Gene Therapy: the Danger of Enhancement
Ryan Troyer
November 25, 1996
Biology Senior Seminar
Outline
Thesis: Ethical guidelines for gene therapy must be established which
emphasize medical uses over uses for human enhancement.
I. Introduction
II. Concepts of Gene Therapy
A. Background information: what is gene therapy?
1. Genetic transfer of foreign DNA
2. Vectors
3. Types of gene therapy
B. Current efficacy of gene therapy and progress in research
1. A hot medical field, but no clinical efficacy thus far
2. The difficulty of vectors
3. Gene therapy's potential
III. The Need for Ethical Analysis of Enhancement Gene Therapy
A. The primary ethical line should not be drawn at germ-line therapy
1. Arguments against germ-line therapy
2. If scientific problems are solved, germ-line therapy will
hold good possibilites for medicine
B. Enhancement therapy is a destructive use of gene therapy
1. Enhancement
a. Eugenics
b. Feasibility
2. Arguments in favor of enhancement
3. Implications for society
a. Genetic discrimination
b. Pressure to use gene therapy
c. Who gets the genes?
4. Concerns of medical risk
C. Public perceptions of gene therapy and DNA
D. Ethical guidelines will clear the way for medical gene therapy
1. Altering the direction of research in a positive way
2. Effective lines may be drawn
IV. Drawing the Line: 'Medical' and 'Enhancement' Uses
A. Definitions of disease and medicine
1. What conditions warrant gene therapy?
2. Modern medicine's model of disease
B. Establishment of ethical guidelines
1. A guiding principle: beneficience
2. RAC should lead the way
V. Conclusion
I. Introduction
Gene therapy has the potential to revolutionize modern medicine. The techniques
of gene therapy are still in their infancy as medical treatments and there
are still many problems which must be solved before gene therapy will live
up to its potential. However, it is very likely that gene therapy will become
a reality at some point in the future and when that time comes, the ethical
questions surrounding gene therapy will be pushed to the forefront of medicine.
Science may find a way to reduce the risks associated with gene therapy
but science alone cannot eliminate the serious ethical and societal risks
which gene therapy brings to bear on the world. We need to put people's
fear about the dangers of altering the genetic makeup of human beings to
rest by establishing ethical principles which clear the way for advancement
in medical therapy. Ethical guidelines for gene therapy must be established
which emphasize medical uses over uses for human enhancement.
II. Concepts of Gene Therapy
Gene therapy involves the transfer of genetic
material into the cells of an organism in order to cause a specific protein
to be produced or in order to cease the production of a specific protein.
This procedure usually involves transferring a specific gene into host cells
to be incorporated into the chromosomal DNA of the host and later to be
expressed. However, according to Dorothy Bonn, the future of gene therapy
may also include the use of antisense DNA strands to disrupt expression
of a gene or the use of homologous recombination to alter host DNA (1996).
In medical terms Jeffrey Leiden, M.D. (1995) defines gene therapy as, "the
introduction and expression of recombinant genes in cells for the purpose
of treating a disease" (p. 871).
In order to transfer foreign genes into a cell, a vector is necessary. Currently,
modified viruses, liposomes and bacteria are being employed as vectors for
gene transfer with viruses being by far the most commonly used (Bonn, 1996).
According to Craig Donegan, there are three basic methods of delivery: the
ex vivo method transfers DNA to cells extracted from the patient
and reinjects those cells, the in vivo method injects vectors into
the bloodstream to seek and bind targeted cells, and the in situ
method injects vectors directly into the affected tissue (1995).
We currently group types of gene therapy by the nature of the cells which
are affected and the goal of the therapy. Nelson Wivel, director of the
Office of Recombinant DNA Activities at the National Institutes of Health
(NIH), and Georgetown University professor of philosophy and ethics Leroy
Walters (1993) group types of gene therapy into three categories: type 1
is gene therapy which affects only non-reproductive or somatic cells, type
2 is gene therapy which involves gene transfer to reproductive or germ-line
cells, types 3 and 4 are the use of somatic and germ-line modifications
respectively to "affect selected physical and mental characteristics
with the aim of influencing physical appearance or abilities" - enhancement
therapy (p. 533). In the U.S., the Recombinant DNA Advisory Committee (RAC)
at NIH oversees research and clinical trials of gene therapy. At present
the RAC permits many somatic cell therapy trials but does not permit germ-line
therapy trials.
