Irving Re Gardner's Rejection of Herranz's New "Theory" on Human MZ Twinning

Dianne N. Irving
copyright March 14, 2014
Reproduced with Permission

Any genuine bench research scientist knows all too well that you can fool some of the scientists all of the time, and all of the scientists some of the time, but you can't fool all of the scientists all of the time -- regardless if they are "prolife" or "prochoice". Such is the case with the very odd phenomenon we are currently witnessing with Herranz's recent claims and new "theory" about the cause(s) of human monozygotic (MZ) "identical" twinning.

Herranz, a physician (not a bench scientist nor a human embryologist), recently published an article in the journal Zygote [see the full article at:] essentially claiming that all human MZ twinning was simply a function of "fertilization", or sexual reproduction (fusion of sperm and oocyte, "conception") -- a claim almost immediately endorsed recently by neurobiologist Maureen Condic [see her articles at:; and at:]. These claims not only reject many decades of scientific documentation and collective wisdom to the contrary (at least since Corner's and many other's experiments and explanations since the 1950's), it also would reject the acknowledged scientific fact that human MZ twinning is a-sexual reproduction and one of many kinds of human cloning. That is, the scientific literature documents that human MZ twinning is definitely not a function of sexual reproduction ("fertilization", conception); it is a function of a-sexual reproduction (without the use of "fertilization").

Yet couldn't such long-standing scientific wisdom be in line for an updating and overhaul? Of course it could, and all genuine scientists welcome that if the counter-claims are empirically well-documented and universally empirically verified (the last step in the genuine scientific method) -- rather than just a subjective (or political) "opinion". Although Herranz's article is loaded with historical references and copious endnotes, he provides little if any empirical evidence or documentation to support his new "theory".

Not unexpectedly, other scientists, including developmental biologist Denker [see his rejection of Herranz's "theory" at:; see also Irving, at:], as well as human embryologists Gasser and Kischer, have recently outright rejected Herranz's new "theory" of human MZ twinning. And now yet another rejection is leveled at it, coming also from a well-established scientist -- who happens to support all manner of research anathema to genuine "prolife" positions.

In his article, copied in full below, biologist Sir Prof. Dr. Richard L. Gardner, a physiologist and developmental biologist at the University of York, Department of Biology [], again scientifically rejects Herranz's new theory out-of-hand, for many of the same reasons identified earlier by Denker. Gardner himself has over 70 related scientific publications to his credit [see:]. Interestingly enough, Gardner is also noted for his advocacy of most of the research now permitted in Great Britain involving destructive human embryo research [see, e.g.:]. In his article, Gardner offers counter-explanations of three types of a-sexual human MZ twinning, e.g., in terms of the separation of blastomeres from the original embryo before implantation, and the "splitting of blastocysts by partial herniation and shearing", with empirical documentation from more recent research -- all of which continue to support the decades-old empirically-grounded explanations.

Although Gardner doesn't address it, but as also scientifically documented for many decades, this would also involve the presence of at least some "totipotent" (rather than just "pluripotent") cells in the early embryo from the 2-cell organism until its development just before implantation, as well as within the inner cell mass of the human blastocyst before and after implantation -- the traditional scientific explanation for natural in vivo MZ twinning. This has usually involved the inherent biochemical mechanisms (usually referred to collectively as the natural biological process of "regulation") that can de-methylate the DNA of the separated cells, thus converting such separated cells or groups of cells to a new human organism. For extensive scientific references explaining human a-sexual reproduction in MZ twinning (cloning), see Irving, , with 21 pages of scientific references, at: This scientific documentation is not -- emphasis "not" -- claiming that separated individual blastomeres (cells) from the early human embryo before implantation, or even halves of human blastocysts just before or after implantation, are literally embryos, but rather explains what has also been known in biochemistry and human molecular genetics for a very long time -- that at least some of these cells are still "totipotent" or at least capable -- have the internal capacity -- of being reverted back to new human embryos if (subjunctive tense) the natural biological processes of "regulation" and the "de-methylation" of the cells' DNA are successful. Indeed, it is by means of the processes of "methylation" and "de-methylation" that all human "stem cells" are produced from mature human cells -- not new. Can't really perform any "stem cell" research without it.

