Report of the IBC on Pre-implantation and Germ-line InterventionDiagnosis
in text I have marked bold black and typed the name (red) for terms I believe are biased and should be replaced with unbiased terms. For example the term "increased risk should" be replaced by "increased probability"
blue are comment in general by me which are made on behalf ofDisabled people international (DPI) www.dpi.org) they are also in bold
Organisation des Nations Unies pour l’éducation, la science et la cultureUnited
Nations Educational, Scientific and Cultural OrganisationComité internationalde
bioéthique (CIB)International BioethicsCommittee (IBC)
Distribution: limited
SHS-EST/02/CIB-9/2 (Rev. 3)
Paris, 24 April 2003
Original: English
Report of the IBC on
Pre-implantation Genetic Diagnosis
and Germ-line Intervention
_____________________
Rapporteur: Hans Galjaard
Division of the Ethics of Science and Technology
I. INTRODUCTION
1. The Universal Declaration on the Human Genome and Human Rights, in Article
2 concerning its implementation, underscores the need to identify practices
such as germ-line interventions that might be contrary to human dignity and
assigns responsibility for this to the International Bioethics Committee of
UNESCO (IBC).
2. Moreover, in the recommendations adopted at its Second Session (Paris 12-14
May 2001), the Intergovernmental Bioethics Committee (IGBC) “invites the IBC
when outlining its detailed two year work programme, to consider at its earliest
convenience the inclusion of the following topics: (i) Pre-implantation genetic
diagnosis, (ii) Interventions on germ-line cells”.
3. At its Eighth Session (Paris, 12-14 September 2001), the IBC therefore retained
these two topics in its work programme for 2002-2003 and set up a Working Group
chaired by Prof. György Kosztolányi (Hungary) that met for the first time at
UNESCO Headquarters from 23 to 24 April 2002 in the presence of Prof. André
van Steirteghem (Belgium), an international expert on assisted reproductive
technology (Annex I, Composition of the Working Group). The IBC considered a
draft report during its Ninth Session (Montreal, 26-28 November 2002), after
which the Working Group met for a second time to finalize the report (Monaco,
3 March 2003).
4. It should be recalled that certain previous reports prepared within the framework
of the deliberations of the IBC are particularly relevant to the subjects under
consideration. These include the “Report on Genetic Screening and Testing” (1994),
the “Report on Genetic Counselling” (1995) and the “Report on Human Gene Therapy”
(1994).
II. CONTEXT
5. During recent decades fundamental research in genetics has developed at an
increasing pace. In human genetics new insights into the molecular background
of diseases and new technologies, especially of DNA analysis, have enabled the
early and exact diagnosis of an increasing number of congenital disorders, the
identification of parents at (red: increased risk) of having ( red:
affected) offspring and genetic counselling.
6. In most wealthy countries a new medical discipline, clinical genetics, has
been incorporated into specialized medical care. Most clinical genetics centres
provide services for the laboratory diagnosis of chromosomal abnormalities and
single gene disorders and genetic counselling. Since the late sixties collaborative
efforts between departments of obstetrics and gynaecology and clinical genetics
have resulted in facilities for prenatal diagnosis. Pregnant women at (red:
increased risk) of having a child with a genetically-caused disease
or (red: malformation) may undergo chorion villus sampling
(around the 11th week of pregnancy) or amniocentesis (at 16 weeks) and, after
cultivation of foetal cells, chromosomal, biochemical or DNA analysis may reveal
whether the unborn child is affected by one of the specifically tested (red:
abnormalities). If this is the case the prospective parents are confronted
with the decision of whether to terminate the pregnancy, thereby avoiding the
birth of an otherwise (red: severely (my comment on behalf of DPI: blue:
not correct if we accept article 65 below) (red: affected) child.
7. An alternative, non-invasive method of prenatal diagnosis is ultrasound examination,
which reveals major structural and sometimes functional foetal (red:
abnormalities) usually later in pregnancy. Experimental work is being
done regarding the diagnostic analysis of foetal cells in maternal blood.
8. There is professional agreement about the major indications for prenatal
diagnosis (my comment on behalf of DPI: blue: what does that mean?).
Most women in developed countries are aware of the possibility of prenatal diagnosis
and, in many countries, the costs are covered by public means c.q. health insurers.
However, in developing countries, prenatal diagnosis is accessible only to a
limited part of the population or it is not available at all. In several developing
countries information may not be readily available or the procedure is not accepted.
9. Pre-implantation genetic diagnosis (PGD) can be considered a new approach
towards early diagnosis of genetic disease (my comment on behalf of
DPI: blue: not just disease. Sex can also be ascertained). It became
possible only after the clinical establishment of in vitro fertilisation (IVF)
(in 1978 in the United Kingdom) for infertile couples and the development of
sufficiently sensitive techniques to analyse chromosomes or genes at a single-cell
level.
10. The technique is based on IVF; cell division in most cases up to 8-cell
stage embryos, biopsy of 1 or 2 cells, analysis by DNA technology for specific
genetic (red: abnormalities) and selection of unaffected embryos
for transfer to the uterus.
11. The first PGDs were published around 1990. Since then a few dozen centres
have acquired the highly specialized, multidisciplinary expertise required for
the technique. In Europe and North America several thousand PGDs have been established
and several hundred (healthy) babies have been born as a result. PGDs have so
far been performed for major chromosomal aberrations and some 30 different monogenic
diseases. It is likely that in the near future the scope of PGD will be widened
to many other conditions, including major multifactorial diseases in adulthood.
12. During the last years it has become more and more customary to test 6-8
cell embryos collected for IVF in infertile couples for chromosomal abnormalities
and to transfer only 1-2 embryos found to have a normal number of chromosomes.
The expectation is that this selective transfer will result in a higher pregnancy
rate and a lower risk of spontaneous abortion.
13. Several centres also accept sex selection under certain conditions. Most
recently there have been a few examples of selecting embryos with certain immunogenetic
characteristics to function after birth as blood stem cell donors in order to
save a sibling with a genetic blood disease or leukaemia that is fatal without
compatible hemopoietic stem cell transplantation.
14. These last three examples of PGD application do not aim to avoid severe
congenital disorders. Instead the purposes are technical (to improve the results
of IVF) or the selection for a desired characteristic (such as male or female
sex) or for use in subsequent donorship.
15. The purpose of this report is to describe PGD and discuss the major ethical
issues related to its applications and to review the ethical aspects of germ
cell intervention in this context.
III. PREIMPLANTATION DIAGNOSIS (sensu stricto)
1. Methodology
16. PGD is based on the IVF procedure originally intended and still most often
used for infertile couples. This procedure involves hormone treatment to hyperstimulate
the ovaries and the invasive procedure of oocyte retrieval. Treatment occurs
over 1-8 cycles, with an average of 12 oocytes retrieved per cycle. The hormone
treatment involves some medical risk (1%). After the oocytes are retrieved,
they are fertilized using the husband’s sperm, with about a 70% success rate.
