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

Morris, Jason, “Substance Ontology Can Not Determine the Moral Status of Embryos”. Journal
of Medicine and Philosophy, 2012 Vol. 37 (4) 331-350.
1
2
well.2 There is a seamlessness to a cell's transiting between levels of potentiality; as one
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
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.
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.
3
each of these, like the zygote, can develop into an embryo; the difference is merely
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
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.
7
8
Elaborated by Morris
Morris (2012) p. 7
4
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
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
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.
5
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
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
11
Apart from bundle and trope theory. What is more contentious is to say what things are
substances and what are not.
6
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
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
“Substance”, Stanford Encylopedia of Philosophy,
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.
12
13
7
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”,
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
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.
8
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
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.
9
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 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
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).
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.
10
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
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
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–
723
21
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.
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.
11
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,
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
24
Condic M. (2008), p. 5.
12
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
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
25
Condic, M.L. Alternative sources of pluripotent stem cells: altered nuclear transfer. Cell
proliferation 2008 41 (Suppl 1) 7-19.
26
This is a well documented objection to our having once been zygotes
13
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 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
27
Leese, et al. Embryo Viability and Metabolism: Obeying the Quiet Rules. Human
Reproduction. (2007) 22 (12): 3047-3050.
28 Beddington, Rosa, 1999: ‘Review: Axis Development and Early Asymmetry in
Mammals.’ Cell, 96 (2) pp .195-209.
14
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.
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
29
Van de Velde, et al. 2008.
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.
30
15
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 1015 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
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.
32
Stier and Seifert p. 22
16
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.
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
17
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
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
33
This makes it infinitely easier than bringing something into existence atom for atom.
Condic, M. Alternative sources of pluripotent stem cells: altered nuclear transfer. Cell
Proliferation, p. 10.
34
18
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
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
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.
36
Van Inwagen, Peter. Material Beings (Ithaca: Cornell University Press, 1990).
p. 96
37
P. 96
35
19
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,
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
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”.
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.
38
20
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.
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
40
van Inwagen, p. 96.
21
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). *****
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 postfertilization, 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
22
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
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.
23
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.
24
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).
25
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:
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Haldane, John and Lee, Patrick (2003). Aquinas on Ensoulment and Abortion and the
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Hershenov, David. (2003). Can There be Spatially Coincident Entities of the Same Kind.
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