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Weighing Risks and Benefits: Smallpox - Lady Montagu and Janet Parker

As we continue to live through the COVID-19 pandemic, the question that keeps coming up is: when will we have a vaccine? The gravity of the situation demands scientists to rush the development of a vaccine, but how can we be sure of its efficiency and safety? How can a vaccine then be made available worldwide and distributed fairly? Will it be enough to wipe out COVID-19 completely?


Throughout history, few diseases have caused global alarm to the same extent as COVID-19. One of these diseases was smallpox, that eerily bears many similarities to the coronavirus. Smallpox, however, is no longer a concern and learning about it can give us some clues to the challenges that we face in combating COVID-19.


Smallpox: A Disease of the Past


In 1980, the World Health Organisation officially declared that smallpox was a disease of the past. It was the first disease for which a vaccine was developed and is the only human disease to be eradicated through vaccination.


Smallpox had been around for thousands of years, with cases documented in ancient civilisations since 1500 BC. Smallpox virus, Variola, is airborne and can be passed between individuals or through contact with contaminated objects. It killed approximately 500 million individuals in the last 100 years of its existence. Thirty per cent of people that contracted smallpox died from the disease. The survivors were marked with severe scars all over their bodies, and a small proportion was left blinded.


Man with Facial Scarring and Blindness due to Smallpox 1972. [Don Eddins / Public domain]

Just like COVID-19 and many other diseases, smallpox has an incubation period. It takes 10-14 days from exposure to the first appearance of symptoms, many of which mimic flu-like symptoms. What follows are lesions on the face, arms and body. These lesions turn into pustules (blisters filled with pus) which eventually form scabs. These scabs come off after about a week, leaving deep scars all over.

While smallpox was poorly understood, it was known that survivors became immune. In some countries, survivors were recruited to nurse isolated patients. Isolating patients from the healthy population was the main strategy for prevention in ancient time.


The first efficient method to prevent smallpox was called variolation, named after the virus. Variolation involves scratching the skin of healthy people with a needle that previously been in contact with smallpox pustules. This way of introducing the virus caused less severe symptoms compared to full-blown smallpox.


Variolation was a common practice in Asia and Africa long before it was introduced to Europe in the 18th century. It is an efficient prevention technique – only about 2-3% of people variolated died from smallpox.


Lady Montagu and Charles Maitland Bring Variolation to England


The person who introduced variolation into England was Lady Mary Wortley Montagu, an ambassador’s wife who learned about this practice while stationed in the Ottoman Empire. Lady Montagu survived smallpox as a child, two years after the same disease took her brother’s life. Upon learning about the practice in Istanbul, she persuaded the embassy surgeon, Charles Maitland, to variolate her 5-year old son in 1717. The procedure was a success – he remained healthy and did not develop smallpox.


In 1721, as another outbreak of smallpox appeared in England, Lady Montagu who had since returned sought Charles Maitland to variolate her other child. Maitland was hesitant as he would be the first to perform this procedure in England. Lady Montagu persisted, agreeing to Maitland’s request of having two other licensed physicians present as witnesses.


This procedure was again a success, and one of the physicians even requested Maitland to variolate his child. News travelled, and with Lady Montagu as an advocate, variolation quickly reached the royal family.


Portrait of Lady Montagu. [Jonathan Richardson the younger / Public domain]

King George II wanted his two daughters to be variolated, so he requested Maitland to conduct a wider trial. He offered a set of trial subjects - six prisoners at the Newgate Prison, who had been promised a royal pardon in exchange for participating. Maitland was initially reluctant, but the royal insistence and growing public interest didn’t give him much option.


Following the success of the trial (and the release of the prisoners), Maitland was instructed to perform public variolations. Six adults and five orphaned children living in the parish of St. James Westminster were variolated in front of the media in 1722. There is no evidence that the children or their guardians consented to this trial. The second trial also worked well and Maitland was allowed to variolate the two princesses. From that point, variolation became common practice.


Vaccination: A Better Prevention for Smallpox


Variolation was replaced in the late 1790s by vaccination, a technique developed by physician Edward Jenner. Jenner noticed that milkmaids and dairy farmers were showing up with pustules similar to smallpox but with less severe symptoms.


