Zygotes, Cells and Substantial Change: A Reorganization of the Matter

(Presented at 2012 PANTC conference)

Recent advances in cell biology have led some scientists and researchers to

conclude that there is nothing ontologically distinctive about the early human embryo,

distinguishing it from other cells. These recent advances, it is argued, are dramatic

enough to present a reductio to an argument for special protection of the human embryo.

This reductio is based on the potential that other cells are said to show, and amounts to a

claim that if the embryo is protected, then somatic (or body) cells should be protected in

the same way.

In this paper, I will review the advances in cell biology that have prompted the

arguments for a reductio, and the arguments themselves. I will argue that the zygote is

not merely another somatic cell, but a new organism, different from somatic cells. This

difference is actually highlighted by the recent advances, if they are examined from a

different perspective.

Totipotency, Pluripotency and Unipotency

There is a traditional distinction between three levels of potential: pluripotency,

totipotency and unipotency. Totipotent cells are cells that have the potential to become

any type of cell. The most dramatic realization of totipotency is the development of an

embryo from the totipotent zygote, for this shows how a single cell can give rise to all of

the cells of the organism able to produce fertile offspring. Pluripotent cells, on the other

hand, can give rise to many types of cells, but not all. The realization of this level of

potential can be found in stem cells, which can give rise to many types of cells, but not to

all. Finally, unipotent cells can give rise to one type of cell. An example of a unipotent

cell is a differentiated body cell, such as a muscle cell, that gives rise only to other cells

of its type.

1

Recent advances in cell biology have appeared to collapse the distinctions

between levels of potentiality. New laboratory findings, it is argued, have shown that the

changes that render a cell pluripotent and even totipotent are on a spectrum of normal

changes that do not alter what kind of thing the cell is. These changes are largely

alterations in the genes that are expressed, accompanied by molecular changes in

cytoplasm. Somatic cells, then, which had previously been thought to be merely

pluripotent, have been revealed to be totipotent, and “so the “super potential” to develop

into a newborn, is lurking behind pluripotency and unipotency”. Because of this intrinsic

potential of a somatic cell to develop into a newborn, it is ultimately claimed that there is

nothing special about the changes that bring about fertilization, and hence there is nothing

special about the zygote. A new type of being is not produced, for these changes are no

different from normal cell changes. Other cells don’t literally undergo fertilization, but

they get the same potential akin to that produced by fertilization.

The challenge that this presents to defenders of the claim that the zygote is one of

us, a human being, is that there appears to be no threshold where it is clear that the human

being has come into existence, at least during the early stages of embryonic

development.1 Rather, somatic cells appear to have a capacity to slide back and forth

between different levels of potentiality, with, it is claimed, merely the environment

causing the same cell to undergo changes that render it pluripotent, and then totipotent.

Because of this capacity to restore the potential it once had, so that a once-differentiated

cell can become totipotent again, it is argued that if the zygote has a special status

because it can give rise to a human being, then all other somatic cells have this status as

well.2 There is a seamlessness to a cell's transiting between levels of potentiality; as one

1 Morris, Jason, “Substance Ontology Can Not Determine the Moral Status of Embryos”. Journal of Medicine and Philosophy, 2012 Vol. 37 (4) 331-350.

2 I am not committed to this view—that any cell can be totipotent—for reasons given below. But this is part of the argument presented in the literature on recent lab advances.

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author writes, "Human development, awe-inspiring as it is, is not a mystical, irreducible

event but a process that we can manipulate handily and predictably by altering the

concentrations of a handful of transcription factors".3

In philosophical parlance, what is lacking in this seamlessness, wherein a cell can

transit back and forth between different degrees of potentiality, is substantial change. If

zygotes are to be protected because they are one of us, a kind of being that is different

than a somatic cell, then there must be a point at which the somatic cell’s realization of its

full potential is actually an event that brings about a new kind of being.

So, what are these recent advances that have prompted this debate? The first of

these is the discovery of the totipotent cells, or blastomeres, of the early embryo. It is

claimed that the first 4-8 cells that descend from the human zygote are totipotent, or able

to give rise to the embryo and extra-embryonic tissues.4 Totipotency, it is also said,

affords the cells a flexibility within the embryo: cells are said to be interchangeable, and a

very young embryo can lose up to a 50% of its cells and still develop.5

Totipotency has been said to pose problems to our origins at fertilization since the

first experiments with embryo splitting in the 1980s. This problem amounts is well

documented in the literature, and amounts to a single cell of the first 4 or even eight cells

of the embryo itself being able to be develop into an embryo. If this is possible, then each

embryo composed of totipotent cells is actually a composed of several zygotes, since

each of these, like the zygote, can develop into an embryo; the difference is merely

3 Morris, J. 2012.4 Van de Velde H. et al. The four blastomeres of a 4-cell stage human embryo are able to develop individually into blastocysts with inner cell mass and trophodecterm. Human Reproduction 2008: 23 1742-1747.5 Van de Velde Prenatal Diagnosis 2000; Veiga A. et al. Pregnancy after the replacement of a frozen –thawed embryo with <50% intact blastomeres. Human Reproduction. 1987: 2 (4) pp. 321-323.

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environmental, rather than intrinsic.6 And if these cells are not pulled out, several zygotes

are subsumed into one embryo, once the cells restrict and are no longer totipotent.