Still, the final question raised by Gardner in his article is rather astounding:

"The question is why, having criticized one explanation for the origin of MZ twins because of the paucity of supporting morphological evidence, for which there are good reasons, Herranz should offer a patently implausible alternative? An obvious answer is that MZ twinning has proved a difficulty for the official Catholic view that the life of a new human individual begins at fertilization. Clearly, this view is not sustainable if a single fertilized oocyte can give rise to more than one individual during its subsequent development. This is an issue which must clearly exercise Herranz as an emeritus member of the Pontifical Academy for Life (not to be confused with the Pontifical Academy of Sciences)."

In other words, given the lack of empirical evidence on which to base his claims, is Herranz really doing prolife "politics" instead of genuine science? Coming from someone who is "pro" all manner of unethical research involving the early human embryo, perhaps the same question could be leveled at Gardner. However, which side has the science straight -- regardless of their subjective "political" opinions? Fortunately, or unfortunately, it would seem that Gardner does, and he raises a good question. Just why is it that the Church continues to claim that all -- all -- human beings begin to exist sexually at fertilization (conception) only, when such a claim is so obviously absurd -- at least to any genuine scientist. While some human beings are sexually reproduced, many are not; many are a-sexually reproduced without "fertilization". Even the Carnegie Stages of Early Human Embryonic Development, instituted in 1942, based on universally acknowledged and accepted research long before that since at least 1885 (Wilhelm His), and updated continuously to the present by the international nomenclature committee on human embryology (FICAT) includes explanations of human MZ twinning as a-sexual human reproduction in describing Stages 2 - 6 (see Irving, "The Genuine Carnegie Stages" (September 8, 2013), at:]. This very strange enigma has caused others to pose the same questions [see Irving, "Junk Science In, Junk Prolife Out" (October 28, 2013), at:]. And as all political lobbyists surely know, if such "scientific terms" are used in legislation and regulations, the courts are legally required to interpret them as "exclusionary" -- literally, thus legally allowing any research that doesn't fall under those reductive selective "definitions". Indeed, there are now dozens of states that have laws and regulations where "conception" is mis-defined as "implantation" (5-7 days post-fertilization), and if such legislations were to define "human reproduction" as only sexual ("fertilization"), then they would not apply to any human beings a-sexually reproduced.

And as Denker has importantly questioned -- what are the real-life in-the-flesh ethical ramifications of either position? Why is there a total absence in these discussions about even the consequences of either position? Painful as it is to suggest, if Herranz is correct that human MZ twinning is just a function of "fertilization" (conception), then twinning is not cloning (and thus the use of "twinning" performed for decades in IVF and ART facilities for "infertility treatments" would not constitute reproductive cloning). If the Church is correct that all human beings begin to exist only by means of "fertilization" (conception), then there is no such thing as any human a-sexual reproduction whatsoever. That would include not just a dozen different kinds of human cloning techniques, but also all human genetic engineering techniques (including synthetic biology and nanotechnology) -- and all of those experimental human embryos could "justifiably" be "ethically" implanted into women as "infertility treatments" as well. It would also include the death and destruction of millions of innocent living a-sexually reproduced human embryos. Are all those a-sexually reproduced human beings just not "persons"? What is "prolife" about that? Oddly enough, if Gardner is correct, then all of the above is unethical.

