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Hamdan Medical Journal 2015; 8:101–110 (http://dx.doi.org/10.7707/hmj.304)
REVIEW
Human gene therapy – the future of health care
Milad Soleimani, Maxime Merheb and Rachel Matar
Department of Biotechnology, American University of Ras Al Khaimah, Ras Al Khaimah,
United Arab Emirates
Abstract
Gene therapy is the use of genes to heal diseases at the genetic level.
It involves insertion, correction or inactivation of specific genes in
organisms suffering from genetic disorders. Ever since it was introduced
as a hypothesis in the 1960s, gene therapy has gone on to become a
medical wonder that promises relief from the likes of Parkinson’s disease
and multiple sclerosis. Today, the technique is used to manipulate the
genome of not only somatic cells but also the germline cells of early
embryos and gametes with a vast range of viral and non-viral vectors.
The diseases targeted by gene therapy are among the deadliest on
the planet: they are categorized into cancers, genetic deficiencies and
autoimmune diseases. On the one hand, gene therapy is deemed by
some to be an ethically and technically problematic technology because
of its cost, its treatment of human dignity and its questionable accuracy
and safety. In contrast to what its opponents say, the pro-gene therapy
arguments support the technique by highlighting its remarkable
efficiency, long-term cost-effectiveness and ability to cure unique
diseases, among others.
Introduction
‘I am sorry. There is nothing more we can do.’
That is what a doctor would say to a patient or the
parents of a fetus suffering from, what might seem
at this point, an incurable genetic disorder. The
string of similar clichéd apologies was broken for
the first time in 1990 by two brave souls,
Dr Anderson and Dr Blaese, who took the initiative
by treating a 4-year-old girl lacking an adenosine
deaminase (ADA) gene with a role in immune
responses.1 Gene therapy is a technique to alter
aberrant phenotypic characteristics caused by
mutations through approaches such as gene
insertion, modification or regulation.2 The technique
is particularly advantageous over conventional
Correspondence: Rachel Matar, Department of Biotechnology,
American University of Ras Al Khaimah, Ras Al Khaimah,
United Arab Emirates. Email: [email protected]
medications in that it aims to correct the underlying
cause of the disease, rather than its symptoms.
Cancer, cardiovascular diseases and multiple
sclerosis are some of the conditions with prospects
for treatment with gene therapy. In addition, there
have been attempts to tackle inherent genetic
disorders at the embryonic stage. This form of gene
therapy, however, has given rise to enormous
controversy arising from the fear of misusing the
technique for non-medical purposes, uncertainties
regarding its success and other ethical issues. To
address the issues, stringent regulations may be
necessary; however, standing in the way of gene
therapy merely out of fear is deemed unreasonable.
Historical perspectives
The idea of manipulating the genome emerged
in the 1960s as the antisense concept, following
the discovery of the DNA double helix and the
explanation of its replication, expression and
regulation.3 Joshua Lederberg was one of the
pioneers who envisaged the possibility of controlling
nucleotide sequences in human chromosomes and
grafting DNA segments onto viral DNA.4 The
hypothesis was reinforced during the 1970s, mainly
as a result of the discovery of reverse transcriptase
and the comprehensive studies on restriction
enzymes.3 Soon after came two unapproved clinical
trials: one to treat the arginase deficiency syndrome
using the Shope papilloma virus, and the other to
counteract β-thalassemia with bone marrow cells
treated with a β-globin-containing plasmid.5 Despite
the success of treating ADA in 1990, the decade that
followed was full of disappointments, the biggest of
which occurred in 1999 with the death of a teenager
who had undergone gene therapy for a rare liver
© 2015 The Author(s)
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disease.6 With improvements in our understanding of
vectors, gene therapy has taken a sharp turn for the
better, promising (science-grounded) miracles in the
future. A concise timeline of the most salient events
that have shaped gene therapy is shown in Table 1.