Gene therapy is an extremely hot field in medical
technology right now with NIH spending $200 million per year on research
and clinical trials and private industry spending about the same amount
according to Eliot Marshall (1995). Progress in gene therapy research has
been steady but no method of gene therapy on humans has yet proven effective.
The field took off in 1980 when it was demonstrated that direct injection
of foreign genes into the nucleus of a mouse egg resulted in the integration
and retention of the injected genes in the newborn animal (Wivel and Walters,
1993). Since that discovery, the understanding of the molecular mechanisms
involved in gene therapy has increased greatly and gene therapy has been
shown to be relatively effective in many animal trials. Some researchers
have made claims of great success in human gene therapy in order to lure
biotech investors or to receive large funding grants. However, an NIH panel
in 1995 stated, "clinical efficacy has not been definitely demonstrated
at this time in any gene therapy protocol despite anecdotal claims of successful
therapy" (Marshall, 1995, p. 1751). In a highly-hyped recent clinical
trial, boys with Duchenne's muscular dystrophy were treated ex vivo
but the transformed myoblasts used showed little or no persistence in the
boys, let alone any corrective function (Leiden, 1995).
The primary difficulty with gene therapy has been finding effective vectors
for the transfer of genes to target cells. A great deal of current research
is being done to find effective vectors. Andy Coghlan notes that one example
is that researchers are working on using transposons or 'jumping genes'
to modify viruses so that corrective genes may insert at 'safe' locations
in chromosomes (1995). The over-hyped, often ill-advised early clinical
trials paint a desperate picture of gene therapy but the truth is that it
is highly likely gene therapy will be a reality at some point in the not-so-distant
future. Dr. Ronald Crystal of Cornell University Medical College states,
"The logic behind gene therapy is so compelling, the science so deep,
there is no question it is going to work." (Begley, 1995, p. 62).
The future may indeed hold great uses for gene therapy which could rival
other past medical innovations such as the discovery of penicillin in importance.
Gene therapy has the possibility of curing inherited genetic disorders such
as Huntington's disease and cystic fibrosis, acquired diseases such as AIDS,
and even a disease as complex and prevalent as cancer. The potential power
of this new therapy necessitates the consideration of ethical issues surrounding
its use.
III. The Need for Ethical Analysis of Enhancement
Gene Therapy
The vast majority of the ethical consideration
surrounding gene therapy has centered on germ-line therapy. In 1992, according
to Coghlan (1996), a government advisory committee recommended that germ-line
therapy not be attempted because of "insufficient knowledge to evaluate
the risks to future generations." (p. 14). Indeed the RAC has banned
trials of germ-line therapy.
However, the primary arguments against the use of germ-line therapy involve
scientific problems with the technique rather than societal implications
of its use. Genes such as the gene for sickle cell anemia, which also confers
malaria resistance, could be wiped out before their role is completely understood
(Coghlan, 1996). In this way, human biodiversity could be threatened. Also,
gene replacement would be needed rather than gene addition because a mixture
of regulatory signals from normal and mutated genes would produce unpredictable
effects on growth and development (Wivel and Walters, 1993). Admittedly,
there are those who argue that by altering the germ-line we would be violating
the "sacred" nature of reproduction but Wivel and Walters (1993)
point out that germ-line gene therapy directly fits into the "therapeutic
continuum" of modern medicine which includes such treatments as giving
chemicals to a fetus to activate dormant genes (p. 536).
Truly there are many valid scientific concerns surrounding germ-line therapy
but scientific problems are of the type which by definition may be solved.
