ANT-OAR: A MORALLY ACCEPTABLE MEANS FOR DERIVING
PLURIPOTENT STEM CELLS. A REPLY TO CRITICISMS
• E. Christian Brugger •
Communio 32 (Winter 2005). © 2005 by Communio: International Catholic Review
“If the cell’s behavior is not commensurate with that of an embryo, the cell is not an embryo.”
In December 2004, Dr. William Hurlbut, physician and professor at Stanford University and a member
of the President’s Council on Bioethics, presented a proposal to the Council entitled “Altered Nuclear
Transfer as a Morally Acceptable Means for the Procurement of Human Embryonic Stem Cells.” 1
Hurlbut’s premise stated that, using modern cloning technology, it may be scientifically possible to
produce embryonic-like (i.e., pluripotent 2 ) stem cells without ever creating and destroying human
embryos. Cloning is accomplished by using somatic cell nuclear transfer (SCNT), in which the nucleus
of a somatic (adult body) cell is removed and transferred into an enucleated oocyte (i.e., an egg cell with
its nucleus removed). The crucial difference between SCNT for purposes of human cloning and SCNT
as proposed by Hurlbut is that in the latter procedure, the genetic material in the somatic cell nucleus is
preemptively altered before nuclear transfer in such a way as to create biological conditions
incompatible with the coming into existence of embryonic human life, but compatible with the
development of pluripotent stem cells. He called his broad conceptual proposal Altered Nuclear Transfer
(ANT).
In June 2005, a group of thirty-five scholars (including ethicists, moral theologians, physicians, and
scientists), including Dr. Hurlbut, published a joint statement proposing a specific type of ANT called
Oocyte Assisted Reprogramming (ANT-OAR). 3 ANT- OAR begins from the assumption that the
identity and function of each cell in the human body depends on the precise interrelation,
communication, and on-off pre-programming of the approximately thirty thousand genes in the cell’s
genome. This condition of cell interaction and expression is called the cell’s “epigenetic state” (or
“genetic imprinting”). The epigenetic state of the single-celled human embryo (or zygote) is totipotent,
that is, it has the developmental capacity to differentiate in an orderly and coordinated way into all the
tissue types necessary for full organismal development, including into the placenta, umbilical cord, and
other extraembryonic tissues. From the perspective of epigenetics, we might say that totipotency defines
a human zygote. It follows that it is reasonable to conclude that where there is a totipotent human cell,
there is a human zygote.
Cloning technology, drawing on this reasoning, has developed a way to “reprogram” the epigenetic state
of a cell. Using SCNT, scientists have observed that the cytoplasm of an enucleated oocyte has a
remarkable capacity to transform the epigenetic state of a transferred diploid nucleus from its original
state to a state of totipotency. The nucleus at the time of transfer has the genetic imprinting of the
differentiated cell type from which it was extracted (e.g., cardiac cell, liver cell, skin cell). After nuclear
transfer into an enucleated oocyte, the epigenetic state is reprogrammed from its formerly highly
specialized state back to a state of totipotency. It goes through a process of epigenetic dedifferentiation.
If it reaches its terminus, the reprogrammed cell is a zygote, a one-celled embryo, with the genotype of
the donor of the somatic cell. It will develop into an adult who is genetically identical to the somatic
cell’s donor. This is how Dolly the sheep was created. 4
Making use of the technique of SCNT, ANT-OAR proposes to utilize the reprogramming capacity of
oocyte cytoplasm. But it intends to do so without ever generating human embryos. We know something
of the molecular mechanisms underlying pluripotent stem cells, including that several transcription
factors are characteristic of the pluripotent state. More than characteristic, certain ones appear to be
essential for establishing and maintaining the state of pluripotency. 5 One such transcription factor (and
only one of a number, all of which individually or in combination, or combined with other genetic
alterations, potentially would be candidates for ANT-OAR) is the homeoprotein Nanog. 6 Its expression
characterizes the unique state of pluripotent cells as neither oocytes nor later differentiated cell types.
Nanog is found expressed in pluripotent stem cells and not expressed in oocytes or single-celled
embryos. When its expression is forced, a cell is not totipotent, but, likewise, cell differentiation is
prevented. When its expression is blocked, cells rapidly begin to differentiate. The Joint Statement
proposes a procedure that combines the reprogramming of the nuclear genome of a somatic cell with
precise genetic alterations forcing the expression of the transcription factor Nanog (or similar factors
that are required for the pluripotent state). The alterations in the nuclear genome would be carried out
prior to nuclear transfer. When the nucleus is transferred into the enucleated oocyte, we create ab initio
a Nanog-expressing cell whose epigenetic character is that of a pluripotent stem cell and incompatible
with zygotic existence. The Joint Statement recommends that ANTOAR be explored first through
experimentation utilizing nonhuman animal cells.
One critic
David L. Schindler, dean and professor of theology at the John Paul II Institute for Studies on Marriage
and Family in Washington, D.C., has accused the 35 signatories of the ANT-OAR proposal of
advancing a “top to bottom” mechanistic account of the origins of human life. 7 His argument goes like
this: the signatories argue that the identity of any particular cell depends on its epigenetic state; if this is
the case, then by altering the epigenetic state of a cell, we can alter the identity of that cell; it follows
that if we make certain precise epigenetic alterations to the genome of a somatic cell nucleus before
transferring it into an enucleated oocyte, the entity that we bring into existence will not be a one-celled
human being (a zygote), but rather its identity will be that of the type of cell whose epigenetics we have
altered it to become, i.e., a pluripotent stem cell. Schindler says this reduces the ontological reality of the
entity brought into existence to its raw epigenetic map. But epigenetics, he says, does not determine the
identity of a cell, it determines only a cell’s observable features, i.e., its phenotype:
Epigenetics can determine only the phenotypical manifestation of the cell whose identity is at
issue, not its (ontological) identity 7 as such. Thus, the mere act of modifying the epigenetic
profile of the OAR product cannot be sufficient to prevent that product from being, or having
been, an incipient human organism. 8
It follows, he concludes, that ANT-OAR fails in what it sets out to produce since the proposal sets forth
a procedure that “is really a means of artificially replicating conception.”
There are two related errors in Schindler’s reasoning. First, he argues that by asserting that the identity
of a cell is determined by a cell’s epigenetic state, ANT-OAR reduces ontology to epigenetics, which he
calls “a classic mechanistic maneuver:”
For what else can we call the confusion of phenotype (based on epigenetics) with substantial
identity upon which the argument for OAR hinges? If, in fact, substantial identity is essentially a
matter of epigenetics, then the organismic whole is no more than the sum of its parts, and the
absence or presence of an organism is simply a matter of reshuffling the epigenetic pieces. 9
Schindler here badly mischaracterizes ANT-OAR. The joint proposal does not assert, and its signatories
would in fact reject, the proposition that “substantial identity is essentially a matter of epigenetics.” The
joint proposal states, and Schindler himself quotes it as stating, that “the nature of each cell depends on
its epigenetic state.” To say a cell’s identity depends on its epigenetic state is not to say a cell’s
“substantial identity” is “no more than” its epigenetic state. Schindler has misinterpreted the joint
proposal as putting forward epigenetic disposition as a sufficient condition for the actualization of
embryonic life, when in fact its authors intended it only as a necessary condition. They do assert that the
identity of a cell depends on the cell’s genetic imprinting, which means that the identity of a one-celled
human embryo too depends on its genetic imprinting. To deny this is to deny the biological basis for
differentiation among cell types in the human body. 10 If cells are not differentiated by their respective
gene expression, what biologically differentiates a skin cell from a liver cell? Not the number of
chromosomes, genes, or nucleotides, nor even the DNA sequence, since in cells from the same person,
these are identical. Rather, there are epigenetic conditions under which a liver cell is able to be a liver
cell, and without which it cannot be a liver cell. Is a liver cell no more than its epigenetic state? No. But
to be what it is depends necessarily (among other things) on that state. So too a zygote has precise
biological conditions under which it is able to be what it is, and without which it cannot come into
existence. Among other things, such conditions include an epigenetic state of totipotency. To assert this
is not to assert that it is no more than its epigenetic state. Its genetic imprinting is a necessary condition,
but not a sufficient condition for its identity as a human being at the zygotic phase of development.
