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Journal ofmedical ethics, 1987, 13, 173-178 J Med Ethics: first published as 10.1136/jme.13.4.173 on 1 December 1987. Downloaded from

Fertilisation and moral status: a scientific perspective

Karen Dawson Monash University, Australia

Author's abstract begins with a , the male , The debate about the moral status ofthe hasgained penetrating the ovum or gamete and culminates new impetus because of the advances in reproductive in the mingling of the genetic material from each to technology that have made early embryo form a single-celled . experimentation a possibility, and because of the public Historically, was believed to be possible concern that this arouses. Severalphilosophical arguments only in the uterine or fallopian tubes of the female, claiming that fertilisation is the event that accords moral but recent medical advances resulting in many births status to the embryo were initiallyformulated in the context world-wide, have demonstrated that in vitro of the debate. Were they formulated with fertilisation is also possible (3). Regardless of the sufficientprecision to accountforthe scientificfacts as we location of the process, its biological consequences are now understand them? Or do these arguments need the same: fertilisation restores the diploid three moralstatus number, enhances genetic variation, results in modification?Aspects of argumentsfor copyright. beingacquired atfertilisation are examined in relation to determination and is a necessary prerequisite for current scientific knowledge, highlighting the reasons why embryogenesis to proceed (4). such arguments, atpresent, seem toprovide an inadequate basis for the determination of moral status. Fertilisation and moral status: the arguments examined Advances in reproductive technology have made it technically possible for the early human embryo to be Arguments in support of fertilisation as the time at an experimental subject. This has enlivened debate which full moral status is acquired either rely solely http://jme.bmj.com/ concerning the moral status of the prenate (1), for on features of the fertilisation process, or on some of some consensus on this issue is essential for policy its aspects in combination with an emphasis on the formation aimed at regulating the future of such potential ofthe newly-formed entity. Those arguments research. depending on potential have been considered Within the context of the , various elsewhere (5), so the focus here is only on those landmarks in are nominated as arguments that rely on features of the fertilisation the determinant of full moral status. Developmentally process. For the purposes of discussing the relevant the earliest of these is fertilisation (2). This paper , these arguments can be considered as three on September 26, 2021 by guest. Protected examines some of the arguments for claiming that major types: the genetic argument, the discontinuity/ fertilisation is the basis for full moral status in the continuity argument and the individuality argument. context of current scientific knowledge. Have these arguments been stated with sufficient precision to cope The genetic argument with the facts as we now understand them? Do they need to be modified and if so, howtnight this be done? But before these questions can be considered some In essence, this approach pin-points fertilisation as the understanding of fertilisation itself is time at which moral status is acquired as it is then necessary. that entities that 'are genetically human beings' (6) What is fertilisation? are created. For this argument the crucial event during fertilisation is the formation of a human genotype. It Human fertilisation is a complex process requiring is claimed that only at fertilisation, and not before, about 24 hours for completion. Viewed simply, it does a new genetic member ofthe species Homo sapiens come about, and at no other point in development is Key words there any 'significant' (7) genetic change. This claim is often coupled with the basic moral principle that it Fertilisation; early human embryo; multiple births; moral is wrong to destroy innocent human beings which, if status; zygote; individual; genetics; numerical continuity. taken to include the zygote, leads to the conclusion 174 Fertilisation and moral status: a scientific perspective J Med Ethics: first published as 10.1136/jme.13.4.173 on 1 December 1987. Downloaded from that it is wrong to destroy early human life from the are needed. moment of fertilisation (8). Variation at the level of the gene is inherent in the Biologically, this view raises two major questions - genetic argument and is extremely common in nature. firstly, what constitutes the state of being genetically The simplest example of this 'natural variation' is the human and secondly, what is meant by a significant occurrence of genetic 'polymorphisms', that is the genetic change? presence in a population ofalternative forms ofa gene, Taking the first question: the genome or genetic known as alleles. This is found, for example, for the make-up of an organism may be considered at three major human blood-typing system, the ABO-blood levels - the