In case of male infertility or as a means of avoiding contamination of the subsequent
laboratory analysis, intracytoplasmic sperm injection (ICSI) may be used.
17. About 70% of the fertilised eggs will develop under in vitro conditions
to the 8-cell stage embryo at day 3. Using micromanipulation, 1-2 cells are
biopsied from the 8-cell embryo and analysed in a highly specialized laboratory.
About 80% of the blastomeres are suitable for biopsy and a diagnostic result
will be obtained in 90-95% of the biopsied blastomeres.
18. Depending on the indication specific tests are performed to detect abnormalities
at the gene or chromosome level. The most common methods are fluorescence in
situ hybridisation (FISH) to detect chromosome abnormalities and a variety of
DNA analyses using the polymerase chain reaction (PCR) to detect specific single
gene mutations known to be associated with severe genetic disease. There is
limited experience in testing for about 30 different monogenic diseases and
about 1% are misdiagnosed, as revealed by follow-up studies.
19. Biopsied embryos found to be affected are discarded or frozen for research
and 1-2 non affected embryos are transferred to the uterus on day 5. Some centres
may transfer more than 2 embryos thereby further increasing the rate of multiple
pregnancies with the accompanying problems of foetal loss, premature birth and
related complications. Even after transferring 2 embryos, the average rate of
twin pregnancy is 25%.
20. After embryo transfer the pregnancy rate is 15-25%; centres with great expertise
report a pregnancy rate of 40% after 2 or more cycles. At day 10-14 a hormone
test is performed to verify if the transferred embryo(s) has implanted and at
7 weeks ultrasonic control of the foetal heart action is carried out. Since
PGD is still considered an experimental procedure, it is recommended that the
early diagnosis is followed-up with “conventional” prenatal testing using analysis
of chorionic villi or cultured amniotic fluid cells.
21. An alternative procedure is the genetic analysis of the polar body of a
single oocyte, which has the ethical advantage that no embryo is involved. However,
the diagnostic disadvantage that only maternally inherited problems can be detected.
22. Genetic analysis has been attempted at a later stage of embryo development
(i.e. the blastocyst stage of about 100 cells reached at day 5-7). The advantage
is that more (5-12) extra-embryonic cells from the so-called trophectoderm can
be removed and analysed. A major drawback is that very few embryos reach this
stage under in vitro conditions. So far no PGD has been clinically performed
after 5-6 days of culture.
23. Some follow-up studies of babies born after PGD have revealed an increased
incidence of congenital malformations or genetic diseases as so-called imprinting
disorders. Other studies did not indicate an increased risk that could be specifically
attributed to IVF/PGD. Clearly more well controlled follow-up studies must be
performed before a definite answer can be given. However, IVF as a prerequisite
for PGD is associated with some risks for the future child especially the high
proportion of multiple pregnancies that may result in premature births and the
associated complications.
24. For each new indication, the PGD procedure has to be tested experimentally
and, as a result, couples at risk for a specific rare genetic disease, often
must wait 6-12 months before a PGD can be attempted at the clinical diagnostic
level.
2. Indications
25. The three main categories of couples who are referred for PGD are:
· couples at (red: high risk) of having a child affected by
a genetically-caused disease or (red: malformation,) and who
have an infertility problem;
· couples at (red: high genetic risk) who have undergone “conventional”
prenatal diagnosis and who did terminate recurrent pregnancies after an affected
foetus was found;
· couples (red: at risk) of giving birth to a child affected
by a genetically-caused disease or (red: malformation) and
who object to termination of pregnancy.
26. In addition, older couples referred for IVF because of infertility may request
PGD of chromosomal abnormalities (see Section 5a).
27. One group at (red: increased risk of affected) offspring
includes carriers of a balanced chromosome translocation. In this situation
the risk of offspring affected by an unbalanced chromosomal abnormality may
be very high.
28. In some instances the (red: risk of) a numerical chromosomal
abnormality due to the advanced age of the mother is a reason for PGD.
29. A third (red: high-risk) group includes those couples where
carriership of a single-gene mutation is involved. In case of autosomal recessive
conditions such as hemoglobinopathies, cystic fibrosis or spinal muscular atrophy,
both partners carry a recessive mutation and are not clinically themselves affected
by the disease. Their probability of conceiving and giving birth to a child
who inherits the mutation from both parents and who will be affected by the
disease is 25%. When the mother is a carrier of an X-linked mutation, such as
the ones that cause Duchenne muscular dystrophy, X-linked mental retardation
and haemophilia, each son will have a 50% chance of inheriting the disease.
In the case of a dominant gene mutation, such as with myotonic dystrophy or
the late onset Huntington’s disease, a mutation in one of the chromosomes is
sufficient to develop a disease; here (red: the risk) of couples
to give birth to an affected child is 50%.
30. Of the more than 1,000 PGDs reported so far an equal number of referrals
were made due to an (red: increased risk) of chromosomal abnormality and those
due to risk of a monogenic disease.
31. However, during the last year, the relative number of chromosome analyses
related to the normal IVF procedure has increased. In future years, the scope
of indications for PGD of monogenic diseases is likely to widen because a total
of more than 5,000 rare diseases are known to be associated with a single-gene
mutation; most of these will be identified in the coming years. Since the technology
of DNA mutation analysis is continuously improving it is likely that, in the
long term, all monogenic diseases will be diagnosable both by conventional prenatal
diagnosis and by PGD.
3. Organisation and Regulation
32. PGD requires a multidisciplinary approach. Usually referral to a fertility
clinic takes place after genetic counselling in a clinical genetics centre.
In the case where one of the parents, one or more children or close relatives
are (red: affected,) an accurate clinical and laboratory diagnosis
must be performed to enable proper genetic counselling (my comment on
behalf of DPI: what is proper counselling? As this document uses very negative
biased language like high risk.. it is to assumed that a non biased non directive
counselling is not possible if the procedure is based under the framework of
a negative connotations such as risk)and to establish an indication
for PGD. After referral to the fertility clinic a proper evaluation of the clinical
aspects of hormone treatment, oocyte retrieval and IVF must be carried out.
The counselees must be informed about these clinical aspects and about the possibilities
and limitations of the IVF and PGD procedures. The 8-cell embryo selection procedure
must be thoroughly discussed as must the fate of supernumerary unaffected embryos
or those carrying genetic or chromosomal (red: abnormalities). Information is
especially important about the relatively low birth rate after IVF and PGD and,
of course, the risk and disadvantages of a multiple pregnancy.
