Panama Story-Chapter 3
Chapter 3

SERENDIPITY -"Oh no! What have we done?"
 

In this Chapter you are a young Doctor that has begun to specialize in a new field of Medicine:
Molecular Hepatology.


In the fall of 1969 you receive the letter that you have been waiting for as a young Doctor. Your appointment
to your first position is one of the finest that anyone could ask for. You ranked second in your class at Yale,
and have been identified as a person that will go places one day. The offer comes in the form of an unofficial
phone call, followed 2 days later by a certified letter. Your first job will be to do research at John Hopkins
University, located in Baltimore, Maryland. You will begin your work in January of 1970. John Hopkins is one
of the finest Ivy league schools in the nation. Your parents are very proud of you, and your siblings boast about you to their friends. You are assigned to the Molecular Hepatology Laboratory under the guidance of a world famous Professor. You are augmented with four other researchers, in various stages of their career, and you spend 6 months with them studying the "Transmembrane potential" of Hepatocytes (liver Cells). You are chosen to publish the researched data and the correlating interpretation of that data. You write the article for the Professional Pathology Journal. Your stellar career is on its way.

Hepatitis A, is discovered and named in 1967 by the future head of the Hepatitis C Branch, Dr. Robert Purcell.
Hepatitis B is discovered by Dr. Howard J. Worman, around the same time, now at Columbia University's
Division of Gastroenterology, New York City. Hepatitis C, has yet to be discovered. However, researchers start to notice that rates of hepatitis infection begin to rise. They can not determine what it is. There are tests for A and B but, not as yet for Hepatitis C. The virus is passed from community to community. Blood banking
procedures are refined so that antigens to Hepatitis can be detected with assays, or tests. Except, there are
no tests to determine antigens for Hepatitis C. The changing virus is allowed to proliferate within the nation's
pooled blood supply.

Much emphasis is placed on detecting viral, or the Hepatitis B virus (HBV). By 1972, researchers around the
world begin to report that the HBV virus is changing or "mutating". Actually, what they see are the surface
antigens for HCV but only a few realize this, and nothing is done. Advances are made in Cancer and Heart
research, Hepatitis is left for another day. We as Americans seem to be able to deal with only one major issue
each decade regarding major diseases. In the 1960's Cancer Research began. The 1970's brought us Heart
Research and of course the 1980's was the decade of AIDS (HIV). I suppose we can consider this, the 1990's,
the decade for Hepatitis Research.

After you publish your first article of research, you begin to study hepatitis at John Hopkins. By 1974 you are
asked to write an article for the Journal of American Medicine (JAMA) relating to the "Transmission of Hepatitis by Dentists". Your career moves forward swiftly at this point due to the increased science funding throughout the nation's great research institutions and your ability to "out think" your colleagues.. You study the Transmission of hepatitis in a family and also dabble in mercury poisoning, because of its toxic efforts on the human liver. Liver cancer rates have begun to climb and your field is wide open for your ascension to the top.

You are on the forefront of history and are considered to be the avant-guard (leading edge) of your field. You spend the next 4 years studying Hepatitis B and its side effects. You study arthritis, iron levels, Predisone therapy, Immune globulins (IgG, IgM and IgA) and the effects of insulin and gylcogen on murine (mice) hepatitis. You begin to study the damaging effects of small blood vessel "cryoproteins". These are important because when the liver is infected (hepatitis) the cells produce globulins, as a defense. When too many globulins circulate in the blood, they tend to attach to each other through "site attachments" . The complex molecules (globulins) are in close proximity when in the smaller blood vessels and hence, tend to attach more readily there. The body does not recognize the "new" complex and begins to develop an auto-immune response. The body is basically turning on itself! You publish your findings' in the Journal of Gastroenterology. You are offered a full Professorship at Yale and decide to move your research and your family there.

It is 1978.

For 33 years the newly formed Hepatitis C virus emerges as a highly variable and unstable RNA sequence. In
fact, it is so unstable that it initially mutates six separate genotypes from its inception within twenty years.
Each mutated genotype has "sub types", and "Quasi species", that make the HCV family tree branch more like
a bush than a tree. By 1998 it will be estimated that at least 80 separate subtypes are known to exists, along
with hundreds of "variants" of these subtypes. In plan language, the virus is changing faster than it should
under "natural selection pressures". Natural selection, first described by Charles Darwin in 1859, are thought
to be the driving force behind evolution. Why was HCV changing rapidly? And into what? At some point in
evolution the branches of the tree become so far apart that they create a whole new classification, be it plant
or animal. Our original serum had changed over the first twenty years, but with the addition of Adenoviruses
in military persons, evolutionary forces were now accelerated. Some young military persons, at this time,
frequented tattoo parlors and also experimented with intravenous drug use. The original HBV traveled with the military because of this. These we would call epidemiological factors (epidemiology = the study of: origin and the distribution of disease). Blood transfusions and medical procedures in military hospitals contributed to the exponential growth of the virus within the general population's blood supply. Tests were just now (1978) being developed to detect "NANB" in the blood supply.

Eleven years will pass before the proper screening procedures are put in place protecting the blood supply.
The American Century is slipping slowly away, and is three quarters over already. The US and the Soviet Union stare across the border in Germany for another 10 years before the best minds in Science are directed to Medical Research, versus "The Arms Race".

At Yale, you are able to continue your work researching Hepatitis B and its chronic effects on the liver. You
are considered to be one of the brightest minds associated with molecular Hepatology. You continue to study Antigens, cryoproteins and another manifestation of them called, Urticaria (similar to the hives). You move, and build with your research, through; Chronic Active Hepatitis, Cutaneous Vasculitis (rashes), and in 1981 you begin to study the newly emerging field of "Genetics". You combine your knowledge of the liver, Hepatitis and now DNA. You are in a position to begin to figure out the Hepatitis C Virus.(HCV).

By spring of 1982 you are offered a fellowship at the National Academy of Sciences, which you eagerly accept!
You publish in the prestigious LANCET magazine an article concerning "Aboriginal exposure to HBV". You
and a group of research scientist conclude that 51% of the population had been previously exposed to HBV.
It is not determined how this exposure occurred. Your studies continue with: Hepatitis in the Elderly, Induced
Liver Tumors in Mice, and then go on to "Monoclonal" and eventually, "Polyclonal" Antibodies. By 1983 you
write an editorial for the newly formed Hepatology Journal, titled; Non-A, Non-B. In 1984 you write that HBV
has "classic subtypes", and an article concerning the detection of HBV "hidden" antigens. You write in 1985,
in the New England Journal of Medicine, about "replicative forms" of HBV DNA, and about a "closely related
virus". You use terms like "high frequency" when describing this new virus. A colleague of yours, from the
other side of the planet, writes in the Journal of Medical Virology, an article about NANB being "possibly
related to, but distinct variants of HBV". This motivates you to write the following month in the Clinical
Microbiology Journal, "Newly Identified HBV Strains", and the following year admitting that "HBV has more
heterogeneity than thought". All you can think of is, "Oh no! What have we done?".

The world strains of HBV are identified and classified either as an "ady", or "ayw" by 1986.

Today, it is well known that there are many subspecies to each "HBV variant". Mother Nature will just Not sit
still! And neither will the mutating Yellow Fever Virus! The "replicative defective", co-dependent, Hepatitis D
virus (HDV, or Delta Virus) has already come from HBV! Ah.....but that's another story!
 



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