Biocthicr ISSN 0269-9702

Volume 9 Numbcr I I995

BEFORE I WAS AN EMBRYO, I WAS A PRE-EMBRYO: OR WAS I?

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D. G A R E T H JONES and BARBARA TELFER

ABSTRACT Issues surrounding human embryos are poignant and profound. Should research be conducted on them? Should they be discarded? Should they be donated to infertile couples? The Warnock Report was a landmark in providing guidelines limiting experimentation on human embryos to thefirst 14 days after fertilization, at which time implantation o f the embryo is complete and the primitive streak has appeared. However, these embryological features were not considered sufficiently distinctive to bestow upon this 14-day period a separate classijication. This situation changed when, in 1986, Anne McLaren suggested the use of the terms )re-embryo or conceptus to designate the entire product of the fertilized egg up to the end of the implantation stage and the term embryo for that small part .f the pre-embryo or conceptus, first distinguishable at the primitive streak stage, that later develops into the foetus. In this Paper we look critically at the term pre-embryo , and we shall present the case for an alternative set of terms, namely, embryo-placenta and embryofetus. We consider this latter to be biologically-based terminology, that does not have any connotation o f restricted moral value as the term pre-embryo does f o r some.

BIOLOGICAL CHARACTERISTICS OF EARLY DEVELOPMENT The fertilized egg is a single cell, the zygote, and is totipotential,
I Department of Health and Society Security, Report oJthe Committee oflnquiry Into Human Fertilisation and Embryology. Chairman, Dame Mary Warnock, Her Majestys Stationery Office, London, 1984, pp. 58-69. Ibid. McLaren, A . Prelude to embryogenesis, In CIBA Foundation, Human Embryo Research: Yes or No, London: Tavistock Publications, 1986a, pp. 5-23.

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giving rise eventually to the fetus and placenta. This single cell undergoes cleavage, during which it divides with little intervening growth to produce two, then four, then eight smaller, identical cells. These are the blustomeres, which at the 8-cell stage are only loosely associated with one another. At this stage individual blastomeres have the potential to develop into complete adults if separated from the remaining blastomeres. There is also evidence that if two 8-cell stages of different parentage are fused into a larger 16-cell aggregate, a single adult is p r o d ~ c e d .This ~ suggests that these blastomeres retain the full developmental potential of the zygote, giving them the capability of producing a complete adult. However, by the 32-cell stage, they have become increasingly adherent and closely packed, and have probably lost this equal developmental potential. By this stage the mass of blastomeres has the characteristics of a multicellular entity, rather than of a loose packet of identical cells. As the number of cells continues to increase, those on the outside of the group become firmly attached to one another, with the internal ones remaining u n ~ o n n e c t e d . These ~ outer cells begin to differentiate and form a surface layer, the trophectoderm, which becomes the trophoblast when implantation occurs. Internally, fluid accumulates to form a cavity, the blastocoele, the entire structure being referred to as a blastocyst (Figure la). The blastocoele increases in size with further cell division, the result being that the relatively unaltered inner cells are pushed to one side. The trophectodermal cells on the outside are the earliest to differentiate, giving rise to extraembryonic trophoblast tissue that establishes the uteroplacental circulation. Even by the midblastocyst stage the differentiation of these cells is irreversible.6 By contrast, the inner cells constituting the inner cell mass are still undifferentiated and represent the residue of totipotential cells.7 Of these inner cells, some are destined to form the fetus (what we shall refer to as embryo-fetus), and the remainder represent forerunners

Ethics Committee of the American Fertility Society., Ethical considerations of the ncw reproductive technologies, Fertility and Sterility, Supplement 1 , pp. 26s-28s. 1986. Austin, C . R . Human Embryos, Oxford: Oxford University Press, 1989, pp. 10- 14. Fleming, T . P . , Warren, P.D., Chisholm, ,J.C. and .Johnson, M.H. Trophectodermal processes regulate the expression of totipotency within the inner cell mass of the mouse expanding blastocyst, Journal OfEmbryology and Experimental MorpholoB 84, pp. 63 -90, 1984. Williams, P.L., Warwick, R . , Dyson, M. and Bannister, L.H., Eds. Grays Anatomy, 37th edition. London: Churchill Livingstone, 1989, pp. 124- 131.

