Infectious Respiratory Disease

CONTENTS OF CURRICULUM UNIT 25.05.04

  1. Unit Guide
  1. Introduction
  2. Demographics and Rationale
  3. Content  
  4. Teaching Strategies
  5. Teaching Activities
  6. Bibliography
  7. Appendix on Implementing District Standards
  8. Science Standards:
  9. Social Studies standards
  10. Notes

A Brief History of Vaccines and Respiratory Diseases

Damon Peterson

Published September 2025

Tools for this Unit:

Content  

Into the Deep: The Biology and Evolutionary History of Viruses

This section will begin with an introduction into the biology of viruses. More specifically, this section will look at the anatomical structures of viruses including their single, or double strands of DNA or RNA that is wrapped in a protein jacket called a capsid, and that some viruses have a protective outer coat called a viral envelope.  This section will also examine how viruses share important characteristics of living organisms, i.e., that viruses and organisms both have chemical structures that are encoded in RNA or DNA, the blue prints for life. However, viruses, unlike living organisms, cannot replicate, grow, or produce energy without infecting another organism’s cellular structures to replicate.

Next, the content will explore how viruses are relatively inactive until they come close to a compatible host cell. When close to the host cell, special proteins on the envelope of the virus can attach to cell receptors on the host cell. Once attached, the viruses and the cell membrane fuse together and allow the capsid and the RNA of the virus to enter the cell.  Then the capsid dissolves leaving the virus’s RNA exposed on the interior of the cell. The RNA is encoded with specific instructions, replicate.  Viral enzymes create replicas of the RNA which are then coated in proteins creating a capsid again. Once the RNA is back in its protective capsid coating, it then leaves the cell, but not before shrouding its capsid and RNA in a coating of the host cell’s membrane.  This coating allows the new replicated virus to continue their search of other cells to use as a replicator and create more replicas. However, it is important to note here that the viruses commandeering of the host cell often interrupts the normal functions of cells and can even kill the cells. This is how viruses not only replicate, but also how they cause sickness and disease.  

Having examined the structures and functions of viruses, the content will then turn to the evolutionary history of viruses and explore when viruses first evolved. Though a definitive answer has yet to be determined, many evolutionary biologists believe that the history of viruses spans into the past billions of years, perhaps before the first cellular life. In A Planet of Viruses, Carl Zimmer explains, “When they try to trace the common ancestry of virus genes, they often work their way back to a time before the common ancestor of all cell-based life. Viruses may have first evolved before the first true cells even existed.  At the time, life may have consisted of little more than brief coalitions of genes, which sometimes thrived and sometimes were undermined by genes that acted like parasites” 2 .

This deep history of viruses reveals that though they are small and relatively simple compared to multi-cellular life, viruses have had a long and influential history on the planet. Their history is so old that they may have evolved before cellular structures and before complex life. Therefore, like life, the nature of viruses is enduring. Despite tremendous environmental factors that have governed the flourishing and decimation of life on the planet, factors such as epochs of significant climate change, as well as the significant evolution of life itself, viruses have survived and have lasted to the present moment. Though simple when compared to multi-cellular life, viruses are no less successful in their ability to replicate and propagate through evolutionary history.

This history also demonstrates the intimate and intertwined nature that viruses have with all forms of life on the planet. Because their origins are ancient, and because they depend on the structures of living cells, viruses have likely been interacting and replicating with diverse and complex forms of life for billions of years. Consequently, viruses are key players in the evolutionary history of life on the planet. Their ancient history not only reveals the complexity of their own existence, but also the complexity of the symbiotic relationship that life and viruses share. More specifically, the perspective reveals the dual nature of viruses, i.e., they are not entirely destructive forces, but in their symbiotic relationship, viruses and life have shared genetic information that has resulted in the evolution of characteristics fundamental to complex life.