comparatively gross level of the group, where various combinations of the alleles of chromosome, the level of the gene itself and the even this gene occur with varying incidences in different finer level ofthe molecular structure ofthe gene. Ifthe populations (16). condition of being genetically human is considered A similar degree ofvariation has also become evident chromosomally, it is either implicit or explicit (9) in at the even finer level ofgene structure since molecular this argument that one prerequisite is the presence of genetics provided an extensive array oftechniques that 46 (23 of which are contributed by the permit fragments of the genetic material, DNA, to be and 23 by the ). Presumably these isolated and their chemical composition identified. Use chromosomes are of an accepted karyotypic of these techniques, especially restriction configuration for the number of 46 is not unique to mapping (17), has demonstrated that not all (10). However, a definition of being phenotypically equivalent alleles exhibit the same genetically human based on chromosome number chemical composition in different individuals. creates problems - for what then is the status of those This variation at the genetic level either in the allele who fail to fulfil this requirement? present or its chemical composition complicates the There are numerous human conditions compatible definition of an entity as genetically a human being. with postnatal life identifiable by the presence of 45, Where should the boundaries of natural variation be 47 or more chromosomes. The most extreme example drawn? Can defining a human being solely in genetic results from dispermy: two rather than one sperm terms take account of this range of variation? This

enter the egg and participate in fertilisation. The result type of definition is likely to become increasingly copyright. may be the formation of a tripoid zygote (a zygote complex as more of the is examined, containing 69 or three sets ofchromosomes as opposed for at present the genetic content of at most 10 per to the usual 46 or two sets). Triploidy is estimated to cent of it is known (18). occur in 1-3 per cent of all human fertilisations (11) Adoption of the claim of Noonan (19) that: '...if and in vitro as many as 8-10 per cent of fertilisations you are conceived by human parents you are human' can be observed to result from the penetration of more may be seen as a possible means of circumventing the than one sperm (12). The majority of triploids are difficulties in defining a genetic human being. In the spontaneously aborted or still-born but there are some light of recent advances in (IVF) http://jme.bmj.com/ reports of live-born individuals who have lived for up this approach raises the question: If you are conceived to seven months after birth (13). by IVF-procedures, from human material, do you still More common conditions showing a variation in qualify as human? An affirmative answer here surely chromosome number and accompanied by much suggests that the origin of the material rather than any longer life-spans include Triple-X (about 1/ of its characteristics is what is important for specifying 1500 live female births), Klinefelter's Syndrome a human being. However, even this possible solution (about 1/500 live male births) and Down's Syndrome may be short-lived, for it relies on species breeding (about 1/500 live births) which are usually associated true to their kind. But consider the situation of on September 26, 2021 by guest. Protected with 47 chromosomes in the karyotype. In contrast to transgenic animals. this range of disorders, postnatal existence with only A transgenic animal is one carrying a gene from 45 chromosomes is more limited. Turner's Syndrome another species, such as a mouse with a gene from a is the only such chromosomal condition in humans in human source (20). How many human genes can be which one chromosome may be completely absent. introduced into a phenotypic mouse before it is The affected females (about 1/4500 live female births) considered as genetically non-mouse or even human? are missing an X-chromosome from the genome (14). Is it the intra-uterine existence of the entity within a The incidence of these chromosomal conditions at mouse that ensures that such a transgenic animal birth is very much lower than at fertilisation, for it is remains a mouse? Alternatively, would the estimated that more than 90 per cent of them are lost introduction of a gene from an animal into a human through very early loss and later gamete or early embryo, say for the purposes of gene spontaneous abortion (15). The possibility of viable therapy, invalidate the humanity of any offspring individuals, recognised as human, but with 45, 47 or produced subsequently? What if many animal genes even more chromosomes, raises a question about the were to be introduced? The advent of transgenic adequacy of using the criterion of chromosome animals blurs the boundaries of the intended meaning number rigidly, or at least solely, to define a genetic of species as 'a discrete breeding unit' and emphasises human being. Some further defining characteristics the need for criteria other than those of