Schindler’s second and related error is philosophical. In denying that epigenetics is a necessary
condition for differentiating a cell’s identity, he implicitly denies that a zygote’s organic bodily material
is necessary for its identity as human. Why is this? Because epigenetics and organic identity are
integrally connected. The epigenetic state of a cell includes the primordial preprogrammed totality of the
activated, inactivated and to be activated and inactivated states of the genes in the cell’s genome. These
epigenetic primordia determine the active potentialities of that cell, 11 including in some cases the
aptitude to be informed by a non-material human soul. A liver, renal, cardiac, immune, or neural cell, as
well as a one-celled human embryo, is what it is, biologically speaking, not because of the presence of
some given organic material per se, but precisely because of that organic material’s active potentialities.
If a human cell has the requisite set of active potentialities to undergo self-directed, human organismic
development, then it is a one-celled embryo. To be sure, an embryo is more than its organic matter and
epigenetic primordia; but without them, an entity is not an embryo. If a cell’s active potentiality is to
function like a liver cell, then it has the nature of a liver cell. And if ab initio it will only ever do what a
liver cell does, then it was ab initio a liver cell. This follows from the 11 principle that the potentialities
of a thing determine the possibilities for that thing’s actuations, and hence its identity. This principle was
first affirmed by Aristotle in his hylomorphic conception of the relationship between body and soul, a
conception Aquinas takes up and develops.
Aristotle holds that matter and form exist together in an individuating, unified relationship. A thing’s
substantial form is what makes the thing the kind of thing it is. It is a thing’s whatness, or essence. 12
Aristotle calls the substantial form in humans the intellectual soul. The human body gets its being as this
kind of body—i.e., a human body, from the soul. Another way of saying this is, the soul is the whole
body’s actuality. (For the Aristotelian-Thomistic hylomorphic tradition, form equals actuality in a thing.)
And so Aristotle writes, “the soul is an actuality of . . . a natural body having life potentially in it.” 13
Saying the same thing, Aquinas writes: “the soul is the primary actuality of a physical body capable of
life.” 14 For the human person, this means the intellectual soul is the actuality of a material body capable
of being a human body (with the presumption here that only living human bodies are, properly speaking
human). 15 What does Aquinas mean when he refers to a body as “capable of life,” and Aristotle when
he says, “having life potentially in it”? Something very specific: in the case of a human being, the body
must have an active potency to be alive in a specifically human way; the body must already be human in
potency: “the actuality of any given thing can only be realized in what is already potentially that thing,
in a matter of its own appropriate to it.” 16 (Matter equals potentiality.) The human soul therefore is the
actuality of some matter already potentially a human being. Only organic material with an active
potential for humanness is informed by an intellectual soul. The constitution of the organic material is a
necessary condition for human life’s actualizability; and the presence of the requisite disposition is
indicative of its state of being already informed by the specifically human form. 17 This means some
organic material precisely because of its active potentialities will be incompatible with the properly
human form of an intellectual soul. The organic material of a liver cell, for example, will be
incompatible. Why? Not because it does not possess a diploid nucleus with a full human genome,
because it does. Rather, because the epigenetic state of that genome excludes the possibility of that cell
doing what humans do at that stage of existence, developing as humans develop, and hence (we
conclude) excludes the possibility of being human, since, as Aquinas says, agere sequitur esse (action
follows being). The organic constitution of a one-celled embryo, on the other hand, is by definition
adequate material. Schindler’s argument fails to understand that it is precisely the character of the
organic material, which includes inter alia the material’s genetic imprinting, that determines the
possibilities for humanness.
Schindler might reply saying he denies nothing of what has just been said about the determining
importance of the character of the material. If we grant him this, it becomes clear that his account of
what constitutes materia apta for the actualization of humanness is badly flawed. He writes:
OAR presupposes an actual fusion of an oocyte and a somatic cell nucleus, and thus mimics
conception. This is true even if the genesis of the new entity and its pluripotent stem-cell-like
manifestation occur simultaneously, or with no apparent time interval at all. What OAR
proponents call the “epigenetic reprogramming” of the somatic cell nucleus by the oocyte might
be more accurately called the pre-planned developmental modification of a human conceptus
(brought about by artificial means). 18
The quote illustrates that at the heart of Schindler’s conception of the conditions for the coming to be of
human life, is the governing erroneous assumption that the fusion of an oocyte and a somatic cell
nucleus, irrespective of the epigenetic character of the so-called “fused” entity, gives rise to a human
embryo. There are two problems with this. First, Schindler’s science is flawed. It is not the “fusion” of a
somatic cell nucleus and an oocyte. There is no nuclear fusion at all. The entity into which the somatic
cell nucleus is transferred, because it has been enucleated, is no longer an oocyte. In fact, it is not even a
cell, but rather an ooplast, a bag of cytoplasm. Transferring an altered nucleus into the ooplast does not
“mimic” conception, since at conception a sperm penetrates an egg, the nuclei fuse, giving rise to a
diploid zygote with a totipotent epigenetic state. Nothing like this is being proposed in ANT-OAR.
Second, if ANT-OAR produced a human embryo, then the entity created would have, or pass
through, a totipotent epigenetic state. But the product of ANT-OAR never is totipotent nor passes
through such a state. This is where Schindler’s governing erroneous assumption imposes itself with
particular force: “ANT-OAR . . . mimics conception . . . even if the genesis of the new entity and its
pluripotent stem-cell-like manifestation occur simultaneously, or with no apparent time interval at all.” 19
In other words, it does not matter if the entity created is pluripotent, it is still an embryo. This belies
scientific fact. A one-celled embryo is by definition totipotent. The entity created by ANT-OAR is ab
initio pluripotent. It therefore cannot be an embryo. But might not it pass, ever so instantaneously,
through a state of totipotency during reprogramming? In principle, no. If Nanog expression (or
expression of some other transcription factor, or combination of transcription factors, or combination of
transcription factors and precise gene modifications, etc.) is definitional of the state of pluripotency; and
forced Nanog expression (or forced expression of . . . ) characterizes ab initio the biological “artifact” 20
that ANT-OAR brings into existence, being intentionally made to do so before nuclear transfer, then the
entity never was totipotent. Further, the reprogramming to a state of pluripotency is not a process of
developmental differentiation beginning with totipotency and moving to pluripotency, as with
embryonic development. It is a process of dedifferentiation moving from the highly specified epigenetic
state of the adult nuclear genome “backwards” (we might say, albeit not without some imprecision) to a
state of pluripotency. It never reaches a state of totipotency, because it is intentionally prevented from
doing so. 21
Schindler may reply: your thesis may work in principle, but how can you ever verify empirically that the
kind of cell ANTOAR produces is not a human embryo? Our answer: the same way we come to know
what any cell type is and is not. We perform a material analysis. We screen and see what genes the cell
expresses. If the genes expressed are characteristic of embryo genes, then we conclude it is a zygote. If
they are not, say they are identical to those expressed in liver cells, then we conclude it is not an embryo
but a liver cell. We also perform a temporal analysis. We observe the cell’s behavior over time. We see
how it acts. If it acts like an embryo we conclude it is an embryo. 22 If it acts like a liver cell, we
conclude it is a liver cell. Schindler writes:
Determination of the presence of life in its most subtle beginnings is precisely not obvious in the
manner of a positivistic fact, but always involves philosophical mediation (even if only
unconsciously). Apprehending life in its most subtle beginnings involves a cognitional act that is
not only empirical but also (at least implicitly) metaphysical in nature, an act which, rightly
exercised, recognizes the mystery characteristic of the organism in its very givenness. . . . God
gives the organism to itself and so creates an originality that by definition we cannot know or
control exhaustively, an originality that we therefore should not attempt or claim to know or
control exhaustively. 23
I see no problem affirming—if I understand Schindler—that we cannot “exhaustively” know and control
the “originality” of life, if by originality he means having its unique, irrepeatable origin ultimately in
God. And certainly we should not attempt to “exhaustively” control human life’s origin. But according
to Schindler’s logic, we can never know through empirical observa-tion—which I take him to mean by
the term “positivistic fact”—that a human cell is or is not a human embryo. This is absurd. We can know
the difference between a one-celled embryo and a liver cell because the cells express different genes and
act differently: agere sequitur esse. If we transplant a liver cell into a female uterus, it does not do what
a human embryo does when transplanted in a female uterus. If the cell’s behavior is not commensurate
with that of an embryo, the cell is not an embryo. To deny that science is able to apprehend such
fundamental biochemical and behavioral cell distinctions, and to apprehend them with certitude, is to
operate from a doubt that can only be termed irrational. Schindler has severed the link between what
something is and our ability to know what it is. This implies an erroneous epistemology, one which
denies that human intelligence, even weakened by sin, can attain to a certain knowledge of reality. 24
Further, if the embryo cannot manifest itself bodily in any observable way, then this implies the embryo
is something other than its body, i.e., that a human being can be present without bodily manifestation.
