APPENDIX 8
Memorandum from Dr Neville Cobbe, University
of Edinburgh
ABSTRACT
The evidence described in this document details
suggested priorities for revision of the HFEA Act, focusing on
the interests of children whilst urging for caution in the application
of technical advances, tackling causes of infertility, discussing
the feasibility of adoption as a solution to childlessness following
reform of abortion law and appraising experimentation on human
embryos.
PRIORITISING THE
INTERESTS OF
CHILDREN
(1.i) A number of contributors to the online
consultation have agreed that the welfare of children should be
paramount. However, it has also become clear that some people
are not prepared to give children conceived artificially the same
entitlements as other children if this might interfere with their
own reproductive freedom. Surely the greatest protection should
be given to those with the least choice available? This is consistent
with the United Nations Convention on the Rights of the Child,
which affirms that "the child, by reason of his physical
and mental immaturity, needs special safeguards and care, including
appropriate legal protection". Similarly, Article 8 of the
Declaration of the Rights of the Child has stated that children
"shall in all circumstances be among the first to receive
protection and relief".
(1.ii) In particular, all future reproductive
practices (including gamete donation and surrogacy) should therefore
defend the right of children to know their parents according to
Article 7 of the Convention on the Rights of the Child, whilst
respecting Recital 24 and Article 14 of the EU human tissue directive.
In keeping with Article 24 of the Convention on the Rights of
the Child, it is also vital that the health of children should
never be compromised whilst seeking to satisfy desires for parenthood.
Consequently, the use of any immature gametes in assisted reproduction
should be prevented until we can guarantee that we are able to
completely replicate in vitro all of the essential epigenetic
modifications naturally acquired by gametes in vivo. Unless
precautions are made to ensure such rights are upheld, the consequences
will certainly include future litigation.
(1.iii) In keeping with Articles 11 and 24 of
the Universal Declaration on the Human Genome and Human Rights,
reproductive cloning and germline modification should remain illegal
due to the impossibility of guaranteeing their safety and the
potential negative social consequences for the individuals concerned.
As embryo splitting with selective delayed implantation may place
similar social pressures and expectations on new children as cloning
by nuclear transfer, this practice should also be discouraged.
Finally, the creation of embryos from unfertilised eggs for reproductive
purposes should also be prohibited as this appears to be unfeasible
without germline modification, in addition to the increased risks
of both homozygosity for deleterious alleles and genomic imprinting
defects.
THE NEED
FOR GREATER
ATTENTION TO
THE CAUSES
OF INFERTILITY
(2.i) The root causes of infertility have
received far less attention than various technological innovations
that try to circumvent the problem itself, resulting in unsubstantiated
claims of infertility on the basis of essentially behavioural
choices. If our society is genuinely interested in treating infertility,
then proportionately more attention should be paid to both epidemiological
studies of infertility and basic research aimed at better understanding
the molecular basis of gametogenesis.
(2.ii) Meanwhile, considerable caution should
be exercised in the current use of ICSI (and possibly IVF generally),
based on possible associations with genomic imprinting disorders.
However, it remains to be clarified whether any increased risks
of these and other congenital defects are primarily due to IVF
procedures or parental genetic backgrounds. In one study, it has
been reported that the prevalence of aneuploidy and structural
chromosome defects are more than tenfold higher among infertility
patients compared to the general population. In particular, Y
chromosomal microdeletions affecting the DAZ gene family are the
most common known genetic cause of human male infertility and
spermatogenic failure whilst disruption of either the Catsper
gene or the Smcp gene has been shown to affect sperm motility.
Consequently, the use of assisted reproduction without parental
genetic screening may simply aggravate the incidence of low sperm
counts or the lack of functional sperm and lead to increased male
infertility in subsequent generations.
(2.iii) In addition to genetic factors,
promiscuous sexual behaviour may also contribute to infertility
by increasing the incidence of venereal disease. For example,
between 1995 and 1999, there was a 73% increase in new reports
of genital chlamydial infection among men in the United Kingdom.
The risk of transmitting Chlamydia to women is particularly
worrying as this can result in serious complications including
infertility. In addition, the number of new cases of gonorrhoeal
infection (another cause of infertility) appears to have risen
every year since 1995, with a 27% increase in cases from England
and Wales between 1999 and 2000. Therefore, any treatment of infertility
must include promoting awareness of the risks of casual unprotected
sex. Lastly, the potential impact of environmental pollutants
on male and female reproductive health deserves further investigation.
In conclusion, it is clear that greater understanding of both
genetic and environmental contributors to infertility will be
crucial to future treatment, with comprehensive counselling available
to anyone trying to conceive.
THE NEGLECTION
OF ADOPTION
(3.i) Although it would be foolish to claim
that all infertile couples would consider adoption to be a satisfactory
solution, it is nonetheless clear that adoption has been sorely
neglected as a possible solution for many childless couples. Although
adoption does not treat the problem of infertility itself, it
could equally be argued that gamete donation does not really treat
infertility but rather side steps around the problem. It would
therefore appear inconsistent to place considerable emphasis on
the use of gamete donation whilst failing to encourage adoption.
