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Running head: GENE THERAPY RESEARCH

Moral Imperative of Gene Therapy Research in Health Care

Jeremy Thong
Northeastern University
Christen Enos
11/7/2014

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Peer Review Response Letter
Dear Nicholas, Linda and Professor Enos,
Thank you all very much for taking the time to review my first draft and as well helping me with
coming up with my thesis and finding sources. I struggled a lot with writing this paper especially at the
beginning, but with your collective advice and motivation I have been able to come up with a
composition that I am proud of.
Nicholas, one of your biggest pieces of advice was to further organize my main ideas, and I could
not agree with you more. At the time of the draft, I was still not entirely sure of what I wanted to say in
my thesis, but further organization helped me to solidify my motive and thesis. Also as you suggested I
narrowed down my audience; I chose to target health professionals working in pediatrics or other
populations that were likely to suffer from genetic diseases. Further on in your review you mentioned
some sentences that were confusing; I actually did not use those sentences in the final draft, but I tried
to make sure that I phrased sentences in a more understandable way in the future.
Linda, I took you suggestion and found some great sources in the Northeastern library data
base. Also, as you recommended, I did compare different scholarly opinions about gene therapy, as this
is the body of my composition. I know that I didnt have a lot to send you with my rough draft, but I still
appreciate the guidance.
Professor Enos, I really appreciate all the help you have given me with finding sources, defining
my motive and thesis and by reviewing my latest draft. I have tried a lot to make my motive and thesis
clear and to make the essay flow well in an organized manner. I have struggled a lot with keeping the
language fitting for the audience, but I think I have improved a lot in setting the appropriate tone and
making sure that what Im saying is intellectually stimulating for the audience. I made most of the
changes that you mentioned in your comments, especially moving the evolution argument earlier, so

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that it is after the other arguments that oppose gene therapy. I also reworded this argument to make it
more intellectually appropriate for the audience. You mentioned that some sections seemed to be
unnecessary because they were repetitive, but I did not take them out. I instead rephrased them in
order to emphasize their importance in the essay.
Thank you so much
Best Wishes,
Jeremy
Context Note
The following essay is a researched argument that surveys various literature on gene therapy
which is genetic engineering on the human genome in order to correct genetic disorders. The literature
reviewed in this essay includes professional writings that discuss the ethical indications and objections
towards gene therapy, cultural acceptance and rejection of gene therapy and modification, as well as
medical successes and failures using gene therapy. In this essay, an argument is made that ethically
supports gene therapy in treatment of disease, and encourages health professionals to take initiative to
further research. The author confirms a need for further research unto the safety and long term effects
of gene treatments. This essay is a response to the lack of current (within the last five years) scholarly
documents that question the morality of gene therapy, as there are many new genetic editing
techniques being developed and cultural acceptance constantly changes. This essay would be published
in the American Journal of Bioethics or the Journal of Genetic Syndromes & Gene Therapy, and the
audience is American health care practitioners and researchers and would be very relevant to those who
specialize in pediatrics as many genetic diseases manifest at birth.

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Abstract
The duty of healthcare providers to relive suffering and to avoid causing harm presents an
ethical dilemma when deciding whether or not to pursue genetic medication for medical use. Patient
risk vs benefit as well as legal and cultural issues complicate this relatively new area of medicine causing
health care practitioners, particularly those who working with populations that suffer from diseases with
a genetic pathology, to take opposing opinions. Through a review and analysis of gene therapy
literature, the following composition claims that gene therapy will help health care practitioners relieve
patient suffering, and gene therapy development is an ethical obligation of the medical community. This
essay is a response to the shortage of recent publications (within the past 5 years) that question the
morality of gene therapy. The review of literature has identified a lack in understanding of the long term
effects of gene therapy. In this publication, arguments that oppose gene therapy are reviewed,
evaluated and then refuted with counter arguments that not only support gene therapy but pose that its
use and development are moral imperatives for health care providers. The role of health professionals
as a trustworthy educational resource is also discussed. This is needed because of conflicted messages
that the public has been given about these therapies in the media. Despite over 320 ongoing clinical
trials for gene therapy, many of which have had great successes, the FDA has still not approved any gene
therapies for marketing due to lack of evidence of efficacy and safety. Developing standards of safety
and efficacy must be of paramount importance to health professionals, as they have the responsibility to
make sure treatments are not inflicting harm unto their patients.
Review
Despite ethical and safety concerns, the use of genetic engineering technology on humans
appears to be inevitable. These ideas bring into question, is gene therapy a legitimate threat to

