Hi! All:
    The following article was nspired by Joan Snyder.  I also have used some
of her sentences and phrases in this article.  I thank her profusely for her
honesty and for letting me use her  catchy phrases generously in this
article.
    I hope you enjoy reading this article and find it useful.
    Raj
[log in to unmask]
 PS: I had to split this into two parts to be accepted by the Parkinsons
list serve.
**************

                    STEM CELLS AND CLONING: FACT AND FICTION - YOU BE THE
JUDGE


Dr. R. Rajaraman

      "Out there on the political arena," lines have been drawn on the
battleground, "sides have been taken" for and against research on stem cells
and cloning, arguments have been put forward, "rounds after rounds have been
fired, and causalities sustained by both sides."  However, in my view,
everything is still obscured by a thick veil of smoke that fills the air and
the public is all but confused as to what is going on.  In this atmosphere
of confusion and misconception, it is almost impossible for the public to
think straight and contribute meaningfully to the ongoing dialogue on this
important issue.  A good appreciation of the concepts and the controversies
surrounding the issues by well-informed public is necessary for a rational
and balanced outcome of these deliberations, because it is their future well
being that will be affected by the decisions that are being hastily made on
these issues today both by the governments of the United States of America
and Canada.  The reasons for this confusion, and the resulting condemnation
of stem cell research outright as an act of crime against humanity are the
misperception and misinterpretation of the language, thoughtless statements
by some overzealous publicity-seeking, irresponsible scientists, and the
media hype and frenzy that has been built around the words "cloning" and
"stem cells" - words that ignite and incite fierce and fervent  reactions
from both the pro-life and the pro-stem cell camps.  In this article, I
attempt to clarify some confusions, and put in perspective the different
terms, what does them really mean, what can they do for us, what can we do
with them, why they are important, and how we move forward from this
stalemate for the betterment of humanity.

 I am a 69-year-old father of two sons, and a grand father if three smart
kids, and live in Halifax, NS. , Canada.  I am a Hindu hailing from South
India and living in North America since 1965.  I am a retired professor and
my field of specialization is cancer cell biology.  The community of
Parkinson's Disease (PD) knows me to some extent.  I am suffering from two
kinds of movement disorders, i.e., Essential Tremor (ET) characterized by
action tremor and PD characterized by resting tremor for the past 40 years
and of late my symptoms of PD have become more pronounced.  Even though I
realize now in hindsight that I have been having some symptoms of PD since
my early thirties, I was diagnosed with PD only about four years ago.  The
news threw me into a state of shock and I promptly went into a denial phase
that lasted for almost a year.  I could have simply accepted the verdict and
take the drugs prescribed for me and disappear in thin air, forgotten by the
community and the society at large and accept what the fate would throw at
me.  But, I decided to get a second opinion for my diagnosis, which led me
to some unpleasant experience.  Therefore, I decided to learn everything
that I possibly can about this disease that creeps on you slowly but surely.
I have now learned to "act like a tiger and think like a fox" in order to
survive the disease and enjoy life at the same time.

WHAT IS PARKINSON'S DISEASE?
  What I found out about the ravages of the PD and the problems caused by
current treatments available for PD were not very encouraging at all.  PD is
a neurodegenerative disease affecting 2% of the people above 60 years old.
However, this disease also affects people in the very young age, often as
early as the 20s and thirties, crippling the useful life span of most of
these patients.  About 10% of PD patients fall in this category.  PD
patients experience progressively reduced capacity to move, rigidity of the
hands and legs, tremors, loss of a voice, speech impediment, loss of
postural instability, inability to swallow, loss of sleep and regularity,
inability to write, and eventually become a vegetable and a burden to
themselves, their family and the society.  PD is caused by progressive
degeneration of neurons that produce a chemical called dopamine, which is
important for movement and the maintenance of the overall normal affairs of
our nervous system, which is taking care of important functions like
movement of muscle involved in smiling, speaking, swallowing, writing,
walking, maintaining a vertical posture, blood pressure etc.  We still do
not know what causes the degeneration of these neurons.  It could be a
repercussion of some post-viral infection phenomenon, environmental toxins,
in addition to genetic susceptibility.  Most disturbingly, there is
currently no consensus of opinion if it is one disease with a variation or
two different diseases, when one develops PD symptoms on top of the chronic
symptoms of ET.   At present, there is no cure for PD.  Most of the drugs
for PD have only temporary symptomatic relief (lasting for about 3 hours)
and have their own unwanted side effects in the long run.  And in some
unfortunate individuals,  these drugs don't have even that transient
beneficial effect and they are slowly progressing toward a miserable life
with no body movement, not being able to swallow or even to talk, especially
in their old age.   One has the last resort of a radical Deep Brain Surgery
(DBS) (literally boring holes in the brain to implant electrodes deep in the
center of the brain), which sounds almost barbaric, nevertheless scientific,
is risky and highly expensive (around US$ 60,000) and even then, there is no
guarantee that the problems will be solved.