In contrast to gamete donation, adoption also provides a practical
and caring solution to children who are unwanted by their genetic
parents.
(3.ii) Similarly, viable excess embryos
generated through IVF could provide a possible solution to many
childless couples incapable of producing functioning gametes themselves.
At the very least, it would seem unreasonable to suggest that
any excess embryos resulting from IVF should be preferentially
used in experimentation and destroyed rather than used to directly
help others to conceive. Obviously the children born to infertile
couples in this way would not be their genetic offspring in the
same way that adopted children do not usually carry half the genes
of each of their adoptive parents. However, at least one of the
individuals bringing up a child also does not contribute any of
their genes in the case of gamete donation.
(3.iii) Given that current practices such
as ICSI may actually select for infertility if sperm motility
defects are due to genetic factors, it would seem that infertile
couples might have an increased chance of also becoming grandparents
if adoption was more readily available as an alternative, since
infertility is evidently not such an issue where unwanted progeny
are concerned.
However, the increased use of abortion for essentially
social reasons has unfortunately resulted in a dramatic decrease
in the number of children available for adoption. By examining
the available national statistics, it can be shown that there
is a strong negative correlation between the total number of adoption
orders and the number of legal abortions registered. For example,
the Spearmann coefficient of correlation between these two data
sets during the period from 1974 to 2001 is -0.814 (±sr
= 0.079). It is therefore clear that in order for adoption to
become more feasible as a solution to childlessness, then it must
be encouraged in preference to abortion.
THE NEED
TO REFORM
ABORTION LAW
(4.i) It is clear from the online consultation
that people hold different views regarding the rights of the unborn,
arguably based on the extent to which one's viewpoint is influenced
primarily by an understanding of basic biology or personal interests.
However, many people (whether disabled, homosexual or members
of an ethnic minority) find the suggestion that they should be
selected against as a group to be completely unacceptable. It
is also clear from various comments submitted during the online
consultation that some people find abortion acceptable either
on supposedly medical grounds or because a child may be unwanted
by their genetic parents, yet find it unacceptable that anyone
like themselves might also be denied the right to life on the
basis of the same criteria. At present, the alarmingly relaxed
criteria for abortion seem to have created a precedent for all
manner of selection against various "unwanted" groups
and minorities.
(4.ii) For example, it appears that well
over 99% of abortions in Britain since the millennium were performed
for essentially social reasons, under the grounds that a pregnancy
may pose any sort of increased potential risk to one's mental
or physical health, with less than one in a thousand abortions
being performed to directly save the life of the mother. Moreover,
in the case of a pregnancy which has exceeded its twenty-fourth
week, the loose criterion for abortion where there is a risk of
"physical or mental abnormalities" apparently results
in both the killing of foetuses with potentially treatable or
less threatening medical complaints and a society more willing
to dispose of its disabled than meet the cost of caring. Unless
a group of people unanimously inform us that they themselves believe
it would have been better if they had never been born, what grounds
do we have to deny anyone the opportunity to experience life,
whether they might be disabled or whether they are likely to be
of a particular gender, race, stature or sexual orientation? We
have no authority to assert that a particular condition is so
debilitating that abortion is justified without the consent and
opinion of all affected individuals regarding the value of their
lives. If we really want to live in a fair society in which prejudice
is not tolerated, then surely we should seek to ensure that the
use of abortion is limited to those rare cases where lives are
irrevocably endangered, in keeping with the constraints of Articles
3, 7 and 25 of the Universal Declaration of Human Rights as well
as Article 6 of the Universal Declaration on the Human Genome
and Human Rights. Unless we do so, we completely fail to recognise
the fundamental equality and rights of all fellow humans.
(4.iii) The Convention on the Rights of
the Child affirms the need for "special safeguards and care,
including appropriate legal protection, before as well as after
birth" and states in Article 6 that "every child has
the inherent right to life" and we should "ensure to
the maximum extent possible the survival and development of the
child", whilst Article 1 defines a child as "every human
being below the age of eighteen years". Unless we radically
change our definition of human being to mean something other than
a member of the species "Homo sapiens" (as defined
by the Oxford English Dictionary), then it is clear that the vast
majority of abortions currently performed fail to comply with
universally recognised rights.
RE-EVALUATING
HUMAN EMBRYO
EXPERIMENTATION
(5.i) No completely convincing argument
has been made regarding why human embryos should be considered
as anything other than human. Although it has been argued that
the blastocyst would die anyway if not transferred to the womb,
the same principle could be applied to the survival of children
deprived of nourishment or nurture. Similarly, low rates of natural
implantation do not justify deliberate destruction of embryos
any more than high mortality rates in developing countries justify
genocide. The argument that an embryo is temporarily unaware of
its own existence and feels no pain could equally be applied to
anyone in a coma or under general anaesthesia. To deliberately
deny experience to an embryo simply because it won't yet know
what it's missing is inconsistent with the desire of most people
to experience what life can offer and further application of the
same principle would suggest that one could deny any future educational,
marital or voting rights to today's infants. The notion of using
emotional links with others as a basis for denying the humanity
of embryos inevitably devalues anyone who lives alone or has difficulty
forming relationships. Lastly, the assumption that the right to
life and all consequent human rights are dependent on one's stage
of development is simply a form of discrimination against the
young. In conclusion, none of the above criteria can be applied
consistently to embryos alone, so the only discernible reasons
for denying human rights from the outset are self-interest and
prejudice.