For example, there are also forms of viruses that replicate by inserting their DNA into the genome of a host cell. These viruses are called retroviruses. They also have a curious history with humanity as approximately 8% of the human genome is composed of the DNA of retroviruses. In his book Pathonogenesis, Johnathan Kennedy explains the astonishing idea that while

many of these DNA sequences don’t seem to do anything in the human body, retrovirus infections allowed our distant ancestors to acquire the capacity to perform functions that are fundamental to human existence.  One remarkable example is a gene inherited from a retrovirus infection about 400 million years ago that plays a crucial role in memory formation.  The gene does this by coding for tiny protein bubbles that help to move information between neurons, in a manner similar to the way that viruses spread their genetic information from one cell to another.  In the laboratory, mice that had this gene removed are unable to form memories. 3

Once again, looking into the deep evolutionary history of viruses reveals a much more complex nature. It demonstrates that viruses are not simply pathogens that create illness. Although this is a major part of the story.  It is not the entire story. The evolutionary perspective shows that yes viruses are dangerous, however, they have also been essential in the development and evolution of life. They have been as essential to something as key to the human experience as having the ability to create memories. It is only with this perspective that students can come to grasp a more complete understanding of viruses: that though they pose serious challenges to human health, they are also essential to the complex ecosystems of our planet.

Zimmerman summarizes this relationship by explaining, “viruses are unseen but dynamic players in the ecology of Earth.  They move DNA between species, provide new genetic material for evolution, and regulate vast populations of organisms. Every species, from tiny microbes to large mammals, is influenced by the actions of viruses. Viruses extend their impact beyond species to affect climate, soil, the oceans, and fresh water. When you consider how every animal, plant, and microbe has been shaped through the course of evolution, one has to consider the influential role played by the tiny and powerful viruses that share this planet.” 4   Ultimately, this evolutionary perspective reveals a complex. It reveals that they are fundamental to the ecology of life on the planet. And that due to their complex nature, they cannot simply be eradicated. Rather the complexity of their nature means that just complex techniques will need to be created to confront navigate and overcome the challenges they present.

Ancient Wisdom in the East: Origins of Inoculation

The next section of the curriculum will shift the study of viruses from a biological and evolutionary perspective to a historical perspective. The historical perspective will focus on early written accounts of treatments for infectious diseases. Here the curriculum will focus on treatments of smallpox in particular. Smallpox is a useful illness to study when examining early forms of prophylaxis because historical records show the long history that the illness has had with humanity.  When looking towards historical accounts of past pandemics, Zimmer notes the long history as well as geographical expanse of past outbreaks of smallpox. Zimmer explains, “Smallpox (orthopoxvirus variola) is known to be an ancient disease.  It flourished in the civilizations in the Fertile Crescent and the Indus Valley three thousand years ago. The first historical record of a disease clearly identifiable with smallpox occurs in China in the second century CE…In China, clinical descriptions of the disease date back to the fifth century CE.” 5

According to historical records, smallpox was an infectious disease that greatly affected past civilizations from across the ancient world. These past civilizations were tormented by the ravages of the disease.  Smallpox can be particularly traumatic because of the immediate and long-term health risks.  The immediate health risks are that it is a highly contagious illness with an R0 of 3.5-6.0. And when infected, the disease can be quite severe.  For example, initial side effects include a high fever, fatigue, and a characteristic red rash that can progress from flat red spots to raised bumps, pus-filled blisters, and finally, scabs referred to as pot marks.  For common forms of the illness, the average mortality rate was about 30%. 6  Additionally, pot marks from rashes could last for life permanently scarring those infected.

Because smallpox was widespread across the ancient world, and because the symptoms and illness ravaged communities, ancient traditions sought explanations, remedies, and treatments for the disease. Early written accounts of treatments include inoculation. Inoculation is a form of prophylaxis where an individual is immunized against illness by introducing infected material into the body. The infected material will create and immune response from the victim which helps them to establish immunity against the illness in the future. Early forms of smallpox inoculation emerged in the ancient history of Eastern cultures and traditions. In War on Small Pox, Michael Bennet explains,

In Asia, there were more sophisticated forms of smallpox prophylaxis whose origins are likewise lost in the mists of time.  The peoples of central Asia may have pioneered the prophylactic practices that subsequently spread eastwards, southwards and westwards.  By the eighteenth century, there were robust traditions of inoculation in China, northern India and pars of the Middle East. In China, the practice of insufflation is first described in medical texts in the sixteenth century.  Described in poetic language as ‘planting the heavenly flowers’, this mode of communicating smallpox involved blowing processed smallpox dust through a pipe into the nostril of the patient. 7

Due to the ravages of pandemics, Eastern traditions searched for and developed the first early and sophisticated treatments.  Among these treatments was inoculation, or also called insufflation. This treatment is rather clever for viral infections because the inoculation utilizes the body’s immune defense system by trigging a response from the immune system that will protect the person from future infections.  Important to note here is this is similar to how modern-day vaccines work.  Modern vaccines also use forms of an illness to trigger the body’s immune response with the intention of protecting the person against the illness in the future.  These early forms of inoculation in the East however were the first forms of this treatment. It was the first discovery of an important idea that would help protect civilizations and societies against the horrible ravages of infectious diseases. It was also an idea that other civilizations and traditions would build upon.  It was an idea that other civilizations would continue to explore for understanding so as to develop and innovate even better treatments for pandemics.

