There will always be opposition to action, because it is human nature to be wary and to resist change. It is also within us to dare and, most importantly, to reason.
The story of vaccines began with fear of infectious disease. For over 3,000 years, smallpox decimated populations, and civilizations collapsed, while on a personal level many surviving individuals suffered hideous scarring or blindness, and parents agonized over the high likelihood of death of their infected children. The need to protect from this disease was desperate. Humankind faced this scourge and discovered a path to a solution which, as in all good stories, involved tragedies and suffering, idealism and courage, villains and heroes. But as a real-life story, this also encompasses medical quackery, objectification of women, war strategies, and an assortment of individuals who bucked convention: a courageous aristocratic mother, a selfless religious leader, an undaunted researcher. Unfortunately, this story does not end with the lauded “medical breakthrough” of vaccination, but continues with fanaticism, deceit, distrust, abuse of power and fame, and misinformation that is propagated to this day with the anti-vaxxer movement.
Ultimately, this vaccine story is about both the scientific and the human side of medical advancement. A not-inconsequential part is the role played by social influencers, who often have little to do with the scientific validity of the vaccine story. Their credibility in the public domain underscores the need to understand how societal structure and the art of persuasion influences scientific discoveries and, ultimately, why people make the decisions they do about health care.
Let’s start our story…
Early civilizations struggled for survival against the elements, natural disasters, starvation, war, and disease. They also struggled within their societies to make and enforce group decisions. However, early recorded histories of scientific advancements do not include insight into the battles for incorporating the new knowledge into medical practice or for social acceptance. (Sidenote: a fascinating example of scientific investigation and social impediment is provided by the story of the identification of cholera in the mid-1800s.1) Scientists, and historians, stick to the facts.
As early as 430 B.C. it was noted that people who survived smallpox did not contract this disease again.2 Practitioners in ancient China acted on the concept of artificial induction of immunity by blowing a powder of dried crusts from smallpox sores into the noses of those susceptible to infection, with the hope of inducing a milder form of smallpox that could be survived. In Persia, people ate prepared crusts from smallpox sores. In India, blankets from the mildly-diseased patients were wrapped around children to intentionally infect them with a less lethal form of disease that would hopefully confer resistance. These records indicate efforts to resist what was felt to be an inevitable scourge, although the level of effectiveness of these protocols was not scientifically monitored.
The concept of grafting disease from person-to-person became known as inoculation or variolation.3 This ultimately involved taking fresh matter from a smallpox pustule and introducing it into a scratch or incision made in the forearm of a child. Although such practices could also induce virulent disease or even spread other diseases such as tuberculosis or syphilis,4 these practices offered some hope of survival in the face of the deadly risk of smallpox.
Fear of tragedy can overcome inaction; Risk-taking itself is avoidance…in action.
Beauty, and a Mother’s Love…
For medical advancement, knowledge is not enough unless put into practice. Despite an eagerness to learn about innovations from other cultures, eighteenth century Europeans did not embrace variolation even after independent descriptions reached Europe from two British physicians in Turkey.4 Interestingly, the practice of variolation had derived from a beauty treatment of Caucasus, whose women were in great demand in the Turkish sultan’s harem because of their legendary beauty.4 Girls were inoculated in parts of their bodies where scars would not be seen. The fact that these girls survived to adulthood through repeated smallpox plagues had not gone unnoticed by the Turks. However, London physicians paid only passing interest to the preventative practice of variolation, loath to stake their reputations on such an unconventional idea.3
It took a woman to shake consciousness into the Royal Society’s Physicians in England. Lady Mary Wortley Montagu moved to Turkey in 1717 with her ambassador husband.4 Two years earlier, her own beautiful face had been disfigured by smallpox, and her brother had died of the illness. After witnessing the practice of variolation, she became determined to prevent the ravages of smallpox and convinced the embassy surgeon Charles Maitland to inoculate her 5-year-old son. When they returned to London several years later, Lady Montagu had the same physician inoculate her 4-year-old daughter in the presence of physicians of the royal court.
This combination of determination and influence within the high-society realm succeeded in bringing variolation to the attention of not only the Royal Society of London but also the royals themselves, who authorized testing first on inmates, then orphans. (These actions were not the result of a philosophy to first protect the weakest and most vulnerable of the population, but rather targeted ethically-unprotected, available, concentrated, and – fortuitously in a research-sense – especially susceptible groups.) The successful trials enticed the Princess of Wales to inoculate her own two children.3 This led to a certain level of acceptance of the procedure, presumably among the elevated classes of society that sought to attain the good life (or even life itself, protected from disease) modeled by the ‘social influencers’ of the time.