the genetic Karen Dawson 175 J Med Ethics: first published as 10.1136/jme.13.4.173 on 1 December 1987. Downloaded from content and its origin, and the site offertilisation being In summary, the questions arising from the genetic applied in attributing human, and hence moral, status argument stem mostly from viewing genetic make-up to the prenate. The question 'What is a genetic human as something static and constant from the moment of being?' does not have a simple answer. From available fertilisation. In reality, differentiation is a dynamic scientific data it is presently essentially indefinable. process and the environment contributes to subtle The second part ofthe genetic argument emphasises continuous changes throughout a life-time. Some fertilisation as the time of acquiring moral status acknowledgement of this needs to be made in because no further 'significant' genetic changes occur arguments emphasising genotype formation as an beyond this time. The meaning of 'significant' is not important aspect offertilisation determining the moral clearly specified in the literature but genetic changes status of the prenate. can and do occur after fertilisation - are they significant? The discontinuity-continuity argument Extreme genetic changes occur during the Proponents of this argument (25) view events post- differentiation of erythrocytes (red blood cells) and fertilisation as comprising a continuum of cells of the lens of the eye. When finally differentiated developmental changes, such that it is impossible to these cells contain no nuclear genetic material at all, isolate any one stage at which to attribute the and conversely, there is a low incidence of cells in the attainment of moral status. In contrast to this liver that double their genetic content during continuity, fertilisation is seen as a radical differentiation (21). Thus, the postnatal human may discontinuity or 'transformation' (26) in development. be considered as composed of various families of cells It is then argued that the union of the two to some of which have been irreversibly genetically form the single zygote at fertilisation is the only changed during development subsequent to discrete stage at which it can be claimed that a human fertilisation. entity begins to exist. Further genetic changes may also occur throughout Emphasis for this interpretation of continuity, the pre- and postnatal phases as a result of randomly known as numerical continuity, is on the change from occurring heritable changes in the genetic material two gametes to one zygote that is continuous known as spontaneous . The significance of throughout all following development (27). As these random changes depends on their location in the previously mentioned, in the formation of triploidcopyright. DNA (22), the stage of development at which they individuals more than two entities may sometimes occur (23) and their nature (24). Mutation is estimated participate in fertilisation. A further deviation of this to occur spontaneously at a rate of one per million occurs with - development of the egg base pairs per round of DNA replication although this without fertilisation by a sperm. At present this holds rate differs for specific genes. only little relevance to human , as so far It may be argued that the above genetic changes are as is known no births have resulted from this process, simply 'variations on a theme' for they are qualitative although the initial stages of parthenogenetic http://jme.bmj.com/ changes following fertilisation, but there are also development have been observed rarely in vitro (28). changes that can occur at this time that alter the genetic Here, there is no numerical discontinuity unless, as make-up of the prenate. These changes result from suggested by Quinn (26) the environmental agent chromosomal non-disjunction, that is failure of the inducing parthenogenetic development is treated as a chromosomes to separate properly during division. pre-fertilisation entity that is incorporated into the The result of non-disjunction during the first division 'zygote' at the onset ofdevelopment. But this approach of the zygote is a mosaic organism, that is an organism implies that environment is irrelevant in the events of composed of two different cell lines, both of which normal fertilisation, which leads to an arbitrary and on September 26, 2021 by guest. Protected differ genetically from the zygote from which they unsatisfactory distinction not reflecting the actual arose. If non-disjunction occurs at a later stage of course of events. development it will theoretically result in the Dispermy and parthenogenesis represent different formation of an individual with three different cell deviations in the number of entities participating in lines, two of which differ genetically from the zygote. the process leading to the initiation of development The chromosomal conditions mentioned previously which may be able to be incorporated into the notion (Triple-X, Klinefelter's Syndrome, Down's Syndrome of numerical continuity. But even if these fluctuations and Turner's Syndrome) may exist in either a mosaic are accepted, the notion also specifies that the result form, resulting