Loomis put it, "an explosion of ignorance." Once rare, measle outbreaks began reoccurring, and have continued to do so. Whooping cough was under control for decades, something that is no longer true. The scrutiny and misinformation campaign surrounding the human papillomavirus (HPV) vaccine has allowed the virus to stick around. The more resistance there is to the idea of preventable disease, the more opportunity said diseases have to evolve. The anti-vaccine movement has the same potential to damage efforts against COVID-19. In October 2020, for example, Nature Medicine released a survey of people in nineteen countries that showed only 71.5 per cent said they would be very or somewhat likely to take a COVID-19 vaccine. The rest said they would hesitate or outright refuse. It's just enough for herd immunity in Canada, but it's still distressing—especially since a December 2020 survey of Canadians showed only 48 per cent would immediately roll up their sleeves for a shot. (It was, at least, a welcome 8 per cent rise from the month before.) As those such as Kelvin and Elnicki do their parts, it will still be up to the rest of us to do ours.