The hope this procedure brought did not bring about a shift in the practices of a population. Reports of sporadic inoculation-related deaths dampened both the lay person eagerness and physician willingness to be connected with such a risk, even at a low level.3 Behavioral shifts within the general European population required more nudging, presumably from those governing not their social affairs, but their spiritual and physical existence. Eventually, engineering the coordinated efforts necessary to affect change required political mandates.
Higher Powers…
Early social influencers cultivated their position with power, money, and reputation for moving in the first circles of society. Researchers and medical professionals held significant authority and responsibility for medical advancement. As immunization began its ascent as a tool of survival for humankind, two other regulating sectors came into play: religious leaders and governmental authority. The interplay between these forces shaped the future of what would come to be known as vaccines.
Disasters have long been felt be to do to God’s wrath, and not surprisingly, early resistance to the concept of inoculations was voiced by religious leaders, who felt that tampering with God’s punishments of disease and illness was the devil’s work.5 Yet it was also a religious leader who became an early champion of variolation (inoculation with pus from an infected person).3 Rev. Cotton Mather learned of variolation from a slave who had been inoculated in Africa as a child and later read the British physician reports about variolation from Turkey. He not only helped create a variolation program during a smallpox epidemic in Boston in 1721, but he sought to sway public sentiment by analyzing the lethality of smallpox by variolation (2%) versus naturally occurring smallpox (14%).3 “This may have been the first time that comparative analysis was used to evaluate a medical procedure.”4 The data helped variolation become widespread in the colonies of New England and had an even more profound impact in England, where despite physician skepticism, the statistical numbers were influential in establishing a new practice of care. From England, rapid adoption of variolation spread throughout Western Europe. Significantly, in 1757, one of the thousands of children to be inoculated was a young boy named Edward Jenner.3
A scientist’s dream is for the data to speak for itself. Surprisingly, this occurred with Mather’s report.3 Smallpox epidemics conveyed such a health threat that the lesser threat of spreading disease through variolation became acceptable. The lowered risk/benefit ratio prompted mass behavioral change that influenced even military policy.4 In 1776, American soldiers under George Washington suffering from a smallpox epidemic significantly reduced the number of healthy troops available to retake Quebec from the British.6 The British soldiers had all been variolated. Subsequently, Washington instituted a new procedure such that by the following year all his soldiers underwent variolation before beginning new military operations.4
Mather’s role in spreading the practice of variolation is largely overlooked by medical historians because the final leap from scientific awareness to public health practice belonged to a physician initially interested in animals.
Dawn of Vaccination…
The young boy who had been variolated in England in 1757 survived the mild case of smallpox with which he became infected and was subsequently immune to the disease.3 Even as a boy, Edward Jenner was very interested in science and nature.4,7 He apprenticed as a surgeon, but in addition, his teacher encouraged his interests as a naturalist and experimental scientist. It was his study of the hatchling behavior of cuckoo birds that resulted in his election as a fellow of the Royal Society in 1788, although many naturalists in England dismissed his work as pure nonsense. It took almost 100 years after his death to have his observation confirmed with photography.4 Mostly, Edward Jenner is known around the world as the Father of Immunology.7
Jenner apprenticed at age 13 to a country surgeon.4 It was at this time he first heard a dairymaid claim she would never have smallpox because she had been infected with cowpox. Later, at age 47 and after having risen to some prestige as a surgeon and researcher, Jenner turned his attention to the idea of disease prevention that he had been hearing from dairymaids for years. Scientifically, Jenner concluded that cowpox (or in Latin, vaccinia) not only protected against smallpox but also could be transmitted from one person to another as a deliberate mechanism of protection. He made this intellectual leap even though the germ theory advanced by the Austrian Marcus von Plenciz in 1762 had not gained traction against the miasma theory of bad air.8,9 Jenner called the procedure vaccination, most likely because it was felt to be uniquely applicable to cowpox.4 Unlike variolation, cowpox transmission through vaccination would not lead to potentially lethal smallpox disease. No one anticipated the immunologic revolution that would grow around ‘vaccination’, nor the lives that could be saved from a myriad of infectious diseases with this approach. His fabled inoculation of 8-year-old James Phipps using matter from Sarah Nelms’ fresh cowpox lesions seemed in hindsight to be a breakthrough that was fated to ultimately rid the world of one of its deadliest scourges. However, the Royal Society rejected his communication on the experiment, and his vaccination idea almost died at the outset.4 A year later and with more example cases, he privately published a booklet, but to a volatile reaction in the scientific community.2 His steadfast belief in vaccination spurred him to dedicate his career and fortune to promoting use of his vaccine. With single-minded intent, he sent vaccine to his medical acquaintances and to anyone else who requested it. It must be noted that vaccination initially became popular not through Jenner himself, but through the activities of others, particularly the surgeon Henry Cline with whom he shared the vaccine.4
The vaccine was propagated by extracting material from a vaccinated individual’s pustule to use on subsequent patients. This arm-to-arm passage was periodically supplemented with cowpox material when an active case of this rare disease was discovered. Not surprisingly, early documentation indicated vaccination had mortality rates similar to those of variolation, likely because this supposedly safer cowpox-induced vaccine material was occasionally contaminated with smallpox.3,10
Nonetheless, cowpox inoculation went ‘viral’ (in the modern sense of the word) and reached the United States in 1800. Why a statistically unremarkable procedure became so sought after remains enigmatic, except that perhaps people were ready to accept that science could provide a safe preventive measure and that medical researchers like Jenner would deliver this advancement. Jenner’s name remained linked to the procedure that he named. Even Thomas Jefferson, who became a fervent proponent, wrote to Jenner thanking him for his work.3 Although it’s been written that Jenner made no attempt to enrich himself through his discovery, he did petition the House of Parliament for recognition of his claim and for recompense.4 By 1801, over 100,000 people were vaccinated,10 and Jenner had devoted so much time to his cause that his private practice and personal affairs had suffered.4 Subsequently, on two occasions, the British Parliament awarded him significant sums of money. Jenner actively sought this compensation, but whether for necessity or for proprietary glory and financial accolades is unclear. Interestingly, later that same year (1801), the U.S. farmer Benjamin Jesty requested recognition of his use of cowpox in 1774.3 He lacked scientific standing and had no vaccine to share, but his claim highlights that the idea was not original or even inaccessible by scientific lay people.