33. Chromosome or gene mutation analysis of 1-2 blastomeres is usually performed
in a highly-specialized laboratory associated with both the department of clinical
genetics and the fertility clinic.
34. The complexity of the multidisciplinary approach has so far limited the
application of PGD. The European Society of Human Reproduction and Embryology
(ESHRE) formed a PGD Consortium in 1997 with the aim of undertaking a long-term
study of the efficacy and clinical outcome of PGD. The third report of the ESHRE
PGD consortium (May 2001) involved 25 centres and reported on 1560 referrals
during the past three years. Recently, the number of participating centres has
increased to 32.
35. About one quarter of the couples applying for PGD have one or more children
affected by a genetically-caused disease or (red:malformation)
and an even larger percentage have experienced spontaneous abortions or termination
of pregnancy after “conventional” prenatal diagnosis. The ESHRE also reports
an increasing number of chromosomal analyses associated with normal IVF. Three
centres submitted data about (red: sex selection for social reasons).
(my comment on behalf of DPI: arbitrary line between social and medical reasons)
The existence of the PGD Consortium enabled a survey about the acceptability
of non-medical reasons for PGD and 15 of the 21 centres that replied were against
it.
36. For a multidisciplinary approach to PGD close collaboration between the
various units and professionals is to be preferred. In about half the cases
the various experts work at the same location but in other instances, especially
in the United States, a fertility clinic may be more than 1300 kilometres from
the laboratory where the diagnostic analysis is performed. As a consequence
blastomeres have to be transported over a long distance.
37. Another problem is quality control. This applies to the clinical and laboratory
methods, to the indications for PGD used and to the counselling procedures and
efficacy.
38. In most European centres PGD is regulated within the context of IVF in fertility
clinics and genetic counselling and often laboratory diagnosis in clinical genetics
centres. Professional organizations have defined recommendations concerning
indications and quality control. For instance, in France, Spain, Sweden and
the United Kingdom, PGD legislation has been implemented. In Belgium, Israel,
The Netherlands, Italy and Greece, PGD is allowed under guidance of a national
authority; usually PGD is allowed for all diseases amenable by “conventional”
prenatal diagnosis. In Europe, public funding is often available via insurers
or national/regional governments. For the clinical use of PGD, consent of local
ethics committees is required. In some instances a national authority has to
review the case.
39. In the United Kingdom, the Human Fertilisation and Embryology Authority
has to grant permission for each new disorder to be tested. At the European
level, the Council of Europe Convention on Human Rights and Biomedicine (1997)
states in Article 36 that countries which already had legislation permitting
more about PGD than the Convention does may opt out. Key clauses regarding PGD
(Art. 18) read:
· Where the law allows research on embryos in vitro it shall ensure adequate
protection of the embryo;
· The creation of human embryos for research purposes is prohibited.
40. In various countries such as Austria, Germany, Ireland and Switzerland,
PGD is not allowed; in Australia some states e.g. Western Australia have prohibited
PGD while others, South Australia and Victoria, permit its use.
41. In the United States of America, the situation seems even more complex.
Not only are there differences among states, the main centres performing PGD
are private institutions. At the federal level there has been a ban on public
funding of research on embryonic cells and private institutions have a considerable
freedom in deciding about the indications and methodologies of PGD. Since 85%
of the costs of IVF are not covered by insurance, individual couples seeking
PGD are confronted with high costs. In different publications the estimates
for the cost of PGD vary from $15,000 to more than $100,000 depending also on
the number of cycles involved. Consequently, in the United States of America,
PGD seems to be accessible only to at-risk couples who are in a financially
strong position
4. Comparison between PGD and “conventional” prenatal diagnosis (PD)
42. Most experts consider PGD as an additional option for couples at increased
genetic (red: risk) of giving birth to a child with a genetically-caused
disease or (red: malformation) and not as a replacement for “conventional” prenatal
diagnosis (PD) by amniocentesis or chorion villus biopsy.
43. A major technical difference is that PGD is still considered to be a highly
specialized experimental procedure with a limited scope; only a few hundred
healthy children have been born during the past decade as a result of PGD. PD
has a 30 year history of clinical application. Annually hundreds of thousands
couples undergo amniotic fluid (cell) or chorionic villus analyses. A full chromosome
pattern and about 1,500, usually rare, monogenic diseases can be tested, whereas
in PGD only a limited number of chromosomal abnormalities and some 30 monogenic
diseases can currently be tested in 1-2 embryonic cells. Amniocentesis may include
biochemical testing for open neural tube defects; this is not possible in PGD
or chorionic villus sampling.
44. Another major difference between PGD and PD is cost and accessibility. PD
costs between $580 and several thousand dollars. In most developed countries
this will be covered by health insurers as clinical genetics services including
PD are incorporated into the health care system. As mentioned above, the cost
of PGD varies considerably in different centres and states and also according
to the number of cycles and the type of analysis. However, in all instances,
the cost is between about $40,000 and $100,000. In many instances, especially
in the United States of America, couples have to pay themselves.
45. PGD and PD are similar in that they offer couples at increased risk an opportunity
to give birth to a child without a genetically-caused disease or malformation.
In PD, this approach may be at the cost of terminating a pregnancy at 11-19
weeks. In PGD, abortion is avoided, but parents are confronted with the selection
of genetically-tested embryos for replacement in the uterus.
46. A special feature of PGD is the tentative creation of human embryos not
as an end in itself but as a means to “ensure” the birth of a healthy child.
In this sense, PGD is an enabling technology where one category of embryo is
discarded and another category is allowed to become a child and a full member
of society. In PD, a comparable choice is made by selective abortion, but here
conception occurs in a natural way.
47. Among clinical geneticists there has been much discussion about the main
goal of PD. Some have argued that the main aim is to avoid the birth of (red:
an affected child). Others have emphasized the reproductive confidence
and the purpose of informing couples at (red: risk) about the
status of the foetus. Several studies indicate that if there is no PD option
a large proportion (up to 50%) of couples at (red: high risk) (15-25%)
of an affected child refrain from pregnancy despite their wish to reproduce.
When PD is possible many more at-risk couples (up to 90%) dare to embark on
a pregnancy.
48. It has been argued that the selection process in PGD lacks the psychological
barrier of having to decide about terminating a pregnancy as in PD. This might
lead more easily to an extension of the selection process to other characteristics
of the embryo than the presence of a specific genetic abnormality. Examples
are testing and selection for gender and maybe other normal characteristics
(my comment on behalf of DPI blue: who decides what normal characteristics are?)
and HLA typing for fitness as a future donor of tissues or organs for a sibling
with a life-threatening disease (see Section 5b).