The second recent advance is Somatic Cell Nuclear Transger (SCNT), which

involves the removal of the nucleus of a somatic cell and its placement into a denucleated

egg. The cytoplasm of the egg reprograms the nucleus of the cell to an undifferentiated

state and an electrical shock is administered to begin cell division. This first cell division

is a sign of the trajectory that the clone is on to develop into a full, adult organism.

The puzzle that this poses to defenders of the claim that the zygote is a human

being is that if the only change that is said (by some) to occur is the reprogramming of a

somatic cell nucleus, and this produces a new kind of being, then every change from one

functional type of cell to another—which is done through nuclear programming—

constitutes substantial change as well.7 In other words, if the change from somatic cell to

clone is a change from somatic cell to human being, and the change merely amounts to a

new expression profile of the nucleus, then substantial changes are happening all of the

time, far more frequently than most biologists and most metaphysicians currently

recognize. More importantly, the distinction that might be afforded the human zygote

appears arbitrary:

In general, although cell types differ only by virtue of their expression profiles,

and although all cells carry out an impressive array of coordinated functions, we

do not ascribe moral status to any single human cell except the human embryo.8

The third advance made in laboratories that appears to either elevate all somatic

cells to special moral status, if that is afforded human zygotes, are tetraploid

6 E.g., Ford, Norman. (1988). When Did I Begin? Conception of the Human Individual in History, Philosophy and Science. New York: Cambridge University; Donceel, Joseph. (1970). Immediate Animation and Delayed Hominization. Theological Studies 31,76-105; Smith, Barry & Brogaard, Berit. (2003). 16 Days. Journal of Medicine and Philosophy, (28) 1, 45-78.7Elaborated by Morris8 Morris (2012) p. 7

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complements. These are the product of two types of cells: induced Pluripotent (iPSCs)

and Embryonic Stem Cells (eSCs). iPSCs are a specific type of somatic cell that are

reprogrammed so that they can become then any type of somatic cell. Transcription factor

genes, which alter what the nucleus expresses, render the cell pluripotent, so that it can be

reprogammed into a different type of somatic cell.9 The second component of these

complements, ESCS, are cells taken from normal embryos that are fused together to

produce cells with nuclei that have 4 sets of chromosomes, rather than the usual 2. These

tetraploid nuclei will force the ESCs to give rise only to the extraembryonic placenta and

trophodecterm. Tetraploid complements are then constructed by sandwiching 10-15

iPSCs between the manipulated cells. When implanted in a uterus, the tetraploid

complement develops into a fetus that is genetically identical only to the iPSCs. And this,

it is claimed, is evidence for the capacity of somatic cells to give rise to a full organism

without substantially altering the cell.10 The cells have merely been placed in the right

environment; nothing about them has changed intrinsically that would amount to more

than an accidental, or qualitative change. For this type of change—an alteration in gene

expression--is one that cells undergo regularly, and is not, in other situations, considered

to be a substantial change. A new type of being, it is claimed, is not brought into

existence: a somatic cell—an iPSC—simply changes its expression profile, all the while

remaining what kind of substance it is: a cell. And yet, because it is placed with other

cells of a different lineage, it develops into a newborn. This, it is argued, demonstrates

that it every cell has an intrinsic potential to develop into a human being; it is merely

their environment that produces this change in developmental trajectory. And so, again, it

9 Kujik EW et al. The different shades of mammalian pluripotent stem cells. Human Reproduction

Update. 2011 Mar-Apr;17(2):254-71.10 Stier, Marco and Schoene-Seifert, Bettina. 2013. The Argument from Potentiality in the Embryo Protection Debate: Finally “Depotentialized”? American Journal of Bioethics 13:1, 19-27.

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is said that behind every pluripotency (and unipotency) lurks that totipotency that is used

in arguments for the zygote’s special status.

These three instances, in which it is said that a somatic cell undergoes a

qualitative change that nonetheless gives rise to a new organism, are presented, then, as

three instances that show a human zygote produced through fertilization (either in vitro or

in vivo) to have no special metaphysical status granted it simply in virtue of its capacity

to give rise to a human organism. This, of course, is the reason given for why the zygote

should be protected as one of us—that in virtue of its giving rise to a human being, it is a

human being. Either one of these possibilities—that it is potentially a human being or

actually a human being—is, it is argued, true of totipotent cells, SNCTs or tetraploid

complements.

What I will contend, though, is that the presentation of these three instances that,

in laboratories, give rise to mature organism, is missing important details. These details

allow for an argument to be made that in each of these instances, substantial change is

taking place. The upshot of this will be that zygotes are a different kind of thing than

somatic cells, for they are the result of a substantial change. The other three instances are

also the result of substantial change, and none of the 4 instances are the same kind of

thing as a somatic cell.

Substances and Substantial Change

It is probably not contentious to say that substances exist, and that a human being is a

substance.11Additionally, there are certain ideas about substances that are widely held to

be true. Substances are ontologically basic, and are independent and durable. They are the

subjects of predication and bearers of properties. Substances are ordinarily the subjects of

change and are typified by what are normally classified as objects or kinds of objects. 12

11 Apart from bundle and trope theory. What is more contentious is to say what things are substances and what are not. 12 “Substance”, Stanford Encylopedia of Philosophy,

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Obvious examples of substances are those “things” in the world around you that

are independent, persist through time and change, and have qualities. Given this, human

beings, are substances: we exist independently of other things (as opposed to a wink or a

wrinkle); we are durable and exist through change; we are predicated of and bear

properties; and we are of the kind, “human being”.13 In fact, we are the fundamental

being of the kind, “human being”. This is how the criteria work together to show us what

a substance is.