 One of the major hopes for people like us relies on the future discoveries
based on stem cell research.  If the current trend of blindly condemning all
types of stem cell research continues, you will be condemning all of us to a
slow and miserable death.   "PD slowly robs its victims of the ability to
move properly and eventually we won't be able to move at all.  About 30% of
us develop dementia, we are three times more likely to develop Alzheimer's
and we cannot speak well or swallow our food.  We have to take about 25
pills / day costing about $12,000 or more / year, yet have increasing
difficulty controlling the problems.  These medications do nothing to slow
down the progression of the disease."  Some that do, have extreme side
effects and one would wonder which is worse: to suffer through the ravages
of the disease or the side effects of the drug.  "In time these drugs fail
us and will leave us totally disabled.  We will leave this (active) world
and enter into a twilight world of immobility, encased in our bodies as in
tombs, able to think but not speak, understand but not able to communicate.
Death will inevitably follow, and by then it may not be unwelcome."

          I cannot overemphasize the importance of looking at the issues and
facts on stem cells and cloning with a clear understanding of the
consequences of our actions we take today.  It would become apparent that
medical research has finally given us a ray of hope in stem cell research,
which has the potential to ultimately give us a unique opportunity, without
compromising our religious beliefs, and moral and ethical responsibilities,
to be able give reassurance to several thousands of our fellow PWPs (People
With Parkinson's).  We have gotten to know them in person or through the
internet, looking at them as if living in a parallel universe, watching our
slow downward progression, sharing our emotions and fears, and seeking
strength, consolation, and companionship in our daily efforts to find the
meaning of life.  It is thought that PD is one of the first diseases to be
amenable for stem cell-mediated regenerative therapy.  We know the specific
neuronal cell type whose loss causes this disease.  Several laboratories
have successfully produced dopamine-synthesizing neuronal cells fro
embryonic stem cells.  After introducing a gene Nurr1 into mouse embryo stem
cells, and transplanting these cells into the rat brain, they differentiated
into dopamine producing neuronal cells, that resulted in the alleviation of
PD symptoms.  A number of strategies are in development to convert human
stem cells into dopamine producing neurons.  Stem cell research, if allowed
to continue without impediments and supported by ample funding, has the
potential to bring into reality the field of regenerative medicine within
the next decade or two.   In addition to PD, the concept of regenerative
medicine has the promise and potential to cure to various defects and
ailments including aging, cancer, diabetes, stroke, heart attack, spinal
cord injuries, autoimmune diseases, developmental defects, and several
degenerative diseases such as Alzheimer's, and other pathological conditions
as well for being useful in screening new drugs, toxins, and in
understanding and correcting birth defects, just to mention a few.  Thus the
impressive and highly promising potential of therapeutic stem cell research
is likely to benefit not only the PD patients, but more than 75% of humanity
at large.

  Without understanding the difference between what these words really mean
and what they are perceived to mean, the policy makers and the public run
the risk of curtailing research that looks highly promising to lead to
effective treatments and even cures for various debilitating diseases, for
which there is no cure available currently.  Let us look at the so called
scary words, why are they scary and what do they really mean.


CLONING:
 Cloning is the process of making several copies of a molecule, a cell or an
organism.  The process of cloning is very common, when you culture cells for
studying different aspects of a population of cells.  It would make sense to
study, for example, the biochemical properties of a normal and a tumor cell.
One may want to have identical cells in each cell population for comparative
studies.  Thus, cloning is a procedure very useful for 'manufacturing' large
population of identical cells.

 These principles and procedures have attained high economic importance in
the field of plant propagation.  One can clone a plant with any desired
property, e.g., beautiful flowers, fragrance, a new mutant variety that
cannot be sexually reproduced, high yields of a given crop, disease
resistance  etc.,  by culturing individual cells and raising the whole plant
from a single cell in a test tube and potting the individual plants
separately after it reaches a healthy stage in a culture flask.

