Joint Ethico-Medical Committee
The Catholic Union of Great Britain
Guild of Catholic Doctors
Submission to Human Genetics Advisory Commission
in response to the consultation document
Cloning Issues in Reproduction, Science and Medicine, January 1998.
We welcome the opportunity to contribute to the discussion on human cloning. We agree that
it is appropriate for the Human Genetics Advisory Committee (HGAC) and Human Fertilisation
and Embryology Authority (HFEA) to consider the moral issues surrounding recent
developments in cloning technology. Decisions and any changes to legislation necessary to
control work in this field can then be made before they become a practical reality, rather
than act after the introduction of any experimental techniques which might be permissible
under current legislation.
As Catholic laymen and women we draw inspiration from the statement: "Human life
must be respected and protected absolutely from the moment of conception. From the first
moment of his existence, a human being must be recognised as having the rights of a person
- among which is the inviolable right of every innocent being to life." From this it
follows that we are opposed in principle to destructive embryo experimentation as
currently allowed by law. Despite our fundamental objection in principle and the
restricted nature of the questions presented in the consultation document which prevent us
from addressing the important issue of the status of the human embryo, we feel that we can
still offer responses to the various questions posed in the consultation document.
Section 7 - Potential Research and Therapeutic Benefits: Ethical implications.
The consultation paper clearly distinguishes between "reproductive cloning" - which is prohibited under current law and which the HGAC/HFEA propose remains illegal - and "therapeutic cloning".
Therapeutic cloning for mitochondrial disease
Under 'therapeutic cloning' it is suggested that nuclear replacement may be used to avoid transmission of inherited mitochondrial diseases. It is only 10 years since the first mutation was identified in mitochondrial DNA. Since then it has been established that mitochondrial DNA codes for 13 proteins, two rRNA and 22 tRNA species, all involved with the oxidative phosphorylation pathway. However, some reading the consultation paper may not realise that the mitochondrial DNA is not an independent and separate genetic pool having complete control of mitochondrial function. The majority of mitochondrial proteins are coded by nuclear DNA and several mitochondrial diseases are inherited in traditional fashion (ie autosomal genes on nuclear chromosomes.)
The scene is further complicated in that mitochondrial DNA has a high mutation rate (5-10 times that of nuclear DNA) and that the more severe mitochondrial mutations show heteroplasmy (ie. the presence of a mixture of mutant and normal mitochondrial DNA in the same cell). Furthermore it has been shown that mitochondrial diseases may be acquired in early embryonic life or induced by chemical/toxic damage; and in some cases biochemical manipulation has been shown to reverse some of the effects of mitochondrial damage. The understanding of these diseases is therefore still in its infancy. With the rate of advance in molecular medicine it is likely that effective treatment will be available within the same timescale that nuclear transfer technology might become available. It is certainly premature to suggest that the legislation should be relaxed at the current state of knowledge to allow even experimentation with such nuclear replacement in humans.
Furthermore, the likely practical reality of nuclear replacement in these circumstances would have the logical consequence of undermining the consensus that reproductive cloning should not be permitted. Currently to enhance the success of IVF a number of ova are fertilised, and a limited number of embryos are replaced in the womb, with the option of cryopreservation of others. If the technique of nuclear replacement for mitochondrial disease should become a practical reality, it is likely that the scientists would wish to have several attempts at nuclear transfer into ova. It may well be that the original embryo is allowed to develop into a several cell stage, and attempts at transferring each nucleus into an unfertilised egg would be made (this is the technique used in the Oregan Primate Research Centre in their cloning experiments on monkey embryos). One could envisage the scenario where the only successful nuclear transfers were from a single original embryo. It would be likely that the clinicians involved would wish to transfer several of these embryos into the woman in order to maximise the chance of a successful pregnancy. In such circumstances it would be difficult for the HFEA to resist and demand that only one embryo is used. The system would therefore have produced identical clones. Once the principle of allowing cloned identical twins to be used under one situation was permitted, what would be the justification for banning it under other circumstances? The techniques of 'therapeutic' cloning would inevitably and logically lead to 'reproductive' cloning and we therefore urge rejection of this type of cloning.
