Louis Pasteur (1822–1895)

For centuries doctors had tried to find out how disease was caused. In the mid-19th century, many people in Britain still believed in Miasma, the idea that disease was caused by polluted air. The real breakthrough in understanding the cause of disease was made not by a doctor, but a chemist called Louis Pasteur.

Who was Louis Pasteur?

Louis Pasteur was a French chemist working as a teacher in a university. He was asked by a wine company in 1857 to explain why some wine turned sour whilst it was being made. Pasteur’s research discovered that there were germs in the air that could cause liquids to go off.

What did he do next?

Having discovered that ‘bad’ wine had germs in it which could be seen through a microscope, Pasteur developed a process for killing the germs by boiling the wine and then cooling it down. He called this process ‘pasteurisation’. Pasteur then set about proving that the germs came from the air and could therefore be prevented from entering the liquid in the first place. He demonstrated this by sealing a quantity of a liquid in an airtight swan necked flask and leaving another quantity exposed to the air. In 1861, Pasteur published his germ theory based on his experiments.

In 1864, Pasteur followed up his theory by discrediting the theory of spontaneous generation as promoted by Félix Pouchet. Pouchet was a leading French biologist of the nineteenth century who was openly advocating the idea of spontaneous generation.

Pasteur later used his discovery of germs to help treat diseases. He knew that the British

doctor Edward Jenner had developed a process of vaccination against the killer disease, smallpox. Pasteur believed that his germ theory could be used to explain how vaccination worked. He examined the blood of healthy people and compared it with the blood of people with various diseases. He observed that when people were infected with disease their blood contained lots of germs.

Louis Pasteur and Robert Koch Booklet 1

What new ideas did Pasteur develop?

The process of boiling a liquid to destroy germs is still used today; most dairy products are pasteurised. Pasteur went on to develop vaccinations for chicken cholera, diphtheria, anthrax and rabies. However, not all of Pasteur’s ideas were accepted. He recommended that surgical instruments be boiled before an operation to kill any germs on them, but most surgeons ignored this advice. This had to wait until aseptic surgery developed in the late nineteenth century following Robert Koch’s discovery of the microbe that caused septicaemia in 1878. How important was Pasteur?

Pasteur’s work was revolutionary in suggesting the link between germs and disease. This led the way for Robert Koch to later prove this theory and also discover how each type of germ caused a specific disease. Koch established the methods that scientists need to satisfy before a particular bacteria can be accepted as causing a specific disease, these are known as ‘Koch’s postulates’.

Robert Koch (1843–1910) was one of the greatest bacteriologists who ever lived. A founder of the science of bacteriology, Koch devised a procedure in 1876 to demonstrate that the bacterium Bacillus anthracis causes anthrax, a disease of animals that can also be transmitted to humans. It was the first time that a particular bacterium was shown to be the cause of a particular disease. Koch also discovered the bacteria that caused tuberculosis in 1882 (Mycobacterium tuberculosis) and cholera in 1883(Vibrio cholerae). He developed improved methods for staining bacteria and introduced the use of gelatin and, later, agar as growing media for bacterial colonies.

Louis Pasteur and Robert Koch Booklet 2

Koch’s Postulates

Koch extracted anthrax bacterium from an infected sheep and injected it into a mouse and allowed it to grow. He then extracted the bacterium from the blood of the mouse and injected it into another mouse and repeated the process through 20 generations of mice before he was confident he had isolated the bacterium that caused anthrax.

The Growth of Chemistry in the Nineteenth Century

Chemistry is the study of material substances. It seeks to explain how interaction between different substances brings about the formation of new substances. Chemicals have been used in medicine for thousands of years. The Egyptians, for example, used natron crystals to mummify the dead and in the Middle Ages, alchemists searched for the ‘elixir of life’ by extracting chemicals, refining liquids and mixing potions.

It was not until the 19th century that chemistry was studied as a separate science. The development in scientific knowledge led to chemists experimenting with gases and discovering anaesthetics. One of the most significant discoveries was Louis Pasteur’s identification of germs as the cause of disease in 1861, followed closely by Robert Koch’s identification of the microbes that caused TB (1882) and cholera (1883).

The chemical industry started to boom in this period (because of the industrial revolution) creating new opportunities for scientists. The search for cures that killed germs and not patients began in earnest with Paul Ehrlich, who worked for several years with Koch’s team of researchers. He exploited the use of synthetic dyes for studying microbes and with this method discovered the presence of antibodies in the blood. He called these antibodies ‘magic bullets’ as they were able to kill off specific bacteria.

Ehrlich then began to experiment with synthetically created antibiotics. In 1906 the microbe that causes syphilis was identified and in 1907 Ehrlich worked with over 600 chemical compounds that might kill the syphilis germ. In 1909 Sahachiro Hata, a member of Ehrlich’s research team, discovered the compound that did in fact kill the syphilis microbe. This drug, named Salvarsan 606, used arsenic as its base compound and seemed to have no adverse effect on the patient.

