Download Gene therapy

Engineering the engineer as well as the engine, we
race our train we know not where.
Leon Kass
2013
Marek Vácha
GENE THERAPY
Gene therapy
 Pills
 Cell therapies
 The gene itself becomes the drug
Gene therapy
 somatic cells
 concerns one single individual
 germ cells
 concerns plenty of individuals
LeRoy Walters:
What does it mean to be human? Adding a
occasional gene here and there is not going to
alter who we are as a human race. But if we
draw no line, if we accept that people have a
right to make what they want of their lives,
then we condone the right of humans to
manipulate their genomes in the absence of any
real knowledge of what they are doing. Might
we add a gene here and alter a gene there until
we become a society of chimeras, uncertain who
we are?
CURRENT GOVERNMENT
POSITIONS
 CONVENTION FOR THE PROTECTION
OF HUMAN RIGHTS AND DIGNITY OF
THE HUMAN BEING WITH REGARD TO
THE APPLICATION OF BIOLOGY AND
MEDICINE:
 CONVENTION ON HUMAN RIGHTS
AND BIOMEDICINE
Oviedo, 4.IV.1997
Oviedo 1997:
CONVENTION ON HUMAN RIGHTS AND BIOMEDICINE
 Article 13 – Interventions on the
human genome
 An intervention seeking to modify the
human genome may only be undertaken
for preventive, diagnostic or therapeutic
purposes and only if its aim is not to
introduce any modification in the genome
of any descendants.
USA
 legally, there is no ban in the United States
on germline engineering research
 1996: New Jersey: the doctors took a client´s
fertilized egg and added 5% of the cytoplasm
(including mitochondria) from a donor egg to
replace any malfunctioning units in the
client´s egg.
 Between 1996 and 2001, a reported 16
babies with the genetic makeup of three
parents (the client mother and father and the
female cytoplasm donor) were born
UNESCO: Universal Declaration on the Human Genome and
Human Rights
11 November 1997


= nonbinding declaration
Article 24
The International Bioethics Committee of UNESCO should
contribute to the dissemination of the principles set out in this
Declaration and to the further examination of issues raised by their
applications and by the evolution of the technologies in question. It
should organize appropriate consultations with parties concerned,
such as vulnerable groups. It should make recommendations, in
accordance with UNESCO’s statutory procedures, addressed to
the General Conference and give advice concerning the follow-up
of this Declaration, in particular regarding the identification of
practices that could be contrary to human dignity, such as germline interventions.
 This declaration was signed by 186 nations.
Biological background
...not very important for obtaining
the credits, but nonetheless very
interesting!
Gene
therapy
 for gene therapy of somatic cells to be
permanent, the cells that receive the
normal allele must be ones that multiply
throughout the patients´s life.
 If the treatment is succesfull, the patient´s
bone marrow cells will begin producing the
missing protein, and the patient may be
cured.
In vivo and Ex vivo gene therapy
The first definite success: a cure for X-linked severe
combined immunodeficiency: X-SCID, Paris 2000
 nine of 11 treated patients were cured and
enabled to lead a normal life
 they showed significant, definitive
improvement after two years, the first
indisputable success of gene therapy.
The first definite success: a cure for X-linked severe
combined immunodeficiency: X-SCID, Paris 2000
 however, three of them have subsequently
developed a leukemia almost certainly as
a result of insertional activation of the
LMO2 oncogene.
 one of them died
 all trials involving retroviral transduction of
large pools of lymphocytes were quickly
suspended worldwide, pending full
understanding of these tragic events.
The first definite success: a cure for X-linked severe
combined immunodeficiency: X-SCID, Paris 2000
 two factors may have contributed to the
development of leukemia:
 the insertion of the retroviral vector near a
gene involved in the proliferation of blood cells
 unknown function of the replacement gene
itself
Contemporary strategies
(A) Loss-of-function conditions.
(B) Gain-of-function conditions.
Contemporary strategies
miRNA
miRNA
1..
2.
3.
4.
5.
1. An enzyme cuts each hairpin from
the primary miRNA transcript
2. A second enzyme, called Dicer, trims
the loop and the single-stranded
ends from the hairpin, cutting at the
arrows (the fragment has about
20bp).
3. One strand of the double-stranded
RNA is degradated; the other strand
(miRNA) then forms a complex with
one or more proteins.
4. The miRNA in the complex can bind
to any target mRNA that contains at
least 6 bases of complementary
sequence.
5. If miRNA and mRNA bases are
complementary all along their length
siRNAs
RISC = RNA-induced
silencing complex
miRNAs and siRNAs
 the same cellular machinery generates miRNAs
and siRNAs and both can associate with the
same proteins, producing similar results
 the distinction between miRNAs and siRNAs is
based on the nature of the precursor molecule
for each
 while an miRNA is usually formed from single hairpin in
a precursor RNA, siRNAs are formed from much
longer double-stranded RNA molecules, each of which
gives rise to many siRNAs
 it has been estimated that expression of up to
one-third of all human genes may be regulated
by miRNAs
Contemporary strategies
Somatic Cell Gene Therapy
 most scientists agree that treating a
disease by inserting a corrected gene into
a patient is not ethically different from
using medicines to treat the disease.
 most of the concerns: the safety of the
procedures