I will also claim here, without defending this particular theory, that human beings

are organisms (that I think we are contingently organisms is a topic for another paper and

not relevant here). Olson, one of the more prominent defenders of a Biological account of

personal Identity, tells us that it is ultimately the business of biologists to answer the

question “what is it to be an organism?” The biologist Clifford Grobstein, to whom Olson

refers, tells us that “an organism is a complex macromolecular structure that behaves as a

unit and is capable of replication through a conversion of materials and energies derived

from its environment through a self-controlled interface or boundary” (1964: 6114).

Olson’s account is captured in Grobstein’s definition, and so he argues that we can infer

three conditions necessary to being an organism. The first is that in order for an entity to

be an organism, it is necessary that it metabolize, or both exchange matter and energy

with its surroundings and at the same maintain a dynamic stability. Like a flame or

fountain, the organism retains its characteristic form and structure despite this rapid

change of matter. And yet, unlike a flame, whose size depends on the surrounding

oxygen and fuel, etc., an organism must also satisfy a second condition: it must have an

internal mechanism, a “teleology” which will allow it to adjust itself and to take

advantage of changes in its surrounding. The teleological or “goal directed behavior”, 13 For the purpose of this paper, I will defend the human being as a human organism. 14 Grobstein, Clifford 1988. Science and the Unborn: Choosing Human Futures. New York: Basic Books.

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Olson claims, is grounded in a third condition necessary to an organism, “an underlying

biochemical structure of unimaginable complexity”15This organized complexity, he

argues, is not reducible to having a vast number of parts. Rather, it involves the

arrangement and interaction of these parts, which in turn allows for the goal-directed

behavior or teleology that consists of metabolic activity. In sum, writes Olson, each

organism has what Locke referred to as a “life” or a “special kind of event, roughly the

sum of the metabolic activities the organism’s parts are caught up in”16.

What I will argue first here is that the zygote and embryo is a human organism

that is a different kind of substance than a somatic cell. That the zygote and embryo is, of

course, controversial: many philosophers claim that the zygote and embryo (the being

that succeeds the first cell division of the zygote) are not, in fact, the same being that is

later a multicellular organism.17 The zygote and early embryo, it is claimed, do not have

sufficient communication between parts: neither is the organized whole that one would

expect of an organism. Furthermore, there are problems with the one-celled zygote’s

survival, for with the first cell division, it would appear that it would “fission out of

existence”. And then there is the problem of monozygotic twinning, which can happen

anytime within the first 16 days after fertilization; this, too, would make it fission out of

existence.

Fertilization and Substantial Change

There is, of course, a point when human beings come into existence, a point at

which a substantial change happens. This, I will argue, is the point at which the sperm

makes contact and fuses with the egg. Once I have (hopefully) briefly presented a case

15 Olson, Eric. (1997). The Human Animal Without Psychology. Oxford: Oxford University Press, p. 128. 16 Olson, p. 136.17 E.g., Olson, Eric. (1997)., Smith, Barry & Brogaard, Berit. (2003). 16 Days. Journal of Medicine and Philosophy, (28) 1, 45-78.

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for fertilization producing a new kind of being, I will return to the cases above, and argue

that they are each cases of substantial change that produce human beings. My

justification for this claim rests, in part, on a defense of the zygote and embryo being a

human organism; hence this digression into embryology. For from that I will build a case

for why these cases are missing relevant features that, once added, shed light, I think, on

what these laboratory creations actually are.

Prior to fertilization, the egg is a large cell that has a 23 chromosome nucleus that

has begun to replicate itself (it will not resume replication until a sperm has penetrated).

It is composed of a layer of eipithelial cells, the corona radiata, followed by a layer of

acellular material, composed of carbohydrates and proteins, called the zona pellucida.

The inner part of the egg is composed of cytoplasm, which contains mitochondria,

proteins, molecules, and the nucleus of the cell.

The sperm is a much smaller motile cell that also has a 23 chromosome nucleus.

When the sperm makes contact with the egg, its penetration of the zona pellucida begins

a new trajectory that is instanteous, for at the moment of contact of the zona pellucida,

there is a zona reaction, or a change in the properties of zona pellucida that prohibit

another sperm from entering. The zona hardens and enters into a biochemical relationship

with the sperm, wherein the cap of the sperm—its acrosome—is broken down by proteins

in the zona pellucida. This acrosomal reaction, dependent on components of the zona

pellucida, allows for release of the content of the sperm’s cap, including the 23

chromosome nucleus, to be emptied into the cytoplasm of the egg.

The point at which the sperm meets the zona pellucida, initiating the zona and

acrosomal reaction, is a point of fusion of the two gametes, wherein their two separate

trajectories come to a halt, and the life of the new substance, the zygote begins.18This new 18 Condic, Maureen. "When Does Human Life Begin? A Scientific Perspective," The Westchester Institute for Ethics and the Human Person, Westchester Institute White Paper Series 1, no. 1 (October 2008).

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substance has its parts caught up in a new trajectory, a life that is entirely different than

the two cells that fused. The whole zygote, which includes the parts of the former sperm

and the egg, has a life directed towards the growth and development of the human

embryo and ultimately the adult human being. This is not a process, but an event that

occurs in an instant.