from chromosomal non-disjunction of fertilisation is the formation of a single entity - the following fertilisation, or a pure form from a non- zygote. Is this necessarily the case? disjunction event during in either Consider the outcome of dispermy. If dispermy parent prior to fertilisation. The genetic changes here occurs it may predispose to a tumorous condition involve the gain or loss of one whole chromosome after known as a hydatidiform mole (29). In such an event fertilisation which may have gross effects on the may not occur. The medical phenotype, genotype and survival of the developing concern with the formation of moles is that they may prenate and should consequently be considered as become malignant and life-threatening for the , significant. but here they serve as an example of how fertilisation 176 Fertilisation and moral status: a scientific perspective J Med Ethics: first published as 10.1136/jme.13.4.173 on 1 December 1987. Downloaded from may not necessarily lead to the formation ofa zygote. is not necessarily that formed at fertilisation; many Now, consider again the outcome of fertilisation. changes can occur subsequently. Similarly, the The one zygote present in the context ofthis argument, individual created at fertilisation may not remain the is said to mark the beginning of a human entity that same throughout life. The simplest demonstration of is numerically continuous throughout all subsequent this is identical twinning which is possible for about development. Is this the case? What if the zygote 12 days after fertilisation. In this process the original should split soon after its formation? Can the notion zygote ceases to exist. Conversely, during this time it of numerical continuity cope with the possibility? is also possible for two derived from the Identical arise from a single zygote that splits. independent fertilisation of two to fuse forming The mechanism involved is not important here, the a chimera - the one individual resulting from two point is that with this type of twinning there is only fertilisation events. In neither of these cases is the temporary numerical discontinuity, ie 1 egg + 1 sperm developing individual the one that was formed at -> 1 zygote -- 2 individuals. In trying to make fertilisation. numerical continuity allow for twinning Quinn (26) Other authors appeal to the potential ofthe zygote: concluded that identical twinning, if environmentally determined, was a developmental abnormality. Such 'We know that a new human individual organism with an approach is analogous to that used when attempting the internal potential to develop into an to reconcile parthenogenesis with numerical continuity adult . .. comes into existence as a result of the for the net result is to discount any possible role process of fertilisation . . .' (34). environment may play in singleton zygote development. At present, the relative contribution of The intention is not to discuss potential here. However, genotype and environment to identical twinning is consideration of this argument does illustrate one unclear. Identical twins occur in about one of every feature inherent in many arguments in support of 270 coming to term (4), and it has been fertilisation: a reliance on the viability of the zygote. observed that a proportion of identical twins are lost It is worthwhile noting that for up to 78 per cent of either through spontaneous abortion (30) or the loss human fertilisations the end-point is loss (35) rather of one fetus which results in singleton development than to the next developmental stage progression copyright. and birth (31). Further studies of twins during which can be seen as weakening the applicability of gestation may show identical twins to be more frequent any argument depending on viability. than currently believed. The techniques for such studies to proceed are now becoming available and if a genetic component to identical formation could Summary be demonstrated their status, as seen by Quinn, as a Scientific facts alone cannot provide the answer to the 'developmental abnormality' would need reappraisal. debate on the moral status of the prenate. The final

The concept of numerical continuity is too narrow outcome is an ethical decision. However, information http://jme.bmj.com/ as initially defined to allow for any variations during about the relevant biological events can create a firmer or subsequent to fertilisation. To be ranked as a valid basis for discussion of such a clearly interdisciplinary determinant of moral status some refinement of the issue. Assessment of the arguments claiming that concept, incorporating current scientific knowledge is fertilisation is the time at which full moral status is needed. acquired is now extremely relevant as policy-formation and legislation for the regulation of reproductive The individuality argument technology and pre-embryo research is considered in Proponents of this argument also claim that many countries. on September 26, 2021 by guest. Protected fundamental moral principles against killing are The arguments discussed basically rely on the applicable from fertilisation, as this event marks the simple equation that: 1 egg + 1 sperm = 1 zygote = time when an individual human being begins to exist. 