From the Renaissance to Colonial Conquest: The Search for a Cure 

Next, the curriculum will examine European scientific inquiry into smallpox prophylaxis during the renaissance/early colonial period. This is an important time period because there was an ethos characterized by a strong return to the search for knowledge.  According to Wikipedia, the Renaissance “marked the transition from the Middle Ages to modernity and was characterized by an effort to revive and surpass the achievements of classical antiquity,” and is “associated with great social change in most fields and disciplines, including art, architecture, politics, literature, exploration and science”. 8   This was a particularly significant moment in the development of inoculations and vaccinations because Europeans began looking towards the past for knowledge.  Here, scholars found forgotten knowledge that would help them develop new ideas and perspectives in the pursuit of developing treatments for infectious diseases.

The Renaissance was also a significant time period in the history of epidemiology because scientists, medical scholars, and those affected by infectious diseases began traveling beyond Europe extensively.  In these extensive travels, they discovered new ideas from other cultures and societies. These novel ideas that were discovered proved to be significant concepts in the treatment of infectious diseases and laid the ground work for further development. More specifically, inoculation was a concept that Western civilizations discovered in the East during the late renaissance. Europeans then developed the idea of inculcation further leading to the creation of the first forms of vaccines. Consequently, this section will explore two prominent figures: Lady Wortley Montagu and Edward Jenner. Both figures were significant in the development of these respective ideas.  

Lady Wortley Montagu [1689 – 1762] was an English aristocrat, medical pioneer, writer, and poet. She was also the wife of Edward Wortley Montagu. Edward served as the British ambassador to the Ottoman Empire [1716-1718]. During his service, both Edward and Lady Wortley traveled to Istanbul and throughout the Ottoman empire.  While traveling, Lady Wortley discovered significant insights into treatment of smallpox that were unknown in Europe. Smallpox was a particularly significant matter for Lady Wortley as her family, including herself, had been deeply affected by the disease. Bennet explains of Lady Wortley’s experience that “one of the brightest women at the Hanoverian court, she had good reason to be interested in prophylaxis.  After losing her brother to the disease in 1713, she declined to lease a house in London that had stood empty after a lady and her child died there from smallpox.  ‘I know tis two or three years ago’, she wrote, ‘but this generally said, that the infection may lodge in blankets etc. longer than that.’” 9 For Lady Wortley, smallpox was a deeply personal and deeply traumatic event that she carried with her throughout her life. “In a poem about her trauma, she described how she became ‘A frightful specter to myself unknown!’” 10

However, Lady Wortley was also deeply curious, intelligent, and compassionate. While traveling through the Ottoman empire with her husband and family, she observed a Greek tradition where women performed a form of inoculation against smallpox by engrafting. This is a method where smallpox material (usually of piece of a postulate) is taken, and then inserted into the body to instigate an immune response. The immune response will then give protection to the person against future infections. On seeing this treatment, Lady Wortley was astonished. She later wrote to a friend, “‘I am going to tell you a thing, that will make you wish yourself here. The small-pox, so fatal, and so general amongst us, is here entirely harmless, by the invention of engrafting.’ 11 ” Lady Wortley was astonished at this treatment because Europe was being ravaged by smallpox. Outbreaks were common and devasting. People did not understand from where, or what caused the illness.  Moreover, common treatments for the illness included blood-letting. This is a treatment where blood is let from the body with the understanding that releasing the blood will also release the illness from the body.  But despite this treatment, smallpox continued to ravage communities leaving people, including Lady Wortley, fearful and in search of a cure.

