ARTICLE
Redefining "Virgin Birth" After Kaguya: Mammalian Parthenogenesis in Experimental Biology, 2004-2014
Eva Mae Gillis-Buck
University of California, San Francisco
gillisbuckem@gmail.com
In 2004, a group of Korean and Japanese scientists reported the birth of a healthy mouse with two mothers and no father. The scientists named the mouse Kaguya, after a Japanese folktale princess born from a bamboo stump, and published a Nature paper entitled "Birth of parthenogenetic mice that can develop to adulthood" (Kono et al., 2004). The word parthenogenesis, from the Greek for virgin birth, is a term scientists use to describe various forms of reproduction and development without sperm. Media headlines, such as "The End of Males?" and "Two Mums Make Baby," fueled public interest in what Kaguya's birth might mean for human reproduction (Fisher, 2004; Trivedi, 2004). But Tomohiro Kono, one of the leading scientists behind the Kaguya experiment, told reporters that the idea of human parthenogenesis was "senseless" (Ritter, 2004). Kono and colleagues argued that Kaguya's birth actually demonstrated how and why males are required for mammalian reproduction. The Kaguya experiment, they explained, was simply an effort to better understand an epigenetic process called genomic imprinting and why the maternal and the paternal genome are both necessary for complete mammalian development.
The idea that a mouse without a father could demonstrate the necessity of males seems contradictory, and ironic given the history of feminist and lesbian engagement with parthenogenesis. All-female reproduction has been a theme of feminist science fiction throughout the twentieth century (Ingram-Waters, 2006, 2008; Squier, 1994), and lesbian separatist groups in the 1970s and 1980s followed parthenogenesis research closely, optimistic for its potential as a new reproductive technology (Kelly, 1977; Rensenbrink, 2010). Scholars have noted that the actualization of a queer imaginary— parthenogenesis—has ironically been used as scientific support for the biological necessity of males, upholding a heteronormative one-father plus one-mother reproductive scheme (Ingram-Waters, 2006, 2008; Lafuente Funes, 2012; Rensenbrink, 2010). However, in this paper, I show that unconventional interpretations of sex and parenthood can be found even in scientific research that claims mammalian parthenogenesis is impossible. Many scientists insist that males are necessary, but they also describe eggs as paternal, embryos as sperm-free, and bimaternal sexual reproduction as something distinct from parthenogenesis. Given the etymology of parthenogenesis, and the tendency of some scientists and media outlets to use parthenogenesis and virgin birth interchangeably, the language used to explain the Kaguya experiment contributes to scientific and cultural understandings of sex, gender, reproduction, and family. I argue that language of the Kaguya experiment both supports a reproductive status quo and simultaneously challenges it.
To better understand how this scientific language has evolved, I first contextualize the Kaguya experiment within the history of parthenogenesis research, which is caught up in what I call a discourse of impossibility. I use this phrase to describe conversations among scientists, taking place in academic journals in the twentieth and twenty-first century, that conclude in a consensus: viable parthenogenesis in mammals is impossible, even though it is a common form of reproduction in many insect, reptile, and bird species. So-called parthenotes—eggs that begin dividing and developing without the contribution of sperm—were made into a routine laboratory technology, and the understanding that parthenotes could never develop to term made them the "right tools for the job" in many ways (Clarke & Fujimura, 1992).
The inviability of mammalian parthenotes was useful to developmental biologists, who compared parthenotes with fertilized embryos to discover the necessary components of sperm in early development. Geneticists found parthenogenesis useful, given parthenotes' haploid or homozygous diploid genome, which could reveal recessive mutations. Parthenotes were also key to the conceptualization of genomic imprinting in the 1980s. Then, in the early twenty-first century, parthenotes became a source of stem cells. At a time when American scientists could not use federal funding for the creation of human embryonic stem cell lines, human parthenogenetic stem cells served as an ethical alternative. Destroying a parthenote for stem cell derivation was not viewed as destroying a potential human life. This line of reasoning was largely dependent on the idea that mammalian parthenogenesis could never result in a live birth. Thus a productive experimental paradigm and strong political forces helped solidify the discourse of impossibility into a consensus: viable mammalian parthenogenesis does not and cannot happen.
The rest of this paper examines how the birth of Kaguya—a healthy mammalian parthenote—affected the discourse of impossibility and the language used to describe gametes and reproduction. Using a data set of 202 peer-reviewed publications that cite the Kaguya experiment, I investigate how scientists interpreted the birth of a mouse with no father and used the words parthenogenesis, maternal, paternal, and bimaternal in their published articles. My focus on language continues a feminist tradition of paying close attention to word choice and metaphor in scientific descriptions of sperm and egg, nucleus and cytoplasm, gene and environment (Butler, 1990; Fausto-Sterling, 1989; Keller, 1995; Martin, 1991; Moore, 2007). The case of mammalian parthenogenesis is particularly well-suited for this type of analysis, given the loaded term virgin birth. Virgin birth is a common theme in religious myths, science fiction, lesbian and feminist imaginaries, and sensational news stories. Virgin birth enters a laboratory setting through biologists' use of the term parthenogenesis, sometimes used interchangeably with virgin birth (Miyoshi et al., 2006; Wilmut, Campbell, & Tudge, 2000). For example, a 2002 Nature article on genomic imprinting and entitled "Immaculate Misconception" stated, "Sex is necessary and 'virgin' births are impossible in humans" (Surani, 2002, p. 491). By investigating scientists' word choice when describing development without sperm, this essay contributes to discussions of how scientific narratives influence and are influenced by gender norms and cultural understandings of reproduction, sexuality, and family.
PART 1: Establishing the impossibility of mammalian parthenogenesis
In the twentieth and twenty-first centuries, biologists compared parthenotes with fertilized embryos to investigate the role of sperm in early development. By examining the historical use of parthenotes in experimental biology, we can better understand how the discourse of impossibility was built up over time and how Kaguya's birth was interpreted within that discourse.