Gene therapy: approaches, types and
vectors
In brief, gene-based therapeutics (gene therapy) may
be generally defined as altering the expression of
specific genes or correcting defective genes by
introducing exogenous nucleic acids in order to
prevent, arrest or reverse a pathological process.13
There are three chief approaches that are adopted
to carry out gene therapy. Gene addition/insertion
is the most common approach and involves
introducing into cells a normal copy of a
non-functional, mutated gene that is otherwise
responsible for the production of a key protein. This
method has been shown to tackle genetic disorders
such as haemophilia14 and cystic fibrosis,15 which are
characterized by the lack of the clotting factor IX and
a chloride channel, respectively. The genes encoding
these proteins are delivered into cells where they are
expressed to provide the patient with the protein
that they lack. Gene knockdown is the second
approach, which entails regulating and/or inhibiting
the expression of a mutant gene with the help of
double-stranded RNA (dsRNA) via the process of RNA
interference (RNAi). RNAi is a biological process
whereby endogenously produced or artificially
introduced dsRNA binds to the target messenger
RNA (mRNA) and causes its degradation and,
therefore, silences the target gene.13,16 Being
a biological response, RNAi can be triggered in
patients by the administration of short synthetic
dsRNAs or by the expression of short hairpin RNAs
(shRNAs). Its mechanism involves a series of events
during which dsRNAs and shRNAs are processed
mainly by an enzyme called Dicer to generate short
interfering RNAs (siRNAs) and microRNAs (miRNAs),
respectively. siRNAs bring about cleavage of their
target mRNAs and can, therefore, be used to
completely suppress disease-causing genes. miRNAs,
on the other hand, follow a non-cleavage-dependent
pathway, which renders them useful in modulating
gene expression.17 The therapeutic applications of
RNAi include, but are not limited to, the treatment
of cancer,18–20 Alzheimer’s disease,21 rheumatic
diseases22 and eye diseases.23,24 Gene correction/
modification is another approach wherein zinc-finger
nucleases and DNA recombination techniques are
applied to either repair a mutation or mutate a gene,
encoding a virus receptor in order to thwart
infection.25 Zinc-finger nucleases are powerful gene
modification tools composed of a sequence-specific,
customizable DNA-binding domain and a nuclease
domain that functions only when bound to the
target site.26 The cleavage of DNA evokes a damage
response that is prominently in the form of
non-homologous end joining which, despite being
inaccurate, can be used to introduce small insertions
and/or deletions to inactivate mutant genes.25,27 To
augment the accuracy of the response, a synthetic
donor DNA template homologous to the target is
TABLE 1 Timeline of the most important events in the history of gene therapy
1959
1968
1970–1973
1974
1980
1983
1984
1990
1997
Physician Stanfield Rogers observed that the warts caused by the Shope papilloma virus on the skin of rabbits were rich in
arginase, which he attributed to the introduction of a Shope virus-encoded arginase gene into rabbit skin cells3
Nobelist Marshall Nirenberg discussed programming cells with synthetic messages7
Stanfield Rogers used the Shope papilloma virus in an unsuccessful attempt to treat two sisters suffering from hyperargininaemia,
as he believed the virus would induce arginase activity in the patients8
Creation of the Recombinant DNA Advisory Committee (RAC) to stringently regulate all gene transfer experiments
(http://osp.od.nih.gov/office-biotechnology-activities/biomedical-technology-assessment/hgt/rac)
Martin Cline conducted an unapproved experiment to transfer the β-thalassemia gene into the bone marrow of two patients with
hereditary blood disorders9
Miller et al.10 built a retroviral vector and used it to transfer a human hypoxanthine-guanine phosphoribosyltransferase gene into
rodent cells in vitro10
The RAC created the Human Gene Therapy Working Group specifically to review gene therapy protocols8
Anderson and Blaese cured a young girl suffering from severe combined immunodeficiency by injecting her with T cells carrying an
adenosine deaminase gene11
A HIV-positive child was treated using recombinant CD34+ cells carrying a HIV-1 PRE decoy gene12
HIV, human immunodeficiency virus; PRE, progesterone-responsive element.