One manifestation of this new trajectory is the organization of a body plan even

prior to the first cell division. With the sperm’s contact with the cytoplasm, the

replication of the genes in one of the nuclear bodies—that inherited from the mother—

begins again, and a very small cell, a polar body, containing a copy of the inherited

genes, is extruded from the cell and is tethered by a thin cytoplasmic bridge between the

zona pellucida and the former egg membrane. This polar body has served as a marker for

what is called the animal-vegetal axis, which can be used to predict, with normal

development (i.e., undisturbed), the body axis of the embryo and fetus, and exhibits the

organization of a body from the point of fusion. Although the cause of organization is

controversial (some researchers claim it is that completion of that first mieotic division;19

others claim it is actually the shape of the zona pellucida.20).21 The point is, though, that

there is a traceable axis that conveys an organized body plan even prior to the first cell

19 Gardner R.L . The early blastocyst is bilaterally symmetrical and its axis of symmetry is aligned with the animal-vegetal axis of the zygote in the mouse. Development, 124, pp 289-90.; Gardner 2001a. Specification of embryonic axis begins before cleavage in normal mouse embryo. Development, 128, pp. 839-847; Piatrowska K. et al. ‘Blastomeres arising from first cell division have distinguishable fates in normal mouse development.’ Development 128, pp. 3739-3748.20 Kurotaki Y, Hatta K, Nakao K, Nabeshima Y, Fujimori T. Blastocyst axis is specified independently of early cell lineage but aligns with the ZP shape. Science. 2007;316:719–72321 For a lengthy discussion of theories see Hiiragi, Takashi, et al. Where do we stand now? – mouse early embryo patterning meeting in Freiburg, Germany (2005). International Journal of Developmental Biology 2006: 50 (581-588) and Yusuke Marikawa and Vernadeth B. Alarcón. Establishment of trophectoderm and inner cell mass lineages in the mouse embryo. Molecular Reproductive Development.   2009 November;   76(11): 1019–1032.

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division, what one researcher described as a “light pencilling in of polarity that is

gradually engraved as the embryo grows older”.22

A second feature of the zygote that demonstrates a trajectory different from the

gametes that fused is the activation of the maternal and paternal genomes. Prior to fusion,

each nuclei is highly methylated: methyl tags attach to the DNA and silence it, so that the

genes are not expressed. With entry into the egg, the sperm immediately begins to

demthylate, due, it is theorized, to proteins and enzymes in the cytoplasm.23 These genes

are expressed even prior to the first cell division, when a gene crucial to the development

of the nucleolus is expressed, allowing for translation of DNA into protein. Other

paternal genes, such as tumor supressors, DNA repairers and cell cycle regulators are also

expressed.

Although the maternal chromosomes are highly methylated, or silence, and

transcription of the paternal DNA is four to five times greater than that of the mother’s,

there is nonetheless interaction between the two pronuclei. This is even despite their

locations in separate parts of the cell. So their gradual movement to the center of the cell,

where they are in closer proximity, does not indicate the beginning of coordinated

activities. In fact, even when they do join together, at a point that is known as syngamy,

the apparent fusion of the two nuclei is merely a breakdown of the nuclear membrane that

separate the two nuclei.24 There is no single nucleus, even after this membrane

breakdown; rather, the chromosomes from each parent are simply in close proximity so

that they can prepare for replication and cell division.

One might object that a new trajectory is not sufficient for substantial change. In

the case of fertilization, fusion ought to entail the cessation of the lives of both gametes, 22 Zernicka-Goetz, M. 2004. ‘First cell fate decisions and spatial patterning in early mouse embryo.’ Cell and Development Biology, 15, pp. 563-572. 23 Oswald J, et al. 2004. ‘Active demethylation of the paternal genome in the mouse zygotr’. Current Biology, 10, pp. 475-478.24 Condic M. (2008), p. 5.

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and a new trajectory might not capture this. For instance, it might be said that although it

appears that the sperm ceases to exist, having been deconstructed and assimilated into the

egg, the egg itself survives and just grows bigger, having a new part (the paternal

chromosomes). I do not think that this is the case. The locus of control of the egg was its

nucleus, and with the acrosomal reaction, the maternal chromosome is highly methylated

(so that many but not all of its genes remain silent) and the paternal chromosomes,

brought in by the sperm, immediately begin to organize a new body, with tumor

surpressor genes, DNA repairers and cell regulators being expressed. The maternal

nucleus is no longer governing, for the trajectory that it was governing went out of

existence with fusion; molecules and genes that supported the life of the egg are no

longer working towards that end. The new substance, the human being, is being governed

by 2 sets of chromosomes, brought about by the fusion of the gametes. These

chromosomes are working physically separately but in tandem, to continue the

organization of the body that came into existence with fusion

Another objection may be that a trajectory and a new locus of control are not

sufficient, for there are other entities that are the result of contact between a sperm and

egg and also develop, at least for a short time. Hydatiform moles are one of these kinds of

things. However, hydatiform moles, which result from a normal sperm fertilizing an egg

that has abnormally lost its genetic material, grow as a disorganized mass of cells and

tissues which are unrelated to each other. Although their origins appear, on the surface, to

be similar (the fertilization of a (defective) egg), their growth and development is not at

all like the life of the embryo.25 They result from fusion, although arguably from different

parts, but the trajectory is not the same. And parthogenesis, or the development of an

25Condic, M.L. Alternative sources of pluripotent stem cells: altered nuclear transfer. Cell proliferation 2008 41 (Suppl 1) 7-19.

