Introduction and a
Brief History of Microbiology
I.
Microbiology involves the
study of those organisms too small to be seen by the unaided eye.
These organisms include bacteria, fungi,
viruses, protozoa and alga. As a group, these organisms are referred to as microbes,
microorganisms or, if they cause disease, pathogens,
germs or “bugs”.
It should be noted that for the most part microbes do
not cause disease. The vast majority of microorganisms live in the soil,
water or in association with organisms other than humans. These microbes are not
adapted for living on or in humans. Of those organisms that are adapted for
living on or in humans most do not appear to cause disease to any significant
degree. Thus when we discuss human pathogens we are talking about a very small
subset of microorganisms.
II.
Before discussing the historical background of the science of
microbiology a short discussion of the philosophy of modern science should be
undertaken. Science
is a way of thinking it is not a body of knowledge. Our current understanding of the nature world is the result
of the vigorous application of the scientific method.
A.
The scientific method involves several steps. Initially a phenomenon must be observed.
From these observations a hypothesis
(educated guess) that attempts to explain how the phenomenon occurs is
ventured. The hypothesis must
explain the phenomenon by proposing a testable and falsifiable set of factors
and/or processes that result in the phenomenon.
Thus if you change one of these factors or in some way alter the
processes you will change the phenomenon in some predictable
manner. Predictable is the key word here.
If your hypothesis does not predict the outcome of an experiment then
the hypothesis needs to be revised.
B.
Altering the factors and observing how the phenomenon is affected is
referred to as experimentation.
The factor that is altered is referred to as to a variable.
C. If the experiments repeatedly turn out as expected, the
hypothesis is said to be “supported”.
It must be stressed that a hypothesis is never shown to be true.
Repeated experimentation that supports a hypothesis and develops the
hypothesis further leads to the hypothesis being accepted as a theory.
Often a well-supported theory will be referred to as a law
or principle.
It should be noted that in reality it is still a theory, just one that
has stood the test of time fairly well.
III.
In
western civilization before the 1500’s, most theories of disease were based
solely on superstition and untestable hypothesis.
For the most part, this was due to the lack of knowledge regarding the
human body and a complete ignorance regarding the presence of microorganisms.
Over the next 400 years with the widespread application of the scientific
method to both human anatomy and disease, along with the development of
technologies that allowed for the visualization of microorganisms a deeper and
more useful understanding of infectious disease would emerge.
A. In the mid-1600's two amateur investigators, Robert Hooke and Anton
van Leeuwenhoek, began using crude microscopes.
1. Hooke
described the structure of cork. Though
he observed the cellular structure in the cork, it would be 200 years before
a comprehensive cell theory (one that included animal tissues as well as
plant tissues) would emerge.
2. van
Leeuwenhoek observed what we now call bacteria and protists.
He described these tiny organisms as "animalcules" (little
animals). This opened up a
whole world of life that had hitherto fore been unknown.
It would be hundreds of years before the true nature of these
microorganisms would be discerned.
B.
For
200 years it was widely believed that van Leeuwenhoek’s animalcules and
many “lower” forms of life arose spontaneously from inorganic precursors
or rotting organic material. This
theory is known as spontaneous
generation or abiogenesis.
This theory held that by combining certain materials a mouse or a bug
could be generated. Microbes
were generally held to arise from the breakdown of more complex organisms.
So as a tissue rotted it would give off “animicules”.
Thus the presence of microbes in a sick patients bloodstream was due
to the internal breakdown of a tissue.
They were just another symptom of some internal dysfunction and were
not widely considered to be the cause of the dysfunction.
1.
Francesco
Redi would dispel the notion of spontaneous generation as it related to
macroscopic organisms (flies, rats, etc.) in 1668. Lazzaro Spallanzani successfully performed experiments
designed to disprove that microorganisms arose spontaneously in 1776 but
these results were not accepted immediately.
All of these men realized that the living organisms that they
studied did not arise by spontaneous generation but arose only from
parental organisms. This is known as biogenesis.
2. Confusion over abiogenesis with regard to microbes stemmed from conflicting results in
experiments performed on broth cultures derived from organic matter. Originally Louis
Jablot demonstrated (correctly) that microbes do not arise spontaneously. But later
experiments performed by John Needham came to the opposite conclusions. Needham's results
were due to improper sterilization of the broth in the first place.
3.
Experiments
performed by Louis Pasteur in the mid-1800's demonstrated that even
microorganisms could not arise via spontaneous generation. Though their
reproduction is somewhat different from that of sexually reproducing
organisms, bacteria only arise from other bacteria.
Laying the debate regarding the origins of microorganisms to rest
would have a profound affect on the development of correct ideas regarding
disease.
C.