This is dualism and is inconsistent with sound reasoning and Catholic moral teaching: “it [dualism]
contradicts the Church’s teachings on the unity of the human person, whose rational soul is per se et
essentialiter the form of his body.” 25 John Paul II affirms that the “spiritual and immortal soul is the
principle of unity of the human being, whereby it exists as a whole—corpore et anima unus—as a
person.” 26 If the human person subsists in a body-soul unity, then human activity, including zygotic
activity, will always also be bodily activity. As bodily activity it will be observable and knowable. By
what criteria does Schindler assess the ontological identity of an entity of human origin? What tells him
the ontological identity if not the physical characteristics?
SCNT: ANT-OAR is different
Schindler is worried because the technique used in ANTOAR (namely, SCNT) is the same technique
that is used in human cloning. And in human cloning a one-celled embryo is created. But why do we, or
Schindler, or anyone know that using SCNT for purposes of cloning human embryos does or can create
a human embryo? Because when it is done, we sometimes get an entity that behaves like an embryo. We
know the entity from what it does, and we draw our conclusions accordingly. We will know ANT-OAR
does not create an embryo and therefore does not “mimic conception,” because we do not get an entity
that expresses itself and acts like an embryo. Scientists did not conclude a priori that SCNT
24 25 26
creates embryos; they concluded that it creates embryos because when it was carried out with that
intention, it sometimes worked. If it did not work, nuclear transfer for the purpose of creating pluripotent
stem cells would be, I presume, non-controversial. It seems that Schindler has stigmatized all forms of
nuclear transfer with a sort of mysterious embryo-creating power simply because SCNT for purposes of
cloning human embryos sometimes works. The fact that in ANT-OAR a diploid nucleus is transferred
into an enucleated oocyte is not sufficient ground for concluding the entity that arises possesses the
active potentiality to undergo organized, self-directed development in a way characteristic of a human
being. Parthenotes, teratomas, 27 and certain kinds of hydatidiform moles 28 begin as oocytes with
diploid nuclei. We can even make a hydatidiform mole: enucleate an oocyte and transfer into it the
nuclei of two sperm cells. We get an oocyte with a diploid nucleus. Have we made a zygote? Nor can
Schindler fall back on the ambiguous term “fusing of oocyte and somatic cell nucleus.” We can “fuse”
an enucleated oocyte and a somatic cell nucleus in a high speed blender. Do we get an embryo? The
constituents after all are very much “fused.” We can “fuse” sperm and eggs in a blender. Have we
mimicked conception? No. How do we know? Because we do not get an entity that expresses itself in
any recognizable way like an embryo. But if the “fusion” of sperm and egg in a blender resulted in
entities that behaved like human embryos, if they went on to divide, differentiate, express the
biochemical patterns of human embryos, then we would conclude that such a procedure gives rise to
human embryos. It is absurd to claim that an entity is a human organism when it expresses itself neither
materially nor temporally in ways characteristic of human organisms. As I said, this is dualist; it denies
discernibly human material characteristics to something human; the entity looks, expresses itself, and
behaves like a pluripotent stem cell; it does not express itself in a way characteristic of a human
organism, nor does it have any peculiarly human organismic behavioral characteristics; but it just might
be informed by a human soul. This is like claiming that a human soul might be trapped inside a stone. If
we can distinguish between any cell and a zygote, we should be able to distinguish between an ANTOAR cell and a zygote. 29
Questions need to be answered
Critical questions regarding ANT-OAR’s fitness for producing pluripotent stem cells in a morally
legitimate way need to be answered through initial research using nonhuman animal cells before the
technique is ever tried with human cells. The signatories state: “if, but only if, such research establishes
beyond a reasonable doubt that oocyte-assisted reprogramming can reliably be used to produce
pluripotent stem cells without creating embryos, would we support research on human cells.” 30 The
presence of Nanog and similarly acting transcription factors in oocytes and zygotes will need to be ruled
out. The incompatibility of their expression with embryonic existence will need to be conclusively
established. Present evidence demonstrates that such factors maintain the pluripotency of a stem cell by
preventing cell differentiation; are we sure their forced expression will also prevent cell
dedifferentiation? Another question is, if oocyte cytoplasm is potent enough to reprogram a genome
back to a state of totipotency, is it possible that it will also reprogram the altered gene for Nanog
expression? This problem may be obviated by employing techniques for forcing gene expression that
circumvent the “reprogramming” mechanisms used by oocytes (e.g., forcing RNA expression—the
oocyte does not “reprogram” RNA).
One criticism maintains that the reliability of the method used for detecting Nanog is not sufficient to
establish moral certitude that the entity created through ANT-OAR is not an embryo: “the lack of
detection of Nanog in the zygote does not mean that it is not present. Thus the biological underpinning
of the OAR hypothesis, namely that the zygote differs from the morula or ICM cells of the blastocyst
because it lacks Nanog, cannot be proven with moral certainty.” 31 This criticism raises a general
question worth asking. Can any scientific protocol be developed that delivers results precise and
consistent enough to establish beyond a reasonable doubt that the entity created through ANT-OAR is or
is not a human embryo? This question brings us back to the fundamental doubt as to whether science is
capable of apprehending the difference between different types of cells. I called the doubt “irrational”
since its affirmation implies a denial that science, and by implication the reasoning that derives from
sensible observation, can know things with certitude. Although the methodological exactitude of any
proof will be limited by the inherent epistemological constraints imposed by the subject matter, and in
the case of the scientific method we operate in the domain, not of doubtless certitude as in the domain of
divine Revelation, but of statistical certitude in which doubt is never ruled out; nevertheless, it is
possible to have certitude beyond a reasonable doubt (i.e., moral certitude) that the entity created
through ANTOAR is not an embryo. Reasonable doubt is expelled through a process of rigorous
material and temporal analysis of the product of the technique. If there is sufficient evidence in animal
experimentation to rule out a reasonable doubt that an embryo comes into existence through ANT-OAR,
then we proceed to human cell experimentation.
Another related question might be asked: having established that the expression of a desired
transcription factor or factors is categorically incompatible with embryonic existence, what is the
possibility that in testing for the expression of that transcription factor the method will deliver false
positives? This too will need to be addressed during experimentation using nonhuman animal cells.
Rigorously testing the products of ANT-OAR will enable us to reliably establish the probability of
methodological test failure. If failure rates are statistically negligible, and testing otherwise consistently
establishes that the entity produced from ANT-OAR is not an embryo but a pluripotent cell; and the firm
intention is to protect the value of human life by never producing a human organism; then it may be
reasonable to proceed with testing in human cells knowing that a very remote possibility exists that an
embryo may result; that 31 possibility is accepted as an unwanted and unintended side effect of an
otherwise morally justifiable act. By analogy, women are sometimes prescribed estrogen pills for the
regulation of the menstrual cycle. One activity of orally administered estrogen can be to render a
woman’s uterine lining inhospitable to a nidating embryo, in the rare instance of a breakthrough
ovulation and subsequent fertilization. Knowing this, many Catholic moral theologians agree that for
serious reasons the choice of a woman, even a sexually active married woman, to take estrogen pills for
purposes of cycle regulation can be legitimate, if a contraceptive intent is excluded.
