1. 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

2. 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?
Koch’s
Pasteur’s work was revolutionary in Postulates
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. 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
Louis Pasteur and Robert Koch Booklet isolated the bacterium that 2
caused anthrax.

3. 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… Paul Ehrlich
• 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

4. 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

5. 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. Emil Behring
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 cholera
1881 Pasteur successfully inoculated sheep against anthrax
1884 Pasteur developed a rabies vaccine
1888 The French government set up the Pasteur Institute in Paris.
Key events in the career of Robert Koch:
1876 Discovered the microbe that caused anthrax
1878 Discovered that microbes cause wounds to go septic
1882 Identified the microbe that caused tuberculosis
1883 Identified the germ that caused cholera
1891 The German government set up the Institute for Infectious
Diseases in Berlin
1905 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
Louis Pasteur and Robert Koch Booklet 5

6. vaccination worked, so his work did not lead directly to other
developments.
• 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

7. 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 scientist
1879 Leprosy Hansen
1880 Typhoid Eberth
1882 Diphtheria Klebs
1884 Tetanus Nicholaier
1884 Pneumonia Frankael
1894 Plague Kitasato 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
Louis Pasteur and Robert Koch Booklet 7

8. tuberculosis (TB). It took him three years to recover completely. In 1889,
he joined Robert Koch’s research team at the Institute for 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 Significance
1861 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 Robert Koch Began to study anthrax by
germs cause disease 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 Robert Koch The microbe was invisible even
microbe that caused with a microscope until Koch
septicaemia (blood worked out a method of using
poisoning) industrial dyes to stain the
microbe.
1882 Discovered the germ Robert Koch
that caused
tuberculosis
1883 Discovered the microbe Robert Koch
that caused cholera
1880-190 The microbes that Various scientists The new science of
0 caused the following in microbiology had begun. The
diseases were Germany, France discoverers of these microbes
discovered: leprosy, and Japan. became well known
typhoid, diphtheria, personalities. Vaccines and
tetanus, pneumonia, later chemotherapy built on
bubonic plague. this work.
Louis Pasteur and Robert Koch Booklet 8

9. 1880 Developed a vaccine Pasteur and By giving chickens a weak
for chicken cholera Chamberland dose of the infection it gave
after accidently immunity against developing
injecting chickens with the full symptoms of the
an old and weakened disease. This is the principle of
dose of chicken attentuation. Pasteur called
cholera. the culture ‘vaccine’ as a
tribute to Jenner.
1881 Vaccination against Pasteur These experiments led to
anthrax. development of vaccinations
for use with humans.
1885 First successful use of Pasteur Joseph Meister a 9 year old
the rabies vaccination. boy was injected with the
untested vaccine after being
bitten by a dog.
1891 On Christmas day the Emil von Behring An assistant of Koch.
first child was cured of Developed a serum from the
diphtheria (a highly blood of animals that had
infectious swelling of survived the same infection.
the throat that is often This substance Behring called
fatal in children). 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 Paul Ehrlich and Ehrlich tested over 600 arsenic
of the so called magic Sahachiro Hata compounds unsuccessfully. He
bullets was developed retested them and found 606
to treat syphilis. This worked on syphilis. In 1911 the
was an arsenic first patient with syphilis was
compound derived from treated successfully.
an industrial dye.
1932 A German scientist Gerhard Domagk In 1935 Domagk used
discovered a dye that prontosil to treat his own
could kill the germs of daughter who had contracted
several diseases blood poisoning from an
without harming the infected needle. Prontosil
human body. This red stopped the Streptococcus
dye was called microbe from multiplying and
prontosil. This was the allowed the body’s own
second of the magic defences time to fight the
bullets. infection.
1935 French scientists French scientists Sulphonamides were soon
discovered that the found to cure many infectious
Louis Pasteur and Robert Koch Booklet 9

10. compound in prontosil diseases such as
which acted on the pneumonia, scarlet fever,
germs was one of a tonsillitis and puerperal
group of chemicals fever. However, they had
known as disadvantages, they
sulphonamides sometimes caused damage to
derived from coal tar. the kidneys and liver. They
were also ineffective against
the more virulent microbes.
1928 Fleming accidentally Alexander Fleming Fleming wrote up his findings
discovered the in 1929 but did little more
penicillin mould killing about his discovery. Penicillin
germs on agar in a was the world’s first
culture dish. ‘antibiotic’ that is derived from
living organisms such as fungi
that prevented bacteria from
growing.
1938-194 Florey and Chain Howard Florey and Mass production of penicillin
5 produced small Ernst Chain began in America in 1 941 and
amounts of pure by 1944 sufficient penicillin
penicillin and was available to supply the
successfully tested it on needs of the Allied forces.
mice that had been In 1945, Fleming, Florey and
injected with Chain were jointly awarded the
streptococci. It was Nobel prize for medicine
equally successful
when used on a patient
in 1940.
Louis Pasteur and Robert Koch Booklet 10

11. 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

12. 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………….
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Germ theory was developed by Louis Pasteur. He discovered that………………...
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ln the 1870s Koch carefully studied many different bacteria. He……………………
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..
By the 1880s Pasteur had developed
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Louis Pasteur and Robert Koch Booklet 12

13. Pasteur and Koch through their work were able to help prevent disease but they
could not cure disease.
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The first cures were developed by Behring and Ehrlich. Behring………………….
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Ehrlich began the real revolution in finding cures for diseases by producing a
chemical compound that destroyed bacteria like a…………………………………..
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Louis Pasteur and Robert Koch Booklet 13

14. 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

15. 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

16. Louis Pasteur and Robert Koch Booklet 16