The engrafting she witnessed Greek woman performing was that cure. Lady Wortley was so amazed by the treatment that she later inoculated her own daughter. But her determination did not stop there.  Wortley was also inspired to bring this method back home to the United Kingdom. There she thought that inoculation could protect families and communities against future outbreaks.  And little did she know that her determination and fortitude would have reverberating affects in The West.  Bennett explains that “In Britain, the inoculation of Lady Worley Montagu’s daughter encouraged the Royal Society to seek opportunities for experimentation. Caroline, Princess of Wales, proved a persuasive advocate.” 12   Because of an ethos of inquiry during this period, and because of determined people like Lady Wortley, foundational principles such as inoculation and engrafting were observed, recorded, and then imported into the West.

However, these ideas were not without harsh criticism. From the beginning, these ideas were controversial and divisive. Lady Wortley herself understood that the idea of inoculation by engrafting would draw sharp public criticism as to the efficacy and ethics of the treatment.  Meyer explains, that Wortley “also anticipated difficulties introducing the ‘Turkish’ innovation into English medicine. Indeed, variolation became a controversial topic in Western Europe and the American colonies for much of the eighteenth century, even as the imported procedure was modified to be made to seem more ‘scientific’ and integrated into the medical marketplace.” 13 Although the idea of inoculation was controversial, Wortley continued to advocate for the treatment as a means to alleviate the terrible horror smallpox imposed not only on individuals and families, but society more broadly.  And with her continued advocacy, inoculation by engrafting garnered more attention from both society and the medical community. Slowly more communities and governments adopted the practice as they saw the benefits in alleviating suffering.

Lady Wortley’s adoption and advocacy for inoculation is a significant moment in the treatment of Smallpox in Europe. However, other individuals also contributed greatly to the treatment of the illness. Another notable figure in the development of treatments for smallpox is Edward Jenner [1749-1823]. Edward Jenner was an English physician and scientist. He is particularly significant in the history of epidemiology for several reasons. Foremost among these are his insights into, and the development of vaccines and vaccinations. Like Lady Wortley, Jenner’s story and the development of vaccination begins with the adoption of a known idea from another community.  This idea was the idea that a similar disease, cowpox, could create immunity against another disease, smallpox. This idea was commonly known among British and Dutch milkmaids who worked closely with cows. “According to Jenner, he first heard about cowpox and the belief that it prevented smallpox from a young woman in Chipping Sodbury in the late 1760s.” 14

Jenner also understood the potential impact this idea could have on epidemiology.  Vaccination was another method by which to inoculate individuals against the harms of smallpox.  Additionally, it was a method that could not only be less harmful, but also less costly. This is because instead of inoculating a person with smallpox material, material that can be dangerous and cause disease, a person is inoculated with cowpox material. This is significant because cowpox is less dangerous and less harmful to humans. Though the cowpox virus can still cause disease in humans, illness is much less common and much less severe.  This means the treatment could be replicated on a larger scale for larger communities and therefore have a larger impact on the disease in general. Bennett explains, “Unlike variolation, vaccination could be made available to the urging poor without risk to the wider community. The Society for the Condition and Increasing the Comforts of the Poor, founded in 1796, rapidly saw the value of the new prophylaxis.” 15  With this insight, Jenner was motivated to further develop the idea of inoculation by cowpox.  Consequently, he undertook a concerted effort to demonstrate the efficacy of the treatment. And like Lady Wortley, Jenner began by treating his own family as a means to demonstrate the efficacy of the method. Bennett explains, “Jenner used it to inoculate his son and two girls in Berkeley, and then confirmed their resistance to smallpox by variolation, with Dr Hickes replicating his findings at the Gloucester Infirmary.” 16

Jenner’s ambitious though were much broader than finding a cure for his family. He wanted to expand the idea of vaccination by cowpox to the international community. To do this, he understood that he needed to demonstrate the efficacy of the treatment on a larger scale if society more broadly was going to accept the novel, and also strange treatment. So Jenner undertook a scientific study of vaccination of willing participants.  Over a period of years, Jenner began vaccinating individuals and recording the effects. During this time, other methods of intervention were also being put forth by the scientific community. Dr. Haygrath, another scientist interested in epidemiology drew correlations between the social proximity of individuals and infection rates. “He found that smallpox spread almost entirely between people in close proximity and, while he recognized the utility of inoculation, he highlighted the importance of isolating smallpox cases and other sanitary measures. When smallpox stuck again in 1777, he organized a Society for the Prevention of Smallpox to promote inoculation but, critically too, ‘rules of prevention’.  The Society gave sums of money to poor parents who were willing to have their children inoculated and commit to keeping them off the streets during the infective stage.” 17