E. CHRISTIAN BRUGGER is assistant professor of theology at the Institute for the Psychological
Sciences in Arlington, Virginia.
1
Hurlbut published an expanded version of the essay with the same title in Perspectives in Biology and
Medicine 48, no. 2 (Spring 2005): 211–228; for a synopsis of the idea, see Hurlbut’s interview with Jennifer Lahl,
National Director of the Center for Bioethics and Culture Network, entitled “Altered Nuclear Transfer: Is it the
Answer for the Embryonic Stem Cell Research Debate?” available at www.cbc-network.org.
I would like to acknowledge the assistance of Dr. Hurlbut; Dr. Maureen Condic of the Department of
Neurobiology and Anatomy at the University of Utah School of Medicine; Thomas Berg, L.C., Executive
Director of the Westchester Institute; and Dr. Michael Augros of the Center for Higher Studies of the Legion of
Christ for their assistance in preparing this essay.
2
“Pluripotency” is the capacity of a cell to develop into all the various tissue types of the human body. It is
important to note that presently no useful embryonic stem cell-based therapies exist. Nonetheless, many scientists
believe that embryonic stem cells, because of their pluripotency, promise to provide important tools for the study
of disease, and possibly to provide cells and tissues for groundbreaking medical therapies.
3
The joint statement was published as: “Production of Pluripotent Stem Cells by Oocyte-Assisted
Reprogramming: Joint Statement with Signatories,” National Catholic Bioethics Quarterly 5, no. 3 (Autumn
2005): 579–583. It should be emphasized that the proposal called for initial research using only nonhuman animal
cells. Only in the case that such research established beyond a reasonable doubt that ANT-OAR could reliably be
used to create pluripotent stem cells without creating embryos would its signatories support research using human
cells. Signatories include: Hadley Arkes, Ph.D., Amherst College; Rev. Nicanor Pier Giorgio Austriaco, O.P.,
Ph.D., Providence College; Rev. Thomas Berg, L.C., Ph.D., The Westchester Institute for Ethics and the Human
Person; E. Christian Brugger, D. Phil., Institute for Psychological Sciences; Nigel M. de S. Cameron, Ph.D.,
Institute on Biotechnology and the Human Future and Chicago-Kent College of Law, Illinois Institute of
Technology; Joseph Capizzi, Ph.D., Catholic University of America; Maureen L. Condic, Ph.D., University of
Utah, School of Medicine; Samuel B. Condic, M.A., University of Houston; Rev. Kevin T. FitzGerald, S.J.,
Ph.D., Georgetown University Medical Center; Rev. Kevin Flannery, S.J., D.Phil., Pontifical Gregorian
University; Edward J. Furton, Ph.D., The National Catholic Bioethics Center; Robert P. George, J.D., D.Phil.,
Princeton University; Timothy George, Th.D., Samford University; Alfonso Gómez-Lobo, Dr. phil., Georgetown
University; Germain Grisez, Ph.D., Mount Saint Mary’s University; Markus Grompe, M.D., Oregon Stem Cell
Center; John M. Haas, Ph.D., The National Catholic Bioethics Center; Robert Hamerton-Kelly, Th.D., Stanford
University; John Collins Harvey, M.D., Ph.D., Georgetown University Medical Center; Paul J. Hoehner, M.D.,
M.A., FAHA, The University of Virginia Graduate School of Arts and Sciences; William B. Hurlbut, M.D.,
Stanford University; John F. Kilner, Ph.D., The Center for Bioethics and Human Dignity; Patrick Lee, Ph.D.,
Franciscan University of Steubenville; William E. May, Ph.D., John Paul II Institute for Studies on Marriage and
Family at The Catholic University of America; Rev. Gonzalo Miranda, L.C., Ph.L., S.T.D., Regina Apostolorum
Pontifical Athenaeum; C. Ben Mitchell, Ph.D., Trinity International University; Most Reverend John J. Myers,
J.C.D., D.D., Roman Catholic Archbishop of Newark, New Jersey; Chris Oleson, Ph.D., Center for Higher
Studies Thornwood, New York; Rev. Tad Pacholczyk, Ph.D., The National Catholic Bioethics Center; Rev. Peter
F. Ryan, S.J., S.T.D., Mount St. Mary’s University; William L. Saunders, J.D., The Family Research Council;
David Stevens, M.D., M.A., Christian Medical & Dental Associations; Rev. Msgr. Stuart W. Swetland, S.T.D.,
The Newman Foundation; M. Edward Whelan III, J.D., Ethics and Public Policy Center; Rev. Thomas Williams,
L.C., Ph.L., S.T.D., Regina Apostolorum Pontifical Athenaeum.
4
It should be noted that such reprogramming is highly inefficient, with typically only 0.1-1% of all transferred
nuclei producing a live birth.
5
A transcription factor is a protein that helps regulate gene expression by binding to the gene and aiding and
directing transcription of the gene’s DNA into RNA. For gene expression to be complete the RNA needs to be
further translated into its corresponding protein.
6
Nanog is just one of a number of transcription factors that have been shown to be essential in maintaining the
pluripotency of inner cell mass cells; for two essays on Nanog’s activity, see Hatano, Shin-ya, Masako Tada, et
al., “Pluripotential competence of cells associated with Nanog activity,” Mechanisms of Development 122 (2005),
67–79; and Mitsui, Kaoru, Yoshimi Tokuzawa, et al., “The Homeoprotein Nanog Is Required for Maintenance of
Pluripotency in Mouse Epiblast and ES Cells,” Cell 113 (30 May 2003): 631–642.
7
David L. Schindler, “A Response to the Joint Statement, ‘Production of Pluripotent Stem Cells by Oocyte
Assisted Reprogramming,’” Communio: International Catholic Review 32, no. 2 (Summer 2005): 369-380. Part II
of the Spring 2005 issue of Communio (vol. 32, no. 1) is dedicated to Hurlbut’s original ANT proposal; Schindler
and Adrian J. Walker criticize Hurlbut’s proposal in two essays; Nicanor Pier Giorgio Austriaco, O.P., offers a
reply. Although several of the arguments and concomitant errors leveled against ANT by Schindler and Walker
correspond to those formulated in Schindler’s later essay, “A Response to the Joint Statement,” my intention in
this essay is to criticize only Schindler’s later essay.
8
Schindler, “A Response to the Joint Statement,” 371–372.
9
Ibid., 372.
10
Nicanor Austriaco, O.P., writes: “if we follow Schindler’s logic, any human cell—a skin cell, a liver cell, or
a kidney cell—regardless of its ‘phenotypical manifestation’ could be ontologically equivalent to a single-cell
embryo” (“Are Teratomas Embryos or Non-Embryos? A Criterion for Oocyte-Assisted Reprogramming,” The
National Catholic Bioethics Quarterly 5, no. 4 [Winter 2005]: 705f).
11
Austriaco discusses the concepts of active and passive potentialities in reference to ANT in “Altered
Nuclear Transfer: A Critique of a Critique,” Communio: International Catholic Review 32, no. 1 (Spring 2005):
172–176.
12
Aristotle, Metaphysics, bk. VII, no. 10, 1035b14, tr. W. D. Ross, in The Complete Works of Aristotle, ed.
Jonathan Barnes, vol. 2 (Princeton, N.J.: Princeton University Press, 1984), 1635. Aquinas will also say that one
sense of “form” is the “what it is” of a thing, its essence or quiddity, which would include its matter taken
universally, like “flesh and bones” in the case of man. Other times, however, Aristotle and Thomas will use
“substantial form” to mean only one part of a thing’s essence. A natural substance is composed of both matter and
form, and neither of these alone is what that substance is—a man is not just a soul. At Metaphysics VI, bk. 1,
1025b29–35, for example, Aristotle insists that the “what” of a natural thing must always include matter. I thank
Dr. Michael Augros for pointing this out to me.