1.1 Artificial mammalian parthenogenesis. In the 1890s, German-American biologist Jacques Loeb developed a technique he called artificial parthenogenesis: inducing division and development in unfertilized sea urchin eggs by altering the salt concentration of seawater.1 American biologist Gregory Pincus—well known for his later work on oral contraceptives—claimed that "Loeb stopped too soon," and Pincus hoped to bring about artificial parthenogenesis in mammals (quoted in Pauly, 1987, p. 187). In the 1930s and 1940s, Pincus experimented with Loeb's methods and found that he could effectively induce cell division in unfertilized, cultured rabbit eggs. He even claimed to produce several live-born, healthy rabbits via artificial parthenogenesis (Pincus, 1939; Pincus & Shapiro, 1940).
In 1957, University of Edinburgh professor Richard Beatty wrote a monograph on parthenogenesis in mammalian development, reviewing a decade' worth of experimental research and clarifying certain terms. Beatty defined parthenogenesis as "the production of an embryo from a female gamete without the concurrence of a male gamete, and with or without eventual development into an adult"(1957, p. 4). Parthenogenesis became a term applicable to embryos and fetuses as well as live-born young. Such organisms became known as parthenogenones in Britain and parthenotes in the United States (Beatty, 1957, p. 4; Graham, 1974, p. 399).
Regarding the possibility of live-born mammalian parthenotes, Beatty was skeptical but entertained the idea, especially since so many non-mammalian species were able to reproduce parthenogenetically.2 He pointed out that even if spontaneous parthenogenesis were to occur, parthenotes were likely to go unnoticed.Throughout the 1950s and 1960s, scientists and physicians searched for rare cases of spontaneous parthenogenesis in animal populations and in humans (Balfour-Lynn, 1956; Rensenbrink, 2010, pp. 294-5; Prasad, 2012, pp. 61-77; Whitten, 1971). However, in all cases, blood tests and skin grafts provided evidence of paternity.
By the 1970s, spontaneous viable mammalian parthenogenesis seemed improbable, and Pincus's results had not been replicated for thirty years. His rabbits were considered an exception to the general observation that mammalian eggs would begin to develop parthenogenetically, but they never made it very far. After a certain stage, development consistently became delayed and disorganized, and eventually mammalian parthenotes turned into tumors or were spontaneously aborted.
1.2 Nuclear transfer experiments. In 1952, American biologists Robert Briggs and Thomas King pioneered animal cloning by removing the nucleus from a frog egg and adding a nucleus from another frog cell. This technique—nuclear transfer via microinjection—quickly became a standard method for amphibian cloning, but it was difficult to replicate in mammals. Oxford-based biologist Derek Bromhall finally managed it in 1975, writing:
Clearly a somatic cell nucleus,
transplanted into an unfertilised rabbit egg, can replace the sperm in
supporting development in the early cleavage stages. After
"fertilisation" of the egg by the transplanted nucleus the
synkaryon or "zygote" is capable of apparently normal division at least
up to
the
morula stage. (1975, p. 721)
Bromhall's words demonstrate how animal cloning reworked the
definition
of fertilization and challenged the reproductive necessity of male
gametes. Were these cloned rabbit embryos actually mammalian
parthenotes, given that they developed without any contribution from
sperm? Cloning refers to the generation of two identical organisms, and
so parthenotes are not clones since they are not identical to their
mothers—parthenotes contain only half their mother's genome.
Bromhall's
mammalian cloning showed that early development without sperm is not
exclusive to parthenotes; in this way, parthenotes' virginity is not their only
defining feature. Rather, parthenotes are distinguishable from clones
in their genetic uniqueness.
In addition to challenging the definitions of fertilization and parthenogenesis, nuclear transfer technique in mammals allowed for the experimental creation of new entities, including gynogenetic and androgenetic embryos: fertilized embryos from which a scientist microsurgically removes the sperm nucleus or egg nucleus, respectively (Figure 1). In the late 1970s and 1980s, scientists experimented with these embryos in order to ask questions about the necessity and sufficiency of different aspects of the egg and sperm. Using gynogenetic embryos, scientists hoped to explain the inviability of mouse parthenogenesis by pin-pointing the necessary paternal component, whether nuclear or cytoplasmic. Note the question was not, Is the sperm necessary? but rather, What part of the sperm is necessary?
Figure 1. A schematic explaining the distinctions between parthenogenesis, gynogenesis, and androgenesis. In parthenogenesis, eggs begin divided and developing without sperm. Scientists create gynogenetic embryos by microsurgically removing the sperm nucleus from the fertilized egg. Androgenetic embryos are created by removing the egg nucleus from a fertilized egg. Source: Leeb and Wutz, 2013, p. 2.
In 1977, biologists Peter Hoppe and Karl Illmensee reported the live birth of gynogenetic and androgenetic mice, suggesting that some non-genetic contribution of sperm, released into the egg at fertilization, was enough to direct proper development. But their results could not be replicated.3 Other research groups reported the opposite result and conclusion: gynogenetic and androgenic mouse embryos failed to develop to term, suggesting both the maternal and paternal nucleus are necessary for complete development (Mann & Lovell-Badge, 1984; Modliński, 1975; Surani & Barton, 1983). Experiments demonstrating the developmental failure of biparental mouse embryos (in which two egg or two sperm nuclei are transferred into an enucleated egg) gave further support for the idea that both the maternal and paternal genome are necessary for mammalian development (McGrath & Solter, 1984; Surani et al., 1984).
1.3 Genomic Imprinting. But why are both maternal and paternal genomes required? In 1984, Cambridge biologist Azim Surani and his colleagues suggested that eggs and sperm undergo differential DNA modification during egg maturation and sperm maturation (1984). Such DNA modification is an epigenetic process, involving chemical and structural changes that effect protein synthesis but do not change the DNA sequence. Differential modification in eggs and sperm would mean that for some genes, only the maternal copy is expressed (translated into protein), while for other genes, only the paternal copy is expressed. Thus, two copies of a maternal genome—as is the case in parthenogenesis—would result in too much of some proteins and a complete lack of other essential proteins (Figure 2). Surani and colleagues named this type of genetic modification imprinting (not to be confused with the term for an animal behavior common in geese). Genomic imprinting (also called parental imprinting) became a classic example of epigenetics and the definitive explanation for the inviability of mammalian parthenogenesis (Ferguson-Smith, 2011).
Figure 2. A schematic explaining genomic imprinting. In the case of androgenesis, gynogenesis, or parthenogenesis, there will be too much of some proteins and none of other essential proteins.
