Dr Edward Jenner, the Father of Vaccination, in the Context of Covid-19 Pandemic

HEALTH, 5 Jul 2021

Prof Hoosen Vawda – TRANSCEND Media Service

The Challenges of Fighting Smallpox and SARS Cov-2 Remain Unchanged

30 Jun 2021 – ‘Necessity is the mother of invention”[1] as the age-old adage goes and this is also applicable to the field of medicine. In early 15^th century various pandemics devasted great parts of United Kingdom and Europe as recorded in western history.  Therein, a need arose for an intense search for cures, at the time, with available knowledge and technology in that era.  These ranged from herbs and spiritual cures, to burning a fire, continuously for two years, around His Holiness Pope Clemens v1, in the plague of the 14^th Century to prevent the His Eminence, The Holy Pope, from being infected with the plague pandemic, which was sweeping across Europe, very much like the SARS Cov-2 pandemic at the present time.

While burning a fire was certainly useful in the prevention of plague affecting His Holiness, little did the Papal physicians know the cause of the plague pandemic.  The fire actually kept away the rats, which in turn kept the fleas at bay, carrying the vector transmissible from rats to humans, causing a rampaging pandemic and death of the citizenry of entire cities in mediaeval Europe and beyond.

The difference is that the Covid pandemic is caused by an ever-mutating virus, giving rise to numerous progenies of the parent body and at present, the Delta variant is killing humanoids at an unprecedented level, while there is great uncertainty about the effectiveness of the vaccines developed by big pharma in the war against this bioterrorist.

Attempts to prevent illness and disease have changed over the centuries due to improvements in medical knowledge and preventive medicine becoming increasingly successful. Vaccination is one such community health strategy. How effective were attempts to prevent illness and disease over time, leaves a great deal to be a source of reflection. Vaccination attempts can even be tracked back to the Chinese emperors who practiced inoculations, which by present day standard would be considered barbaric.

Several accounts exist of early Chinese inoculations from the 16^th century, which describe smallpox inoculation as practiced in China and India[2]. Glynn and Glynn, in The Life and Death of Smallpox[3]. The scourge of smallpox affected rich and poor alike, killing many and disfiguring the rest. ‘Cures’ included bleeding, purging, oil of scorpions and even crabs’ eyes. Edward Jenner’s breakthrough in 1796 started the slow, often controversial, process of controlling the virus. It is recorded that in the late 17^th century, Emperor K’ang Hsi,[4] who had survived smallpox as a child, had his children inoculated. That method involved grinding up smallpox scabs and blowing the matter into nostril.  This is not surprising, considering that a new anti-Covid vaccine is developed and submitted for emergency use. This is the Convidecia nasal spray vaccine, developed by vaccine maker CanSino Biologics, in China[5], which will be inhaled via the nasal route, obviating injections and the need for low storage temperatures, totally. Inoculation may also have been practiced by scratching matter from a smallpox sore into the skin. It is difficult to pinpoint when the practice began, as some sources claim dates as early as 200 BCE.

During the late 18^th and 19^th centuries, a more scientific approach to the study of medicine was adopted. Scientists and medical professionals began to use observations, carry out experiments and record their findings.  This is classified as Evidence Based Medicine. However, many doctors still based their treatment on the four humours, as expounded by the works of Galen[6]  which were: blood (sanguine), yellow bile (choleric), black bile (melancholic), and phlegm (phlegmatic) and other ancient writers who gradually became less important and faded into historical records.

For many centuries, smallpox devastated mankind.[7] In modern times we do not have to worry about it thanks to the remarkable work of Edward Jenner and later developments from his endeavors. With the rapid pace of vaccine development in recent decades, the historic origins of immunization are often forgotten.

Unfortunately, since the attack on the World Trade Center on September 11, 2001, the threat of biological warfare and bioterrorism has reemerged. Smallpox has been identified as a possible agent of bioterrorism[8]. It seems prudent to review the history of a disease known to few people in the 21^st century.