102
© 2015 The Author(s)
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delivered along with zinc-finger nucleases to replace
the target with desired genetic information through
homologous recombination.27,28 The method has
been utilized in the treatment of HIV29 and diseases
such as haemophilia,30 sickle-cell anaemia31 and the
X-linked chronic granulomatous disease,32 and also in
the creation of knockout models.33 Alternatively, a
donor template that has only one mismatch with the
target gene can be used to induce a site-specific
correction of a point mutation in a process referred
to as site-directed mutagenesis. A more commonly
practised approach involves the use of RNA/DNA
oligonucleotides, as they are more active in
homologous pairing than DNA alone.34 Alexeev et al.35
used this approach to demonstrate that injection
of albino mice with RNA/DNA oligonucleotides
tailored to correct a point mutation in the tyrosinase
gene would result in permanent and inheritable
restoration of tyrosinase activity and melanin
synthesis. Other disorders against which this method
has been employed include sickle cell anaemia,36
Fabry’s disease34 and haemophilia B.37
Depending on the type of target cell, gene therapy
is broadly classified as somatic or germline. Clearly,
the former refers to correcting anomalies in
non-reproductive cells in the patient, whereas the
latter is often performed in early embryos, such that
the change will be passed on to posterity.38 Somatic
gene therapy could be implemented either in vitro
or in vivo. The in vitro method consists of three key
steps: (1) transforming a virus and suppressing its
ability to reproduce; (2) transfecting the virus into
cells isolated from a patient; and (3) injecting the
genetically modified cells into the patient.39
Conversely, the in vivo method involves direct
administration of injectable self-eliminating vectors
(e.g. adenoviral vectors) to patients.40 Germline gene
therapy is relatively cumbersome and sensitive
with a protocol that comprises eight major steps:
(1) isolation of undifferentiated cells from an
embryo or a gamete; (2) culturing the cells in vitro;
(3) transfection of the cells; (4) selection of the
transfected cells; (5) replacement of the targeted
gene; (6) removal of marker genes; (7) nuclear
transfer into an unfertilized ovum; and
(8) reimplantation of the ovum in the uterus.38
Vectors play a crucial role in transferring DNA into
cells. They fall under the two classes of viral and
non-viral vectors. Viral vectors are essentially viral
particles composed of nucleic acid contained within
a capsid protein that is, more often than not,
covered by a membrane envelope. Generally, some
of the structural genes of these vectors are deleted
in order to prevent them from replicating in host
cells.41 Gene delivery by means of replicationincompetent viral vectors has been demonstrated to
be more efficient and less demanding in terms of
dose number because of the presence of strong
promoters in viral vectors.42 The genetic material of
each type of viral vector may be different from
those of others, which confers unique features for
the therapeutic exploitation of the virus (Table 2).
Notwithstanding their high efficiency and specific
uptake, viral vectors are plagued by their stimulation
of the host immune system that recognizes the
vector and the transgene product(s) as a foreign
agent.44 Non-viral vectors are deemed superior to
viral vectors in some respects as they are safer, can
be more easily constructed and modified and display
a higher packaging capacity.45 Typically, non-viral
vectors are in the form of either naked DNA or a
complex of DNA and nanoparticles.46 Liposomes are
known to be the most popular type of nanoparticles
composed of natural or synthetic phospholipids
and steroids or other surfactants. Thanks to their
ability to fuse with biological membranes, liposomes
have been successfully employed to transfect DNA
into cells.47 Polymers constitute another class of
non-viral vector for therapeutic gene delivery.
