From Cowpox to COVID: The Remarkable History of Vaccines

Editor’s Note: This article is Part 1 of 8 in our series, “The Vaccine Paradox”. This series explores the stunning success of vaccination and the parallel rise of a skepticism that threatens to undo one of the greatest public health achievements in human history.

From Cowpox to COVID: The Remarkable History of Vaccines

I. Introduction: A Silent Revolution

Imagine a world without vaccines. It’s a world where parents live in constant fear of a cough that could signal diphtheria, a fever that could lead to measles-induced blindness, or a summer swim that could result in a life spent in an iron lung due to polio. For most of human history, this wasn’t imagination; it was reality. The arrival of a contagious disease in a community was a terrifying, often unstoppable force, leaving a trail of death, disability, and grief.

The history of vaccines is one of a silent, ongoing revolution. It is a testament to scientific curiosity, human ingenuity, and global cooperation. From a simple observation about milkmaids to the lightning-fast development of mRNA platforms, vaccines represent one of humanity’s most profound public health achievements, saving billions of lives and fundamentally reshaping our relationship with infectious disease. It is the story of how we learned to teach our bodies to defend themselves, turning the tide against our oldest microbial adversaries.

II. The Dawn of Immunization: Jenner and the Defeat of Smallpox

For centuries, smallpox was one of the most feared diseases on Earth. Caused by the variola virus, it was brutally efficient, killing roughly 30% of those it infected and leaving survivors permanently scarred or blind.¹

Long before Jenner, physicians in Qing-era China, the Ottoman Empire, and parts of India and Africa practiced variolation—deliberately introducing powdered smallpox scabs into the nose or making small cuts in the skin and inserting infected material. While this reduced mortality compared with natural infection, it still killed up to 2% of recipients and could spark new outbreaks.²

The breakthrough came from an English country doctor, Edward Jenner. He was intrigued by the local folklore that milkmaids who contracted cowpox—a mild disease of cattle—were mysteriously immune to smallpox. In 1796, Jenner decided to test this hypothesis. He took pus from a cowpox lesion on the hand of a milkmaid named Sarah Nelmes and inoculated an eight-year-old boy, James Phipps, on May 17. The boy developed a mild fever but quickly recovered. Weeks later, Jenner exposed Phipps to smallpox material. The boy remained healthy. He was immune.³

Jenner called his method “vaccination,” derived from the Latin word for cow, vacca. It was the birth of modern immunology—a safer, more reliable method that did not risk spreading the deadly disease itself. The practice spread rapidly across Europe and the Americas, marking the first great victory in the war against infectious disease.

III. Expanding Horizons: Pasteur and the Golden Age of Bacteriology

If Jenner’s discovery was a brilliant flash of empirical observation, the work of Louis Pasteur nearly a century later provided the scientific foundation. A French chemist and microbiologist, Pasteur’s germ theory of disease proved that invisible microorganisms were responsible for illnesses. This led him to wonder: could these germs be weakened, or “attenuated,” to produce a protective immune response without causing serious disease?

His theory was famously put to the test in 1885. A young boy, Joseph Meister, had been mauled by a rabid dog. Facing certain death, his mother brought him to Pasteur. Using a weakened form of the rabies virus developed in his lab, Pasteur administered a series of 13 injections over 11 days in July 1885. The boy survived.⁴ It was a landmark achievement that moved vaccinology from inspired guesswork to a deliberate, scientific discipline. The late 19th and early 20th centuries became a golden age of bacteriology, yielding vaccines for diphtheria, tetanus, pertussis, and tuberculosis, further taming the microbial world.

IV. Conquering Childhood Scourges: The War on Polio

By the mid-20th century, many bacterial diseases were in retreat, but viral scourges remained. None struck more fear into the hearts of parents than polio. The poliovirus often caused paralysis, confining thousands of children to “iron lungs”—massive metal ventilators that breathed for them. Public pools closed, and parents kept their children home, terrified of the invisible threat.