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Figure 1 Diagrams to illustrate the early deuelopmental stages of the human embryo (modified from FittGeraldsB and McLaren5).
uterus

ulerus

sparer tilled with mlernal blood chorion omniolic covily

epiblast

p=p+
yolk sac cavity extra- enbryonic coelom
prochordal pblc bilammar embryonic disc hypoblasl

w
h

I4 days
primtlive Intraaabryontr

prochordal plale

nOloChOrdGl process,

prlmltlre slieak

endnderm

5B
59

FitzGerald, op. cit., p. 35. McLaren, 1987, op. c i t . , p. 42.

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of extraembryonic, auxiliary tissues including amniotic ectoderm, extraembryonic endoderm of the yolk sac, and extraembryonic mesoderm of the amnion, chorion and yolk sac8 (what we shall designate embryo-placenta). There is a discrepancy in number between cells of the inner cell mass and trophoblast. In a landmark paper,g only five out of 60 cells belonged to the inner cell mass in one case, and only eight out of 107 cells in another. In addition, the inner cell mass itself is heterogeneous. For instance; in a chimaeric mouse blastocyst of 64 cells, only three of the 10- 15 cells comprising the inner cell mass were considered to serve as the source of the cells destined to form the embryo-fetus.lo These observations apply to the blastocyst 4- 5 days after fertilization, as it travels through the fallopian tube into the uterus. The differentiation of the trophoblast cells has as its goal implantation of the blastocyst into the uterine wall (beginning about six days following fertilization), a process involving invasion of maternal tissue and the opening-up of blood-filled spaces to facilitate metabolic exchange (Figure lb). The latter is accomplished by multiplication of the outside cells to form the sponge-like chorion, the cavities of which become filled with maternal blood. These events take place during the early part of the second postfertilization week, at about the same time as the inner cell mass undergoes reorganization into two layers, epiblast (giving rise to embryonic ectoderm, mesoderm, and endoderm) and hypoblast (giving rise to extraembryonic endoderm) which together constitute the bilaminar embryonic disc, as in Figure lc. By 14 days after fertilization, the embryo has a mass about ten times that of the fertilized egg, and has two fluid-filled cavities, the amniotic sac and the yolk sac, with the embryonic disc between them (Figure Id). A localized increase of the hypoblast of the embryonic disc designates the future head end of the embryo, and is referred to as the prochordal plate. This bestows upon the embryo an

Luckett, W.P. Origin and differentiation of the yolk sac and extraembryonic mesoderm in presomite human and rhesus monkey embryos, American Journal o j Anatomy 152,pp. 59-98, 1978. Hertig, A . T . , Rock, J., Adams, E.C. and Mulligan, W.J. On the preimplantation stages of the human ovum: a description of four normal and four abnormal specimens ranging from the second to the fifth day of development, Contributions .f the Carnegie Institute Washington 35, pp. 199-220, 1954. l o Markert, C.L. and Petters, R.M. Manufactured hexaparental mice show that adults are derived from three embryonic cells, Science 202, p. 58, 1978.
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orientation, or axis, with discernible ends and sides." At this age, the early embryo consists of the embryonic disc (the embryo proper according to some terminology), and the fetal membranes, including the amnion, yolk sac, and chorion. The primary yolk sac is present by 10-11 days, but is soon reduced in size as the secondary yolk sac develops by 12 - 13 days. l 2 At days 15- 16 most cells are committed to an extra-embryonic fate; the exceptions are a group of a few thousand cells in the ectodermal (epiblast) layer of the embryonic disc.13 These cells migrate to the midline and form the primitive streak (Figure le), the significance of which is often said to be that, from this point (1 5 - 18 days) onwards, the embryonic disc is committed to forming a single being; twinning is no longer possible, unless two primitive streaks form.'4,'5 The primitive streak elongates by addition of cells at one end, while at the other end (the cranial or head end) it thickens to form a primitive node. With elongation of the embryonic disc, the notochordal process forms, projecting forwards from the node between the ectoderm and endoderm. At the same time, a narrow primitive groove develops in the primitive streak and deepens to form the primitive pit. Following this, ectodermal cells migrate to the primitive streak and move into the primitive groove and pit, while other cells within the embryonic disc become organized into a layer that migrates between the ectoderm and endoderm; this is the (intra)embryonic mesoderm. The result is that the embryonic disc now has three layers - the trilaminar disc (Figure le). The mesoderm from the primitive streak spreads rapidly between ectoderm and endoderm, forming around the primitive node and notochordal process. With further growth of the embryo, the primitive streak is displaced and becomes relatively smaller. This is because once the intraembryonic mesoderm is formed, its work is done. This continues throughout the third and fourth weeks of development. l 6 The notochordal process becomes transformed into the notochordal plate, and finally the notochord (first element in the skeletal system) early in the third week. The other structure of relevance in the present context is the neural plate, from which