The most studied polymers are dendrimers that
are highly branched macromolecules, consisting
of a central atom (e.g. nitrogen), interior layers of
polymers and an exterior, cationic functionality
layer.48 Microprojectiles such as tungsten and
gold nanoparticles coated with DNA also serve as
effective non-viral vectors that are blasted into target
cells using a gene gun.46 Other notable modes of
delivery for non-viral vectors, in general, include
electroporation (relies on electrical pulses to create
pores in the cell membrane),49 ultrasound50 and
hydroporation (uses a highly pressured aqueous
solution to generate membrane pores).51
Applications: case studies
As far as its applications are concerned, gene
therapy is a versatile tool, potentially capable of
treating a range of disorders that require gene
correction or replacement. Cancer remains, by far,
the most investigated potential application of gene
therapy (Table 3). The most successful clinical trials,
however, are those that address cardiovascular
diseases.52 This review will discuss specific studies in
© 2015 The Author(s)
Journal Compilation © 2015 Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences
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TABLE 2 Genetic material, advantages and disadvantages of viral vectors43
Viral vector
Genetic
material
Retroviral vectors
dsRNA
Lentiviral vectors
dsRNA
Adenovirus vectors
dsDNA
Herpes virus vectors
dsDNA
Poxvirus vectors
dsRNA
Adeno-associated
virus (AAV)
dsDNA
Advantages
Disadvantages
Insert capacity for transgene <7–8kb
Stable integration into host DNA
Low immunogenicity
Broad cell tropism of infectivity
Prolonged expression
Infect proliferating and non-proliferating cells
Stable gene expression
High transfection efficiency
Efficient targeted transfection
Infects dividing and non-dividing cells
Infects a wide variety of cell types
Insertion capacity of up to 50kb
Generation of high virus titres
High insertion capacity
High expression levels
Infect dividing and non-dividing cells
Very prolonged expression
Low immunogenicity
Non-pathogenic
Difficult targeting of viral infection
Transfect only proliferating cells
Concern of insertional mutagenesis
Potential insertional mutagenesis
No clinical trials
Immune response to viral proteins
Insert size limit of 7.5kb
Transient gene expression
Possible toxicities
Risk of recombination
Possible cytopathic effects
Insert size limit of 4.5kb
Insufficient clinical trials
Requirement of adenovirus or herpes virus for
AAV replication
dsDNA, double-stranded DNA.
the application of gene therapy against colon
cancer, heart failure, multiple sclerosis and type 1
diabetes mellitus.
Given their high death toll, cancers, both benign
and malignant, are relentlessly investigated for the
possibility of using gene therapy as a form of
treatment. Researchers are constantly improving the
technique for the purpose of presenting it as a safe
and superior alternative to chemotherapy, which
has the potential to cause systemic toxicity and/or,
in the long run, lead to other types of cancer.53
TABLE 3 Proportions of gene therapy clinical trials for
various diseases52
Disease/indication
Proportion of trials (%)
Cancer
Monogenic diseases
Cardiovascular diseases
Infectious diseases
Neurological diseases
Ocular diseases
Inflammatory diseases
Other diseases
Gene marking
Healthy volunteers
64.4
8.7
8.4
8.0
2.0
1.5
0.7
1.4
2.7
2.3
104
The studies in this regard are largely focused on
two strategies, namely immunotherapy and
oncolytic virotherapy. Briefly, immunotherapy
involves use of cells transfected with cytokine genes
in an attempt to provoke a robust immune
response against existing tumour(s).54 Oncolysis, on
the other hand, uses viruses that replicate within
tumours, destroying them in the process. As a case
study on oncolysis, Yoon and collaborators55
assessed the efficacy of a herpes simplex virus (HSV)
mutant hrR3, containing a β-galactosidase insert
within its ribonucleotide reductase gene for cancer
therapy. The virus was expected to proliferate in
tumours, depending on the ribonucleotide
reductase supply by cancer cells. In cell culture
studies, human, as well as murine, colon carcinoma
and hepatocytes were infected with hrR3, and
subsequently subjected to viral cytotoxicity assays.