The fight against polio became a national crusade, funded by millions of small donations to the March of Dimes. This massive public effort fueled a fierce scientific race. In 1955, Jonas Salk announced he had developed an inactivated polio vaccine (IPV), made from killed poliovirus. On April 12, 1955, Salk announced that the vaccine was safe and effective. The public met the news with jubilation. Church bells rang, and people wept in the streets. Salk’s injectable vaccine was a triumph of medical science.⁵

Just a few years later, in 1961, Albert Sabin developed an oral polio vaccine (OPV), which used a live, attenuated virus. Administered on a sugar cube, it was cheaper to produce and easier to deliver, making it ideal for mass vaccination campaigns around the globe.⁶ While highly effective, health authorities now use the inactivated vaccine for global eradication campaigns to avoid the rare risk of vaccine-derived poliovirus associated with the oral vaccine.⁷ Together, these vaccines drove polio to the brink of extinction. Cases in the United States plummeted from over 57,000 in 1952 to fewer than 100 by the mid-1960s.

V. The Ultimate Triumph: Smallpox Eradication

The success of the polio campaigns inspired an even bolder ambition: to completely eradicate a human disease from the planet for the first time in history. The target was humanity’s old nemesis, smallpox. In 1967, the World Health Organization (WHO) launched the Intensified Smallpox Eradication Programme.⁸

It was a monumental undertaking, requiring unprecedented global cooperation during the height of the Cold War. Health workers traveled to the most remote corners of the globe, from the villages of India to the deserts of Africa, to track outbreaks and vaccinate populations. The strategy, known as “ring vaccination,” involved vaccinating everyone in a circle around a new case to break the chain of transmission.⁹

The last known natural case of smallpox occurred in Somalia in 1977, in a hospital cook named Ali Maow Maalin. He survived. After two years of careful surveillance with no new cases, on May 8, 1980, the WHO officially declared that smallpox had been eradicated.¹⁰ It remains one of the most extraordinary achievements in the history of medicine, a permanent gift to humanity from a generation of dedicated health workers.

VI. Modern Marvels: The Age of mRNA and Beyond

For decades, vaccine development continued to advance with new technologies like subunit, conjugate, and viral vector vaccines, which offered improved safety and efficacy for diseases like hepatitis B, Hib, and HPV. But the next great leap forward would come in response to a global crisis.

When the COVID-19 pandemic struck in 2020, the world needed a vaccine faster than ever before. The answer came from a technology that had been in development since the 1990s: messenger RNA (mRNA). The first mRNA vaccine prototypes were tested in animals in the 1990s, and by 2017, BioNTech had published positive data on mRNA influenza vaccines.¹¹ Unlike traditional vaccines, which introduce a piece of a virus to the body, mRNA vaccines work by delivering a set of genetic instructions. They teach our cells how to make a harmless piece of the virus’s “spike protein,” allowing our immune system to recognize and prepare for the real thing without ever being exposed to the virus itself.¹²

The result was astonishing. Scientists developed, tested, and deployed highly effective COVID-19 vaccines in less than a year—a process that once took a decade or more. This revolutionary platform holds immense promise for the future, with researchers now exploring mRNA vaccines for influenza, HIV, cancer, and autoimmune diseases.

VII. The Unseen Benefits: A World Transformed

The impact of vaccines is so profound it can be hard to comprehend. It is measured not just in the infections that happen, but in the countless illnesses, disabilities, and deaths that do not.

A 2024 study specifically examining vaccination against 14 different pathogens estimated that these programs saved 154 million lives over the past 50 years—the equivalent of saving one life every 10 seconds.¹³ The WHO estimates that vaccines prevent 4–5 million deaths every single year. Beyond the staggering number of lives saved, vaccines have fueled economic prosperity. They reduce healthcare costs, protect the workforce, and allow communities to thrive, free from the devastating cycles of epidemics. This population-level “herd immunity” also creates a protective shield around the most vulnerable—newborns, the elderly, and the immunocompromised—who cannot be vaccinated themselves.