1.4 Parthenogenetic stem cells. At the turn of the twenty-first century, mammalian parthenotes became a technology of stem cell science. In 2002, a Massachusetts-based biotech firm isolated stem cells from primate parthenogenetic embryos (Cibelli et al., 2002). In 2007, scientists at the California-based International Stem Cell Corporation derived human parthenogenetic stem cells (Revazova et al., 2007), an accomplishment quickly replicated (Kim et al., 2007; Lin et al., 2007; Mai et al., 2007).4
Some scientists and bioethicists argued that human parthenogenetic stem cells had advantages over human embryonic stem cells. First, they were genetically similar to the adult egg donor, and thus better for therapeutic use (less risk of immune rejection). Second, the process of deriving the stem cells did not destroy a human embryo. At a time when American scientists could not use federal funding for the creation of human embryonic stem cell lines, it was argued that parthenogenetic stem cells could "circumvent ethical concerns" because the process of deriving them did not damage a "normal competent embryo"(Cibelli et al., 2002, p. 819). The idea that parthenotes are not normal, competent embryos is largely based on the claim that viable mammalian parthenogenesis is impossible. For example, a group of American bioethicists argued:
I see scientists' observations, manipulations, and descriptions of parthenogenesis as a kind of domestication process, a way of making parthenotes into a productive laboratory tool. The discourse of impossibility was part of that process; the idea that mammalian parthenotes are inviable arose out of their experimental use and then became the basis of future experimentation. Experimental questions transitioned from Can parthenotes develop to term? to Why can't parthenotes develop to term? and finally to How can we use these inviable parthenotes to better understand genomic imprinting and to derive stem cells? This latest question led to the routine use of parthenotes as puzzle-solving tools in experimental biology, in which the impossibility of viable mammalian parthenogenesis was taken for granted.
PART 2. Making sense of Kaguya by redefining sex, parenthood, and virgin birth
In the first half of this paper, I describe the development of the scientific consensus that viable mammalian parthenogenesis is impossible. Next, I investigate scientific reactions to the 2004 live birth and healthy development of a mammalian parthenote, Kaguya. The history of science is full of impossibilities later found to be possible, for example: vacuum, airplanes, black holes, in vitro fertilization (IVF), and mammalian cloning. Kaguya's birth might have similarly overturned a consensus of impossibility, as did the birth of Dolly the cloned sheep.5 Yet Kaguya's birth was frequently interpreted as supporting, not overturning, the idea that viable mammalian parthenogenesis is impossible. In making sense of this apparent contradiction, some scientists redefined parthenogenesis and thus virgin birth.
2.1 The Kaguya experiment. In the early 2000s, Tomohiro Kono and colleagues—based in universities and biotech companies throughout Japan and Korea—et out to investigate whether genomic imprinting was the only barrier to parthenogenesis. To do so, Kono and colleagues bred a genetically modified female mouse that lacked a functional copy of an imprinted gene called H19. They took an immature egg from that mouse and transferred the egg's nucleus, containing a modified genome, into a typical adult female mouse egg (Figure 3). The resulting embryo (with two egg nuclei and no sperm contribution) began dividing, as expected, but what happened next was not expected: 28 out of 457 embryos appeared to develop normally, and eight were born alive. One mouse, Kaguya, grew into adulthood, mated with male mice, and gave birth to a typical litter.
Figure 3. The Kayuga Experiment. Kono and colleagues first made a genetically modified female mouse that lacked a functional copy of an imprinted gene H19. They took an immature egg from that mouse and transferred the egg's nucleus, containing a modified genome, into a typical adult female mouse egg. The resulting bimaternal embryo (Kayuga) developed normally.
Recall that genomic imprinting is an epigenetic process, which controls how DNA is made into protein. For most genes, protein is made from both maternal DNA and paternal DNA. But some genes are imprinted or silenced, so that protein is made from only the maternal copy or from only the paternal copy. In parthenogenesis, where exclusively maternal DNA is present, the embryo ends up with too much of some protein and entirely without other essential proteins (Figure 2). The placenta doesn't develop correctly and the pregnancy fails. In the Kaguya experiment, one mother's egg lacked H19. That lack of H19 caused many epigenetic changes, silencing some genes and activating others. When the genetically modified egg was combined with a normal egg, the combination of proteins produced in the embryo was adequate to support development and bring about the birth of Kaguya.
In 2004, Kono and colleagues published these results in Nature. The article, "Birth of parthenogenetic mice that can develop to adulthood," emphasized Kaguya's relevance to earlier ideas about genomic imprinting. They wrote:
Kaguya's birth provoked dozens of headlines about virgin birth and unnecessary men, such as "The Mouse that Roared: Virgin Birth!" (Connor, 2004) and "The Obsolescence of Men" (Highfield, 2004). Provocative first sentences included "Here' a new scientific theory: men really are useless" (Shin, 2004); and "Men, your gender just took a hit in the animal kingdom" (Ritter, 2004). Universally, reporters asked if Kaguya's birth meant that men were no longer necessary for human reproduction.6 Scientists interviewed about the meaning of Kaguya's birth were quick to dispel the idea that parthenogenesis was a reproductive option for humans. They argued that human parthenogenesis was ethically and practically impossible, and Kaguya's birth only reinforced the necessity of a paternal contribution. Kono dismissed questions about human parthenogenesis as "senseless" and "insignificant"(Weiss, 2004, p. 13). Azim Surani supported Kono's position, telling reporters that the techniques used to make Kaguya were too inefficient for human application (Connor, 2004; Rincon, 2004). Surani also insisted that Kaguya's birth did not demonstrate male redundancy, but actually "show[ed] the opposite" (Pagán Westphal, 2004). Anne Ferguson-Smith, clinical director of the Centres for Assisted Reproduction, told reporters, "This does not mean that males are obsolete. The requirement for paternal chromosomes for normal development is still with us"(Connor, 2004, p. 3; Highfield, 2004, p. 16).
These interpretations of Kaguya's birth surprised and intrigued me: how could a mouse without a father demonstrate the necessity of the paternal contribution? Perhaps the interviewed scientists were reacting to media sensationalism. Did they make similar statements in their peer-reviewed scientific publications? Did most scientists agree with this interpretation, or did any describe Kaguya as a revolutionary demonstration of all-female mammalian reproduction that foreshadows new human reproductive technology?