The number of surviving cells was greater in the
case of hepatocytes, indicating the effectiveness of
the virus as an antitumour agent. Results of animal
studies were equally favourable, as mouse models
suffering from carcinoma showed tumour lysis with
blue (β-galactosidase) spots in the cleared regions
upon infection with hrR3.55
Similar to cancer, cardiovascular diseases are
frequently cited among those that gene therapy is
© 2015 The Author(s)
Journal Compilation © 2015 Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences
Hamdan Medical Journal 2015; 8:101–110 (http://dx.doi.org/10.7707/hmj.304)
REVIEW
expected to cure. These diseases include, among
others, heart failure, arrhythmia and coronary artery
disease.56 Both the in vivo (percutaneous) and the
in vitro approaches to gene delivery may involve
non-viral and/or viral vectors.57 That said, viral
vectors are given preference, as they have proven
more efficient and some of them (e.g. adenoviruses)
can even infect the non-dividing cells of the
cardiovascular system.56 Jessup et al.58 specifically
exploited adeno-associated viruses in a study on
39 patients to examine the efficacy of sarcoplasmic
reticulum-calcium (Ca2+)-adenosine triphosphatase
(ATPase) (SERCA2a) in alleviating the symptoms of
heart failure. It is worth noting that reduced calcium
uptake, which has been observed in failing hearts, is
closely associated with a decrease in the expression
and activity of SERCA2a. To normalize intracellular
calcium cycling and correct cardiac metabolism,
the authors randomly administered the patients
with either one of the three different doses of
SERCA2a-transformed adeno-associated virus type 1
or a placebo by coronary artery infusion over a
12-month period. In the end, their results attested
to the effectiveness of the method, as the patients
who had received higher doses exhibited
considerable improvement in functional capacity,
symptoms and cardiac structure.58
Multiple sclerosis (MS) is an autoimmune disease
with good prospects for a gene therapy-based
cure. Patients afflicted by this chronic, neurological
disease of the central nervous system experience
episodes of neurological deficits in the earlier stages,
followed by progressive neurological deterioration.59
Currently, a wide range of disease-modifying
therapies, such as those using interferon-β (IFN-β)
(down-regulating T-helper cells), glatiramer acetate
(Copaxone®, Teva UK, Essex, UK; preventing
lymphocyte proliferation) and mitoxantrone
(inhibiting repair by topoisomerase), are in use or
under study.60 However, the fact that most of these
drugs do not elicit an optimal response in many
patients has directed attention towards gene
therapy. Ryu and colleagues61 reported the use of
IFN-β as a therapeutic gene to reduce the
autoimmune effects of MS. Initially, human bone
marrow-derived mesenchymal cells (MSCs) were
cultured and infected with adenoviral vectors
transformed with either green fluorescent protein
(GFP) or murine IFN-β. To induce experimental
allergic encephalomyelitis (an animal model for MS),
the mice were given the MOG35–55 peptide
emulsified in Freund’s adjuvant containing
Mycobacterium tuberculosis. Later, the models were
divided into two groups, each receiving either
MSCs–GFP or MSCs–IFN-β. The impact of the
therapy was evaluated, taking into account its
various aspects and likely consequences. Histological
analysis of spinal cord sections taken from mice
containing MSCs–GFP (control) and MSCs–IFN-β
revealed that demyelination and infiltration were
more severe in the former. In addition, the results of
an enzyme-linked immunosorbent assay confirmed
the immunomodulatory effect of the therapy by
indicating that cytokine levels were far lower
in MSCs–IFN-β recombinants. To those, one has
to add the relatively high expression levels of
a regeneration stimulant called the neurotrophic
factor in the MSCs–IFN-β models that further added
weight to the reliability of the method.61
Type I diabetes mellitus (T1DM) is another
autoimmune disease, among several others, that has
been shown to be a viable candidate for treatment
by gene therapy. T1DM occurs as the result of the
autoimmune destruction of insulin-secreting β-cells
that induce the removal and metabolism of glucose
by muscle and liver cells, respectively.62 T1DM is a
polygenic disease, as it is caused by the combined
effect of more than one underlying susceptibility
gene. About 18 loci (regions) of the genome,
besides environmental factors such as diet and
infection(s), are known to contribute to the onset of
T1DM. Most of these loci harbour multiple genes
and are labelled insulin-dependent diabetes
mellitus 1 (IDDM1) to 18 (IDDM18). The two most
researched loci, IDDM1 and IDDM2, contain genes
that encode immune response proteins and
preproinsulin, respectively.63 Currently, the sole
treatment option for diabetic patients is insulin
administration. However, exogenous insulin is not
physiologically regulated. Moreover, the occasional
lack of patient adherence exacerbates the condition,
resulting in suboptimal control and secondary
complications.64 These setbacks can be avoided
with gene therapy; nevertheless, ectopic insulin
expression alone cannot cure T1DM unless it is
accompanied by a regulatory system that responds
to variations in glucose concentration in the blood.65
In a recent effort to counteract T1DM using gene
therapy, Callejas and coworkers66 aimed at increasing
the muscular uptake of glucose through the
coexpression of insulin and glucokinase (GK) in
skeletal muscle cells. Insulin was required to ensure
transport of glucose by insulin-stimulated glucose
transporter 4 (GLUT4) and GK was made available to
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facilitate glucose uptake by muscle cells in the
event of hyperglycaemia (high blood glucose).