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humankind, or is it a new way for us to adapt and progress as a society? The answer seems to lie in
between these two contrasts. Although proposed superficial uses of gene therapy cause controversy,
the potential medical uses could improve the lives or even save numerous people suffering from genetic
diseases. Therefore, healthcare providers have a moral obligation to further research in the field of gene
therapy. There is a need for further the limited research of the long term effects of gene therapy
because health care providers have a duty to improve the lives of their patients and definitely not cause
them harm. There is also a need for more current ethical analyses of gene therapy because our cultural
values are constantly changing and adapting.
Even though gene therapy technology has recently been making huge advancements, there are
a limited number of recent publications on the ethical implications of gene therapy. Concern over abuse
of gene therapy has been argument against gene therapy development ever since its conception in the
1980s (Bergeson, 1997). However, upon review of professional bioethical literature of gene therapy,
there is a severe lack of current publications. Perhaps this is because the arguments for and against gene
therapy have remained consistent, but this seems unlikely because the technology for gene editing has
not remained stagnant because of methods such as using CRISPR-Cas9 enzymes. Furthermore, newer
analysis of the moral validity of gene therapy in American culture, particularly within the medical field, is
needed. This essay aims to provide some insight on this issue by providing ethical analysis of current
gene therapy practices and potential uses.
To understand the need for caution within the medical field, it is beneficial to understand some
common fears about gene therapy. According to the publication, The Inevitability of Genetic
Enhancement Technologies by Franoise Baylis and Jason Scott Robert, some of the concerns include
an unacceptably high risk for physical harm, transgression of natural or divine law, threat to a
common human genome, the widening the economic and educational divides, the promotion of social
conformity, genetic discrimination and undermining of free choice (Baylis, Robert 2004). Also, the

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correct gene placement and regulation is not always flawless, and the side effects are often unknown
(Bergeson, 1997). Hence, it is important for medical researchers and healthcare practitioners to take
these qualms into account as the mantra of medicine is to first do no harm.
Another argument that opposes genetic therapy is that genetic engineering would irresponsibly
change the complex and balanced human genome which has been constructed through innumerable
years of evolution. This argument is valid but also disputable because through evolution genetic
advances happen unintentionally and often lead to suffering of less fit populations. Also, humans have
modified their environment to a point where societal advancement is no longer reliant on evolution, so
the human genome is not necessarily optimal for their environment. As Russell Powell argues in,
Breaking Evolution's Chains: The Prospect of Deliberate Genetic Modification in Humans, [intentional
genetic modification] is potentially morally preferable to [unintentional] because often natural
selection often leads to mass scale suffering (Powell, 2011). For example, genetic diseases are a result of
genetic mutations, and with natural selection these people would suffer and probably not pass on their
genetic heritage. Powell also makes the point that, natural selection tends not to act on the postreproductive period of life as natural selection is a mechanism to promote reproduction. There are
several conditions that humans suffer from latter in life that natural selection would never select out of
the gene pool on its own, such as increased risk for muscle and bone loss, cognitive decline and cancer
to name a few (Powell, 2011). On the other hand, perhaps increased risk for certain complications with
age is a natural mechanism for population control and beneficial to society. That being said, population
control does not justify prohibiting gene therapy because the same argument of population control
could be used against any other medical treatments that are currently used to extend life. In American
culture, patients have autonomy over their treatment, so they have the right to seek out gene therapy if
they see it fit. Overall, Health professionals have the opportunity to use gene therapy to relieve some of