I' FitzGerald, M.J.T. Human Embryology: A Regional Approach, Hagerstown, Maryland: Harper and Row, 1978, p. 34. I' Luckett, op. cit., pp. 59-98. l 3 McLaren, op. c i t . , pp. 1 1 , 12. " Ethics Committee of the American Fertility Society, op. cit., p. S27. I 5 McLaren, op. c i t . , pp. 1 1 , 12. l6 FitzGerald, op. c i t . , pp. 33-37.

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BEFORE I WAS AN EMBRYO 37 arises the first rudiment of the nervous system early in the third week. The neural plate is essentially a thickening of the ectoderm where it overlies the notochordal process, and includes the primitive node and part of the primitive streak. The neural plate grows differentially to become the neural fold, and finally neural tube. Once this has closed at the beginning of the fourth week of development, it begins to differentiate into the various regions of the central nervous system (the first sign of organ formation). As a result, by 21 - 22 days gestation, the features of the embryo include a notochord, somites (the first segmented structures of the body), neural tube with the beginnings of a brain and spinal cord, and remains of the primitive streak. This description has raised a crucial consideration, that of terminology. What is meant by the term embryo? Austin has expressed the conundrum in these terms: The whole egg certainly becomes the embryo, and the whole fetus becomes the child, but the whole embryo does not become the fetus - only a smaLL)action of the embryo is thus involved, the rest of it continuing as the placenta and other auxiliary structures. He argues that the embryo can be thought of as continuing as the placenta, with the fetus arising as an offshoot of the embryo, the offshoot coming from the embryonic disc. Within this framework, the embryo can be regarded as an organ (like the ovary) rather than as an entity destined to become a person. Useful as this analysis is, problems remain. Austin favours confining the term embryo to that which will become the fetus, so that use of the same term to denote all products of conception for the first few weeks is confusing. It is because of such considerations that some introduce another term, namely, pre-embryo (or proembryo) to describe the products of conception up to the appearance of the primitive streak at 14 or 15 days after fertilization, although some limit the time period to the first 6 or 7 days following fertilization. Either way, pre-embryo refers to the major developmental events concerned with formation of extraembryonic structures, leaving the term embryo to cover the developing structure from these times onwards for the next few weeks. However, as Austinlg points out, use of the term pre-embryo indicates that an embryo originates as a very small part of a pre-embryo, and co-exists with the pre-embryo as the latter differentiates into the placenta, prior to the embryo becoming a fetus.

Austin, op. d., pp. 17, 18.

l9

Ibid. Ibid.

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PRE-EMBRYO TERMINOLOGY The term pre-embryohas been readily accepted particularly by the scientific community20,21,22 it also appears in news items23 and in general texts dealing with e m b r y ~ l o g y ,although ~~ there are exception^.^^ There are commentators who question the use of the term pre-embryo.26 It is noticeable that the transition between the pre-embryonic and embryonic stages varies. It may be put at 6 - 7 days,27 10 days,28most frequently at 14- 16 day^,^',^' or even at 21 days.31 This latter timing emphasizes the somite stage rather than the primitive streak, and by inference the closure of the early neural tube and folding of the embryo. These different emphases highlight, respectively, the bilaminar embryonic disc, the primitive streak, and somites. Some writers emphasize that use of the term is not intended to prejudge any moral i s s ~ e s . ~ ~ , ~ ~ Recent usage of the term pre-embryo stems from certain characteristics of the early embryo, including the observations that the entire early embryo is not involved in forming a fetus, and is not

