Edward Jenner, an English doctor, is widely credited with creating the first vaccine in 1796, when he used material from a cowpox sore to protect an eight-year-old boy against smallpox. But the idea of deliberately exposing people to a disease to build immunity is far older, stretching back centuries before Jenner’s famous experiment. The full story of who “discovered” vaccines involves practitioners across multiple continents, several landmark scientists, and breakthroughs that continue today.
Immunity Before Jenner: Centuries of Variolation
Long before anyone used the word “vaccine,” people in Asia, Africa, and Europe were practicing variolation, a technique that involved taking pus or dried scabs from a smallpox patient and introducing them into a healthy person’s skin. The goal was to trigger a mild infection that would protect against a full-blown case of the disease. It worked surprisingly often, though it carried real risks, including death in a small percentage of cases.
The earliest written account of variolation in China appears in a book published in 1549, with one text dating the practice to between 1567 and 1572. Chinese methods were distinctive: practitioners would grind dried smallpox scabs into a powder and blow it into a child’s nose, or soak the scabs in water and insert a cotton plug carrying the fluid into the nostril. An even older oral tradition, associated with Taoist practitioners around 1000 AD, combined the technique with spells and ritual, though because it was passed down verbally and considered taboo to write about, no written records survive.
In India, itinerant Brahmins performed inoculations by dipping a sharp iron needle into a smallpox pustule and puncturing the skin repeatedly in a small circle on the upper arm. One report placed the start of this practice around 1580, though some commentators believed it had been used in Bengal for hundreds of years before that. Meanwhile, in Wales, variolation appears to have been in use since at least 1600. Welsh methods were rougher: people bought scabs from someone with smallpox and rubbed them into scratches on their own skin, sometimes made with a penknife.
By the early 1700s, the practice had spread across the Ottoman Empire. A Greek woman reportedly introduced it in Constantinople around 1660, and by the early 18th century it was common among Circassians, Georgians, and Arabs in North Africa. The technique in cities like Tripoli and Tunis involved a surgeon making an incision on the back of the hand and pressing smallpox matter into the wound.
Lady Montagu Brings Variolation to England
The person most responsible for bringing variolation to Western medicine was Lady Mary Wortley Montagu, the wife of the British ambassador to the Ottoman Empire. In 1717, she observed the practice in Constantinople and became a passionate advocate. By 1721, she had persuaded the Princess of Wales to support a dramatic test: several prisoners and abandoned children were inoculated with smallpox material inserted under the skin. Months later, they were deliberately exposed to the disease. None of them contracted it, and the procedure was judged safe enough for members of the royal family.
Variolation spread through Britain and colonial Massachusetts that same year. It was a genuine medical advance, but it was not vaccination. Variolation used actual smallpox, which meant recipients could develop serious illness or spread the disease to others. The leap from variolation to vaccination required a safer source of immunity.
Edward Jenner and the First True Vaccine
Edward Jenner made that leap. Working as a country doctor in Gloucestershire, he noticed that milkmaids who had previously caught cowpox, a mild disease they picked up from infected cows, seemed immune to smallpox. Cowpox caused only minor sores and was far less dangerous than smallpox itself.
On May 14, 1796, Jenner took material from a cowpox sore on the hand of a milkmaid named Sarah Nelmes and scratched it into the arm of James Phipps, the eight-year-old son of his gardener. The boy developed a mild fever and some discomfort but recovered quickly. Months later, Jenner exposed Phipps to the actual smallpox virus multiple times. Phipps never developed the disease.
Jenner called his technique “vaccination,” from the Latin word “vacca” meaning cow. The distinction between his approach and variolation was critical: instead of using smallpox itself, he used a related but far less dangerous virus to train the immune system. This principle, using a weakened or related pathogen to create immunity without causing serious illness, became the foundation of every vaccine that followed. Nearly two centuries later, on May 8, 1980, the World Health Assembly officially declared smallpox eradicated from the planet, the ultimate vindication of Jenner’s insight.