49. It is not possible to make general statements about the psychological impact
of the decisions involved in PD and PGD. After PD, couples may be confronted
with the difficult decision of whether or not to terminate the pregnancy. The
later a termination is performed, the more stressful it is. It has been well
documented that the termination of a desired pregnancy when an affected foetus
is detected by PD results in temporary sadness or depression with great individual
variations. It is also known that nearly all couples who undergo PD and abortion
request another PD if they become pregnant again.
50. A small proportion of couples who have experienced repeated abortions ask
for referral for PGD. Within the PGD group this comprises about 21% of the referrals.
The perception of couples in making decisions about selection, transferral and
the fate of supernumerary normal and abnormal embryos varies considerably. The
same is true concerning this attitude in case of failure.
51. After selection and transferral of 1-2 embryos, a vital pregnancy will occur
only in 20-25% of cases and the birth rate of a child is even lower. In order
to give birth to a healthy child after PGD, most women therefore have to undergo
IVF and PGD several times. It has been documented that in cases of IVF failure
the psychological consequences can be serious and in some cases requires professional
help.
52. More subtle differences between PD and PGD concern the process of procreation
and decision-making involved. In PD, the couple or the woman decides, after
the establishment of a pregnancy, whether or not to continue it. In that situation,
a relationship with the developing child may already exist and influence the
woman’s or the couple’s decision. They may still decide to continue the pregnancy.
In PGD, the decision in favour of selection is done before medical treatment
is started; it therefore becomes a constitutive part of procreation.
5. Extension of Indications for PGD
a. Sex Selection
53. The first published example of PGD concerned sex determination in a couple
at risk of an X-linked genetic disorder, where only males may be clinically
affected. Since then DNA research has revealed the responsible mutations for
various X-linked disorders so that sexing of the embryo is less relevant.
54. In the meantime the third ESHRE report (2002) has revealed that three centres
reporting to the consortium have performed over 70 cycles and PGD for sex chromosomes
because of non-medical reasons. The term used is “family balancing” but this
does not change the fact that 8-cell embryos of a specific sex are discarded
for non-medical reasons. (my comment on behalf of DPI blue : arbitrary
use of the term non-medical reasons) It is likely that commercial centres are
increasingly involved in sex selection (see also Chapter IV).
55. On the basis of cultural and/or socio-economic background, in several parts
of the world there is a strong preference for male children. (my comment
on behalf of DPI blue :in many parts of the world there is a strong desire to
have a as able kid as possible therefore most deselection based on disease disorders
and disabilities could be labelled as being done for social reasons)
At present PD by chorionic villus sampling and direct foetal sexing or early
ultrasonography are means to determine the foetal sex allowing couples to abort
a foetus of a non-desired gender. As soon as PGD technology is available it
will certainly be used for this purpose as well, although only by a small elite
that can financially afford it.
56. According to the ESHRE report 70% of the participating centres oppose to
the idea of embryo sexing and authoritative clinical geneticists have made a
plea to limit PGD to medical indications.
b. Immunogenetic Typing
57. A recent example of extension of the indications for PGD has been the HLA
typing of blastomeres. Some forms of leukaemia or genetic blood diseases that
are fatal when untreated can be cured by transplantation of normal bone marrow
cells. For a bone marrow transplantation to be successful the donor cells must
be immunogenetically (as tested by HLA markers) identical to those of the recipient.
Especially in small families the chances are small that an HLA matched sibling
or parent is available.
58. In two such situations the parents of an affected child have requested PGD
not only for the disease concerned but in addition for an HLA test to select
8-cell embryos that have a suitable immunogenetic match to act as a donor. Here
there is a combination of PGD for medical reasons (testing for a specific blood
disease) and typing for a non-medical characteristic i.e. fitness to donorship.
The first is in the interest of the prospective child, the second does not benefit
the child but may be life saving for an affected sibling. In the United States
of America a child with Fanconi anemia has been cured by transplantation of
stem cells present in the cord blood of a newborn who was conceived under PGD
conditions as described above.
6. Ethical Considerations
59. In dealing with PGD, the International Bioethics Committee (IBC) recognizes
that several general ethical considerations need to be taken into account, concerning
for instance the status of the human embryo, the selection and destruction of
human embryos, or the health implications for women. In particular, the IBC
has reported in detail on the philosophical, socio-cultural and religious issues
related to the status of the human embryo in its report on “The Use of Embryonic
Stem Cells in Therapeutic Research” (2001). Paragraphs 22-36 of the abovementioned
report, are therefore relevant to the present ethical considerations.
60. As is the case in many other international and advisory groups it is not
possible to make a generally-accepted statement about the moral acceptability
of PGD. Several different positions for philosophical, socio-cultural or religious
reasons can be identified:
a) PGD is ethically unacceptable on whatever indication because:
- it is considered that a human being, defined by some as a person, comes into
existence at the time of fertilization;
- it is considered that PGD requires tentative creation of human embryos for
selection;
- it is considered that PGD puts too much burden on the woman.
b) PGD may be ethically acceptable under specific conditions because:
- it is considered that the full status of a human being is acquired gradually
during intrauterine development;
- it is considered that the embryo is ensouled at some stage during intrauterine
life;
- it is considered that the well being and health of the mother-to-be and prevention
of suffering of the future child (my comment on behalf of DPI blue :
why does the child future suffer? Because of it’s characteristic or because
of the negative reaction of society towards it?) justifies the procedure.
61. In the light of such heterogeneous positions, a pluralistic approach is
chosen as in the report on “The Use of Embryonic Stem Cells in Therapeutic Research”
(2001). As in the case of research on embryonic stem cells or termination of
an early pregnancy on the basis of prenatal diagnosis, each society should determine
what appears to be an acceptable position towards PGD and regulate the issue
accordingly.
62. More generally, concern has been expressed that the emphasis on avoiding
the birth of an (red: affected) child will have a negative
effect on our perception and care of handicapped children who are born. However,
in developed countries in terms of budget and care there has never been so much
attention given to the care for the handicapped as today. (my comment
on behalf of DPI blue: not true! Furthermore the term ‘care for the handicapped’
is a very patronizing one. The handicapped want equal human rights not being
taken care of. And the reality is that in comparising with other human rights
groups their right lack behind tremendously. Furthermore it is very questionable
if they are even taken care of in a dignified manner. Experiences show otherwise.)
63. It is difficult to evaluate whether the existence of new technologies like
IVF and PGD puts extra pressure on couples to have children. One can also point
to the greater reproductive choice couples at genetic risk have thanks to the
availability of those new technologies.
64. It should be emphasized that there is a strong imbalance of burden-sharing
between the two partners: it is the women who carry the physical and most of
the psychological burden of the procedures in an attempt to overcome infertility
and/or genetic problems.