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 200)
Treatment or Enhancement?
 the boundary between treatment (for
disease) and enhancement (for cosmetic
or athletic purposes) can be indistinct
 is short stature a disease?
 is infertility a disease?
 is baldness a disease?

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 200)
Myostatin
„Schwarzenegger mice“
 studies in mice
showed that if the
gene for myostatin is
absent, the mice grow
into muscular rodents
who are stronger and
faster than their nonmutant littermates
Myostatin
„Schwazenegger mice“
 individual muscles from myostatin mutants mice
weighed 2-3 times more than muscles taken
from normal mice
 the increased muscle mass resulted from both
an increased number of muscle fibers and an
increased size of individual fibers
Myostatin
„Schwazenegger mice“
 a human child has been found who is
deficient in this gene
 he has an exceptional musculature and is
much stronger than other boys of his age
 although he is healthy, physicians are
watching him closely because the same
gene is active in heart muscle, where such
enlargement can be dangerous

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 201)
Somatic gene therapy
 A notable example is the trials conducted
on patients suffering from cystic fibrosis,
who inhale an aerosol spray of liposomes
containing the gene that patients lack.
 if they were more promising, such therapies
might appear to be ethically unproblematical,
because any changes induced would be
limited to the patient and not passed on to
their children

(Mepham, B., (2008) Bioethics. An Introduction for the Biosciences. Oxford University Press,
Oxford, p. 139)
 squirrel
monkeys have two opsin genes
 the opsin encoded by one gene is
sensitive to blue light
 the other opsine is sensitive to either red
or green light, depending on the allele
 because the red/green opsin gene is Xlinked, all males have only the red
sensitive or green sensitive versions and
are red-green color blind
 in
a gene therapy experiment,
researched injected a virus containing
the gene for the missing version into the
retina of adult male monkeys.
 After 20 weeks, the new opsin allele was
being expressed in cones and the
monkeys had begun to distinguiosh red
from green in a field color dots.
 Gene
therapy has already been used to
treat Leber´s congenital amaurosis (LCA),
an inherited retinal degenerative disease
that dauses severe oss of vision at birth.
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After using gene therapy to restore vision in dogs
and mice with LCA, researchers succesfully
treated the disease in humans by injecting the
functioanl LCA gene in a viral vector.
(Reece, J.B., Urry, L.A., (2011) Campbell Biology. 9th. ed. Pearson Publication, Inc. , New York. p. 1146)
Germline Gene Therapy
Germ-line genetic modification
 A therapeutic effect of a somatic-cell gene
therapy would be limited to the treated
patient a would not affect progeny
 animals carrying foreign genes in their
germ line (transgenic animals) have been
produced using mice, rats, rabbits and
some others.
Germline Gene Therapy
 = IGM = Inheritable Genetic Modification
 in laboratory animals, IGM has been
accomplished in two ways:
 by modifing the parental germ cells or the fertilized egg
 such that a new genome is in every cell of the person´s
body and is therefore transferred to the next generation
through the germ cells
 by modifying embryonic stem cells so that the adult
body contains a high percentage of cells derived from
these genetically altered blastomere

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer Associates, Inc. W.H.
Freeman & comp. Sunderland, MA U.S.A. p. 196)
Germline Gene Therapy
 Gregory Stock: the question is not if, but
when.
 given that IGM might be able to eradicate
inhereited genetic diseases and enable us
to expand our genetic repertoire, why
should anyone be against it?

