Smallpox Vaccination 1798 – The First Vaccine in History

Medical historian Robert Mulcahy: "Smallpox, a disease that had terrified humanity since the beginning of history, claimed approximately 400,000 lives in Europe alone in the 1700s and condemned hundreds of thousands to live with scars and disfigured faces. The smallpox virus could sweep through an entire city as suddenly as a forest fire, causing high fever, unbearable itching, and fluid-filled skin blisters in everyone infected. Half of those who contracted the disease died within a few weeks, and there was no treatment."

Smallpox, whose history can be traced to Egyptian mummies with smallpox lesions on their faces (1100 BC), is a viral disease transmitted through a patient's belongings, proximity to the patient, flies, and inhalation of virus-containing air.

One of the Most Important Milestones in Medical History

For many years, the English physician Edward Jenner had heard stories that milkmaids who had contracted cowpox , a disease fatal to cows but harmless to humans, were protected against smallpox. In 1796, he took material from a milkmaid's cowpox lesions and introduced it into two scratches in the skin of an eight-year-old boy. The child developed a mild fever but soon recovered completely. Jenner then inoculated the boy with material from smallpox lesions, and the child developed no illness. In 1798, Jenner published additional findings in "An Inquiry into the Causes and Effects of the Variolae Vaccinae" (a study of the causes and effects of Variolae Vaccinae). He called the procedure "vaccination" —a word derived from the Latin term for cow , "vacca"—and began sending cowpox vaccine material to anyone who requested it.

Jenner was not the first person to vaccinate against smallpox. Nevertheless, his work ranks among the first "scientific" attempts to control infectious disease. The physician Stefan Riedel writes: "Jenner's determined approach to vaccination and dedicated research changed the way medicine was practiced." Eventually, the cowpox vaccine came into use worldwide, and by 1979 the world was almost completely free of smallpox, without a need for routine vaccination.

Why Has the Success of Smallpox Vaccination Not Been Repeated for Every Virus?

Developing a smallpox vaccine and eradicating the disease worldwide was a major achievement. However, developing vaccines against other viruses can be more difficult. There are several reasons:

1. Viral structure and characteristics: The structures and life cycles of some viruses make vaccine development difficult. For example, certain viruses, such as HIV, integrate into cells, establish long-term infections, and develop strategies to evade the immune system.

2. Mutation rate: Some viruses mutate rapidly, generating new variants. This complicates vaccine development because vaccines may need continuous updating. For example, the influenza virus produces different variants each year, requiring new vaccines every year.

3. Duration of the immune response: Vaccines against some viruses have limited effectiveness because of the duration of the protective response generated by the immune system. For example, short-lived protection from vaccines may require repeated vaccination.

4. Lack of natural immunity: Some viruses do not provide natural immunity in infected people. This can complicate vaccine development because vaccines must provide immunity that natural infection cannot.

5. Technical challenges: Vaccine development is generally time-consuming and costly. Developing an effective vaccine for every virus can involve scientific and technical challenges.

6. Economic and political factors: Economic and political factors also affect vaccine development and distribution. Vaccine research for diseases with low prevalence or affecting low-income countries can face particular difficulties because of insufficient funding and attention.

What Other Successful Viral Vaccines Are There?

Many successful viral vaccines have been developed throughout history. Here are some examples:

1. Measles vaccine: Measles is a contagious viral infection that can cause serious complications and death. The measles vaccine was developed in the 1960s and led to a major decline in measles cases.

2. Mumps vaccine: Mumps is a contagious viral infection particularly common in children. Developed in the 1960s, the mumps vaccine greatly reduced the spread of the disease.

3. Rubella vaccine: Rubella is a viral infection that is usually mild but can cause serious congenital abnormalities during pregnancy. Developed in the 1960s, the rubella vaccine reduced disease transmission and the number of congenital rubella syndrome cases.