Henry Miller suggests that possibly gene therapy could be put under positive
control and thus be inducible rather than permanent (1994). It may be possible
for a protocol to be established with gene replacement in which no insertional
mutagenesis occurs along with few side effects. Even with some side effects,
germ-line gene therapy could be useful in extreme cases of disease such
as those which cause the early death of children. In these cases, somatic
cell therapy would likely be ineffective and limited side effects might
be deemed acceptable in order to save the child's life. Examples of diseases
which would fit this category are Tay-Sachs and Lesch-Nyhan syndrome (Coghlan,
1996). Even with the risk of side-effects which might not show up in the
patient for years, germ-line therapy may be judged worthy of that risk in
cases of therapy for fatal diseases. Genetic diseases affect only two percent
of live births and among those very few are serious fatal conditions, thus
the danger of large-scale effects on the gene pool is minimal (Wivel and
Walters, 1993).
Much more scientific knowledge about gene therapy
is necessary before germ-line therapy could become a reasonable possibility.
However, drawing the primary ethical line for gene therapy at germ-line
therapy ignores the real ethical danger of gene therapy: its use for the
purpose of human enhancement. The true danger of germ-line therapy is that
it might be used to produce genetically enhanced 'designer' people but this
same danger of enhancement exists also in the realm of somatic cell therapy.
Thus, the RAC should be much more concerned with defining the use of gene
therapy for enhancement as unethical and detrimental to the medical possibilities
for gene therapy rather than attempting to draw a line at germ-line therapy.
What is meant by 'enhancement' gene therapy? Gene therapy for the purpose
of enhancement simply signifies the use of gene therapy to alter a medically
normal person physically (including mental capacity) in a way which is thought
to be an improvement. Thus, it falls under the category of eugenics - improving
human character through genetic manipulations. The idea of eugenics is not
new. As noted by Rebecca Voelker, nineteenth century British scientist Francis
Galton founded a 'eugenics movement' with the idea of 'improving' humans
through selective breeding (1993).
Realistically, gene therapy for enhancement is not feasible with our current
level of understanding. However, advances in gene therapy techniques will
almost undoubtedly bring the possibility for enhancement to bear on society.
Some examples of possibilities for genetic enhancement which may first become
possible include genes coding for an appetite suppressant hormone, anti-baldness
hormone, a brain chemical enhancing memory, growth hormone, and resistance
to industrial toxins (Miller, 1994). One can easily imagine these possibilites
becoming reality but many other more extreme possibilities may certainly
exist.
Arguments in favor of the use of gene therapy for enhancement center around
personal autonomy and individual choice. Indeed we live in a pluralistic
democratic Western society which highly prizes the individual. Some view
gene therapy for enhancement on a long continuum of treatments which has
grown to give people more freedom and control over their lives. Henry Miller
(1994) asks, "On what scientific, legal, or ethical basis should [somatic
gene therapy for enhancement] be subjected to a higher standard then liposuction,
radial keratotomy, or the application of permanent makeup by tattooing?"
(p. 317). Miller claims that people have a right to make what they want
of their lives and so they should have a right to increase their mental
powers with extra neurotransmitters, or change hair and skin color, run
faster and lift heavier weights (1994).
The answer to Miller's call for autonomy must be that we cannot view the
altering of human genes as a solely personal decision. Leading scientists
in gene therapy certainly recognize this fact. Wivel and Walters (1993)
state, "The human gene pool is a joint possession belonging to all
members of the human species" (p. 536). W. French Anderson, M.D. (1991),
leading scientist in the area of gene therapy, believes that enhancement
degrades the human species. He points out that gene therapy becomes bad
"when it detracts from, rather than contributes to, the dignity of
[humans]." (p. 685). Whether one views this issue from a theological
or humanist point of view, gene therapy for enhancement is a threat to human
values which we feel are important to the dignity of humans.
The primary 'value' of which Anderson speaks, that enhancement therapy would
violate, is the value of social justice. Our society has become one in which
people place a great deal of value on genetics. Genetic testing is now commonplace
and many claim that genetic discrimination is already occurring. Wendy McGoodwin
of the Council for Responsible Genetics notes that insurers have sought
genetic information on persons who want health or life insurance and employers
have used genetic data to look for liabilities in prospective employees
(Donegan, 1995). This is clearly discrimination against healthy people with
suspect genes. The most famous example of this kind is certainly the 1970's
discrimination against African Americans carrying the sickle cell anemia
gene by employers and insurers (Voelker, 1993). In this social climate,
the ability to 'improve' one's genetic makeup would certainly perpetuate
and increase the focus on genes as a means to discriminate. As more genes
are located, this discrimination would intensify. NIH researcher Dean Hamer
claims to have found a 'gay gene' and already there is talk of 'corrective
measures' (Donegan, 1995).
