The Man—and Woman—Who Beat Smallpox

Edward Jenner vaccinates James Phipps, 1798

Zoë Sharp

If you have a scientific bent, you have probably heard of Edward Jenner, an English surgeon and scientist who is credited with the discovery of vaccination against smallpox. Born in Gloucestershire in 1749, Jenner was the eighth of nine children of the local vicar and his wife. Jenner was apprenticed at fourteen to a surgeon and in 1770 he moved to London to complete his training.

 

Two years later, Jenner returned to Berkeley in Gloucestershire to become the local doctor and surgeon. One of his regular tasks was to help guard his patients against smallpox by a procedure called variolation. (And I’ll come back to this later.)

 

Smallpox got its name in 16^th Century Britain, to distinguish it from syphilis, which was known as the ‘great pox’. It is a highly infectious disease caused by the Variola major and Variola minor virus variants. Nobody knows exactly where it came from, but some of the earliest instances have been found in Egyptian mummies from the 3^rd Century BCE. During the last hundred years—up to the last known naturally-occurring case in 1977—smallpox is thought to have killed 500 million people, with approximately 300 million of those deaths taking place since 1900. The overall mortality rate was thirty percent, although some strains of the disease were noted to be almost invariably fatal.

 

In Edward Jenner’s time, outbreaks of smallpox across Europe accounted for one third of all cases of blindness, and 400,000 deaths a year. But, for some years Jenner had been intrigued by local country lore which claimed that dairymaids never got smallpox.

 

This was because they tended to catch cowpox, which appeared to offer them protection against smallpox. Cowpox is a mild viral infection in cows, causing a few similar symptoms, although to a far lesser degree and without apparent discomfort. Humans developed a few weeping pocks on their hands and felt unwell for a few days.

Edward Jenner

 

When Sarah Nelmes, a local dairymaid, came to see Jenner in 1796 with pocks on her hand, the doctor took the opportunity to gather some of the pus. He tested his theory on the eight-year-old son of his gardener, a boy called James Phipps, by making scratches on one of James’ arms and infecting these with some of the material from Sarah’s hand.

 

A few days later, James developed mild cowpox, but soon recovered. Six weeks later, Jenner inoculated the child with smallpox, which had no effect. Jenner concluded that James was now immune, and to prove his theory, inoculated the poor kid another twenty times. James never caught the disease, which might be considered reward enough, but Jenner later gave him a free lease on a cottage in Berkeley.

 

Jenner published an account of his vaccination of James Phipps in 1798, becoming the first person to do so, although he was not the first to carry out vaccination using cowpox. Most notably, Benjamin Jesty of Dorset in 1774, inoculated three members of his family, and Peter Plett from Kiel in what is now Germany in 1791, inoculated three children.

 

Up until the new method of vaccination with cowpox became the norm, the only protection against smallpox was variolation. (See, I promised I’d come back to that.) This practise developed in Asia, possibly as early as the 16^thCentury. It involved exposing someone to a very small dose of smallpox—taken either from a smallpox patient, or a recently variolated patient. The idea was that this person would contract a mild form of the disease, and would then be immune.

 

Usually, scabs from the smallpox pustules were dried and then blown up the nose of the person being inoculated, which sounds delightful. It wasn’t without risk, either—between one and two percent of those receiving variolation died as a result. Still better odds than catching full-blown smallpox, however.

 

By 1700, variolation had spread from Asia to Africa, India, and the Ottoman Empire. It was in Constantinople in Turkey that Lady Mary Wortley Montagu first learned about variolation. Lady Mary (1689-1762) was the wife of the British ambassador. She survived a bout of smallpox in 1715, but had suffered the subsequent scarring. Her brother had died of the disease two years earlier.

 

Lady Mary Wortley Montagu

Perhaps because of these events, she was keen to protect her own children. In 1718, while still in Turkey, she had her five-year-old son inoculated by a process of ‘engraftment’—inserting smallpox under the skin. This was carried out with the help of Charles Maitland, the surgeon at the Embassy. Her daughter was too young to undergo the procedure at the time. It was only after Lady Mary returned to England, and a smallpox epidemic broke out in 1721, that she had her daughter inoculated by this process of variolation, named after the smallpox virus itself. Again, Charles Maitland carried out the procedure—the first in Britain—which was much publicised.

