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 2

 Anti-vaxxers are nothing new

Opposition to vaccination is not a 20th-21st century phenomenon. It has been prevalent for much longer than many may realize. Here's an intriguing anti-vaccination flyer from 1807 called "The Vaccine Monster," clearly designed to engender feelings of suspicion, disgust and fear.

The Vaccine Monster, 1807 (Image: Wiki Digital Methods)

The text that accompanied this image proclaimed that, "A mighty and horrible monster, with the horns of a bull, the hind of a horse, the jaws of a krakin, the teeth and claws of a tyger, the tail of a cow, all the evils of Pandora's box in his belly, plague, pestilence, leprosy, purple blotches, foetid ulcers, and filthy running sores covering his body . . . has made his appearance in the world, and devores mankind —especially poor helpless infants—not by sores only, or hundreds, or thousands, but by hundreds of thousands." 

Another flyer from 1894 was accompanied by text warning of the dangers of vaccination.

(Image originally from Historical Medical Library of The College
of Physicians of Philadelphia)

Notice the reference to vaccines being poison and not only ineffective, but actually producing death. Most important is this sentence: "Any dogma of a class, medical or religious, that needs the fostering care of legislative enactment to force it upon the people, shows inherent weakness and condemns it at once among all men." It also claims that the smallpox vaccine caused greater mortality than smallpox itself. 

A Supreme Court Case

In Part 1 of this two-part series, we saw how important the smallpox vaccine became as a preventive measure against a grossly disfiguring and highly contagious disease. By 1902, smallpox vaccination was well established in Boston. Nevertheless, the disease stubbornly hung around, and officials took drastic measures. For instance, public health doctors, accompanied by guards, went to the railway yards and forcibly vaccinated “Italians, negroes and other employees.”

In 1902, Cambridge's Board of Health mandated smallpox vaccination for all residents who had not been vaccinated since 1897. But a naturalized Swedish American called Reverend Henning Jacobson refused to take the vaccination, claiming that Sweden's mandatory vaccination when he was six years old had caused him "great and extreme suffering." He was convicted and fined $5, which he refused to pay. 

                                            Henning Jacobson (Image: New England Historical Society)

In a legal brief, Jacobson stated he rejected a law that compelled ". . . a man to offer up his body to pollution and filth and disease," on the basis of the 14th Amendment, which states in part, "No state shall make or enforce any law which shall abridge the privileges or immunities of citizens of the United States."  Of note, Jacobson made dire references to vaccinations ("filth and disease") that echoed those of the 1807 "Vaccine Monster" flyer. The Jacobson case went to the U.S. Supreme Court, which held that individual liberty is not absolute and is subject to the police power of the state. Jacobson lost the case.

But in 1926, a group of health officers who went to Georgetown, DE to vaccinate the townspeople were met by an armed mob led by a retired Army Lieutenant and a city councilman. The "vaccinators" were driven out. If any of the residents of Georgetown were aware of the 1905 Supreme Court ruling, it evidently made no difference to the ire directed against the authorities.

In 1935, two separate polio vaccine trials using killed and attenuated poliovirus resulted in catastrophic morbidity and mortality in many subjects out of the 11,000 total number of people vaccinated. This doesn't say vaccines are bad; rather it emphasizes the absolute importance of conducting careful trials before a large number of people are administered a vaccine. In 1953, Jonas Salk produced an injected vaccine for polio using a killed virus, and in fact he injected his own family members with it. In 1959, Albert Sabin brought out his oral attenuated virus, which was tried out on, strangely enough, Soviet citizens. In modern times, only the inactivated (injected) poliovirus is used in the U.S., while other countries use the oral form. Throughout the 1900s, many of the vaccines with which we've come to be familiar, e.g. mumps, measles, rubella, rabies, diphtheria, pertussis, meningitis, and chickenpox were developed. In 1972, the smallpox vaccine was no longer routinely administered in the U.S. 

