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Speaking of Science: To eradicate a virus

Speaking of Science: To eradicate a virus

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Deaths from smallpox (left) and Covid-19 (right) over time. Notice the sharp decline in both graphs following the beginning of vaccination. Our records of smallpox numbers are very limited compared to modern records on Covid-19, so only Sweden's smallpox infections are shown.

The past year and a half has been a dramatic demonstration of what a new virus can do to our world. Nearly 4 million people have died so far (in the US, Covid-19 surpassed heart disease as the leading cause of death back in February), over half of those infected are still experiencing long-term Covid-19 symptoms (everything from fatigue to continued difficulty breathing), and economies throughout the world are still trying to recover.

But what’s equally amazing is how quickly we’ve fought back. In under a year, around a dozen different vaccines with varying effectiveness and levels of testing made it through production and clinical trials to reach citizens. Dozens more are making their way through clinical trials. Along with this has been a dramatic decrease in infection numbers, leaving us to dig ourselves out of the rubble, salvage what we can, and consider what we have learned for next time a new virus comes our way.

Covid-19 isn’t the first pandemic to be taken down by modern science and medicine, but we also have not yet won. As long as the SARS-CoV-2 virus continues to circulate and infect others, new variants will continue to evolve and strain our vaccines and outbreaks will easily pop back up in areas with low vaccination levels. Could it ever be possible to be free of SARS-CoV-2 for good?

When we reduce the number of global cases of a viral infection to zero, we say we have eradicated that disease. It’s a pretty exciting deal: it’s gone forever and can’t possibly come back. Unfortunately, eradication is not easy. In all of human history we’ve done it twice, and once was on a virus infecting cattle (rinderpest, aka the cattle plague, which can have mortality rates of nearly 80-100%). The only virus we’ve ever eradicated that infects humans is smallpox, but the way in which it was done might provide some guidelines for what we’ll need to do if we want Covid-19 to follow the same path. So how did we get rid of smallpox? Vaccination was definitely key, but it wouldn’t have been enough without a global education and surveillance program.

What was smallpox? Smallpox is an ancient disease, possibly dating back at least 3,000 years. Like Covid-19, it is caused by a virus, but as each species of virus has unique genetic information, the smallpox virus (variola virus) looked rather different from the Covid-19 virus (SARS-CoV-2). The way a virus looks dictates everything about that virus: how it spreads (water, air, blood, etc) what type of cells in the body it can attack (lung, skin, etc), and what symptoms it causes. In the case of the variola virus, which causes smallpox, the symptoms were particularly gruesome: fever followed by a rash covering most of the body that gradually turned into fluid-filled blisters. Around 30% of those infected by the variola virus died, and those that lived often were permanently disfigured or blinded by large scars left once the blisters dried.

The first vaccinesVaccination works by training the immune system to recognize a virus without risking infection in the same way bootcamps train soldiers before battle. The idea actually originated with smallpox. As early as the 10th century, countries such as China exposed healthy individuals to puss from smallpox sores to make them immune to future infection. The practice spread throughout Europe until 1796, when an English doctor named Edward Jenner built upon this idea to create the first vaccines. Jenner noticed that milkmaids infected with cowpox (a very similar disease to smallpox, but with milder symptoms) didn’t seem to get sick with smallpox and correctly suspected exposure to cowpox somehow protected against smallpox. Even better, exposure to cowpox to gain immunity was much safer than using smallpox sores, which could lead to actually smallpox infection.

To test his idea, Jenner took puss from a cowpox sore on one of his milkmaids (Sarah Nelmes) and injected it into the arm of a 9-year-old farm hand named James Phipps. After a few months, Jenner deliberately exposed Phipps to people infected with smallpox several times and found that he never got sick. After some additional experiments, Jenner published the new idea of vaccination (vacca meaning “cow” in Spanish) hoping that it would lead to “annihilation of the smallpox, a most dreadful scourge of the human species.”

The way in which Jenner developed his vaccine was extremely problematic in more ways than one: he benefited in both recognition and money by using Sarah Nelmes and James Phipps in an experiment that could have easily harmed both of them, but which neither of them profited from as much as Jenner. Neither Nelmes nor Phipps likely understood or consented to what was being done to them or the risks involved. But despite its morally awful start, Jenner’s work led to a turning point in the war against smallpox. Further tests backed up the safety and effectiveness of Jenner’s original vaccine, and more modern vaccines built on it. In one study of smallpox cases in Europe during the mid 1900s, scientists determined that the fatality rate from smallpox for unvaccinated people was nearly 50 X greater than vaccinated individuals. And of course, those vaccinated were much less likely to even get sick in the first place.

Global CooperationDespite the promise of early smallpox vaccines and continuous improvements that made the vaccines more widely available, smallpox remained a deadly foe throughout the 1800s and 1900s. In response, the World Health Organization (WHO) launched a global campaign in 1959 to wipe out smallpox for good. It was highly unsuccessful; suffering from lack of resources to vaccinate and educate the community and the same vaccine hesitancy we see against Covid-19 vaccines today. They stepped up their program in 1966, introducing a disease surveillance method to help locate outbreaks and containment methods to stop spread in these areas by quarantining and vaccinated all possibly exposed people. Many countries made smallpox vaccination mandatory. In 1978, medical photographer Janet Parker, became the last person to die from smallpox. To prevent an outbreak, over 500 of Parker’s close contacts were vaccinated or put into quarantine.

ConclusionsEradicating smallpox was an extended global effort. Despite the fact that ways of training the immune system to reduce the risk of smallpox infection were around for thousands of years, it took painstaking surveillance, containment, and education programs to successfully stop outbreaks before they could spread. Unlike Covid-19, smallpox doesn’t have an asymptomatic period of transmission. While this undoubtedly made it easier to locate and isolate cases, we have the advantage of a larger global vaccination plan and the technical ability to widely educate the world about the importance of vaccination. It would be a pretty amazing thing to continue our success against SARS-CoV-2 in vaccine development with programs like this to rid the world of Covid-19 entirely.

Hannah Margolis is a NSF GRFP Fellow at the Massachusetts Institute of Technology with a degree in biochemistry from Dartmouth College. She can be reached at


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