Further, if Herranz's scientific claims about "twinning" and the Church's scientific claims about human reproduction in general are accurate, then how do they explain why "reproductive cloning" is unethical? In a recent article I give 40 pages of scientific references that all acknowledge a-sexual human reproduction, including cloning by "twinning". [See Irving, "Any Human Cell -- iPS, Direct Programmed, Embryonic, Fetal or Adult -- Can Be Genetically Engineered to Asexually Reproduce New Human Embryos for Purposes of Reproduction ('Infertility')" (November 2011), at:]. This article is also based on a recent UNESCO report, with its own scientific references, concerned with the human trafficking of asexually reproduced human embryos for the explicit purpose of implanting them into women. And a recent Dutch report [] includes "forced or coerced surrogacy" in the categories of "human trafficking" for the first time -- the obvious question arising as to whether illegally trafficked women (including young girls) could be forced to be surrogates for a-sexually reproduced experimental human embryos? Would Herranz and the Church need to deny that those reports and situations exist in order to maintain consistency with their "scientific" positions -- or even argue that they are "ethical" since they don't involve the implanting of real human embryos? If a-sexual human reproduction is denied, then how can they possibly keep up with or even debate about the plethora of unethical research exploding today? [See also Irving, "Why Accurate Human Embryology Is Needed To Evaluate Current Trends In Research Involving Stem Cells, Genetic Engineering, Synthetic Biology and Nanotechnology" (November 20, 2012), at:].

In fact, if Herranz et al, and the Church, keep publishing their "science", how is anyone able to form their consciences correctly on all these related issues involving the early human embryo [See Irving, "A One-Act Play: 'Crippled Consciences and the Human Embryo'" (November 17, 2010), at:; see also Irving, "Human Embryology and Church Teachings" (September 15, 2008), at:; also published in The New Catholic Encyclopedia, 2nd ed., Supplement 2009, (Detroit: Gayle), pp. 287-312, as "Embryology, Human"]?

The stakes for the credibility of science, the Church and "prolife", as well as for the extensive and profound risks to humanity, couldn't be higher. It is long past time for some genuine scientific and genuine ethical and legal discussions and resolutions on these related issues involving the early human embryo. As every genuine scientist knows, sooner or later the real empirical facts come out, like it or not. And any genuine ethics and legislation should be based on those accurate empirical scientific facts. No more fooling around.

Reproductive BioMedicine Online (2014) 28, 276- 278
Journal of Reproductive BioMedicine


The timing of monozygotic twinning: a pro-life challenge to conventional scientific wisdom

RL Gardner

Centre for Immunology and Infection, University of York, Heslington, York, YO10 5DD, UK E-mail address:


A recent paper in Zygote criticizes the 'theory of origins' of the various classes of monozygotic twins originally proposed and developed by Corner. It does so on the basis of recent observations on human IVF embryos. Here, the validity of one of the evidential sources is upheld, but an alternative explanation is proposed that is more plausibly based on evidence than the explanation offered in Zygote. RBMOnline

KEYWORDS: human embryo, IVF, monozygotic twins, Vatican

Fascinating questions that continue to exercise theologians and ethicists, as well as those working in the fields of mammalian embryology and obstetrics, are when and how monozygotic (MZ) twins originate. The overwhelming majority of those concerned with these issues, whether within or outside the scientific community, accept the explanation for the origin of such twins that was advanced many years ago by Corner (1955). According to this authority, the differing extraembryonic relationships between the three categories of MZ twins, namely dichorial diamniotic (DC/DA), monochorial-diamniotic (MC/DA) and monochorial-monoamniotic (MC/MA), are attributable to their originating at progressively later stages in early development. Thus, twins of the DC/DA category, which account for approximately one-third of all MZ twins, are presumed to result from the preimplantation conceptus forming two distinct blastocysts, each with its own inner cell mass (ICM), while those of the MC/DA category, which account for about two-thirds, result from two ICM forming within a unitary blastocyst. The third, MC/MA category, which is by far the rarest, is attributed to peri- or post-implantation subdivision of the epiblastic derivative of the ICM (Edwards, 1980). The decreasing difference in patterns of X-chromosome inactivation between pairs of female MZ twins of the DC/DA, MC/DA and MC/MA classes fully accords with this view, with the first category originating before inactivation, the second at about the time of its occurrence and the third significantly later (Chitnis et al., 1999).

