More than a million Americans have died of Covid-19, and the World Health Organization estimated this Thursday that the global death toll is around 15 million — a horrifying, and largely unnecessary, tragedy.

But for all that the world has lost in the last few years, the history of infectious disease has a grim message: It could have been even worse. That appalling death toll resulted even though the coronavirus kills only about 0.7 percent of the people it infects. Imagine instead that it killed 30 percent — and that it would take centuries, instead of months, to develop a vaccine against it. And imagine that instead of being deadliest in the elderly, it was deadliest for young children.

That’s smallpox.

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The horrors of the past year have given us a brief glimpse into what it’s like to live in a world ravaged by infectious disease. It’s easy to take for granted now that very few babies in rich countries die of disease in infancy, that most infectious diseases are treatable, and that there are vaccines available when we need them. But humanity only made the transition into that new world fairly recently.

Smallpox eradication was a major part of that. Over the course of the 20th century, country after country fought it back. The World Health Assembly declared on May 8th, 1980 that it was gone for good. Its gradual eradication meant ending the needless suffering and death of millions and millions of people every year.

It’s not minimizing the suffering wrought by the coronavirus pandemic — or forgiving the negligence that made the Covid-19 death toll so much higher than it needed to be — to take a step back and realize that diseases can be much more contagious, and much deadlier, than this one. And there’s something reassuring about the fact that, at least in the case of smallpox, humanity eventually rose to the challenge.

With luck, aggressive vaccination, and ambitious international coordination, we made the toll of infectious disease lower than at any point in history, and though it won’t be easy, we can do it again. As we learn how to address current and future pandemics, it is worth understanding what we learned from the great infectious disease fights of the past.

Smallpox, explained

Smallpox has been around for a very long time. It’s believed that pharaohs died of it in ancient Egypt. It devastated the Americas in the early 1500s after being introduced through contact with Europe. It altered the course of the Revolutionary War, with outbreaks in New England that cost the Continental Army the Battle of Quebec.

Its toll throughout history is hard to measure, but in the 20th century alone it is estimated to have killed between 300 million and 500 million people. “In the contest of Smallpox versus War, War lost,” D.A. Henderson, former director of disease surveillance at the Centers for Disease Control and Prevention, wrote in his 2009 book Smallpox: The Death of a Disease, noting that even the most devastating wars of the 20th century — World War I and World War II — had a combined death toll much smaller than that of smallpox.

Smallpox was spread by a virus (technically, two viruses: Variola major and the significantly less common Variola minor). It caused fever, then a rash, which over the course of a few days developed into the skin-covering lumps that are the disease’s trademark. The more serious strain, Variola major, killed about 30 percent of people infected with it, with even higher death rates in infants. Death usually occurred within eight to 16 days.

Variola minor had similar symptoms but was much less deadly, with death rates around 1 percent. No effective treatments were discovered by the time the disease was eradicated.

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A year ago, most people were unaware of epidemiological statistics like a disease’s R0 (the number of people that an infected person will infect in a population without immunity), and a disease’s “case fatality rate” (the percentage of sick people who die). But the Covid-19 pandemic prompted an epidemiological crash course for many of us, which ought to give us a new perspective on the horror of smallpox.

The disease, like Covid-19, was primarily transmitted through close contact, especially in indoor spaces. Our best estimate, though, is that it had an infectiousness between 5 and 7, putting it between that of Covid’s delta (4) and omicron variants (8). Due to smallpox’s high R0 and the devastating mortality rate, it was not uncommon for an outbreak of smallpox in an area without preexisting immunity to kill 30 percent of everyone in the community. In some contexts, such as when it spread through the Americas after being introduced by Europeans, the death rate is believed to have been even higher.

How we eradicated smallpox

Before modern vaccine development, humans had to get creative in slowing the spread of infectious disease. It was known that people who’d survived smallpox didn’t get sick again. In China, as early as the 15th century, healthy people deliberately breathed smallpox scabs through their noses and contracted a milder version of the disease. Between 0.5 percent and 2 percent died from such self-inoculation, but this represented a significant improvement on the 30 percent mortality rate of the disease itself.

In England, in 1796, doctor Edward Jenner demonstrated that contracting cowpox — a related but much milder virus — conferred immunity against smallpox, and shortly after that, immunization efforts began in earnest across Europe. By 1813, the US Congress passed legislation to ensure the availability of a smallpox vaccine that reduced smallpox outbreaks in the country throughout the 1800s.

