Dowling
College
ASC
128 Ethics in the New Genetic Era
Jennifer
Bush
Genetic Therapy
It
is the stuff of science fiction: tailor-made babies with exceptional
intelligence and any other qualities we choose. How close are we to this
reality? The Human Genome Project is well under way in its endeavor to map out
all the genes that comprise the human body.
Genetic knowledge is indeed rapidly expanding, but most research centers
around understanding the content and function of the human genome; less applies
to the manipulation of human genetic material.
Scientists know much more than ever before about our genes. We have successfully cloned animals;
invoking images of a future society of cloned human beings. We have also used this increased knowledge
to research the possibilities of using genes to cure disease such as cystic
fibrosis, cancer and AIDS. The attempt
to find cures for these diseases using genetic therapy is well underway.
The first step to understanding what gene therapy
is and how it works is in truly understanding exactly what genes are and what
they do. Genes are tiny, invisible
packets of biochemical information (DNA) that direct how our bodies develop and
function. We all inherit tens of
thousands of genes from our parents, arranged on 46 chromosomes. Genes turn on and off to control our growth,
body chemistry and even the color of our hair and eyes. An individual gene in the human cell is a
stretch of DNA that, in most cases, acts as a blueprint for making a specific
protein; it spells out the sequence of amino acids composing that protein”. All
cells in a body carry the same genes in the chromosomes of the nucleus.
Different cells use, or express, different subsets of genes and therefore make
separate sets of proteins.
Most genes work correctly, but some do not.
Sometimes they change and begin to work
poorly or not at all. Changes can be caused by radiation or certain chemicals,
or by unexplained accidents within our cells which are beyond are immediate
physical control. Certain diseases are
caused by faulty genes which produce defective proteins. The symptoms of genetic disease are the
result of subsequent disrupted vital cell processes caused by missing or
defective proteins. If a particular
gene is defective, its protein product may not be made at all, may work poorly
or may behave too aggressively. In any
case, the flaw may disturb vital functions of cells and tissues that use the
normal gene product. This is the recipe
for cell abnormality which can thereby cause symptoms of disease.
ADA deficiency is a rare genetic disease. The
normal ADA gene produces an enzyme called adenosine deaminase that is essential
for effective immune system function. Patients with ADA deficiency have no
intact copies of this gene, and their defective copies do not produce
functional ADA. ADA-deficient children
are born with severe immunodeficiency and are prone to repeated serious
infections. Even the most minor viral illness may pose a dire threat. Many of these children are forced to live
their lives in enclosures that protect them from the many viruses that lurk in
the outside world. This is why the
disease if often referred to as the bubble boy syndrome. If untreated, the disease often results in
death within the first years of life.
Another genetic disease is Cystic Fibrosis. It is caused by a missing or mutated gene
that results in a defective cell membrane transport protein. This ultimately results in a build-up of
thick mucus in the lungs and the body's airways causing chronic respiratory
infections.
Cancers are caused by cells that divide and grow
uncontrollably. Particular genes can
cause such cell growth to occur if they are defective. Such defective genes are
called oncogenes. Cancer remains the
second leading cause of death in the United States.
Anytime a gene has the potential to malfunction and
cause a disruption in cell functionality health related problems will
result. Other examples are AIDS,
cardiovascular disease; which is the number one cause of death in the United
States; and even mental illness.
Gene therapy refers to
the process of changing human genetic material to repair or compensate for the
effects of a mutation or abnormality.
For example, a gene therapy for a single gene disorder might aim to
replace the mutated copy of the gene with a normal one.
To reverse disease caused by genetic damage, researchers
isolate normal DNA and package it into a vector, a molecular delivery truck
usually made from a disabled virus. Doctors then infect a target cell —usually
from a tissue affected by the illness, such as liver or lung cells—with the
vector. The vector unloads its DNA cargo, with the hope that the gene will then
begin producing the missing protein and restore the cell to normal.
The first disease approved to be treated with gene
therapy was ADA deficiency. ADA
deficiency was selected for the first sanctioned human gene therapy trial for
several reasons. The disease is caused by a defect in a single gene, which
increases the likelihood that gene therapy will succeed.
The ADA gene therapy trial
began in September 1990. “Using a
genetically altered mouse retrovirus as a vector, a properly functioning ADA
gene was spliced into the nucleic material (RNA). The vector delivered its genetic "payload" to the
T-lymphocytes, as the protein shell of the retrovirus binds to the cells'
receptors. During cell replication, when the cell is actually synthesizing DNA,
the RNA from the retrovirus is converted into DNA and incorporated into the DNA
of the cell. The genetically altered cell now has a functioning ADA gene which
produces ADA within the cell. Cultured T-lymphocytes are then reintroduced into
the children. The results of the gene therapy were quite impressive. The first
children to have the gene therapy had tremendous increases in their immune
functions. The children even grew tonsils. Because T-lymphocytes have shorter
life spans than stem cells, the treatment needs to be repeated every six
months”.
“Scientists are also
working on ways to genetically alter immune cells that are naturally or
deliberately targeted to cancers. They
are interested in arming such cells with cancer-fighting genes and returning
them to the body, where they could more forcefully attack the cancer. Clinical
trials along these lines are in progress for the treatment of melanoma.
“Gene therapy could be used to make
immune cells resistant to HIV (the AIDS virus). It could also be used to help
patients destroy HIV and HIV-infected cells by increasing the body's immune
response to these elements. Results from the ADA trial support the idea that
genetically altered lymphocytes or stem cells might help prevent immune system
failure in AIDS patients. T-lymphocytes enhanced with genes that block the
spread of HIV could be tested in humans soon”.
