Smallpox, named for the numerous pus-filled blisters (or pocks) that it caused on those infected with the disease, was one of the greatest scourges in human history. The earliest evidence of its devastation is seen on mummified remains from the Egyptian dynasties (1570-1085 bc). Chinese writings from 1122 bc and Sanskrit texts from India are some of the earliest written recordings of the illness.⁶ Smallpox traveled with settlers and merchants and made its way to Europe sometime around the fifth to seventh centuries. It was epidemic at various points throughout the Middle Ages and played an important role in the development of Western civilization. The Plague of Antonine killed nearly 7 million people and coincided with the beginnings of the fall of the Roman Empire. When Spanish and Portuguese conquistadores came to the New World, they brought smallpox with them, an introduction that was instrumental in the destruction of the great Aztec and Incan empires. Settlers on the eastern coast of North America introduced the native population to smallpox. It was later used as one of the first examples of biological warfare when the British used smallpox to kill off the “hostile” American Indian population during the French and Indian War.

The earliest efforts at inoculation against this deadly disease were first documented in China and the Middle East in the 15th century. Writings describe a process later named “variolation,” whereby scabs from a person infected with smallpox (variola virus) were dried and powdered then introduced to a healthy person via nasal insufflation (blowing the powdered pox into the nose) or during which pustular matter was taken from an infected person and introduced to a healthy individual via scratches in the skin. Smallpox carried a 20% to 60% fatality rate. However, the process of variolation itself resulted in death for 1% to 2% of those on which it was used and had the potential to cause outbreaks if those infected spread the disease to others. This process was continued with varying success through the ages and across continents, finally making its way to England and North America with the slave trade in the 1700s.⁷ However, as we still see today, albeit with much safer inoculation methods, the process of conferring immunity faced opposition. Injecting healthy people with a potentially fatal disease to induce a lesser case of illness and hopefully prevent more serious and deadly consequences was a hard pill to swallow (Figure 1.2).

It wasn’t until the early to mid-1800s that variolation was largely abandoned in favor of a process termed “vaccination.” The father of vaccination was an English physician scientist named Edward Jenner. Although he was not the first to observe that milkmaids infected with cowpox had immunity to smallpox, nor likely the first to test the observation, he was the first to disseminate results of his studies to the world and, thus, gains credit for the discovery. In 1796, to test his theory, Jenner used the matter from a milkmaid’s cowpox lesion to infect his test subject, a boy named James Phipps. Cowpox is a member of the orthopoxvirus family, as is smallpox. However, cowpox is a much milder and generally nonfatal disease. Phipps came down with a mild illness but quickly recovered. Jenner then injected his subject with smallpox and found that Phipps never became ill. He repeated this exposure several times and Phipps remained immune. Thus was born the world’s first vaccine, a term derived from the Latin word for cowpox (vaccinia),⁶ a milestone that set us on the path to ultimate worldwide eradication of the virus in 1980, following a global immunization campaign led by the World Health Organization.

More modern history recalls other deadly pandemics. In 1918, the world saw the greatest pandemic in centuries. The Spanish flu, so named for the reports of its particular devastation in Spain, a country not subject to the news blackouts that affected other countries during wartime, swept across the continents, killing 50 million people world-wide (with some estimates as high as 100 million). It killed even more people than
died during World War I (which claimed an estimated 16 million lives). One-third of the world’s population was infected. Most families were touched by loss, for some, many times over. The average life expectancy was diminished by 12 years during that one flu season as a result of this particularly virulent influenza strain.⁸ Moreover, in an unusual fashion, the Spanish flu had a predilection for killing younger, healthier individuals sometimes within hours, their lungs filling with fluid and blood causing suffocation and death.

The influenza virus was not identified until 1933, and the first vaccine wasn’t introduced until 1938. However, that initial vaccine and those soon to follow were only variably successful. The reasons for this, we ultimately discovered, were the multiple strains of influenza and the propensity of those influenza strains to mutate, changing their anti-genic (infectious) properties as rapidly as from the time it takes to produce the vaccine to the time it is administered. Influenza can even mutate during the production phase, when it is being grown in its most common growth medium, the chicken egg. New methods of production, which are less prone to mutation, are in development, and we have hopes of a more universal flu vaccine in the future. However, for now, our current flu vaccine is the best way to decrease the chances of infection with influenza and its severe and potentially deadly consequences.

Even more recently, we may recall the polio epidemics that ravaged the United States and other parts of the world. Polio is a virus that is spread rapidly by close per-sonal contact, through secretions from the mouth and nose, or by contact with contam-inated feces. Although polio did not uniquely affect children, the name initially used to describe the condition (infantile paralysis) hints at its greater impact on the very young. Not everyone suffered so severely. In fact, nearly 95% of people had no symptoms of their infection at all. However, when the virus did impact the nervous system, resulting in a paralysis of the muscles including those muscles required for breathing, it caused devastating results. In a single year (1952), nearly 60,000 US children were infected with the polio-virus. Thousands were permanently paralyzed, and 3000 children died.⁹ It’s not difficult to find photographs from the United States in the 1950s that show children walking with braces, children with withered legs from the muscle atrophy that resulted from infection, and rows upon rows of iron lungs used to keep those whose breathing muscles had become paralyzed alive. Between 2% and 5% of children infected with the paralytic form of polio would ultimately die of their disease. Although fewer adults were affected, their prospects were even more dismal with up to 15% to 30% with paralytic polio dying of complications of their illness.¹⁰

In the 1900s, as vaccine science progressed, building upon the lessons learned from early immunization development, production, and large-scale vaccine deployment, the medical and lay worlds saw a growing number of available vaccines (Table 1.1). It is important to recognize here, and to be able to express to our questioning patients, that vaccinations are not produced for illnesses that are “not that severe,” as those who oppose vaccines would claim. There are no vaccinations against the common cold or hand, foot and mouth disease, for example. That is because these infections very rarely cause illness severe enough to require hospitalization, leave permanent brain or other organ damage, or result in death. Immunizations are produced against those illnesses that have the propensity to cause significant risk to life. For example, in the United States, “in 1920, 469,924 measles cases were reported, and 7575 patients died; 147,991 diphtheria cases were reported, and 13,170 patients died. In 1922, 107,473 pertussis cases were reported, and 5099 patients died.”¹¹ On a worldwide scale, this represents the loss of millions of lives. Immunizations are developed to fight against some of the greatest killers of children and others across the globe.