Memory time…

Louis Pasteur made the connection between germs and disease in 1861. Robert Koch’s pioneering work with anthrax in 1876 helped to identify the

microbes that caused a specific disease. Koch identified the TB microbe in 1882 and cholera in 1883. Paul Ehrlich was the first scientist to use chemical dyes to stain microbes

in order to study their structures. Salverson 606 in 1909 was the first chemical ‘magic bullet’, it killed the

syphilis germ without harming other parts of the body.

Louis Pasteur and Robert Koch Booklet 3

Paul Ehrlich

Disease & its treatment: Robert Koch and the birth of Microbiology

Robert Koch (1843-1910)

In the late 19th century two of the most dangerous killer diseases were cholera and tuberculosis. Cholera was nicknamed ‘King Cholera’ because no one seemed to be able to cure it. Tuberculosis was known as the ‘White Death’ because sufferers vomited up white matter as their lungs disintegrated. The man who made a breakthrough in the fight against these diseases was Robert Koch.

Who was Robert Koch?Koch was a German scientist, born in Hanover in 1843. Koch read Louis Pasteur’s work and in 1872 began research into the microbes affecting diseased animals and people.

What brought him to prominence?In 1875 Koch began his pioneering research to identify the cause of anthrax, the methods that he developed subsequently became the standard method used by all scientists to conclusively prove the accuracy of their research. This approach is sometimes known as Koch’s postulates (postulate meaning a requirement or prerequisite). In 1878 Koch discovered that microbes cause wounds to go septic, but his big breakthrough came when he decided to stain microbes with dye, enabling him to photograph them under a microscope. Using this method he was able to study them more effectively and prove that every disease was caused by a different germ. He identified the microbes that caused tuberculosis in 1882 and cholera in 1883.

How did he do this?Koch’s discoveries were the result of careful research and observation using the microscope, photography and dyes. As a result of his work, the German government also set up an ‘Institute of Infectious Diseases’ in Berlin in 1891 for medical research and development. These developments set the pattern for the future. In the 20th century medical research has increasingly involved teams of researchers supported by large public or private funds.

What did his research result in?The scientific evidence of microbes helped reformers in public health prove that pollution spread disease. It meant certain kinds of action could

Louis Pasteur and Robert Koch Booklet 4

be taken to prevent certain types of disease, since cholera was carried in water, for example, its spread could be prevented with clean water supplies.

What was his legacy?Koch was responsible for establishing the new ‘Science of Modem Bacteriology’. By 1900 he and his students had identified 21 germs causing diseases. Koch’s assistant, Emil Behring, developed the first anti-toxin that could help to destroy the poison spread by bacteria in the blood stream, this was used for the treatment of diphtheria in 1891.

Koch’s research on bacteria won him the Nobel Prize in 1905.

The Causes of Disease

Key events in the career of Louis Pasteur:1861 Pasteur published his ‘Germ theory’1880 Pasteur and Chamberland immunise chickens against cholera1881 Pasteur successfully inoculated sheep against anthrax1884 Pasteur developed a rabies vaccine1888 The French government set up the Pasteur Institute in Paris.

Key events in the career of Robert Koch:1876 Discovered the microbe that caused anthrax1878 Discovered that microbes cause wounds to go septic1882 Identified the microbe that caused tuberculosis1883 Identified the germ that caused cholera1891 The German government set up the Institute for Infectious

Diseases in Berlin1905 Koch was awarded the Nobel Prize for his work in microbiology

SUMMARY Smallpox was a feared epidemic disease in the 18th century. Inoculation was introduced into Britain by Lady Mary Wortley

Montague. Though popular, it was risky and did not reduce the toll from smallpox.

Jenner saw that cowpox victims became immune from smallpox. He vaccinated people with cowpox which made them immune to the

disease. Opposition was overcome because vaccination worked, was widely

publicized and had many supporters. Jenner had no idea how or why vaccination worked, so his work did not lead directly to other developments.

Louis Pasteur and Robert Koch Booklet 5

Emil Behring

In 1850 there were still several different ideas about what caused disease.

In 1857 Pasteur was asked by Monsieur Bigo to explain why his alcohol fermentation had gone bad. His experiments showed that germs caused decay.