The "Case" Against Vaccines

The objections and resistance to vaccination fall into a number of categories:

• Religion: It isn't that multiple Christian denominations like Roman Catholic, Amish, Anglican, Episcopalian, have an official stance against vaccination. They do not. What we see is the individual who believes that "God is more powerful than any virus," or some similar declaration. These people refuse vaccinations on the basis of their faith. All but two US states allow vaccination exemption on the basis of religion.
• Misconceptions: Just as in foregoing centuries, some believe that vaccines actually give a person the disease or even cause death. This is still the case with the annual influenza vaccine. I have personally taken it every year for more than 20 years, but people still swear (including a surprising number of people in health care) that whenever they get the flu shot, they get the flu. It isn't true. There may be a mild local or systemic reaction, but it is not the flu.
• Concerns about adverse effects: In 1998, Andrew Wakefield published a study in the influential British medical journal, The Lancet, claiming to show that the mumps-measles-rubella (MMR) vaccine could be associated with the development of autism in twelve children. What followed was a circus of accusations and conspiracy theories that the manufacturers of the MMR vaccine were hiding the truth about its causing autism. When the cause of a disease is unknown, those affected will readily latch onto any explanation offered, no matter how flawed. Wakefield's paper was deeply flawed, yet it took The Lancet 12 years to officially retract it. However, humans being what they are, a planted seed puts down deep roots and continues to grow unabated.
• Fear of vaccine ingredients: in 1926, Alexander Glenny increased the effectiveness of the diphtheria toxoid by treating it with aluminum salts. Called an adjuvant, this increases the immune response in a subject. Much later, in 1964, the American Academy of Pediatrics recommended aluminum adjuvant in the combination diptheria-tetanus-pertussis (DTP) vaccine. The amount of aluminum salts contained is in fact less than the amount in normal human breast milk, but many people are under the impression that there are pieces of the metal aluminum floating around in the vaccine. Like the MMR vaccine itself, thimerasol, a preservative containing ethyl mercury, was implicated--falsely--to autism. Since 2001, thimerasol hasn't been used in children's vaccines, although it is still used in the adult flu vaccine unless preservative-free vaccine is specifically requested.
• Immune overload: Many parents falsely believe that the multiple immunizations given to children at a single doctor visit is detrimental to a child because their immune system can't handle them all at once.
• Genocidal agent: prevalent in Africa especially is the belief that vaccines are really an attempt by western countries to kill off black Africans. Most recently, this conspiracy theory has been applied to the putatively upcoming Covid vaccine, and of interest is that Bill Gates is central to that plot. But don't scoff at Africans just yet. Since Gates famously predicted a pandemic back in 2015, some Americans also believe that he started the pandemic himself. (Others decry why he shows up on CNN talking about medical issues when he is not a physician.). But guess what? President Barack Obama actually beat Gates to it (at least on YouTube) when he precisely foresaw a global airborne pandemic such as Covid back in 2014.

Individual Liberty

All those above reasons aside, a powerful theme that has run through the anti-vaxxer's cry from way back in the 1800s until the present day is a strong objection to being told what to do by authorities. People go to a physician for a sore throat and demand antibiotics, but being asked to take a vaccine to prevent illness is a different matter. That is an imposition on one's freedoms, as is wearing a mask to prevent spread of Covid. There are emotional, cultural, and ideological objections to vaccination. Conservative people are less likely to accept or recommend vaccination. Donald Trump has used Twitter to perpetuate the long-debunked linkage between autism and vaccines since as far back as March 2012. However, a well-known liberal, Robert F. Kennedy, Jr. also was a vaccine skeptic. 

Suspicion of government and the perception that authorities are trying to take away personal freedoms are often tied to any number of dark conspiracy theories. These are sometimes triggered by signals from sharply partisan individuals with a platform, such as conservative TV and radio hosts, celebrities such as Jenny McCarthy, and leaders such as President Trump, who has cast aspersions on the CDC, for example. The tangle of ideology, politics, and conspiracy theories is complex, and unfortunately it can have negative and dangerous consequences when it comes to vaccines and vaccination. Since the 19th century, we have made tremendous progress in science and technology, but for some, that "Vaccine Monster" of 1807 is still a reality. 

(Addendum: A correction was made to reflect that the Robert Kennedy who is a vaccine skeptic refers to Robert F. Kennedy, Jr.)

Disease Fighting Woman: Mary Montagu

Annmaria on Monday

Lady Mary Wortley Montagu did not invent inoculation.  She found out about the practice in the 18th century, from Turkish women.  Sad to say, history did not record the Turkish women's discovery, so we cannot laud them for their priceless contribution to disease prevention. But at least, today, I can set the MIE record straight on part of the contribution of women to this critical endeavor.

Last Wednesday, my colleague Kwei Quartey told us about early advances in immunization, beginning with the Scots physician Edward Jenner's fight against smallpox.  A brilliant contributor, no doubt, but Jenner was only thirteen years old when my entry into this pantheon. Lady Mary Wortley Montagu died.  She had already brought inoculation to England.