1 child. The meaning of individual differs among authors. An This process is seen as marking the beginning of a emphasis on genetics is sometimes integral to the human life, and thus determining that fertilisation is notion: the time at which moral status is accorded. The point of whether or not fertilisation is the beginning of '. . . the unique genetic package of an individual is human life will not be debated here. Leaving this laid down at fertilisation' (32) aside, it seems that overall the different arguments for fertilisation determining moral status of the prenate while others highlight continuity: oversimplify actual biological events. Among the problems encountered are an '. . . it is the same individual right through from that overemphasis on the role of genetics in directing the moment (fertilisation) on to the end' (33). course of events after fertilisation, and a dependence on the fidelity of the new genotype formed at The problems with these views have largely been fertilisation throughout all subsequent development. discussed. The genotype of an individual later in life Also sometimes inherent in this argument is the Karen Dawson 177 J Med Ethics: first published as 10.1136/jme.13.4.173 on 1 December 1987. Downloaded from assumption that birth will follow from fertilisation. stages of development thus reserving the specific terms Several instances where biology diverges from these 'pre-embryo', 'embryo' and 'fetus' for proper usage claims have been discussed and many more equivalent when applicable. examples could be cited. (2) The term 'fertilisation' is used throughout in preference When assessing the claim that fertilisation to 'conception'. As has been noted 'conception' has become an ambiguous term that is increasingly establishes full moral status, several facts should be associated with implantation, rather than the specific kept in mind: union of the sperm and ovum that is denoted by fertilisation. For example see Federal Republic of 1) Given suitable environmental conditions, Germany, Judgement at Karlsruhe. In: Ethical aspects development may sometimes commence without ofabortion: some European views. IPPF Report. Appendix fertilisation occurring (parthenogenesis). 2. 1975. 2) The genotype of any individual may not be that (3) The number of births from IVF is increasing daily. The formed at fertilisation. highest estimate thus far is in excess of 2000, according 3) Development and differentiation after fertilisation to Dr Howard Jones at the 4th World Conference on In vitro fertilisation held in Melbourne, Australia in result in changes to the genetic complement of the November, 1985. prenate. (4) Moore K. The developing human (3rd ed). Philadelphia: 4) Environment is a potent force in the course of W B Saunders and Co, 1982. development both prenatally and postnatally. (5) Singer P, Dawson K. IVF technology and the argument 5) The formation of a single zygote at fertilisation may from potential (in preparation). be the forerunner of the development of multiple (6) Werner R. Abortion: the moral status of the unborn. individuals that may or may not be genetically Social theory and practice, 1974; 3:201-222. identical. (7) See reference (6): 202. 6) Successful completion of fertilisation in no way (8) R Werner is the chief proponent of this argument but similar arguments are also provided, by for example, assures development through to birth or even the R Wertheimer: Understanding the abortion argument. commencement of embryo development. Philosophy and Public Affairs 1971; 1: 67-95; Brody B. Until arguments claiming fertilisation as the On the humanity of the fetus. In: Beauchamp T R,

determinant of moral status take into account such Walters L, eds. Contemporary issues in bioethics.copyright. facts by being modified to incorporate them, they California: Wadsworth, 1978: 229-240, and Santamaria J. provide an inadequate basis for policy-formation or In vitro fertilisation and embryo transfer. In: Brumby M N legislation regulating reproductive technology as they ed. Proceedings of the conference: In vitro fertilisation: hold little relevance to Presently, problems and possibilities. Clayton, Victoria: Centre for only actual biology, Human Bioethics, Monash University, 1982: 48-53. this situation serves to raise the questions of whether (9) For example see Noonan J T. An almost absolute value the whole issue of moral status needs reappraisal and in history. In: Noonan J T, ed. The morality ofabortion. whether any legislation, either actual or proposed, in Harvard: Harvard University Press, 1970: 1-59. this area is premature. (10) Hsu TC and Benirschke K. An atlas of mammalian http://jme.bmj.com/ chromosomes(Vol 10). New York: Springer-Verlag, 1977. Acknowledgements (11) Jacobs P A, Angell R R, Buchanan I M, Hassold T J, Matsuyama A M and Mannel B. The origin of human This work was supported by an NH and MRC Special triploids. Annals of human genetics 1975; 42: 49-57. Initiative Grant to Professor J Swan, Professor L (12) Plachot M, Mantelbaum J, Junca A, Salns-Baroux J Waller, Dr M Brumby and Dr H Kuhse who provided