May 22, 2022

The First Vaccine

The first vaccine was invented to tackle smallpox, a virus that is the single greatest killer humankind has ever faced.

Extent of Egyptian civilisation, 4 000 years ago.
Extent of Egyptian civilisation, 4 000 years ago.

4 000 years ago, a large and thriving civilisation was already well established in Egypt.

This is a time of famous leaders and their monuments: the Great Pyramid of Egypt, one of the wonders of the world, was only a few hundred years old. Living along the Nile delta, several million Egyptians worked for their pharaohs, or tended their farms. It was the blueprint of many civilisations to follow.

In support of their large population, the Egyptians had domesticated several animals, including the camel.

Camels are a large genus of ungulates, well adapted to life in the harsh desert climate. The Egyptians used them as pack animals, and also as a food source. Camel milk became a staple of the local diet, older camels were slaughtered and eaten.

Camels were valuable property in this society, and many thousands lived alongside the human population.

The variola virus
The variola virus

But camels also brought with them an unseen enemy.

The ‘variola’ virus is thought to have originated some time beforehand in African rodents, and had made the jump to camels before their domestication. Now, it made the jump to humans.

And while it has no effect on the camels themselves, in our species it wreaked havoc. Variola is the virus that causes smallpox.

Smallpox patient covered in pustules
Smallpox patient covered in pustules

Smallpox is a highly infectious disease, often lethal to humans. Its initial symptoms are similar to other viral illnesses like a cold or the flu; high temperature, muscle pains, fatigue.

But after about 48 hours, smallpox causes a rash on the skin, which then erupts into the fluid filled pustules that give the disease its name. A ‘pox’ was a term often used to describe visible skin conditions.

As the virus rages, the pustules spread all over the body, including the face. The agony they cause is immense, the escalating symptoms often deadly.

Historical fatality rates for smallpox were around 30%. There was no cure or treatment available: if you caught smallpox, there was a 1 in 3 chance you would die from it.

You could only rest, suffer, and hope for the best.

The mummified remains of Ramses V: victim of smallpox
The mummified remains of Ramses V: victim of smallpox

The high population of the Nile delta allowed variola to spread quickly.

It raged through the population, infecting farmers, then making its way up the social strata. Our knowledge of the origins of smallpox can be traced to mummified Egyptian remains; two government officials who were buried in the 4th century BCE were shown to have died of the virus.

No one was above its reach. Pharoah Ramses V, the most powerful man on earth at the time of his death, was also a victim.

Artist's depiction of smallpox decimating Rome, with the illness rendered mythically
Artist’s depiction of smallpox decimating Rome, with the illness rendered mythically

Around 3 400 years ago, Egypt fought a war with Turkey. Turkish accounts of the conflict contain descriptions of a horrifying new illness the Egyptians brought with them, that the returning Turks then spread to Europe and Asia.

Smallpox travelled along existing trade routes, carried by merchants. Wars and conflicts also helped it progress.

The incubation period, about a week, meant that infected people would spread the virus without ever knowing they were sick.

In 165 AD the virus reached Rome, and killed an estimated 10% of the 75 million population of the Roman Empire.

‘Victims were known to endure fever, chills, and diarrhoea, that turned from red to black. They also developed horrible black pocks over their bodies, both inside and out, that scabbed over and left disfiguring scars.

 

For the worst afflicted, it was not uncommon that they would cough up or excrete scabs that had formed inside their body. Victims suffered in this way for two or even three weeks.’

 

– Smithsonian Magazine

Smallpox was so vicious it was thought to be a scourge, sent by demons or evil spirits.

16th century Mesoamerican artwork, showing smallpox victims
16th century Mesoamerican artwork, showing smallpox victims

In the new millennium, European explorers would carry smallpox with them to the Americas, where its devastating impact was even more pronounced.

The exposed population in Europe had slowly developed some natural resistance to the virus, Native Americans had no such protection.

It decimated populations in North and South America. In some instances, it was deliberately introduced on infected blankets and supplies, as a kind of primitive biological weapon.

The overall death toll from smallpox is impossible to calculate. In 18th century Europe, it is estimated 400 000 people died of it every year.

Across the 20th century, the era of modern science, it killed 500 million people.

Early Chinese artwork showing smallpox inoculation
Early Chinese artwork showing smallpox inoculation

But as the illness burned through countries and then continents, some strategies against it were developed.
Even in antiquity, it was noticed that surviving smallpox provided subsequent immunity. No one ever caught the virus twice.

This observation led to a radical approach in ancient China.

About 1 000 years ago, medical practitioners there began deliberately infecting people with minute quantities of smallpox. The idea was simple: catch a mild dose of the virus, in a controlled environment, and you would then be immune to catching it in future.

The technique came to be known as ‘inoculation’.

Early inoculation was rudimentary, and done in a fashion that seems highly alarming from a modern perspective:

‘The inoculator usually used a lancet wet with fresh matter taken from a ripe pustule of some person who suffered from smallpox. The material was then subcutaneously introduced on the arms or legs of the nonimmune person.’

 

– US National Library of Medicine

The mechanism responsible, the introduced virus causing the body to create protective antibodies, was not fully understood until much later. But the approach brought success.

The mortality rate for the deliberately infected dropped to about 2%, compared to the 30% who caught the virus in the wild. This new method to tackling a pandemic gradually spread, and was adopted in many countries across Asia and Europe.

But inoculation brought its own risks.

The mortality rate of 2% was a dramatic improvement, but in a large, modern population, this still represented an enormous number of people. As inoculation relied on using the actual smallpox virus, the infected were also contagious, and could still spread the illness.