With this intense focus on genetics, the pressure to use gene therapy would
be immense. Miller claims that restricting enhancement would threaten autonomy.
However, autonomy is challenged a greater way when intense pressure exists
to receive gene therapy. In order to survive in an enhanced society, one
would need to keep up with the level of enhancement competitors for school
admissions or jobs. Coghlan cites two negative results of this type of pressure:
a significant reduction in the size of the human gene pool and a huge 'black
market' of genetic enhancement (1996).
With medical gene therapy, the person in need is given therapy based on
medical need, but with enhancement gene therapy who gets the genes? Those
with the most urgent need? Those most able to benefit society? Those able
to pay for it? Enhancement, not falling within the medical realm, would
likely be a treatment for sale to those who could afford it. John Habgood,
the Archbishop of York, stated in reference to this problem, "People
who are less than perfect would be steadily more disadvantaged, and this
would tend to push people further into the realm of the unacceptable."
(Coghlan, 1996, p. 14).
Using gene therapy with possibly unforeseen ill side-effects is a risk that
may be worth taking in the case of a life-threatening or very serious disease,
however, the use of this technology for enhancement warrants more serious
consideration of the amount of scientific non-knowledge present. Is the
possibility of the activation of an oncogene or the inactivation of tumor
suppressors worthy of the risk? Wivel and Walters point out that subtle
adverse effects on the brain may not be detected in animal models or noticed
in patients for decades (1993).
With so many adverse possibilities for gene therapy,
it is no wonder that much of the general public has a negative view of gene
therapy in general. Dorothy Nelkin (1996) notes that a large part of this
belief is also due to scientists' use of religious imagery to convince people
of the power of genes and subsequently the importance of their research
- calling DNA the "holy grail" of biology, the "stuff of
life" or the "master genetic code" (p. 24). Some Christian
journalists also write about DNA as something which in itself has spiritual
importance (Nelkin, 1996). Even in the secular world, DNA is often assigned
a value equal to the core of our 'humanness.' It is true that using DNA
for the purpose of enhancing people is likely not consistent with Christianity
or secular humanism (an explanation of which is outside the scope of this
paper). However, as John Fletcher (1985) pointed out a decade ago, an approach
to disease treatment with DNA is not different from using other human products
such as "blood, organs, hormones and bone marrow" in therapy (p.
301).
These ideas create a culture in which people are
afraid of gene therapy. Much of this fear is warranted because of enhancement
technology. Thus in order to promote a more educated culture ready to accept
medical gene therapy, we must prevent applied research which has enhancement
technology as its goal. As ethicist Hans Jonas says, "not only have
the boundaries between theory and practice become blurred, but ... the two
are now fused in the very heart of science itself, so that the ancient alibi
of pure theory and with it the moral immunity it provided no longer hold."
(Wright, 1989, p. 183). Donegan (1995) points out that in an open market
in the $200 million per year gene therapy industry, "there will be
more scientists working on male pattern baldness than sickle-cell anemia"
(p. 1091). This would be a true shame, and that is why restrictions are
needed - not to decrease gene therapy research but to aim it in a positive
direction. Richard Wright (1989) states, "It is possible to develop
biotechnologies that will bring help to those who need it most - the poor,
those in Third World countries who suffer from hunger, parasites, and diseases.
Is there any hope that these will be the priorities of a profit-motivated
biotech industry?" (p. 218).
Many argue that effective lines can not be drawn between gene therapy for
medical reasons and gene therapy for enhancement purposes. However, as Fletcher
points out, meaningful moral lines between acceptable and unacceptable research
and clinical practices have emerged over the past forty years (1985). We
are currently in the process of drawing meaningful lines on terminal illness
and there are certainly enough people with training in medical ethics to
begin meaningful dialogue on this issue. Still others argue that legislation
of morality is unjust in our pluralistic society. However, as previously
stated, the use of gene therapy affects not only the individual, but all
of society. Wright (1989) notes that government should legislate morality
on matters dealing with "public justice and the social order"
(p. 190).