 

Sadly, it was also greeted with much condemnation from the exclusively male scientific and medical communities. They were unimpressed by the fact that, in Turkey, variolation was usually carried out by elderly women with no education. Lady Mary was able to convince the Princess of Wales, Caroline of Ansbach, to take it seriously, however. In August of 1721, seven condemned prisoners awaiting execution at Newgate were offered variolation as an alternative. Not surprisingly, they accepted. All survived the experience, and were released.

 

In the East, inoculates knew that they must self-isolate after undergoing variolation, as live smallpox was used. In England this was not always understood or advised by medical practitioners. Nor was the dose of smallpox being administered always as tiny it was supposed to be, and some doctors bled and purged their patients unnecessarily. As a result, there were a number of deaths and complications. Politics and misinformation became involved, and Lady Mary’s reputation suffered as a result.

 

Nevertheless, having introduced smallpox inoculation to Western medicine, she continued to campaign for its widespread implementation. Edward Jenner built on the foundations of her work to come up with his vaccine. By doing so, on May 8^th 1980, the World Health Assembly announced that the world was free of smallpox.

 

This year, it is 300 years since Lady Mary’s three-year-old daughter, also Mary, became the first person in the West to be protected against a deadly virus. To celebrate, award-winning TV drama and comedy producer, Jo Willett has penned a new biography of Lady Mary, celebrating the remarkable life of this early feminist among the greatest politicians, writers, artists, and thinkers of her day. Sounds like a brilliant story.

 

THE PIONEERING LIFE OF MARY WORTLEY MONTAGU: SCIENTIST AND FEMINIST

 

This week’s Word of the Week is vaccination, created by Edward Jenner to describe his new treatment against smallpox. It comes from vacca, Latin for cow, from the cowpox virus Jenner used. (Although, Jenner experimented with horsepox virus as well, and when vials from 1902—which had contained the oldest known strains of smallpox vaccine—were subjected to DNA sequencing in 2017, scientists discovered it was more closely related to horsepox. So, perhaps that should be equusination?)

VACCINES--HOW A MILLENNIA-OLD LIFESAVER WAS, AND STILL IS, CONTROVERSIAL--Part 1

Wednesday--Kwei

In the era of Covid-19, we've heard a lot about vaccines and the international race to produce one. However, even if a successful vaccine emerges relatively quickly in the US, studies suggest that only 30-40% of Americans will accept the vaccine. In other words, hurry up and wait. The joint NIH-Moderna Phase 3 trial, which shows a lot of promise, has just hit a snag because they haven't enrolled enough African Americans and Latinx subjects. Because of a long and shocking history of unethical experimentation on black people by white doctors, e.g. the Tuskegee Syphilis Study of 1932-1972, black people's response to the suggestion of taking part in anything remotely experimental has been mostly, hell, no.

Terminology

Vaccination, inoculation and immunization are often used interchangeably, but there are distinctions:

• Inoculation is the introduction of an infectious agent or toxin designed to produce an immune response without overt illness.
• Vaccination is a specific type of inoculation named by Edward Jenner in reference to vaccinia, which is cowpox. Vacca is Latin for cow.
• Immunization is development of immunity by any means, whether artificial or natural.
• Variolation: the deliberate inoculation of an uninfected person with pustular matter containing the smallpox virus.

Famous Infection Fighters

When I was a nerdy teenager, I loved to read murder mysteries, but my other interests ranged from philosophy to science. I recall being riveted to a paperback that chronicled the history of how scientists discovered bacteria and viruses, and the luminaries who marked the milestones along a fascinating journey that included the development of vaccines. We're talking about Louis Pasteur, Robert Koch, Alexander Fleming, and so on.

My vivid imagination took me back to those bygone centuries when people ignored or misunderstood clues that science freely thrust under their noses. In May 1796, Edward Jenner, in an experiment that would have been deemed unethical in modern times, inoculated an 8-year-old boy, James Phipps, with fluid from a fresh cowpox lesion on the skin of a milkmaid. For years, Jenner had heard milkmaids say, “I shall never have smallpox for I have had cowpox. I shall never have an ugly pockmarked face.” Now Jenner wanted to see if that was true.

 

Edward Jenner vaccinating James Phipps, 1796 (Image: Everett Historical/Shutterstock

Over the next 2 weeks, Phipps had mild flu-like symptoms, but when exposed to the highly infectious smallpox, Phipps was protected from contracting the disease.  Jenner then did a little promotion of his vaccine, basing the word on vacca, Latin for "cow." The 30% lethality rate and horrendous optics of smallpox drove the urgency of finding a cure or prevention. If a person survives, smallpox leaves the most appalling scarring--enough to make one suicidal.