Five beagle dogs induced with streptozotocin and
alloxan to exhibit symptoms of T1DM were injected
in the leg with adeno-associated viral vectors
that carried either an insulin- or a GK-encoding
gene. The immunohistochemical analysis and
radioimmunoassay of insulin in conjunction with the
measurement of blood glucose using a Glucometer
Elite analyser (Bayer, Leverkuser, Germany)
indicated the normalization of insulin and glucose
levels. Further, northern blot analysis confirmed the
expression of the two transgenes in the skeletal
muscle biopsies of the models. The long-term efficacy
of this approach was established as the models, so far,
have lived in good health for more than four years.
The prospects of gene therapy go well beyond the
current scope of its applications. Researchers are
constantly pursuing new strategies that tap into
the therapeutic potentials of various cellular
components and machineries. Pseudogenes, for
instance, can be thought of as suitable tools for
gene therapy. In simple terms, a pseudogene is a
(usually) non-functional DNA sequence that bears a
resemblance to one or two functional parent
genes in the genome. The lack of function is
because of either the presence of mutations in the
pseudogene or the loss of regulatory sequences,
resulting in the disruption of transcription or
translation.67,68 Dewannieux et al.69 showed that the
human endogenous retrovirus HERV-K (HML2)
(a non-functional remnant of ancestral retroviral
infections) could regain its infectiousness and repeat
its life cycle following a multistep recombination
event with functional alleles.69 This suggests the
possibility of resuscitating beneficial pseudogenes
such as ψ connexin 43 (ψCx43), which tends to
suppress the growth of breast cancer cells,70 for
therapeutic purposes.
Arguments: for and against
Although everyone more or less acknowledges
the tremendous potential of gene therapy to
revolutionize clinical sciences, some sceptics with
backgrounds in both science and ethics have raised
questions that not only pose a challenge to its
technical aspects but also underline the moral issues
provoked by gene therapy. The vast majority of
these questions concern the germline mode of gene
therapy, as its outcomes are, contrary to the somatic
mode, not confined to the patient under treatment.
106
Yet some of the opponents even revile somatic gene
therapy, despite its wide public acceptance.
Among the critics, some have gone so far as to argue
against gene therapy in its entirety. One of their
arguments is that gene therapy is still in its infancy,
with a scope that is too limited to overcome its
limitations and prevent its possible adverse
consequences. These consequences usually arise
from flawed gene transfer that may result in
mutations (insertional mutagenesis), up-regulation of
oncogenes or inactivation of tumour suppressor
genes.71 In addition, the present shortcomings of
gene therapy are pointed out as major obstacles to
its success. Some of the most common genetic
disorders such as T1DM, hypertension and
Alzheimer’s disease are polygenic in nature. Such
disorders, unlike their monogenic counterparts, are
extremely complicated to treat effectively and
permanently using gene therapy.72 The opponents
also assert that the very high cost of gene therapy
renders it against fairness and equality, as it would
allow only the affluent minority to benefit from
treatment.73 Yet another concern raised is that
altering the human genome, which is perceived as
the blueprint of life, in any form or fashion is an act of
‘playing God’, with serious threats to human dignity.74
As for somatic gene therapy in particular, its
opponents express their fear of the probable
technical errors and the slippery slope that could
lead to crossing the barrier between the somatic
mode and the germline mode of therapy. From a
technical point of view, they state that the incorrect
choice of vectors and target cells could pave the
way for a therapeutic transgene to spread to the
gonads and affect the genotype of the offspring.73
Socioethically, they claim that permitting somatic
gene therapy is a preliminary step on a slippery
slope towards what is described as the horrendous
manipulation of humankind that is made possible
by germline gene therapy.75
When it comes to germline gene therapy, the
debate get more intense and the naysayers’ tone
more resentful. Their argument is essentially based
upon the consequences of deviating from a
treatment-centred use of the therapy. The most
frequently mentioned concern is employing the