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unfertilized egg into a multicellular organism, at the molecular level, is not even similar

to a zygote or embryo.

Approximately 2 days after the fusion of the gametes, the first body cell of this

new organism divides. The zygote itself is a composite substance: the zona pellucida and

its cell are its parts, so that, unlike a one celled organism, it does not fission out of

existence, as an amoeba would, with this cell division.26 Rather, this is a division of a

body cell, and it is literally a division: the cell cleaves, rather than replicates, so that the

new embryo is the same size as the zygote. Again, this point of first cleavage can be

predicted based on the position of that polar body extruded with the sperm’s fusion with

the egg. This cleavage continues to the 16 cell stage, wherein the zona pellucida is shed

and the embryo begins to grow in size.

The upshot of this is that from an empirical perspective, there is evidence of a

new substance coming into existence with proper contact of the sperm and egg. An

immediate zona and acrosome reaction, and the subsequent new trajectory of new

developing body, shows fusion of the two cells, so that a new substance, whose parts are

caught up in a new “life”, comes into existence. The cascade of events that follows

includes the immediate exclusion of other sperm, dissolution of the sperm that gained

entry, the activation of paternal genes that begin to direct and promote development, and

the organization of a body that is traceable from fertilization onwards.

This new substance bears the marks of an organism, as well. Its parts behave as a

unit, and it is goal-directed as a whole, with its purpose being the development of a body.

Its use of proteins and molecules for cell repair, differentiation and division constitute

metabolism; in fact, different levels of metabolism have been shown to indicate the health

of the pre-implantation embryo.27 And its maintenance of a dynamic stability is evidenced 26 This is a well documented objection to our having once been zygotes27 Leese, et al. Embryo Viability and Metabolism: Obeying the Quiet Rules. Human Reproduction. (2007) 22 (12): 3047-3050.

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by regular, predictable growth and development even if body cells (e.g., embryonic stem

cells) are removed. In fact, even if the cells are disturbed—perhaps even forceably

rearranged—signal molecules in the zygote’s cytoplasm called morphogenetic gradients

serve to direct development and function for the cell. The gradients in the zygote’s

cytoplasm signal to the newly rearranged cell what their function is, and shows that there

is an overarching plan that is directing the organism as a whole towards a developed

body.28

So what bearing does this have on the recent laboratory experiments given above?

For one, each of these experiments produces a being that is said to have the same

developmental capacity as the zygote or early embryo. This I believe to be true: each of

these laboratory experiments can produce a human being. In fact, some have. However,

the biological analysis has been oversimplified, and, at times, relevant details have been

overlooked, and so relevant metaphysical implications have been overlooked.

Totipotency Revised

A 2008 study showed for the first time that a single embryonic cell, or blastomere, could

be removed from a human embryo and demonstrate totipotency, by developing into

fertile offspring.29 Each blastomere that was removed, however, was placed inside an

empty zona pellucida. It was then that the blastomere began to develop. And remember:

the blastomeres are not duplicates of the zygote, but part of an embryo. The first several

cell are the result of cleavage and so have some of the same cytoplasm of the zygote,

including epigenetic elements. This totipotent cell is a clone of the zygote that has been

constructed. It is not simply a cell whose proteins have been altered in such a way; it also

needs the zona pellucida in order to develop.

28 Beddington, Rosa, 1999: ‘Review: Axis Development and Early Asymmetry in Mammals.’ Cell, 96 (2) pp .195-209.29 Van de Velde, et al. 2008.

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The construction of the zygote from a zona pellucida and the blastomere is the

creation of a new substance from parts. I will offer more analysis of this below, but here

it is sufficient to say that recent reports of this are inaccurate: it is not the case that a

“totipotent” cell can be removed and subsequently develop into a human being, given the

right environment.30 The “totipotent” blastomere is placed into what is a part of a zygote

—the zona pellucida— so that between the two parts, a new zygote is brought into

existence.

Somatic Cell Nuclear Technology: Revised

As we saw above, a clone produced by SCNT has its nucleus from a body cell placed in

the cytoplasm of the denucleated egg, whose zona is still surrounding it. Placing the

somatic nucleus in the cytoplasm of the denucleated egg allows for the epigenetic factors

to strip the nucleus of the effects of development and to respond to factors that initiate the

genetic component of zygotic development.31 The clones that then result from SCNTs are

physically the same as a one-celled zygote; in fact, they are a one celled zygote. The

clone’s cytoplasm is the cytoplasm of an unfertilized egg, and the zona pellucida is a part

of the newly formed clone; if the cell and oocyte were that of a human being, a human

being has just come into existence. Even the jolt of electricity mimics ionic channels

opening and closing during the first hours of the zygote’s life in vivo.

Tetraploid Complements

Tetraploid Complements are composed of pairs of diploid embryos that have 10-

15 iPSCs or ESCs sandwiched in them. The resulting organism is genetically identical to

the iPSC or ESC. The cells that make up the tetraploid sandwich are embryonic cells, or

blastomeres, that have been fused together, using electric voltage, so that they have 4 sets

30 MacFarlan, T.S., et al. 2012. Embryonic stem cell potency fluctuates with endogenous retrovirus activity. Nature 487: 57-63.31 Condic, M. 2008. Alternative sources of pluripotent stem cells: altered nuclear transfer. Cell Proliferation 41 (Suppl. 1), 7-19.

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of chromosomes. They are genetically altered so that they will produce the trophopblast,

or the part of the embryo that attaches to the uterine wall. The blastomeres are like

totipotent blastomeres, in that they, too, have the egg’s original cytoplasm.