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 196)
Some Comments.
Ethics
 there
is no fundamental difference
between the transplantation of genes into
somatic cells and the transplantations of
organs
Gene therapy
 Most human disease results from
interaction of a born genetic factors with
environmental influences.
 Therapy only modifies the symptoms of
disease, thereby giving the body an
opportunity to heal itself
 gene therapy: effective treatment should
correct the underlying genetic defect itself
and not just a symptoms
Gene Therapy
 is it true that…
 the natural is good and the unnatural is
bad?
...not particularly important for obtaining the credits, but interesting
enough
GENETIC ENGINEERING
Genetic Engineering
 = a proceess of inserting new genetic
information into a cell with the intention of
changing that cell´s function and ultimately
modifying the phenotype of the organism.
 Gene therapy = specific apllication of
genetic engineering techniques with the
primary objective of correcting defective
genes to treat a genetic disorder.
The General Nature of Biological
Engineering
 engineering = designing and constructing
of complex material artifacts for human
use
 up to the present, all technology has been
concerned with lifeless material (most
typically metals), shaping them into
human artifacts for human use
 man was the subject, „nature“ the object
of technological mastery
 Biological engineering: man becomes the
direct object as well as the subject of the
engineering art.

(Jonas, H., (1974) Philosophical essays: from ancient creed to technological man. Prentice-Hall)
Engineering:
man
nature (metal)
Biological engineering:
man
man
 ENGINEERING
 from first element to final
product
 designing
 maker is the sole agent vis-
à-vis the passive material
 building
 predictability is 100 %
 the engineer can accurately
predict the properties of his
product
 BIOLOGICAL
ENGINEERING
 work on pregiven structure;
rather improvement than
making de novo
 design alteration
 modifier is a co-agent with
the self active material
 intervention
 number of unknown is
immense
 prediction is reduced to
guessing, planning – to
gambling
 ENGINEERING
 BIOLOGICAL
 experiments are performed
ENGINEERING
with substitute models
which can be altered,
tested and retested
 everything in mechanical
construction is reverisble
 conventional engineering
can always correct its
mistakes in the planning
and testing stages, even
inthe finishing product
automobiles f.e.) can be
recalled to the factory for
correcting of faults
 the intended redesigning or
modification or
improvement is in fact an
experiment
 for valid experiment, it must
operate with the original
itself
 the experiment is the real
deed
 modifications are
irreversible
 what is done is done (the
baby is born f.e.)
History
Gene therapy
 The first approved gene-therapy protocol
began on September 14, 1990, in NIH,
Maryland
ADA
a four-year-old girl suffering
from adenosin deaminase
(ADA) deficiency was given
back her own immune cells
(specifically her blood T
lymphocytes) that had been
corrected by inserting a normal
copy of ADA gene
 within a few weeks after gene therapy began,
her immune system showed improvement, and
after several months she began living a
relatively normal life
W. French Anderson, 1990
 In the treated children, a sample of their own
(ADA-deficient) immature lymphocyte stem cells
was cultured. The functioning ADA gene was
inserted into the genome of a harmless virus,
which was then allowed to „infect“ the cultured
precursor cells. These cells incorporated the
corrected gene and were injected back into the
patient. The treatment has been successful in
several cases; the patients´immune system
function was restored, although they undergo
continual medical treatment