method for genetic enhancement. This is often
illustrated with healthy individuals such as athletes
who seek physiological improvements6 and
‘designer babies’ possessing their parents’ favourite
© 2015 The Author(s)
Journal Compilation © 2015 Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences
Hamdan Medical Journal 2015; 8:101–110 (http://dx.doi.org/10.7707/hmj.304)
REVIEW
traits.76 Such activities may, as the commentators
suggest, set in motion a chain of events leading to
the re-emergence of eugenics. Another concern
surrounding germline gene therapy is that any
accidental mistakes in the process will undoubtedly
create a lineage of people whose genomes have
been not only manipulated without their consent
but also disrupted before they were born.77
On the other hand, the pro-gene therapy arguments
hail the technique as a highly efficient and absolutely
ethical saviour of human beings in the face of
otherwise incurable diseases. People holding this
perspective view gene therapy as a continuation
of other conventional therapies with bigger,
life-saving promises and exaggerated drawbacks.
They contend that germline gene therapy is
exceptionally efficient, as its application in one
individual can preclude the reappearance of a
disorder in succeeding generations. Evidently, it
would also be less costly for patients and useful in
conserving future health care resources.73,78
Furthermore, the advocates put forth the rationale
that gene therapy is necessary owing to its ability to
cure unique diseases such as Parkinson’s disease79
and retinoblastoma80 that other therapies have
consistently failed to beat. On ethical grounds, gene
therapy is considered pro-life by the likes of French
Anderson, a leading National Institutes of Health
investigator, who believes ‘it would be unethical to
delay human trials’, as he thinks that ‘the patients
have little other hope’.81 In addition, germline gene
therapy provides the opportunity for couples to save
their genetically challenged embryos, rather than
discard them outright.78
those against gene therapy overstate a few points,
such as the lack of morality in modifying genes and
the possibility of the non-medical use of gene
therapy, without appreciating its very real prospects.
First, the notion that altering DNA poses a threat to
human dignity is subjective, and may vary from one
belief system or theory of ethics to another. This
raises the question of whose beliefs should be
preferred to those of others who might possibly be
in favour of gene therapy. Second, the fear that
allowing one form of gene therapy could facilitate
the emergence of the other, which in turn could be
exploited for non-medical purposes, is merely
justified by a rhetorical slippery slope that an action
will ultimately culminate in havoc via a chain of
uncontrolled events. Although regulation is
essential, the slippery slope argument, as it is put
forth, would call a halt to most of the ongoing
medical and non-medical research across the globe.
Third, the fact that gene therapy could be error
prone holds true for most scientific developments.
However, rigorous research on the technique to
verify its safety could significantly minimize the
likely errors. In addition, devising and enforcing
such regulations as prohibition of non-medical uses
of gene therapy, requirement of the patient’s
informed consent and proof of the necessity of
gene therapy to treat a disease can further help
address the issue. In the end, bringing mankind’s
creativity, which fuels developments in gene
therapy, to a standstill is taking the easy way out,
rather than dealing with the issue.
References
1
Conclusions
2
The premise of gene therapy as a novel therapeutic
technique, capable of introducing new genes and/or
correcting existing defective genes in an organism,
is as ethically controversial as it is scientifically
ground breaking. Both the somatic and germline
modes of gene therapy have spurred vehement
debates among those who consider it immoral and
unreliable and others who admire it on account of
its unique and medically plausible potentials. An
overall look at the issue and the positions on either
side reveals that some aspects or others are being
undermined by either the supporters or the critics.
On the one hand, those that support gene therapy
usually downgrade the fact that it could lead to
unexpected repercussions, and, on the other hand,
3
© 2015 The Author(s)
Journal Compilation © 2015 Sheikh Hamdan Bin Rashid Al Maktoum Award for Medical Sciences
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