These tetraploid complements are clearly a different case, since it is not the

construction of a zygote that is taking place. However, is it true that “by converting a skin

cell into an iPSC, and by subsequently assisting this cell via tetraploid cells, it is

ultimately normal to develop a newborn from a normal skin cell”?32 Does every human

skin cell need to be only to be in the right environment in order realize its

“superpotential” to become a human being?

I think that in all three of these cases, the same solution can be given. In each

case, a substance is created in vitro by composing the parts in such a way that these parts

become caught up in the life of a new substance, a human being. In the first two cases,

what is added together are the parts of a zygote, albeit at a later stage in a zygote’s life

(after sperm and egg have fused). In both the totipotent cell and the clone case, the parts

—the zona pellucida, the egg cytoplasm, and all that it contains—and a diploid nucleus,

are placed together, so that a zygote is constructed.

Both clones and the product of totipotent cell transfers, however, are slightly more

mature developmentally than the youngest human being. In the account of the human

substance coming into existence under natural conditions given above, the point of fusion

of the sperm and the egg is the moment of substantial change. The construction of a clone

or the transfer of a totipotent cell, on the other hand, brings into existence a body that is,

developmentally, many hours older than the newly created human being in vivo. In the

former cases, that of the clone and the product of totipotent cell transfer, the nucleus has

fused; in the latter case of the zygote created under natural conditions, the fusion of

nuclei is hours away. 32 Stier and Seifert p. 22

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The tetraploid complement presents a slightly different scenario. Here we have

embryonic cells that are fused together, and then the body cells, induced to be

pluripotent, or embryonic cells, already pluripotent, are placed within these cells. It is

important to note, though, that this composite is put inside of an empty zona pellucida to

grow. This whole new being, then, is developmentally or structurally equivalent to an

embryo, rather than a zygote. It is constructed of cells differentiating into the so-called

“embryo proper” (induced pluripotent cells, or ESCs, which can become any type of

body cell, and so meets the needs of becoming the body cells of the embryo) and of cells

differentiated into the placenta, all of which are placed into a zona pellucida. And so an

embryo is constructed and this whole develops into a newborn.

What I believe this to be is the construction of an embryo, rather than the less

developed zygote. The parts of the embryo are placed together, and these parts, when

placed together in the right way, become a living organism. But we can at least see, I

think, that there is some order to what is going on here: an embryo is “built”, and built of

living parts, so it makes sense to me that these parts would become parts of a whole that

is greater than the parts composing it. It is the creation of a substance, and if this were a

human embryo built, it is the creation of a human being, one that is structurally several

days older than the newly created human being described above.

In these three cases, then, I am claiming that human beings are made in laboratory

settings. One justification for this claim is that we know a good amount about

embryological development, and we can see that in each of these cases, the “materials”

that are brought together are living materials and the appropriate ones to compose a

human being at that point in its development. In addition, these experiments show us

what one would expect: it seems that the fewer separated macro-level parts needed, the

more successful the experiment. It is also likely that this can be accomplished because

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there are so few parts needed. Although the molecular composition of each part is

complex and vast, they are contained within the larger parts:33 in all three cases, the

cytoplasm, which contains many of the crucial epigenetic factors and other molecules, are

intact, the zona pellucida is intact, and the nucleus either intact or manipulated naturally,

in the sense that the cytoplasm is what works on the somatic nucleus to strip it.

It is nonetheless noteworthy that somatic cloning is rarely successful; in less than

one in a 100 transfers, the nucleus of the clone is successfully stripped down34. And

tetraploid complements have only been made with animals (which have different

embryological development than humans do). Clearly, we are still in the experimental

stages of creating human beings.

A second, more important justification for this claim that human beings are

produced in these laboratory settings, are the results. Totipotent cells, when placed in a

zona pellucida have produced human beings.35 (And it seems that it is just a matter of

time before human being tetraploid complements and clones are created). There is

continuous, uninterrupted development from the instant that these parts are brought

together. The parts are caught up, as a whole, in an entirely different trajectory than each

of the parts. The whole acts like an organism and develops into a mature one. This

creation of the organism is the moment of substantial change, when a human being comes

into existence, and from this moment on, the substance—the human being—persists.

Through a metaphysical lens, I would say that each of these cases is one of what

van Inwagen calls generation, where “x is generated out of the ys at t just in the case that

33 This makes it infinitely easier than bringing something into existence atom for atom.34 Condic, M. Alternative sources of pluripotent stem cells: altered nuclear transfer. Cell Proliferation, p. 10.35 Van de Velde and Andrew French et al., “Development of Human Cloned Blastocysts Following Somatic Cell Nuclear Transfer with Adult Fibroblasts”, Stem Cells 26, no. 2 (February 2008), 485-493.

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the ys come to compose x at t and x does not exist before t.”36 This, van Inwagen, claims,

is the way that an object can become a part of a thing. To illustrate his point, he writes,

If, however, God in an instant, were to take certain atoms and, all in an instant,

make a living cat out of them, then He would cause it to be the case that that cat

was generated out of those atoms, and each of them would become a part of the

cat—would be caught up in its life ab initio—without being assimilated by it.37

One difference, of course, between van Inwagen’s Divine Being’s actions, and the

experimenter’s actions, is that the experimenters have an easier job putting relatively

macro-level organic parts together, as opposed to atoms (although, in virtue of this, they

are putting atoms together). In any case, though, this is what we have: the parts of the

future zygote or embryo are not merely assimilated into a whole, as would be the case

with an organism digesting or metabolizing a molecule; rather, the parts compose a whole

so that something that did not exist prior to the composition now exists.38 This is a classic

case of substantial change: a new organism, the human being, comes into existence and

persists until death.