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In the rest of the world, similar efforts were undertaken, with varying levels of commitment and success. In 1807, Bavaria declared vaccination for smallpox mandatory. In 1810, Denmark followed. Cases fell across Europe. Efforts by the British Empire to conduct a smallpox vaccination program in India made less progress, due in large part to mistrust by the locals of the colonial government.

By 1900, smallpox was no longer quite as much of a scourge in the world’s richest countries. In the 1800s, about 1 in 13 deaths in London were caused by smallpox; by 1900, smallpox caused only about 1 percent of deaths. Several countries in Northern Europe had also declared the disease eradicated. Over the next few decades, more of Europe, and then the US and Canada, joined them.

Our World in Data

But as long as smallpox ravaged other parts of the globe, continual vaccination was necessary to make sure it wasn’t reintroduced, and millions of people continued to die of it. Data is spotty — this is before there was any international authority on infectious disease statistics worldwide — but it is estimated that 10 to 15 million people caught smallpox annually, with 5 million dying of it, during the first half of the 20th century.

It was not until the 1950s that a truly global eradication effort began to appear within reach, thanks to new postwar international institutions. The World Health Organization (WHO), founded in 1948, led the charge and provided a framework for countries that were not always on friendly terms to collaborate on global health efforts.

Even then, there were skeptics. “One hurdle the Eradicators faced was skepticism within the scientific community,” Henderson writes, “about the feasibility and practicality of eradicating an infectious disease.”

After all, no disease had ever been eradicated before. There were billions of people in the world, under myriad governments, many of them in regions actively at war. Global coordination on the scale eradication would demand was unprecedented. Plus, there had already been a failed attempt to eradicate malaria. The goal of eliminating every smallpox case in the world, rather than just suppressing the virus, sounded implausibly lofty.

“There was no shortage of people telling [the people involved in the eradication effort] that their effort was futile and they were hurting their career chances,” former CDC director William Foege wrote in his 2011 book House on Fire about the smallpox eradication effort.

But other advances had brought it within reach. Needle technology had improved, with new bifurcated needles making it possible to use less vaccine. Overseas travel improved, which made it easier to ship vaccines and get public health workers where they were most needed, and provided impetus for worldwide eradication as it made it more likely that a smallpox outbreak anywhere in the world could spread.

A 1947 outbreak in New York City, traced back to a traveler from Mexico, resulted in a frantic effort to vaccinate 6 million people in four weeks. Europe, Henderson says, repeatedly saw the virus reintroduced by travelers from Asia, with 23 distinct importations (different occasions of someone bringing smallpox into the country) in five years.

As we face down Covid-19, with effective vaccinations finally in hand, we’re encountering the same challenge that the world faced with smallpox in the 1950s: It doesn’t matter if a vaccine exists unless there also exists the international will and creativity to get it to all the people who need it, many of whom will be reluctant and skeptical.

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As Henderson and Foege detail in their books, there were extraordinary challenges that often looked utterly insurmountable in the quest to eradicate smallpox. In poor corners of the world, there were no roads or hospitals and no infrastructure to notify the WHO of a smallpox outbreak. Civil wars, famines, and refugee crises made disease surveillance and vaccination very difficult.

But other features of smallpox made it easier to eradicate than many other diseases. For one thing, it didn’t have animal reservoirs; that is, unlike diseases like Ebola, smallpox doesn’t live in animal populations that can reintroduce the disease in humans. That meant that once it was destroyed in humans, it would be gone forever. And, once a person has survived it, they are immune for life. Only one vaccine is needed for immunity in almost all cases.

Additionally, it largely doesn’t have asymptomatic transmission and has a fairly long incubation period of about a week. That made it possible for public health officials to stay on top of the disease with a strategy of “ring vaccination” — whenever a case was reported, vaccinating every single person who may have come into contact with the affected person, and ideally everyone in the community could keep the disease at bay.

Henderson calls the switch to ring vaccination a pivotal strategic change for the fight against smallpox. Instead of fighting for 100 percent vaccination, which was proving unachievable in low-income countries, it let public health teams focus their resources where they were needed most.

