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Transcript
HISTORY OF MICROBIOLOGY
Aristotle (384 B.C.) was one of the greatest scientists of his time. He noticed that mice
were commonly found in barns where grain was stored. He thought that the mice grew
from the grain, and he coined the term “Spontaneous generation”, the hypothesis that
living organisms arise from nonliving matter. He theorized that ‘a vital force’ forms life.
No one doubted this for more than a thousand years. Eventually, a new theory arose
called biogenesis. Biogenesis is the hypothesis that living organisms arise from preexisting life. For many years it was debated as to which of these hypotheses was correct.
During the 1st century AD (year 100), glass had been invented and the Romans were looking
through the glass and testing it. They experimented with different shapes of clear glass and
one of their samples was thick in the middle and thin on the edges. They discovered that if you
held one of these “lenses” over an object, the object would look larger.
These lenses were not used much until the end of the 13th century when spectacle makers
were producing lenses to be worn as glasses.
The early simple “microscopes” which were really only magnifying glasses had one power,
usually about 6X - 10X . One thing that was very common and interesting to look at was fleas and
other tiny insects. These early magnifiers were hence called “flea glasses”.
In 1590, a Dutch spectacle maker, Zacharias Janssen started experimenting with these
lenses. He put several lenses in a tube and made a very important discovery. The object
near the end of the tube appeared to be greatly enlarged, much larger than any simple
magnifying glass could achieve by itself! He had just invented the compound
microscope (which is a microscope that uses two or more lenses).
Galileo heard of their experiments and started experimenting on his own. He described
the principles of lenses and light rays and improved both the microscope and telescope.
He added a focusing device to his microscope and of course went on to explore the
heavens with his telescopes.
1673 - 1723: Antoni Van Leeuwenhoek (Dutch parisitologist) is called the Father of
Microscopy, but he did not invent the first microscope. He became very interested in
lenses while working with magnifying glasses in a dry goods store. He used the
magnifying glass to count threads in woven cloth. He became so interested that he
learned how to make lenses. By grinding and polishing, he was able to make small lenses
with great curvatures. These rounder lenses produced greater magnification, and his
microscopes were able to magnify up to 270X. He described live microorganisms that he
observed in teeth scrapings and rain water. He drew pictures of what he saw and defined
names for bacteria based on their shape. He called round bacteria cocci, rod shaped
bacteria bacilli, and spiral bacteria spirochetes. He also described movement of bacteria
by observing Giardia lamblia in stool specimens. He was the first person to record
drawings of microbes and he introduced the world to the existence of microbes. The
Royal Society of London published his drawings in their journal.
In 1685, Robert Hooke spent much of his life working with microscopes and improved
their design and capabilities. He reported that living things were composed of little boxes
that he called “cells.”
In 1668, Francisco Redi doubted the theory of spontaneous generation. He believed that
maggots in meat were caused by flies laying eggs, not by spontaneous generation as
commonly believed. He filled six jars with decaying meat. He noted that no maggots
grew in the meat when the jars were covered. It was argued that air was needed for the
vital force to create life. Therefore, he put a screen over some of the jars so that flies
could not come in and lay their eggs, but air could get in. He demonstrated that maggots
grew only in the meat in which the flasks were not covered. However, the theory of
spontaneous generation persisted.
In 1858, Rudolf Virchow helped create the Cell Theory, which said:
1. All living things are composed of cells.
2. Cells are the smallest working units of living things.
3. All cells come from preexisting cells by cell division.
Louis Pasteur (1857-1914) joined the spontaneous generation debate. He made a glass
flask with an “S” shaped bend in it so that bacteria could not enter into it. He placed
chicken broth in the flask and boiled it so that it was sterile. Over the next few weeks, he
observed that there was no bacterial growth in the broth, so this proved that spontaneous
generation was impossible. No bacteria could grow unless pre-existing bacteria were
able to get in to the nutrient broth. That ended the debate and the theory of biogenesis
was accepted.
The Golden Age of Microbiology (1880-1930)
Louis Pasteur
Once the debate over spontaneous generation was over, the Golden Age of Microbiology
began. Louis Pasteur went on to discover vaccines by accident. During his time, chicken
cholera was hurting the poultry industry. Pasteur made a pure culture of chicken cholera
and told his assistant to inoculate a chicken. They both left on vacation and forgot to
inoculate the chicken. When they came back, they inoculated the chicken with the same
culture, which had run out of nutrients and had become weak. They found that the
chicken never developed symptoms. They then tested all of the chickens to make sure
that weakened culture did not cause symptoms in any chickens. They then exposed the
chickens to chicken cholera and none of them became sick. They therefore discovered
the concept of an immune system. They found that the old culture was weakened (he
called this “attenuated”), and thus he discovered how to make the first vaccine.