65. An often-debated subject is line-drawing in case of the indications both
for PGD and PD. So far all professional organisations in clinical genetics and
reproductive technology and all advisory groups on bioethics have argued against
lists of diseases that can be defined as severe enough to justify PGD or PD.
The number of monogenic diseases alone exceeds 5,000 and nearly each of these
has variants of different severity and clinical course. Also the same disease
may be perceived differently by different couples depending on their family
history, religious and socio-economic background, life situation and future
expectations.
66. It has also to be kept in mind that decisions about natural reproduction
are not subject to social control; it is known that couples embark on a pregnancy
for a variety of reasons, several of which might not be beneficial for the well-being
of the future child. In medically-assisted reproduction, however, doctors have
to justify the intervention according to their professional values and norms.
67. In the case of assisted reproduction technology the professionals involved
do have a responsibility especially for proper genetic counselling, informed
consent, quality control and clear information about the possibilities and limitations
of the technology. As far as the indications are concerned most experts have
pleaded to limit PGD to medical reasons.
68. Destruction of embryos for non-medical reasons (my comment on behalf
of DPI blue : arbitrary term) or termination of pregnancies because
of a specific gender are not “counterbalanced” by avoiding later suffering (my
comment on behalf of DPI blue : arbitrary term) by a severe (my
comment on behalf of DPI blue : inaccurate useless term if article 65 is accurate)
disease. Sex selection by PGD or PD is therefore considered to be unethical.
69. In the case of HLA typing, in addition to PGD for a specific (blood) disease,
a normal characteristic of the embryo is investigated but the purpose is a medical
intervention for somebody else, later on. After publication of the first clinical
example of PGD and HLA typing in 2001 the term “designer-baby” has been used
to highlight ethical reservations towards an instrumental use of PGD. In this
context it should be noted that parents of an affected child might want a pregnancy
anyway and ask for PGD in order to avoid PD and possible abortion. HLA typing
of amniotic fluid cells or chorionic villi and subsequent abortion in case of
a non-matched foetus is considered unethical. Once PGD is granted for a specific
disease it is difficult to raise moral objections against additional HLA typing
to save the life of a sick sibling. PGD with the only goal of HLA typing and
selecting embryos fit for donorship after birth is, however, considered unethical,
since the embryo becomes instrumentalized for the benefit of others.
70. There have been exceptional requests by couples who themselves are affected
by a genetic disease (deafness, dwarfism by achondroplasia) to perform PGD and
select embryos carrying the same mutation for transfer to the uterus. In this
way an affected baby would be conceived on purpose with the idea that such a
child would better integrate in the family. The International Bioethics Committee
of UNESCO (IBC) considers such an approach to be unethical because it does not
take into account the many lifelong and irreversible disadvantages that will
burden the future person. (my comment on behalf of DPI blue: would they
be burdened? why would they be burdened? Because of who they are or because
of societies reaction?)
71. The literature on psychological and behavioural aspects of PGD is relatively
scant. Are parent/child relatives influenced by the choices prospective parents
make about their offspring? Do parents have higher expectations after selection
of embryos for specific biological characteristics? More generally, the issue
was raised whether a child’s “open future” is sacrificed through an uncompromising
respect for parental liberty in reproductive decisions, including avoidance
of potential harm.
72. An important issue is the possible effect of embryo selection on the parents
perception of children born after PGD. Do their expectations of a child’s development
and performance differ from those after a natural conception? Since a person’s
identity and sense of self are at least partially a product of social interactions,
does the knowledge of being selected in vitro affect parent-child relationships?
IV. ANEUPLOIDY TESTING TO IMPROVE IVF RESULTS
73. As long as in vitro fertilisation (IVF) is being practised in case of infertile
couples its low success rate in terms of children born and the frequent occurrence
of multiple pregnancies have concerned both professionals and couples. In time
the number of 8-cell embryos that were transferred to the uterus has decreased
because of negative experiences with multiple pregnancies, premature births
and associated complications for the children. Most fertility clinics now transfer
two embryos selected in vitro by morphological criteria; some already transfer
one embryo only.
74. Various studies on spontaneous abortions have shown that more than half
are associated with chromosomal abnormalities at the early stages of the embryo.
With the development of PGD it became possible to test 1-2 blastomeres for certain
chromosomal abnormalities. Using specific fluorescent-labelled DNA probes, the
most common chromosomal abnormalities like trisomy 21 (Down syndrome), trisomies
13, 16, 18 and 22 and numerical abnormalities of the sex chromosomes X and Y
can be tested (aneuploidy testing).
75. One of the common indications for PGD-aneuploidy testing is a combination
of infertility and advanced maternal age, which in itself is associated with
an increased risk of certain chromosomal abnormalities. Other indications have
been recurrent abortions and repeated IVF failures after transfer of morphologically
normal embryos.
76. During recent years aneuploidy testing has been increasingly performed in
cases of IVF without increased risk of affected offspring. The expectation is
that, by selecting and transferring embryos shown to lack the tested chromosomal
abnormalities, the chance of becoming pregnant increases and that of having
a miscarriage decreases. It is also hoped that in the future transfer of one
well-selected embryo will be sufficient and problems of multiple pregnancy will
be avoided.
77. Although retrospective studies without proper controls seem promising, reliable
prospective studies are needed to provide evidence of the clinical value of
aneuploidy testing. For those who accept PGD and PD as a means to avoid the
birth of an affected child there seem to be no moral objections against aneuploidy
testing aimed at improving the efficacy of IVF and at the same time preventing
the development of a child with an abnormal chromosome pattern.
78. The third report of the ESHRE Consortium (2002) indicates that in Europe
13 out of 20 centres perform aneuploidy testing. In the United States of America
there is increasing activity in this field. This seems especially important
in view of the high rate of multiple pregnancies in this part of the world as
a result of the higher number of embryos that are transferred.
V. GERM-LINE INTERVENTION
79. Germ-line interventions aim at the correction of a specific genetic (red:
abnormality) in the germ cells or early embryo or at the introduction
of genes that may confer to the embryo additional traits like increased resistance
to certain diseases. Spermatozoa cannot be used for diagnosis or genetic correction
because these procedures would at the same time result in the destruction of
the germ cell. Oocytes have a so-called polar body that in principle could be
used for diagnosis of gene (red: abnormalities) that are transmitted
along the female line.
80. Technically there are currently no ways to correct a genetic (red:
defect) in germ cells and the progress of research in this field is
very modest. A major obstacle is that the introduction of genes cannot be controlled
and random incorporation of foreign genetic material may well lead to unwanted
effects at the cellular level and may harm the developing embryo, foetus and
child.