2.2 Methodology. Given existing scholarship on media coverage of Kaguya's birth (Ingram-Waters, 2008; Lafuente Funes, 2012), my research questions focused on what scientists have said about Kaguya in peer-reviewed publications. I examined 202 scientific publications, published between 2004 and 2014, that cite the Kaguya experiment. To identify these articles, I used Thomson Reuters Web of Science, a comprehensive database that has indexed more than one billion references and is especially designed for identifying networks of citation (King, 2015). I searched for English-language scientific articles and reviews that cited the 2004 Nature article "Birth of parthenogenetic mice that can develop to adulthood" by Kono and colleagues.7 This search yielded 226 publications. After excluding book chapters, since book chapters are not necessarily peer-reviewed, there were 202 publications in my data set to analyze. For each article, I asked how the author(s) interpreted the Kaguya experiment, with the goal of identifying consensus and variability. I focused particularly on how the authors discussed the possibility of mammalian parthenogenesis and used the words maternal, paternal, parthenogenesis, and bimaternal.
Similar methods have been used to great effect by social scientists Rebecca Jordan-Young (2010) and Sarah Richardson (2013). Jordan-Young conducted an extensive critique of brain organization research by identifying a founding paper in the field and using Web of Science and other databases to collect more than three hundred peer-reviewed scientific publications that cited that paper (2010, pp. xi-xii). Sarah Richardson has also used Web of Science to identify and qualitatively analyze highly cited scientific articles that report genetic sex differences (2013, pp. 219-224). Given the size of my data set, contextualizing each and every article or author in time, geography, and discipline is beyond the scope of this paper and a limitation of these methods. However, directly engaging with hundreds of primary scientific articles published over a ten-year time period offers insight into common and unusual scientific language to describe a mouse without a father.
2.3 Scientists' mixed interpretations of the Kaguya experiment. Between 2004 and 2014, scientists from across the globe cited the Kaguya experiment in their published work, which appeared in journals specializing in genetics, reproductive and developmental biology, human and animal fertility, stem cells, cancer, and ethics (Figure 4). This diverse group of authors interpreted the Kaguya experiment differently, but after reading all 202 articles, three main trends emerged: 1) seventy-five publications (37%) explicitly stated that viable mammalian parthenogenesis is possible and/or the paternal genome is unnecessary; 2) seventy-four publications (37%) explicitly stated that mammalian parthenogenesis is impossible and/or the paternal genome is necessary; and 3) forty-three articles (21%) described mammalian parthenogenesis as artificial: something that can occur, but not in nature (Table 1).
Figure 4. Summary of peer-reviewed scientific publications that cite the Kayuga experiment. Analysis by publication year, top ten authors, top ten journal titles, and top ten author's country/territory affiliations by Thomson Reuters Web of Science.
Table 1. Interpretations of mammalian parthenogenesis after Kayuga's birth.
There were exceptions: several articles did not mention parthenogenesis at all, but cited the Kono et al. study solely for its methods (Choi et al., 2006; Kim et al., 2008; Ma et al., 2005; Oh et al., 2005; Shao et al., 2007; Sim & Min, 2014). Other authors cited the Kaguya experiment when discussing imprinted genes in early development, but they did not mention parthenogenesis explicitly (Ahmad et al., 2005; Kobayashi et al., 2012; Li et al., 2012; McConnell et al., 2005).
2.4 Viable mammalian parthenogenesis is artificial. I was most intrigued by publications that stated viable mammalian parthenogenesis was impossible but also acknowledged Kaguya's birth—an apparent contradiction. This happened in fifteen articles (7%).8 For example, an article in the International Journal of Molecular Medicine read:
The framing of viable parthenogenesis as artificial is significant with regard to the politics of stem cell research. Twenty-one publications (10%)9 stated that because mammalian parthenotes can never spontaneously or naturally develop to term, human parthenotes are distinct from human embryos, making human parthenogenetic stem cells an ethical alternative to human embryonic stem cells. For example:
Yet one article suggested that the genetic engineering necessary to create Kaguya could be used to restore an embryo to a more natural state:
2.5 Genomic imprinting is a barrier to parthenogenesis. In sixteen articles (8%), the Kaguya experiment is cited for the idea that genomic imprinting prevents or blocks viable parthenogenesis (Table 2, column 1). For example, in a review of cancer epigenetics, an author wrote, "One remarkable feature of the wild type H19 ICR is that it provides a barrier to parthenogenesis via so far unknown mechanisms," and cited Kono et al. (Göndör, 2013, p. 95). The same language was used by Kono and colleagues themselves in the original 2004 Nature publication: "There is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development [...]Our study shows that imprinting is a barrier to parthenogenetic development in mice"(p. 860, 863). This use of the Kaguya experiment seems to uphold the discourse of impossibility and a reproductive status quo, because Kono and colleagues are credited for discovering why parthenogenesis doesn't happen, as opposed to the accomplishment of actually making it happen. However, like the requirement for genetic modification, this barrier language also implies newfound control over reproduction. Once the barrier is known, it can be torn down. The Kaguya experiment revealed the key obstacle to parthenogenesis by overcoming it, thus demonstrating the practical tools and methods needed to make viable mammalian parthenogenesis a reality.
Table 2. Scientific language redefining sex, parenthood, virgin birth.
2.6 Maternal and paternal are qualities within scientific control. In the 2004 Nature publication, Kono and colleagues wrote, "These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant" (Kono et al., p. 860). This perspective relies on subtle distinctions between paternal, father, and sperm. One of Kaguya's mothers lacked a functional H19 gene, a genetic manipulation, which altered a vast number of imprinting genes such that the maternal genome resembled a paternally imprinted genome. Therefore, paternal imprinting was necessary for Kaguya to be born, but a father's sperm was not. But is a female genome with a paternal imprint a paternal contribution?
