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The Eradication of Smallpox

The 8th of May 1980 was a momentous day in human history. A resolution endorsed by the World Health Assembly signalled victory in a war that had already claimed an estimated 300 million lives since the start of the 20th Century alone. A war not fought with guns and bombs, but on the battlefields of hospitals and medical facilities around the world.

The eradication of smallpox, a disease that had savaged humanity for thousands of years with the earliest known case dating from the 3rd century BCE in Egyptian mummies, signalled the first, and still only time that a human disease has been entirely eliminated. 

When we look at the great medical megaprojects throughout history, this must surely stand as one of the most astounding. But it’s difficult to know exactly where to begin. Humans have been battling smallpox since the age of Tutankamen – and probably before – but for a long time, we were losing miserably. Yet a series of medical breakthroughs that began in the 16th Century slowly – and I do mean very slowly – began to turn the tide. A mere three hundred years or so after the world’s first smallpox vaccine appeared, the virus was on the run.   

This is the story of one of the world’s biggest viral killers and the enormous global undertaking over hundreds of years that finally brought it down. 


Pustular eruption of smallpox on face
Pustular eruption of smallpox on face, By wellcomeimages.org.
Is licensed under CC-BY

The smallpox disease can be divided into two variants, variola major and variola minor, that each come with drastically different dangers and outcomes. 

Variola minor was the far less severe variant that came with a historical death rate of about 1%, while variola major was the hellish spectre that stalked much of the world with a general death rate of 30%, which could jump to 80% in infants.  

Initial symptoms that appeared often gave the impression of the flu or the common cold, with a fever, muscle pain, malaise, headache and fatigue all common. This was typically followed by nausea, vomiting, and backache, as smallpox compromised the digestive tract, with this early stage of the disease normally lasting 2-4 days. 

Between 12 and 15 days in, the first lesions – small reddish spots called enanthem – normally began appearing in the mouth, tongue, palate, and throat, which gradually grew until they burst, releasing large amounts of virus into the saliva. This period usually lasted between 24 and 36 hours and at this point, the virus could take one of four paths set out by the Rao classification, a clinical smallpox method of classification; ordinary, modified, malignant, and hemorrhagic smallpox.

This classification doesn’t necessarily distinguish between milder and more severe cases – though as we’ll get to some are far more extreme than others – but instead how the virus developed and in what form. The modified version was just that, a smallpox virus that was usually found in those who had already been vaccinated against the disease, while the ordinary version was your basic, run of the mill, 30% chance of death smallpox. 

Those who developed the malignant and hemorrhagic versions were in serious trouble, and while they developed slightly differently, most cases ended in death – and I’m afraid to say not an easy or pretty way to go. For those who survived, many were left horribly disfigured with deep scarring and blindness common – in fact, it’s thought that a third of blindness in Europe before immunization was caused by smallpox.     

Origins & Transmission   

The origins of this horror virus, which is brick-shaped measuring approximately 302 to 350 nanometers by 244 to 270 nanometers, aren’t clear, but the consensus is that it probably evolved from a terrestrial African rodent virus between 68,000 and 16,000 years ago, but only really emerged in its present form between 3,000 and 4,000 years ago. Most likely it evolved from Taterapox – a member of the Orthopoxvirus genus which also includes cowpox, horsepox, camelpox, and monkeypox. 

Smallpox was highly contagious, which helped its spread, and could be transmitted through airborne droplets. If you were sitting directly opposite an infected person for a prolonged period in an enclosed area, you would probably contract the virus, but it could also be transmitted by direct contact with infected bodily fluids or contaminated objects, such as bandages, bedding or clothing.  

Early Preventions and Treatment 

Edward Jenner.
Edward Jenner. By wellcomeimages.org, is licensed
under CC-BY

The earliest smallpox vaccine was developed in 1796 by British doctor Edward Jenner, but for thousands of years before those suffering from smallpox were treated in a variety of ways. By far the most common was inoculation with variola minor, the virus’ far less deadly side, and there’s plenty of debate over who began this first, though it seems China and India are the most likely contenders. Essentially this meant infecting patients with the better version of smallpox in the hope that it would provide immunisation against the worst.  