Another logical consequence of permitting this type of 'therapeutic' cloning is the acceptance, in principle, of the manipulation of the germline genes. Presumably the only reason for wishing to undergo nuclear transfer to avoid mitochondrial disease is that the parents wish their children's genetic make-up to be predominantly from their own genes - otherwise current methods using a donor ovum and its nucleus would be acceptable. Allowing 'therapeutic' cloning for mitochondrial disease establishes the principle that it is permissible to discard part of the genetic constitution of an embryo and replace it with the genetic material from a third individual. This is a variation on germline gene therapy to which there is universal opposition. An illustrated example follows.
The consultation paper is asking for views on procedures not yet technically feasible and so it is permissible to consider further hypothetical situations. We are now beginning to recognise that contrary to Mendel's original theory that genes from either parent have an equal effect, it is now clear that expression of some genes is dependent on their parent of origin. The mechanism involved is called genomic imprinting, which refers to the differential effects of maternally and paternally derived chromosomes, segments of chromosomes, or genes - i.e genomic imprinting is where either the paternal or maternal genes are selectively expressed. A classical example of genomic imprinting is seen in the two distinct but overlapping syndomes - Prader-Willi syndrome (mild mental retardation, 'floppy' infant with feeding problems in newborn but voracious appetite and obesity with behavioural problems in later childhood) and Angelman syndrome (severe mental retardation, epilepsy, happy social mood with paroxysms of laughter). In Prader-Willi syndrome there is deletion of segments q11-q13 from paternal chomosome 15; whereas the maternal chromosome 15 is normal. In Angelman syndrome the reverse is the case, with the deletion being from an identical part of maternal chromosome 15. (Both syndromes can also occur in uniparental disomy - that is where both chromosomes 15 come from one parent.) Let us consider the hypothetical situation where a disease was due to a transmissible problem associated with maternal chromosome 15 in which there was maternal genomic imprinting. Would it be permissible, if technically feasible, to remove chromosome 15 from the fertilised egg and replace it with chromosome 15 from another woman? This suggestion is not unrealistic as scientists are already using lasers to remove parts of chromosomes. Most would feel that such chromosomal manipulation constituted the path to 'designer' babies and was dangerous manipulation of the germline genes. But logically there is no difference between this scenario and discarding the native mitochondrial DNA and using the mitochondrial DNA of a third parent - the principle involved in 'therapeutic' cloning for mitochondrial disease.
Cloning might advance knowledge about cancer and ageing.
Research allowed by the embryology act includes research to increase knowledge concerning causes of congenital disease and to increase knowledge about the causes of miscarriages. Many claims for the potential benefits of embryo research in these areas were made during the debates leading up to the passing of the act. The validity of many claims were challenged and prominent scientists involved in embryo research at the time did admit that "Research using human pre-embryos is not, and never has been, concerned with the treatment of genetic disorders or chromosomal abnormalities." Examination of the titles of research projects licensed in the UK shows that these areas have not been areas of primary concern of the researchers. The huge numbers of embryos created for research, treatment and cryopreservation shows scant respect for them. In addition examination of world scientific literature fails to reveal any evidence that research on early human embryos has advanced our understanding into these problems. It is in this light that we examine some of the claims made to the potential benefits from cloning techniques.
The consultation document suggests that nuclear replacement research might advance insight in to the origins of cancer and ageing. It is difficult to refute such a claim, but equally there is no evidence on which to base such claims and it is difficult to imagine how research limited to the first 14 days of life of cloned embryos will produce significant data in these areas. It is important to recognise that molecular genetics has made substantial inroads into understanding the basic mechanisms of cancer behaviour and tumorigenesis. But it must not be forgotten that the most dramatic advances in understanding normal physiological processes have come about using molecular medical techniques either in diseased states - whether they be genetically inherited conditions or acquired - or by deliberate genetic manipulation in animal modes, such as transgenic and knockout mice. An example is the inherited disease thalassaemia; molecular medicine was crucial in unravelling the complex clinical presentations as well as revealing the developmental switch changing through embryonic haemoglobin, fetal haemoglobin and then adult haemoglobin. On current evidence it is much more likely that currently available techniques will continue to advance our knowledge about cancer and aging rather than suggesting that cloning on human embryos is needed.