As large parts of the world were declared smallpox-free, resources could be more intensively focused in the areas where outbreaks were still happening. While in 1950 a smallpox outbreak in a developing country might attract little international interest, by 1970 it attracted the world’s best disease surveillance and response resources. Contact tracers tried to identify everyone exposed and figure out where the virus might have come from. Communities were swiftly vaccinated. Case numbers kept declining.

In 1975, the world marked the last wild Variola major case, in Bangladesh. In 1977, it marked the last wild Variola minor case, in Somalia. Doctors tracked down and vaccinated every potential contact of the case; none of them contracted the disease. Surveillance around the world found no more cases anywhere.

Two years later, on May 8th, 1980, the World Health Assembly declared victory over smallpox.

Lessons for the present, and the future

Humanity’s triumph over smallpox should stand out as one of our proudest moments. It called on scientists and researchers from around the world, including collaborations between rival countries in the middle of the Cold War.

Unfortunately, we’ve never replicated that success against another virus that affects humans. With some, such as polio, we’re drawing close. Wild polio has been eradicated in Africa and remains only in conflict-torn regions of Afghanistan and Pakistan. “Ring vaccination,” as practiced in the smallpox battle, has been successfully used in public health efforts against other diseases, most recently with the new Ebola vaccine, used against outbreaks in the Democratic Republic of Congo.

But in other cases, like HIV and Covid-19, we’ve let new diseases grow to pandemic proportions. And while those diseases have had devastating effects, it’s worth keeping in mind that they could have been even worse. Some viruses with the potential to escape laboratories or make the jump from animals to humans are as deadly and transmissible as smallpox, and Covid-19 has made it clear that we’re not prepared to handle them.

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Why has it been so hard to build on our success with smallpox? One part of it is that many diseases present all the challenges that smallpox did — plus some additional ones. Some, like malaria or Ebola, have animal reservoirs, which means that ensuring no humans are sick isn’t sufficient to stamp them out. Some, like HIV or Covid-19, have asymptomatic transmission, which makes disease surveillance trickier. (An important public health clarification: HIV can be transmitted by people who don’t feel sick, which is “asymptomatic transmission,” but it cannot be transmitted by people whose virus levels are undetectable through medication management.)

But as far as things that we can control, there are some takeaways. The first is that the smallpox eradication program took both heroic efforts and a well-funded, well-supported public health system. People trying to do disease surveillance and vaccination in war-torn, dangerous, remote parts of the world are risking their lives in our current fight. They can only succeed if their efforts are matched by a commitment by governments of rich countries not to leave poor countries behind, to meet the funding needs of an eradication project, and not to undermine one with CIA spy operations that imitate vaccine campaigns.

“The coronavirus we are grappling with today is not smallpox,” Richard Horton, editor-in-chief of The Lancet, said in December 2020, but “those old enough to remember the story of smallpox eradication” will recognize many of the lessons we’re rapidly learning now, from the importance of vaccine distribution and infrastructure to the essential role of international coordination and leadership at the World Health Organization.

A global Covid-19 suppression effort — and a better response to future pandemics —requires a CDC and WHO that is well-funded, attracts top scientific talent, and isn’t subject to political manipulation that gets in the way of accurate disease surveillance.

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Another critical takeaway is that once the work has succeeded, we have to make sure never to undermine it. After telling the history of the eradication of smallpox, Henderson’s account switches to a different theme: the vials remaining in the hands of governments. He wants them destroyed lest some accident or malicious act unleash smallpox on the world again. There have already been a few close calls. A year after smallpox was declared eradicated, bad lab safety procedures led to another outbreak in Birmingham in the UK. Just a few years ago, improperly stored smallpox vials were found in a lab in the US. We need to take biosecurity and pathogen research much more seriously.

In the broader context of humanity’s fight against infectious disease, it’s fair to think of the coronavirus as a close call. As bad as it has been, it could have been much worse. It could have been more transmissible; it could have been deadlier. Diseases far worse than Covid-19 have appeared throughout human history, and there’s every reason to believe we may someday face one again.

The devastation of Covid-19 has hopefully made us aware of the work public health experts and epidemiologists do, the crucial role of worldwide coordination and disease surveillance programs (which are still underfunded), and the horrors that diseases can wreak when we can’t control them.

We have to do better. The history of the fight against smallpox proves that we’re capable of it.