Edward Jenner is well known around the world for his innovative contribution to immunisation and the ultimate eradication of smallpox.[9] Jenner’s work is widely regarded as the foundation of immunology, despite the fact that he was neither the first to suggest that infection with cowpox conferred specific immunity to smallpox nor the first to attempt cowpox inoculation for this purpose. It is a well-known fact that “In science credit goes to the man who convinces the world, not the man to whom the idea first occurs”, according to Sir Francis Galton[10].  It is also stated that “if it is not published, it never happened”[11] and the innovator is not credited for her or his efforts. Infact smallpox and inoculation with cowpox was also practiced by early Persian and Islamic physicians[12].  By definition, inoculation or vaccine inoculation, where in Latin vacca refers to a cow, smallpox inoculation continued to be called variolation, whereas cowpox inoculation was called vaccination.[13]

The origin of smallpox as a natural disease is lost in prehistory. It is believed to have appeared around 10,000 BC, at the time of the first agricultural settlements in northeastern Africa.[14] It seems plausible that it spread from there to India by means of ancient Egyptian merchants.[15] The earliest evidence of skin lesions resembling those of smallpox are found on faces of mummies from the time of the 18^th and 20^th Egyptian Dynasties (1570–1085 BC). The mummified head of the Egyptian pharaoh Ramses V who died in 1156 BC bears evidence of the disease[16]. At the same time, smallpox has been reported in ancient Asian cultures: smallpox was described as early as 1122 BC in China and is mentioned in ancient Sanskrit texts of India.

Smallpox was introduced to Europe sometime between the 5^th and 7^th centuries and was frequently an epidemic during the Middle Ages. The disease greatly affected the development of Western civilization. The first stages of the decline of the Roman Empire AD 108, coincided with a large-scale epidemic: the plague of Antonine, which accounted for the deaths of almost 7 million people.[17] The Arab expansion, the Crusades, and the discovery of the West Indies all contributed to the spread of the disease.

Unknown in the New World, smallpox was introduced by the Spanish and Portuguese conquistadors. The disease decimated the local population and was instrumental in the fall of the empires of the Aztecs and the Incas. Similarly, on the eastern coast of North America, the disease was introduced by the early settlers and led to a decline in the native population. The devastating effects of smallpox also gave rise to one of the first examples of biological warfare[18]. During the French Indian War (1754–1767), Sir Jeffrey Amherst, the commander of the British forces in North America, suggested the deliberate use of smallpox to diminish the American Indian population hostile to the British. Another factor contributing to smallpox in the Americas was the slave trade because many slaves came from regions in Africa where smallpox was endemic.

Smallpox affected all levels of society. In the 18^th century in Europe, 400,000 people died annually of smallpox, and one third of the survivors went blind.[19] The symptoms of smallpox, or the “speckled monster” as it was known in 18^th century England, appeared suddenly and the sequelae were devastating. The case-fatality rate varied from 20% to 60% and left most survivors with disfiguring scars. The case-fatality rate in infants was even higher, approaching 80% in London and 98% in Berlin during the late 1800s.

The word variola was commonly used for smallpox and had been introduced by Bishop Marius of Avenches, near Lausanne, Switzerland, in AD 570. It is derived from the Latin word varius, meaning “stained,” or from varus, meaning “mark on the skin.” The term small pocke , pocke meaning sac, was first used in England at the end of the 15^th  century to distinguish the disease from syphilis, which was then known as the great pockes.[20]

Procedure of variolation and early attempts of treatment, was based on the common knowledge that survivors of smallpox became immune to the disease. As early as 430 BC, survivors of smallpox were called upon to nurse the afflicted.[21] Man had long been trying to find a cure for the “speckled monster.” During medieval times, many herbal remedies, as well as cold treatment and special cloths, were used to either prevent or treat smallpox. Dr. Sydenham (1624–1689) treated his patients by allowing no fire in the room, leaving the windows permanently open, drawing the bedclothes no higher than the patient’s waist, and administering “twelve bottles of small beer every twenty-four hours”.[22]  These wide and varied modalities of treatment, are reminiscent of the range of options offered for the treatment of SARS Cov-2, presently and humanity in the 21^st  century is also faced with similar dilemmas, as encountered by our early ancestors when faced with epidemics and pandemics, in the past.