For those with a slightly queasy disposition, you have been warned, because early inoculations were a little cringe-worthy, to say the least. In China, smallpox scabs were sometimes broken down as fine as possible then blown up the nose of the healthy, which sounds like the most ludicrous medical procedure that you’re ever likely to see, but it often did work. Another method was to simply pour the powered scab into a scratch on the patient, which sounds a little better, but still a far cry from what we see today. 

As the process reached the 16th Century, a needle infection was the most common form of inoculation, which resulted in a death rate of 0.5–2.0% – which is still ridiculously high, but far lower than the 30% mortality rate the variola major variations typically carried. Inoculation was far from perfect, but it gave a very rudimentary option in the fight against smallpox.    

The First Vaccine      

By the mid-16th Century, there had been plenty of anecdotal evidence of a link between cowpox and smallpox with those who contracted cowpox first often finding that they didn’t contract smallpox afterwards 

Edward Jenner, who began working as an apprentice apothecary aged just 13, also witnessed this connection, but like so many others, didn’t initially dwell on it too much. Now, the exact details of who administered the first, of what we would today call a vaccine, is up for debate. We have the traditional story involving Jenner who treated a local milkmaid, Sarah Nelmes, with cowpox in 1796, then inoculated 8-year-old James Phipps, the son of his gardener, with material taken from the cowpox lesions from Sarah. After a short fever, the young boy recovered fully and two months later, Jenner injected the child with live smallpox, twice, once in each arm for good measure, with no effects. 

However, there are at least six more instances where people may have done something very similar before Jenner, but the history books will forever use his name as the man who created the first smallpox vaccine. 

And one further point before we move on. This wasn’t just the first smallpox vaccine, this was the first vaccine full stop, and in fact, the word vaccine comes from the Latin word vacca, meaning cow. Of course, we’re now living a time of extreme scrutinization over vaccines, but whether you’re an avid fan or believe they’re part of Bill Gates’ master plan to take over the world, it’s impossible to deny they haven’t had a dramatic impact on humanity. Cases and deaths relating to measles, whooping cough, the common flu, polio, tetanus, meningococcal disease, hepatitis b and mumps have all declined drastically since the introduction of vaccines.  

Worldwide Vaccination Begins 

Vaccination set, London, England, 1925-1928
Vaccination set, London, England, 1925-1928. By wellcomeimages.org, is licensed under CC-BY

So as I mentioned earlier, it took just short of three hundred years from Jenner’s first vaccination until smallpox was entirely eradicated – which might sound obscenely slow to you, but remember, this is still the only human disease that we have ever fully eliminated. Malaria, Plague, AIDS, Ebola, and of course Covid-19 are all still active around the world. If you thought the plague was something that only happened in the olden days, think again, the last major outbreak of pneumonic plague occurred in Madagascar in 2017, while the ugly monster that is ebola continues to rear its head in parts of Africa. Long story short, it’s incredibly difficult to completely eradicate a disease.   

The closest we’ve come to eliminating another disease has been polio, which has been teetering on the edge of extinction for decades now but remains a nagging thorn, particularly in Afghanistan and Pakistan. And while we’re on the topic, we have already done a Megaproject video on the Worldwide Polio program, so if you’re into highly contagious diseases and feel you need another video on it directly after this, why not give it a watch.

Jenner spent much of the following years doing further trials and publishing his work in various scientific journals – and as you can probably imagine, plenty of people took some convincing. In 1798, the first widespread vaccinations were given in Trinity in Newfoundland, Canada, by a doctor who was also a close friend of Jenner and obviously trusted his work. 

The following year it was administered in the United States for the first time and by 1801, with mortality rates over the vaccines close to zero, their popularity increased dramatically. In 1803, the Balmis Expedition began which was a Spanish healthcare mission that sailed around the world for three years vaccinating millions of inhabitants of Spanish America and Asia against smallpox. This is considered the first international healthcare expedition in history and made stops in the Canary Islands, Colombia, Ecuador, Peru, Mexico, the Philippines and China. 

By the mid-17th Century, several countries, including the UK, had made vaccinations compulsory. By 1871, parents in the UK could be fined if their children weren’t vaccinated, though by the end of the century a few loopholes had begun to appear, mainly on compassionate grounds. 

