1. Understanding the cause of disease
A major feature of the history of medicine before the 19th century was the lack of understanding of the causes of disease.
Without that knowledge, attempts at the prevention and treatment of disease were based on superstition and guesswork.
In the 1850s, however, one man was to make a major breakthrough in the discovery of what caused disease – Louis Pasteur, a French scientist.

2. Louis Pasteur and germ theory
Pasteur trained as a chemist in Paris and then developed an interest in biology.
He worked at Lille University, in the heart of an industrial area. There he specialized in fermentation. He investigated why vats of beer kept going bad at a local brewery.
Pasteur discovered it was because of micro-organisms in the beer.
He called these germs because they were germinating, or growing. His theory was that these germs were causing the decay.

3. Spontaneous generation and germ theory

4. How did he do it?
Pasteur was not the first to discover micro-organisms, but he was helped hugely by the powerful microscope lenses developed in the 19th century, which could magnify 1,000 times without distortion.
Pasteur’s ideas were ridiculed by some scientists and he knew he had to have undisputed proof. He carried out a number of carefully planned and recorded experiments.
Next you will learn how Pasteur carried out his experiments. Think how individual genius and technology helped the discovery of the germ theory.

5. Pasteur’s experiments
To prove that micro-organisms lived in the air, Pasteur collected air in sterile flasks in Paris. He found that bacteria grew in the flasks.

6. Air from a less polluted area
By repeating this experiment in different places he found that the air in some places, like Paris, had far more micro-organisms in it than places without so many people or so much pollution.
Air from Paris
Air from a less polluted area

7. Pasteur applied his theory of decay by micro-organisms in beer to the cause of disease in humans.
If bacteria could cause beer to go bad, then presumably they could make animals and humans ill.
He looked at the French silk industry, which was suffering because of a disease attacking silkworms. Pasteur identified the bacteria which was causing the disease.
He also proved that bacteria could be killed by heating a liquid in a flask which he then sealed. It remained fresh. Today we have pasteurized milk – heated to kill harmful bacteria.

8. Robert Koch
Robert Koch was a German doctor who built on Pasteur’s germ theory. During the late 1870s he identified the bacteria which caused anthrax, a disease in cattle, sheep and sometimes humans.
He achieved this by meticulous experiments and research. He injected the bacteria that he thought caused anthrax into 20 generations of mice. All the mice caught the disease and the bacteria he isolated in the last generation were the same as those that he had started with.

9. What were Koch’s main contributions to medical development?
Koch used the painstaking method of experiment in his work. Using the same process, his team of scientists identified the bacteria causing cholera and tuberculosis.
He also developed a medium for growing the bacteria and a method of staining them so that they could be identified and classified.
What were Koch’s main contributions to medical development?

10. There was great competition between Koch and Pasteur, not just scientifically, but also because of Germany’s defeat of France in the Franco-Prussian war of 1871.
vs.
How might the rivalry between Pasteur and Koch have been both good and bad for the progress of medicine?

12. Pasteur’s search for vaccinations
Pasteur continued his search for vaccines by trial and error.
He was asked to look at chicken cholera, because it was devastating French farming.
He isolated the chicken cholera bacteria and injected chickens with different strengths of it, without success. His laboratory closed for the holidays in the summer of 1879.

13. Pasteur was now to have a bit of luck
Pasteur was now to have a bit of luck. Some chicken cholera bacteria were left out, exposed to the air. The bacteria were weakened severely and when injected into chickens had no effect.
When subsequently injected with new bacteria (which should have killed them) the chickens suffered no ill effects. Pasteur had found a vaccine against chicken cholera.
Apart from helping the French farming industry, why was Pasteur’s discovery so important?

14. Injected with weak anthrax strain
By 1881, Pasteur and his team had developed a vaccine for anthrax.
To prove it worked, he vaccinated 25 sheep with a weak strain of the disease.
Injected with weak anthrax strain
No injection

15. Koch criticized Pasteur’s methods, but in spite of this Pasteur achieved international acclaim for his discoveries.
Two years later he had developed a vaccine for rabies, a terrible disease in dogs. A bite from a rabid dogs was fatal to humans.

16. Doctors now knew that once the bacteria causing a disease had been identified, a vaccine could be searched for. By the end of the 19th century the causes of the following diseases had been identified:
smallpox, TB, cholera, typhus, tetanus, pneumonia, meningitis, plague, diphtheria and dysentery.
All of these were killer diseases against which there had previously been no protection.

18. What do you think this means?
The fight against infection
World War I interrupted an important research programme into fighting infection. Research had been going on for years to find a chemical compound which would kill bacteria in the body.
Robert Koch had found a way of staining bacteria to identify them. Paul Ehrlich, a member of his team, decided to take this idea further.
Ehrlich thought that a chemical compound could be used not only to stain the bacteria causing an infection, but which would kill them (and only them) as well. Ehrlich said this would be like a magic bullet.
What do you think this means?

19. Magic bullets
A magic bullet would ‘shoot’ the bacteria, but not harm the patient.
Ehrlich had seen how the body produces antibodies to attack the specific bacteria causing an infection, and believed he could find a chemical which would work in the same way.
After many years, in 1909 he was proved right. His team had tried 605 varieties of an arsenic compound to cure syphilis, a common venereal disease. The 606th one killed the syphilis bacteria. They had discovered the first magic bullet, and they called it Salvarsan 606.

20. In 1932 Gerhard Domagk found the second magic bullet after years of methodical research. This was a red dye called Prontosil.
He injected mice with a lethal dose of a streptococcal infection. He then injected them with Prontosil, which cured them.
Soon he had the chance to try it out on a human, his own daughter, who was seriously ill with the same streptococcal infection. Having no other cure, he injected her with Prontosil and she recovered.
The next task was to find out which component of Prontosil made it a magic bullet.

21. Fleming and the discovery of penicillin
Alexander Fleming had worked on wounds and infections during World War I and spent years researching the body’s natural defences against infection.
In 1928, chance helped the scientific search for anti-bacterial drugs, as it had helped Pasteur.
Fleming returned from holiday to find that mould had grown on the cultures in some of the petri dishes in his laboratory.
He noticed that in one dish the staphylococci cells had disappeared around the edges of the mould. He realised that the mould had killed the bacteria. He identified the mould as penicillium, which had probably blown in through the open window.

22. The development of penicillin
Fleming had discovered that penicillin would attack certain forms of bacteria, but he did not have the resources to research whether or not it could be used to fight infection.
Two British scientists, Howard Florey and Ernst Chain and their assistants, continued with the study.
Florey and Chain grew penicillium (the mould which produces penicillin) to experiment with, and tested successfully on mice. In 1941 they conducted a trial on a dying man, who recovered until they ran out of penicillin.

23. The first antibiotic had been created.
To continue their research, they looked to the USA, who had entered the war in 1941 and feared heavy casualties. It financed drugs companies to mass-produce penicillin. By 1945 the US army used 2 million doses a month.
The first antibiotic had been created.