(5.ii) During the online consultation, no
unbiased statistical evidence could be produced to support the
view that most scientists and physicians favour either therapeutic
cloning or stem cell research involving human embryos. By contrast,
a recent survey in the U.S.A. to explore public opinion on stem
cell research is particularly revealing. The participants were
asked if they felt they had heard much about research involving
embryonic stem cells but no prior attempt was made to objectively
evaluate awareness of the issues concerned. Indeed, it is doubtful
how informed the participants really were, as the assertion that
"support grows with more information" was based on changes
in voting after hearing information that highlighted only the
potential of embryonic stem cells but made no reference to current
therapeutic obstacles (such as teratoma formation) or additional
concerns specific to therapeutic cloning such as the source of
donor eggs. Another critical assumption inherent in the information
presented to participants was that such research would not lead
to any further destruction of embryos than is currently the case
in IVF, whilst the current need to generate excess embryos remained
unchallenged. In Britain, the success rate of IVF between 1986
and 2001 rose from 9% to 22% of treatment cycles leading to a
live birth, such that the Human Fertilisation and Embryology Authority
revised its guidelines to reduce the number of embryos used in
IVF from three to two in order to decrease the likelihood of multiple
births. Increased success rates have been partially attributed
to improved culture conditions for early embryos or their transfer
to the Fallopian tube rather than uterus. As pregnancy rates over
30% have been reported following single embryo transfer, this
raises serious questions regarding the continued need to generate
so many excess embryos.
(5.iii) Nevertheless, one can agree that
research should be pursued on both stem cells from adult or extraembryonic
sources and some embryonic stem cells. Whilst trials with various
mesenchymal cells have shown particular therapeutic promise, widespread
clinical use and understanding of any stem cells is still in its
infancy. It is therefore highly questionable that current basic
research should necessarily require human embryos. In particular,
given that we now have sequenced genomes for both the rat and
the mouse, this should greatly facilitate the transfer of insights
from stem cell research in model organisms to our own species.
Indeed, it has been shown that the overall expression of markers
of the pluripotent state is essentially similar in mouse and human
embryonic stem cell lines, with most identifiable differences
thought to reflect different stages at which stem cells had been
harvested from the inner cell mass in different organisms or contamination
with differentiated human cells. Most observed differences are
consistent with the reported ability of human embryonic stem cells
(unlike their mouse counterparts) to differentiate into trophoblast-like
cells and to propagate in a pluripotent state even in the absence
of LIF, whilst the greater resistance of human embryonic stem
cells to apoptosis indicates that their application in a clinical
context may pose an even greater risk of cancer than observed
with mouse cell lines. As mouse stem cells provide a convenient
model for studying differentiation requirements, one must conclude
that the urgency to use human embryos at this stage in the search
for therapies arguably contrary to the Nuremberg code and the
Declaration of Helsinki is motivated primarily by quests for fame
or fortune, whilst downplaying recognised risks and ethical concerns.
(5.iv) The grave risks currently associated
with any therapeutic use of embryonic stem cells are nevertheless
acknowledged even by proponents of research involving human embryos
and are referred to in Recital 11 of the EU human tissue directive.
One should therefore be concerned not only by the questionable
morality of destroying potentially viable human lives but also
that the rush to apply preliminary embryonic stem cell data in
a clinical setting may result in patients being subjected to premature
trials, placing them at risk of complications such as teratocarcinomas.
Regardless of the moral status of human embryos themselves, the
feasibility of any research necessitating their destruction needs
to be critically assessed in relation to practical alternatives.
By contrast, such complications in the use of adult stem cells
have so far only been reported as a consequence of forced telomerase
expression, whilst the risks of cell fusion in vivo have
been grossly exaggerated without challenging the established use
of bone marrow transplants and umbilical cord blood to treat leukaemia
patients. Moreover, it should be noted that adult stem cells rarely
acquire oncogenic mutations due to propagation of replication
errors as the original DNA templates are selectively segregated
into daughter stem cells, whilst their propagation by treatment
with xanthosine (to reversibly suppress asymmetric cell division)
does not appear to result in either senescence or tumorigenic
properties.
(5.v) Regarding the naïve proposal
to create interspecific chimeras for therapeutic cloning, it would
appear that host mitochondrial function is not properly supported
by donor nuclei from more distantly related species. Although
reports differ regarding the preferential replication of donor
or host mitochondria, it is nonetheless possible that supplying
more donor mitochondria may alleviate some incompatibility problems.
However, preliminary data from comparative cloning experiments
and interspecific crosses also suggest that nuclear reprogramming
in ova from other species would lead to even greater epigenetic
dysregulation than previously observed with nuclear transfer.
Given the association with cancer of both global DNA hypomethylation
and hypermethylation of tumour suppressor gene promoters, this
should surely be avoided.
May 2004
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