Pasteur demonstrated that germs caused disease in animals. Robert Koch was able to prove that each type of germ caused a

specific disease by his work on anthrax. A variety of factors enabled these pioneers to make their discoveries:

o Both Pasteur and Koch built teams of scientists and doctors to help their developments.

o Individual genius enabled them to recognize opportunities for progress.

o Development did not happen in isolation. Communications enabled pioneers to improve upon each other’s discoveries.

o Technological improvements in microscopes, chemical dyes etc. helped to accelerate the rate of change,

Sulphonamides and the search for magic bullets

Using pages 154-155 in the White book and page 118 in the Blue book plus the revision booklet produce a memory map that tells the story of the search for magic bullets in the treatment of disease. Your memory map should include the following words and phrases:

Paul Ehrlich, Sahachiro Hata, Salvarsan 606, sulphonamides, Prontosil, Gerhard Domagk, Strepococci, Robert Koch, syphilis, coal tar, Hildegarde Domagk,side effects, pneumonia, scarlet fever, meningitis, 1935, electron microscope, 1909.

Louis Pasteur and Robert Koch Booklet 6

The Microbe hunters

The work of Pasteur and Koch meant that ihe real cause of disease was known at last. Pasteur’s advice to ‘seek the microbe’ was followed and the new science of bacteriology was established. ‘Microbe hunters’ became the stars of scientific research. The chart below lists some of the other microbes (or germs) which were found.

Year Microbe discovered Name of scientist187918801882188418841894

LeprosyTyphoidDiphtheriaTetanusPneumoniaPlague

HansenEberthKlebsNicholaierFrankaelKitasato and Yersin

The discovery of specific microbes led on to the production of vaccines and, later the pioneering of chemotherapy. The mass killer diseases of earlier times were steadily being controlled.

Pasteur’s team: Charles Chamberland

Charles Chamberland (left) was one of the scientists who were attracted to work in Pasteur’s team and helped to develop the vaccine for chicken cholera. Often they gave up more comfortable careers elsewhere to take part. Others included Emile Roux, who discovered the diphtheria toxin, Alexander Yersin, the Swiss scientist, who discovered the bubonic plague bacillus, and Albert Calmette, who became director of the Pasteur Institute in Paris, and, together with Camille Gurin, found the vaccine for tuberculosis.

Koch’s team: Paul Ehrlich

Ehrlich was born in the town of Strehlen in Silesia, Germany, in 1854. He studied at the University of Leipzig, researching in chemistry and bacteriology. He worked first as a doctor but, in 1886, caught

tuberculosis (TB). It took him three years to recover completely. In 1889, he joined Robert Koch’s research team at the Institute for

Louis Pasteur and Robert Koch Booklet 7

Infectious Diseases in Berlin. He helped Emil Behring to find an anti-toxin that cured diphtheria. From 1899, until his death in 1915, he was the Director of the Royal Institute of Experimental Therapy in Frankfurt. It was here that he carried out his research into chemotherapy (the treatment of disease by chemical drugs). In 1908 he shared the Nobel Prize for medicine with the Russian bacteriologist EIie Metchnikov.

The Microbe Hunters Chronology 1861-1945

Year Development Individual Significance1861 Germ Theory Louis Pasteur Research for a local

brewery led him to prove that the microbes that cause things to go bad float about in the air.

1876 Koch proves that germs cause disease

Robert Koch Began to study anthrax by 1876 he had identified the microbe. Found a way to stain microbes with dyes so they could be seen with a microscope and photographed. An assistant developed the Petri dish to grow microbes in a solid culture (agar). Koch carried out careful tests to prove his theories.

1878 Koch discovered the microbe that caused septicaemia (blood poisoning)

Robert Koch The microbe was invisible even with a microscope until Koch worked out a method of using industrial dyes to stain the microbe.

1882 Discovered the germ that caused tuberculosis

Robert Koch

1883 Discovered the microbe that caused cholera

Robert Koch

1880-1900

The microbes that caused the following diseases were discovered: leprosy, typhoid, diphtheria, tetanus, pneumonia, bubonic plague.

Various scientists inGermany, France and Japan.

The new science of microbiology had begun. The discoverers of these microbes became well known personalities. Vaccines and later chemotherapy built on this work.

1880 Developed a vaccine Pasteur and By giving chickens a weak

Louis Pasteur and Robert Koch Booklet 8

for chicken cholera after accidently injecting chickens with an old and weakened dose of chicken cholera.

Chamberland dose of the infection it gave immunity against developing the full symptoms of the disease. This is the principle of attentuation. Pasteur called the culture ‘vaccine’ as a tribute to Jenner.

1881 Vaccination against anthrax.

Pasteur These experiments led to development of vaccinations for use with humans.

1885 First successful use of the rabies vaccination.

Pasteur Joseph Meister a 9 year old boy was injected with the untested vaccine after being bitten by a dog.

1891 On Christmas day the first child was cured of diphtheria (a highly infectious swelling of the throat that is often fatal in children).

Emil von Behring An assistant of Koch. Developed a serum from the blood of animals that had survived the same infection. This substance Behring called an ‘anti-toxin. He was able to prove it was the toxin that killed not the germ itself. This built on the work of other scientists in both France and Germany. Other anti-toxin vaccines followed.