Though
the vast majority of microorganisms do not cause disease in a normal, healthy
person, many of the diseases that afflict mankind are due to the invasion of
the body by particular bacteria. Before
the mid-1800's disease was believed to be the result of "bad vapors"
or some other non-specified cause (including many supernatural causes such as
curses, retribution from God, etc.). The
bacteria found at the site of an infected wound or in the lungs of persons
with respiratory infections were thought to have arisen spontaneously from the
necrosis of human tissue. In this
theoretical framework, bacteria resulted
from disease they did not cause it.
Once Pasteur’s experiments laid spontaneous generation to rest the
correct relationship between bacteria and disease could emerge.
During the period from the 1880’s to the early 1900’s, the
germ theory of disease
emerged and was embraced by the medical community.
This monumental step forward was due largely to the work of Louis
Pasteur and Robert Koch. The germ
theory of disease holds that disease was the caused by microorganisms.
Any organism capable of causing disease is referred to as a pathogenic
microorganism or simply a pathogen.
1. Even before the medical community had embraced the germ theory, two physicians
had observed that the use of sloppy methods and contaminated instruments during surgery
led to increased mortality of the surgical patient.
a. Around 1845, Ignaz Semmelweis observed increased maternal mortality in delivery
wards if a resident physician delivered the baby. These physicians often came directly
from the autopsy room to the delivery room without washing or changing clothes. Semmelweis
deduced that these physicians were transferring something from the corpse to the mother
that led to the development of puerperal fever. He forbid the physicians from delivering
babies until they had washed their hands and changed into clean clothes. Mortality from
puerperal fever dropped substantially. These restrictions so aggravated the staff that
Semmelweis was fired.
b.
In
the mid-1860’s, Joseph
Lister developed protocols for the sterilization of surgical instruments
and procedures meant to minimize the contamination of the surgical wound. These methods were collectively referred to as aseptic
technique. When surgeons utilized these procedures, mortality from
surgery dropped substantially. Due
to the changing attitudes regarding the role of microorganisms in the
development of disease and the measurable drop in mortality post-surgery,
Lister’s ideas were accepted.
2.
In
1876 Robert Koch isolated the bacteria Bacillus
anthracis and proposed that it was responsible for the disease anthrax.
To prove this, he isolated the bacterium from a dead animal, cultured
it and reintroduced it into a healthy animal.
The animal contracted anthrax. He
was then able to isolate the bacteria from the second (experimentally
infected) animal. This way of
approaching the identification of a disease causing microorganisms came to
be known as Koch's postulates.
These postulates state that to consider a specific bacteria as the
cause of a specific disease (etiologic agent), the bacterium must be isolated, introduced
into a healthy host and cause the same disease as seen in the originally
infected organism (Click
to read Koch's original article).
D. Acceptance of the germ theory led to rapid advances in the understand of infectious
disease. This deeper understanding of disease and the pathogens that cause them led
to more rational approaches to therapy and prevention. Almost immediately the search
for a "magic bullet" that would kill the microorganism but not harm the host was
begun. Leading this search was Paul Ehrlich. In 1912, he announced
the discovery of a drug known as
salvarsan which was able to limit the growth of the organism that causes syphilis.
The problem with salvarsan was that it was only slightly more toxic for the microbe than
for the host. But for almost four decades salvarsan remained the most
effective antimicrobial drug. In 1935, a German chemist named Gerhard
Domagk identified a more selectively toxic compound that was named prontosil
(or prontosil rubrum). Prontosil, is converted by the
liver to a compound known as sulfanilamide. Sulfanilamide is a member of a class of
compounds known as the sulfonamides commonly referred to as the sulfa
drugs. Many sulfa drugs are still in widespread usage today (Click
to read original article).
E.
The big push for developing better chemotherapeutics was partially driven by
the appalling death rate from infection suffered by soldiers during World War I. The
next step major step in development of chemotherapeutic agents was driven by
the threat of war that became World War
II. In the mid-1930's the Germans produced most of the antimicrobial
drugs. Britain
recognized that without the development of some alternative chemotherapeutic they would be
left with limited amounts of drugs to treat soldiers during the ensuing conflict.
This let to the development of the first antibiotic. Nearly a decade earlier (the
late 1920’s), an English microbiologist named Alexander Fleming observed that a
colony of the mold Penicillium notatum which had contaminated a plate of
Staphylococcus
aureus inhibited the growth of Staphylococcus aureus. This inhibition he
termed antibiosis. It would be ten years before the chemical responsible for this
phenomena was exploited to make the first antibiotic, Penicillin (Click
to read original article). It should be noted
that antibiotics are chemicals produced by living microorganisms to inhibit the growth of
other microorganisms. Drugs like protonsil which are produced in the laboratory are
referred to as synthetic drugs. Though the phenomenon of antibiosis was
described by Fleming, it would take the work of Howard Florey, Edward
Abraham and Ernst Chain in the late 1930's and early 1040's to isolate the
compound that is now known as penicillin (Click
to see a review of these scientists contribution).