In the U.S, the situation was fragmented, with some states making it compulsory, others prohibiting compulsory vaccination, while others sat on the fence and allowed the local authorities to make their own decisions. In many ways, echoing exactly what’s going on in the United States today. 

So, as we neared the 20th Century, the situation was very different around the world. Rich nations like the UK and the USA, along with other European countries had pressed ahead with their vaccination programs and were seeing huge drops in numbers. Let’s take Boston as a quick example, the city experienced a series of smallpox outbreaks throughout the first half of the 16th Century which killed between 4,000 and 8,000 people each year, prompting a large push with inoculations (the vaccine hadn’t been developed yet) and the numbers dropped to less than 1,000 each year. In 1800, when the vaccination was first used, the data dropped again to around 50 in really bad years and close to zero for most years. 

The situation in other parts of the world, however, was very different. Apart from medical missions like the Balmis Expedition, distant or remote corners of the world had little of ever getting a smallpox vaccine, while vaccine hesitancy sometimes meant it either wasn’t taken up or people preferred to continue with the inoculations they had been doing for centuries.

As the 20th Century dawned, a period that would define not only the fight against smallpox, but global cooperation also, the virus remained present across the world, but three countries were leading the way.  

Drum roll, please. Iceland became the first country to free itself from the scourge of smallpox when it recorded its final case in 1872 – after it had brought in mandatory vaccinations in 1802. In 1895, just sneaking into the 19th Century club, Sweden and Norway also declared themselves smallpox free.    

Early 20th Century 

It’s fair to say that a lot was going on in the 20th Century. Not only did we choose to wage two wars on a multi-million casualty rate, but the Spanish flu pandemic of 1918 added another horrifying layer as the world staggered through the first half of the Century. 

The first few decades of the 20th Century saw smallpox cases explode around the world and by the 1920s & 1930s there were frequent outbreaks in a majority of countries – but this was also when the tide began to turn, in more developed countries at least. Australia, New Zealand – and Madagascar of all places – had already declared themselves free of smallpox in the 1910s and the 1920s saw much of Eastern Europe and patches of Central America follow suit. The 1930s and 1940s saw most of the rest of Europe declared smallpox free, while the U.S saw its final case in 1949.     

Ideas on Eradication

As the world began picking up the pieces from the carnage that had been World War II, smallpox was still causing a horrifically high number of deaths, around 2-3 million each year, and by the 1950s, there were an estimated 50 million cases per year around the world. Now, at this point, it’s worth saying that not everybody was on board with the idea of trying to eradicate a disease. This had nothing to do with their desire to see healthy people suffer horribly – at least I hope not – but rather the twin dilemma of whether it was even possible to completely eliminate a disease and what kind of huge costs would accompany it. 

A large-scale campaign to eliminate malaria had begun in 1955, but crashed and burned during the 1960s because of political and practical matters, despite huge strides having already been taken. Malaria then surged back and today kills between 1 and 3 million each year.

The failure of the malaria campaign had left a sour taste for many, and at this point, there had been no international efforts to address the smallpox problem. Each country had dealt with the virus in its own way, with varying degrees of success. The first large-scale, multi-country attempt to eradicate the disease came in the Americas with the Pan American Health Organization, which had great success in some areas but not in others, with Argentina, Brazil, Colombia, and Ecuador all seemingly falling through the cracks – so basically most of South America. 

Now, if you’re a regular viewer of Megaprojects you’ll know that we’re not averse to sticking the boot into the Soviet Union from time to time. Looking back, many decades after the spectre of nuclear war has dimmed significantly, it remains an easy target for many of the absurdities that went on during the 20th Century. However, this is one area where they were very much a global leader and deserve plenty of credit. In 1958, it was the USSR that first called on the World Health Assembly to begin a global initiative to eradicate smallpox. Resolution WHA11.54 passed the following year and the world, in theory at least, began a huge undertaking to rid itself of smallpox. 

Since we’re handing our credit to the Soviet Union, it’s also worth mentioning that by this point, all of the USSR was already free from smallpox, as were large sections of the world. North America, Latin America, Europe, Australia and New Zealand had already eradicated the disease, while pockets of South America, Northern Africa and Central Asia were also free. In fact, only 60 countries still had smallpox, but with India and China two of them, this number accounted for 60% of the world’s population, with around 2 million people still dying each year from the disease.