However, the most successful way of combating smallpox before the discovery of vaccination was inoculation. The word is derived from the Latin inoculare, meaning “to graft.” Inoculation referred to the subcutaneous instillation of smallpox virus into nonimmune individuals. 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. The terms inoculation and variolation were often used interchangeably. The practice of inoculation seems to have arisen independently when people in several countries were faced with the threat of an epidemic. However, inoculation was not without its attendant risks. There were concerns that recipients might develop disseminated smallpox and spread it to others. Transmission of other diseases, such as syphilis, via the bloodborne route was also of concern.

Inoculation, hereafter referred to as variolation, was likely practiced in Africa, India, and China long before the 18^th century, when it was introduced to Europe.[23] In 1670, Circassian traders introduced variolation to the Turkish “Ottoman” Empire. Women from the Caucasus, who were in great demand in the Turkish Sultan’s harem in Istanbul because of their legendary beauty, were inoculated as children in parts of their bodies where scars would not be seen. These women must also have brought the practice of variolation to the court of the Sublime Porte[24].  Variolation came to Europe at the beginning of the 18th century with the arrival of travelers from Istanbul. In 1714, the Royal Society of London received a letter from Emanuel Timoni describing the technique of variolation, which he had witnessed in Istanbul. A similar letter was sent by Giacomo Pilarino in 1716. These reports described the practice of subcutaneous inoculation; however, they did not change the ways of the conservative English physicians.

It was the continued advocacy of the English aristocrat Lady Mary Wortley Montague that was responsible for the introduction of variolation in England. In 1715, Lady Montague suffered from an episode of smallpox, which severely disfigured her beautiful face. Her 20-year-old brother died of the illness 18 months later. In 1717, Lady Montague’s husband, Edward Wortley Montague, was appointed ambassador to the Sublime Porte. A few weeks after their arrival in Istanbul, Lady Montague wrote to her friend about the method of variolation used at the Ottoman court. Lady Montague was so determined that she even dressed up as a male, to gain access to the Hagia Sophia Mosque in Istanbul, at the time, to learn and empower herself, as how to prevent the ravages of smallpox.  She also ordered the embassy surgeon, Charles Maitland, being the determined lady she was, to inoculate her 5-year-old son. The inoculation procedure was performed in March 1718. Upon their return to London in April 1721, Lady Montague had Charles Maitland inoculate her 4-year-old daughter in the presence of physicians of the royal court.

The greatest medical development before 1850 was the discovery by Edward Jenner of a successful method of preventing smallpox, one of the deadliest diseases of the time. He was, therefore, a pioneer in preventive medicine.[25]

Smallpox epidemics occurred every few years, leaving many dead. It killed about 30 per cent of those infected, while survivors were left horribly marked. In the 1730s, a young Welsh poet, Cadwaladr Roberts described himself as this grubby elf with perforated skin and thought that only a keen witch would now marry him.

As the U.S. COVID-19 vaccination program reaches full stride, approximating 3 million shots per day, the time is ripe to recall the contributions of the physician-scientist who first put vaccines on the map, Edward Jenner. Some claim that Jenner saved the lives of more people than any other figure in history, yet his approach is often poorly understood.[26]  There are four lessons of Edward Jenner, the “Father of Vaccination”.

1. Jenner built on the work of others

Born in England in 1749, Jenner was inoculated as a child against smallpox, a dread disease that appears to have scarred 3,000-year-old Egyptian mummies. Caused by the Variola virus, the disease manifested as fever and the development of a blistering skin rash referred to as pox. It is thought that about 30% of infected people died of the disease, especially infants and young children.

