1-12 The power of vaccination is discovered

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• Variolation, immunization against smallpox, was a common practice before vaccination was common. This worked because the patient was exposed to a weak strain of smallpox, which did not kill, yet provided immunity to the disease.
• Edward Jenner discovered that cowpox could protect against smallpox, with a much lower incidence of complications than variolation.
• Pasteur discovered a general method for immunizing people against disease while working on chicken cholera. He coined the term vaccination to describe the technique.

As soon as it was realized that microbes cause illness, the search was on for ways to kill or to prevent them from causing disease. In this section and the next, we will look at two series of events that illustrate the emergence of modern treatment of infectious disease: the development of vaccines and the discovery of antimicrobial compounds.

Smallpox was a feared disease throughout human history and justifiably so. It was highly contagious and almost everyone eventually became infected. Mortality rates were as high as 25% in adults and closer to 40% in children. Those who did survive often had scarring due to the blister-like pustules that form on the skin, but they obtained life-long immunity to the disease.

As far back at the 11^th century in India and China it was realized that liquid from the pustules of a smallpox victim, when scratched on the skin of a healthy patient, would most often cause mild disease. This intentional infection, termed variolation, would also give life-long protection against the virus. Lady Mary Wortley Montgue, wife of ambassador to the Ottoman Empire, introduced variolation to England in 1721 and it became a popular practice throughout Europe. Washington even began variolating the Continental Army in 1776.

Variolation had some deleterious side effects. Serious skin lesions inevitably resulted at the site of inoculation, often accompanied by a generalized rash or even a full case of smallpox. The fatality rate from variolation was 1 to 2 %. Today we would find this level of fatality to be unacceptable, but at the time this risk still represented a significant advance.

In 1796, Edward Jenner, an English country physician pictured in Figure 1-8, went in search of a more predictable and safer method of protection against the disease. He noticed that milkmaids rarely contracted smallpox. Further investigation revealed they often contracted cowpox from their charges. Jenner hypothesized that cowpox was related to smallpox and contraction of the former would protect against the latter. In a classic experiment (and one that would land you in jail today), Jenner inoculated a young patient with cowpox and later challenged him with smallpox. The boy did not become ill and Jenner was responsible for the creation of a safer method of protection against smallpox. It is important to stress that the nature of these diseases and their viruses would not be known for over 100 years. Jenner was ahead of his time.

Beginning around 1876 Pasteur's studies on chicken cholera led to the development of vaccines to fight the disease. Cholera was a serious problem since it was able to spread through a barnyard and wipe out a flock in as little as 3 days. It was transmitted by contaminated food or animal excrement. Pasteur identified the cholera bacillus and grew it in pure culture. When injected with it, a chicken invariably died within 48 hours.

Then, as often happens in scientific research, luck intervened. During the heat of the summer, Pasteur returned to Paris and left the cholera cultures used for infection stored on the shelves of his laboratory in Arbois, France. Upon returning, something had happened to the cultures, they no longer caused disease when tested in chickens. With some impatience for the time they were wasting, his group set to work making new cultures of the bacillus and tested these batches on both new birds and also those previously inoculated with the ineffective strain. To their amazement the previously injected birds were unaffected by the fresh bacillus culture, while the new birds all died. Pasteur immediately realized that this was similar to the studies of Jenner.

Pasteur then developed a method for creating cultures that would confer immunity, but not cause disease. Sometimes this involved growing the microbe in medium in the laboratory where they would spontaneously loose their virulence. In other cases it involved multiple passes through a susceptible host. For example, the rabies virus was attenuated by passing it through rabbits. In honor of Jenner's accomplishments Pasteur coined the term vaccination (vacca = cow in Latin) for the process of immunization against disease. In this and several of Pasteur's other discoveries, luck played a part, but it was only helpful because he tenaciously pursued "odd" results and had the insight to arrive at important conclusions. In Pasteur's famous words, " In the field of observation, chance favors only the prepared mind."

Pasteur's technique of weakening a strain by a damaging treatment or passing it through a susceptible host was termed attenuation and resulted in the creation of vaccines against anthrax, plague, yellow fever, rabies and many other diseases. Many vaccines have been developed over the years and children today receive a number of shots, greatly decreasing infant mortality.

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