Seventeen scientific publications (8%) that cite the Kaguya experiment have described certain female gametes as male-like. Often a neonatal egg genome, which lacks a maternal imprinting pattern, and a genetically modified egg genome are both described as mimicking or simulating a male or paternal genetic contribution (Table 2, column 2). This language could be interpreted as upholding a heteronormative status quo by defining the manipulated egg as masculine, reflecting the idea that in two-mother families, one woman must be more masculine or act as the father figure. But there is also an interpretation that destabilizes the concept of binary sex. These authors are describing the sex of a genome as something independent of the sex of a gamete: a female egg can have a male-like genome and a paternal imprint. In this way, imprinting pattern could be considered a new sex characteristic. Anne Fausto-Sterling (2000) has convincingly argued that sex characteristics—hormone levels, chromosomes, genitalia, fat and hair deposition, internal reproductive organs—are a product of scientific and medical norms. These characteristics often do not align or fit neatly into a male-female binary. Similarly, eggs with a paternal imprinting pattern defy the biological basis of a simple two-sex system.
Moreover, after Kaguya, scientists described modifying the epigenetics of gametes to determine their maternity and paternity (Table 2, column 2). For example, "The deletion of the IG-DMR on chromosome 12 which causes paternalization of the maternal chromosome alone could restore some imbalance imposed by two maternal genomes" (Kawahara et al., 2006, p. 2877, emphasis mine). The functional maternity or paternity of eggs and sperm is not necessarily dependent on the biological sex of the parent, but on the pattern of genomic imprinting, which scientists can manipulate. This idea furthers scientific control over sex characteristics, adding to existing technologies such as hormone replacement therapy and surgery. It also challenges the alignment between father/paternal/male/sperm or the assumption that they are interchangeable terms. The egg—a female gamete—an be paternalized so that it provides a necessary paternal contribution to the embryo.
2.7 Bimaternal reproduction is not parthenogenesis. Finally, the statement Viable mammalian parthenogenesis is impossible makes sense, even in light of Kaguya's birth, if Kaguya is not considered parthenogenetic. And indeed, twenty-nine articles (14%) used gynogenetic or bimaternal to describe Kaguya, instead of parthenogenetic. The exclusion of Kaguya from parthenogenesis implies what is and is not considered virgin birth, thus challenging the role of sperm and males in the definition of virginity and sexual intercourse.
Several scientists explained why they decided to use a term other than parthenogenesis to describe Kaguya. For example, in a review of genomic imprinting in mammals, geneticists at the Russian Academy of Sciences wrote:
Seven
articles (3%) referred to Kaguya as gynogenetic
rather than parthenogenetic.
Recall that gynogenetic
usually describes embryos in which the sperm nucleus has been removed
after fertilization (Dadoune, 2009; Dilkes & Comai, 2004; Miller
& Ostermeier, 2006; Miller, Ostermeier, & Krawetz, 2005; Penkov
et al., 2010; Platonov & Isaev, 2006; Sciamanna et al., 2009).
Platonov and Isaev argued that the microsurgical injection of an egg
nucleus into another egg, or the introduction of any genome from the
outside, should be considered gynogenetic, not parthenogenetic. Perhaps
the micropipette's penetration of the egg, or the fact that another
individual's chromosomes contribute to those already inside egg,
makes
the term virgin birth seem
not quite right. Ann Kiessling, director of the Bedford Stem Cell
Research Foundation, also considered Kaguya as not exactly
parthenogenetic. She has written:
Kiessling
considered Kaguya's two genetically unique mothers to be the
distinguishing factor, something that makes her birth not canonical parthenogenesis.
Kono and colleagues have most clearly excluded bimaternal reproduction from parthenogenesis. Though the group originally referred to Kaguya as parthenogenetic in their 2004 article, later publications by the team refer to Kaguya and similar mice as bi-maternal conceptuses instead of parthenotes (Kawahara et al., 2006; Kawahara et al., 2007a; Kawahara et al., 2007b; Kawahara et al., 2008; Kawahara, Wu, & Kono, 2010; Kono, 2009; Wu, Kawahara, & Kono, 2008). A 2008 Nature Protocols publication clarified that this was an intentional redefinition:
The
Kono group also used sperm-free
rather than parthenogenesis
to describe the generation of these mice (Kono, 2009, p. 34; Kawahara
& Kono, 2010, p. 457; Kawahara & Kono, 2012, p. 175). Moreover,
authors outside the Kono group began referring to Kaguya as bimaternal rather than parthenogenetic (Table 2, column 3;
Figure 5).
Figure 5. Schematic that accompanies a description of the Kayuga experiment. Note that "bi-maternal" is considered distinct from "parthenogenetic" because one of the maternal genomes has been genetically modified to more closely resemble a "paternal" imprinting pattern (shown in blue). Source: Sasaki and Matsui, 2008, p. 135. Adapted by permission from Macmillan Publishers Ltd: NATURE REVIEW GENETICS (Sasaki & Matsui), copyright 2008
A literal interpretation of this distinction between bimaternal and parthenogenetic, and the use of sperm-free rather than parthenogenesis, would be that reproduction involving two females is not virginal —an idea that suggests sperm and penetration are not necessary components of sexual intercourse. Virgin birth now refers to eggs that begin dividing and developing without sperm and without any additional genetic contribution, male or female. This redefinition of parthenogenesis means that Kaguya does not contradict the idea that viable mammalian parthenogenesis is impossible. This redefinition also defies the idea that males are necessary for sexual intercourse. Lastly, it reveals the absurdity of trying to use a word like virgin—a social concept full of ambiguity—to define a group of genetically modified, experimental organisms.
Conclusions and Future Directions
This paper has documented biologists' use of the words parthenogenesis and bimaternal reproduction to describe various developmental processes in mammals, particularly the birth of a mouse with two mothers and no father. Regarding the power of scientific language, Judith Butler has written, "The language of biology participates in other kinds of languages and reproduces that cultural sedimentation in the objects it purports to discover and neutrally describe" (1990, p. 109). Parthenogenesis presents a clear case in which the language of biology participates in other languages. Definitions of parthenogenesis are inextricably bound to definitions of virginity, and biological descriptions of dividing eggs contribute to the cultural sedimentation of maternity, paternity, male, female, sexually experienced, and virgin.
