Microbiology is the study of microorganisms. It could also be called the study of very small living things.
These are living organisms that are so small as to be visible only through microscopes. Groups of plants and
animals that are included in the term microorganisms are yeasts, molds, bacteria, protozoa and viruses. Many
scientists regard present-day microorganisms as more or less direct descendants of some of the earliest forms of life on earth. In reviewing the ancestors of present-day living things, the farther we go in point of time, the simpler and more lowly were plants and animals. It could be inferred then that the simplest and most lowly creatures alive today would be descendants of those that existed in the earliest ages of life on the planet, probably more than four billion years ago. Remember, the Universe itself is theorized to be 15 billion years old by cosmologists. A Cosmotologist studies the cosmos (Universe) and it's origins. A Cosmetologist puts makeup on! Do not the confuse the two!

Although the first compound microscope was discovered in 1590 by Zacharias Jannsen, the first person to
see and also describe microorganisms was Antony van Leeuwenhoek (1632-1723). Leeuwenhoek was a Dutch
dry goods merchant of Delft, Holland who wanted to observe the weave of fine cloth. He made a small hand-
held microscope that he held-up to a candle flame and observed closely. One of his original microscopes still
exists today at the University of Utrecht. Electron Microscopes are widely used today to view viruses. HCV has not been photographed yet by anyone, but there is an all-points-bullentin out on it!

When Paul Ehrlich (1845-1915), the famous German Bacteriologist, Physician and Immunologist was trying to
invent a "stain" for viewing microscopic slides under a light microscope, he had it all wrong! He left the glass
slides, with the test-stain material on it, out in the open on top of his laboratory desk. Mrs. Ehrlich came in to
clean up and carefully placed the tray of slides on top of the slightly heated stove. When Dr. Ehrlich returned
to his laboratory he yelled at Mrs. Ehrlich for moving the tray. Much to his surprise the heat was the additional step needed to develop and use "dyes" and "stains", as we now know them today. Without these versatile visual microscopic enhancers we would not be able to see much of anything under a compound light microscope. Never mind a virus. Only the largest viruses can be seen under a light microscope, the smallpox virus. All of the other viruses need to be viewed with a modern electron microscope. This includes the HCV virus.

Paul Ehrlich's research was instrumental towards a cure for Syphilis. Syphilis is cased by a corkscrew shaped
microorganism called a Spirochete (Treponema Pallidum). It was brought back to the new world in 1493 by
Spanish sailors. The disease was carried into Italy by the Armies of Charles VIII of France and spread
throughout Europe. It was also known as the Napolititan disease and French Pox. The disease had followed
the Armies of Napoleon across a crowded Europe and into the frozen Russian Steppe Capitol of Moscow. It
is estimated that more defeated French soldiers died from Syphilis than from exposure on the death march
back from Moscow. Napoleon's great defeat was written about in Tolstoy's "War and Peace". The French Army
had been badly beaten by both the Cossacks and by the Spirochete! Armies learned early in history that the
greatest enemy is the one you can not see. Just like HCV! If we do not see it then it must not be there! Right?
Militaries must confront disease. How they do it is subjected to history.

Viruses often follow Armies because of epidemiological factors, i.e., wine, women and song, or today's
version, sex, drugs and rock + roll. It is estimated over history that more famous persons have died of syphilis than of any other communicable disease. Up until at least AIDS and HCV came along! Persons with wealth in the past two milleniums could live an Epicurean, or loose, lifestyle. The opposite of Epicureanism is Stoicism (Socrates's philosophy) . As people had more leisure time to do as they pleased, diseases followed the more sorted behaviors of their times. When in Rome do as the Romans. The Romans were using and sharing baths. Disease was spread through these bath waters. Doctor Ehrlich's revolutionary staining techniques enabled him to find and finally view the deadly spirochete that caused syphilis. Because he now could test for syphilis, he could also monitor suspected cases. In addition, Dr. Ehrlich could treat potential victims for the first time. Once Syphilis was able to be overcomed, Armies again could be on the move. And they were! The American Century had just begun on the other side of the planet! The social and intellectual forces that had opened the Century would soon lead to World War I. The forces that were not resolved after WWI lead inevitably to WWII. Because of WWII the U.S. Military needed a vaccine for Yellow Fever. Because of this vaccine that went bad in 1942 we now have HCV today. Understand?