We must also be reminded that although recent research has increased our basic understanding of physiological processes and has opened up many theoretical avenues of potential therapy, none of these have yet been realised into significant advances in cancer treatment. A principle of medical research is that before human beings have experimental treatments, there must be strong evidence from animal work that this is likely to succeed. It is of note that in 1975 the World Medical Associations declared that in research on human subjects the possible benefits to society must never take precedence over possible risks to the individual. We therefore oppose use of human embryo clones for basic science research, which would not benefit those or even other embryos, as contrary to human dignity.
Cloning might lead to production of organs for transplantation
It is suggested that tissue/organ production for transplantation may result from nuclear transfer techniques. Because such tissues and organs would have the genetic identity of the patient they could be used for transplantation without the problem of rejection or donor shortage. Again it is difficult to refute this suggestion but on what evidence is this claim made? The cloning of Dolly has demonstrated that the total potentiality of the genome is present in adult nuclei, and that this potential is not permanently inactivated. This being the case it is also theoretically possible that adult cells could be induced to differentiate into different tissues/organs without the necessity of cloning into an ovum/early embryo. Doctors are being reminded to use evidence based medicine and so we ask on what evidence is the claim that cloning might lead to tissue / organ production based? Although there is a place for purely speculative research it is not justified to use human beings, including embryos, for such research.
An increased understanding of how genes control development continues after the pioneering work of Lewis, Nusslein-Volhard and Wieschaus, for which they shared the 1995 Nobel Prize in Physiology and Medicine. They laid the foundations concerning the genetic control of early embryonic development in Drosophila flies. Much of the work was done by looking at deliberately induced mutants and by manipulation of the homeobox genes, to produce flies with eyes, legs and other body parts in abnormal positions.
We now know that in both vertebrates and invertebrates two families of genes, and a number of others, are important in development. These are the homebox (hox) genes and the paired box (pax) genes. Of greater significance is that there is remarkable interspecies homology of the genes; a 94% sequence homology has been shown between the pax 6 gene of Drosophila, mouse and man. For example transplantation of either the mouse or squid pax 6 gene (important in development of the eye) into Drosophila caused production of ectopic eyes which were of Drosophila morphology. Such studies indicate that the genetic control mechanisms of body development are much more universal than anticipated and the repeated demonstrations of the evolutionary conserved and critical role of almost identical genes from insects to molluscs and mammals suggests that many animals use the same master control genes for morphogenesis. This indicates that animal research is likely to be beneficial. The sequential expression of the Hox genes in the developing kidney has been well documented in the mouse. Targeted mutations of both Hox and the Pax-2 genes, in vivo, have already revealed discrete developmental defects affecting the development of the kidney.
The proteins produced by these genes have DNA binding properties and it has been shown that they play a part in the transcriptional control of other genes. As understanding increases it may be possible to selectively switch these genes on and off and maybe stimulate production of organs from tissue culture rather than go back to the embryo and complete totipotentiality. Certainly the manipulation of early human embryos in similar fashion, to reproduce results done in animal experiments, would be completely unethical. It is more realistic to suggest that current and ethically acceptable molecular genetics techniques will lead to advances in transplantation, including possible production of new organs, rather than invoking a need to allow cloning in human embryos.
Answers to questions posed in Section 7
7.4. Would the use of nuclear replacement techniques or embryo splitting to create embryos raise any new issues in relation to the special status of the human embryo?
Yes. Recent advances in understanding of normal physiological (and pathological) processes have come not from the study of entire normal organisms but from study of abnormal organisms, which in the research scenario are usually those where specific mutations or deletions (eg knock-out cell lines and knock-out mouse strains) have been created. Studying the effects and abnormalities subsequent to the mutations then helps deduce the normal action of the mutated /deleted gene. The deliberate creation of mutants or other genetic manipulation in a human embryo would completely remove any 'special status' applicable to the human embryo; it would be no different from any experimental animal. Such basic science research cannot be done on human embryos whilst still trying to argue that they are given some special status.
