A round of shots for everybody!

One of my most vivid childhood memories is getting an injection at the doctor’s office. He resembled a salt-and-pepper-haired Santa, and would always greet me with a smile. I remember the growing feeling of dread I had every time he took out the needle, the stab of pain, and the worst of all – him telling my parents that I would need to come back for a booster shot. Today, as I read about the measles outbreak in different parts of the world, I am grateful to all those vaccines I received over the course of my childhood.

Vaccination stimulates the defense mechanisms of the immune system, enabling the body to defend itself against future infection. Vaccines contain antigens – molecules that resemble the target pathogens and are therefore used to elicit an immune response. The response involves mounting a defense against the antigens and activating memory cells that will “remember” the antigens. The latter is especially important because if on a later occasion, the pathogen is detected in the body, it will be recognized immediately, and the immune system will mount a much stronger response, preventing the development of the disease.

As early as 430 B.C. it was observed that smallpox survivors were immune to subsequent infections of the disease, and they could nurse the afflicted. In the 10th century, the Chinese attempted to immunize susceptible individuals by transferring the contents of the smallpox pustules on cotton and putting the cotton up the nostrils, or the ground-up pustule powder was blown into the nostrils of children. There are also documented examples of inoculation from the 17th century in Africa, India, and China. The process involved introducing the smallpox virus subcutaneously into non-immune individuals.

The concept of inoculation spread to Europe in the 18th century via Turkey. The Turks were aware of the benefits of inoculation because it was a routine practice among women. They would introduce smallpox pustules into their infants via arm incisions. Inoculation was carried out to prevent facial disfiguration, a common outcome of the disease. The procedure was important because girls were sold as slaves and retaining their beauty was paramount. Reports on the process of inoculation were presented to the Royal Society of London in 1714 by the physicians Jacob Pylarini and Emanuel Timonius; both had independently sent their accounts from Constantinople. Unfortunately, their accounts were not taken seriously at the time. The practice was later popularized by Lady Montagu. She lived in Turkey with her husband who was a British ambassador to the Ottoman Empire. She had witnessed the inoculation process firsthand, and in 1721 had her daughter inoculated under the scrutiny of the King’s physician, Sir Hans Sloane. This event, coupled with studies done in America, helped spread the idea from England throughout Western Europe.

In America, the idea of inoculation was introduced by Cotton Mather, a reverend who is known for his support of ‘Salem witch trials’. In 1706, Mather’s slave Onesimus, explained to him how he had been inoculated as a child in Africa. Fascinated by this idea, Mather convinced Zabdiel Boylston, a physician, to inoculate people in Boston during the smallpox outbreak in 1721. Of the 248 people inoculated only six died, confirming the effectiveness of the procedure. These statistics helped convince the British physicians to adopt the practice. After repeated trials, it spread among the royal families of Europe and was adopted later by the public.

In 1757, a boy from Gloucester was one of the thousands to be inoculated. He developed a mild case of smallpox and was subsequently immune to the disease. His name was Edward Jenner and he went on to become the pioneer of the world’s first vaccine – the smallpox vaccine. Before Jenner popularized vaccination, it was well documented that individuals infected with cowpox (a disease that affects both humans and cows) were immune to smallpox. The mechanism was unknown at the time; we now know that the cowpox virus is similar to, but much milder than, the smallpox virus making it the perfect antigen for a smallpox vaccine. Nevertheless, this phenomenon had been reported in 1768, by an English physician John Fewster, and later in 1782 by a French politician Jacques Antoine Rabaut.

The first person to apply these findings to practice was a Dorset farmer, Benjamin Jesty in 1774. Since he had already been inoculated, he tried to immunize his wife and sons during a smallpox outbreak. He used a darning needle to transfer the pustular material from diseased cows to the scratched areas on their arms. It worked perfectly. Unfortunately, his neighbors treated his discovery with hostility and labelled him “inhuman”. On May 14th, 1796, Edward Jenner performed his first vaccination from a cowpox pustule of a milkmaid to the arm of a young boy. Two weeks later he inoculated the boy with smallpox. The boy was immune. Jenner published his findings in 1798 and also coined the term vaccination. By 1801, his report was translated into six languages and over 100,000 people were vaccinated.

