The field of public health was transformed by the introduction of vaccination, from the Latin word “vacca” meaning cow, to guard people against infectious diseases. It was well known that exposure to infectious diseases and surviving them conferred some natural immunity against subsequent outbreaks. Pioneers in the use of vaccinations included Edward Jenner, Louis Pasteur, and Gaston Ramon, and their work ensured many of the world's deadliest diseases could finally be tamed.

The immune system is the body’s defensive mechanism against bacterial and viral diseases. The immune system will recognize the unique characteristics of a disease called antigens. Antibodies are produced to target the infectious agent, and then T cells are sent to kill the infection. The immune system also remembers previous infections to protect against future infections. Vaccines help train the immune system to effectively react to an infection, thus lessening the severity of the disease. These new protections against lethal diseases greatly reduced child mortality rates, extended life expectancy, and contributed to eradicating smallpox (the first successful attempt to rid humanity of a lethal, infectious disease that previously claimed nearly 30% of infected people).

The first known attempts at vaccination emerged from China, probably developed by a Buddhist monk around 1000 CE. Traveling westward toward the Ottoman Empire, the first reports, in the mid-16th century, describe attempts directed at smallpox, which killed half of those who became infected. In those early procedures, the smallpox scabs taken from an infected person were dried and crushed into a powder, which was blown into another person’s nostrils or applied to scratches made in the person’s skin. This was known as variolation or inoculation. Attempts were also occurring in India and Africa.

In March 1718, while living in Constantinople, Lady Mary Wortley Montagu (1689 to 1762), who was married to the English ambassador to the Ottoman Empire, Edward Wortley Montagu, arranged for her son and daughter to be inoculated against smallpox. This practice used material from the live smallpox virus and was commonly employed as folk medicine. Lady Mary’s brother had died from smallpox, and she herself survived the disease, though she was left with significant scarring. Neither of her children contracted smallpox after inoculation.


The mounting evidence, favorable to inoculation, demonstrated that, under a doctor's guidance, a person was better off being inoculated than catching the disease naturally. By 1721, the practice of inoculation had spread to Europe, but the initial attempts not only caused additional outbreaks but also resulted in a 2 to 3% death rate of those who were inoculated. Nonetheless, when introduced into children in lesser amounts, the children experienced milder cases, rarely leading to death. The children generally recovered more quickly and developed lifelong immunity to the disease.

Across the Atlantic, similar attempts were made to inoculate the population against a smallpox outbreak. Cotton Mather (1663 to 1728) successfully inoculated his son and two household slaves during an April 1721 outbreak. Attempts by Mather to promote inoculation to the leading physicians of Boston were met with scorn, except for Zabdiel Boylston (1676 to 1766), who not only inoculated his own son but also a household slave and the slave’s son. After a few weeks of a mild outbreak of the disease, Boylston inoculated his older son and seven other Bostonians. Despite his successes, Boylston’s practice was still met with scorn and ridicule as some inoculated patients died while others transmitted the disease to the unaffected. Religious objections surfaced claiming smallpox was a righteous punishment from God for folks’ sinfulness. Inoculation was also opposed as unscientific, instead branded as a folk remedy. Nonetheless, opposition slowly diminished as the numbers began to demonstrate a lower death rate among the inoculated versus the non-inoculated. While doctors still could not scientifically prove why inoculation worked, it did. The positive numbers convinced George Washington, in the early years of the American Revolution, to require smallpox inoculation for all of his troops.

An English physician, Edward Jenner (1749 to 1823), believed that becoming infected with cowpox (an illness transmitted by cattle) offered protection against smallpox. Jenner observed that milkmaids who contracted cowpox from milking cows did not contract smallpox. On May 14, 1796, Jenner’s first attempt at inoculation, performed on 8-year-old James Phipps (1788 to 1853), was performed using cowpox pus. James contracted cowpox but recovered quickly. Jenner tried the experiment a second time, but this time with smallpox material. James remained unaffected by smallpox even months after the vaccination. Subsequent inoculations with others proved Jenner’s theory.