The scientific language used to describe parthenogenesis also contributes to societal beliefs about what kinds of reproduction are natural or artificial, possible or impossible. As Donna Haraway has written, "Sex, sexuality, and reproduction are central actors in high-tech myth systems structuring our imaginations of personal and social possibility" (1990, p. 211). When scientists describe the paternal genome as necessary and mammalian parthenogenesis as impossible, the myth of Adam and Eve—an ideal nuclear family composed of one heterosexual male father and one heterosexual female mother with their biological children—is maintained and naturalized. When scientists describe eggs as sperm-like or mimicking a paternal contribution, this naturalizes the idea that two-mother families are in fact impossible because one woman must act as the man or father.
Though the Kaguya experiment can solidify a heteronormative reproductive status quo, it can simultaneously disrupt it by offering bimaternal sexual reproduction as a queer alternative. I use queer to describe something outside of and counter to heteronormativity—the cultural privileging of two distinct, complementary genders (male and female), in which there is an alignment of biological sex, gender identity, gender roles, heterosexual practice and heterosexual desire. Defining queer as oppositional can be problematic, perpetuating binaries and essentialism (Walters, 2005). Others have conceptualized queer as something difficult to define, an ever-changing "perpetual dialogue between sexual identity and its critique" (Merck, 2005, p. 187). Queer can be a helpful to think about how parthenogenesis has challenged reproductive norms, which are very much tied to gender and sexual norms.
Heteronormative and queer interpretations of the Kaguya experiment produce tension and ambivalence in parthenogenesis research that is not new or exclusive to reproductive technologies. Many feminists, including Shulamith Firestone in 1971 and Donna Haraway in 1983, have noted that technologies—whether atomic energy, fertility control, or genetics—can be used to support both a feminist cause and its antithesis. Thus, to see parthenogenetic technology and its language as entirely upholding heteronormative values would be to overlook their potential for advancing queer feminist thought.
For, when scientists describe maternity or paternity as something independent of gamete sex, they destabilize the conflation of female with maternal and of male with paternal. When scientists describe all-female reproduction as not virginal, they challenge the necessity of males for sexual intercourse. This allows for the existence of genderqueer gametes and a family composed of two sexually experienced mothers and their biological children. The myth of Adam and Eve is replaced by a myth of active eggs and the (female) developmental biologist's pipette. Moreover, when scientists use the terms sperm-free and bimaternal instead of parthenogenesis, there is an acknowledgement that at times existing language, ambiguous and seeped in cultural meaning, is inadequate to describe nature.
Was this change in language an example of a productive feminist intervention in science? After all, developmental biology has an especially successful track record of feminist intervention (Gilbert & Rader, 2001; Keller, 1997; Schiebinger, 1999). Or, as Emily Martin has argued (1991), perhaps the changing language is part of a historically consistent story, one that mirrors changing social beliefs about gender and family. The Kaguya experiment and scientific articles that cite it were published during a decade of rapid changes in LGBT politics in the United States, which included the legalization of same-sex marriage. Since 2004, five scientific articles that cited the Kaguya experiment (2%) also explicitly discussed the possibility of human same-sex biological reproduction, (Testa & Harris, 2004; Edwards, 2007; Deng et al., 2011; Sparrow, 2014; Palacios-Gonzalez, Harris & Testa, 2014). For example, Bob Edwards, awarded the Nobel Prize for his role in developing IVF, wrote:
Future research could also investigate the feasibility of human bimaternal reproduction, with careful consideration of the practical and ethical challenges of translating basic science results to clinical medicine. Recent advances in reproductive technology include the creation of human sperm and egg precursor cells derived from both male and female skin cells (Cyranoski, 2014; Irie et al., 2015); so-called three parent children derived from one woman's egg mitochondria, another woman's egg nucleus, and a man's sperm (Gallagher, 2015); and uterus transplantation (Brown, 2015). Scientists, physicians, and heterosexual couples are actively developing and demanding these new reproductive technologies. What about bimaternal reproduction?
Using the Kaguya experiment techniques on human eggs has been deemed "far too complicated and risky" (Connor, 2004, p. 3) and "even more complex, inefficient and unsafe than cloning" (Highfield, 2004, p. 16). But since 2004, the Kaguya experimental protocols and results—viable mice with two mothers and no father—have been replicated and optimized, with a "success rate equivalent to the rate observed with in vitro fertilization of manipulated normal embryos" (Kawahara et al., 2007a, p. 5183).
Skeptics point to the genetic engineering practices essential to mammailian bimaternal reproduction as the main reason why it is not a practical or ethical option for humans. Recall that one of Kaguya's mothers was genetically engineered to produced eggs without a functional copy of the gene H19. Indeed, the random insertion of altered genes into the genome can lead to fatal cancers. However, the development of the Crispr-Cas9 system in 2011 has made DNA editing easier and less error-prone, and in 2015, scientists at Sun Yat-sen University in China used the system in human embryos to modify the gene responsible for a life-threatening blood disorder (Liang et al., 2015).
Figure 6. Schematic of aberrant imprinting patterns found in Beckwith-Wiedemann Syndrome patients. Note the loss of H19 expression on the maternal allele in example b-1. Kono and colleagues genetically engineered a mouse that lacked a functional copy of H19. Some people with Beckwith-Wiedemann Syndrome do not express H19, due to aberrant imprinting. Source: Weksberg et al. 2010, p. 10. Reprinted by permission from Macmillan Publishers Ltd: EUROPEAN JOURNAL OF HUMAN GENETICS (Weksberg et al.), copyright 2010
Altering the human genome, with or without the Crispr-Cas9 system, will likely remain tightly regulated and ethically controversial (Wade, 2015). But even in the absence of genetic engineering, imprinting differences currently exist in the human population due to genetic variation. For example, a subpopulation of people with Beckwith-Wiedemann syndrome are known to have genetic errors on the chromosomal region encompassing H19—the gene missing in one of Kaguya's mothers (Figure 6; Weksberg et al., 2010). Symptoms of Beckwith-Wiedemann syndrome include subfertility (Greer, 2008). Could individuals with imprinting disorders like Beckwith-Wiedemann Syndrome have eggs with a paternal imprint or sperm with a maternal imprint? Could unintentionally combining a paternally imprinted egg with paternally imprinted sperm help explain the low success rate (~30%) of IVF (Centers for Disease Control and Prevention, 2015; Figure 7)? If so, couples struggling with IVF failure could also benefit from advances in human bimaternal reproductive technology.
