Kathleen Crowther, Louis Pasteur

France was the first country where it was possible to make a living doing science. The number of professorships in the sciences was expanded, and universities (which were all state-supported) started to expect and support research. Medical schools in particular began to promote research. By the end of the century, there were also some state-funded research institutes, where men could devote themselves full time to research. The career of one of the most famous nineteenth-century French scientists, Louis Pasteur (1822-95), illustrates these changes. Pasteur is one of two scientists (the other is the German Robert Koch) who developed the germ theory of disease.

Louis Pasteur was trained in chemistry and biology at the École Normale Supérieure in Paris. In 1854, he was appointed to a university chair in a newly created faculty of science at Lille, a French manufacturing center. In 1857, he moved back to Paris as the director of scientific studies at the École Normale Supérieure. In 1887, he had achieved considerable fame for his scientific accomplishments that he was able to establish the state-funded Pasteur Institute, an institute devoted to scientific research and its practical applications. He was the director of the Pasteur Institute until his death.

Some of Pasteur’s earliest scientific work was on the processes of fermentation and putrefaction, including the souring of milk, the alcoholic fermentation of wine and beer, and the formation of vinegar. Since the beginning of the nineteenth century (if not earlier), chemists had been interested in the phenomena of fermentation and putrefaction (or decomposition). These were not just questions of intellectual interest; they had direct practical implications. Fermentation was the process by which grape juice is turned into wine, and wine turned into vinegar. Controlling this process was critical to the wine industry. Putrefaction was the process by which organic substances – including foodstuffs like meat and fruit – decomposed. Controlling this process was critical to successful agriculture. In the mid-nineteenth century, the German chemist Justus von Liebig (1803 – 1873) offered a chemical explanation of fermentation. He noted that yeast was necessary for various fermentations, but he believed it acted as a chemical catalyst. He posited that a related chemical process took place in putrefaction. Other nineteenth-century chemists and physicians saw striking similarities between putrefaction and certain disease processes. The putrefaction of dead organic matter seemed to resemble gangrene, wound infection, and suppuration in living organisms, including people. Perhaps all three proccess – fermentation, putrefaction and disease – were related chemical processes?

Pasteur challenged the earlier chemical theories of fermentation and putrefaction. He showed that these processes were the result of the action of particular living microorganisms. So fermentation, for example, required yeast, as Liebig had correctly observed, but this was because the yeast contained specific microorganisms.  Because of his work on the microorganisms that cause fermentation and putrefaction, Pasteur became involved in a heated and long running debate about spontaneous generation. Many scientists in Pasteur’s day believed that microorganisms arose by spontaneous generation. That is, they came into existence because of some vital force in the air. Pasteur believed that microorhanisms came from other microorganisms. The Italian scientist Lazzaro Spallanzani (1729 – 1799) had done a series of experiments in the eighteenth century attempting to disprove the notion of spontaneous generation. Spallanzani had previously demonstrated that boiling killed microorganisms. So he devised an experiment in which he boiled broth in flasks to kill all microorganisms in the broth. One set of flasks he left open to the air and the other set he hermetically sealed. The broth that was left open to the air became cloudy and microorganisms could be seen when it was examined under a microscope. The broth that was sealed remained clear with no microorganisms. Spallanzani argued that this demonstrated that there were microorganisms in the air that got into the broth. Critics argued that air was necessary for spontaneous generation to occur. Pasteur read about Spallanzani’s experiments and improved upon them in his famous “swan-neck flask” experiments.  Pasteur identified microorganisms in air responsible for spoiling wine, milk, and beer. He showed that heating could kill them and prevent spoiling. “Pasteurization” was a major step towards the purification of foods.

If fermentation and putrefaction are caused by microorganisms, why not disease? In 1865, Pasteur turned his attention to disease, and to investigating whether some diseases might be caused by microorganisms. He did not begin with human diseases. Instead, the first disease he tackled was pébrine. Never heard of pébrine? That’s because it’s a disease of silkworms. In the 1860s the disease was devastating silkworm farms in Alais (now Alès) in southern France, and threatening the French silk-making industry. Pasteur showed that pébrine was caused by a microorganism that attacked the silkworm eggs, and he devised techniques for eliminating the microorganism from the silkworm nurseries, thereby eliminating the disease.

On February 19, 1878, Pasteur gave an address to the French Academy of Medicine in which he laid out the germ theory of infection. This was the first articulation of what came to be called “the germ theory of disease.” In this address, Pasteur argued that microorganisms were responsible for disease, putrefaction and fermentation. Specific microorganisms caused specific diseases, and once a disease-causing microorganism was identified, it would (in theory!) be possible to develop vaccines to protect against this microorganism. At this point in time, the germ theory was an unproven hypothesis. What Pasteur laid out was more a program for further research than a well-established explanation for disease. His subsequent work provided further evidence for his hypothesis.

In 1879, he began studying chicken cholera and anthrax, two diseases that were extremely destructive to French agriculture. He identified the microorganism responsible for chicken cholera. He then infected (or inoculated) healthy birds with “stale” microorganisms (two weeks or more old). These aged microorganisms did not make the birds sick. Then he exposed the inoculated birds, and other birds who had not been inoculated, with fresh microorganisms. The previously inoculated birds did not get sick, and the others did. Thus Pasteur had found a way to immunize chickens against chicken cholera. He performed a similar series of experiments on anthrax, a disease that primarily affects cattle and very occasionally humans. He identified the microorganism and produced a vaccine.

The first human disease that Pasteur investigated was rabies, a disease that affects both animals and humans. Pasteur began his studies of rabies in the 1880s. Rabies was a disease that annually killed dozens of people. It was not a major killer like tuberculosis, pneumonia, or smallpox, diseases that killed hundreds of thousands of people each year. However, rabies – or hydrophobia – was invariably fatal, and it often affected children, who were more likely than adults to be bitten by rabid dogs. Unlike the other diseases Pasteur had studied, rabies is caused by a virus, so Pasteur could not see the causal agent with a microscope. (Viruses are very much smaller than bacteria.) Nonetheless, he reasoned that the disease must be caused by a microorganism, albeit one too small for him to see. Because the disease affects the brain and spinal cord, he reasoned that the microorganism must be present in these organs. He created a vaccine using spinal cord tissue from animals with rabies. The great test of this vaccine came on July 6, 1885, when a nine-year-old boy named Joseph Meister, who had been bitten by rabid dog, was brought to Pasteur. Rabies has a long incubation period, so the vaccine can be given after infection. After a fourteen-day series of injections, Joseph survived. This spectacular cure made national and international news. On the wave of national enthusiasm created by rabies immunization, Pasteur was able to garner the support to set up his own research institute, the Pasteur Institute, in 1887.