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this suffering that is a side effect of the unperfected system of unintentional genetic modification that
happens through reproduction.
Further on in the previously mentioned essay, Baylis and Robert explain that despite these fears,
human desire to secure health, success, wealth and happiness will overpower and drive genetic
enhancement, and that these concerns about misuse should not impede scientific advancement. (Baylis,
Robert, 2004) The argument for integration of these technologies into American consumerist culture
seems very logical, as Americans are consistently seeking out new ways to self-better themselves
through any means necessary. Healthcare itself is a form of self-betterment, but always striving for a
morally justified goal of relieving suffering and improving health and quality of life. If gene therapy is
accepted into our culture just like any other product of self-betterment, then it is the responsibility of
the health care field to use this technology to treat disease and to make sure that these technologies are
effective and safe.
There are currently over 320 ongoing gene therapy clinical trials, yet no gene therapy
treatments have be approved by the FDA for marketing. According to Daniel Takefman and
Wilson Bryan in their Molecular Therapy journal editorial The State of Gene Therapies: The
FDA Perspective this setback is due to lack of evidence of safety and effectiveness necessary
for FDA marketing approval (Takefman & Bryan 2012). The ability for gene therapies to be

marketed could have positive effects on the technologys public image and help advance research.
Furthermore, the field is also hindered by the apprehension caused by clinical trials with adverse events,
even some that were fatal. Therefore, although the prospective use of gene therapy to treat and even
cure diseases causes great enthusiasm, health professionals need to still proceed with caution. As
premature implementation of gene therapy technology has been shown have harmful effects both for
the patients being treated and for the movement itself.

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In support of this movement, healthcare providers have a duty to be role models for the
scientific community as well as to educate the public about gene therapy. The fear of genetic
modulation that many experience is valid, as many clinical trials have been done prematurely and
without the understanding of long term adverse effects. Also through books like Brave New World and
movies like GATTACA, which show genetic engineering as a means for inequality and discrimination,
and news stories which instill fear such as the death of gene therapy patient Jesse Gelsinger in 1999
(Sibbald, 2001), American media has introduced genetic engineering as a frightening technology that
could ruin the integrity of human society. Healthcare practitioners have the ability to build trust with the
communities they serve, and therefore have the ability to reintroduce gene therapy as not something to
unconditionally fear, but something to cautiously embrace as a medical treatment. Fear of infection and
pain does not prevent surgeons from operating on patients who are in need; instead these worries have
caused further innovation to improve surgical safety. Likewise, the same high level of precaution should
be used with gene therapy. Just like with any procedure, gene therapy will require interdisciplinary
collaboration in order to have safe and effective results. With high levels precaution as well as public
education, huge potential lies within gene therapy to improve the lives of patients and their families
who are currently living with untreatable genetic diseases.
Gene therapy has been shown to be efficacious in certain genetic diseases. In a study led by
Peter A. LeWitt, a gene therapy, AAV2-GAD infusion, has been shown in a double blind study to
significantly improve motor control in Parkinisons patients (LeWitt, 2011). In another study of nine
extremely immunocompromised boys with X-linked severe combined immunodeficiency, led by Salima
Hacein-Bey-Abina, gene therapy was found extremely effective, ultimately saving the lives of eight out
of the nine boys (Hacein-Bey-Abina, 2014). This gene modified cell treatment had profound effects on
these boys immune systems via T cell reconstitution, but the long term effects of this treatment, as in
most other cases of gene therapy, is unknown. In some cases gene therapy has rendered ineffective,