This may seem too Frankensteinien for some: organic parts put together to

compose a new human being! And, in the cloning case, there is even an electric shock

administered! The novelty of these laboratory creations does wear off, though. The

artificial fertilization of a human egg, resulting in a zygote, was viewed as too

Frankensteinien as well. In fact, the birth of the first in vitro baby, Louise Brown,

36 Van Inwagen, Peter. Material Beings (Ithaca: Cornell University Press, 1990).  p. 9637 P. 9638 Formally, van Inwagen’s principle of assimilation is: “x assimilates the ys at t just in case that the ys become parts of the x at t and x exists throughout some interval that includes t but of which t is not the earliest member”.

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prompted the president of the Hastings Institute to write an article for the NY Times,

“Frankenstein Myth Becomes a Reality”.39

The point I am making here, though, is that all of these cases—cloning, totipotent

cell transfer, and tetraploid complements—are cases of substantial change. These are

biological organisms, and the classic criterion for substantial change for organisms—one

that marks it as distinct from a phase change—is a new life, manifested by a new

trajectory. They are cases of generation, where parts are composed to create a new

substance. And these three cases produce the same kind of being as the fertilized egg,

using the same metaphysical principle. As van Inwagen writes,

Or, take a more common case, a sperm and an egg unite to form a zygote. Then

the zygote is generated out of the atoms that had composed the sperm and the

atoms that had composed the egg. (But the zygote is not generated out of the

sperm and the egg, since the sperm and the egg do not compose the zygote.)40

In each of these cases, a human being structurally older than the zygote is brought into

existence, but it seems evident to me why they would be structurally older: the parts that

are used for their composition are the parts appropriate for that stage. When the parts are

put together, they are somehow transformed so that they are greater than the whole. A

new trajectory of development that belongs to the new human being begins. With some

luck and some knowledge (and a lot of hubris), even older-stage human beings may be

able to be composed in laboratories. But it fits that these very young human beings, made

of very few parts, at least at the cellular level, are the ones that scientists are able to

compose.

39 Gaylin, Willard. (1972) "The Frankenstein Myth Becomes a Reality – We Have the Awful Knowledge to Make Exact Copies of Human Beings.” The New York Times Magazine March 5, 1972, p. 12 ff.

40 van Inwagen, p. 96.20

This analysis of the embryological data gives us a new framework to use when

considering these 3 laboratory cases. Each case presents a zygote or embryo somewhere

on the developmental spectrum. And this framework, which gives us a zygote that is a

human organism, also removes other problems presented in the literature. One of these is

Morris’ point that embryonic cells can cycle out in and out of totipotency, thereby, he

says, showing that the zygote’s allegedly special status is transitive. With the framework

given above, it does not matter if cells cycle out of totipotency, for the “totipotent” cell is

not sufficient for production of a zygote. The zona is needed as well. Morris also makes

the point that an embryo’s cells can be rearranged and even removed to produce a new

line of cells, and so this shows us the instability of the embryo, which in turn implies

something about its metaphysical status. But is this not true of our bodies? Our cells can

be removed to produce a new line of cells; they can be manipulated so that a different

type of cell is produced; and they can be rearranged. All of this is standard iPSC

treatment. While this similarity between us and them is not sufficient to show that the

embryo and zygote are one of us, it is certainly not evidence that they are not. In fact,

given other arguments (hopefully including the ones above), these sorts of things help to

build the case that we were once zygotes.

What I have argued thus far is that a human zygote comes into existence with

fusion of the sperm and egg, and that recent advances are compatible with this view. A

lingering question, of course, is twinning. Although beyond the scope of this paper, I will

briefly offer something along the lines of a solution I’ve offered elsewhere.

***This section is taken from an article of mine on twinning in the Journal of

Medicine and Philosophy. I plagiarized myself for a conference presentation, and have

yet to revise this (largely by adding solutions and not plagiarizing myself). So, really, the

paper on Morris, Stier and Seifert stops here). *****

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The problem with monozygotic twinning is that it appears to be the division, or

fission, of an organism, for what appears to be single organism (the zygote and embryo)

divides into two genetically identical organisms that ultimately are recognized as

monozygotic or identical twins. Since we human beings are not capable of dividing and

surviving, a basic understanding of persistence conditions would entail that the entity that

divides into twins can not be one of us. This entity exists during the first few weeks post-

fertilization, while twinning is still possible, and so it has been argued that the earliest

point at which we could come into existence is after twinning is possible, around 16 days.

However, I have argued elsewhere that an organism that is a hylomorphic

composite of matter and form is both compatible with embryology and can offer a

solution to twinning. The form of the organism that I have offered is a neo-Aristotelian

Thomistic soul that serves as an intrinsic life principle that purposefully configures matter

towards a proper end. This is our form, and the matter configured is the organism. In

cases of twinning, two human beings come into existence at fertilization when two souls are

infused into the unicellular body. Upon infusion, the souls of each of these human beings are

colocated, sharing the same matter.i Each of these twins, though, is a composite of matter and

form, and so each is a human being (this maintains that each human being is essentially an

individual soul united to a material body). As the matter is configured by each form, the two

human beings usually separate (but in some cases fail to and are conjoined). And so on this

account, monozygotic multiples were both (or all) present at fertilization, and, in typical cases

separate during the first two weeks or so after fertilization.