Eventually, in 1798 Jenner published his findings in his book, Inquiry into the Causes and Effects of the Variola Vaccine. Here one can find the origin of the word ‘vaccination’. Vaccination, was the word that Jenner derived for his treatment against smallpox by taking the Latin word for cow, ‘vacca’. Jenner’s “vaccination” was a novel method, built on the ideas of the past, to instigate an immune response to an illness.  However, instead of taking smallpox substance itself, Jenner used a similar disease and one less lethal to humans, cowpox. “So successful did his innovation prove that by 1840 the British government had banned alternative preventive treatments and the word [vaccination] was adopted by Pasteur for immunization against any disease” 18 Jenner’s book and the idea of vaccination, though slow to gain the attention from the scientific communities at first, later began to garner critical interest.  Soon other physicians, intrigued by Jenner’s method of inoculation, began experimenting.

This process by which vaccination disseminated into the public sphere was a bit unorthodox by today’s standers. The idea was not tested in research labs or universities. Rather, professional physicians played a large role in adopting and advocating for vaccination. Bennett explains that the “mobilization on behalf of cowpox inoculation was driven by personal and professional networks, supported by a growing number of books, pamphlets, journal articles and newspaper reports that informed and promoted a nationwide conversation, and not a little argument, about cowpox.” 19 Eventually Jenner’s ideas gained interest among a wide population throughout Europe, even drawing the attention of notable people such as Napoleon Bonaparte 20 who himself became a strong advocate for vaccination. However, this development was not without fierce criticisms and controversy. As vaccination proliferated, so did public debate over the efficacy and the ethics of the practice.

COVID-19: The Continued Search for Knowledge and New Cures

The COVID-19 pandemic was an unprecedented global health crisis in contemporary history. Caused by the novel SARS-CoV-2 virus, the pandemic first started in the Hubei province in Wuhan China. Though the exact origin of the virus has yet to be verified, and may never be, on December 31st, 2019, a hospital in Wuhan reported a cluster of pneumonia cases from an unknown cause.  Two weeks later, a new variant of coronavirus was identified, which was named 'severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Since then, the virus continued to transmit extensively 21 . On March, 11, 2020 the World Health Organization (WHO) declared the spread of the infection a global pandemic. Eventually the disease would spread to all continents, with the exception of Antarctica. To date, the SARS-COVID-2 virus is estimated to have infected 778,417,964 people, resulting in approximately 7,098,699 deaths. 22 Ultimately, the pandemic significantly affected societies around the globe including sectors such as; the global economy, food securities, education, tourism, domestic violence, and mental health. 23

The SARS-CoV-2 virus is a virus that belongs to a wider family of viruses known as coronaviruses. These types of viruses were first detected in 1930s by scientists studying infectious diseases in other animal groups.  Arthur Frederick Schalk and Merle C. Fawn at the North Dakota Agricultural College were the first to report on an infectious agent that would later come to be categorized as a coronavirus. 24   They were studying a new respiratory disease that was particularly affecting young chickens.  Frederick and Fawn, noticed that the symptoms of the disease were a severe shortness of breath and weakness. They also noted that the disease easily spread through the direct contact with chickens, or by the transfer of the bronchial exudates from infected to healthy chickens.

Since Schalk and Fawn, scientists have continued to research for novel respiratory diseases in chickens and many other animals. In this research, new and yet distinctly similar diseases have been identified in other animals. In 1949 Francis Sargent Cheevers, Joan B. Daniels, Alwin M. Pappenheimer and Orville T. Bailey investigated an infectious disease in mice. They discovered a disease that targeted the liver of mice in particular.  This targeting of the liver often caused severe neurosis and hepatitis. They named the new virus JHM after John Howard Muller, a pioneer of microbiology at Harvard. Then in 1959, John A. Morris, at the national institute of health in Bethesda, discovered a new mouse virus.  The new virus, again highly contagious, also caused severe cases of hepatitis and encephalitis in mice. After comparing this new virus to other mouse viruses, the JHM virus in particular, Morris discovered that the new virus was antigenetically related. Having discovered a significant commonality in the viruses, Morris created a common name "hepatoencephalitis group of murine viruses.”