Pasteur also developed the concept of pasteurization. In this process milk is boiled at
58°C for 30 minutes to destroy microbes that spoil milk, beer, and wine. Shortly after
that, the relationship between microbes, disease, immunity, and anti-microbial drugs was
discovered.
He also discovered the concept of fermentation. He found that some microbes could live
in anaerobic conditions (without oxygen) by fermenting sugars. This has useful
applications in the alcoholic beverage industry.
Pasteur was the first to study diseases and develop the “Germ Theory of Disease”. This
was useful in Streptococcus, Staphylococcus, pneumococcus, and anthrax infections.
Louis Pasteur went on to work with anthrax, silkworm disease, and rabies. He developed
the first vaccine for rabies, which is a disease that spreads to the brain and spinal cord.
Rabies is caused by a virus and is too small to see under a microscope. Therefore, he was
the first to work with human diseases caused by viruses. He worked with rabbits that had
rabies; he dissected out the spinal cords, put them in a jar, let them drive for a few weeks,
ground them up into a powder, and made his suspension. He then inoculated dogs with
this rabbit tissue. When the dogs were exposed to rabies, they did not get the disease.
A young boy named Joseph Meister was bitten by a rabid animal. Back then, everyone
who was exposed to rabies died. Pasteur injected the boy’s abdomen with a vial of the
spinal cord suspension once a week for 12 weeks. He was the first person to survive
rabies. After Louis Pasteur died, Joseph became a caretaker of Pasteur’s estate. During
World War II the Nazis invaded Paris. They wanted to raid Pasteur’s tomb, but rather
than allow that, Joseph committed suicide.
Robert Koch, MD (contemporary = modern doctor)
Unlike Pasteur, Koch was an MD, and he worked with a team of scientists, rather than
alone, like Pasteur. He developed “Koch’s Postulates” which establish the cause of
disease. This was developed using the scientific method, including stating a hypothesis
and drawing a conclusion. He studied anthrax in sheep and cattle, and he also worked
with tuberculosis. He is the one that proved the link between microbes and disease.
Koch’s Postulates
1. Obtain the disease causing microbe from the sick animal via a sample.
2. Isolate this microbe in pure culture.
3. Inoculate a healthy animal with this pure culture, and the healthy animal should
develop the same disease.
4. Re-isolate the microbe from the second animal. If it is the same microbe obtained
from the first animal, this proves the etiology (cause) of the disease.
Koch is also the one who developed the use of agar, a solid medium used to make a pure
culture of a certain organism. Colonies of bacteria from the patient’s specimen grew on
the agar. After examining each colony under a microscope, he selected one that he
thought was causing the disease. This one colony was then scraped off and placed on a
new agar plate, creating a pure culture of the organism that he wanted to study. He was
known for saying “Chance favors a prepared mind”.
Joseph Lister (1827-1912)
During his lifetime, 50% of people who had surgeries died from post-op infections. It was
thought that exposure of a wound to oxygen caused the infection, but Lister doubted that
explanation. He was put in charge of a new hospital in London that was designed to keep
air away from post-op wounds. However, 50% of the amputation cases still were dying.
Then, in 1865, when Louis Pasteur suggested that decay was caused by living organisms
in the air, Lister made the connection with wound sepsis. He considered that microbes in
the air were likely causing the putrefaction and had to be destroyed before they entered
the wound.
In the previous year Lister had heard that carbolic acid was being used to treat sewage in
cattle fields that were causing a parasite disease in the cattle.
Lister began to clean wounds and dress them using a solution of carbolic acid. He
reported that the surgery patients were now recovering without infections. In 1877 he
performed the first surgery using aseptic conditions, including sterilization of instruments
and hand washing before surgeries. Thus, he is the founder of aseptic medicine. Later, his
product was refined by another doctor who named it Listerine® after Dr. Lister.
Edward Jenner, MD
Jenner invented the vaccine for smallpox, the first disease to be eliminated from the earth
by vaccine. Some of his patients, especially women who milked cows, would come in
with lesions filled with pus on their hands. He went to their farms to examine the cattle
and noticed lesions on the udders of the cattle as well.
Around this time smallpox was greatly feared, as one in three of those who contracted the
disease died, and those who survived were commonly badly disfigured. Noting the
common observation that milkmaids did not generally get smallpox, Jenner theorized that
the pus in the blisters which milkmaids received from cowpox (a disease similar to
smallpox, but much less virulent) protected the milkmaids from smallpox. In 1796,
Jenner tested his theory by inoculating James Phipps, a young boy, with material from the
cowpox blisters of the hand of Sarah Nelmes, a milkmaid who had caught cowpox from a
cow called Blossom. Phipps was the 17th case described in Jenner's first paper on
vaccination.