While vaccines represent one of our greatest public health triumphs, their safety is continuously monitored through systems like the Vaccine Adverse Event Reporting System (VAERS) and other surveillance networks that track any potential side effects, ensuring that the benefits consistently outweigh the risks.¹⁴

VIII. Conclusion: A Legacy of Health, A Looming Challenge

From Jenner’s humble cowpox experiment to the sophisticated mRNA platforms of the 21st century, the history of vaccines is a powerful narrative of human progress. They are a cornerstone of modern civilization, transforming our relationship with infectious disease and granting billions of people the freedom to live longer, healthier lives, unburdened by the fear of diseases that crippled and killed our ancestors.

Yet, this triumph has created a paradox. The very success of vaccines has made them a victim of their own effectiveness. With the memory of these diseases fading, the perceived risk of the vaccine can sometimes feel greater than the risk of the disease itself. This growing hesitancy is a complex and dangerous challenge.

---

Next in “The Vaccine Paradox”: Why do people fear a technology with such a profound track record of success? In Part 2, we will explore the surprising history of vaccine controversy, from the earliest anti-vaccination leagues in 19th-century England to the modern movements that spread doubt and misinformation online.

References

1. World Health Organization. (2020). Smallpox. Retrieved from https://www.who.int/teams/health-product-policy-and-standards/standards-and-specifications/norms-and-standards/vaccine-standardization/smallpox
2. Riedel, S. (2005). Edward Jenner and the history of smallpox and vaccination. Baylor University Medical Center Proceedings, 18(1), 21–25. https://doi.org/10.1080/08998280.2005.11928028
3. Jenner, E. (1798). An Inquiry into the Causes and Effects of the Variolae Vaccinae. London: Sampson Low.
4. Institut Pasteur. (2020). The history of the first rabies vaccination in 1885. Retrieved from https://www.pasteur.fr/en/research-journal/news/history-first-rabies-vaccination-1885
5. Oshinsky, D. M. (2005). Polio: An American Story. Oxford University Press.
6. Passport Health. (2024). Flashback to vaccination with sugar cubes. Retrieved from https://www.passporthealthusa.com/2024/11/flashback-to-vaccination-with-sugar-cubes/
7. Our World in Data. (2024). Polio. Retrieved from https://ourworldindata.org/polio
8. Fenner, F., Henderson, D. A., Arita, I., Jezek, Z., & Ladnyi, I. D. (1988). Smallpox and Its Eradication. World Health Organization.
9. Centers for Disease Control and Prevention. (2023). Ring vaccination and smallpox control. Retrieved from https://pmc.ncbi.nlm.nih.gov/articles/PMC3323203/
10. World Health Organization. (2020). Commemorating smallpox eradication – a legacy of hope for COVID-19 and other diseases. Retrieved from https://www.who.int/news/item/08-05-2020-commemorating-smallpox-eradication-a-legacy-of-hope-for-covid-19-and-other-diseases
11. Sahin, U., Muik, A., Derhovanessian, E., et al. (2020). COVID-19 vaccine BNT162b1 elicits human antibody and TH1 T cell responses. Nature, 586(7830), 594-599. https://doi.org/10.1038/s41586-020-2814-7
12. Mayo Clinic. (2024). History of COVID-19: Outbreaks and vaccine timeline. Retrieved from https://www.mayoclinic.org/diseases-conditions/history-disease-outbreaks-vaccine-timeline/covid-19
13. Watson, O. J., et al. (2024). Contribution of vaccination to improved survival and health: modelling 50 years of the Expanded Programme on Immunization. The Lancet, 403(10441), 2307-2316. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(24)00850-X/fulltext
14. Centers for Disease Control and Prevention. (2023). Vaccine Adverse Event Reporting System (VAERS). Retrieved from https://www.cdc.gov/vaccinesafety/ensuringsafety/monitoring/vaers/index.html