Louis Pasteur Expands the Science
Jenner showed that vaccination worked, but he didn’t fully understand why. That deeper understanding came from Louis Pasteur, the French chemist and microbiologist whose germ theory of disease transformed medicine in the second half of the 1800s. Pasteur realized that weakening (or “attenuating”) a pathogen in the laboratory could make it safe enough to use as a vaccine while still prompting the body to build defenses.
He applied this principle to anthrax in livestock and then, most famously, to rabies. On July 6, 1885, Pasteur and his colleagues began treating nine-year-old Joseph Meister, who had been severely bitten by a rabid dog two days earlier. Over 14 consecutive days, they injected the boy with suspensions made from rabbit spinal cord tissue containing progressively weakened rabies virus. Meister survived, and the basic approach Pasteur developed for rabies treatment remained in use in many countries well into the modern era. Pasteur’s work proved that vaccination could be extended far beyond smallpox, opening the door to protection against a wide range of infectious diseases.
Toxoids, Polio, and the 20th Century
The early 20th century brought a new category of vaccine. Some diseases, like diphtheria and tetanus, cause harm not through the bacteria themselves but through the toxins they release. In the 1920s, a French veterinarian named Gaston Ramon found that treating these toxins with formaldehyde neutralized their poisonous effects while preserving their ability to trigger an immune response. The resulting “toxoids” could safely train the body to recognize and neutralize the real toxins. By 1926, researchers discovered that adding aluminum salts made these toxoid vaccines even more effective, and by the mid-1940s, diphtheria and tetanus toxoids were being combined with a pertussis (whooping cough) vaccine into a single shot.
The mid-century fight against polio produced two of the most recognized names in vaccine history. Jonas Salk introduced his inactivated polio vaccine in 1955, using virus that had been killed with chemicals so it couldn’t cause disease but could still prime the immune system. Mass vaccination campaigns followed almost immediately. Then in 1961, the United States began widespread use of Albert Sabin’s oral polio vaccine, which used a live but weakened form of the virus. The oral version was cheaper, easier to administer (a few drops on the tongue rather than an injection), and could spread limited immunity to unvaccinated people nearby. Together, the two vaccines drove polio to the brink of global eradication.
One scientist stands out for sheer breadth of impact. Maurice Hilleman, a microbiologist who spent most of his career at a major pharmaceutical company, was responsible for developing more than 40 vaccines. His work covered measles, mumps, rubella, hepatitis A, hepatitis B, meningitis, pneumonia, and infections caused by Haemophilus influenzae bacteria. Many of the routine childhood immunizations given today trace directly to Hilleman’s research.
mRNA Vaccines and a New Platform
The most recent revolution in vaccine science came from a biochemist named Katalin Karikó. For decades, researchers had known that messenger RNA (mRNA) could theoretically instruct human cells to produce a specific protein, training the immune system to recognize it. The problem was that synthetic mRNA triggered intense inflammation, making it useless as a medical tool.
Karikó, working with immunologist Drew Weissman at the University of Pennsylvania, discovered that swapping one of the chemical building blocks in synthetic mRNA with a naturally occurring variant called pseudouridine allowed it to slip past the body’s inflammatory sensors. Their key paper was published in 2005, but it took more than a decade for the broader scientific community to fully embrace the finding. When COVID-19 emerged in late 2019, the mRNA platform was ready. Vaccines built on Karikó and Weissman’s modification were developed, tested, and authorized in under a year, a speed that would have been unimaginable with older vaccine technologies. The two researchers received the 2023 Nobel Prize in Physiology or Medicine for their work.
The mRNA platform is now being explored for vaccines against influenza, respiratory syncytial virus, and even some cancers. Other technologies are advancing alongside it, including microneedle patches that deliver vaccines painlessly through the skin, nasal sprays that target the immune defenses lining the nose and lungs, and combination vaccines that protect against multiple diseases in a single dose.