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The Story of Vaccines: From Jenner’s Cowpox to mRNA

The Story of Vaccines: From Jenner’s Cowpox to mRNA
History storyLong read · 9 min · interactive

In 1796 an English country doctor scratched a little fluid from a cowpox sore into the arm of an eight-year-old boy. It was one of the most consequential experiments in history. Vaccination went on to wipe out smallpox, a disease that had killed hundreds of millions of people, and to bring polio, measles and many other killers under control. This guide explains how vaccines work, how the idea developed, what herd immunity means, and how India fought smallpox and polio.

1796Jenner’s first vaccination
1980WHO declares smallpox eradicated
2014India certified polio-free
2023Nobel Prize for mRNA vaccine research
Quick facts
First vaccineEdward Jenner, smallpox, 1796
Name fromLatin vacca, cow
Disease eradicatedSmallpox, declared 8 May 1980
PrincipleTrain the immune system with a harmless form of a germ
Herd immunityWhen enough people are immune, outbreaks fade out
Newest platformMessenger RNA (mRNA) vaccines
Reading time10 min read
A note on health
This guide is general education, not medical advice. For questions about your own or your child’s vaccines, speak to a doctor or your local health service.
In this guide

    Smallpox: the great killer

    Smallpox was among the deadliest diseases in history. It caused high fevers and a rash of pus-filled blisters, killed roughly three in ten of those infected, and left survivors scarred or blind. It struck rulers and beggars alike and spread easily from person to person.

    People noticed long ago that survivors did not catch it again. In parts of Asia, Africa and the Middle East, healers practised variolation: they gave a healthy person a small dose of material from a smallpox sore, usually through a scratch or by inhaling dried scab, hoping to cause a mild case that would protect them. In India this was done by traditional inoculators known as tikadars, and it was practised in China, too. The practice was risky, because some people died of the inoculation or spread the disease, but it saved many lives. Lady Mary Wortley Montagu, who had seen it in Istanbul, helped bring it to England in the early 1720s.

    Jenner and the cowpox experiment

    Edward Jenner, a doctor in Gloucestershire, England, heard a piece of country wisdom: milkmaids who caught cowpox, a mild disease from cattle, seemed not to get smallpox. In May 1796 he took matter from a cowpox sore on the hand of a dairymaid, Sarah Nelmes, and scratched it into the arm of James Phipps, the eight-year-old son of his gardener. Phipps had a mild fever. Weeks later Jenner exposed him to smallpox material, and the boy did not become ill.

    Jenner published his results in 1798 and the technique spread rapidly across Europe and beyond. The word vaccine comes from the Latin vacca, cow. Today we would not accept an experiment on a child like this, and Jenner’s trial was tiny, but the principle was right and was soon confirmed on a large scale.

    How a vaccine works

    Training the immune system

    A harmless piece of the germ

    A vaccine contains an antigen: a weakened or inactivated germ, a fragment of it, or instructions for making one protein from it. It cannot cause the disease.

    The body spots the stranger

    Immune cells recognise the antigen as foreign and raise the alarm.

    Antibodies are made

    B cells produce antibodies that stick to the antigen, and T cells coordinate the response.

    Memory cells remain

    After the immune response settles, memory B and T cells stay in the body for months to decades.

    The real germ meets a trained defence

    If the real germ arrives, the memory cells respond within hours or days, usually stopping illness or making it milder.

    Try it: the herd immunity calculator

    Vaccination protects the person who gets it, and also those around them. When enough people are immune, an infection cannot find enough new people to spread. The share needed depends on how contagious the disease is, measured by R0, the average number of people one case infects in a fully susceptible population. A simple estimate of the threshold is 1 minus 1 divided by R0.

    Interactive: herd immunity threshold
    R0:   Vaccine effectiveness: %
    Simple textbook model with random mixing. Real thresholds vary with age, geography and how contagious each variant is.

    Herd immunity in Python

    for r0 in (1.5, 3, 6, 15):
        threshold = 1 - 1 / r0
        print(f"R0 = {r0:>4}: about {threshold * 100:.0f}% must be immune")

    Output:

    R0 =  1.5: about 33% must be immune
    R0 =    3: about 67% must be immune
    R0 =    6: about 83% must be immune
    R0 =   15: about 93% must be immune

    The more contagious the disease, the higher the bar. That is why measles, one of the most contagious diseases known, returns quickly when vaccination coverage slips even a little.

    Try it: an outbreak on a grid

    This toy model shows the same idea. Each square is a person. Vaccinated people (green) cannot catch the disease. One infected person (red) starts in the middle and can pass the infection to each neighbour with 60 percent probability. Change the vaccination coverage and press Run.

    Interactive: outbreak simulator
    Vaccinated: %

    Milestones in vaccination

    Vaccine milestones

    1721: Variolation in England

    Lady Mary Wortley Montagu promotes inoculation against smallpox.

    1796: Jenner

    First cowpox vaccination of James Phipps.

    1885: Pasteur’s rabies vaccine

    Louis Pasteur treats a boy bitten by a rabid dog.

    1955: Salk polio vaccine

    The first effective polio vaccine, an injection, is announced.

    1967: Smallpox eradication drive

    The WHO launches an intensified global campaign.

    1980: Smallpox eradicated

    The WHO declares the disease eradicated.