2. Jenner took bold risks

Jenner was not the first to suspect that prior infection with cowpox provided immunity against smallpox. At least five physicians had tested cowpox, and a farmer named Benjamin Jesty had used cowpox to vaccinate his wife and children during a smallpox epidemic. Jenner, however, was the first to study vaccination in a scientifically rigorous way.

Knowing that milkmaids were generally immune to smallpox, Jenner hypothesized that the pustules on the hands of milkmaids could be used to confer immunity. In 1796, he tested the idea by inoculating James Phipps, the 8-year-old son of his gardener. He scraped material from the hands of Sarah Nelmes, a milkmaid with smallpox, and inoculated Phipps in both arms.

After several weeks, he variolated Phipps. Although the boy did develop a mild fever, he did not develop full-blown smallpox. After a time, Jenner variolated him again, with no effect. The procedure had apparently conferred immunity. We now know that the viruses that cause cowpox and smallpox are sufficiently similar that the immune response to one can confer immunity to the other.

3. Jenner Was Not Deterred by Uncertainty

Today we talk easily of viruses, but in Jenner’s day they were completely unknown. The great microscopist Antony van Leeuwenhoek had discovered bacteria around 1676, but viruses are far too small to be seen through light microscopes. It was not until the invention of the electron microscope in 1931 that viruses were visualized for the first time.

Unanswered questions about the mechanism of vaccination led the Royal Society not to publish Jenner’s first manuscript, but after he conducted other trials, including one on his infant son, his paper was published. His greatest contribution was his insistence on challenging those who had received the cowpox inoculation with smallpox to prove they were immune.

Some decades before Jenner’s work, U.S. founder Ben Franklin decided not to variolate his young son Francis, a decision he regretted the rest of his life when the boy died of the disease at age 4 in 1736.

4. Jenner Dreamt Big

Smallpox vaccination quickly spread around the world. Spanish expeditions carried it to far-flung lands such as America and China. Napoleon had his troops vaccinated. Jenner received a host of domestic and foreign honors. To allow him to focus his attention on his investigations, Parliament awarded him huge grants of 10,000 and 20,000 pounds.

However, Jenner could not have anticipated where his work would lead. Immunisation by cowpox held sway until the 19^th century, when a more modern live-virus vaccine was developed using the lymph of calves. Today, versions of smallpox vaccine are available that do not use live viruses and thus cannot cause disease.

Yet no one is being immunized against smallpox today, because of a worldwide immunization program that led the World Health Organization to declare the disease eradicated in 1980. U.S. vaccination ceased in 1972, though many older adults still bear scars of it. Today the smallpox virus is found only in a few secure laboratories.

Edward Jenner died of apoplexy today described as a stroke in 1823 at the age of 73. He continued his scientific investigations until the end, presenting a paper on bird migration to the Royal Society in the year of his death. Whether or not Jenner truly saved more lives than any other figure in history, there is no doubt that his habits of mind offer deep insights to readers today.[27]

Jenner’s work represented the first scientific attempt to control an infectious disease by the deliberate use of vaccination. Strictly speaking, he did not discover vaccination but was the first person to confer scientific status on the procedure and to pursue its scientific investigation. However, the recognition of these facts should not diminish our view of Jenner’s accomplishments. It was his relentless promotion and devoted research of vaccination that changed the way medicine was practiced.

Late in the 19th century, it was realized that vaccination did not confer lifelong immunity and that subsequent revaccination was necessary. The mortality from smallpox had declined, but the epidemics showed that the disease was still not under control. In the 1950s a number of control measures were implemented, and smallpox was eradicated in many areas in Europe and North America. The process of worldwide eradication of smallpox was set in motion when the World Health Assembly received a report in 1958 of the catastrophic consequences of smallpox in 63 countries . In 1967, a global campaign was begun under the guardianship of the World Health Organization and finally succeeded in the eradication of smallpox in 1977. On May 8, 1980, the World Health Assembly announced that the world was free of smallpox and recommended that all countries cease vaccination: “The world and all its people have won freedom from smallpox, which was the most devastating disease sweeping in epidemic form through many countries since earliest times, leaving death, blindness and disfigurement in its wake” (22).