Child with active smallpox (Image:CDC/James Hicks)

Nothing Really New Under The Sun

However, Jenner wasn't the first person to use the inoculation technique against smallpox. Variolation, introducing a person to smallpox material from a patient in the hope that a mild, but protective, infection would result, was practiced in China and India as far back as 1000 or before.  

In 1648, there was a situation that will sound rather familiar to our modern ears: because of an outbreak of yellow fever in Barbados, Cuba, and the Yucatan, strict quarantine was imposed in Boston for all ships returning from the West Indies. Apparently, viruses weren't done with Boston, because in 1657, there was a measles outbreak. In 1694, Queen Mary II died of hemorrhagic smallpox (variola hemorrhagica).

The African Pioneer Very Few Know About

As a child in Ghana, I learned about Jenner, Pasteur, Koch et al., but no one told me nor did I read about a West African slave who brought the practice of inoculation to New England. In 1706, a prominent Puritan minister called Cotton Mather purchased an enslaved West African whom he named Onesimus (Greek for "useful") after the Biblical slave of the same name. This appears in the Epistle of Paul to Philemon, in which Paul says, "I beseech thee for my son Onesimus, whom I have begotten in my bonds: Which in time past was to thee unprofitable, but now profitable to thee and to me . . ."

Onesimus was one of about a thousand Africans in Massachusetts who were servant or slave. Mather hoped Onesimus would repent of "some Actions of a thievish aspect." Apparently the irony of Mather's slave ownership was lost on himself. Onesimus was clearly a smart cookie, because later on, he was able to buy his way out of bondage by paying Mather to purchase another youth, Obadiah, to serve in Onesimus's stead. Slick move, although I feel sorry for Obadiah.

Onesimus, who brought inoculation to Boston
(Photo: Face2faceAfrica.com) 

In 1721, yet another outbreak of smallpox ripped through Boston. At that time, Mather advocated  a technique of "ye Method of Inoculation," remarking that six years before, he had learned about it from "my Negro-Man Onesimus, who is a pretty Intelligent Fellow." Mather had informed the Royal Society of London that Onesimus "had undergone an Operation, which had given him something of ye Small-Pox, and would forever preserve him from it, adding, That it was often used among [Africans] and whoever had ye Courage to use it, was forever free from ye Fear of the Contagion. He described ye Operation to me, and showed me in his Arm ye Scar.” Accounts of smallpox variolation appear from scattered areas of ancient Africa, including Sudan, Ethiopia, and Southern Africa.

Hearing that this technique was also practiced in Turkey, Mather mounted a public campaign in favor of inoculation, but the large majority of white doctors in town were unwilling to try something suggested by an African, except for one physician by name of Zabdiel Boylston, who was the first American doctor to perform gallstone and breast removal surgery. In that same spirit, Boylston went ahead and performed variolation on 282 Boston inhabitants, keeping records on them and 5,759 non-inoculated residents who contracted smallpox. At the time, most people considered variolation ran counter to the will of God, and both Boylston and Mather met with strong opposition and even threats of violence. If this all sounds vaguely familiar, it's because it is. Anti-vaxxers existed in the 1700s just as they do now, and the irony is that 300 years later, the rhetoric is almost identical. Eventually, Boylston was arrested and released only on condition that he would not inoculate anyone else without government approval.

But Boylston was eventually triumphant. Of the 282 inoculated patients, only 2% died from smallpox. Of the nearly 6000 non-inoculated, 15% died. Boylston presented his findings in 1726 to the Royal Society chaired by the Royal Society.

Lessons & Summary

The history of vaccination and inoculation goes back millennia. Many people do not understand that large populations have given their lives through outbreaks of smallpox and other hideous and lethal diseases in order for us to reach modern times in which lifesaving vaccination is available. Smallpox has been largely eradicated in the world as a result, and countless deaths are prevented from diseases like rabies, meningococcus, polio, diphtheria, and yellow fever. Anti-vaxxers should carefully consider whether we really want to return to the 17th and 18th century.

The inoculation story has been largely told from the Eurocentric standpoint, but variolation, a procedure of the same principle, was practiced elsewhere, including in Africa, long before Jenner unveiled vaccination. Yet one would be hard pressed to cite Onesimus's contributions to a medical practice that has been a bedrock of public health and the eradication of disease.

For a detailed history of vaccines, I highly recommend you spend a few minutes looking at this timeline, and next post, I'll talk about the modern age of vaccines.