Jenner inoculated Phipps with cowpox pus in both arms on one day. This produced a
fever and some uneasiness but no great illness. Later, he injected Phipps with variolous
material, (weakened smallpox). No disease followed. Jenner reported that later the boy
was again challenged with variolacious material and again showed no sign of infection.
The word vaccination comes from the Latin vaccinia, cowpox, from vacca, cow.
In 1980, the World Health Organization declared smallpox an eradicated disease.
Paul Ehrlich (1854 –1915)
He coined the term "chemotherapy" and developed the first antibiotic drug in modern
medicine.
After his clinical education in Berlin in 1886 he received a call from Robert Koch to join
the Institute for Infectious Diseases in Berlin (1891).
Ehrlich spent two years in Egypt, recovering from tuberculosis. Thereafter he worked on
the development of the diphtheria serum.
Ehrlich received the Nobel Prize for Medicine in 1908. In 1906 he discovered the
structural formula of atoxyl, a chemical compound that had been shown to be able to treat
sleeping sickness. Following this discovery, he tried to create a less toxic version of the
medicine. In 1909 he developed Salvarsan, a chemical effective against syphilis. This
work was of epochal importance, stimulating research that led to the development of
sulfa drugs, penicillin and other antibiotics.
Von Behring (1901): First to study how a toxin (Diptheria) can be neutralized by an
antitoxin.
Metchnikoff (1908): Discovered that white blood cells phagocytize (eat) foreign
particles as a fundamental part of the immune response. He studied mobile, amoeba-like
cells (later known as white blood cells) in starfish. He thought they served as part of the
defences of these organisms and, to test this idea, he stuck the starfish with small thorns
from a tangerine tree which had been prepared as a Christmas tree for his children. Next
morning he found the thorns surrounded by the mobile cells, and, knowing that, when
inflammation occurs in animals which have a blood vascular system, leucocytes escape
from their blood vessels, it occurred to him that these leucocytes might take up and digest
bacteria that get into the body. This began the field of immunology.
Alexander Fleming (1881-1955)
Fleming is the key person involved in the discovery of penicillin.
One morning in the fall of 1928, Fleming noticed a culture plate displaying a colorful
green mold. The culture plate was covered with staphylococci except in the vicinity of
the mold, which was near the edge of the plate where there was a transparent zone of
inhibition. The bacteria that were close to the mold had not grown. Fleming
photographed the plate and made it permanent by exposing it to formalin vapor that killed
and fixed both the bacteria and the mold. (The original plate is now in the British
Museum.) Fleming investigated a list of microorganisms that were inhibited by the mold,
among them were streptococci, staphylococci, pneumococci and meningococci. Fleming
identified the mold as a Penicillium that is similar some molds grown on bread. In 1945
Fleming received the Nobel Prize in Medicine and Physiology for his work with
penicillin.
Chain and Florey
The biggest problem was how to produce large quantities of penicillin, especially for
casualties during WWII. American scientists Chain and Florey were successful in
producing it for large-scale manufacture.
Rebecca Lancefield (1895 - 1981)
American microbiologist. She is most famous for her serological classification of
streptococcal bacteria based on the antigens in the cells walls.
She also demonstrated that one of these groups, group A streptococci (S. pyogenes), was
specific to humans and human disease, including pharyngitis ("strep throat"), scarlet
fever, rheumatic fever, and impetigo. Group B streptococci were subsequently shown to
be associated with neonatal disease.
Frederick Griffith (1928): found a “transformation principle” in bacteria, known as
DNA today. Non-virulent streptococci (can’t cause disease) were formed into virulent
strains.
Watson and Crick discovered the structure of the DNA molecule in 1953. Watson and
Crick were awarded the 1962 Nobel Prize award, for their body of research on nucleic
acids. Their work became the basis for the Human Genome Project, which was a worldwide effort to list all of the sequences of amino acids in human DNA. This knowledge is
helping to understand genetic disorders. This also opened up the field of Molecular
Genetics, understanding how genes work at a molecular level.
François Jacob and Jacques Monod (1965), discovered the role of messenger RNA in
protein synthesis. They won the Nobel Prize in Medicine in 1965.
Delbruck and Hershey (1969): Received the Nobel prize for their discoveries
concerning the replication mechanism and the genetic structure of viruses.
Prusiner (1997): American neurologist whose discovery of the disease-causing protein
called prion in 1982 won him the 1997 Nobel Prize for Physiology or Medicine. Prions
are simpler than viruses and can cause disease. They have no DNA or RNA. They cause a
brain disease called spongiform encephalopathy (bovine form is Mad Cow Disease).