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer Associates, Inc. W.H.
Freeman & comp. Sunderland, MA U.S.A. p. 192)
The first definite success: a cure for X-linked severe
combined immunodeficiency: X-SCID
 later other patients received similar
treatment, with up to 10-12 treatments per
patients
 several patients reported dramatic clinical
improvements
 however, all the patients continued also to
receive treatment with an enzyme preparation,
making it uncertain how much of their
improvement was due to the gene therapy
The first definite success: a cure for X-linked severe
combined immunodeficiency: X-SCID
 X-linked SCID was the first unambigous
success
 the treatment was ex vivo, using a
retroviral vector encoding the γc chain of
cytokine receptor gene IL2R
 bone marrow cells expressing CD34, a
marker of hematopoietic stem cells, were
incubated for 3 days with the retroviral
vector…
 …and then returned to the patient
CASES
Angelina Jolie underwent a
preventive double
mastectomy
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MY MOTHER fought cancer for almost a decade and died at 56. She held out long enough to meet the first of her grandchildren and
to hold them in her arms. But my other children will never have the chance to know her and experience how loving and gracious she
was.
¶We often speak of “Mommy’s mommy,” and I find myself trying to explain the illness that took her away from us. They have asked if
the same could happen to me. I have always told them not to worry, but the truth is I carry a “faulty” gene, BRCA1, which sharply
increases my risk of developing breast cancer and ovarian cancer.
¶My doctors estimated that I had an 87 percent risk of breast cancer and a 50 percent risk of ovarian cancer, although the risk is
different in the case of each woman.
¶Only a fraction of breast cancers result from an inherited gene mutation. Those with a defect in BRCA1 have a 65 percent risk of
getting it, on average.
¶Once I knew that this was my reality, I decided to be proactive and to minimize the risk as much I could. I made a decision to have
a preventive double mastectomy. I started with the breasts, as my risk of breast cancer is higher than my risk of ovarian cancer, and
the surgery is more complex.
¶On April 27, I finished the three months of medical procedures that the mastectomies involved. During that time I have been able to
keep this private and to carry on with my work.
¶But I am writing about it now because I hope that other women can benefit from my experience. Cancer is still a word that strikes
fear into people’s hearts, producing a deep sense of powerlessness. But today it is possible to find out through a blood test whether
you are highly susceptible to breast and ovarian cancer, and then take action.
¶My own process began on Feb. 2 with a procedure known as a “nipple delay,” which rules out disease in the breast ducts behind
the nipple and draws extra blood flow to the area. This causes some pain and a lot of bruising, but it increases the chance of saving
the nipple.
¶Two weeks later I had the major surgery, where the breast tissue is removed and temporary fillers are put in place. The operation
can take eight hours. You wake up with drain tubes and expanders in your breasts. It does feel like a scene out of a science-fiction
film. But days after surgery you can be back to a normal life.
¶Nine weeks later, the final surgery is completed with the reconstruction of the breasts with an implant. There have been many
advances in this procedure in the last few years, and the results can be beautiful.
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¶I wanted to write this to tell other women that the decision to have a mastectomy was not easy. But it is one I am very happy that I
made. My chances of developing breast cancer have dropped from 87 percent to under 5 percent. I can tell my children that they
don’t need to fear they will lose me to breast cancer.
¶It is reassuring that they see nothing that makes them uncomfortable. They can see my small scars and that’s it. Everything else is
just Mommy, the same as she always was. And they know that I love them and will do anything to be with them as long as I can. On a
personal note, I do not feel any less of a woman. I feel empowered that I made a strong choice that in no way diminishes my