When we speak of epidemiology, we hear terms like epidemic, endemic and pandemic. In addition we hear
about disease transmission routes and sources are studied in order to understand and eradicate the causative agent. Epidemic means to infect many and to spread rapidly. Endemic means native or belonging to a people. The Australian Aborigines are endemic to Australia. Pandemic means disease widely spread. HCV is becoming pandemic and is close to being in epidemic proportions in our society. Transmissions routes and sources for HCV are blood-to-blood contacts between a carrier and the victim. Your blood is the source host for the virus. It likes you so much that it moves into your liver and rents out a room. Actually, it knows that you will do all the hard work (survival) and it will just replicate and wait to be transmitted one day to a new host reservoir. Viruses get into trouble when they go where they do not belong. Adenovirus is a respiratory virus that the military says is now an intestinal and liver virus! Viruses cause trouble when they get into places they do not belong! Lung virus in the liver? Trouble!

The CDC reports that 43 percent of all HCV transmission cases are unaccounted for. It is estimated also that
a large percentage of these "unaccounted for" transmission cases are attributed to Intravenous Drug use in
the past. The reasoning is that many patients infected with HCV are mainstream society members today that
would be embarrassed by a previous history of drug use if it became known. In the military IV drug use is
considered "misconduct" and the veteran receives no assistance from the government because of their own
misdeeds and or malfeasance. When we speak of epidemiological factors what we really mean to say is "how
did I get this virus?". When the government speaks of epidemiological factors what they mean to say is "it
must be your own fault, we had nothing to do with it!". The government is elected and put in place to "have"
something to do with it. The first responsibility of government is to safeguard it's citizens, and not to harm
them. When this happens the system is broken. As the bard William Shakespeare said himself, "thou dothst
protest too much!". The government looks to blame everyone else for HCV. Even you! If you were caught with
your hand in the RNA cookie jar what would you do? The best defense is a good offense!

When Dr. Paul Ehrlich caught tuberculosis in the late 1890's he was sent to where all other persons of his heath and wealth could afford to go to at that time, Morocco, in order to recooperate. The French had claimed North Africa for their own much as the Americans did the western hemisphere with the Monroe Doctrine a hundred years earlier. Tunisia, Chad, the Sudan, Algiers and Morocco were all considered to be French colonial territories. Morocco is located on the north west coast of the African Continent. It was in Morocco's Capital city of Rabat about 1898 that the French painter and sculptor Edgar Degas (1834-1917) met with the famous French novelist and writer, Emile Zola, the father of Naturalism, (1840-1902). Degas was recovering from a sickness with tuberculosis also and Emile Zola had come to pay his sick friend, Degas, a visit. Dr. Ehrlich was also in Rabat and proceeded to observe some strange occurrences on one particular day in the city's market square.

The three gentlemen were sitting at a table in a street cafe watching a local "snake charmer" and his son
hypnotize deadly Cobras. The snakes were very poisonous and the father and son had to be very careful when handling them. They had been "charming snakes" to earn a living for many years now. As the three men sat in the market place sipping french wine they were surrounded by 15th Century Byzantine architecture. Suliman the great Arab had once crossed here in the 13th Century, and so had the Islamic Moors and Sarcerans. This was also one of the homes of ancient Coptic Christianity. On the north eastern part of the African continent is Egypt. The country with the 2000 year old giant Pyramids at Giza and the Sphinx located along the Nile river has the largest percent of it's population infected (14.5%) with the HCV virus today. Africa knows about viruses. Remember Ebola?

As the father and son snake charmers were finishing for the day Dr. Ehrlich noticed that the father was
attacked and bitten by a very large and poisonous Cobra. As the tourists from Europe ran over to the scene
of the incident someone in the crowd cried out, "Get a Doctor!". Knowing their friend was a Doctor, Degas and Zola offered Ehrlich for assistance. The hot Moroccan sun baked the market place as Ehrlich ran immediately into the swelling crowd of onlookers and promptly to the father's aid. As the large crowd parted Dr. Ehrlich was stunned by the father's reaction to the snake bite. The father had none! Upon further examination the Doctor noticed many old snake-bite wounds on the elder man's arms. The Doctor asked about the bites and the father replied that they had helped him become a snake charmer. His son does not have as many bites, the father continued to explain to Ehrlich, and so the son is not allowed to work with the larger and more deadly Cobras yet. Ehrlich postulates and formulates the theory of immunity within months and the science of Immunology was born! In Morocco, snake charmers can get bitten! Are you surprised to hear that?