O Dawson, K. Introduction: an outline of scientific aspects of human embryo research. In P. Singer et a l . , Eds. Embryo Experimentation, Cambridge: Cambridge University Press, 1990, pp. 3- 13. Trounson, A. Why do research on human pre-embryos? In P. Singer el a l . , Eds. Embsyo Experimentation, Cambridge: Cambridge University Press, 1990, pp. 14-25. Braude, P.R., Bolton, V.N. and Johnson, M . H . The use of human preembryos for infertility research. In CIBA Foundation, Human Embsyo Research: Yes or N o , London: Tavistock Publications, 1986, pp. 63-82. 23 Clarke, M. Another bill bites the dust, Nature 319, p. 349, 1986. Moore, K.L. The Deueloping Human, Philadelphia: W.B. Saunders, 1993 5th edition, pp. 38-64. 25 Larsen, W.J. Human Embryology, New York: Churchill Livingstone, 1993, pp. 33-51. 26 Davies, D. Embryo research, Nafure 320, p. 208, 1986. 27 US Congress, Office of Technology Assessment. Infertility: Medical and Social Choices, OTA-BA-358. Washington, DC: US Government Printing Offce, May 1988, p. 41. Glover, J. Fertility and the Family, London: Fourth Estate, 1989, p. 94. Ethics Committee of the American Fertility Society, op. Lit., pp. 56S, 57s. 30 McLaren, A. Can we diagnose genetic disease in pre-embryos? New Sczentzxt 116, pp. 42-47, 1987. 3 Williams, P.L. and Wendell-Smith, C.P. Basic Human Embryology, London: Pitman Medical, 1969, pp. 50-53. *Ethics Committee of the American Fertility Society, op. czt., pp. 29s-31s. 33 Glover, op. c z f . , p. 99.

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a coherent entity,34 plus the additional observation that its first cellular differentiation relates to physiological interaction with the mother rather than to establishment of the embryo itself.3511 is also contended that the term helps clarify the major watershed character of the developmental change involved in the initiation of an embryonic axis. M~Laren writes: ~ ~ About sixteen days after fertilization, all the cells derived from the fertilized egg are finally committed to being either part of the individual embryo or outside it. Alternatively it is stated that: . . . the embryo does not exist for the first two weeks after fertilization. It is formed from a tiny subset of the mass of cells generated during that period by the fertilized egg . 3 7 And again: If one tries to trace back further than that [the primitive streak] there is no longer a coherent entity. Instead there is a larger collection of cells, some of which are going to take part in the subsequent development of the embryo and some of which arent . . . To me the point at which I began as a total whole individual human being was at the primitive streak, the formation of the embryo . . . . 3 8 In similar vein, Clifford G r o b ~ t e i n has ~ ~written: Preembryos are best regarded scientifically as a transitional stage between two major developmental landmarks - fertilization that establishes genetic individuality and the initial organization of a developmentally unitary individual. Norman Fordw proposes that the term embryo be applied from the primitive streak onwards for a different reason: for him, the human individual begins at this stage. He would like to see the term proembryo rather than preembryo used prior to this, to indicate that the developing embryonic cells have not yet become an embryonic human individual but are definitely developing towards that goal.

3*
35

36 37

39

McLaren, 1986a, op. cit., p. 22. Ethics Committee of the American Fertility Society, op. cit., p. 27s. McLaren, 1986a, op. cit., pp. 1 1 , 12. McLaren, A. Embryo research, Nature 320, p. 570, 1986b. McLaren, 1986a, op. tit., p. 22. Grobstein, C . Science and the Unborn, New York: Basic Books, 1988a, pp. 81, Ford, N . When Did Z Begin? Cambridge: Cambridge University Press, 1988, p.

82.