femininity.
¶I am fortunate to have a partner, Brad Pitt, who is so loving and supportive. So to anyone who has a wife or girlfriend going through
this, know that you are a very important part of the transition. Brad was at the Pink Lotus Breast Center, where I was treated, for every
minute of the surgeries. We managed to find moments to laugh together. We knew this was the right thing to do for our family and
that it would bring us closer. And it has.
¶For any woman reading this, I hope it helps you to know you have options. I want to encourage every woman, especially if you have
a family history of breast or ovarian cancer, to seek out the information and medical experts who can help you through this aspect of
your life, and to make your own informed choices.
¶I acknowledge that there are many wonderful holistic doctors working on alternatives to surgery. My own regimen will be posted in
due course on the Web site of the Pink Lotus Breast Center. I hope that this will be helpful to other women.
¶Breast cancer alone kills some 458,000 people each year, according to the World Health Organization, mainly in low- and middleincome countries. It has got to be a priority to ensure that more women can access gene testing and lifesaving preventive treatment,
whatever their means and background, wherever they live. The cost of testing for BRCA1 and BRCA2, at more than $3,000 in the
United States, remains an obstacle for many women.
¶I choose not to keep my story private because there are many women who do not know that they might be living under the shadow
of cancer. It is my hope that they, too, will be able to get gene tested, and that if they have a high risk they, too, will know that they
have strong options.
¶Life comes with many challenges. The ones that should not scare us are the ones we can take on and take control of.
¶Angelina Jolie is an actress and director.
„The Bubble Boy“
 David Phillip Vetter
(September 21, 1971 –
February 22, 1984)
 he suffered SCID
 at the age of 12, he died
after hematopoietic stem
cell transplantation
„The Bubble Boy“
What was wrong?
pros
cons
 effort to save the life
 career of the researchers
 doing everything is
 publications
possible
 popularity for the
researches
 giving too much hope to
the parents
Celý životopis JG sepsaný jeho otcem Paulem Gelsingerem je na
http://www.jesse-gelsinger.com/
Jesse Gelsinger
 Jesse Gelsinger, 18 yrs old, was the first
person publicly identified as having died in a
clinical trial for gene therapy. He suffered from
ornithine transcarbamylase deficiency, an Xlomked genetic disease of the liver which
include an inability to metabolize ammonia - a
byproduct of protein breakdown. The disease
is usually fatal at birth, but Gelsinger’s disease
was not inherited but rather, the result of a
genetic mutation and as such was not as
severe - some of his cells were normal which
enabled him to survive on a restricted diet and
special medications.
Jesse Gelsinger
 Gelsinger joined a clinical trial run by the
University of Pennsylvania that aimed to
correct the mutation. On Monday,
September 13 1999, Gelsinger was
injected with adenoviruses carrying a
corrected gene in the hope that it would
manufacture the needed enzyme. He died
four days later, apparently having suffered
a massive immune response triggered by
the use of the viral vector used to
transport the gene into his cells.
Jesse Gelsinger
 Treatment for JG: low-
protein diet and cca 32
pills per day
 the day he turned
eighteen he left to
Pennsylvania and gave
the informed consent
with the gene therapy
Jesse Gelsinger
 he was pronounced dead on September 17, 1999
 His death was the first reported death ever directly
attributable to a gene therapy experiment
 There were questions about the quality of informed
consent at University of Pennsylvania and
accusations that the university had failed to report
toxic side effects earlier that could have shut down
the study.
Jesse Gelsinger
 the announcement of Jesse´s death made for
headlines, shocked the public and terryfied the
scientific community
 gradually, increasing numbers of articles
suggested, that his death had been avoidable
 there were 18 participants in this OTC gene
therapy trial, JG was the youngest