Lady Mary and Alexander Pope

I first learned about Lady Mary while studying 18th Century lit with my mentor and forever hero Sister Mary Catharine O'Connor PhD, PhD.  (Aside: This is not a typo.  This woman who had entered the convent at fourteen had two PhDs, both from Columbia University!) While teaching the works of Alexander Pope, SMC, as those who still love her called her, told us of Mary Montagu - her relationship with Pope and her many accomplishments.

Therefore, I already knew about Mary Montagu's medical exploits when Kwei told us, last week, about Onesimus, an African slave, who introduced the Bostonian Cotton Mather to the technique of inoculation.  Kwei quite rightly decried the fact Onesimus was left out of the history he had had read as a child.  Stan also quite rightly blamed Eurocentrism as the culprit.  I applaud anyone who corrects the historical record, especially when it comes to the almost total emphasis on the accomplishments of the white men.  Today I am here to correct the record on behalf of Lady Mary, a largely ignored woman when it comes to fighting disease.

Mary Pierrepont - born 15 May 1689 - aristocratic, beautiful, powerfully intellectual, owed her accomplishments entirely to herself.  Ignoring the "superstitious tales and false notions" that her governess tried to foist upon her, Mary, as a child and young woman, spent just about all her waking hours everyday in her father's extensive library, teaching herself Latin, mastering the classics in many subjects, and beginning extensive correspondences with a couple of Bishops who added to her self-education.

A celebrated beauty, even as a small child, she was on her way to being auctioned off to the highest bidder. Her father was putting the finishing touches on her marriage contract: an alliance with the most valuable possible suitor, a man with the absurd name of Clotworthy Skeffington.  But Mary was already in love with a friend's brother, Edward Wortley Montagu.  Just in the nick of time, the young couple eloped.

In the early 18th century, smallpox was a huge curse on humanity.  Intensely infectious and deadly - it killed twenty-five percent of the people who caught it.  Those who got out of it alive remained disfigured with scars.  Standard medical practices at the time included purging with emetics and bleeding, either through cuts in the flesh or the application of leeches.

Just a year after Lady Mary married, her favorite brother died of smallpox.  Two years later (1715), she herself contracted the dreaded ailment.  She survived, but her legendary beauty was spoiled.

 Meanwhile, her husband's career was going well.  He was named Ambassador to the Ottoman Empire.  She and their children went with him to Constantinople.  Her greatest claim to fame today comes for the letters she wrote while there.  As a woman, she was allowed to visit the women's quarters in Turkish court homes.  She wrote into the record vivid first-hand accounts of how those women lived.

She also learned how they prevented smallpox.  By taking live bacteria from the mildly infected and scratching it into the skin of well people.  Women practiced this technique.

Intent on protecting her own children, she talked over the issue with the British Embassy Surgeon, Charles Maitland.  Though he wasn't exactly keen on the idea, he did agree when she decided to have her nearly five-year-old son inoculated.  Young Edward Wortley Montagu was the the first English person ever to receive such a preventative treatment.  As was the ordinarily the case, the boy became mildly sick, recovered in a few weeks, and was safe from smallpox for the rest of his life.

Caroline, Princess of Wales

The family was back in England in 1721, when a major outbreak occurred.  Maitland, also then in London, agreed to inoculate Lady Mary's daughter - the first time such a treatment was used in Britain.  The medical profession was outraged.  But sisterhood took over.  Lady Mary convinced the the Princess of Wales, Caroline Ansbach to sponsor a test of the procedure.  Seven prisoners awaiting execution in Newgate Prison got an offer they couldn't refuse.  If they would agree to inoculation, they would earn their release.  They all survived and lived free.  The outcry against the procedure ramped up.  But the women involved stuck it out.  The Princess had Caroline and Amelia, her two daughters inoculated the following year.  In Russia, Catherine the Great herself and her son Paul, the future Tsar were inoculated later in the century.

In those early days, when the procedure was in its infancy, there were some dangers.  A small percentage of the people treated did develop serious cases.  But most lived on with immunity.

When Lady Mary died in 1762, Edward Jenner was still a child.  He did, as Kwei reported last week, develop a safer protection against smallpox using cowpox bacteria.  I maintain that these later improvements, while certainly great achievements, would not have been possible were not for the pioneering work done by the anonymous Turkish women and Lady Mary's insistence that the technique had merit.  They led the way.  The men who came along later built on the base of the women's idea.  And took the credit.