In an article published recently in the journal Zygote, Herranz (2013) challenges the Corner 'model' on the grounds of paucity of supporting morphological evidence. However, in so doing he neglects to point out the rarity with which MZ twinning occurs, even when allowance is made for its increased incidence in assisted conception, and the fact that, due to the vanishing twin phenomenon, it is initiated somewhat more frequently than is discernible later in pregnancy. Hence, only a small minority of early conceptuses are likely to prove informative even at stages that are amenable to close observation.

Herranz is correct in stating that DC twinning is most unlikely to occur during cleavage because of the ease with which these stages aggregate to form unitary blastocysts when divested of the zona pellucida. However, it is relevant to point out that Corner raised the possibility of such early twinning several years before the aggregation of denuded cleavage stages was first demonstrated by Tarkowski (1961). Herranz is on much less secure ground in arguing against the occurrence of twinning at the blastocyst stage. Even a small discontinuity in the zona pellucida can lead to herniation of part of the trophectoderm which, depending on its location, may include cells of the ICM. The process whereby the blastocyst loses its zona pellucida has been investigated in several species of mammals, most extensively in rodents (Seshargiri et al., 2009). Roles for both the trophectoderm and a maternally produced lytic enzyme have been implicated. That blastocysts can hatch in vitro shows that the maternal enzymic activity is not essential, progressive expansion of the blastocoelic cavity, possibly aided by local activity of a trophectodermal lysin, being sufficient to cause spatially restricted breaching of the zona and subsequent hatching of the blastocyst (Perona and Wassarman, 1986). Significantly, mouse cleavage stages developing in vivo following focal damage to the zona not infrequently yield two blastocyst-like structures on subsequent recovery from the uterus. This phenomenon can only readily be accounted for by herniation of part of the blastocyst followed by its shearing from the remainder that is still encased by the zona. These herniated trophectodermal vesicles may include ICM tissue, so that twin blastocysts can be formed (Malter and Cohen, 1989; author's own observations). Partial herniation, leading to the formation of twin blastocysts and DC/DA post-implantation twins, has also been encountered among human blastocysts developing in vitro (Behr and Milki, 2003; Malter and Cohen, 1989; Van Langendonckt et al., 2000). Its occurrence after transfer of zona-included blastocysts to the uterus could account for cases of DC/DA twinning (Kyono, 2013), which are held by Klein et al. (2005) to challenge conventional wisdom. Hence, the origin of DC twins by subdivision at the blastocyst stage cannot be dismissed as implausible. That 'zona drilling' can also result in a dramatic increase in the incidence of MC/MA twinning (Alikani et al., 2003) has yet to be explained.

So far as MC/DA twins are concerned, blastocysts with two more or less discrete ICM have been reported in several species of eutherian mammals, including the human (e.g. Sills et al., 2000). According to Corner's model, MZ twins of the MC/MA class originate following implantation at a stage before ultrasound imaging is practicable and, in view of their relative rarity, are unlikely to be included in limited collections of conceptuses preserved at the relevant stage. However, partial duplication of the embryonic axis has been noted in serial histological sections of a day 15 rhesus monkey embryo (Enders, 2002).

Studies in the mouse have addressed the issue of size regulation whereby the epiblast of chimaeras produced by aggregating two or more cleavage stages or bisecting individual ones attain normal size and cell number postimplantation, a phenomenon that is now being enlightened by studies at the molecular level (Claveria et al., 2013; Lewis and Rossant, 1982; Rands, 1986). Perturbation in the regulation of epiblast cell number, or in partitioning of its cells between its embryonic and extraembryonic derivatives, might very occasionally result in enlargement of the former to an extent that permits a second axis to form.