Antigens and Antibodies are really very simple. An Antigen is any substance that when it gains entrance to the blood or tissues of the body, stimulates the production of Antibodies. Antibodies are defined as globulins
released by certain cells of the blood and tissues (example: the liver) into the blood in response to an
Antigenic stimulation. See! Easy! An Antigen is an instigator! Antigens are basically foreign material to the
body. It may be a splinter, Virus, or a molecule that your body does not recognize and can not identify any
longer. Cyroproteins are excess joined protein molecules that may be manufactured individually by the body
(at a construction site), or be part of a viral infection process. They attach and form a new unrecognizable
protein molecule.

We hear the phrase, "the virus encodes a polyprotein that is cleaved into four structural and six non-structual proteins". Structural proteins are just that! Building blocks for cell membranes (lipo-proteins) and antibodies. Non-structual proteins are "chemical" proteins. They are like chemists! They function by chemical reactions. To cleave means to chop. If too many of these foreign chopped materials float around the blood stream then the body will produce an Antigenic reaction to the materials. Any of these protein molecules may be used or not used by the body in molecular reactions. Viruses produce proteins that may or may not be used by the body. The body may utilize some, none, or all of the proteins produced. The excess unused proteins can cause an auto-immune reaction in the body.

Dr.Ehrlich spent many years working on and researching immunity after the snake charming incident in
Morocco. He worked on Soluable Proteins, also called immunoglobulins. His immunity theory ultimately proved slightly wrong, but he made many key advances that other researchers built their foundational knowledge and the scientific field of Immunology on. Science was much too young to fully understand chemical reactions at the time. The Atomic Age was still 40 years away. Quantum Physics is a theory and also the science that developed the Atom Bomb. Quantum Physics was developed and theorized by Max Planck in the 1930's. His Duality of Matter Theory enabled him to comprehend and develop his Quantum Physics Theory. The Atomic bombs of Hiroshima and Nagasaki were dropped on August 6th, 1945 and August 9th, 1945, respectively. Dr. Ehrlich was fifty years ahead of his time. We know today that proteins, different and similar, can bind to each other by attaching at certain sites or surface binding epitopes. These areas act like magnets attracting other oppositely charged magnets to them. Think of an epitope as a magnet!

When a protein is binded then it is in a straight jacket for life, unless someone has the key. Proteins can bind
to one another at epitopes by ionic bonding, covalent bonding, peptide bonding and other forms of molecular bonding and attachment. If your liver is attacked by a virus then the cells will produce lots of (Interferon) gamma globulin. Gamma is the cell's own cytoplasm producing an immune response. When the cell produces gamma it designates a group of ribosomes (construction sites) in the Smooth Endoplasmic Reticulum (SER - think of like an industrial park) of the cytoplasm of a liver cell to produce the antibodies to that antigen (HCV in our case). Once the infection is gone then the ribosome will remain in a dormant state and not produce Antibodies anymore. Think of this as the boss on vacation. The workers begin to goof off. If the boss comes back (reinfection) someone is going to pay with their DNA! The cells are warned!

However, if a lot of gamma proteins are produced in the cells then they may accumulate in numbers all around the body. Especially in joints and small blood vessels. They bind together by bonding loosely to each other. This commonly occurs in the hands and finger tips where the proteins in the small blood vessels are in close proximity to one another. The epitope magnets are attracted to each other and stick together. The body's Antibody response may be to destroy your gamma molecules. It can do this by attacking your liver cells as if "they" were the foreign material! This is also called an auto-immune Hepatitis response. The body attacks itself. A liver revolution! Viva la Hepatocyte! The Hepato- citizens turn on themselves and begin to murder each other and commit general mayhem throughout the organ! Let's quickly peek back into the infected liver cell and see how they are doing with the revolting HCV virus. As you can see the entire Hepatocyte interior has changed. Most construction projects (ribosome substrate sites in the industrial park) have been placed on hold or outright abandoned by the workers! You can tell they are working overtime by their lethargic appearance and harried activities. Notice that everyone is fighting over the scarce resources of building materials available to the cell. There is literally a "building boom" of Gamma molecules being constructed all around the cell. That yelling you hear over the loud speaker system is the Boss. The Boss is tough on the workers when virus infections occur in the cell. A virus infection is like a natural disaster, everyone pitches in for as long as it takes until the disaster is over with. "No breaks!" the Boss constantly encodes! The life of the cell is at stake now, he reminds the workers. We can see that at the Nucleus Headquarters it is very busy. Messenger workers are scurrying in and out of the building. The Headquarters is sending dozens of messengers to the individual construction sites located out here in the cytoplasm. The ribosome construction site here in the smooth
endoplasmic reticulum industrial park has loading zones on each outward side of the Ribo-site. There is only one loading zone per ribosome. But there are many, many ribosomes in the SER industrial park.