In the following decades, new advancements in technology allowed for further comparisons of similar viruses to be made. In 1967 Kenneth McIntosh and fellow colleagues used electron microscopy to create images of these groups of viruses.  The images showed clear and similar features among the viruses. McIntosh wrote, “This appearance, recalling the solar corona, is shared by mouse hepatitis virus and several viruses recently recovered from man, namely strain B814, 2289E and several others…In the opinion of the eight virologists these viruses are members of a previously unrecognized group which they suggest should be called the coronaviruses, to recall the characteristic appearance by which these viruses are identified in the electron microscope.” 25

Today, scientists have identified many different kinds of coronaviruses that find viral reservoirs in many different species. For example, “As of 2022, there are 52 species of coronaviruses in the subfamily Orthocoronavirinaeunder the family Coronaviridae, of which seven are of humans while 45 are those of other animals such as pigs, dogs, cats, rodents, cows, horses, camels, Beluga whales, birds and bats.” 26 However, genetic sequences shows that the SARS-CoV-2 viruses likely came from bats. Although, there are still many unknowns of the exact origin of the virus.  For example, though it is possible, it is not known if there was an intermediary reservoir for the SARS-COV-2 virus, or whether the virus’s virulence towards humans was cause by the mutation in the original strain. 27

What is certain however, is the seriousness of the SARS-CoV-2 virus. From the beginning, the virus showed a strong proclivity to transmit between people. This was reported from the first health officials in China who reported an atypical-like pneumonia that was spreading through the city.  Later, the World Health Organization (WHO), would estimate the R0 of SARS-CoV-2 at 1.4 – 2.4. And though countries took initial precautious such as lock-downs and travel restrictions, cases continued to spread. As cases spread, the dangers of the infection became apparent. COVID-19 is often a biphasic illness, i.e., the illness shows distinct phases.  The first phase of upper respiratory systems can rapidly progress to profound hypoxemia and respiratory failure. SARS-CoV-2 can also impact other systems including the gastrointestinal, cardiovascular, renal, hepatic, and central nervousness systems, potentially resulting in multi-organ failure. 28

The severe circumstances of the COVID-19 pandemic led many nations and their medical institutions to create a vaccine that could possibly help mitigate the spread of the infection and also help those who were most susceptible to the illness. Countries and their medical institutions began working to develop vaccines to stop the spread of the virus. A new development in the science of vaccination, mRNA vaccines were among the methods scientists were pursuing to help combat COVID-19. mRNA vaccines can be potentially useful for a few reasons.  First, mRNA vaccines do not use a form of a virus to instigate an immune response, well not a form of the virus in the sense that Edward Jenner used the cowpox virus.  Rather, mRNA vaccines use genetic sequences from a virus, i.e., their messenger RNA that are then put into the body.  The mRNA then instigates cells to create an immune response to the viruses that the mRNA correlates to. 

This approach can be beneficial for several reasons. First, mRNA vaccines can be a safer approach to instigating an immune response. This is because mRNA vaccines use genetic information from a virus, and not the virus themselves. This reduces the risk of infection. “Instead of delivering a virus or a viral protein, RNA vaccines deliver genetic information that allows the body’s own cells to produce a viral protein. Synthetic mRNA that encodes a viral protein can borrow this machinery to produce many copies of the protein. These proteins stimulate the immune system to mount a response, without posing any risk of infection.” 29 In a sense mNRA vaccines are the next step in the long tradition of vaccinology. The story of vaccinology in a sense has been to use the illness itself to produce a cure for the illness.  In the case of the ancient Chinese: they were using small portions of the infection to create immunization.  Then there is Edward Jenner.  Jenner used a similar virus, one that is less harmful, to create immunization. This technology has now progressed again.  Now, vaccinology takes the most fundamental parts of viruses, their genetic sequences, and uses only the genetic sequence to create an immune response.

Another reason that mRNA vaccines are beneficial is they can be easier to create in the lab.  This is because once researches know the sequences of the viral protein, they can then more easily synthesize the sequence in labs. This approach stands in contrast to methods of the past. In the past, whether it was the Chinese inoculating by insufflation, or Lady Wortley inoculation by engrafting, or Edward Jenner inoculating by exposure to cowpox, all the previous methods required direct access to the virus. For example, the ancient Chinese needed to have access to a small pox postulate to inoculate another individual.  The same with Lady Wortley.  When she inoculated her daughter, she had to have found small pox material.  Even the same with Edward Jenner: he needed direct access to cowpox to vaccinate individuals.  In the modern iteration of vaccinology however, vaccinologists need access to the virus – yes. However, once they do, they are able to synthesize the genetic sequence. In the case of COVID-19, once China released the genetic sequence of the virus, researchers around the world could look for the genetic sequence that produced immunization.