The Eradication Program 

Despite the international will, things moved slowly and at times it appeared as if the battle was being lost. Be it through war, refugee crises, funding issues or bureaucratic red tape, the grand plan to rid the world of smallpox was failing.  

In 1966 however, things intensified with the formation of an international smallpox eradication unit and a ten-year target to kill the virus once and for all. This included a much more rigorous surveillance program which typically saw the ‘ring vaccination’ method used, in which small communities would be carefully monitored and if there were any outbreaks, those infected would be immediately isolated while those around them were vaccinated – which was in contrast to mass vaccinations that had been tried before, with mixed results. The WHO began setting up partnerships in countries around the world and gradually detection and careful monitoring became more and more common – resulting in a steady decline in cases in most countries.     

But several important technological breakthroughs also significantly helped this intensified program. The development of a freeze-dried vaccine that didn’t require refrigeration and was more potent, and the bifurcated needle which allowed the delivery of vaccines in a much simpler way by using two tiny prongs, completely changed how vaccines could be distributed. 

Say what you will about the two superpowers at the time, but the vast majority of vaccines donated in the early years came from the U.S and the Soviet Union, but by the early 1970s, 80% of all vaccines were produced in developing countries.   

I’m not overstepping the mark here by saying that the work done during this time was absolutely extraordinary as more and more countries were certified as smallpox free. By the mid-1970s, the disease had disappeared everywhere except the Horn of Africa that was suffering horribly from civil war and famine. But an international team led by Australian microbiologist Frank Fenner homed in on the area and in early 1977, work began in earnest to finally push the disease to extinction.


The final naturally occurring case of variola major, the more deadly of the two, was found in October 1975 in a three-year-old Bangladeshi girl, Rahima Banu, while the final case of the milder variola minor came two years later in Ali Maow Maalin, a hospital cook in Merca, Somalia, on 26th October 1977. At this point, the world knew it was on the brink of eradicating smallpox. 

But there was one final enormous scare. In August 1978, 40-year-old medical photographer Janet Parker who lived in Birmingham began feeling unwell. Parker, who worked in the anatomy department at Birmingham Medical School, was initially diagnosed with chickenpox, but as her condition rapidly deteriorated, it soon became apparent that she was in fact infected with smallpox. The cause has never been fully established, but it’s presumed that it escaped from a laboratory in the medical school, one of the few places in the world allowed to continue studying smallpox. 

As fear began rising, those who had come into contact were isolated and vaccinated, while the world held its breath and waited to see if it would lead to a mass outbreak. Janet Parker died on 11th September 1978, and with no further infections, except her mother who only developed mild symptoms, she became the last smallpox victim anywhere in the world. On 9th December 1979, a group of scientists certified that the world was smallpox free and 8th May 1980, the World Health Assembly released a simple message in which it 

Declared solemnly that the world and its peoples have won freedom from smallpox, which was a most devastating disease sweeping in epidemic form through many countries since earliest time, leaving death, blindness and disfigurement in its wake and which only a decade ago was rampant in Africa, Asia and South America.   

The grand plan back in 1966 had missed its target by only 9 months and 26 days and had cost roughly $300 million ($1.5 billion today) – a third of which came from the developed world. That’s not small change, but to give you an idea of long-term benefits, it’s been said that the United States recoups its contribution to the smallpox program every 26 days by not having to vaccinate or treat anybody with smallpox. I think most would agree, money well spent. 

And that brings us both to the end of the video and the end of smallpox, one of the worst diseases humanity has ever known. A disease that frequently ravaged parts of the world and by the 18th Century was still killing around 400,000 per year. It’s impossible to say how many people died throughout history with smallpox, but it’s certainly in the top 5 most deadly diseases we’ve ever experienced.

And yet, it was beaten. The eradication of smallpox must be one of the most important medical triumphs we’ve ever accomplished, done so with relentless drive, ever-changing technology and one of those rare instances when the world briefly seemed on the same page and worked together to drive smallpox to extinction.  

Smallpox (amnh.org)

Smallpox – Wikipedia

A history of eradication—successes, failures, and controversies – The Lancet

• Number of countries where smallpox was eradicated 1872-1977 | Statista

Smallpox is the only human disease to be eradicated – here’s how the world achieved it – Our World in Data

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