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.

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 ultimatelyclaimed 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 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, andamounts 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 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 complements. These are the product of two types of cells: induced Pluripotent (iPSCs) and Embryonic Stem Cells (eSCs). iPSCsare 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, arecells 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 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.[11]Additionally, 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 changeand 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: 61[14]). 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”, Olson claims, is grounded in a third condition necessary to an organism, “an underlying biochemical structure of unimaginable complexity”[15]This 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 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 ofthe 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.[18]This new substance has itsparts 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 division, what one researcher described as a “light pencilling in of polarity that is gradually engraved as the embryo grows older”.[22]