Although vaccination had become commonplace, it did not confer lifelong immunity to smallpox. This became apparent during the smallpox pandemics of 1824 and 1837 during which there was a high incidence of mild illness in previously vaccinated adults. In the 1930s, Germany was one of the first countries that recognized the need for revaccination, which lead to a decline in the incidence of smallpox. These additional rounds of vaccination are known as booster doses – they increase the immunity towards an antigen back to its protective levels. This is important because memory against an antigen declines over time.

Standing on the shoulders of giants

The next breakthrough in vaccine development came from Louis Pasteur, a French microbiologist who is famous for his contributions to the field of Microbiology. He was working on chicken cholera caused by the bacteria Pasteurella multocida. In 1879, Pasteur asked his assistant Charles Chamberland, another famous French microbiologist, to inoculate the chickens with bacteria when he was on holiday. Chamberland failed to do so because he went on a holiday himself. When he came back after a month, he introduced the month-old culture into the chickens. After a brief period of illness, the chickens recovered. When Pasteur subsequently inoculated the chickens with the infectious form of bacteria, the chickens survived. He thus invented the first attenuated vaccine – vaccines that are created by reducing the virulence of a pathogen without affecting its viability. This vaccine was different from the smallpox vaccine because the strains had been artificially weakened and so a naturally weakened form of the disease organism was not required.

Another famous attenuated vaccine is the BCG (Bacillus Calmette-Guérin) vaccine. In 1908, Albert Calmette, a French physician, and Camille Guérin, a veterinarian, were trying to develop less virulent strains of the tuberculosis bacteria. They noticed that bacteria grown in a mixture of glycerin, potato, and bile were less virulent. They wanted to test whether transferring bacteria from a previous growth medium to a fresh growth medium could produce a strain that was sufficiently attenuated. After 239 transfers over 13 years, they isolated the attenuated BCG strain which failed to produce progressive tuberculosis when injected into guinea pigs, rabbits, cattle, or horses. The vaccine was first used on humans in 1921 and was the first live tuberculosis vaccine. The WHO (World Health Organization) currently recommends the vaccine be given to children in countries that are highly endemic for tuberculosis.

During the first half of the 20th century, there were outbreaks of polio all around the world. Many famous people including President Roosevelt and the nuclear physicist Robert Oppenheimer were victims of the disease. From 1935-1950 many scientists tried to invent polio vaccines, which they tested on themselves and their families. Unfortunately, all their efforts failed.

In 1952, Jonas Salk developed the first effective polio vaccine. He used formaldehyde to kill the three types of poliovirus and then administered the inactivated strains by intramuscular injection. The vaccine worked and the resulting vaccination program was the first of its kind involving 20,000 health officials, 220,000 volunteers, and 1,800,000 school children participating in the trail. Although the Salk vaccine helped prevent most of the complications from polio, it did not prevent the initial intestinal infection. In 1954, Albert Sabin developed a live, attenuated vaccine which could be administered orally, provided a long-lasting immunity, and was cheaper to produce. These advantages enabled the mass production of the vaccine and played a key role in nearly eradicating polio.

Another important contributor to the field of vaccination was Maurice Hilleman. He was an American microbiologist and developed over 40 vaccines; eight of which are now routinely used in recommended vaccine schedules. Of these, one of the most noteworthy vaccines is the mumps vaccine which was developed in 1967. Hilleman’s daughter Jeryl Lynn had mumps and he cultured the mumps virus from her throat to develop the vaccine. This strain is still used today in the MMR vaccine, also developed by Hilleman and is the first approved vaccine that incorporates multiple live virus strains.

The work done on vaccine development has contributed largely to the increase in life span from 47.3 years in 1900 to 78.7 years today.

According to the CDC, there are 59 vaccines that are currently available in the U.S. These cover a wide range of diseases from bacterial to viral infections. Some are administered at birth, some are required yearly, even at the age of 60. The work done on vaccine development has contributed largely to the increase in life span from 47.3 years in 1900 to 78.7 years today. It is exciting to think of all the vaccines that are currently being developed, including those for cancer treatment and neurogenerative diseases. It is likely that many more diseases that currently plague our society can become extinct within a few generations.