Figure 7. Potential explanation for some IVF failures. A-B: Successful reproduction requires combining one maternally imprinted genome and one paternally imprinted genome, regardless of whether the paternal genome comes from sperm (A) or egg (B), as it did in the Kaguya experiment. C: If a paternally imprinted sperm is combined with a paternally imprinted egg (due to an imprinting error), the embryo will have double the amount of some protein but lack other essential proteins. Early development will progress normally in the IVF petri dish, but development will fail after the embryo is implanted into the uterus.
In an interview about Kaguya's birth in 2004, Kate Kendell, the executive director of the American National Center for Lesbian Rights, compared bioengineered same-sex reproduction to the colonization of Mars. She told reporters, "[It's] not a realistic possibility, but something that will provoke a number of interesting conversations"(Hall, 2004, para. 12). A decade later, Jennifer Pizer, the law director for a prominent LGBT rights advocacy organization stated, "I do think it's sex or sexual orientation discrimination to treat a man with a female partner and a very low or absent sperm count differently than a lesbian with a female partner and nonexistent sperm count" (Fairyington, 2015, para. 19). Pizer's statement appeared in a New York Times article about health insurance, but I believe it also applies to new reproductive technologies. Is there an ethical imperative to develop same-sex reproductive technology, given existing efforts to assist subfertile heterosexual couples? Japanese artist Ai Hasegawa's work provokes just this question. In her (Im)possible Baby project, Hasegawa outlined several potential same-sex reproductive technologies and then created computer-generated models of a lesbian couple’s potential children, based on genetic traits of the future parents (2015a; 2015b). A documentary about the simulation and its ethical implications aired on Japanese national television. Hasegawa argues, "Even if the society concludes to ban this [same-sex reproductive] procedure in the end, these potential parents must have a chance to think and raise their voice" (2015a).
All-female human reproduction has been considered imaginary, mythical, and impossible, but the Kaguya experiment, changes in LGBT politics, and advances in reproductive technology make human bimaternal reproduction feasible. IVF became a human reproductive technology nine years after demonstrating its feasibility, and only with the support of private funding (Johnson, 2011; Johnson et al., 2010). It has been ten years since the Kaguya experiment. But even if human same-sex reproduction does not become a reality, the scientific language used to describe the Kaguya experiment is significant in itself. The language and reality of bimaternal sexual reproduction contradicts the idea that biological sex, paternity, maternity, and sexual experience are easily defined and unalterable. The Kaguya experiment does not foreshadow the elimination of men, but offers a future where sex and family are chosen expressions of joy and pleasure rather than determinants of reproductive destiny.
Acknowledgements
Thank you to Sarah Franklin and Helen Curry for supervising the essay and dissertation that evolved into this paper.
Notes
2 By this time, scientists had reported viable parthenogenesis in insects, reptiles, amphibians, fish, and turkeys (Bataillon, 1912; Mirouze, 1942; Olsen & Marsden, 1954; Smith, 1935).
3 For a detailed account of Hoppe and Illmensee's cloning experiments, others' conflicting results, accusations of fraud, and the aftermath, see Wilmut, Campbell and Tudge (2000) and Kolata (1999).
4 Retrospectively, Woo Suk Hwang and colleagues at Seoul National University have been credited with the first generation of human parthenogenetic stem cells in 2004. The so-called"Hwang scandal" arose in 2006, when Hwang's report of the first cloned human embryonic stem cells (Hwang et al., 2004) appeared to be falsified. Hwang and colleagues were accused of research misconduct and their results were discredited. In 2007, a group of Harvard biologists discovered that Hwang's supposed cloned human embryonic stem cells were actually parthenogenetic (Kim et al., 2007).
5 Dolly's creators provide an insightful commentary on the (im)possibility of mammalian parthenogenesis in their 2000 book, The Second Creation. They write, "Parthenogenesis in mammals'—development of a whole new animal from an unfertilised egg—really does seem 'biologically impossible' [...] In the absence of divine intervention, virgin birth for mammals is not an option" (Wilmut, Campbell, & Tudge, p. 147). But the authors go on to propose, "Parthenogenesis might be achieved in the future if biologists learn how to convert a maternally imprinted genome into a paternally imprinted genome, or vice versa. No one is even close to this but there is no present reason to doubt that it is possible" (p. 147). Only four years later, Kono and colleagues did just that.
6 See also Casci, 2004; Cookson, 2004; Dayton 2004; Fisher, 2004; Gorman, 2004; Hall, 2004; Pagán Westphal, 2004; Rincon, 2004; Utton, 2004; von Radowitz, 2004; Weiss, 2004
7 Thomson Reuters Web of Science search query: CITED TITLE: ("Birth of parthenogenetic mice that can develop to adulthood") Refined by: DOCUMENT TYPES: (ARTICLE OR REVIEW) AND RESEARCH DOMAINS: (SCIENCE TECHNOLOGY) AND LANGUAGES: (ENGLISH) Timespan: 2004-2014.
8 Krawetz, 2005; Zadeh et al., 2005; Wang et al., 2007; Lampert, 2008; Paffoni, et al. 2008; Chen et al., 2009; Hikichi et al., 2010; Neaves & Baumann, 2011; Kwak et al., 2012; Ragina et al., 2012; Strogantsev & Ferguson-Smith, 2012; Kyurkchiev et al., 2012; Han et al., 2013; Isom et al., 2013; Ma et al., 2014
9 Guenin, 2005; Hurlbut, 2005; Kiessling, 2005; Cibelli, Cunniff & Vrana, 2006; Mertes, Pennings & Van Steirteghem, 2006; Hikichi et al., 2007; Lengerke et al., 2007; Mai et al., 2007; Wakayama et al., 2007; Watt, 2007; Lampert, 2008; Lampton et al., 2008; Sanchez-Pernaute et al., 2008; Koh et al., 2009; Li et al., 2009; Bebbere et al., 2010; Schwartz, 2011; Kwak et al., 2012; Ragina et al., 2012; Li et al., 2014; Yin et al., 2014
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Bio
Eva Gillis-Buck is a medical student at the University of California, San Francisco. She received an M.Phil. in the history and philosophy of science from the University of Cambridge and an A.B. in developmental biology and gender studies from Harvard University. Her research interests include reproductive technologies and the immunology of pregnancy.