1909 Salvarsan 606 the first of the so called magic bullets was developed to treat syphilis. This was an arsenic compound derived from an industrial dye.

Paul Ehrlich and Sahachiro Hata

Ehrlich tested over 600 arsenic compounds unsuccessfully. He retested them and found 606 worked on syphilis. In 1911 the first patient with syphilis was treated successfully.

1932 A German scientist discovered a dye that could kill the germs of several diseases without harming the human body. This red dye was called prontosil. This was the second of the magic bullets.

Gerhard Domagk In 1935 Domagk used prontosil to treat his own daughter who had contracted blood poisoning from an infected needle. Prontosil stopped the Streptococcus microbe from multiplying and allowed the body’s own defences time to fight the infection.

1935 French scientists discovered that the compound in prontosil which acted on the

French scientists Sulphonamides were soon found to cure many infectious diseases such as pneumonia, scarlet fever,

Louis Pasteur and Robert Koch Booklet 9

germs was one of a group of chemicals known as sulphonamides derived from coal tar.

tonsillitis and puerperal fever. However, they had disadvantages, they sometimes caused damage to the kidneys and liver. They were also ineffective against the more virulent microbes.

1928 Fleming accidentally discovered the penicillin mould killing germs on agar in a culture dish.

Alexander Fleming Fleming wrote up his findings in 1929 but did little more about his discovery. Penicillin was the world’s first ‘antibiotic’ that is derived from living organisms such as fungi that prevented bacteria from growing.

1938-1945

Florey and Chain produced small amounts of pure penicillin and successfully tested it on mice that had been injected with streptococci. It was equally successful when used on a patient in 1940.

Howard Florey and Ernst Chain

Mass production of penicillin began in America in 1 941 and by 1944 sufficient penicillin was available to supply the needs of the Allied forces.In 1945, Fleming, Florey and Chain were jointly awarded the Nobel prize for medicine

Louis Pasteur and Robert Koch Booklet 10

Why were Pasteur and Koch so successful in solving the riddle of disease?

Find examples of how the following factors helped Pasteur and Koch to be successful:

Individual genius

Improved technology

Links with industry

Role of chance

The support of governments

Warfare

Louis Pasteur and Robert Koch Booklet 11

Improved communications

How did scientists discover cures for disease?

Study Source 8 on page 133 in the SHP text and use this worksheet as a framework to explain how scientists discovered the first cures for disease.

The problem facing doctors in the middle of the nineteenth century was………….

.................................................................................................................................

.................................................................................................................................

.................................................................................................................................

Germ theory was developed by Louis Pasteur. He discovered that………………...

.................................................................................................................................

.................................................................................................................................

.................................................................................................................................

ln the 1870s Koch carefully studied many different bacteria. He……………………

.................................................................................................................................

.................................................................................................................................

.................................................................................................................................

.................................................................................................................................

.. By the 1880s Pasteur had developed .................................................................................................................................

.................................................................................................................................

................................................................................................................................

.................................................................................................................................

Pasteur and Koch through their work were able to help prevent disease but they could not cure disease..................................................................................................................................

Louis Pasteur and Robert Koch Booklet 12

.................................................................................................................................

.................................................................................................................................

.................................................................................................................................

The first cures were developed by Behring and Ehrlich. Behring…………………. .................................................................................................................................

.................................................................................................................................

.................................................................................................................................

.................................................................................................................................

Ehrlich began the real revolution in finding cures for diseases by producing a

chemical compound that destroyed bacteria like a………………………………….. .................................................................................................................................

.................................................................................................................................

.................................................................................................................................

Louis Pasteur and Robert Koch Booklet 13

Improvements in Technology

Anthony Leeuwenhoek was a Dutch clockmaker who in the late seventeenth century invented one of the earliest microscopes with a single lens in. He noticed that everything he studied contained tiny organisms which he called animacules. He described his findings in papers he wrote for the Royal Society in London.

In 1826, a British scientist called Joseph Jackson Lister developed a microscope that magnified 1,000 times without distortion. It is the basis of the modern microscope. For the first time red blood corpuscles could be seen. It was this type of microscope that Louis Pasteur used.

In the 1860s Carl Zeiss in Germany started to make microscopes with wider lens which allowed

greater magnification without distortion. These improved microscopes were used by Robert Koch and his team.

Louis Pasteur and Robert Koch Booklet 14

Explain how Robert Koch and his team made use of the following to make their discoveries about the causes of disease:

Glass slides

Petri dishes and agar jelly

Chemical dyes

Zeiss lens microscope

Louis Pasteur and Robert Koch Booklet 15

Louis Pasteur and Robert Koch Booklet 16