7.5 A non-reproductive application of this technology would be to use the nuclear replacement technique to create in-vitro stem cells. Are there any medical or scientific areas that might benefit from research involving the creation of a cloned human embryo? Would embryo research involving nuclear replacement technology raise any new issues in respect of what may ethically be done within the 14 day period?
The suggestion that nuclear replacement may lead to creation of in-vitro stem cells is speculative and not based on evidence. It is becoming apparent that the key genes involved in the control of development are conserved across the species, and animal work is likely to yield valuable data applicable to humans. Furthermore as our understanding of these genes advances, it may well be that differentiated cells could be induced to de-differentiate and then form primitive stem cells with subsequent development into different directions without the need for cloning. There is no justification for arguing that the basic research needs to be done on human embryos
7.6 Would any of the potential applications of nuclear replacement, some of which are exemplified above, that would not result in cloned fetuses or babies raise any new ethical concerns?
As has been argued above, future advances in molecular science may allow scientists to create stem cells from differentiated cells. Nuclear transfer into an ovum/early embryo would create a new individual, distinct and separate from the donor (in the same way that identical twins are regarded as distinct and separate individuals). The arguments relating to the status of the human embryo are therefore crucial to this discussion.
8.2 Therefore what is meant by the assertion that individuals have the right to their own genetic identity? What does this mean for identical twins?
See answer to Q3 in section 9 below.
8.3 What implications do these considerations have for the ethics of human reproductive cloning?
Human development is in large part dependent on the upbringing of the child. This is critically dependent on that child receiving unconditional love. It is not difficult to find examples of how children can be psychologically damaged when this is not the case. The creation of a cloned child, as a replacement for a dead child, or as a source of compatible organs for transplantation, or merely to cheat death and continue an individual's genetic identity would undermine that fundamental characteristic of human parent / child relationship. It is difficult to envisage what damage cloning would cause not only to that individual but to society as a whole.
8.5 Would the use of nuclear replacement techniques be beyond the limit of what is ethically acceptable to resolve a couple's infertility problem?
Yes. Just because something may be technically possible, it should not be regarded as necessarily desirable or beneficial. For reasons already given cloning to resolve a couple's infertility problem is well beyond ethically acceptable means. It has been stated that each year 150,000 couples approach doctors with infertility problems. This number is close to the number of abortions performed annually. Society should be looking at ways of solving the problems of "unwanted" pregnancies and infertility by changing society's view of adoption, rather than discussing cloning technology.
8.6 Any attempt to develop this technology in humans would be expensive and would require a large amount of human experimentation. Do these considerations make experimentation in humans involving the implantation of cloned embryos ethically unacceptable? How does this case differ from the experiments that first led to successful in vitro fertilisation (IVF) procedures?
If cloning is undesirable, there can be no justification for experimentation in embryos which are not destined for implantation. See also answer to Q5 in section 9 below.
8.7 Is there a distinction between different artificial technologies according to whether they have natural counterparts or not? Should society adopt a graded scale of "unnaturalness" with some variation from the natural regarded as being unacceptable?
See answer to Q 6 in section 9 below.
Answers to specific questions
1. Would research using nuclear replacement technology raise any new ethical issues in relation to what is permitted in work with embryos in the 14 day period?
Yes - As has been previously stated, we have a fundamental objection to the principle of destructive research on early embryos. Both the Warnock Commission and the HFEA have stated that the human embryo ought to have a special status. It is difficult to envisage how any special status can be preserved for the embryo, if it is to be used for basic science research. It would be regarded no differently as a laboratory experimental animal.
2 Are there any medical or scientific areas that might benefit from research involving human nuclear replacement?
Cloning work in animals has demonstrated that the nuclear environment is important in controlling nuclear function. However there is no evidence, only speculative conjecture, that research involving nuclear transfer technology in human embryos will bring benefits to mankind. There has been an explosion of information using molecular biological techniques and it is just as likely that these may produce medical advances without the need for human cloning. All research involving humans must be done whilst respecting human dignity. We are more than mere animals, and any potential benefits should be made without the use of nuclear transfer into an ovum/early embryo. Human dignity also implies that the process of procreation carries dignity which has been referred to as 'dignity of procreation'.