182.
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ARGUMENTS SUPPORTING THE PRE-EMBRYO CONCEPT

The argument that the early embryo prior to about two weeks gestation is conceptually different from the 3- or 4-week embryo rests on various dominant characteristics: much of it gives rise to the placenta and supporting tissue, it is neither a coherent nor a spatially defined entity, and its early developmental potential is unrestricted. While these features can be treated independently, there is considerable interplay between them. As has already been discussed, the early embryo is not committed to developing into an individual embryo. Such commitment, it is argued, can first be distinguished at the primitive streak stage, from which point onwards a spatially defined entity capable of developing into a fetus and infant begins to exist. The thrust of this trophoblastic argument stems from the nature of that into which it develops, namely, the placenta. Although both trophoblast and placenta are alive and are necessary for sustenance of the human embryo, they have no nerves, are insentient, have always been regarded as extraembryonic, and in most societies the placenta is discarded at birth. It is the loss of a still-born fetus that is grieved, not the loss of the accompanying placenta. Additionally, differentiation of the trophoblast may result in the production of hydatiform moles or semimalignant troph~blasts,~ neither of which is viewed as worthy of human status. The trophoblast is also developmentally non-specific, as demonstrated by the success of intra- and interspecies grafting of t r o p h o b l a s t ~ . ~ ~ A complementary argument in favour of the pre-embryo concept is the appearance of the primitive streak at 14- 15 days after fertilization. It is the time at which (i) the precursor cells for the basic body tissues are laid down in the correct relative position; (ii) the embryonic disc has a front and back, left and right, and top and bottom; (iii) twinning of the conceptus can occur, the number of embryos being determined by the number of primitive streaks that develop.43By this point in development, all cells derived from the zygote are committed to an extraembryonic or embryonic location.
4 Grobstein, C . Biological characteristics of the preembryo, Annals o f the New York Academy o f Sciences 541: 346-348, 1988b. 42 Gardner, R.L. Manipulation of development. In C.R. Austin and R.V. Short, Eds. Embryonic and Fetal Development, Reproduction in Mammals, Book 2, Cambridge: Cambridge University Press, 1972, pp. 110- 133. 43 Braude, P.R. and Johnson, M . H . The embryo in contemporary medical science. In G.R. Dunstan, Ed. The Human Embryo: Aristotle and the Arabic and European Traditions, Exeter: University of Exeter Press, 1990, pp. 208-221.

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Further, cells of the inner cell mass are committed to forming specific regions or parts of the developing embryo. Ford44writes: Potency for differentiation, development and growth can only be actualized through this regional specification. Without this, I fail to see how an actual individual human being could be present. This would be a condition required to pass from the presence of a potential human individual to an actual human individual with arrived ~~ at a similar conclusion when she potential. M ~ L a r e n wrote: The primitive streak stage is a vitally important landmark in development because it marks the onset of individuality . . . once the primitive streak has formed, we can for the first time recognize and delineate the boundaries of a discrete coherent entity, an individual . . .. These arguments emphasize singleness, individuality, coherence, differentiation, and positional specificity, all of which are useful pointers along the developmental path. However, do they negate the biological and moral significance of those cells that from 4- 5 days gestation are destined to form the adult? Between gestational days 4 and 14, these cells may not be readily distinguishable from those that are destined to be extra-embryonic, neither can they be isolated from them, but are these negative characteristics of either biological or moral importance?

QUERIES REGARDING THE PRE-EMBRYO CONCEPT

S;Sn$icance o f Extra-Embryonic tissue^
That the bulk of the pre-embryo will become extra-embryonic rather than embryonic has biological and moral significance only if the extra-embryonic tissues can be shown to have no biological and moral significance. Two points are immediately evident: the trophectoderm is not the embryo, either actually or potentially; the placenta is human tissue rather than a human person. The crucial issue for discussion is the nature of the value ascribed to the trophectodermal/placental tissue. The placenta is an extraembryonic organ for exchange of nutrients and wastes between the mother and embryo. As such, it may be compared with an artifical respirator. Both are vital for the survival of the individual using them, and neither is within the body of the one they support. Neither is thought of as being that individual. If a person supported by a respirator dies, that person
Ford, op cit., p. 172. McLaren, A. Where to draw the line? Proceedinp of the Royal Institution, Great Brit& 56, pp. 101-121, 1984.
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rather than the respirator is mourned. However, in terms of status, an individuals dependence on the placenta or respirator leads to conferment of that individuals worth upon the organ in question. Imagine a sick person on a small hospitals only respirator: if the latter begins to malfunction, it will be repaired as if the malfunctioning respirator had considerable moral status. Had a persons life not been dependent upon it, the urgency to repair it would have disappeared. In practice, the value ascribed to a person is conferred (for a time at least) upon that which directly sustains her life. The basis of this rationale is provided by D e ~ i n e * with ~ his overflow principle, according to which our respect for persons extends to things closely associated with persons, for example, corpses are given respect. In similar vein we can confer upon the placenta a status comparable to that of the embryo-fetus as long as it is essential for the survival of the embryo-fetus during gestation. Consequently, the placenta cannot be dismissed as merely human tissue. Destruction of the placenta is equivalent to destruction of a fetus, since it is essential for the continued life of an individual and is to be appropriately valued. During early development, the trophectoderm is essential for the developing embryos interaction with the uterine environment. Since this interaction is essential for the survival of the inner cell mass, the trophectoderm should be valued as the embryo is valued, regardless of whether or not it is actually embryonic tissue. These conclusions are strengthened by the placentas function, namely, its sustenance of fetal growth by supplying it with substrates, and its modulation of fetal growth and development together with maternal metabolism through the synthesis and secretion of steroid and peptide hormone^.^' Additionally, the placenta is a potential competitor with the fetus for maternal substrates. Soon after implantation placental weight exceeds that of the fetus, but fetal growth subsequently proceeds at a greater rate than that of the placenta for the remainder of gestation. Significantly, there is a relationship between placental and fetal growth; in humans, a correlation between the two is observed as early as 10-20 weeks gestation. Not only this, placental growth is regulated by, or together with, that of the fetus. Experimental evidence suggests that when placental size is sufficiently reduced,