“In science credit goes to the man who convinces the world, not the man to whom the idea first occurs.”
Francis Galton
What is clear is that although Jenner received worldwide recognition and many honors, he also found himself subjected to attacks and ridicule. Prominent philosophers such as Robert Thomas Malthus felt smallpox provided a necessary means of population control, particularly among the overcrowded lower class.3 Antivaccination groups proliferated and used the supposed defects of Jenner’s earlier cuckoo study to cast doubt on his credibility for more than a century. The National Vaccine Agency in the U.S., established in 1813, lost its funding in 1822 due to legitimate safety concerns about the vaccine. The scientifically valid issues of questionable duration of immunity, contamination and decomposition of the vaccine, and shortage of cowpox matter plagued early practitioners. Nonetheless, by 1821, vaccination was required by law in Bavaria, Norway, Sweden, and Denmark and gradually replaced variolation, which became prohibited in England in 1840.11 The political endeavors helped cement widespread propagation of vaccination.
Societies subjected to ruling classes, religious leaders, and the educated elite learned to accept rules that provided cohesion and safety.
“It’s the law!”
In 1979, the World Health Organization declared smallpox an eradicated disease. Edward Jenner is credited with saving over 200 million lives.12 His work is said to have “saved more lives than the work of any other human”.7
Propelling innovations in healthcare…
Why, then, did Edward Jenner’s ideas take off and ultimately rid the world of its oldest scourge, smallpox? His idea of using a related disease (cowpox) to confer specific immunity to smallpox was not original nor was he the first to attempt inoculation for this purpose. However, reexamination of the historic context of his work demonstrates that Jenner’s contribution was a vital step toward the elimination of smallpox. People had been injecting smallpox-infected matter subcutaneously to prevent disease for centuries before his time, which meant there was a foundation in Jenner’s time for rapid acceptance of his recommendations. Significantly, his relentless promotion of vaccination and his influence within the medical community capitalized on the confluence of social, religious, political, and scientific factors to make an impact on the practice of medicine and provide focus for future vaccine advancements.
Jenner succeeded for three crucial reasons:
1) His interest in zoology primed him to study the protective effects of a cow disease. He recognized the species disparity between man and cow that resulted in affliction with different diseases (cowpox and smallpox, respectively), yet made the intellectual — but at that time biologically unexplainable — leap that resistance to a human disease could be acquired by resistance to a cow disease. Although cowpox was well-known to protect against smallpox, Jenner used deliberate human-to-human transmission of cowpox to render smallpox infection nonlethal.
William Osler records that … Jenner …(was given) advice, well known in medical circles (and characteristic of the Age of Enlightenment), “Don’t think; try.”7
Smallpox was so common and devastating that any proof of protection provided hope. The success of variolation despite the risk of disease strengthened that hope. Finally, communication of the hope through social, scientific, religious, and political arenas bolstered widespread adoption.
2) His medical and biological research training provided the pedigree, the network, and also the publication avenue to sway a skeptical medical community.
