Narrative
Gene Therapy: A Review of the Past & A Dilemma for the Future
Between 1970 and 1973, a physician from the United States and another from Germany treated two young girls
for a condition in which their bodies overproduced the amino acid arginine. To combat the potentially dangerous
build-up of arginine, the doctors injected the girls with a virus to express a gene that regulated arginine
production. The therapy was unsuccessful, but this episode nevertheless initiated the dawn of human genetic
engineering (Friedmann, 1999).
In 1979 and 1980, an American researcher attempted the first human gene therapy by transferring DNA into bone
marrow cells of two patients suffering from hereditary blood disorders. Interest from the general public as well as
the scientific community concerning both methodological and ethical considerations grew in light of this incident.
The National Institutes of Health (NIH), the governmental agency charged with reviewing procedures such as
gene therapy, adopted a position supporting further explorations of gene therapy but tightened its regulation on
research practices. These new regulations effectively outlawed any human genetic experimentation without the
express consent of the NIH. The NIH also drew a distinction between two kinds of gene therapy: somatic and
germ-line. Developed cells that make up organs and tissues of the human body are called somatic cells, and
somatic gene therapy refers to manipulating the genetic material of these cells. Germ-line therapy targets gametes
(sperm and eggs) prior to fertilization or zygotes just after fertilization. Germ-line therapy, therefore, changes the
genetic structure of all cells of the patient and will be heritable as opposed to somatic therapy which only affects
certain somatic cells of the patient and cannot be passed on to offspring (Friedmann, 1999; Mueller & Young,
2001).
In 1990, the NIH received its first two proposals for somatic gene therapy, and both were approved. In one study,
researchers altered genes in white blood cells, enabling them to produce proteins that kill tumor cells. This kind of
research has great potential in the battle against cancer. In the other study, approved in 1990, doctors designed a
treatment for children suffering from severe combined immune deficiency (SCID). SCID patients lack a single
gene that helps their white blood cells fight common infections such as chicken pox and the flu. Children with
SCID must live in isolation from others, unable to go to school or play with other children because of the danger
of contracting infectious diseases; most do not live into adulthood. Doctors treated these patients by inserting the
missing gene into patients' white blood cells. The therapy worked, but it had to be repeated every few months as
the genetically altered cells died off.
Over the last decade several somatic gene therapy projects have been initiated, with varying degrees of success,
but germ-line therapy has not been approved. Supporters of gene therapy point to somatic cell successes, such as
the work with SCID, and call for expanding programs to target other heritable diseases such as cystic fibrosis,
Huntington's disorder, and sickle cell anemia. They also call for lifting the ban on germ-line therapy so that
patients can be cured of diseases rather than temporarily treated by somatic therapy. However, opponents cite the
dangers associated with gene therapy, such as the accidental deaths of seven patients involved in gene therapy
research and the unknown consequences of altering the genetic composition of humans (Friedmann, 1999).
The NIH Committee on Genetic Engineering now stands at a crossroads of genetic technology; a research group
with a successful track record in somatic gene therapy has submitted a proposal for germ-line experimentation on
SCID. The Committee's decision will drastically alter the course of gene therapy in the United States. By denying
this proposal, the NIH will be upholding the informal ban on germ-line gene therapy. By accepting the proposal,
the NIH will set a precedent for future germ-line studies. The leaders of the U.S. Congress are monitoring this
case closely because they plan to introduce legislation that supports the position formulated by the NIH, thereby
legally accepting or outlawing germ-line gene therapy.
Given the gravity of this decision, the NIH is requesting the input of all interested parties. Your task is to gather
information about different perspectives on the issue, share this information with one another, and finally come to
consensus on a recommendation for how your group thinks the NIH should proceed.
Position 1. Stop All Gene Therapy
A vocal group of opponents believe that all forms of human genetic engineering, including both somatic and
germ-line gene therapy, are irresponsible and dangerous. Individuals advocating this position suggest that altering
human genes is ethically wrong, and gene therapy directed towards disease only opens the possibility for people
to pursue genetic changes to features such as intelligence, appearance, etc. Consider the remarks made in support
of this position by individuals involved in the genetic engineering debate as your focus group negotiates a report
that you will bring back to your home group (for supporting quotes, see Table 1).
Position 2. Proceed with All Gene Therapy
Several leaders in the field of human genetic engineering believe it to be their right and responsibility to pursue all
means available in their quest to improve the human condition. Whereas somatic gene therapy provides a
temporary treatment, germ-line therapy offers the promise of permanently altering genetic code thereby
improving the human genome. Consider the remarks made in support of this position by individuals involved in
the genetic engineering debate as your focus group negotiates a report that you will bring back to your home
group (for supporting quotes, see Table 2).
Position 3. Use Somatic but Not Germ-Line Gene Therapy
Some participants in the gene therapy controversy believe that somatic and germ-line therapies represent two
divergent procedures. Whereas somatic gene therapy is a viable treatment option, germ-line gene therapy is
potentially dangerous, both medically and ethically. Therefore research on somatic therapies should continue, but
germ-line studies should be disallowed. Consider the remarks made in support of this position by individuals
involved in the genetic engineering debate as your focus group negotiates a report that you will bring back to your
home group (for supporting quotes, see Table 3).
Position 4. Proceed with Extreme Caution
One of the primary concerns related to gene therapy, both somatic and germ-line, is the risk to patients
undergoing novel protocols. Human subjects in any medical research projects assume some degree of risk; gene
therapy is no different. Many opponents of gene therapy claim that the dangers associated with this line of
research are too great to continue. Consider the remarks made in support of this position by individuals involved
in the genetic engineering debate as your focus group negotiates a report that you will bring back to your home
group (for supporting quotes, see Table
Appendix A. Focus Questions.

What are the main ideas expressed by arguments you have read?

How are these arguments supported? What kinds of information or
evidence are offered in support of the arguments?

What are the strengths and weaknesses of these arguments?

What evidence could be shown to you that would lead you to
support this position?

What evidence could be shown to you that would lead you to
oppose this position?

How can this position be succinctly summarized?

What points of view have not been expressed by the arguments you
have seen?

Are the statements you have read based on any assumptions that
require further exploration?
STOP ALL GENE THERAPY
PROCEED WITH ALL GENE THERAPY
USE SOMATIC BUT NOT GERM-LINE GENE THERAPY
PROCEED WITH EXTREME CAUTION