13
Aristotle, De Anima, bk. II, no. 1, 412a27, tr. J. A. Smith, in The Complete Works of Aristotle, ed. Jonathan
Barnes, vol. 1 (Princeton, N.J.: Princeton University Press, 1984), 656.
14
Aquinas, Commentary on Aristotle’s De Anima, bk. II, lecture IV, par. 271, tr. Kenelm Foster, O.P., and
Silvester Humphries, O.P. (Notre Dame, Ind.: Dumb Ox Press, 1994), 88.
15
Aquinas asserts that at death, when life passes from the body, a substantial change takes place; the body is
no longer, properly speaking, a human body, except in an equivocal sense; the eyes and flesh of a corpse are only
equivocally referred to as human eyes and human flesh since neither possesses its proper operation qua human.
He says this in response to Platonic dualism, which holds that since the soul is united to the body as a driver is to
a machine, the body is what it is apart from the soul; therefore at death, when the soul departs, the body remains a
human body and its parts human body parts; see Aquinas, Summa Contra Gentiles (SCG), bk. II, ch. 57, no. 10, tr.
James F. Anderson (South Bend, Ind.: University of Notre Dame Press, 1975), 171.
16
Aristotle, De Anima, bk. II, 414a25.
17
The idea of materia apta is not that we have, in one instance, the proper organic matter, and then the soul
that comes to inform it, but rather, evidence of a characteristically organismal disposition of the matter bespeaks
the presence of the in-forming substantial human form.
OAR presupposes an actual fusion of an oocyte and a somatic cell nucleus, and thus mimics conception. This
is true even if the genesis of the new entity and its pluripotent stem-cell-like manifestation occur simultaneously,
or with no apparent time interval at all. What OAR proponents call the “epigenetic reprogramming” of the
somatic cell nucleus by the oocyte might be more accurately called the pre-planned developmental modification
of a human conceptus (brought about by artificial means). 18
18
Schindler, “A Response to the Joint Statement,” 371.
19
Ibid.
20
In his original proposal for ANT, Hurlbut uses the term “biological artifact” to refer to the entity created by
the method, an entity, he says, “with no inherent principle of unity, no coherent drive in the direction of the
mature human form, and no claim on the moral status due to a developing human life” (William B. Hurlbut,
“Altered Nuclear Transfer as a Morally Acceptable Means for the Procurement of Human Embryonic Stem
Cells,” 225).
21
Edward Furton makes this point against Schindler’s argument; see Edward J. Furton, “A Defense of OocyteAssisted Reprogramming,” The National Catholic Bioethics Quarterly 5, no. 3 (Autumn 2005): 467.
22
The idea that we know what a thing is by observing how it behaves is more fully developed in Maureen L.
Condic and Samuel B. Condic, “Defining Organisms by Organization,” The National Catholic Bioethics
Quarterly 5, no. 2 (Summer 2005): 331–353, esp. 339–340.
23
Schindler, “A Response to the Joint Statement,” 375.
24
John Paul II rejects this view in his 1998 encyclical Fides et ratio; there he strongly affirms “the human
capacity to know the truth, to come to a knowledge which can reach objective truth by means of that adaequatio
rei et intellectus to which the Scholastic Doctors referred” (82, Vatican translation). Vatican II also teaches:
“intelligence is not confined to observable data alone, but can with genuine certitude attain to reality itself as
knowable, though in consequence of sin that certitude is partly obscured and weakened” (Gaudium et spes, 15,
Vatican translation).
25
John Paul II, Veritatis splendor (1993), 48, Vatican translation. Emphasis original.
26
Ibid.
27
Austriaco, “Are Teratomas Embryos or Non-Embryos?”
28
Condic and Condic, “Defining Organisms by Organization,” 341–342.
29
I am indebted to Maureen Condic for several of the ideas set forth in the preceding two paragraphs.
30
“Production of Pluripotent Stem Cells by Oocyte-Assisted Reprogramming: Joint Statement with
Signatories,” The National Catholic Bioethics Quarterly 5, no. 3 (Autumn 2005): 579.
31
Women for Faith and Family, “Is Oocyte Assisted Reprogramming (OAR) A Moral Procedure To Retrieve
Embryonic Stem Cells?” (15 August 2005, updated 22 September 2005), available at www.wff.org/OAR_StemCells.html .
REASONABLE DOUBTS. A REPLY TO E. CHRISTIAN BRUGGER
Adrian J. Walker
Communio 32 (Winter 2005). © 2005 by Communio: International Catholic Review
“Schindler, and not Brugger, is the real Aristotelian here.”
1.
E. Christian Brugger devotes a considerable portion of his essay”ANT-OAR: A Morally Acceptable
Means for Deriving Pluripotent Stem Cells. A Reply to Criticisms” 2 to responding to David Schindler’s
critique of the OAR proposal in the pages of Communio. 3 Brugger singles out for particular rebuttal
Schindler’s claim that supporters of OAR have not yet given us sufficient assurance that the procedure
would not produce human embryos. As Brugger reads him, Schindler is demanding more evidence on
this score than he can reasonably ask for. His interrogation of OAR, lacking any sound scientific or
philosophical foundation, rests instead on an irrational, ultimately dualistic unwillingness to let the
physical evidence garnered in laboratory experiments decide whether OAR produces embryos or not:
It is absurd to claim that an entity is a human organism when it expresses itself neither materially
nor temporally in ways characteristic of human organisms. As I said, this is dualist; it denies
discernibly human material characteristics to something human; the entity looks, expresses itself,
and behaves like a pluripotent stem cell; it does not express itself in a way characteristic of a
human organism, nor does it have any peculiarly human organismic behavioral characteristics; but
it just might be informed by a human soul. This is like claiming that a human soul might be
trapped inside a stone. If we can distinguish between any cell and a zygote, we should be able to
distinguish between an ANT-OAR cell and a zygote. 4
Brugger boils Schindler’s position down to this: there are serious grounds for thinking that OAR
produces embryos even if the OAR product “looks, expresses itself, and behaves like a pluripotent stem
cell.” Unfortunately, Brugger is setting up a straw man here, for Schindler’s actual contention is
precisely that the OAR product does not and cannot look and act like a pluripotent stem cell in at least
one decisive respect: its coming into being. For if we compare OAR with SCNT, Schindler insists, we
find that OAR uses exactly the same event—exactly the same fusion of an enucleated egg and a somatic
cell nucleus—that SCNT uses to clone a human embryo. What Schindler is really asserting, then, is that,
even if the OAR product looks and acts more or less like a pluripotent stem cell in other respects, its
coming into being looks and acts sufficiently like the coming into being of a human embryo to raise
serious questions about OAR. Far from asserting that physical tokens in general are irrelevant to
distinguishing embryos from stem cells, Schindler is simply insisting that there is one physical token
that trumps all the others in the particular case of OAR: has the new entity come into being in a
sufficiently human species-specific way? In the following essay, I would like to restate and defend
Schindler’s reasons for thinking that OAR supporters have not yet ruled out a Yes answer.
2.
As just noted, Schindler’s critique of OAR in the first part of his essay rests on the claim that OAR
involves the same fusion of an enucleated oocyte and a somatic cell nucleus as cloning does. One
element of Brugger’s response is based either on a misquotation of Schindler’s text or on Brugger’s
reliance on a draft version of the article. His citation from Schindler refers in one place to a “fusion of an
oocyte,” without the adjective “enucleated,” 5 which is duly present in the published text. Brugger tries
to make the case that Schindler’s insistence on the notion of “fusion” betrays an ignorance of the basic
scientific structure of OAR: “[i]t is not the ‘fusion’ of a somatic cell nucleus and an oocyte,” 6 Brugger
reminds us. This is correct, of course, but it does not affect Schindler’s point in the least, which is that
the fusion in question is the fusion of an enucleated egg cell and a somatic cell nucleus, as in SCNT. 7 In
Schindler’s view, this fusion is prima facie a “mimicked conception,” not because its mechanics are the
same as in natural conception, where “a sperm penetrates an egg, [and] the nuclei fuse, giving rise to a
diploid zygote with a totipotent epigenetic state,” 8 but because its result is the same—as the (admittedly
rare) successes of SCNT show can be the case. Obviously, OAR is not in vitro fertilization. Schindler’s
question is simply whether, given its dependence on the same fusion of cellular materials as SCNT
depends on, OAR might not be cloning. One may think that Schindler’s answer to this question is
wrong, but one has to refute his arguments, rather than ruling them out of court as resting on flawed
science. What, then, are these arguments?