3) Most of his success, though, came from his desire to forward vaccination, which meant that he worked tirelessly and without the stimulus of financial gain to provide vaccine to the medical community. He even built a hut in his garden to vaccinate the poor for free. Indeed, it was his relentless promotion and devoted research of vaccination that paved the way to a smallpox-free world.4
This third reason suggests Jenner’s success rests on his intent to implement his theory as a new medical procedure. Despite mixed reactions from the scientific community, he sent vaccine to his medical acquaintances and to anyone else who requested it.4 The support from these other doctors popularized the smallpox vaccine, which ultimately allowed Jenner to conduct a nationwide survey in 1799 to prove that cowpox infection protected against smallpox infection.4 The vaccine’s effectiveness convinced two noteworthy proponents who then helped secured worldwide acceptance of Jenner’s vaccine:7 1) a Spanish explorer named Dr. Francisco Javier de Balmis, who led a three-year expedition of the Americas and China, and who propelled the vaccine’s use into these parts of the world by successfully completing his aim of giving thousands the smallpox vaccine, and Napoléon Bonaparte, who vaccinated all his French troops and named Jenner as “one of the greatest benefactors of mankind.”
The elimination of smallpox in the world as an unqualified success story required an insightful and untiring champion who addressed a critical need with a scientific approach to change the world. However, history has buried incredible insights from those whose ideas did not make it on the world scene. The difference is that Edward Jenner’s story also exists within a societal time frame that shaped the outcome of his endeavor.
“However, opposition against vaccines was not only manifested in theological arguments; many also objected to them for political and legal reasons. After the passage of laws in Britain in the mid-19th century making it mandatory for parents to vaccinate their children, anti-vaccine activists formed the Anti-Vaccination League in London. The league emphasized that its mission was to protect the liberties of the people which were being “invaded” by Parliament and its compulsory vaccination laws. …Since the rise and spread of the use of vaccines, opposition to vaccines has never completely gone away, vocalized intermittently in different parts of the world due to arguments based in theology, skepticism, and legal obstacles.”5
Even early on Jenner’s vaccine faced fierce opposition from those who wanted the freedom to continue getting sick and die. Besides not being “God’s Will”, vaccines require subjugation of one’s body to outside influences, public policy that promotes the common rather than solely personal good, and acceptance of expertise beyond one’s own in the development and administration of public health initiatives. The innate belief is that illnesses are ‘natural’ and governmental influence is therefore unnatural. These beliefs persist and are propagated in the anti-vaxxers campaign in modern times, with the direct result that infectious diseases that were previously being controlled are increasing in prevalence in susceptible populations around the world. The next modern infectious-disease savior may not be a scientist cresting the world’s struggles with a dire medical need as much as a reformist overhauling social cohesion and medical belief issues.
References:
1. Buczek M. (2018, Feb 20). Wells and Wellness Part I: The History of Cholera. American Society for Microbiology. https://asm.org/Articles/2018/February/wells-and-wellness-part-i-the-history-of-cholera 2. Helfert, S.M. (2015). Historical Aspects of Immunization and Vaccine Safety Communication. Current Drug Safety, 10 (1), 5-8. https://doi.org/10.2174/157488631001150407103723 3. Gross, C.P. & Sepkowitz, K.A. (1998). The Myth of the Medical Breakthrough: Smallpox, Vaccination, and Jenner Reconsidered. Int J Infect Dis, 3:54-60. https://doi.org/10.1016/S1201-9712(98)90096-0 4. Riedel, S. (2005). Edward Jenner and the history of smallpox and vaccination. BUMC Proceedings, 18:21-25. https://doi.org/10.1080/08998280.2005.11928028 5. Hussain, A., Syed A., Madiha A., & S. Hussain. (2018). The Anti-vaccination Movement: A Regression in Modern Medicine. Cureus, 10(7): e2919. https://doi.org/10.7759/cureus.2919 6. Thompson, M.V. (2020, Nov 23). Smallpox. George Washington’s Mount Vernon. https://www.mountvernon.org/library/digitalhistory/digital-encyclopedia/article/smallpox/ 7. Edward Jenner. (2020, Nov 12). In Wikipedia. https://en.wikipedia.org/w/index.php?title=Edward_Jenner&oldid=988325290 8. Germ theory of disease. (2020, Oct 9). In Wikipedia. https://en.wikipedia.org/w/index.php?title=Germ_theory_of_disease&oldid=986022465 9. Eriksen, A. (2013). Cure or Protection? The meaning of smallpox inoculation, ca 1750-1775. Med. Hist, 57(4):516-536. https://doi.org/10.1017/mdh.2013.37 10. Vaccination. (2020, Nov 12). In Wikipedia https://en.wikipedia.org/w/index.php?title=Vaccination&oldid=988298689 11. Thein, M.M., Goh L.G., & Phua K.H. (1988). The Smallpox Story: From Variolation to Victory. Asia Pacific Journal of Public Health, 2(3):203–210. Retrieved Nov 14, 2020, from https://www.jstor.org/stable/26720502 12. Ochmann, S. & Roser M. (2018). Smallpox. Our World In Data. Retrieved Nov 13, 2020, from https://ourworldindata.org/smallpox#costs-of-smallpox-and-its-eradication
Science of Reasoning 