Scientific advances during the two centuries since Edward Jenner performed his first vaccination on James Phipps have proved him to be more right than wrong. The germ theory of disease, the discovery and study of viruses, and the understanding of modern immunology tended to support his main conclusions. The discovery and promotion of vaccination enabled the eradication of smallpox: this is Edward Jenner’s ultimate vindication and memorial.

Today, ethical principles are foremost when a new modality of treatment is used, hence reflections on Edward Jenner’s experimental treatment [28]  The question which begs to be asked in retrospect, is that Would Jenner’s smallpox experiment pass a research ethics committee?[29]

Edward Jenner develops a vaccination for smallpox, saves countless lives in the process and eradicates one of the greatest scourges of humanity, yet is often accused of conducting unethical experiments. The case seems indisputable. On May 14, 1796 Jenner vaccinated James Phipps, the eight-year-old son of his gardener, with material obtained from a milkmaid who had cowpox. A few weeks later he deliberately infected Phipps with smallpox to see if he would develop the disease. What could be more unethical than exposing a young boy to one of the deadliest diseases in the world simply to see if an unknown procedure would work? However, the story is more complex than this narrative suggests. In the 18^th century, doctors carried out a procedure known as variolation to protect people from smallpox. It was not a risk-free procedure, and people often died as a result. However, given the terrible mortality of smallpox this was seen to be worthwhile.

n 1798 Dr Edward Jenner published his famous account of “vaccination”. Some claim that a Research Ethics Committee, had it existed in the 1790s, might have rejected his work.   This is most relevant today in the context of SAR Co-2 pandemic as it provides the historical context of his work and argue that it addressed a major risk to the health of the community and given the devastating nature of smallpox as well as the significant risk of variolation, the only alternative preventative measure, Jenner’s study had purpose, justification and a base in the practice of the day.

The bottom line is exemplified in 1808 cartoon showing Jenner, Thomas Dimsdale and George Rose seeing off anti-vaccination opponents[30]  Today, the SARS Cov-2 pandemic has raised many ethical issues.  The first one was the use of unapproved medication in the fight against the pandemic, Invermectin.[31]  This is being used extensively with excellent outcomes, but ironically controlled clinical trials have shown no difference in the clinical outcomes, in Covid patients.  Then, as in the time of Jenner, we have the vaccine hesitancy group, the prominent anti-vaccine lobby and the big pharma who need to recoup their investment for fast tracking the development of the vaccine.  The spectre of serious diverse events from the use of the registered vaccines is another problem, that the general public, the “vaccine consumer” has to bear in mind. as well.  Only history will judge us in decades to follow, knowing fully well that the pandemic is here to stay for a long time, as the retribution of the Lord, as in Biblical times against the transgressing humanoids.

References:

[1] https://en.wikipedia.org/wiki/Necessity_is_the_mother_of_invention

[2] https://books.google.com/books/about/Science_and_Civilisation_in_China_Volume.html?id=n0wFT_u00FgC

[3] https://www.goodreads.com/book/show/2029373.The_Life_and_Death_of_Smallpox

[4] https://www.historyofvaccines.org/timeline#EVT_1

[5] https://www.yicaiglobal.com/news/china-first-inhaled-covid-19-vaccine-is-applying-for-emergency-use-top-epidemiologist-says

[6] https://retrospectjournal.com/2021/05/02/the-four-humours-understandings-of-the-body-in-medieval-medicine/#:~:text=Put%20simply%2C%20the%20four%20humours%20were%3A%20blood%20%28sanguine%29%2C,around%20the%20four%20seasons%2C%20and%20even%20around%20planets.