3.
Schindler’s claim that OAR involves “mimicked conception” is not a description of the stated intent of
the OAR proposal, but rather the conclusion of an argument that goes like this. If SCNT fuses an
enucleated oocyte and a somatic cell nucleus to produce an embryo—to “mimic conception” as to result,
though not as to method—and if OAR can succeed only under the same conditions under which SCNT
succeeds, then OAR prima facie involves a “mimicked conception,” too. The force of this argument
rests on Schindler’s demonstration that epigenetic modification of the cellular materials, pre-transfer or
no, is not sufficient to guarantee, beyond a reasonable doubt, that the procedure does not involve the
creation and/or destruction of embryos. In his rebuttal, Brugger offers two arguments against this
demonstration, one scientific and one philosophical. Both, I will suggest, do not suffice to vitiate the
prima facie appearance that OAR is a form of cloning. In explaining why this is so, I will also be
restating what I take to be the core of Schindler’s argument that “epigenetics is not enough.”
(1) Brugger’s scientific counter-argument is that the zygotic epigenetic state, while not a sufficient
condition for the existence of a new human individual, is certainly a necessary condition of it. The
zygotic epigenetic state is, or is co-essential with, the materia apta, the requisite material platform for
the actualization of a new human individual (more on the materia apta below). By the same token, he
would argue, if, prior to transfer, we can prevent the epigenetic reprogramming action of the enucleated
oocyte from yielding a zygotic epigenetic state, then we can effectively remove this platform and, in so
doing, prevent any human individual from ever coming into existence in the first place. Conversely, if
we can ensure that the enucleated egg’s reprogramming action results in a pluripotent stem-cell-like
epigenetic state, then we can create an entity that, ab initio, was never a human embryo, but always a
human pluripotent stem cell:
A one-celled embryo is by definition totipotent. The entity created by ANT-OAR is ab initio pluripotent.
It therefore cannot be an embryo. But might it not pass, ever so instantaneously, through a state of
totipotency during reprogramming? In principle, no. If Nanog expression (or expression of some other
transcription factor, or combination of transcription factors and precise gene modifications, etc.) is
definitional of the state of pluripotency; and forced Nanog expression (or forced expression of . . .)
characterizes ab initio the “biological artifact” that ANTOAR brings into existence, being intentionally
made to do so before nuclear transfer, then the entity never was totipotent. 9
The main problem with Brugger’s argument here is that it overlooks the fact that there is an interval of
time between (1) the fusion of the enucleated oocyte and the somatic cell nucleus and (2) the completion
of the reprogramming process. 10 One implication of the existence of this interval is that the enucleated
oocyte cannot carry out its epigenetic reprogramming without first fusing with the somatic cell nucleus
into a new cell. Brugger notwithstanding, OAR is not literally a form of direct cellular dedifferentiation,
but the creation of a new cell that is the suppositum, the “ontological subject,” both of the
reprogramming process and of whatever epigenetic states that process eventually results in. 11 The
fusion of the cellular materials results, in other words, in an entity that puts itself in the zygote epigenetic
state through self-directed action. In other words, the simplest interpretation of the facts is that a new
human being has come into existence and is running itself through the epigenetic reprogramming
process. 12 But the OAR proposal aims to modify only the outcome of this process. For the same reason,
it leaves completely open the possibility that the procedure has created a human embryo with a defective
developmental path. The fact that OAR programs-in modifications in its product’s epigenetic state
before nuclear transfer does not affect this situation in the least. Since these modifications would
actually take effect only at the end of the logical sequence of fusion—new cell—initiation of
reprogramming process, programming them in before nuclear transfer does not guarantee that there was
no embryo at the beginning of that sequence. Brugger’s insistence that OAR modifies prior to nuclear
transfer turns out to be something of a red herring. 13
(2) Brugger bases his philosophical argument againstSchindler on the Aristotelian-Thomistic notion
of materia apta, the material organization required as a platform to sustain a given substantial form.
According to Brugger, materia apta provides this platform because it is the seat of what he calls the
“active potencies” that enable the substantial form to display its characteristic operations in the given
matter. On Brugger’s account, however, the zygotic epigenetic state is definitive of the materia apta for
humanness and so determines the “active potencies” for the behavior characteristic of human organisms.
14
By the same logic, suppressing the OAR product’s zygotic epigenetic state deprives it of the platform
for the active potencies of humanness—and so deprives it of its human status. If this suppression can be
made to coincide with the new entity’s coming into being through pre-transfer biochemical modification
of what will be its initial epigenetic state, then, by the same logic, it will never have been a human
organism at all. Since agere sequitur esse, Brugger reasons, the prevention of the materia apta for the
active expression of a human being’s characteristic operations is necessarily the prevention of the
genesis of any human being in the first place.
There are two main problems with Brugger’s argument here. (i) First, Brugger’s invocation of the
Aristotelian-Thomistic doctrine of materia apta misses the point. Schindler is not denying this doctrine,
but claiming that the fusion of the enucleated oocyte and the somatic cell nucleus itself already provides
a sufficient materia apta for the existence of a human being. Brugger fails to address the crucial
question, which is not whether or not OAR can modify the outcome of epigenetic reprogramming, but
whether or not such modification is by itself sufficient to rule out the creation of a new human embryo.
(ii) This brings me to the second problem with Brugger’s philosophical argument, which is that it comes
perilously close to overturning the Aristotelian-Thomistic priority of act over potency, especially when
Brugger faults Schindler for failing to understand that “it is precisely the character of the organic
material, which includes inter alia the material’s genetic imprinting, that determines the possibilities for
humanness.” 15 As far as I can tell—and it is difficult to tell because his argument is vague and tangled
here—Brugger seems to be confusing the active potencies, as nature-rooted powers, with the material
basis of their expression, and then taking the latter as quasi-constitutive for human identity. But if active
potencies flow from actualized natures, and not vice versa, then the absence/modification of the zygotic
epigenetic state is not by itself sufficient to dispose of the question Schindler has raised. It leaves
completely open the possibility that OAR creates embryos with developmental defects set to go off
already in the zygotic stage of their existence. And so we find ourselves back at square one.
4.
The scientific and philosophical battering rams that Brugger deploys to knock down Schindler’s doubts
against OAR leave them not only unbowed, but also unbloodied. Let me briefly explain why I do not
think that any possible arguments would be enough to dispel them.
Normal conception follows a certain logical-temporal sequence: first, the process of fertilization and the
concomitant coming-into-being of a new human individual, and then the initiation of the epigenetic
reprogramming process. 16 SCNT also follows this process, except that it substitutes the fusion of an
enucleated egg and a somatic cell nucleus for fertilization—which is why Schindler speaks of a “mock
fertilization” in this context. 17 Now, OAR, as a form of SCNT, also replicates this pattern. It differs
from normal SCNT in one respect only: it tries (prior to transfer) to get the epigenetic reprogramming
process to move towards a pluripotent stem cell-like epigenetic state. Is this enough to distinguish OAR
from cloning? Since, in the normal case, the zygotic epigenetic state logically presupposes the
fertilization event that constitutes a new human being as the suppositum of that state, the mere premature
forcing of transcription factors associated with the epigenetic state of pluripotent stem cells is not by
itself sufficient to ensure that OAR involves no “mock fertilization,” and so cannot guarantee an
affirmative answer to this question. In order to deliver a warranted Yes, OAR would have to change the
entire pattern of fusion—new entity—reprogramming, rather than just modifying the outcome of the last
element in the series.