At the construction site the foreman takes the message and has an assistant call for the flat-bed trucks of
Amino Acid protein building blocks to arrive. The body uses 22 different types of amino Acids in order to
survive. Amino Acids are simply a sequence of three nucleic acids attached to each other with a sugar and
phosphate between them. The large flat-bed truck is backed into a loading zone and then docked into a loading bay (only one construction project per loading zone please). Messenger RNA workers empty the trucks of Amino Acids off the flat-beds and other workers assemble them to one another like a ladder. Energy is required by the workers and is supplied in the form of ATP (Adonine Tri- Phospate). Our workers need to eat in order to have energy. We will call the traveling lunch wagons, ATP vehicles. When the food is all eaten off the truck by the workers we will rename the empty energy truck, ADP (Adonine Di-Phosphate). A phosphate is lost during the energy transfer. Consider the phosphate to be the money or cost of the meal! The truck goes back to its warehouse in the Mitochondria.

The Ribosome workers are very busy creating a horizontal radio- like tower. They add to its length as each
truck unloads the Amino Acid contents and are then are assembled one after another. Assistant supervisors
at the loading bay know when to have the workers stop building one tower and begin to build another. Loading zone workers transport the tower away after construction. The tower is like a long chemical protein. If the tower had places for hooks or other attachments we would call those areas epitopes or surface attachment sites!

If two towers get attached to each other by mistake, anywhere in the body, we would then refer to them
together as a "cyroprotein". If a bunch of towers get caught in your minute fingertip capillaries then they will
not only cause pain and swelling to occur but you will also begin to develop an auto-immune response (lets
call it a Law suit). Your body will file a "notice of intent" and begin legal immunity actions against the maker
of that tower! - Your liver cell! The hepatocyte will be sued by the body! (Hepatocyte versus the State). A Body
Product liability case, I suppose. This is what happens if you are given "immunity". You will not have to worry
about liver law suits! (blink, blink).

The plans to assemble the towers come partly from the foreign material invaders themselves. Blood police
always cruise the body. When they see trouble they call it in! A scout cell goes to investigate. The scout (a
small WBC) tries to gain as much information about the invader as possible. Also to subdue it, if possible.
Other spy cells (different WBC's) get the secret information and have it mailed to the hepatocyte The mailman
delivers the message to the exterior wall of the liver cell and secretly rings twice. A special delivery messenger carries the "secretly encoded" message through the cell wall and gives it to a speedy cytoplasm messenger. The messenger speeds quickly to the Headquarters (nucleus) and to the back room where the Boss' office is. The Boss (DNA Genome) "decodes" the encrypted message and orders an immediate immune response! From the many contingency plans that have been stored in the DNA, that has been accumulated over four billion years, the Boss decides which plan to use. The Genome Boss orders a specific Antigenic-Antibody response, right or wrong! Immunologic, or auto-immune, or both. HCV can trigger either response or both responses. It will always trigger an immunologic response. That is why HCV persons are tested for Antigens and Antibodies.

The Boss' contingency plans are then taken to a ribosome construction site foreman. He instructs the workers to have the blue prints expressed, encoded or built to specifications. Quality control is a must! This particular ribosome is a Gamma Globulin construction site. Sometimes a virus infects the liver cell cytoplasm itself. If an unruly gang of HCV viruses cause trouble at a lot of construction sites then the workers will be harassed off the job (union rules, sorry!). and the HCV gang viruses will continue their destructive ways with impunity. Once destroyed the liver cell dies and the walls turn hard with fibrotic collagen tissue. The gang will continue to vandalize any site they can, including the abandoned ones. Some times they take over an abandoned site and make their own arsenal of weapons. This is what Adenovirus helps HBV do!