why JG did die when others who received the same
treatment did not is not known
 in the aftermath of this tragedy, the gene therapy
institute in Pennsylvania has stopped working with
human subjects and returned to work on animal model
system
ETHICS
Gene Therapy
Arguments for
Gene Therapy
Arguments FOR
 Isolating a disease-inducing aberrant
gene looks fairly continuous with isolating
a disease-inducing intracellular virus
 Suppllying diabetics with normal genes for
producing insulin has the same medical
goal as supplying them with insulin for
injection
Gene Therapy of Germ Cells
Arguments FOR
 it solves the problem once and for all. Why
leave the patient´s descendants at risk of
a disease if you could equally well
eliminate the risk?
Germinal Choice Technology (GCT)
 GCT could be accomplished by adding auxiliary
human chromosomes (numbers 47 and 48),
which will carry artificial genes for characteristics
promoting attributes like increasing intelligence
and longevity
 each successive generation could have a
genetic update, rather as you currently update
your computer!
 If we could make our baby smarter, more
attractive, a better athlete or musician, or keep
him of being overweight, why shouldn´t we?
(Gregory Stock)

(Mepham, B., (2008) Bioethics. An Introduction for the Biosciences. Oxford University Press,
Oxford, p. 150)
Gene Therapy
Arguments against
Germ cells gene therapy
objections
 present men have the power over the
future men, who are the defenseless
objects of antecedent choices by the
planners of today
 there is no right to existence for
hypothetical individuals not yet conceived
 but though not the right of merely
imagined offspring, the right to offspring of
the hindered progenitor is involved.
Germ cells gene therapy
objections
 it could lead to people being viewed as
products capable of being manufactured,
with the result that people could be „made
to measure“.
 our actions might come to be viewed as
genetically determined rather than a
matter of free will
Germ cells gene therapy
objections
 germ line therapy is not necessary.
Candidate couples would most likely have
dominant or recessive Mendelian disorders
(recurrence risk 50 % and 25 %
respectively). Given a dish containing half a
dozen IVF embryos from the couple, it would
seem crazy to select the affected ones and
subject them to an uncertain procedure,
rather than simply to select the 50 % or 75
%of unaffected ones for re-implantation
Germ-line Therapy
Objections
 there are several alternative procedures
 prenatal genetic diagnosis
 gamete donation
 embryo selection
 adoption
 ...these are currently available and would
not evoke the issues involved in germline
manipulation

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 201)
Germ-line Therapy
Objections
 it is not safe
 when altered genes are inserted into the genome,
they may disrupt presently functional genes
 this has certainly been encountered in laboratory
mice. In one case, the disruption of single gene
resulted in mice who were born without eyes,
semicircular ear canals, or a sense of smell
 some effects may take several generations to
manifeste themselves - and any mistakes made
will be permanent

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer Associates, Inc.
W.H. Freeman & comp. Sunderland, MA U.S.A. p. 202)
Germ-line Therapy
Objections
 it is not safe
 IGM is not a drug that can be discontinued if
the side effects are disastrous
 ...but we may one day use artificial
chromosomes to add genes that could be
induced to lose their centromeres by a signal
from exogenous factor. Once the signal was
administered, such chromosomes would not
survive meiosis or mitosis and would not be
passed on to the next generation.

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 202)
Germ-line Therapy
Objections
 we know that there are genes that affects
height and muscle mass, so we could
conceivably make our offspring taller and
stronger
 if genes involving intelligence were found,
those who could afford this procedure might
enhance themselves in the hopes of
producing highly intelligent offspring

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 202)
Germ-line Therapy
Objections
 Lee Silver (1998) envisions a world where,
due to such economic inequality, the genetic
haves and have-nots are far apart in their
abilities: genetic engineering would convert
economic differences into inherited biological
differences.

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 202)
 some question a consequence if a trait
chosen in one generation falls out of fashion
in the next or becomes particulary ill-suited to
a change in the environment
 one genration preffering a certain hair color, height
or organ endowment
 if parents were to select genes for height and
body musculature, they might then pressure
their child to succeed at sports, regardless of
whether the chilod wants to play the game

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer Associates, Inc.
W.H. Freeman & comp. Sunderland, MA U.S.A. p. 204)
 a genetic engineering could convert a
child into a commercial product with
expected parameters of normality and
function
 ...and people who fell short of some
technically achievable ideal would be seen
as "damaged goods", increasing
prejudices and discrimination

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer
Associates, Inc. W.H. Freeman & comp. Sunderland, MA U.S.A. p. 204)
Gene Therapy
Arguments AGAINST
 "Still harder will it be for most people to live easily
and wisely with less certain information - say,
where multigenic traits are involved or where the
predictions are purely statistical, with no clear
implication for any partictlar "predisposed"
individual
 The recent case of a father who insisted that
ovariectomy and mastectomy be performed
on his ten-year-old daughter because she
happened to carry the BRCA-1 gene for
breast cancer dramatically shows the toxic
effect of genetic knowledge"

(Kass, L.R., (2002) Life, Liberty and the Defense of Dignity. Encounter Books. New York, London.
p. 125)
Gene Therapy
Arguments AGAINST
 Hans Jonas:
 "knowledge of the future, especially one´s
own, has always been excepted /from the
injunction to "Know thyself"/ and the attempt
to gain it by whatever means (astrology is
one) disparaged - as futile superstition by the
enlightened, but as sin by theologians; and in
the latter case with reasons that are also
philosophically sound"

