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  1. In 1872, despite enduring a stroke and the death of 2 of his daughters to typhoid, Louis Pasteur creates the first laboratory-produced vaccine: the vaccine for fowl cholera in chickens. In 1885, Louis Pasteur successfully prevents rabies through post-exposure vaccination.

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    Awareness of Edward Jenner’s pioneering studies of smallpox vaccination (Milestone 2) led Louis Pasteur (1822–1895) to propose that vaccines could be found for all virulent diseases.

    Pasteur began to study chicken cholera in 1877 and by the following year had succeeded in culturing the causative organism, Pasteurella multocida. In 1879, Pasteur discovered by chance that cultures of this bacterium gradually lost their virulence over time. Before leaving to go on a holiday, Pasteur had instructed an assistant to inject the latest batch of chickens with fresh cultures of P. multocida. The assistant forgot to do this, however, and then himself went on holiday. On his return, Pasteur’s assistant inoculated the chickens with the cultures, which by this time had been left in the laboratory for a month, stoppered only with a cotton-wool plug. The inoculated chickens developed mild symptoms but recovered fully.

    Another scientist might have concluded that the cultures had (mostly) died, but Pasteur was intrigued. He injected the recovered chickens with freshly cultured cholera bacteria. When the birds remained healthy, Pasteur reasoned that exposure to oxygen had caused the loss of virulence. He found that sealed bacterial cultures maintained their virulence, whereas those exposed to air for differing periods of time before inoculation showed a predictable decline in virulence. He named this progressive loss of virulence ‘attenuation’, a term still in use today.

    Pasteur, along with Charles Chamberland and Emile Roux, went on to develop a live attenuated vaccine for anthrax. Unlike cultures of the chicken cholera bacterium, Bacillus anthracis cultures exposed to air readily formed spores that remained highly virulent irrespective of culture duration; indeed, Pasteur reported that anthrax spores isolated from soil where animals that died of anthrax had been buried 12 years previously remained as virulent as fresh cultures. However, Pasteur discovered that anthrax cultures would grow readily at a temperature of 42–43 °C but were then unable to form spores. These non-sporulating cultures could be maintained at 42–43 °C for 4–6 weeks but exhibited a marked decline in virulence over this period when inoculated into animals.

    Accordingly, in public experiments at Pouilly-le-Fort, France, conducted under a media spotlight reminiscent of that on today’s COVID-19 treatment trials, 24 sheep, 1 goat and 6 cows were inoculated twice with Pasteur’s anthrax vaccine, on 5 and 17 May 1881. A control group of 24 sheep, 1 goat and 4 cows remained unvaccinated. On 31 May all the animals were inoculated with freshly isolated anthrax bacilli, and the results were examined on 2 June. All vaccinated animals remained healthy. The unvaccinated sheep and goats had all died by the end of the day, and all the unvaccinated cows were showing anthrax symptoms. Chamberland’s private laboratory notebooks, however, showed that the anthrax vaccine used in these public experiments had actually been attenuated by potassium dichromate, using a process similar to that developed by Pasteur’s competitor, Jean Joseph Henri Toussaint.

    •Nature Milestones in Vaccines: Interactive Timeline

    •An address on vaccination in relation to chicken cholera and splenic fever. (Pasteur, L., 1881)

    • Caroline Barranco
    • 2020
  2. During the mid- to late 19th century, Pasteur demonstrated that microorganisms cause disease and discovered how to make vaccines from weakened, or attenuated, microbes. He developed the earliest vaccines against fowl cholera, anthrax, and rabies.

  3. Awareness of Edward Jenner’s pioneering studies of smallpox vaccination (MILESTONE 2) led Louis Pasteur (1822–1895) to propose that vaccines could be found for all virulent diseases.

  4. By the time of his experiment on Joseph Meister, Pasteur had already developed a vaccine against chicken cholera and anthrax in cattle. He had also shown that spontaneous generation was non-existent, proving that food spoiled from something landing on it from the environment.

  5. Pasteur and the Modern Era of Immunization On July 6, 1885, Louis Pasteur and his colleagues in­ jected the first of 14 daily doses of rabbit spinal cord sus­ pensions containing progressively inactivated rabies virus into 9-year-old Joseph Meister, who had been severely bitten by a rabid dog 2 days before. This was the begin­

  6. Sep 28, 2020 · Edward Jenner (1749–1823), a physician from Gloucestershire in England, is widely regarded as the ‘father of vaccination’ (Milestone 2). However, the origins of vaccination lie further back ...

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