81. Furthermore any genetic change of germ cells or early embryos may be passed
to future generations, which may imply irreversible risks. Given these facts,
the complexity of the relationships between genes and environment and the notion
that some genes associated with disease may be beneficial in another context,
the most elementary prudence requires that germ-line intervention should not
be undertaken on the basis of the “precautionary principle”.
82. If the safety of germ-line intervention could be guaranteed in the future
there is still the alternative of selecting normal embryos by PGD as described
in Chapter II. If selection of embryos were unacceptable and germ-line intervention
were preferred, the complexity of the procedure would limit the beneficial effects
to a very small group of people. The idea raised in some discussions that germ-line
intervention would enable the elimination of “harmful” genes from entire human
populations is more utopian than realistic.
83. On ethical grounds most national and international institutions have strongly
discouraged or prohibited germ-line interventions. In many considerations it
also plays a role that a distinction between “therapeutic” purposes and “enhancement
of normal characteristics” is far from being clear. Future insights and new
technologies may enable intervention aimed at “good” and “bad” human traits
and raise fundamental moral questions (see Chapter VI).
84. A considerable number of States as well as supranational institutions have
adopted legislation or recommendations against the use of germ cell intervention
(see Annex II). The Universal Declaration on the Human Genome and Human Rights
states in Article 24 that “germ-line interventions could be contrary to human
dignity” and there is no reason to date to modify this position.
VI. FUTURE DEVELOPMENTS AND DILEMMAS
85. The development of new technology during the past two decades has led to
a shift in the perception of the purpose of medically assisted reproduction.
IVF aims at having a child, PGD aims at having a healthy child and PGD/HLA testing
aims at having a healthy and helpful child. Undoubtedly research and technology
related to genetics will further develop in the years to come and will also
provide new opportunities for couples to select their offspring. In this Chapter
the possibilities and dilemmas related to the testing for genes associated with
an increased risk of multifactorial diseases in adulthood (susceptibility genes)
and the issue of testing for normal physical and mental characteristics will
be discussed.
1. Testing for susceptibility genes
86. Until now the main emphasis in clinical genetics has been on congenital
malformations and genetic diseases associated with chromosomal abnormalities
or mutations in single genes. Most diseases in adulthood however, such as cancers,
cardiovascular disorders, diabetes, rheumatoid arthritis, several psychiatric
diseases and neurodegenerative disorders including dementias are caused by a
complex interaction of several genes and environmental factors including life
style. Because of the high incidence and social importance of these diseases,
genetic research and its clinical application are increasingly directed towards
multifactorial diseases of adulthood.
87. Already many DNA sequences are being identified that are linked to an increased
or decreased risk of developing a specific disease. Examples of gene mutations
related to a high (60-90%) risk are those for breast cancer and colorectal cancer.
Many other specific DNA sequences double or quadruple the population risk, which
in itself varies considerably. Examples include venous thrombosis, diabetes,
manic depression and certain forms of Alzheimer dementia.
88. With improving insights and technology, especially the development of DNA
chips, which enable the simultaneous analysis of tens of thousands of DNA sequences
it is likely that testing for combinations of genes will become possible even
at the level of 1-2 cells like in PGD.
89. A major dilemma will be whether it is ethically acceptable to test and select
embryos for an increased risk of developing a particular disease later in life.
Some authors have pleaded to restrict PGD to severe diseases, others have pointed
out that it is impossible to exactly define a “severe disease”. Here not only
the clinical features and the risk of mortality and chronic handicap are at
stake, but also the perception of severity by the couples involved. In many
instances couples requesting PGD already have experience with a particular disease
in their own family.
90. Testing for susceptibility genes does not, however, imply a diagnosis or
certainty that the embryo will later be clinically affected, but only an estimation
of a risk. Is a risk in itself an indication for testing and selecting embryos?
Some experts have expressed fear that in the long run every embryo and person
will appear to be genetically at increased risk for some medical condition,
so where is the limit? Others defend that only couples who are very motivated
by family experience will request testing for susceptibility genes. In fact
there have already been a few requests for PD by women who carry one of the
high-risk breast cancer gene mutations, but the health professionals involved
have so far not reached an agreement on this issue.
91. In our Committee there is also no unanimous opinion about the acceptability
of testing for susceptibility genes. It is considered too early to express a
conclusion because of the as yet limited scientific and clinical data and the
scarcity of debate both among professionals and the public. It is, however,
felt that testing for risk genes associated with diseases in (late) adulthood
has a low priority in PGD, although future applications are not categorically
rejected. If applied, this testing should be restricted to couples with a high
genetic risk of severe diseases and a hard family history.
92. By testing for multiple genes, related to disease or normal characteristics,
we undoubtedly approach the “designer baby” and the earlier remarks about the
loss of an “open future” for children (see Chapter II.6) and adults seem of
extra importance. In this context it should be underlined that the future functioning
of an individual results from a complex interaction of genetic and environmental
factors. Also, it will be difficult to predict which “ideal characteristics”
will be required in future societies.
2. Enhancement of normal characteristics
93. Most but not all professionals involved would endorse that PGD and PD be
limited to medical indications. Fertility clinics where sex selection is performed
for non-medical reasons apparently have a different view and would argue that
the psychosocial disadvantage for a specific gender or the need of “family balancing”
justifies the procedure.
94. The IBC endorses limiting PGD to medical indications. However, it is recognized
that the distinction between medical indications and typing for normal characteristics
is not always clear. One illustration of this would be the testing for normal
immunological characteristics and subsequent attempts at enhancing some of these
so as to prevent infectious diseases in later childhood. Another example would
be the enhancement of later growth in case of a risk of remaining very small.
95. It is easy to describe a slippery slope of searching for genes related to
a variety of normal characteristics and either selecting embryos with “the best
constitution” or enhancing those characteristics considered to be desirable.
Although such scenarios are not within technical reach there have already been
reports on DNA sequences linked to human behavioural characteristics. In this
respect, the importance of education, living conditions and environment must
be stressed (see par. 92).
96. In many public debates fear is being expressed that in the future it will
be possible to screen for characteristics such as stature, baldness, obesity,
skin and hair colour, intelligence, musicality and specific abilities required
for top sports. Without further elaboration our Committee rejects the idea of
testing and/or enhancing any human characteristic other than those of importance
in alleviating suffering by disease. (my comment on behalf of DPI blue:
very dangerous as it even ethically approves enhancement if it is only labelled
as an medical intervention. This will further drive the push for medicalizing
characteristics.) (blue: my coment on behalf of DPI: the term disease is a social
construct. Who says that obesity is not a disease or baldness or…… and if enhanced
features are available they might become the norm and the characteristic fitting
the old norm might be seen as diseases….)
97. With regard to germ-line interventions, the most fundamental argument is
that we do not have the right to predetermine characteristics of future generations.