The problem, of course, is that, if OAR hopes to get stem cells, it has to use nuclear transfer, and if it
uses nuclear transfer, it can only modify the outcome of the reprogramming process, while working
within the overall fusion—new entity—reprogramming pattern. Thus, whatever OAR may do to the
terminus ad quem of the reprogramming process, the terminus a quo has to remain substantially what it
is—and therefore what it would be in successful cloning as a “mock fertilization.” Yes, indeed: in
SCNT, as in general, agere (the epigenetic reprogramming process/resulting zygotic epigenetic state)
sequitur esse (the nature of the entity established through “mock fertilization”) and the problem with
OAR—its inherent conceptual flaw—is that it tacitly relies on this sequitur while claiming to have
dispensed with it. The only way to justify, or not notice, this contradiction is to make the fallacious
inference that, since agere sequitur esse, any change in agere is automatically a change in esse. 18 To
reason in this way—as Brugger appears to do—amounts either to question-begging or a mechanistic
reduction of agere to esse. In either case, the principle gets turned on its head, and agere sequitur esse
comes to mean esse sequitur agere.
What I have called OAR’s conceptual flaw is not superficial, for it sits in the very attempt to get stem
cells without embryos while using nuclear transfer to do it. Nor can scientific experimentation remedy
this inner contradiction in the OAR proposal. The reason for this is not that experimental testing in itself
is worthless. It is that the construction of the experiments for testing OAR will necessarily partake of the
OAR proposal’s conceptual flaw, and so will either bypass the central issue—when is a human organism
actually present?—or yield outcomes that can appear favorable only on the assumption of some form of
mechanism. I am not suggesting, of course, that we should move the discussion to a purely theoretical
plane, without any reference or deference to the empirical phenomena. I am rather suggesting that
OAR—and so the experiments designed to test it—focuses on the wrong set of empirical phenomena
and then justifies this wrong focus with untenable arguments. I am suggesting, in other words, that OAR
has a built-in, fatal neglect of what may be the one decisive phenomenon in the present context: the
fusion of the enucleated egg and the somatic cell nucleus that, very arguably, establishes a human esse
whose agere OAR modifies in its expression, but not in its substantial basis. Even if OAR succeeds in
producing a pluripotent epigenetic state, then, there remain serious reasons for doubting whether it has
not obtained it on the back of an embryo. 19
If I am right, Schindler and Brugger, or, more generally, the editors of Communio and the signers of
the Joint Statement in favor of OAR, do not disagree because the former foolishly deny the principle of
agere sequitur esse, while the latter sensibly defend it. No, both parties agree about the centrality of
agere sequitur esse, but differ as to when they think it starts to be relevant: with fertilization or its
“mock” equivalent, the fusion of enucleated egg and somatic cell nucleus (the editors of Communio), or
only on the completion of epigenetic reprogramming (OAR supporters)? Moreover, although the two
answers are symmetrical in their intention to privilege the agere sequitur esse principle, they are not at
all symmetrical in their respective fidelity to it. Interpreting epigenetic reprogramming as a teleological
self-unfolding revelatory of an already-existing human organism, the first answer expresses the
Thomistic principle to a tee, whereas the attempt to establish the second answer and vitiate the first ends
up with an inversion of this principle that logically requires question-begging and/or mechanism. The
tables, in other words, have been completely turned, and it turns out that Schindler, and not Brugger, is
the real Aristotelian here. For Schindler is not, as Brugger asserts, dualistically ignoring the human
body, 20 but arguing that proponents of OAR are—and, that, in so doing, they are unwittingly colluding
in the erosion of respect for that body in the earliest stages of its existence.
5.
In conclusion, I would like to point out that, even if the argument I have just outlined is shown to be
mistaken, and the concept of OAR is not problematic from the point of view of natural philosophy and
morality, the fact remains that the procedure will not be 100 percent reliable. Even if I am dead wrong in
the foregoing essay, in other words, OAR will still occasionally mistakenly produce embryos. 21 Now,
Brugger admits this, but he argues that, so long as the incidence of mistaken embryos is “statistically
negligible,” there can be no reasonable doubts about the morality of OAR. Why not? Because the
intention not to produce embryos can justify the risk of occasionally mistakenly producing some by the
principle of double effect, as Brugger explains in the following passage:
If failure rates are statistically negligible, and testing otherwise consistently establishes that the
entity produced from ANTOAR is not an embryo but a pluripotent cell; and the firm intention is to
protect the value of human life by never producing a human organism; then it may be reasonable
to proceed with testing in human cells knowing that a very remote possibility exists that an
embryo may result; that possibility is accepted as an unwanted and unintended side effect of an
otherwise morally justifiable act. 22
There are two serious problems with this argument, it seems to me. First of all, even if we were to
suppose that it is statistically very unlikely that OAR would mistakenly produce an entity that even
Brugger would call an embryo, a supposition that is not at all clear given the highly speculative nature of
the OAR proposal, the fact of the matter is that no one could be sure that it would not produce such an
entity—until it was too late. Imagine a parallel situation: a friend gives you a gun with 20,000 chambers
and invites you to play Russian Roulette with the assurance that only two or three of the chambers are
actually loaded. Since any given chamber might be loaded, you would be foolish to accept the challenge
on the grounds that the odds were seemingly in your favor. After all, the first pull of the trigger might
put one of the 3/20,000 bullets into your skull. Would it not be just as foolish to pursue human OAR,
since on any given trial you might be making an embryo-producing mistake? Wouldn’t trying human
OAR be tantamount to playing Russian Roulette with embryos?
My second problem is with Brugger’s invocation of the principle of double effect. While double
effect does legitimate the knowing risk of side-effects otherwise impossible to be chosen ethically, it
does not do so in just any situation. It confers this legitimacy only in view of abnormal circumstances
that pressingly require or recommend the action to which the knowing risk of otherwise unchooseable
side-effects is inevitably attached. Since the—let us be perfectly honest—remote possibility that the
scientific community may one day give up conventional methods of embryonic stem cell research for
something like OAR, or the less remote, but still distant, potential for medical advances, does not meet
this test of urgency, the principle of double effect has no real relevance to Brugger’s case. But if double
effect does not apply here, then what Brugger’s argument logically amounts to is this: a possible future
good (the conversion of the scientific community; potential medical advances) justifies a present evil
(the possibility of accidentally making a “statistically negligible” number of embryos). This sort of
argument logically entails, or expresses, something less like traditional Catholic moral theology and
more like proportionalism. Does Brugger really want to go this route?
6.
Brugger’s precipitous appeal to double effect bears out, it seems to me, the pertinence of one of the
central questions of Schindler’s essay that Brugger nowhere addresses: whence the haste to make ANTOAR work—even at the (supposedly acceptable) risk of possibly sacrificing a few human lives? Is it
really so important to assure embryonic stem cell researchers that they can have what they want, after
all? Wouldn’t it be better to put the brakes on the ANTOAR project, at least for a while, and to ponder
the implications of what, I hope to have shown, are not at all irrational cavils, but strong and serious
reasonable doubts about its conceptual and moral viability? It strikes me that advocates of ANT-OAR
have nothing to lose and everything to gain by doing so.
1
I would like to thank Dr. W. Malcolm Byrnes for invaluable criticisms of an earlier draft of this essay. Of
course the claims I express here, as well as the mistakes I might make, are mine, and not Dr. Byrnes’s.
2
E. Christian Brugger, “ANT-OAR: A Morally Acceptable Means for Deriving Pluripotent Stem Cells. A
Reply to Criticisms,” Communio 32, no. 4 (Winter, 2005): 753–769.
3
In particular, Brugger is replying to David L. Schindler, “A Response to the Joint Statement, ‘Production of
Pluripotent Stem Cells by Oocyte Assisted Reprogramming,’” Communio 32, no. 2 (Summer, 2005): 369–380.
4
Brugger, “ANT-OAR: A Morally Acceptable Means,” 766–767. Emphasis original.
5
Cited in Brugger, “ANT-OAR: A Morally Acceptable Means,” 762.
6
Ibid.