4. Hepatitis A vaccine: Hepatitis A is a virus that causes liver inflammation. The Hepatitis A vaccine, developed in the early 1990s, has significantly reduced the spread of the disease.

5. Hepatitis B vaccine: Hepatitis B is another virus that causes liver infection, and chronic infections can lead to liver cirrhosis and liver cancer. Developed in the 1980s, the Hepatitis B vaccine has significantly reduced disease transmission and lowered liver cancer risk.

6. Polio vaccine: Polio (poliomyelitis) is a contagious viral disease that can cause paralysis and death. Thanks to the inactivated polio vaccine (IPV) developed in the 1950s and the oral polio vaccine (OPV) developed in the 1960s, polio cases have fallen substantially worldwide.

7. Human papillomavirus (HPV) vaccine: HPV is a sexually transmitted virus that can cause cervical cancer, genital warts, and other cancers. Developed in the 2000s, the HPV vaccine has reduced the number of cancers and genital wart cases caused by this virus.

8. Coronavirus (SARS-CoV-2) vaccine: Several vaccines developed against the COVID-19 pandemic demonstrated high efficacy and safety in phase 3 clinical trials. These include Pfizer-BioNTech (BNT162b2), Moderna (mRNA-1273), AstraZeneca (ChAdOx1 nCoV-19), Johnson & Johnson (Ad26.COV2.S), and Sinovac (CoronaVac). These leading vaccines have been used to immunize millions of people worldwide and have significantly reduced disease transmission. Coronavirus vaccination can therefore be considered among the successful viral vaccines.

9. RSV vaccine: The first RSV (Respiratory Syncytial Virus) vaccine trial in the 1960s had disastrous outcomes, increasing disease severity and causing the deaths of some children in the trial. Since then, safer and more effective methods have been used in efforts to develop an RSV vaccine, but an effective RSV vaccine usable across all age groups had not been developed by 2023. A notable study published on February 16, 2023, in NEJM showed significant efficacy, placing the RSV vaccine among successful vaccines. Of course, further regulatory approvals and processes are needed for licensing, large-scale production, and widespread availability. Nevertheless, based on current data, the RSV vaccine can be considered a successful viral vaccine.

Which Viral Vaccines Have Not Yet Achieved the Desired Level of Success?

Unsuccessful viral vaccine trials are common, particularly in the early stages of development. Some vaccine trials that have failed for various reasons include:

1. HIV vaccine: Developing a vaccine against human immunodeficiency virus (HIV) remains one of medicine's greatest challenges. Although many HIV vaccine trials have been conducted to date, none has provided a satisfactory level of protection.

2. Dengue vaccine: Dengue virus is transmitted by mosquitoes and causes dengue fever, a sometimes fatal disease. Dengue vaccine development has faced challenges because the virus, which has several serotypes, can trigger immune responses that increase disease severity in previously uninfected people. A vaccine with limited effectiveness is currently available and is given only to people previously exposed to dengue virus.

3. Norovirus vaccine: Norovirus spreads rapidly, especially in enclosed settings, and causes severe gastrointestinal problems. Norovirus vaccine development faces challenges because the virus has numerous genotypes and natural infections provide short-lived immunity. No approved norovirus vaccine is currently available.

4. Zika virus vaccine: Zika virus is transmitted by mosquitoes and can cause serious birth defects, particularly in pregnant women. Zika virus vaccine development is ongoing, but no vaccine has yet been approved.

Unsuccessful viral vaccine trials help scientists and researchers learn more about viral biology and effects on the immune system, develop new technologies and methods, and ultimately produce successful vaccines. Although vaccine development is generally time-consuming and challenging, successful vaccines can have a major impact on human health.

About the Article Image: The cartoon drawn in 1802 by English satirist James Gillray caricatures the debate surrounding Jenner's vaccination theory. The cows emerging from people's bodies are a striking detail.

Historical Figures Mentioned in the Article: Edward Anthony Jenner (1749–1823)

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