[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1200696/

[8] Henderson DA, Inglesby TV, Bartlett JG, Ascher MS, Eitzen E, Jahrling PB, Hauer J, Layton M, McDade J, Osterholm MT, O’Toole T, Parker G, Perl T, Russell PK, Tonat K Working Group on Civilian Biodefense. Smallpox as a biological weapon: medical and public health management. JAMA. 1999;281:2127–2137. [PubMed]

[9] Lakhani S. Early clinical pathologists: Edward Jenner (1749–1823) J Clin Pathol. 1992;45:756–758. [PMC free article] [PubMed]

[10] https://en.wikipedia.org/wiki/Francis_Galton

[11] Personal communication and opinion of the author 1996.

[12] https://en.wikipedia.org/wiki/Cowpox

[13] https://www.bing.com/search?q=inoculation+with+cowpox+was+also+practiced+by+early+Persian+and+Islamic+physicians&aqs=edge..69i57.5660199j0j1&pglt=43&FORM=ANNTA1&PC=U531

[14] Hopkins DR. Chicago: University of Chicago Press; 1983. Princes and Peasants: Smallpox in History.

[15]Barquet N, Domingo P. Smallpox: the triumph over the most terrible of the ministers of death. Ann Intern Med. 1997;127(8 Pt 1):635–642.

[16] Lyons AS, Petrucelli RJ., II . New York: Abradale Press, Harry N Abrams Inc; 1987. Medicine—An Illustrated History.

[17] Littman RJ, Littman ML. Galen and the Antonine plague. Am J Philol. 1973;94:243–255.

[18] Christopher GW, Cieslak TJ, Pavlin JA, Eitzen EM., Jr Biological warfare. A historical perspective. JAMA. 1997;278:412–417.

[19] Barquet N, Domingo P. Smallpox: the triumph over the most terrible of the ministers of death. Ann Intern Med. 1997;127(8 Pt 1):635–642.

[20] Moore JC. The History of the Smallpox. London: Longman; 1815.

[21] Gross CP, Sepkowitz KA. The myth of the medical breakthrough: smallpox, vaccination, and Jenner reconsidered. Int J Infect Dis. 1998;3:54–60.

[22] Willis NJ. Edward Jenner and the eradication of smallpox. Scott Med J. 1997;42:118–121.

[23] Gross CP, Sepkowitz KA. The myth of the medical breakthrough: smallpox, vaccination, and Jenner reconsidered. Int J Infect Dis. 1998;3:54–60.

[24] Willis NJ. Edward Jenner and the eradication of smallpox. Scott Med J. 1997;42:118–121.

[25] https://www.bbc.co.uk/bitesize/guides/zq8xk2p/revision/3#:~:text=In%20the%20late%2018th%20century%2C%20Edward%20Jenner%2C%20a,a%20series%20of%20experiments%20to%20test%20his%20idea.

[26] https://www.psychologytoday.com/us/blog/fully-human/202104/4-lessons-edward-jenner-the-father-vaccination

[27] https://www.psychologytoday.com/us/contributors/richard-gunderman-md-phd

[28] https://jme.bmj.com/content/33/3/174

[29] https://bioethics.georgetown.edu/2016/02/would-jenners-smallpox-experiment-pass-a-research-ethics-committee/

[30] https://en.wikipedia.org/wiki/Edward_Jenner#/media/File:Jenner_and_his_two_colleagues_seeing_off_three_anti-vaccinat_Wellcome_V0011075.jpg

[31] https://www.drugs.com/ivermectin.html

______________________________________________

Professor G. Hoosen M. Vawda (Bsc; MBChB; PhD.Wits):
Director: Glastonbury Medical Research Centre; Community Health and Indigent Programme Services; Body Donor Foundation SA.
Principal Investigator: Multinational Clinical Trials
Consultant: Medical and General Research Ethics; Internal Medicine and Clinical Psychiatry:UKZN, Nelson R. Mandela School of Medicine
Executive Member: Inter Religious Council KZN SA
Public Liaison: Medical Misadventures
Activism: Justice for All
Email: vawda@ukzn.ac.za

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