3. To what extent can a person be said to have a right to an individual genetic identity?
The presence of naturally generated genetically identical twins demonstrates that we cannot argue for a 'right' to an individual genetic identity, although it may be argued that individuals have a right to a genetic identity distinct from that of their parents. There are numerous studies on the psychology of twins. In all these studies it is difficult to separate to what extent environment, including prenatal existence together, and to what extent genetic similarity is responsible for the psychology of identical twins. What must be addressed is not the right of an individual to their genetic identity, but what motive would an individual have to clone another
person having their own genetic identity. The relationship could not be one of a natural parent and it is likely that any such clone would be viewed as an object of ownership by its genetic parent and equally it is difficult to envisage how such a child might view its existence in relationship to its genetic parent and others. From both aspects there will be a devaluation of human dignity with severe psychological problems for those involved very likely.
4. Would the creation of a clone of a human person be an ethically unacceptable act?
Yes. Non-sexual reproduction is not compatible with human or reproductive dignity. The controlled selection of genetic material represents a dominance that would seriously undermine human dignity with grave consequences not only for that individual, but for society as a whole.
5. Would the likely cost in terms of failures and/or malformations inevitable in developing a programme of human reproductive cloning be ethically acceptable?
Even if animal experimentation were to reduce the failure rate, the fundamental ethical objections remain - as addressed above. However, the high cost be in terms of failure and/or malformations will inevitably lead to a loss of dignity and respect which many in society give to the early embryo. The great mystery whereby we are involved in the creation of new life would be reduced. It would be viewed as a material process and society would develop a consumer attitude towards reproduction.
6. What ethical importance might be attached to the distinction between artificial processes for which there are parallels in natural processes and those for which there are not?
This form of moral reasoning is not valid. The morality, i.e. whether an action it is right or wrong, does not depend on how much the action deviates from natural processes. Much of what we do both in medicine and in daily living could be construed as unnatural, i.e. it is difficult to find a natural parallel, but is morally acceptable.
Parliament permitted destructive embryo experimentation. The HFEA move to regulate it. The number of embryos produced and the titles of some of the research conducted graphically illustrates the devaluation of human embryos that has followed. Cloning would be a further step towards extreme human exploitation.
Examination of the parliamentary debates during passage of the Human Fertilisation and Embryology Act clearly demonstrate that the will of parliament was to outlaw cloning. It appears that due to a deficient drafting of the Bill, there is a loophole in the law and it is legally possible to perform nuclear transfer into an ovum, although because it creates an embryo the HFEA would need to be involved. We submit that this loophole should be closed and that all forms of cloning of human embryos, for whatever purpose, should be prohibited.
27th March 1998
The Lord Craigmyle, President, Catholic Union of Great Britain
Mr Patrick Coyle F.R.C.S., K.C.S.G, Master, Guild of Catholic Doctors
Dr A. P. Cole F.R.C.P., D.C.H., Chairman, Joint Ethico-Medical Committee
References used in preparation of this submission
- Catechism of the Catholic Church. Para 2270. Geoffrey Chapman. 1994.
- Progress. Freedom to Choose: Research into Infertility and Congenital Handicap. Campaign for Research into Human Reproduction. 1989
- Halder G et al. Induction of ectopic eyes by targeted expression of the eyeless gene in Drosophila. Science, 1995; 267: 1788-1792.
- Tomarev SI et al. Squid Pax-6 and eye development. Proc. Natl. Acad. Sci. USA 1997; 94: 2421-2426.
- Clapp WL and Abrahamson DR. Development and Gross Anatomy of the Kidney. In Renal Pathology. Ed. Tisher CC, Brenner BM. 2nd edn. Lippincott. 1994.
- Dressler GR et al. Deregulation of Pax-2 expression in transgenic mice generates severe kidney abnormalities. Nature. 1993; 362: 65-67.
- R J Trent. Molecular Medicine, 2nd edn. Churchill Livingstone. 1997.
- Berns MW. Laser scissors and tweezers. Scientific American April 1998.