IV. Drawing the Line: 'Medical' and 'Enhancement'
Uses
If a line is to be drawn between 'medical' and
'enhancement' uses of gene therapy, these terms must be defined. What shall
we define as a disorder worthy of medical attention? Miller asks the following
question: is obesity a serious disorder at triple ideal body weight, thirty
percent above ideal weight, or anything above the ideal? (1994). What about
'disorders' such as myopia, color-blindness, and left handedness? (Fletcher,
1985). Is skin color a disorder which needs medical attention?
In order to find a definition for which genetic conditions are worthy of
medical attention, we must first recognize the way in which contemporary
medicine looks at genetic disorder. Wright (1989) states that in our model
of modern medicine, "Health constitutes the freedom from disease, pain,
or defect; the normal human condition is health." (p. 186). This generates
unreal expectations of health when 'normal' life "excludes headaches,
tensions, depression, deformity, and the like" (p. 186). Even death
is considered abnormal. When one puts genetics into this context, essentially
any genetic variation which society does not view as 'healthy' is automatically
abnormal. Also, 'abnormality' may be solely attributed to genetic factors
without consideration for the complex interplay between genetics and the
environment. However, Rochelle Hirschhorn, M.D., chief of medical genetics
at NYU Medical Center, claims that "contemporary medicine is awakening
to the fact that everyone has some type of genetic anomaly" (Voelker,
1993, p. 2273). Despite this awakening, the view of genetics as being faulty
when one is not perfect is still prevalent. Thus our modern model of medicine
does not provide an automatic answer to this question of definitions.
W. French Anderson (1991) defines enhancement genetic engineering as, "the
supplying of a specific characteristic that individuals might want for themselves
or their children which would not involve the treatment of a disease"
(p. 682). This definition of enhancement places emphasis on disease. The
Random House Dictionary of the English Language defines 'disease' as "a
disordered or incorrectly functioning organ, part, structure, or system
of the body resulting from the effects of genetic or developmental errors,
infection, poisons, nutritional deficiency or imbalance, toxicity, or unfavorable
environmental factors" (1987). Again, this definition of disease really
does not clear up the questions posed above of when a treatment for medical
reasons becomes one of enhancement.
Some type of guiding principle is needed to draw
a line and I believe that this should be the principle of beneficence. It
is my opinion that the most meaningful moral distinction between 'enhancement'
and 'medical' gene therapy is that 'medical' gene therapy would relieve
real suffering while 'enhancement' gene therapy would change characteristics
that have little to do with real suffering. Real suffering involves, as
Fletcher (1985) says, "morbidity and mortality" (p. 303). A condition
which dominates a person's life and is characterized by intense pain or
early death should be relieved. The question to be asked of any new potential
gene therapy protocol should be: can these improvements be justified on
the basis of relief of human suffering? If not, then the technique must
be considered as an enhancement use.
I believe that at this point in time, the RAC is in the best position to
create policy against the use of gene therapy for enhancement purposes.
This would set a standard for research and technology in the U.S. which
would promote the development of positive uses of gene therapy. Abbey Meyers,
or the National Organization for Rare Diseases, points out that it is likely
that each country will make its own rules regarding gene therapy as it develops
(Coghlan, 1986). Thus enhancement technology may be developed regardless
of U.S. resolutions. However, the U.S., as the current world leader in medical
research, is in a position to take a stand against the exploitation of gene
therapy for enhancement uses.
V. Conclusion
In summary, much current consideration is given to the ethics of germ-line
therapy. However, this practice of drawing ethical lines at germ-line therapy
avoids questioning the truly ethically dubious possibilities for gene therapy
- uses of the technology for human enhancement. Gene therapy for enhancement
should not be permitted because it would be extremely unjust and oppressive
to society. By drawing a distinct ethical line between medical and enhancement
uses, we would eliminate a great deal of the fear which surrounds gene therapy
and also aim research interests in a positive direction towards medical
goals.
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