(Kass, L.R., (2002) Life, Liberty and the Defense of Dignity. Encounter Books. New York,
London. p. 125)
Gene Therapy
Arguments AGAINST
 C.S.Lewis:
 "In reality (...) if any one age really attains, by
eugenics and scientitfic education, the power
to make its descendants what it pleases, all
men who live after it are the patients of that
power. They are weaker, not stronger „for
though we may have put wonderful
machines in their hands we have preordained how they are to use them..."

(Kass, L.R., (2002) Life, Liberty and the Defense of Dignity. Encounter Books. New York,
London. p. 127)
Germ-line Therapy
Objections
 because the technology is imprecise, any
errors in the therapy (e.g. involving the insertion of
a gene in the middle of another gene, disrupting its
would also be inherited
 outcomes are unpredictable, for examle eradicating
expression)
the gene for sickle cell anaemia might increase the susceptibility of
some carriers of the gene (e.g. in tropical Africa) to malaria, against
which the gene confers resistance
 manipulating of the embryo is seen as
intrinsically ethically objecionable
Germ cells gene therapy
objections
 germ line therapy is not necessary.
Candidate couples would most likely have
dominant or recessive Mendelian disorders
(recurrence risk 50 % and 25 %
respectively). Given a dish containing half a
dozen IVF embryos from the couple, it would
seem crazy to select the affected ones and
subject them to an uncertain procedure,
rather than simply to select the 50 % or 75
%of unaffected ones for re-implantation
Genetic Enhancement
 Beacause memory is good, can we say
how much more memory would be better?
 If sexual desire is good, how much more
will be better?
 Life is good, but how much extension of
the lifespan would be good for us?
 Only simplistic thinkers believe they can
easily answer such question

Kass, R.L., (2002) Life, Liberty and the Defense of Dignity. Encounter Books, New York, London.
p. 132
Religions
Judaism
 The jewish posture should be, in the
briefest formula: education - yes; genetic
manipulation - no. (...)
 We have not been authorized, so Jewish
piety would say, to be makers of a new
image (...)
 The protest should always be against
turning men into things

Jonas, H., (2001) Contemporary Problems in Ethics from a Jewish Perspective in Yaffe, M.D.,
(ed.) Judaisms and Environmental Ethics. Lexington Books. Lanham. p. 259)
Judaism
 The older and comforting belief that
human nature remains the same and that
the image of God in it will assert itself
against all defacements by man-made
conditions, become untrue if we
"engineer" this nature genetically and be
the sorcerers (or sorcerer´s apprentice)
that make the future race of Golems

Jonas, H., (2001) Contemporary Problems in Ethics from a Jewish Perspective in Yaffe, M.D.,
(ed.) Judaisms and Environmental Ethics. Lexington Books. Lanham. p. 259)
Judaism
 The jewish posture should be, in the
briefest formula: education - yes; genetic
manipulation - no. (...)
 We have not been authorized, so Jewish
piety would say, to be makers of a new
image (...)
 The protest should always be against
turning men into things