 When molecular biology bloomed as a separate science in the past two
decades,  people made several copies of a piece of DNA containing a gene,
and thus molecular cloning became a very powerful tool in the study of the
function of gene products.   All types of genes that are responsible for the
growth of cancer and genes that inhibit growth of cancer have been cloned
for various diagnostic, prognostic and therapeutic purposes.  Similarly,
studies of genes that have undergone changes (mutations) causing various
diseases are being cloned in order to understand their modes of action by
themselves or their interaction with other gene products.  These studies
form the basic tenet of modern molecular medicine.
 Cloning organisms is also not new.  In the late 1800's, Hans Dreish created
the first cloned sea urchins, by taking the developing embryo and splitting
it into two halves, forming two identical sea urchins.  This is what happens
accidentally in humans that results in what we call identical maternal
twins.  In 1914, Hans Spemann showed that the nucleus from a 16 cell newt
embryo, when placed into a fresh enucleated egg, developed into an adult
newt.  This probably was the first nuclear transplantation experiment that
resulted in a cloned organism.  However, the nucleus in this case  also
comes from an embryonic cell, much different from the current technology of
adult somatic cell nuclear transplantation or SCNT (see below).  In the
early 1950s, Dr. F.C. Steward of Cornell University cloned thousands of
carrot plants.  Since then, carrots, tomatoes, fruit flies, and numerous
other plants and  animals have been cloned.   However, in the year 1963, Dr.
J.B.S. Haldane introduced the word 'clone' for the processes of making
identical copies of organisms. In 1993, Dr. Jerry Hall and Dr. Robert
Stillman starting with seventeen 2- 8- cell stage human embryos produced 48
different human embryos.  This saw the beginning of ethical challenge to
such studies.  In 1996, Dr. Ian Wilmut in Scotland produced the first closed
mammal, Dolly, by adult nucleus transplantation into an egg from which the
nucleus has been previously removed (SCNT).  One would think that nobody in
the right mind would even attempt at cloning humans, let alone claiming they
have done it.  Think again!  On Aug 7, 2001 came the irresponsible
announcements of Dr. Panos Zavos of Kentucky and Dr. Severino Antinori of
Italy that they plan to impregnate 200 women volunteers with cloned human
embryos by November, 2001.  Dr. Richard Seed, a physicist, wanted to
establish a laboratory solely for the purpose of cloning humans.  Time
magazine (Feb 19, 2001) sensationalized the issue by stating,  "Human
cloning is closer than you think!"  To make things worse, we are all aware
of the recent claims by the Bahamas-based company called Clonaid that they
have successfully cloned human babies, without producing any evidence.  I
agree, "Human lives, souls and dignity are at stake!" if we do not do
anything about this issue.

 Apart from the ethical and moral aspects of the issue, technologically it
is not feasible as yet to safely clone human beings.  It was recently
reported that for every successful animal clone, there have been about 300
fetal deaths.  Fetal casualties of this order will be almost certain to
happen when anybody attempts at cloning humans with the current technology
and, for sure, these deaths would be equivalent to cold-blooded murder.  In
addition, other issues including genetic (e.g., telomere erosion - the lost
of a small piece of DNA from the end of chromosomes when we age) and
epigenetic modifications (e.g. imprinting, changes in the gene expression
pattern (not gene mutation) that are induced permanently during development)
occur in the embryos by  handling procedures and other unknown factors, have
not yet been understood.  Irrespective of the technical feasibility, simply
based on the moral and ethical reasons, human reproductive cloning should be
permanently banned forthwith.

STEM CELLS:
 Stem cells have the unique potential to maintain themselves without
undergoing any genetic change and they also can differentiate into different
cell types that are found in our body.  They can be classified into two
different types based on their origin from the embryo or from adult tissues.
(Please see www.nih.gov/new/stemcell/primer.htm for additional info.)

       The Embryonic Stem cells or ES cells are obtained from the inner mass
cells at the 4-5 day old developing embryonic stage called the "blastocyst"
(a spherical early embryonic stage with  central mass of 30 embryonic cells
enclosed within spherical envelope of a single layer of cells; for a nice
picture of blastocyst check at
www.advancedfertility.com/blastocystimages.htm ). ES cells are the
undifferentiated, embryonic cells, which have the potential to multiply into
two cells, of which one daughter cell will be destined to maintain
population of stem cells by further division without undergoing any changes,
while the other daughter cell can multiply with the potential to
differentiate into different type of cells in our body, e.g., skin cells,
brain cells, heart cells, pancreatic cell, blood cell etc., if given the
right kind of stimulus from the microenvironment.  For this reason, these
are called pluripotent stem cells, meaning they can differentiate into any
type of cells given the right stimulus.  For example, the human body has at
least about 200 different types of cells, just as many different kinds of
cancers, we know, the humans can suffer from.  All these different types of
mature or fully differentiated cells in the adult human body, have been
derived from these stem cells.  Therefore, they provide a potential source
of different tissue and cell types for replacement in diseases caused by
non-functional or destroyed native cell types.  Simplest procedure to
culture pluripotent stem cells is to extract them from the early embryo
before these cells start their journey towards differentiation into
different cell types.  Thus, the early embryo possesses truly pluripotent
cells that can give rise to all cell types present in the embryo and the
adult.
        (CONTINUED IN PART II)

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