Although my co-location solution to monozygotic twinning is not advanced by

Aquinas, it is arguably permitted by his argument for the transcendent nature of the

human form. On Aquinas’ account, the human form has an existential independence from

matter in virtue of its transcendent nature and so is not reducible to the arrangement or

organization of matter. In fact, Aquinas argues that although the human form begins to

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exist in its natural state of configuring matter, it will exist when separated from matter at

death, albeit in a deprived state. (ST I q.76; q. 90 a. 4).ii Because of this existential

independence, it seems that the human form could maintain its distinction as an

individual, even if co-located, in virtue of what will individuate it when separated from

the body: what would allow for this distinction as an individual after death would also

allow for the distinction as a co-located individual. (The individuality of the soul,

however, does not render it a Cartesian soul. Aquinas argues that even thought the soul

can exist apart from the body, the soul is not identical to the human being (or the person),

but is a very important part of the human being.

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Perhaps the most problematic objection, once you accept a Thomistic metaphysics, is that

Aquinas makes repeated references to “material dimensions” as the principle of

individuation for material beings. The human form is special, however, since it is on the

“boundary between corporeal and separate substances@(Quaestiones De Anima (QDA)

q.1). We are “metaphysical amphibians”: like the pure intelligences that exist without

matter, the soul of the human being can (and will) exist apart from the body.iii In virtue of

the special features of the human form, arguments have been advanced which interpret

Aquinas as attributing some kind of individuation to the human form. In fact, among

others, this is Joseph Owens= understanding of the Aquinas= writings on the human

soul:

Where a substantial form exists in itself, as in the case of pure spirits, it is an

individual of itself. This doctrine allows form to be something that is individualized

by itself in the case of angelsYBut the same criterion holds in the case of the human

soul, despite the differences in the two types of spiritYEven without the body the

soul continues to be an individual. The individuality stays with the form, and in that

way it can be said to come from the form (p 178).iv

This twinning solution is not a major part of this paper, but twinning is certainly a part

of human embryology that needs to be explained. The major portion of this paper is

devoted to recent laboratory creations. However, the organism as a composite of form

and matter is not incompatible with the solutions that I have put forth as a response to

these recent creations.

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25

i For arguments against the Lockean claim that colocated entities cannot be of the same kind see

Hershenov, David. (2003); Hughes, Christopher. (1997); and Fine, Kit (2000).

ii It should be noted that the form does not exist prior to its unity with matter since if this were

so, the soul=s Aunion with the body would be an accident of the soul: and consequently the

man resulting from this union will not be per se but an accidental being@ (SCG II 58))

iii The term Ametaphysical amphibians@ is from Eleanor Stump (1995).

iv See also Gilson, Etienne (1956). The argument that is made by Gilson (and, in part, by

Owens) is that the individuation of a being is ultimately due to its act of existence, as opposed

to its material dimensions. Gilson writes:

It becomes true to say, then, that every subject has individuation in the same way it

has existence. This is why the individuation survives the death of the body just as

surely as the soul itself does. When the body dies, it is because the soul ceases to

make it exist. But why should the soul cease to exist because of this fact? It does not

receive its being from the body but only from God. And if it keeps its being, how could it

lose its individuation? AThe act-of-being and of individuation always belong

together@YNo doubt, St. Thomas adds, in a significant remark, the individuation of the

soul has some relation to its body, but the immortality of the soul is the immortality of

its esse. The survival of its esse involves as a consequence that of its individuation (p.

190 fn 10).

References

Fine, Kit (2000). A Counterexample to Locke=s Thesis. Monist, 83 (3), 357-361.

Gilson, Etienne. (1956). The Christian Philosophy of Saint Thomas Aquinas. New York: Random House.

Grobstein, Clifford. (1988). Science and The Unborn: Choosing Human Futures. New York: Basic Books.

Hall, J.L. et al. (1993). Experimental Cloning of Human Polyploid Embryos Using an Artificial Zona Pellucida. The American Fertility Society conjointly with the Canadian Fertility Society and Andrology Society, Program Supplement. Abstracts of the Scientific Oral and Poster Sessions, Abstract 0-001, S1.

Haldane, John and Lee, Patrick (2003). Aquinas on Ensoulment and Abortion and the Value of Life. Philosophy, 78, 255-278.

Hershenov, David. (2003). Can There be Spatially Coincident Entities of the Same Kind. Canadian Journal of Philosophy, 31 (1)

Hughes, Christopher. (1997). Same-Kind Coincidence and the Ship of Theseus. Mind, 106 (421), 53-67.

Olson, Eric. (1997). The Human Animal Without Psychology. Oxford: Oxford University Press.

Owens, Joseph. (1994). Thomas Aquinas. In Jorge J.E. Gracia (ed.), Individuation in Scholasticism, The Later Middle Ages and the Counter-Reformation, 1150-1650 (173-194). New York: SUNY.

Smith, Barry & Brogaard, Berit. (2003). 16 Days. Journal of Medicine and Philosophy, (28) 1, 45-78

Unger, Peter. (1992). Identity, Consciousness and Value. New York: Oxford University Press.

Van Inwagen, Peter. (1990). Material Beings. Ithaca: Cornell University Press.