*6 Devine, P. The Ethics ofHomicide, Ithaca, New York: Cornell University Press, 1978, p. 101. 47 Owens, J . A . and Robinson, J.S. The effect of experimental manipulation of placental growth and development. In G. Chamberlain and F. Cockburn Eds. Fetal and Neonatal Growth. F. Cockburn, Ed. Volume 5, Perinatal Practice, Chichester, New York: John Wiley and Sons, 1988, pp. 49-77.

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fetal weight in late gestation or at term is also reduced, and is correlated with placental weight. Thus the placenta influences or limits fetal growth when its own growth is restricted. When the placentas functional reserve has been exceeded, placental size limits fetal growth. For instance, when the fetus: placenta ratio is greater than 11, there is a large increase in the incidence of perinatal problems. What this discussion brings to the fore is the intimate dependence of the embryo and fetus upon the placenta. While this may appear a self-evident observation, it directs our attention to the essential role served by the placenta in maintaining the embryo and fetus thoughout the period of their existence. The embryo-fetus cannot exist without the placenta, so that whatever value is ascribed to the former must, by association, be ascribed to the latter as long as it is functioning to maintain the embryo-jetus. Hence, far more ethical weight should be ascribed to the placenta and its forerunners than has been done in some recent discussions on the early embryo. This has been well expressed by Holland4a who has argued that the nature of the progeny of a given set of cells, such as trophectoderm, in thefuture, is irrelevant to the present status of those cells. But what about the placenta itself? The process of decidualization commences at the inception of conception and is complete by the end of the first month. During this time the mothers uterine endometrial tissue is transformed by pregnancy. Generally, three decidual layers are described: a basal layer immediately external to the embryo (and constituting the maternal vasular socket in which the placenta is plugged), a capsular layer outside this, that expands to fuse with a parietal layer at the junction of the uterine tube with the end~metrium.~ This intimate structural relationship between the placenta and fetus highlights the intimate functional interrelationship previously discussed. Consequently, to attempt to view the embryo-fetus in isolation of the placenta, is to sever a crucial link, thereby reducing the context of the embryo-fetus to an artificial one. The significance of this conclusion for the early embryo or pre-embryo is that, even though f it is committed to theformation o f extra-embryonic tissues, the whole o f much o it is essential f o r the well-being, growth and jirther development of that particular prenatal individual. There can be no future embryo and fetus without the extra-embryonic tissues. To compartmentalize the two

* Holland, A. A fortnight of my life is missing: A discussion of the status of the pre-embryo. Journal o f Applied Philosophy 7 , pp. 25-37, 1990. Segen, J.C., Ed. The Dictionary of Modem Medicine, Camforth, Lancs: Parthenon Publishing Group, 1992, p. 160.
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as though this were not the case is to fail to do justice to the maternal-fetal environment.
Primitive Streak