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such as in a study led by Tim WR Lee and Kevin W Southern in attempts to use gene replacement to
treat cystic fibrosis (CF) related lung disease (Lee, Southerland, 2013). The therapy showed no symptom
improvement and only adverse effects, yet the mechanism of CF is understood to be caused by the gene
encoding a protein: cystic fibrosis transmembrane conductance regulator. Due the pathophysiological
knowledge of CF, gene therapy treatments could be developed from future research. Overall, gene
therapy successes display the huge potential of gene therapy and promote further research, and the
shortcomings indicate a need for further research as well.
Conclusion
Overall, healthcare providers have a moral obligation to further research in the field of gene
therapy, but they must advance this technology with caution. As this technology is relatively new, there
is not much understood about the long term effects on individuals who have and edited genome or the
effects on their offspring. Therefore post therapy studies and long term follow up are of vital importance
to the advancement of the field. There is a lack of new publications regarding the moral implications for
gene therapy, yet American culture and genetic technology is continually progressing. Thus, revaluation
of the ethical use of gene therapy in the United States is necessary. In Americas self-bettering and
consumerist culture, gene therapy appears to be inevitable. Therefore health professions who strive to
improve lives and avoid causing harm need to determine gene therapy safety and efficacy, especially
because premature implementation has historically led to horrible outcomes. Changing the human
genome that has been crafted over innumerable years of natural selection may be seen as one of these
averse outcomes, but intentional genetic modification actually has the potential to be more ethically
just because it can expedite adaption and help to mitigate suffering. To the support of furthering
research, health care providers also have the duty to educate the public on gene therapy letting their
patients understand the risks as well as benefits. In terms of its efficacy, gene therapy has had incredible
successes as well as discouraging failures; both show that more research is needed. Gene therapy will

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help health care practitioners relieve suffering, and its development is an ethical obligation of the
medical community.

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References
Baylis, F., & Scott Robert, J. (2004, January 20). THE INEVITABILITY OF GENETIC ENHANCEMENT
TECHNOLOGIES. Retrieved November 5, 2014, from
http://onlinelibrary.wiley.com/doi/10.1111/j.1467-8519.2004.00376.x/pdf
Bergeson, E. (1997). The Ethics of Gene Therapy. Retrieved November 5, 2014, from
http://www.ndsu.edu/pubweb/~mcclean/plsc431/students/bergeson.htm
Hacein-Bey-Abina, S., Pai, S., Gaspar, B., Armant, M., Berry, C., Blanche, S., & Bleesing, J. (2014, October
9). A Modified -Retrovirus Vector for X-Linked Severe Combined Immunodeficiency. Retrieved
November 5, 2014, from http://www.nejm.org/doi/full/10.1056/NEJMoa1404588#t=article
Lee, T., & Southern, K. (2013, November 26). Topical cystic fibrosis transmembrane conductance
regulator gene replacement for cystic fibrosis-related lung disease. Retrieved November 5, 2014,
from http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD005599.pub4/full#CD005599sec1-0006
LeWitt, P., Rezai, A., Leehey, M., Ojemann, S., & Flaherty, A. (2011, April 4). AAV2-GAD gene therapy for
advanced Parkinson's disease: A double-blind, sham-surgery controlled, randomised trial.
Retrieved November 7, 2014, from
http://www.sciencedirect.com/science/article/pii/S1474442211700394
Powell, R., & Buchanan, A. (2011, January 12). Breaking Evolutions Chains: The Prospect of Deliberate
Genetic Modification in Humans. Retrieved November 5, 2014, from
http://jmp.oxfordjournals.org/content/36/1/6.full.pdf html
Sibbald, B. (2001, May 29). Death but one unintended consequence of gene-therapy trial. Retrieved
November 5, 2014, from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC81135/
Takefman, D., & Bryan, W. (2012, May 1). The State of Gene Therapies: The FDA Perspective. Retrieved
November 6, 2014, from http://www.nature.com/mt/journal/v20/n5/pdf/mt201251a.pdf