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Hunting for Genetic Mutations and Cancer
The current paradigm in medical research holds that the cause of most
cancers is a genetic mutation. For instance, according to the National
Human Genome Research Institute (NHGRI), an institute at the NIH, "all
cancers are based on genetic mutations in body cells." In fact,
mutation hunting is big business. Just look at the NIH budget allocated
to discoveries of genetic mutations, the number of biotech companies
chasing genetic mutations, the magnitude of the licensing agreements
between biotech and pharmaceutical companies aimed to utilize newly
discovered genetic mutations, and the number of stories in the media on
genetic mutations and their so-called "link" to disease. However, this huge effort and billions of dollars has produced few discoveries and little benefits to the public. The reason for this limited success is simple. The cause of cancer is not a genetic mutation.
The story of the BRCA1 gene is a typical example of mutation hunting.
The Mystery of BRCA1
Genes, in general, produce proteins, which are the building blocks of
cells. The concentration of the protein is tightly regulated. A mutated
gene produces an abnormal concentration of its protein, which may lead
to disease. In 1994, Mark Skolnick, PhD, discovered the BRCA1 gene
(BRCA1 is short for BReast CAncer 1). Following the discovery,
scientists observed an abnormally low level of the BRCA1 protein in
breast cancer tissues. The BRCA1 protein is a cell cycle suppressor,
which means that the protein prevents cell replication. This
observation created a lot of excitement. At the time, scientists
believed that they were on the verge of finding the cause of breast
cancer. The reasoning was that breast cancer patients must have a
mutated BRCA1 gene, which would explain the decreased production of the
protein, and the excessive replication of breast cancer cells in tumors.
In the United States, 180,000 cases of breast cancer are diagnosed each
year. However, the BRCA1 gene is mutated in less than 5% of these
cases. In more than 95% of breast cancer patients the gene is not mutated.
So here is the mystery. If the gene is not mutated in the great
majority of the breast cancer patients, why are the tumors showing low
levels of the BRCA1 protein? Today, this is one of the biggest
mysteries in cancer research.
The BRCA1 gene is not unique. Many normal (non-mutated) genes exhibit a
mysterious abnormal (increased or decreased) production of proteins in
cancer. Moreover, studies also report abnormal gene expression of
normal genes in other diseases, such as atherosclerosis, obesity,
osteoarthritis, type II diabetes, alopecia, type I diabetes, multiple
sclerosis, asthma, lupus, thyroiditis, inflammatory bowel disease,
rheumatoid arthritis, psoriasis, atopic dermatitis, and graft versus
host disease.
The Discovery
A virus is a collection of genes. To replicate, some viruses settle in
the nucleus of the host cell and use the cell machinery to replicate.
What is the effect of a viral gene on the production of cellular
proteins?
Think of a gene as an assembly line of a protein. Like all assembly
lines, the gene has two parts, a conveyor (the gene coding section),
and a control panel (the gene promoter/enhancer). Imagine a cellular
shop that assembles a product called BRCA1. One of the many buttons on
the control panel is called N-box. Pressing the button increases
production. However, only a small number of operators (called
transcription factors), those who pass a special certification (called
the p300 test), have permission to press this button. What happens when
a virus opens a shop across the street from the cellular shop (called
latent infection) to produce its viral products? The control panel in
the viral shop also has an N-box button. To start production, the virus
begins to hire away some of the certified operators. What is the effect
of this "hiring away" on the number of available BRCA1 units? The
number decreases. Moreover, the decrease becomes apparent even before
the virus starts production (the "hiring away" is what creates the
effect, not the viral proteins). The viral assembly line competes with
the BRCA1 assembly line for the certified operators, and by hiring them
away prevents the cellular shop from producing the optimum, or
"healthy" number of BRCA1 units. The lower number of BRCA1 units leads
to excessive cell replication and breast cancer. (See a more technical
description in a recent paper published in the European Journal of
Cancer.)
The infection with the latent virus causes abnormal production of other
genes, and as a result, the development of other chronic diseases. This
sequence of events easily explains why people who suffer from obesity
are also more likely to suffer from diabetes, cancer, and heart
disease, and why a recent large scale study found that a low-fat diet
does not protect against breast cancer. It also explains another
surprising observation that male pattern baldness is associated with
heart disease and prostate cancer. In general, this sequence of events
easily explains the numerous observations indicating a co-existence or
co-morbidity of some chronic diseases.
This discovery was first described by Dr. Hanan Polansky in his book,
Microcompetition with Foreign DNA and the Origin of Chronic Disease,
published by The Center for the Biology of Chronic Disease.
To summarize: the cause of cancer, and other chronic diseases, is not a
genetic mutation, it's an infection with a latent virus.
Reaction of the Scientific Community
What is the scientific community saying about Dr. Polansky's discovery?
Consider what the famous heart surgeon and "Living Legend," Michael E.
DeBakey, said about the discovery, "The theory underlying the basic
concept concerning the origin of chronic diseases presented by Dr.
Polansky is most interesting, indeed fascinating … Perhaps a symposium
could be held to provide a forum for further discussions and critiques
of this fascinating theory."
Elena N. Naumova, PhD, Associate Professor, Department of Family
Medicine and Community Health, Tufts University School of Medicine,
said, "Dr. Polansky's work compellingly demonstrates a framework that
could bring together researchers from different fields. His proposed
theory will work its magic by clarifying ambiguous definitions,
identifying similarities and differences in various biological
processes, and discovering new pathways … I believe that Dr. Polansky's
book will catalyze the scientific learning process, promote
interdisciplinary cross-fertilization, stimulate development of
treatment strategies and drug discovery, and leave the reader
inspired."
Sivasubramanian Baskar, PhD, Senior Scientist from the National Cancer
Institute, NIH, said, "At first, I wish to congratulate Dr. Hanan
Polansky for his scientific bravery to take such a unique, novel
approach to further stimulate our understanding of the origin and
establishment of chronic diseases. The philosophy underscored is an
excellent one ... The amazing correlation between theoretical
predictions and observed in vivo effects seems to bring us a step
closer to a deeper understanding of such complex biologic processes."
Marc Pouliot, PhD, Assistant Professor, Department of Anatomy and
Physiology, Faculty of Medicine, Université Laval, Canada, said, "The
concept of microcompetition will change our approach in the study of
chronic diseases and will furthermore give scientists a higher level of
understanding in biology. Presentation of this concept undoubtedly
provides a new set of opportunities for attacking chronic diseases …
They lead the way to new approaches in chronic disease treatment."
Howard A. Young, PhD, Section Head, Cellular and Molecular Immunology
Section, Laboratory of Experimental Immunology, National Cancer
Institute, NIH, said, "In summary, Dr. Polansky is to be applauded for
his attempt to provide a unifying basis for chronic diseases. His
theories are stimulating and offer a basis for experimental testing and
possible treatment."
Michael J. Gonzalez, PhD, Professor, Medical Sciences, University of
Puerto Rico, said, "I know this book will profoundly impact medical
research, drug discovery, as well as natural therapies. I also believe
it will benefit the scientific community and society in general by
providing further means of treatment for conditions in which only
palliative care is available."
You can find more reactions and the biographies the scientists reacting
to Dr. Polansky's discovery on the publisher's (see link below).
Hope for Cure and Protection
The significance of Dr. Polansky's discovery cannot be overstated. For
the first time, we can start to feel a little better about these
diseases. With his discovery, pharmaceutical and biotech companies can
now start to design medications that will target the cause of the
disease rather than its symptoms, and therefore, cure the sick and
protect the healthy from these deadly diseases. |