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GENETIC INTERVENTION
Genetic Intervention: A Case Study
By Dennis M. Sullivan, M.D.
Somatic cell gene therapy is the most frequently discussed form of genetic intervention, which involves
the alteration of genes of a diseased individual, sometimes in just one specific organ or sometimes in the entire
individual. The word “somatic” comes from the Greek soma, meaning body (Mirriam-Webster, 2005), and
refers to genetic therapy that affects the adult cells of an individual’s body alone, without affecting subsequent
generations. A vector such as a virus is used to insert a normal gene into the DNA of cells to compensate for a
nonfunctioning defective gene (Human Genome Project, 2005).
For example, cystic fibrosis (CF) is a genetic disease causing a defect in the cellular transport of chloride
ions across cell membranes. This leads to thick mucous in the airways of the lungs, causing obstruction and
infections. Gene therapy of this disease involves use of a modified cold virus to “infect” the lungs of CF
patients. The virus inserts a normal copy of the affected gene into the DNA of the nucleus of airway cells,
which (hopefully) may then be capable of functioning normally (CF Foundation, 2005). To date, therapeutic
trials have had only limited success, but this form of treatment holds great promise for the relief of symptoms
and the prolongation of life.
Somatic cell gene therapies such as this affect only non-reproductive cells (in this case, the lining cells
of a CF patient’s lungs). There are no genetic alterations of germ-line cells (sperm and eggs), so no changes can
be passed on to the patient’s children. Germ-line therapy, on the other hand, would affect all subsequent
generations of offspring (Walters & Palmer, 1997). This would represent a permanent change in the genetic
heritage of human beings, and thus has been much more controversial. Despite this concern, some ethicists have
urged cautious approval of germ-line genetic therapy as a way to forever rid mankind of certain loathsome
genetic disorders.
Case History:
Jim Wilson, 32, is a successful businessman with a wife and one young son. He has been a Type I
diabetic since adolescence. Diabetes mellitus (hereafter just called “diabetes”) is caused by a failure of the
body’s pancreas to make the hormone insulin, needed to transport blood sugar (glucose) into cells. As a result,
the level of glucose in the bloodstream can be chronically elevated, leading to many long-term complications.
Diabetics typically have problems with nerve damage and circulatory problems, so that they have trouble with
wound healing.
Jim monitors his blood glucose and takes daily insulin injections to control his disease. Despite normal
blood glucose levels, he has developed a chronic non-healing ulcer on his right foot. Jim’s family doctor
referred him to a researcher with the National Institutes of Health, who proposes to place Jim in a clinical trial
of gene activated matrix (GAM) technology. This would treat Jim’s non-healing wound with a gel containing a
virus that could infect Jim’s fibroblasts (wound healing cells), genetically altering them to produce a protein
(PDGF) that will stimulate collagen formation and healing. The hope is that genetically altering Jim’s own
fibroblasts in this way will make them much more efficient at healing, thus curing his chronic problem. By the
way, such a research study of GAM technology actually exists (Sosnowski & Kinsey, 2002).
GENETIC INTERVENTION
Questions for Discussion:
1. If the usual methods of treatment for his chronic foot ulcer have failed, should Jim participate in this
study? Is there any ethical difference between such treatment and other traditional methods (e.g.,
antibiotics and wound care)?
2. This study targets a specific complication of diabetes. What if Jim could participate in a different sort of
clinical trial, one that used a viral vector to genetically alter the islet cells of his pancreas so that they
produce insulin? Though such a trial does not currently exist, this might be a “lifetime cure” of Jim’s
diabetes, so that he never has to take insulin injections again. Should Jim get involved in this?
3. Type I diabetes is thought to be due to a gene-environment interaction, with strong genetic risk factors in
the HLA region of chromosome 6 (Huether & McCance, 2004) Should Jim participate in a research trial
(currently unknown) of a germ-line form of therapy that would genetically alter his sperm, so that if he
has any more children they will not have a genetic susceptibility for diabetes?
4. Jim would prefer to have children with blue eyes (Jim has brown eyes). Should Jim participate in a
research trial (currently unknown) of a germ-line form of therapy that would genetically alter his sperm,
so that if he has any more children they will all have blue eyes?
5. Is it even possible to distinguish between “good” and “bad” uses of gene modification techniques?
Should the potential for harmful abuse of the technology keep us from developing new techniques?
6. Genetic therapy is very expensive (Jim and his family are rich), and will never be cost effective enough
to merit high social priority. Poor people will not be able to afford such treatments. Does this mean they
should be prohibited?
7. Germ-line gene therapy could violate the rights of subsequent generations. After all, they could not give
“informed consent” to have their genes altered in this way. How does this factor influence your thoughts
about germ-line therapy as opposed to somatic cell therapy?
References:
Branscomb, E. (1996). Human Genome News. Human Genome Project (U.S. Department of Energy).
Online at http://www.ornl.gov/TechResources/Human_Genome/publicat/hgn/v8n2/02brans.html
Gene Therapy and CF. (2005). Cystic Fibrosis Foundation. Online at http://www.cff.org/home/
Huether, S. E., & McCance, K. L. (2004). Understanding Pathophysiology. Saint Louis: Mosby.
Human Genome Project Information. (2005). Human Genome Project. Online at
http://www.ornl.gov/TechResources/Human_Genome/medicine/genetherapy.html
Sosnowski, B., & Kinsey, S. E. (2002). Gene Therapy to Improve Wound Healing in Patients With
Diabetes. National Institutes of Health. Retrieved October 27, 2005 from http://clinicaltrials.gov
Unabridged Dictionary. (2005). Mirriam-Webster. Retrieved October 27, 2005, from
http://unabridged.merriam-webster.com/cgi-bin/unabridged?va=somatic
Walters, L., & Palmer, J. G. (1997). The Ethics of Human Gene Therapy. New York: Oxford University
Press.