Rabies plagued Europe. Rabid forest animals bit dogs and cattle. The infected dogs then bit humans, or people consumed the infected meat of the cattle. In 1885, Louis Pasteur (1822 to 1895), a French biologist, after speculating that humans were contracting rabies from dog bites, inoculated a young man bitten by a rabid dog. Pasteur injected the boy with a weakened or attenuated form of the rabies virus, which prevented the boy from developing the disease.

Later in the 19th century, scientists discovered antibodies, crucial to the body’s immune system, which attach to viruses, rendering them inactive. These efforts launched the era of antitoxins, produced in large enough quantities to provide people with some protection while their own bodies produced sufficient levels of antibodies. The production of antitoxins was initially achieved by infecting large mammals with the virus, which caused the animals to produce massive quantities of antibodies, which scientists harvested and purified to inject into people showing signs of a similar disease. Because it was not always a safe method, the United States created the Food and Drug Administration to regulate the manufacture of drugs to minimize harm to patients.

The development of the electron microscope in the 1930s allowed doctors and scientists to see the specific viruses that afflicted people. The “wait and see” method of observing infected people or lab animals to see the disease develop ended. Vaccines could now be produced much more quickly.

All of these developments in knowledge and technologies expanded the understanding and effectiveness of vaccines beyond smallpox protection, ultimately leading to global adoption of vaccines against a host of infectious, lethal viruses:

By the late 1940s, vaccine production was sufficient to attempt the eradication of diseases worldwide. The most famous of the efforts was the battle against smallpox, started in 1967, which affected roughly 10 to 15 million people, of whom 30% died. Smallpox was finally declared eradicated by the World Health Organization in 1980, the only infectious disease eliminated from the human population to date.

Central to vaccination efforts has been the aim of developing “herd immunity.” If a large enough proportion of the population is vaccinated against a particular virus, herd immunity slows the spread and provides protection to individuals who cannot be vaccinated due to underlying medical conditions or who have not been vaccinated. A major benefit of effective herd immunity is the virus's inability to replicate, and so it eventually disappears, effectively ending the threat of sickness and death within the affected population.

Not all of the efforts have been as successful as the smallpox campaign. In developing nations, many children remain unvaccinated. The outstanding problem is not the lack of vaccines; in many instances, poorer countries cannot afford the doses needed. The Bill & Melinda Foundation, along with other global entities, established the Global Alliance for Vaccines and Immunization in 2000 to encourage manufacturers to lower drug prices. These types of efforts have been successful in lowering the death rates, but are still short of complete eradication.

From its earliest days, controversy has followed vaccination efforts. On February 28, 1998, the British medical journal The Lancet published a paper co-authored by Andrew Wakefield that asserted a link between the mumps-measles-rubella vaccine and autism. A global effort followed to authenticate Wakefield’s findings, but they were unsuccessful in replicating the link. Subsequently, it was discovered that Wakefield had manipulated the study’s data, and The Lancet retracted the article in 2010. Wakefield’s medical license was revoked while Wakefield was subjected to public scorn and professional repudiation.

Nonetheless, concerns about vaccinations persisted due to some negative publicity, which continues today. Religious opposition and tribal conflicts stymied the polio efforts in Nigeria, Pakistan, and Afghanistan, sometimes threatening the safety and well-being of the vaccinators. In the United States, various states have allowed exemptions from vaccination based on religious, medical, or personal preference, sometimes resulting in small outbreaks of diseases previously declared eradicated, such as the 2024 measles outbreak.

Vaccination against lethal viruses became a cornerstone of modern public health measures to save people’s lives and reduce the impact of illness on the human population. Many of the public health measures, especially vaccinations, became mandatory in many nations. Vaccines prevent deaths among 3 million children per year, although 2 million children die from deaths that could have been prevented with vaccines. Additionally, vaccination programs help reduce healthcare costs, increase productivity by reducing the number of days workers are off the job sick, and extend herd immunity to the broader community, including people who cannot receive a vaccine due to allergies or underlying health conditions. The future of vaccines appears bright despite some level of opposition. Medical science is already offering needle-free vaccines administered by patches or nasal sprays to improve comfort and accessibility. Research into universal vaccines that can target multi-strain viruses such as influenza is well underway. Finally, in the realm of emerging diseases, new vaccine types, such as mRNA and AI-developed vaccines, are currently in use to better meet current and future challenges.