Jonas, H., (2001) Contemporary Problems in Ethics from a Jewish Perspective in Yaffe, M.D.,
(ed.) Judaisms and Environmental Ethics. Lexington Books. Lanham. p. 259)
Catholic Church
 in the present state of research, it is not
morally permissible to act in a way that may
cause possible harm to the resulting
progeny. In the hypothesis of gene therapy
on the embryo, it needs to be added that this
only takes place in the context of in vitro
fertilization and thus runs up against all the
ethical objections to such procedures. For
these reasons, therefore, it must be stated
that, in its current state, germ line cell
therapy in all its forms is morally illicit.
Enhancement
Nontherapeutical gene
modifications
Nontherapeutic genetic modification
ethical issues
 Issue of eugenic - are we allowed to
make hereditary „improvements“?
 Slippery slope - might we slide into a new
age of eugenic thinking by starting with
small genetic improvements?
Nontherapeutic genetic modification
ethical issues
 since more and more scientists believe
that all traits of personality have at least a
partial biological basis, how will we
distinguish the biological "defect" that
yields "disease" from the biological
condition that yields shyness or
melancholy or irascibility?
Neterapeutické genetické modifikace
etické problémy
 everyone would welcome a gene therapy
to alleviate muscular dystrophy and to
reverse the debilitating muscle loss that
comes with old age.
 But what if the same therapy were used to
improve athletic performance?
Nontherapeutic genetic modification
ethical issues
 researches have developed a synthetic gene
that, when injected into the muscle cells of
mice, prevents and even reverses natural
muscle deterioration. The gene not only
repaires wasted or injured muscles but also
strenghtens healthy ones
 suppose that muscle-enhancing gene
therapy turned out to be safe - or at least no
riskier than a rigorous weight-training
regimen. Would there be a reason to ban its
use in sports?
Nontherapeutic genetic modification
ethical issues
 it might be argued that a genetically
enhanced athlete, like a drug-enhanced
athlete, would have an unfair advantage
over his unenhanced competitors...
 ...but it has always been the case that
some athletes are better endowed than
others, and yet we do not consider this to
undermine the fairness of competitive
sports

(Sandel, M.J., The Case Against Perfection. The Atlantic Monthly (April 2004): 51-62 in
(Pierce, J., Randels, G., (2010) Contemporary Bioethics. Oxford University Press, NY,
Oxford. p.599)
Runners
Nontherapeutic genetic modification
ethical issues
 researches have produced smart mice by
inserting extra copies of a memory-related
gene into mouse embryo. The altered mice
learn more quickly and remeber things longer
than normal mice.
 The extra copies were programmed to
remain active even in old age, and the
improvement was passed on to offspring.
 .. we are now looking for "a Viagra for the
brain"
Nontherapeutic genetic modification
ethical issues
 there are 81 million Americans over fifty, who
are beginning to encounter the memory loss
that comes naturally with age
 such use would straddle the line between
remedy and enhancement
 unlike the treatment for Alzheimer´s , it would
cure no disease...
 ...but insofar as it restored capacities a
person once posessed, it would have a
remedial aspect
Neterapeutické genetické modifikace
etické problémy IGF - 1
 IGF-1 shows great promise in animal
studies to increase muscle mass, and
would be very difficult to detect by current
monitoring systems. Most would consider
this just as unacceptable as steroids in the
atletic setting
 but IGF-1 appears potentially able also to
slow down the aging process
 If that turns out to be true, would this use
alo be immoral? (Collins, F., (2006) The Language of God. Free
Presss, New York, p. 266)
Nontherapeutic genetic modification
ethical issues
 What distinguishes a serious disease from
a“minor“ disease or from genetic variation?
Should an adolescent whose parents are
both 150 cm tall be provided with a growth
hormone gene on result?
 If the gene transfer extends one day to
allowing a normal individual to acquire, for
example, a memory-enhancing gene?
 since more and more scientists believe
that all traits of personality have at least a
partial biological basis, how will we
distinguish the biological "defect" that
yields "disease" from the biological
condition that yields shyness or
melancholy or irascibility?
 everyone would welcome a gene therapy
to alleviate muscular dystrophy and to
reverse the debilitating muscle loss that
comes with old age.
 But what if the same therapy were used to
improve athletic performance?
Finasteride and Propecia
 there is a very fine line between treatment and enhancement
 the drug finasteride stops the prostate from enlarging and is
medically prescribed to men with this serious condition
 in smaller doses, the same drug will retard male pattern
baldness
 both prostate growth and pattern baldness result from the
metabolizing of testosterone to a more potent steroid
hormone, and finasteride blocks that metabolism
 those men who can afford the drug can impede baldness by
using it, and it is widely marketed for this purpose under the
brand name Propecia

(Gilbert, S.C., Tyler, A.L., Zackin, E.J., (2005) Bioethics and the New Embryology. Sinauer Associates, Inc. W.H. Freeman &
comp. Sunderland, MA U.S.A. p. 195)