The Genome Boss is like a Civil War General that can watch his troops in battle from the top of a hill but can
only send written communications to direct the battle. By the time the message gets there, if it is not lost or
intercepted along the way, the battle may have already occurred and quite possibly be lost. The Boss can see
the immense trouble out in the cell's cytoplasm but must stay inside and direct the battle. They can only send
sectional copies of the original blueprint itself to the foreman. By the time the forces and resources are
mustered for battle it may very well be much too late.

Back at the loading dock, assistant supervisors direct the unloading of flat-beds and other assistants direct
the detachment of the cabs from the flatbed trucks as they arrive. The cabs are lined up by special peptide-
bond drivers that connect the cabs in a row like a commuter train. The many connected cabs wind their way
around the loading zone area and beyond in single file. After so many cabs are hooked up in line to one
another a different assistant supervisor has workers begin to form a new line of cabs. The towers go one way
and the line of truck cabs goes the other. The empty flat beds are hauled away by different transport molecules to be re-used. As you can see this is a very busy site. There are hundreds like them throughout just one cell. There are tens-of-thousands of cells in the liver. The liver is a very busy place.

The constructed tower is like a "non-structual protein". It maybe used as an enzyme to facilitate (speed up)
a chemical reaction or it may be used as a molecular transport carrier. It may also be used as an Antibody to
bind to surface epitopes of antigens, thereby making it inert, or not harmful any longer to the body. Surface
epitopes may attach to each other creating new structural molecules. Just like two mistakenly hooked towers
would create a double tower molecule. The body may also attack the new molecule as being foreign. The line
of cabs are like "structural proteins" that are used to build things, like Antibodies. or other structures.

Since the original foreign material was encoded (by the scout) and then encoded back into a secret message
and mailed, the Antibody's binding epitopes reflect this initial scouting. The result is an exact mirror image
of it's antigenic companion (the invader's identification is now known and the proper contingency plans may
be used.). Some Antibodies are so close in common epitope positioning along the protein molecule that they
can be fooled into being used for other purposes. Fooled epitopes are useful in medical vaccinations. The
single vaccination used for the thousands of different pox viruses is a good example of fooled epitopes being used in medicine today. HCV vaccinations in the future may include "oglio-nucleotides" (a long string of nucleotides with epitopes) that take advantage of fooled epitopes on the virus. Syphilis was once considered unstoppable, until Ehrlich's wife began to clean up, that is!

When HCV comes into the liver cell it unwinds it's RNA coil, separates itself and begins to encode on both
open halves of the zipper. Eventually, there is one long polyprotein and one replicating virus! The envelope
protein that the virus was delivered to the cell in was considered to be a foreign body by your immune system and blood police that first called it in. The envelope is not used for anything that is known about, but it creates an immune response anyway. That means a construction site has to stop building what it is constructing and must begin to build Gamma Antibodies for this surface Antigen (of the envelope protein).
The RNA virus itself is called the "core". It contains the blueprints for destruction of your liver cell. It too is
considered foreign (the core) by the body. Antibodies for it must also be manufactured. The polyprotein (many proteins attached in a line) is cleaved (broken) into four "structural" and six "non-structual" proteins. Each of these is also considered a foreign body. This is why we hear about "envelope surface Antigens" and
Antibodies, and all about core antibodies and protein Antigens. Serological testing looks for these in you
blood. If they find them, you are positive for HCV!

Not all of the structural and non-structual proteins are fully understood yet in HCV. This is where the future
research is much needed. The fact that there are so many parts of the virus considered to be foreign materials makes it very difficult for the body's immune system to constantly fight them off. Now, compound that with a constantly changing "wild-type " virus! If the virus initially mutates into six separate genomic sequences then you have six totally different viruses. Each virus needs over ten separate Antibody responses per virus and in due time the body just can not keep up without suffering debilitating physical effects to itself. The fact that the virus is changing is what will harm HCV patients.

The immune system can not stay on top of an ever changing virus and all it's sub-parts. When you are tested
for HCV some of the blood serology tests (ELISA and RIBA) that your Doctor ordered confirm the viruses
presence by verifying surface Antigens and/or core Antibodies. You would not have the Antibody if you did
not have the immune response necessary that came from a specific Antigen or foreign material like the HCV
RNA virus. You test positive because you have the virus or gene sequences (fragments) of the virus and the
related Antibodies and Antigens. Remember, Antigens are any foreign body that stimulates an Antibody
response. HCV is a foreign body!

The snake charmer had built up an immunity to the snake's poison over the years. That is why this Chapter
is called Immunology and Poisonous Snakes!