The primitive streak is frequently regarded as occupying a position of strategic significance in the transition from an unordered preembryo to an ordered embryo. Accordingly, it is viewed as instigating a new level of development, on the presumption that it is a long-term feature of the embryo. We shall argue that the distinctiveness of the primitive streak as a developmental landmark may be more illusory than real in biological terms, since its transitoriness and also its intimate interrelationships with closelyaligned developmental phenomena tend to be overlooked. Since the primitive streak occupies a place within a set of developmental events, it is doubtful whether all the weight of scientific understanding should be placed on it rather than on other embryological features, such as the notochord, somites, neural crest, or neural tube. The primitive streak is a transitory phenomenon, on its way to being transformed into more definitive features of the early embryo. Without it there would be no neural tube or neural crest, and in some species it sets the stage for anteroposterior development of the whole embryo.50It provides an important and orderly controlling step in body patterning, with its regression constituting one of the key events for subsequent development. Its biological significance, therefore, needs to be . seen within a developmental context rather than as the sole organizer for an individual beings existence. Ford appears to be placing more weight on the primitive streak than it should bear, when he contends that prior to this stage it would be pointless to speak about the presence of a true human being in an ontological sense; he writes: A human individual could scarcely exist before a definitive human body is formed. The question is whether a 1 7 - 18 day old embryo can be classed as being or possessing a definitive human body. Any major move in this direction reflects more of the biological potential of early embryos than of what they actually are as embryos. Undoubtedly, more of this potential has been realized than at 2 3 days after fertilization, and the nature of cellular and tissue organization is quite different,

50 Bellairs, R . The primitive streak and the neural crest: Comparable regions of cell migration? In P.F.A. Maderson, Ed. Developmental and Evolutionary Aspects of the Neural Crest, New York: Wiley, 1987, pp. 123-145. Ford, op. czt., pp. 171, 172.

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but these are the differences of an interrelated developmental phenomenon. Emphasis on the primitive streak appears to serve a largely negative function, in deciding that the level of organization present before its appearance fails to constitute an ontogenetic individual. The pre-embryo has not as yet become something organized. This leaves unanswered the question of what the pre-embryo actually is. Grobstein5' goes some way towards answering this question, contending that human pre-embryos are unquestionably human in biological terms, they are alive by scientific criteria, and have a profound potential - that of developing into a human infant and adult. The cells of the inner cell mass have an especially valuable potential, namely, that of culturing them for the study of cell differentiation and malignancy in human cells, and the controlled production of specific tissue for transplantation therapy. Such use of human pre-embryos would give continuing meaning and significance to human pre-embryos and their constituent cells. Accordingly, he considers that the human pre-embryo merits the same respect given to all human cells, tissues, and organs. Interesting as these comments are, they illustrate how readily the barriers between scientific description and moral directives are broken down. The value to be placed on embryos is closely linked, in this instance, not only with their stage of development, but more specifically with one developmental landmark, that of the primitive streak. Perhaps this approach is an inevitable one for all who take seriously scientific criteria. But it provides further evidence that any conclusions drawn about the scientific significance of the primitive streak will have ethical significance when society asks how embryos before and after this point should be treated. If this is true, the preembryo/embryo terminology cannot be regarded as solely of scientific interest.

The Gradualism o f a Developmental Continuum

The recurring motifs of embryonic development are: gradually decreasing potentiality, increasing determination and differentiation, and increasing complexity and interaction. This development occurs smoothly rather than in quantum leaps and its object is the transformation of a single fertilized ovum into a complex organism. Any attempt to distinguish between clearly-delineated developmental stages, such as pre-embryo and embryo, has all the inherent problems of a developmental continuum. This is because
52

Grobstein, 1988a, op. cit., pp. 67-69.

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the transition from one stage to the next is not instantaneous, while the later stage is totally dependent on the successful completion of the former stage. Any developmental errors occurring during the former stage will be reflected in errors manifesting themselves l l subsequent stages. This is not to deny that the primitive during a streak does indeed represent a watershed, but within a developmental context the commencement of an essentially new level of development in no way denies the developmental significance of that which preceded it. Gradualism also leads to an awareness that, although no cell in the early stages of development is earmarked for a particular future role, cell commitment is a gradual process . . . That many of the cells are destined to be extra-embryonic does not mean that the whole does not contain some very important part.53What is significant, morally and biologically, is the whole, regardless of whether some parts of the whole will or will not continue through into postnatal existence. They are all essential for prenatal existence, without which there would be no postnatal existence. It is the whole that is the individual-human-life-to-be. The preembryolembryo is becoming an individual in this sense. We are not interested in cells, as such, but in the whole composed of cells becoming organized in particular ways. The pluripotential nature or otherwise of cells tells us nothing about how it is right to treat the early embryo. Neither does the first appearance of the primitive streak tell us anything of moral significance. What is more interesting is organogenesis, that is, what lies beyond the primitive streak stage. But even this only underlines our emphasis on the human-life-that-is-in-the-making. Even if we are provided with evidence that a single human life is in the making from some point onwards, whereas more than one human life was possible before this point, we still do not possess categorical evidence that there is a moral gulf between the two. The problem from which we cannot escape has been well expressed by Alan Holland54 when he argues that: . . . we live forwards not backwards. The very question, When did I begin?, encourages one to overlook this simple fact. Precision is unattainable scientifically and may be of only limited importance morally. The whole picture is far more important, and this leaves ambiguity at these developmental stages.