And although the science of mRNA began before the COVID-19 pandemic, the technology during the outbreak of the pandemic was still new and there were still many challenges in the process that needed to be solved before an effective vaccine could be produced. For example, the proper sequence of the mRNA needed to be solved so that cells would create an immune response.  The reason being is that the genetic sequence of viruses, though shorter than multi-cellular life, is still long and the proper sequence of genetic coding must be identified to create the desired immune response. Additionally, there were also challenges of inserting the proper coding of genetic sequencing (the mRNA) into the host cells to produce an immune response that also needed to be solved.  This can be a challenging part of the process because mRNA molecules can be fragile and destroyed during the process of inserting them into the host cell. However, because COVID-19 was a worldwide pandemic, creating a vaccine to meet the demands of the global health crises would take the collaboration and cooperation from nations and many scientific institutions around the world.

The remarkable development of the mRNA vaccines was the product of human ingenuity, creativity, and collaboration to overcome a tremendous challenge. The ingenuity of such a rapid development of a vaccine, and the challenges that needed to be overcome was celebrated by the Nobel Laureate Organization.  Specifically, the organization recognized the work of Drs. Katalin Kariko and Drew Weissman.  Dr. Kariko built her career on studying mRNA and genetic sequencing.  Fascinated by the science of mRNA, her original work was focused on creating mRNA anti-cancer vaccines. However, when the COVID-19 pandemic unfolded, she shifted her sights to a COVID-19 vaccine. Dr. Weissman on the other hand was interested in another important problem for creating a mRNA vaccination. He was particularly interested in studying how to safely insert delicate molecules into cells. Together, they proved to be a powerful team. Dr. Kariko had the knowledge and understanding of mRNA molecules and Dr. Weissman had knowledge and expertise in how to deliver delicate molecules into cells.  In their collaboration, Dr. Kariko and Dr. Weismman managed to achieve a safe and effective delivery of mRNA molecules into living cells. Once the mRNA is safely inserted into a cell, the cell can then recognize a recognizable genetic sequence of a legitimate genetic sequence (even from an invading virus), and then produce an immune response and a working vaccine. 30

Though it was a tremendous undertaking, Park et. al explains, “As a great surprise, Moderna Biotechnology, Inc. delivered a vaccine named mRNA-1273 in only 42 days from the date when the spike protein-coding sequence of SARS-CoV-2 was published on January 10, 2020. Together, it took less than one year to complete the design, manufacture, efficacy and safety tests, and evaluation and approval for use.” 31 And despite the immense challenges, both the Moderna and Pfizer mRNA vaccines demonstrated a 94% - 95% efficacy against the COVID-19 infection. The vaccines also demonstrate something much deeper; they demonstrate the ingenuity of humanity when confronted with existential challenges.  But the mRNA vaccines are only the last chapter in a billion’s year long story.  

In coclusion, this story begins with the long and deep history of viruses as a symbiotic entity, one that is perhaps a precursor to multi-cellular life, but is also necessary to the evolution of life on the planet. Then the narrative evolves to one of humanity searching for absolution from the terrible afflictions placed on it by viruses. The story then continues to the earliest civilizations in their pursuit of knowledge that will bring a cure to these afflictions placed on them by the natural world. In particular, the ancient Chinese civilization intimated the first approximation of the cure with insufflation.  This formative idea was later adopted, practiced, and evolved by other civilizations. Lady Wortley and Edward Jenner are particular characters in this story for their appreciation and advocation for inoculation and vaccination as formative treatments for viral diseases. Then, with the COVID-19 pandemic, the world read the latest chapter in this story. Thanks to the giants of the past, Dr. Kariko and Dr. Weissman possessed the necessary knowledge to create new knowledge, understanding that penetrates the levels of cellular antonymy and genetic sequencing. Now from atop a formative promontory, one built upon billions of years of evolution – and millennia of human ingenuity, one is left with the reasonable question: what challenges can we overcome in the pursuit of knowledge, and where do we go next?

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