The pustules were caused by cowpox, a disease that jumps from cows to humans that they come into contact with. Individuals who contracted cowpox were also immune to smallpox, and Jenner realised that exposing people to cowpox lesions was a safer way to protect against the more severe disease of smallpox.


The introduction of the vaccine was met with opposition and mockery. The idea of variolation was strange enough, but to expose someone to a different disease that originally came from an animal was stranger. Medical professionals at the time were slow to accept Jenner’s new concept, but we can now appreciate that it was a wonderful invention that has saved millions of lives.


Vaccination works by introducing a small dose of the virus into a healthy body. In response, the body produces an immune reaction that teaches the body to prepare for a bigger and more damaging attack. Side effects are minimal compared to the full-blown disease, and in the case of smallpox, boosts were required every 3-5 years. This was the norm until it was eradicated.


Smallpox vaccination became a global effort in the mid-1960s, and the last naturally occurring smallpox case was reported in Bangladesh in 1975.


The Last Victim of Smallpox, Janet Parker, Died from the Research Next Door.


Nowadays, smallpox can only be found in highly controlled research settings. Advances in science and technology are used to study smallpox to gain information about the virus. This knowledge can be applied to other viruses and other diseases. Parts of our understanding in combating new viral diseases such as COVID-19 can be traced back to smallpox research.


Any research laboratories working on smallpox are tightly regulated. These regulations, however, can vary from one country to another. This often makes the public nervous as they suspect some countries might develop infectious viruses into a biological weapon.


The research community was shaken when in 1978 when a research laboratory in Birmingham, UK, was found to be responsible for the death of a medical photographer named Janet Parker. Parker worked in the University of Birmingham Medical School and presented at the East Birmingham Hospital with flu-like symptoms. The doctors eliminated bacteria as a possible cause as antibiotics didn’t improve her condition.


An infectious disease specialist was called to examine Parker. He was surprised to find symptoms of the eradicated disease. He was familiar with smallpox because he was at the forefront of the eradication programme in Bangladesh five years prior.


How Janet Parker got the virus was a mystery. Natural infection was ruled out – the officials traced Parker’s movement and found no other new case locally. An unnatural source was a possibility – Parker worked one floor above the smallpox research laboratory in the university.


It was suspected that her office was connected to the research lab by an air duct, or she had unknowingly come into contact with a contaminated object. While the research staff who worked directly with the virus received regular boosters, Parker last received a vaccination 12 years earlier. Vaccination and boosters were no longer compulsory in the UK in the 1970s because of the rarity of cases.


Parker’s mother also contracted smallpox but managed to recover. To make matters worse, Parker’s father died from a heart attack during her hospitalisation and the head of the research group took his own life under scrutiny. The university was legally cleared of any wrongdoing, but in the court of public opinion, the university had failed to protect their staff and the public.


The last case of smallpox was a tragic one and ended up taking several lives.


The ward at East Birmingham Hospital where smallpox victim Janet Parker was admitted in 1978 [Dr Graham Beards / CC BY-SA (https://creativecommons.org/licenses/by-sa/3.0)]

Learning from History: Proceed with Caution


History teaches us that efforts to eliminate diseases are complicated and carry risk. Research can seem slow and tedious to the general public, but many do not realise that there are multifold regulations, procedures and controls in place for their protection.


While COVID-19 is the most pressing health issue globally at the moment, it isn’t practical to convert existing research groups to address it. Researchers might not have the right qualifications or experience to work with such an infectious virus, and the laboratories might not have the right design or specification to ensure safe handling and containment. When we cut corners we put others at risk.


Nowadays, research can no longer be done without ethics and consent. Our history books tend to overlook the failed experiments, treat mass casualties as nameless victims, and skip to the positive results. The truth, however, is not as clear cut.


References:

  • Behbehani A. M. (1983). The smallpox story: life and death of an old disease. Microbiological reviews, 47(4), 455–509.

  • History of Vaccines | Smallpox |

  • Riedel S. (2005). Edward Jenner and the history of smallpox and vaccination. Proceedings (Baylor University. Medical Center), 18(1), 21–25. https://doi.org/10.1080/08998280.2005.11928028

  • Vaccine Basics | Smallpox | CDC

  • Williams G. (2010) Legacy of an Angel. In: Angel of Death. Palgrave Macmillan, London. https://doi.org/10.1057/9780230293199_16


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