53 Morgan, D. and Lee, R.G. Blackstones Guide to the Human Fertilisation and Embryo Aci 1990,London: Blackstone Press, 1991, pp. 72, 73. Holland, op. cit., p. 31.

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BEFORE I WAS AN EMBRYO 47

CONCLUSION We have rejected exclusive emphasis upon the embryo-fetus at the expense of the extra-embryonic tissues. We have come to the conclusion that the early embryo (inner cell mass plus extraembryonic tissues) should be viewed as a whole. This leads us to reject the pre-embryo terminology since we are not convinced that it helps clarify either the scientific or ethical issues at the beginning of human life. B a y l i ~ considers ~~ that use of the term pre-embryo might suggest an attempt to finesse some of the more difficult moral questions and since development of the embryo is a continuous process with each part of equal importance, she continues to use the term embryo. The prefix pre in pre-embryo may suggest to some that it is of less value than the embryo and so to avoid any such inference we have employed the terms embryoplacenta and embryo-fetus, to depict the parts of the early embryo that will give rise respectively to the placenta and fetus. Accordingly, the conceptus at time-point A in Figure 2 is represented principally by embryo-placenta, a , and to a much lesser extent by embryo-fetus, a. Both are represented, a situation that applies as far back as 4-5 days gestation. Hence, whatever term is used to cover the early embryo from about 4 days onwards should include reference to the embryo-fetus even when the latter consists of only a very limited number of cells. The much later stage, B, shows the reverse arrangement, with a (embryo-fetus) predominating; nevertheless, a (embryo-placenta) is still crucial to the survival of a. The two, while readily distinguishable structurally and conceptually, are intimately associated functionally. The whole cannot be arbitrarily separated into a and a , even if the sole object of our moral concern is a (embryo-fetus). Timepoint B commences at about 6 weeks gestation, by which time the embryo is well on its way to being a fetus, and by which stage the trophoblastic tissues have become a well-defined placenta. Timepoint, C , is at birth, by which stage a has outgrown a considerably, and by which stage a is capable of surviving in isolation of a . The placenta now ceases to have any ethical significance beyond that ascribed to it as human material. The position at which we have arrived is similar to that proposed by Holland,56 when he argued that the pre-embryo is not just a cradle in.which an embryo appears. We can extend that analogy by regarding the cradle and baby as being coextensive and
55 Baylis, F.E.The ethics of ex ufero research on spare non-viable IVF human embryos, Bioefhics 4, pp. 311-329, 1990. 56 Ibid.

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Figure 2 Diagram representing the growth of the embryo-fetus (a ') and the embryo-placenta (a ")from fertilization (at left) to around the time of birth (at right). For further discussion, see text. Not to scale.

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interdependent. Holland further comments that we have yet to be given convincing reasons against identifying the whole early embryo (pre-embryo) as the same individual as the later fetus (compare the respective situations at A and C in Figure 2). One may wish to make tentative distinctions at various places along a biological continuum, and these may serve a variety of purposes, including scientific ones. In these terms, the pre-embryo concept may have some merit. However, it gives an impression of
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BEFORE I WAS AN EMBRYO 49 precision that is misleading and that fails to grasp the significance of the whole as represented by the interrelationships of the embryoplacenta and the ernbryo-fetu~.~

Department of Anatomy and Structural Biology, and Bioethics Research Centre, University of Otago, Dunedin, New Zealand, and Edith Cowan University, Perth, Australia

57 We would like to thank Hamish Love and Tracey OFlynn for many stimulating discussions of this topic during their honours course in Anatomy.

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