(my comment on behalf of DPI blue: but we do so with PD and PGD if it
is only the direct next generation) The notion of justice between generations,
defended by philosophers from completely different backgrounds, demands respect
for the living conditions of future individuals who should be free to develop
their potentialities without being biologically conditioned by the particular
conceptions of “good” and “bad” human traits that were dominant at the time
they were conceived. (my comment on behalf of DPI blue: that also would
be true for any child to have the right to live their life without being prevented
by their parents based on the fact that the parents judged the child’s characteristics
as deficient or not compatible with living) Neither PGD nor genetics
in general should become instruments for “intergenerational tyranny”.
98. Another argument against genetic enhancement of normal human characteristics
is that it would profoundly affect our self-perception as “persons” that is
as autonomous beings.( my comment on behalf of DPI blue: the same is
true if we define more and more characteristics as diseases defects and act
on it with medical solutions such as PD and PGD) Instead we might consider
ourselves to be mere “things” or biological artefacts designed by others.
99. A final objection against testing for normal characteristics, selection
and enhancement is that even if social agreement on the “ideal” human being
is reached, it will inevitably reinforce stigmatisation and discrimination of
those who do not fall into the accepted standards of genetically desirable traits.
And who is able to define now the ideal human characteristics for the future?
(my comment on behalf of DPI blue: The same again is true for the subnormal
as this is an arbitrary decision reinforcing stigmatisation and discrimination
of the subnormal)
VII. CONCLUSIONS
100. On the basis of the above considerations, the International Bioethics Committee
(IBC) has therefore reached the following conclusions:
· Correction of a specific genetic abnormality in germ cells or early stage
embryos (germ-line intervention) has not yet been carried out in medical practice.
Because of the many technical problems and uncertainties about possible harmful
effects on future generations, germ-line intervention has been strongly discouraged
or legally banned.
· Pre-implantation genetic diagnosis (PGD) may be an additional option for parents
at (red: increased risk) of giving birth to a child with a
genetically caused disease or malformation.
· Despite a decade of clinical use, PGD is still considered an experimental
procedure requiring highly specialized skills and a multidisciplinary approach.
So far several dozen centres in wealthy countries have applied PGD in a few
thousand couples at risk and a few hundred healthy babies have been born.
· Given the different ethical views about the value of human prenatal life,
the IBC cannot make a general statement about the moral acceptability of PGD;
instead it has taken a pluralistic approach comparable to that in the Report
on “The Use of Embryonic Stem Cells in Therapeutic Research” (2001).
· In most cases the reproductive history, risks and the demanding procedure
of PGD will prevent couples from making unjustified decisions about their future
offspring. The appropriate use and possible misuse of PGD technology should
be debated. At a national level, protocols of PGD, including the process of
information and consent of the couples involved, should be reviewed.
· More psychosocial studies are needed to evaluate the possible pressure originating
from the availability of new technologies like PGD, the possible influence on
the parent-child interactions as a result of high expectations after embryo
selection and the effect of PGD on couples because of greater reproductive choice.
Also the possible impact on disabled people and their parents should be considered.
· It is recommended that PGD be limited to medical indications (my comment
on behalf of DPI blue : arbitrary term). Therefore sex gender selection
for non-medical reasons is considered to be unethical.
· Embryonic HLA typing for fitness as a donor of blood stem cells after birth
to save the life of a sibling with a genetic blood disease or leukaemia is considered
ethically acceptable only if it is carried out simultaneously with PGD for the
disease concerned and if mismatching of the HLA type is not considered in itself
as a basis for selecting against the embryo unaffected by the disease concerned.
· PGD to select and implant embryos with a similar genetic disease or condition
as (one of) the parents is considered unethical.
· PGD of chromosomal abnormalities to enable selection and implantation of unaffected
embryos thereby possibly improving the results of in vitro fertilisation (so-called
aneuploidy testing) is considered ethically acceptable. Because of its high
cost the technology of PGD is presently not equally available to couples that
need it.
· A decision about the acceptability of PGD for DNA sequences that are associated
with an increased risk of multifactorial diseases, including many forms of cancer,
cardiovascular disease and neurodegenerative disorders, requires more public
debate and discussion among professionals. If such forms of PGD were considered,
they should be restricted to cases involving high genetic risk and clinically
severe diseases.
· The recommendation that PGD be limited to medical indications implies that
testing for normal physical and mental characteristics is rejected. The same
applies to germ-line intervention.
…
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COMPOSITION OF THE IBC WORKING GROUP
ON PRE-IMPLANTATION GENETIC DIAGNOSIS AND GERM-LINE INTERVENTIONS
_____________
Chairperson
KOSZTOLÁNYI Dr (Mr) György (Hungary)
Professor and Chair of the Department of Medical Genetics and
Child Development, University of Pecs
Vice-President of the Faculty of Medicine of the University of Pecs
Former President of the Hungarian Society of Human Genetics
Rapporteur
GALJAARD Prof. (Mr) Hans (The Netherlands)
Professor of Human Genetics
Head of the Department of Clinical Genetics, University Hospital Rotterdam
Members
ANDORNO Dr (Mr) Roberto Luis (Argentina)
Professor of Civil Law
GONÇALVES DOS SANTOS Prof. (Mrs) Heloisa (Portugal)
Professor of Medical Genetics
Head of the Medical Genetics Service, St Maria Hospital, Lisbon
Coordinator of the Bioethics Committe of the Portuguese Society of Human Genetics
(SPGH)
Founding Member and Former Chairperson of the SPGH
GUESSOUS-IDRISSI Dr (Mrs) Nouzha (Morocco)
Professor and Head of Parasitology-Mycology Laboratory,
Faculty of Medicine and Pharmacy of Casablanca
Member of the Biomedical Research Ethics Committee, Faculty
of Medicine and Pharmacy of Casablanca
Founding Member of the Moroccan Organization of Human Rights
IDA Prof. (Mr) Ryuichi (Japan)
Professor of International Law
Rapporteur of the Committee of Regional Economic Development Law
of the International Law Association
JEAN (Mme) Michèle (Canada)
Adviser in programme development, Faculty of Higher Education, University of
Montreal
Member of the Commission of Ethics of Science and Technology
Former Special Adviser to the Minister of Foreign Affairs of Canada to the European
Commission
Former Vice-Minister of Health
KIGONGO Prof. (Mr) James Kayolo (Ouganda / Uganda)
Professor and Head of the Department of Philosophy of the University of Makerere
Chairperson of the National Bioethics Committee of Uganda
KOLLEK Prof. (Mrs) Regine (Germany)
Professor of Health Technology Assessment
Vice-Chairperson of the German National Ethics Council
Former Chairperson of the Advisory Board on Ethics, Federal Ministry of Health
LE DINH Dr (Mr) Luong (Vietnam)
Professor and Head, Laboratory of Molecular Genetics, Vietnam National University
Vice-Chairperson and General-Secretary of the Genetics Society of Vietnam
Editor-in-chief of Genetics & Applications
Invited Expert
VAN STEIRTEGHEM Dr (Mr) André (Belgium),
Clinical Director of the Centre for Reproductive Medicine,
Vrije Universiteit Brussel (VUO)
Some Guidelines and Legislation on Germ-line Intervention
_____________
INTERGOVERNMENTAL ORGANISATIONS
Council of Europe. Convention on Human Rights and Biomedicine, 1997, art. 13.