Having argued rather unpersuasively that the Corner 'model' is inadequate to account for the three categories of MZ twins, Herranz feels obliged to offer an alternative explanation, namely that all categories of MZ twins originate at fertilization through two zygotes, rather than via a pair of sister blastomeres being produced by the first mitotic division. DC twins are attributed to separate development of the two zygotes ab initio, while the two MC categories are held to originate through the zygotes fusing at the late morula or blastocyst stage so as to yield two ICM within a common trophectoderm. Whether these develop di- or monoamniotically is presumed to depend on their proximity. To account for the occurrence of MZ triplets, quadruplets and quintuplets, this view obviously requires fertilized oocytes also to be capable of yielding new zygotes following their second and even third mitotic division.

However, this alternative explanation is much less plausible biologically than the one it seeks to displace, inasmuch that it requires the occurrence of two processes that can effectively be discounted by extensive research on early mammalian development. The first is the improbability, given the facility with which cleavage blastomeres aggregate, that two zygotes residing within a common zona pellucida could continue to develop separately. Formation of twin zygotes rather than sister blastomeres would not constitute a barrier to aggregation and the consequent formation of a common blastocyst, since this occurs very readily between cleavage stages of different genotypes and even species. Herranz makes this very point in one of his criticisms of the Corner 'model'.

One last weakness of the model on the origin of DC DA twins consists in its inability of finding its own confirmation in IVF. Despite the countless human embryos produced and examined in vitro, the problem remains unsolved: the splitting and growth of twins within the pellucida has been never observed or live recorded.

Herranz is thus effectively hoist with his own petard! What Herranz describes as 'convincing documentation of the presence inside the zona pellucida of two independent blastocysts prior to hatching' relates to a single specimen that was cultured following vitrification (Shibuya and Kyono, 2012). Given the very obvious focus of cell lysis lying between the two cavitating masses, this can hardly be claimed to represent a typical situation.

Secondly, once the advanced morula stage is reached embryo aggregation has never been achieved other than by use of extremely non-physiological conditions (Tarkowski et al., 2005). This presumably reflects the increasingly sophisticated junctional complexes formed between outer, nascent trophectoderm, cells. However, as noted earlier, formation of DC/DA twins via herniation of part of trophectoderm plus ICM through a discontinuity in the zona has been documented in the human, although both members of the pair in question lacked heartbeat at insonation (Van Langendonckt et al., 2000). To account for this finding on Herranz's hypothesis, one would have to suppose the products of two zygotes developing separately within a common zona fused to form a unitary blastocyst which subsequently engaged in fission to form two distinct blastocysts once again. Altogether, an absurdly improbable scenario!

The question is why, having criticized one explanation for the origin of MZ twins because of the paucity of supporting morphological evidence, for which there are good reasons, Herranz should offer a patently implausible alternative? An obvious answer is that MZ twinning has proved a difficulty for the official Catholic view that the life of a new human individual begins at fertilization. Clearly, this view is not sustainable if a single fertilized oocyte can give rise to more than one individual during its subsequent development. This is an issue which must clearly exercise Herranz as an emeritus member of the Pontifical Academy for Life (not to be confused with the Pontifical Academy of Sciences).

While the mode of origin of MC/MA twins may remain shrouded in mystery, the increasing use of continuous timelapse monitoring of preimplantation development of human embryos produced by assisted conception in vitro will undoubtedly cast further light on the origin of the other two categories. It should prove particularly informative regarding the incidence of blastocysts with two ICM. Splitting of blastocysts by partial herniation and shearing will not be seen in vitro unless culture is extended to an advanced stage which is typically not reached before their transfer to the uterus. However, the 'partial herniation' hypothesis has the merit of falsifiability since blastocysts that are zona-free on transfer should never give rise to DC/DA twins.

Altogether, this is rather an odd paper to be published in a journal that is concerned with studies aimed at elucidating the biological basis of gametogenesis and fertilization.


Declaration: The author reports no financial or commercial conflicts of interest.

Received 28 October 2013; refereed 23 November 2013; accepted 3 December 2013.

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