Historical Perspective

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The discipline of immunology grew out of the observation that individuals who had recovered from certain infectious diseases were thereafter protected from the disease. The Latin term immunis, meaning "exempt," is the source of the English word immunity, meaning the state of protection from infectious disease.

Perhaps the earliest written reference to the phenomenon of immunity can be traced back to Thucydides, the great historian of the Peloponnesian War. In describing a plague in Athens, he wrote in 430 bc that only those who had recovered from the plague could nurse the sick because they would not contract the disease a second time. Although early societies recognized the phenomenon of immunity, almost two thousand years passed before the concept was successfully converted into medically effective practice.

The first recorded attempts to induce immunity deliberately were performed by the Chinese and Turks in the fifteenth century. Various reports suggest that the dried crusts derived from smallpox pustules were either inhaled into the nostrils or inserted into small cuts in the skin (a technique called variolation). In 1718, Lady Mary Wortley Montagu, the wife of the British ambassador to Constantinople, observed the positive effects of variolation on the native population and had the technique performed on her own children. The method was significantly improved by the English physician Edward Jenner, in 1798. Intrigued by the fact that milkmaids who had contracted the mild disease cowpox were subsequently immune to smallpox, which is a disfiguring and often fatal disease, Jenner reasoned that introducing fluid from a cowpox pustule into people (i.e., inoculating them) might protect them from smallpox. To test this idea, he inoculated an eight-year-old boy with fluid from a cowpox pustule and later intentionally infected the child with smallpox. As predicted, the child did not develop smallpox.

Jenner's technique of inoculating with cowpox to protect against smallpox spread quickly throughout Europe. However, for many reasons, including a lack of obvious disease targets and knowledge of their causes, it was nearly a hundred years before this technique was applied to other diseases. As so often happens in science, serendipity in combination with astute observation led to the next major advance in immunology, the induction of immunity to cholera. Louis Pasteur had succeeded in growing the bacterium thought to cause fowl cholera in culture and then had shown that chickens injected with the cultured bacterium developed cholera. After returning from a summer vacation, he injected some chickens with an old culture. The chickens became ill, but, to Pasteur's surprise, they recovered. Pasteur then grew a fresh culture of the bacterium with the intention of injecting it into some fresh chickens. But, as the story goes, his supply of chickens was limited, and therefore he used the previously injected chickens. Again to his surprise, the chickens were completely protected from the disease. Pasteur hypothesized and proved that aging had weakened the virulence of the pathogen and that such an attenuated strain might be administered to protect against the disease. He called this attenuated strain a vaccine (from the Latin vacca, meaning "cow"), in honor of Jenner's work with cowpox inoculation.

Pasteur extended these findings to other diseases, demonstrating that it was possible to attenuate, or weaken, a pathogen and administer the attenuated strain as a vaccine. In a now classic experiment at Pouilly-le-Fort in 1881, Pasteur first vaccinated one group of sheep with heat-attenuated anthrax bacillus (Bacillus anthracis); he then challenged the vaccinated sheep and some unvaccinated sheep with a virulent culture of the bacillus. All the vaccinated sheep lived, and all the unvaccinated animals died. These experiments marked the beginnings of the discipline of immunology. In

Pasteur And Joseph Meister


Wood engraving of Louis Pasteur watching Joseph Meister receive the rabies vaccine. [From Harper's Weekly 29:836; courtesy of the National Library of Medicine.]


Wood engraving of Louis Pasteur watching Joseph Meister receive the rabies vaccine. [From Harper's Weekly 29:836; courtesy of the National Library of Medicine.]

1885, Pasteur administered his first vaccine to a human, a young boy who had been bitten repeatedly by a rabid dog (Figure 1-1). The boy, Joseph Meister, was inoculated with a series of attenuated rabies virus preparations. He lived and later became a custodian at the Pasteur Institute.

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Essentials of Human Physiology

Essentials of Human Physiology

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