Inoculation was an unpredictable strategy, often times dangerous. But a better strategy was not developed until the 1790s.

Edward Jenner, inventor of the first vaccine
Edward Jenner

Edward Jenner was born May 17, 1749, in Gloucestershire.

He developed an interest in biology and medicine at a young age; at 13 he was apprenticed to a country surgeon, and later he would study medicine in London.

Jenner’s interests were broad, and he also studied natural science, geology, and even aeronautics. In 1784, having witnessed a demonstration of a hot air balloon, then a new novelty, Jenner constructed his own and flew it 12 miles.

During his medical training, Jenner had come across ‘cowpox’, an illness related to smallpox which was common in rural areas.

Cowpox lesions in a human patient
Cowpox lesions in a human patient

Cowpox was caused by a virus known as ‘vaccina’, which had been known for hundreds of years. It was most common in cows, which provided the name: the Latin word for cow is ‘vacca.’ But it was also found in cats and rodents.

In an infected cow, cowpox caused ulcerous growths to form on the animal’s skin. It could be transmitted to humans, with a similar effect.

Cowpox was similar to smallpox, but its effect was milder. In addition to the skin lesions, it also caused some flu-like symptoms and discomfort, but was rarely fatal.

What piqued Jenner’s curiosity was a tale that was told about the disease, one he had first heard during his youthful medical apprenticeship. Milkmaids who caught cowpox, were then immune to smallpox.

The first vaccine: James Phipps receives the first dose
Jenner vaccinates James Phipps, artist’s impression

Jenner began investigating this claim, and was surprised to find that his research bore it out. Dairy workers who had caught cowpox, had seemed to have immunity to subsequent outbreaks of smallpox.

Jenner’s investigation culminated in a famous experiment in 1796.

In May that year, Jenner examined a young milkmaid, Sarah Nelms, who had an active cowpox infection. He took a sample from lesions on the girls’ hand, and used it to infect a healthy 8 year old boy, James Phipps.

Within a few days, Phipps showed cowpox symptoms, including a fever and loss of appetite. He was ill for 9 days, although his condition remained stable throughout, after which he regained full health.

In July, in a move unimaginable in the present day, Jenner infected the boy with smallpox. He was amazed to see his theory seemingly proved: Phipps did not get sick.

Humanity’s great viral scourge was rendered harmless by cowpox. The similarity between cowpox and smallpox had prepared the boys immune system, which had developed the required antibodies to fight the later infection.

Jenner's pamphlet detailing the first vaccine
Jenner’s 1798 pamphlet on the first vaccine

Jenner continued his research, and in the next two years repeated the Phipps experiment with other patients. The same protective effect of cowpox was replicated.

In 1798, he self-published a pamphlet containing details of his experiments, having had a formal paper rejected by the Royal Society. He called his new technique ‘vaccination’, after the vaccina virus.

Other doctors and scientists read Jenner’s research, eager to find a better defence against smallpox. His experiments were repeated in London in 1799.

In 1800, a national survey of people who had contracted cowpox confirmed Jenner’s theories on a larger scale. No confirmed cowpox case reported a subsequent smallpox infection.

The Temple of Vaccina, where Jenner vaccinated patients for free
The Temple of Vaccina, where Jenner vaccinated patients for free

With the science validated, vaccination spread quickly. By the end of 1800, Jenner’s technique was already widespread in England, and it was adopted across Europe from the following year.

Jenner dedicated the rest of his career to promoting vaccination, often at the expense of his health and personal fortune.

After his discovery he bought a property in Berkshire, ‘Chantry House’, where he lived with his wife and children. In the garden he erected a shed, known as ‘The Temple of Vaccina’, where he vaccinated impoverished patients for free.

Jenner treated his last patient on January 23, 1823. He died of a stroke the following day. Jenner’s work laid the groundwork for all modern vaccines, which remain our primary defence against viral illnesses.

Ali Maow Maalin
Ali Maow Maalin

By the 20th century, vaccinations had reduced the threat of smallpox, although outbreaks still occurred. It remained a lethal threat, especially in developing countries.

Starting in 1959, the World Health Organisation (WHO) began a mass, global vaccination campaign to eradicate the disease outright. It took nearly 20 years.

The final case of smallpox was found in a Somalian cook named Ali Maow Maalin, in 1977. The hospital Maalin worked in had a free smallpox vaccination program, which Maalin had avoided as he had a fear of needles.

In October 1977, Maalin contracted the illness from two immunised young girls he had met (who were not sick themselves). He was placed in isolation while contract tracing was completed, luckily no one else he had interacted with had been infected.

Maalin recovered the following month, the last case of smallpox known to history. The WHO declared smallpox beaten in 1980, the only disease that has been eradicated completely by a vaccination program.

Thye Center for Disease COntrol and Prevention, where the US stockpile of smallpox is kept
The Center for Disease Control and Prevention, where the US stockpile of smallpox is kept

With smallpox eliminated, the WHO ended its vaccination program. Vaccinations on a large scale are expensive, the need to defend against a now non-existent virus was deemed unnecessary.

With this protection removed, humanity is again vulnerable to its greatest killer; our bodies are no longer primed with protective antibodies.

‘If you were to come down with a case tomorrow, a hospital wouldn’t improve your chances of survival any more than a witch doctor.

And if someone distributed variola over a modern city thousands, millions, would die.’

 

– Cody Cassidy, ‘Who Caught the First Case of Smallpox’

Both the United States and Russia maintain small quantities of smallpox, under heavy security. Both governments claim the samples are for future scientific research, critics of the program believe they are kept to be used as a potential bioweapon.

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