1. After the testing and widespread use of penicillin during WWII, the hunt for
other antibiotics yielded a large number of other agents that could be used in treatment
of bacterial infections.
2. By chemically modifying antibiotics, chemists were able to develop the
semisynthetic drugs. These drugs start as antibiotics but by the addition of
chemical groups the characteristics of the antibiotic can be radically altered.
3. Different antibiotics (and synthetic drugs) are effective against different types
of organisms. The range of organisms over which a drug exerts an effect is that
drug's spectrum of activity. For some drugs this is an extremely narrow range while
other drugs will adversely affect most bacteria (broad spectrum drugs).
F. Widespread usage and misusage of antimicrobial drugs has led to the rapid emergence
of bacteria that are resistant to the effects of these drugs. This problem was
predicted by microbiologists in the 1950's and 1960's. They observed that strains of
the bacteria that cause gonorrhea were no longer killed by penicillin. In recent
years many pathogens have become resistant to the antimicrobials that have been effective
against them for the last 50 years. This problem can not be understated! We
will revisit this phenomena in that section that deals with antimicrobial therapy.
IV.
In European society by the early 18th century, long before the
acceptance of the germ theory, both physicians and veterinarians began to
realize that certain diseases only affected a person once in their lifetime.
The reason for this “protection” would not become clear for almost
300 years but the harnessing the body’s ability to react to pathogens in
such a way as to provide immunity to that pathogen would begin in the early
1700’s (this phenomenon was noted and harnessed much earlier in other
cultures but their practices did not significantly impact the development of
western medicine).
A.
Smallpox was a disease that ravaged Europe for centuries.
Those that contracted the disease often died and those the survived
were often left with scars. The
control of this scourge was the first complete success that has been achieved
by western medicine. Over the last two hundred years, the use of vaccination
against smallpox has led to the eradication of naturally occurring cases of
this disease.
1. Lady Montagu introduced a technique known as variolation
in which a thread was soaked in the fluid from a smallpox vesicle.
This thread was then drawn through a small incision in the skin.
Though this often led to immunity against small pox there was the
chance that the patient would a case of smallpox. Furthermore, those that were
inoculated with smallpox in this manner often were able to pass the virus on
to those that they came in contact with.
2.
In the late 1700’s, Edward Jenner realized that milkmaids
contracted a disease from cows (Cowpox) that seemed to lead to immunity that
protected them from smallpox. Jenner
intentionally exposed persons to the fluid from a cowpox vesicle. This
procedure came to be known as vaccination.
This procedure eliminated the possibility of the vaccinated person
catching smallpox or being able to pass it smallpox on to those with whom they
had contact.
B. With the acceptance of the germ theory and the
identification of many of the pathogens responsible for disease, development
of vaccines became a high priority. Many diseases that once caused considerable death and
disability are now almost unheard of. For
respiratory tract diseases this is due, in large part, to the proper
utilization of vaccines.
V.
Our understanding of how vaccines worked is an ongoing scientific enterprise. As
the immune system is quite complex with several different ways of reducing the
impact of pathogens, our understanding of this system emerged very slowly.
A.
Early advances in what would come to be known as cellular immunity were made
by Ilya Metchnikoff in 1882 when he recognized that certain cells were capable
of engulfing of "eating" other cells (Click
to see original article). This phenomenon came to be known as phagocytosis
and the cells that carry it out as phagocytes. B.
Emil von Behring and Shibasaburo Kitasato working together in Berlin in 1890
announce the discovery of diphtheria antitoxin serum. This antitoxin was
derived from the serum of those that had been exposed to the agent that causes
diphtheria but had not succumbed to the disease. Giving this serum to a
patient that was suffering from diphtheria greatly improved the chances of
that patient surviving. In 1890, Paul Ehrlich proposes that substances
in the serum which he termed antibodies are responsible for this protection
from disease. C.
In 1890, Robert Koch described a phenomenon where exposure to certain
substances causes the skin to become inflamed after a period of delay
(exposure to poison ivy is an example). This was originally termed the
"Koch effect", but later came to be known as delayed
hypersensitivity. D.
By 1900 we understood that the body had complex mechanisms for responding to
pathogens to eliminate them when they are causing disease and to keep them
from reinfecting the body. A century later, though we have made
significant progress in understanding these systems we still have a long way
to go. For an in-depth examination of this progress visit http://www.keratin.com/am/amindex.shtml.
Since
my notes are a little sparse here are some good links!!!
The
American Society for Microbiology Significant Events
Of The Last 125 Years
http://www.asm.org/MemberShip/index.asp?bid=16731
I
have no idea who did this page but it is pretty cool!!
http://microbes.historique.net/history.html
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