The science of genetic therapy is still in its
infancy. The possible cures we have previously
described may seem like we now have the ability to wipe out many diseases
entirely. This conclusion is a
dangerous one and could not be any farther from the actual truth. There are many hurdles still to be
overcome. One such hurdle is
understanding gene functionality. Of
the estimated 100,000 genes, scientists know the function of a very few. Attempting gene therapy without knowing how
everything works could address only some of the genes implicated in particular
diseases. Likewise, genes may have more
than one function.
Another obstacle is the way that genes are
introduced into the body. As we have
already discussed, this is done via vehicles called vectors (gene carriers),
which deliver normal genes to the patients' cells. Currently, the most common vectors are viruses. Viruses have evolved a way of encapsulating
and delivering their genes to human cells in an invasive manner. This is why they are so effective as a
vehicle. Scientists have tried to take
advantage of the virus's biology and manipulate its genome to remove the
disease-causing genes and insert the normal genes.
This lack of genetic information, along with the
somewhat dangerous quality of the genetic delivery vehicle can make the therapy
a very risky procedure. Last year an
American, Jesse Gelsinger, 18, died after taking part in a gene therapy trial
at the University of Pennsylvania that sought to use a genetically modified
adenovirus to cure his liver disease.
Such risks necessitate the much of the genetic therapy trials are
performed in the most extreme, life threatening cases.
Another
major hurdle genetic therapy faces is the abundance of multi-gene disorders.
Most genetic disorders involve more than one gene. Most diseases involve the interaction of several genes as well as
the environment. Many people who
develop cancer not only inherit the disease gene for their disorder, but they
may also have not inherited particular tumor suppressor genes. Diet, exercise, smoking, and other
environmental factors may have also contributed to their disease.
Despite many of its shortcomings, the future of
genetic therapy is an alluring one.
Some, however, may argue otherwise.
Are we playing God? Do we have
the right to change the natural order of things. Mutations, after all, are responsible for the world as we see it
today. Mutations, both helpful, and
harmful. The technology of genetic
therapy and genetic engineering pose some serious ethical questions. “The issues being confronted are the same
ones that are faced whenever a powerful new technology is developed. Such
technologies can accomplish great good, but they can also result in great harm,
either inadvertently or because of deliberate misuse.
Genetic therapy is currently focused on correcting
genetic flaws and curing life-threatening disease, and regulations are in place
for conducting these types of studies. But decades from now, when the
techniques of gene therapy have become simpler and more accessible, society
will need to deal with more complex questions.
One such question derives from the possibility of
genetically altering human eggs or sperm, thereby permanently changing the
process of human genetic inheritance. Another relates to the potential for
enhancing human capabilities -- for example, improving memory and intelligence
-- by genetic intervention.
Although both genetic therapy and genetic enhancement have the potential to
produce extraordinary benefits, the possible downsides of these procedures
worry some. Genetic therapy would change the genetic structure of an
individual's offspring. Thus, the human
gene pool would be permanently affected.
Although these changes would presumably be for the better, an error in
technology or judgment could have far-reaching consequences.
In the case of genetic enhancement, there is
concern that such manipulation could become a luxury available only to the rich
and powerful. Some also fear that widespread use of this technology could lead
to new definitions of "normal" that would exclude individuals who
are, for example, short, unattractive, or of merely average intelligence.
The 21st century is here. The new technology is upon us. Genetic
therapy holds the promise of curing many of today’s society diseases that have
frustrated man since the dawn of technology.
Only time will tell whether or not our discoveries are fruitful or
harmful. We have seen the harmful
effects of such technologies as nuclear power.
Will genetic engineering pose the same effects. If history holds true, it probably
will.
Overall the class had a lot of positive feedback,
some of the comments were “nicely done”, “very organized”, “very detailed”, and
“A lot of information presented”. The
majority of the class was not present, so there wasn’t as much feedback as I
would of hoped for. I noticed however
that a few said I read from my notes quit a bit, and I realized that, but as I
had explained earlier the presentation topic was not my paper topic and there
was just so much information to cover, and being that this topic has so much
information on it, I wanted to make sure I was giving the class the correct
information. Overall I believe that the presentation went very well and I am
satisfied with it.
References
Mak, Julie S. “Genetic Engineering and Gene Therapy.” Jan.
2000.
< http://www.geocities.com/geneinfo/facts/engineerfr.html>.
Friedmann, Theodore. “Overcoming
the Obstacles to Gene Therapy.” Scientific
American. Jun. 1997. < http://www.genethik.de/therapy/therapy1.htm>.
Magnus, David. “Gene Therapy and the Concept of Genetic
Disease.” < http://www.life.sci.qut.edu.au/templect/htdocs/lectures/lsp735/ethart3.htm>.
Author Unknown. “Gene
Therapy.” Human Genome Project
Information. US Office of Biological and Environmental Research. Oct. 2000.
<http://www.ornl.gov/hgmis/medicine/genetherapy.html>.
Author Unknown. “Gene Therapy.” Arizona State University.
Aug. 2000.
< http://photoscience.la.asu.edu/photosyn/courses/BIO_343/lecture/therapy.html>.
Author Unknown. “Gene Therapy.” Industry Canada – Life Sciences Branch. Oct. 2000. < http://strategis.ic.gc.ca/SSG/tc00029e.html>.
Author Unknown. “Fundamentals of Gene Therapy.” FDA/Office of Public Affairs. Aug. 2000. < http://www.fda.gov/fdac/features/2000/gene.html>.