The History of Immunology

Vaccines are truly amazing, learn about how they were developed, their success in eradicating diseases, and the power of immunity.

Definition & Concept of Immunity

The word *immunity* comes from the Latin, meaning ‘free or exempt’, and was originally used in the context of ‘being exempt from performing public service.’ Its association with medicine and the meaning of ‘being exempt from disease’ didn’t come about until the late 19th century.

The *concept* of immunity from disease, however, dates back to ancient Greece in the 5th century BCE. This was a time when Athens was ravaged by the plague, killing thousands of people. During this time, Thucydides, one of the greatest ancient historians, wrote of individuals who had contracted the disease, recovered from it, and become *immune* to it.

It is interesting to note that, while Thucydides referred to the disease as the *plague*, the term was used in ancient times for any epidemic and, according to many scholars, most of the symptoms that he described align more closely with smallpox.

Variolation

While the medical concept of immunity dates back to antiquity, the earliest recorded attempt to intentionally induce immunity against an infectious disease was in 10th century China where smallpox – also known as *variola* – was prevalent at the time. Through a process known as *variolation*, healthy individuals were exposed to the disease by either inhaling powdered scabs of smallpox collected from an infected person or having the powder scratched into their skin.

*Variolation* eventually became common practice in the Ottoman Empire in the late 1600s, and even became fashionable in Europe in the early 18th century. However, this form of inoculation came with a 2-3% death rate or, in some cases, disfiguration from the disease itself, so European physicians deemed it far too risky, and its use became increasingly limited.

From Variolation to Vaccination

Variolation, in other words the inhalation or skin insertion of powdered smallpox scabs, stopped being used as a method of inoculation against smallpox in the mid-18th century due to its potentially lethal side-effects. However, in 1798, British country doctor Edward Jenner noticed that milkmaids that had been infected with *cowpox* – the bovine equivalent of smallpox – were protected against smallpox.

As a result of his discovery, Jenner became the first to test this method through scientific means. He decided to inoculate an 8-year-old boy with *cowpox* pus extracted from lesions on a milkmaid’s hands and inserted the fluid into the boy’s arm. After 6 weeks, Jenner exposed the boy to smallpox and the boy did not become infected, nor did he after 20 subsequent exposures. In the years that followed, the evidence that Jenner collected was conclusive enough for the concept of *vaccination* against smallpox to be born – the word itself originating from the word *Vacca* which means cow in Latin.

 

Expanding the Meaning of Vaccine

In 1798, Edward Jenner was the first to develop a successful technique in creating a vaccine against smallpox. In 1885, French biologist Louis Pasteur used the same technique to save the life of a 9-year-old boy who had been bitten by a rabid dog. Pasteur injected the boy with a weakened form of the rabies virus every day for 13 days. The treatment was so successful that the boy survived and never even developed rabies. Following in his predecessor’s shoes, Pasteur had developed the ‘rabies vaccine,’ thus expanding the meaning and use of vaccines beyond their original scope.

Pasteur’s success influenced the medical field, leading to the development of groundbreaking treatments that produced immunity against an infectious disease. These treatments contained live, weakened viruses or killed viruses. Scientific advances in the first half the 20th century led to development of vaccines against whooping cough (1914), diphtheria (1926), tetanus (1938), and influenza (1945). Those were followed by vaccines against polio (1955), measles (1963) and rubella (1969). Thanks to their efficacy and successful global health campaigns, vaccination rates shot up dramatically.

 

How Vaccines Work – the Technical Bit

To understand how vaccines work, it is vital to understand how the body fights illness. When germs invade the body in the form of bacteria or viruses, they attack healthy tissue and multiply, causing an infection. The white cells contained in our blood are there to fight such invasions, with the help of *B-lymphocytes* and *T-lymphocytes*. *B-lymphocytes* produce antibodies that attack the germs initially, while some *T-lymphocytes* go into action quickly if the body is attacked by the same germ again. As a result, the immune system remembers what it learned about a specific disease and is equipped to protect the body against that disease if it attacks again.

Vaccines work very much in the same way: by introducing the body to a very small amount of a live weakened – or killed – pathogen, they are imitating an infection and help the body build immunity against it. This type of infection almost never causes disease but will encourage the immune system to produce *T-lymphocytes* and *B-lymphocytes* to fight that disease in the future.

Different Types of Vaccines

According to the US Department of Health & Human Services, there are 5 types of vaccines.

*Live, attenuated vaccines*, contain a weakened version of the living virus, like the MMR vaccine for measles, mumps, and rubella, while *inactivated vaccines* contain an inactivated or killed virus, like the inactivated polio vaccine.

There are also vaccines which contain only parts of a germ and not the entire bacteria or virus, like the pertussis component of the DTaP (Diptheria, Tetanus and Pertussis) vaccine – these are called *subunit vaccines*. In addition, for diseases caused by toxins, vaccines containing a weakened version of the toxin, are called *toxoid vaccines*, such as the DTaP vaccine which contains diphtheria and tetanus toxoids.

Finally, *mRNA (messenger RNA)* vaccines create proteins in order to trigger an immune response to a virus. mRNA vaccines can be manufactured relatively quickly, making them very useful when fighting rapidly evolving contagious disease outbreaks like COVID-19.

The Significance of Vaccines

Vaccines are one of the most important advances in modern medicine and have increased our quality of life by reducing or even eliminating many infectious diseases. A disease is considered *eliminated* when it stops circulating in a region, and if it is eliminated worldwide, it is then considered *eradicated*. In 1980, the World Health Assembly declared smallpox eradicated, with the last recorded case occurring in Somalia in 1977. There was a time when smallpox killed up to 35% of infected patients and, to date, it is the only human infectious disease to be eradicated.

There are 14 diseases that have been eliminated in the U.S. due to extensive vaccination programs, including polio and rubella. The same trend applies to the rest of the developed world, and, while the diseases still exist, they aren’t as threatening as they once were because vaccines have immunized the majority of those populations.

Controversies & Misconceptions Surrounding Vaccines

Despite the fact that vaccines help prevent serious disease and unnecessary deaths, and even though they have been proven to be incredibly safe, vaccines have always been surrounded by controversy and misconceptions. Some of the most common are that vaccines have serious side-effects, that the MMR vaccine in children is linked to autism, and that children’s immune systems are overloaded with too many vaccines all at once, causing adverse effects.

However, none of these misconceptions and controversies are based on reliable scientific research or evidence. Quite the contrary – there have been numerous conclusive epidemiological studies proving vaccine safety. The risk, though, is that these misconceptions may lead people to become hesitant about vaccinations, which could lead to a resurgence of previously eliminated infections. As emphasized in a review of vaccine controversies published in *Clinical Infectious Disease* “concerns about vaccine safety can lead to decreased acceptance of vaccines and resurgence of vaccine-preventable diseases.”

The Future of Vaccines

Vaccines have been a part of medicine’s fight against disease for over 200 years. Smallpox has been eradicated, polio has been eliminated in most countries around the world, and childhood vaccination programs in the developed world have substantially reduced mortality from infectious diseases.

There are diseases however, such as malaria and HIV/AIDS, for which scientists have been unable to create effective vaccines, so research is continuing. Also, new techniques are being developed to create different types of vaccines such as DNA vaccines and mRNA vaccines. Furthermore, researchers are looking into creating vaccines that are simpler to administer, can survive transport without refrigeration, and provide more substantial immune response.

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