7
As Brugger insists, the egg used in nuclear transfer is an enucleated one, with only its cytoplasm left. But
that is just the point: the egg is enucleated so that the somatic cell nucleus—which has been detached from its
cytoplasm—can receive a new cytoplasm so as to form a single cell. If no such fusion of the enucleated egg and
the somatic cell nucleus into a new cell took place, then OAR proponents would be in the difficult position of
maintaining the—frankly absurd—claim that OAR has the (magical?) power to turn this nucleus, which is itself
not a cell, but a part of one, into a whole cell complete with a new cytoplasm.
Brugger, “ANT-OAR: A Morally Acceptable Means,” 762.
Brugger, “ANT-OAR: A Morally Acceptable Means,” 762–763. Emphasis original.
10
I am indebted for this valuable insight, as well as for much that I will say in the present paragraph, to José
Granados, “ANT-OAR: Is Its Underlying Philosophy of Biology Sound?” in the present issue of Communio. It
should be pointed out that, even if the time of the interval mentioned here is reduced to a seeming zero, the doubt
that OAR produces an embryo remains as alive as before. Why? Because the time interval reflects a deeper
logical sequence of defining events that come in the following order: fusion of the relevant cellular materials,
initiation of the reprogramming process, formation of the “zygotic” epigenetic state. OAR has to work with this
logical sequence, no matter how much it shortens the time between the stages: it needs the fusion of the cellular
materials to have the reprogramming process, and it needs the reprogramming process to end up with (it hopes)
pluripotent stem cells. According to Schindler, this shared sequence indicates enough identity with cloning to
raise serious doubts whether OAR does not produce embryos, after all.
11
See Brugger, 756; 763. Brugger’s vagueness about the subject of epigenetic reprogramming is very telling:
“[a]fter nuclear transfer into an enucleated oocyte,” he writes on pages 755–756, “the epigenetic state is
reprogrammed from its formerly highly specialized state back to a state of totipotency. It goes through a process
of epigenetic dedifferentiation. If it reaches its terminus, the reprogrammed cell is a zygote, a one-celled embryo,
with the genotype of the donor of the somatic cell.” In the first sentence, and at the beginning of the second, the
subject of the reprogramming is the epigenetic state of the somatic cell nucleus. In the middle of the second
sentence, though, the subject suddenly shifts to the “reprogrammed cell.” This shift of subjects gives the
impression that the cell resulting from SCNT is the same entity as the somatic cell nucleus—only reprogrammed
epigenetically. This is wrong: the somatic cell nucleus is only part of a cell, not a whole cell. Consequently, if
SCNT results in a whole cell, it can only be because it has made a new cell out of the somatic cell nucleus and the
enucleated egg cytoplasm. As we will see in a moment, this fact has a huge bearing on the argument at hand.
12
If we do not follow this interpretation, then we have to deal with at least two problematic implications. First,
we commit ourselves to saying that the process of fertilization is not the beginning of human life, but is itself an
intermediate stage prior to the completion of the zygotic epigenetic state. Second, we have the difficulty of
explaining what is the ontological subject of the obviously teleological, directed process of forming the zygotic
epigenetic state. If this subject is not already a human being, then how can it direct itself into the epigenetic state
of a human being?
13
It is also worth pointing out that Brugger is vague on just how the transcription factors like Nanog involved
in OAR are “characteristic of the pluripotent state” (Brugger, 756). Sometimes he seems to suggest that they are
definitive of what a pluripotent stem cell is. But then he also acknowledges that they are just necessary conditions
for the appearance of pluripotency. Which is it? It seems to me that the latter alternative must be the correct one,
since, as Brugger says, the factors in question “appear to be essential for establishing and maintaining the state of
pluripotency” (ibid.)—which means that they are (so far as we know based on the current state of the research)
effective/instrumental causes of pluripotency, not the sum and substance of it. But if the mere presence of Nanog
(or whatever) is not what defines a stem cell as such, but only what helps it establish and maintain its stemcellness, then the premature forcing of its expression is perfectly compatible with the possibility that we have
created an embryo with a developmental defect, rather than a pluripotent stem cell.
14
See Brugger, “ANT-OAR: A Morally Acceptable Means,” 761.
15
Ibid.
16
See Granados, “ANT-OAR: Is Its Underlying Philosophy of Biology Sound?”
17
One of the connotations of the term “mock” or “mimicked conception/ fertilization” is that even SCNT,
which alters the natural event of conception, still has to rely on it in some sense. Whatever else it does, SCNT
relies on the same logical-temporal sequence as nature does: fusion of the relevant cellular materials—coming
into being of a new individual—epigenetic reprogramming. The fact that the relevant cellular materials are no
longer sperm and egg, but somatic cell nucleus and enucleated oocyte, does not change this fact, for if the fusion
of the enucleated oocyte and the somatic cell nucleus did not have by nature at least some of the powers that the
fusion of the egg and the sperm does, then SCNT would never produce embryos. The fact that, in spite of this,
most trials of SCNT fail to produce viable embryos is no argument against this consideration.
18
Cloning failures are better explained by the unnatural conditions to which it subjects the cellular materials
than by the assumption that they retain nothing of the natural teleology inherent in the sperm-egg fusion. SCNT
does not replace nature, but mutilates it—while keeping just enough of it to lend it whatever (limited) efficacy it
has.
8
9
Of course, Brugger might retort that there are certain characteristic attributes that, like the “inseparable
accidents” of Scholastic philosophy, cannot be lacking to a human organism, so that their non-appearance always
and necessarily signifies that no human organism is present, either. Now, this retort is partly correct, in that there
are such “inseparable accidents” that, while being accidents, are nonetheless necessarily entailed by the essence of
the species homo. Nevertheless, this retort overlooks the fact that an entity can have the specific essence of man,
and so be “owed” the attributes that follow inseparably from that essence, while failing to have the actual physical
wherewithal to instantiate those attributes. For example, a child born with a neck disease that made it physically
impossible for him to laugh would still be a human being who, by virtue of his sharing in the specific essence
“man,” ought to be able to laugh. Put more simply, the child is naturally a “laughing animal,” even if he cannot
laugh because of a grave physical impediment. I recognize, of course, that a typical physical equipment goes with
the essence of the human being; my point is simply that the equipment can be defective in individual cases
without this meaning that there is no human being present who, by virtue of his human status, ought to have that
equipment ceteris paribus and, indeed, would have it if not for the defect. It seems to me that Brugger’s position
logically undermines this all-important distinction between abnormal humans and non-humans, and so amounts to
the absurd claim that the physical impediment to our hypothetical child’s ability to laugh—at least if it is
engineered prior to the child’s conception—means that the child is not by nature a “laughing animal,” that is, a
human organism.
19
Let me record, however, my skepticism about the likelihood of OAR’s really managing to produce
pluripotent stem cells. The OAR concept supposes, after all, the theoretical possibility of sufficiently replicating
the conditions under which a pluripotent stem cell normally arises—in what is in fact an abnormal environment,
whose distinctive commonality with the normal one is the presence of certain pluripotency-related transcription
factors, such as, for example, Nanog. This decision to treat the normal environment and process in which stem
cells arise as if it were cleanly replaceable or simply irrelevant seems logically to entail the mechanistic
assumption that, for all practical purposes, a stem cell is nothing but a nucleus+cytoplasm+active Nanog (and/or
other similar factors). Unless we live in a mechanistic universe, however, such a decision is very likely to have
visible consequences that will render the claim that OAR has directly created stem cells suspect even from a
(sufficiently perceptive) empirical point of view. We just do not, and probably never will, have the sort of control
over the nature of human origins which OAR seems to bank on. If we did, then, as I said just now, there would be
no need for nuclear transfer, and direct cellular dedifferentiation would be firmly within our grasp.
20
Indeed, it is Brugger who risks dualism when he argues that the zygotic epigenetic state must already be
present in “active potency” before humanity can be instantiated, forgetting that the organization of matter required
for that state is itself logically dependent on the instantiation of humanity already having happened.
21
I leave aside the fact that the transition from animal to human experimentation will also require a certain
number of trials before a reliable experimental protocol for human OAR is established—a time in which similar
mistakes are also very likely.
22
Brugger, “ANT-OAR: A Morally Acceptable Means,” 768.
18
ADRIAN J. WALKER is an associate editor of Communio.