    2014: India polio-free

    The WHO certifies the South-East Asia region, including India, as polio-free.

    2020-21: mRNA vaccines

    The first mRNA vaccines are authorised and used around the world.

    2023: Nobel Prize

    Katalin Kariko and Drew Weissman win the Medicine prize for work that made mRNA vaccines possible.

    Pasteur extended Jenner’s idea to other diseases, and it was Pasteur who made “vaccine” a general term. The 20th century brought vaccines for diphtheria, tetanus, whooping cough, polio, measles and many more. Smallpox, the first disease to be targeted, became the first to be wiped out. The last natural case occurred in Somalia in 1977, and the World Health Organization declared the disease eradicated in May 1980.

    mRNA vaccines: the new platform

    Traditional vaccines use weakened or inactivated viruses, or pieces of them. An mRNA vaccine delivers a short strand of messenger RNA with instructions for making a single viral protein. The body’s own cells make the protein briefly, the immune system learns to recognise it, and the mRNA breaks down quickly. Katalin Kariko and Drew Weissman discovered that modifying the building blocks of mRNA stopped it from triggering harmful inflammation, a breakthrough that earned the 2023 Nobel Prize in Physiology or Medicine. The first mRNA vaccines were authorised for COVID-19 in late 2020.

    Vaccines in India

    India has a deep history with vaccination, from tika inoculation to modern campaigns. Smallpox cases were numerous in India in the 1960s, but a nationwide effort that included house-to-house searches brought them down, and India was declared smallpox-free in 1977. The Universal Immunisation Programme began in 1985 and was expanded by Mission Indradhanush from 2014. The Pulse Polio campaign, launched in 1995, used mass campaigns to give drops to children under five, and India recorded its last wild polio case in January 2011 and was certified polio-free in March 2014.

    India is also a vaccine manufacturing giant. The Serum Institute of India in Pune, founded in 1966, is one of the world’s largest producers of vaccines by number of doses. During COVID-19 India produced Covishield, made by the Serum Institute, and Covaxin, developed by Bharat Biotech, and its vaccination drive began in January 2021 and administered more than two billion doses.

    Mind map: vaccines at a glance

    Vaccines
    • Vaccines: Teaching the immune system before the real enemy arrives.
      • Before vaccines: Inoculation traditions.
        • Variolation: Deliberate exposure to mild smallpox, practised in Asia and Africa.
        • India’s tika: Traditional smallpox inoculation.
        • Lady Montagu, 1721: Brings the idea to England.
      • Jenner, 1796: The first vaccine.
        • Cowpox observation: Milkmaids seemed protected from smallpox.
        • James Phipps: The first test, May 1796.
        • The word vaccine: From vacca, Latin for cow.
      • Pasteur and after: New vaccines.
        • Rabies, 1885: Pasteur’s vaccine.
        • Polio, 1955 and 1961: Salk and Sabin vaccines.
        • MMR, 1971: Combined childhood vaccine.
      • Big wins: Diseases beaten.
        • Smallpox, 1980: Declared eradicated worldwide.
        • Polio-free India, 2014: Certified by the WHO.
      • How they work: Memory cells.
        • Antigen: A harmless piece or weakened germ.
        • Immune response: Antibodies and memory cells form.
        • Booster: Reminds the immune system.
        • Herd immunity: Protects the unvaccinated.
      • mRNA: The newest platform.
        • Messenger RNA: Instructions for one protein.
        • Karikó and Weissman: Nobel Prize 2023.
        • Fast design: Adapt quickly to new variants.
    Click a branch to open it. Drag to move the map. Use Ctrl and the mouse wheel, or the + and minus buttons, to zoom.

    Common myths

    • Myth: Vaccines cause autism. Large studies of millions of children have found no link, and the original paper that claimed one was retracted.
    • Myth: Natural infection is always better. Natural infection with measles, polio or tetanus can cause severe harm or death, while a vaccine gives protection with far lower risk.
    • Myth: Herd immunity means everyone must be vaccinated. It needs a high share, not everyone, and the share depends on the disease.
    • Myth: Vaccines contain mercury that harms children. Some multi-dose vials once contained a mercury-based preservative at tiny doses; most childhood vaccines today do not.

    Key takeaways

    • Vaccines train the immune system using a harmless form of a germ, creating memory cells.
    • Jenner’s 1796 experiment started the field and smallpox was eradicated in 1980.
    • Herd immunity depends on how contagious a disease is: the higher the R0, the higher the coverage needed.
    • India beat smallpox and polio, and is one of the world’s biggest vaccine makers.
    Test yourself

    Frequently asked questions

    How do vaccines differ from antibiotics?

    Vaccines prevent infections by training the immune system, mostly against viruses and some bacteria. Antibiotics treat bacterial infections that already exist.

    Why do some vaccines need boosters?

    Immunity from some vaccines fades over time, so a booster reminds the immune system and keeps protection high.

    Why are children vaccinated so young?

    Many diseases are most dangerous in infancy, so schedules aim to protect children before they are likely to meet them.

    Are side effects normal?

    Mild effects such as a sore arm or low fever are common and pass quickly. Serious side effects are rare and are monitored closely by health authorities.

    Sources

    Featured image: Image: Gaston Mélingue, via Wikimedia Commons, Public domain. This guide is for general education and is not medical advice.

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