and Cohen J. Impairment of human embryo helpful discussion of this manuscript. Special thanks development after abnormal in vitro fertilisation. In: to Ms L Fleming who provided some of the Seppiala M, Edwards R G, eds. In vitro fertilisation and on September 26, 2021 by guest. Protected philosophical material and Professor P Singer for his embryo transfer. Annals of the New York Academy of Sciences 1985; 442: 336-341. helpful criticism and comments. (13) Schinzel A. Catalogue of unbalanced chromosome aberrations in . New York: Walter de Gruyter, 1984. Karen Dawson gained her Phd in Genetics, from La (14) Wilson M G. Cytogenetics update for pediatricians. Trobe University, Victoria, in 1981. Following this she Current problems in pediatrics 1985; 15: 1-47. spent four years as a Senior Tutor in the Genetics (15) Boue A, Boue J, Bropp A. Cytogenetics of pregnancy Department, Monash University, teaching Genetics to wastage. Advances in human genetics 1985; 14: 1-59. science and medical undergraduates. In 1985 she took up (16) See Bodmer W F, Cavalli-Sforza L L. Genetics, evolution her current as Research in the and man. San Francisco: W H Freeman, 1976, for-a full position Scientific Officer discussion of racial and population differences. Centre for Human Bioethics and is currently involved in (17) For a general discussion of restriction mapping see a research project concerned with ethical issues arising Norvick R P. Plasmids. Scientific American 1980; from reproductive technology. 243:76-91. (18) McKusick V A. The human gene map. Clinical genetics 1984; 27:207-239. (19) See reference (9): 51. (20) Palminter R D, Brinster R L. Transgenic mice. Cell References and notes 1985; 41: 343-345. (1) 'Prenate', in this paper, is used as a term for all prenatal (21) Davidson E H. Gene activity in early development. New 178 Fertilisation and moral status: a scientific perspective J Med Ethics: first published as 10.1136/jme.13.4.173 on 1 December 1987. Downloaded from

York: Academic Press, 1977. (25) See for example Grisez G C. Abortion: the myths, the (22) Much of the DNA in humans is apparently never used realities and the arguments. New York: Corpus Books, for the production of proteins (the usual gene product) 1970. Iglesias T. In vitro fertilisation: the major issues. and so spontaneous in this genetic material Journal ofmedical ethics 1984: 1: 32-37 and also reference will have no effect on the phenotype of the organism. (8). Also, the genetic material that is read for protein (26) Quinn W. Abortion: identity and loss. Philosophy and production is read as a triplet code and the code is such public affairs 1984; 13: 24-54. that any mutation in the third base of a triplet will not (27) See references (6) and (26) always affect the protein being produced. In contrast a (28) Edwards R G, Trounson A. Discussion on the growth mutation in the first or second positions of a triplet may of human in vitro. In: Edwards R G, Purdy J have a range of effects on the protein being produced, M, eds. Human conception in vitro. London: Academic and may even stop its production. Press 1982: 219-233. (29) Snell R S. Clinical for medical students (2nd (23) Some genes are only functional at certain stages of ed). London: Little Brown and Co, 1972. development and once that stage is past remain switched (30) Morison J E. Foetal and neonatal pathology (2nd ed). off. One instance of this is in the production of human London: Butterworths, 1968. haemoglobin where different clusters ofgenes are active (31) Walters W A Renou P M. In: during the embryo phase, fetal phase, and child and W, Pregnancy care. Wood adult phase. Mutations during adult life in the embryo C, Trounson A, eds. Clinical in vitro fertilisation. New phase gene complex would have no effect on the adult, York: Springer-Verlag, 1984: 147-156. as (32) See reference (8) Santamaria J: 49. these genes are then inactive. (33) Daly T. Discussion in Conference Proceedings. In vitro (24) Mutations are of various types - deletion, insertion, fertilisation: problems and possibilities. Clayton, Victoria: base substitution, inversion and duplication - which may Centre for Human Bioethics, Monash University. 1982: involve only small regions of the genetic material. There 62. are also relatively large-scale structural changes such as (34) See reference (25) Iglesias T: 36. transposition, inversion, translocation and duplication (35) Roberts C J, Lowe C R. Where have all the conceptions which have major effects on the function ofthe genome. gone? Lancet 1975; 1:498-499. copyright.

News and notes Institute of Medical Ethics London Medical Group http://jme.bmj.com/ 25th annual conference Children at risk

The conference will examine moral dilemmas in the treatment and abuse of children by parents and doctors. on September 26, 2021 by guest. Protected Date and place: Friday and Saturday 12 and 13 February 1988 at the Royal College of Surgeons of England, Lincoln's Inn Fields. Conference fee: £75 (IME members £60, students £10). Details and application form (SAE PLEASE) from the Conference Secretary, London Medical Group, PO Box 20, Tavistock House North, Tavistock Square, London WC1H 9LG (tel 01-387 8132).