“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.” (art. 13)
“Whilst developments in this field may lead to great benefit for humanity, misuse of these developments may endanger not only the individual but the species itself. The ultimate fear is of intentional modification of the human genome so as to produce individuals or entire groups endowed with particular characteristics and required qualities.” (Explanatory Report to the European Convention, point 89)
European Union. Group of Advisers on the Ethical Implications of Biotechnology
to the European Commission, Opinion n° 4 on the Ethical Implications of Gene
Therapy, December 13, 1994.
“Because of the important controversial and unprecedent questions raised by germ-line therapy, and considering the actual state of the art, germ-line gene therapy on humans is not at the present time ethically acceptable.” (point 2.7)
NON-GOVERNMENTAL ORGANISATIONS
CIOMS (Council for International Organizations of Medical Sciences), Declaration
of Inuyama on Human Genome Mapping, Genetic Screening and Gene Therapy, 1990.
“Before germ-line therapy is undertaken, its safety must be very well established, for changes in germ cells would affect the descendants of patients.”
Council for Responsible Genetics, Paper on Human Germline Manipulation, 1992.
“There is no universally accepted ideal of biological perfection. To make intentional changes in the genes that people will pass on to their descendants would require that we, as a society, agree on how to classify ‘good’ and ‘bad’ genes. We do not have the necessary criteria, nor are there mechanisms for establishing such measures. Any formulation of such criteria would inevitably reflect particular current social biases. The definition of the standards and the technological means for implementing them would largely be determined by economically and socially privileged groups (...).
The following arguments lead us to unequivocally oppose germline modification:
(1) Germline modification is not needed in order to save the lives, or alleviate
the suffering, of existing people. Its target population are "prospective
people" who have not even been conceived.
(2) The cultural impact of treating humans as biologically perfectible artefacts
would be entirely negative. People who fall short of some technically achievable
ideal would be seen as "damaged goods", while the standards for what
is genetically desirable will be those of the society's economically and politically
dominant groups. This will only increase prejudices and discrimination in a
society where too many such prejudices already exist.
(3) There is no way to be accountable to those in future generations who are
harmed or stigmatized by wrongful or unsuccessful germline modifications of
their ancestors.
The Council for Responsible Genetics therefore calls for a permanent ban on germline gene modification.”
NATIONAL LEGISLATION
Australia. National Health Medical Research Council (NHMRC). Guidelines for
Ethical Review of Research Proposals for Human Somatic Cell Gene Therapy and
Related Therapies, 1999 (http://www.nhmrc.health.gov.au/issues/humangenetics.htm).
“While the introduction of DNA or RNA into somatic cells is ethically acceptable, the introduction of DNA or RNA into germ (reproductive) cells or embryos is ethically unacceptable, since there is insufficient knowledge about the possible consequences including hazards and effects on future generations (...). HRECs [Human Research Ethics Committees] would not be expected to receive, and should not approve, research proposals for the introduction of DNA or RNA into germ (reproductive) cells or embryos” (Introduction).
Brazil. Law n° 8974 on Genetically Modified Organisms, 1995, art. 13.1.
“The following acts shall constitute crimes:
1. the genetic manipulation of human germ cells.”
Canada. Tri-Council Policy Statement: Ethical Conduct for Research Involving
Humans, 1998, art. 8.5. (http://www.nserc.ca/programs/ethics.htm).
“Gene alteration (including ‘gene therapy’) that involves human germline cells or human embryos is not ethically acceptable. Gene alteration for therapeutic purposes and involving human somatic cells may be considered for approval.”
Denmark. Danish Council of Ethics, Humans and Genetic Engineering in the New
Millenium, 1999 (http://www.etiskraad.dk/english/).
“(...) there has also been an international consensus to date among researchers and politicians that gene therapy is only to be conducted on the gravely ill, and only on their somatic cells that will not be passed on to the next generation.”
France. Civil Code, art. 16-4 (introduced in 1994); National Advisory Committee on Ethics, Opinion n°22 on Gene Therapy, December 13, 1990.
“Without prejudice to research seeking to prevent or treat genetic diseases, no alteration can be made to genetic characteristics with the aim of modifying a person’s offspring.” (Civil Code, art. 16-4)
There must be formal prohibition of any attempt to perform germinal gene therapy.” (French National Advisory Committee on Ethics)
Germany. Embryo Protection Law, 1990, art. 5.
“Article 5
(1) Any person who artificially alters the genetic information of a human germline
cell shall be punished by up to five years' imprisonment or by a fine.
(2) The same penalty shall be imposed on any person who uses a human germ cell
with artificially modified genetic information for fertilisation.”
Switzerland. Constitution, art. 119a.
“Any form of human cloning and any intervention in the genetic information of gametes and human embryos are forbidden.”
United Kingdom. Human Fertilisation and Embryology Act, 1990, Schedule 2, arts.
2(4), 3(4); Report of the Committee on the Ethics of Gene Therapy (Chairman:
Cecil Clothier), 1992; British Medical Association, Ethics Committee, Human
Genetics. Choice and Responsibility, Oxford University Press, 1998, p. 198-199.
“A [treatment] licence ... cannot authorise altering the genetic structure of any cell while it forms part of an embryo.” (Human Fertilisation and Embryology Act, 1990)
“We are clear that there is at present insufficient knowledge to evaluate the risks to future generations of gene modification of the germ line. We therefore recommend that gene modification of the human germ line should not yet be attempted.” (Committee on the Ethics of Gene Therapy)
“Alternation of a defective gene in the germ cell or in the early embryo would enable future generations to benefit from the treatment but its safety is not, and in the short term cannot be, proven. In view of these concerns, there is widespread agreement that germ cell gene therapy should not be undertaken.” (British Medical Association)
United States of America. NIH, Guidelines for Research Involving Recombinant DNA Molecules, 1998, Appendix M (http://www.niehs.nih.gov/odhsb/biosafe/nih/rdna-apr98.pdf).
“RAC [Recombinant DNA Advisory Committee] will not at present entertain proposals for germ line alterations but will consider proposals involving somatic cell gene transfer.”
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