In addition to challenging the definitions of fertilization and parthenogenesis, nuclear transfer technique in mammals allowed for the experimental creation of new entities, including gynogenetic and androgenetic embryos: fertilized embryos from which a scientist microsurgically removes the sperm nucleus or egg nucleus, respectively (Figure 1). In the late 1970s and 1980s, scientists experimented with these embryos in order to ask questions about the necessity and sufficiency of different aspects of the egg and sperm. Using gynogenetic embryos, scientists hoped to explain the inviability of mouse parthenogenesis by pin-pointing the necessary paternal component, whether nuclear or cytoplasmic. Note the question was not, Is the sperm necessary? but rather, What part of the sperm is necessary?
Figure 1. A schematic explaining the distinctions between parthenogenesis, gynogenesis, and androgenesis. In parthenogenesis, eggs begin divided and developing without sperm. Scientists create gynogenetic embryos by microsurgically removing the sperm nucleus from the fertilized egg. Androgenetic embryos are created by removing the egg nucleus from a fertilized egg. Source: Leeb and Wutz, 2013, p. 2.
In 1977, biologists Peter Hoppe and Karl Illmensee reported the live birth of gynogenetic and androgenetic mice, suggesting that some non-genetic contribution of sperm, released into the egg at fertilization, was enough to direct proper development. But their results could not be replicated.3 Other research groups reported the opposite result and conclusion: gynogenetic and androgenic mouse embryos failed to develop to term, suggesting both the maternal and paternal nucleus are necessary for complete development (Mann & Lovell-Badge, 1984; Modliński, 1975; Surani & Barton, 1983). Experiments demonstrating the developmental failure of biparental mouse embryos (in which two egg or two sperm nuclei are transferred into an enucleated egg) gave further support for the idea that both the maternal and paternal genome are necessary for mammalian development (McGrath & Solter, 1984; Surani et al., 1984).
1.3 Genomic Imprinting. But why are both maternal and paternal genomes required? In 1984, Cambridge biologist Azim Surani and his colleagues suggested that eggs and sperm undergo differential DNA modification during egg maturation and sperm maturation (1984). Such DNA modification is an epigenetic process, involving chemical and structural changes that effect protein synthesis but do not change the DNA sequence. Differential modification in eggs and sperm would mean that for some genes, only the maternal copy is expressed (translated into protein), while for other genes, only the paternal copy is expressed. Thus, two copies of a maternal genome—as is the case in parthenogenesis—would result in too much of some proteins and a complete lack of other essential proteins (Figure 2). Surani and colleagues named this type of genetic modification imprinting (not to be confused with the term for an animal behavior common in geese). Genomic imprinting (also called parental imprinting) became a classic example of epigenetics and the definitive explanation for the inviability of mammalian parthenogenesis (Ferguson-Smith, 2011).
Figure 2. A schematic explaining genomic imprinting. In the case of androgenesis, gynogenesis, or parthenogenesis, there will be too much of some proteins and none of other essential proteins.
1.4 Parthenogenetic stem cells. At the turn of the twenty-first century, mammalian parthenotes became a technology of stem cell science. In 2002, a Massachusetts-based biotech firm isolated stem cells from primate parthenogenetic embryos (Cibelli et al., 2002). In 2007, scientists at the California-based International Stem Cell Corporation derived human parthenogenetic stem cells (Revazova et al., 2007), an accomplishment quickly replicated (Kim et al., 2007; Lin et al., 2007; Mai et al., 2007).4
Some scientists and bioethicists argued that human parthenogenetic stem cells had advantages over human embryonic stem cells. First, they were genetically similar to the adult egg donor, and thus better for therapeutic use (less risk of immune rejection). Second, the process of deriving the stem cells did not destroy a human embryo. At a time when American scientists could not use federal funding for the creation of human embryonic stem cell lines, it was argued that parthenogenetic stem cells could "circumvent ethical concerns" because the process of deriving them did not damage a "normal competent embryo"(Cibelli et al., 2002, p. 819). The idea that parthenotes are not normal, competent embryos is largely based on the claim that viable mammalian parthenogenesis is impossible. For example, a group of American bioethicists argued:
Embryos result from fertilization
and thus contain genetic material from two parents. Additionally, they
have the potential to develop into a live birth baby. In contrast,
parthenotes do not undergo fertilization, have genetic material from
one source (the oocyte), and cannot move beyond early stages of
development. (Rodriguez et al., 2011, p. 22)
Embryonic stem cell politics made human parthenotes a valuable
source of alternative stem cells, and their inviablity was a
particularly advantageous attribute that distinguished them from human
embryos.I see scientists' observations, manipulations, and descriptions of parthenogenesis as a kind of domestication process, a way of making parthenotes into a productive laboratory tool. The discourse of impossibility was part of that process; the idea that mammalian parthenotes are inviable arose out of their experimental use and then became the basis of future experimentation. Experimental questions transitioned from Can parthenotes develop to term? to Why can't parthenotes develop to term? and finally to How can we use these inviable parthenotes to better understand genomic imprinting and to derive stem cells? This latest question led to the routine use of parthenotes as puzzle-solving tools in experimental biology, in which the impossibility of viable mammalian parthenogenesis was taken for granted.
PART 2. Making sense of Kaguya by redefining sex, parenthood, and virgin birth
In the first half of this paper, I describe the development of the scientific consensus that viable mammalian parthenogenesis is impossible. Next, I investigate scientific reactions to the 2004 live birth and healthy development of a mammalian parthenote, Kaguya. The history of science is full of impossibilities later found to be possible, for example: vacuum, airplanes, black holes, in vitro fertilization (IVF), and mammalian cloning. Kaguya's birth might have similarly overturned a consensus of impossibility, as did the birth of Dolly the cloned sheep.5 Yet Kaguya's birth was frequently interpreted as supporting, not overturning, the idea that viable mammalian parthenogenesis is impossible. In making sense of this apparent contradiction, some scientists redefined parthenogenesis and thus virgin birth.
2.1 The Kaguya experiment. In the early 2000s, Tomohiro Kono and colleagues—based in universities and biotech companies throughout Japan and Korea—et out to investigate whether genomic imprinting was the only barrier to parthenogenesis. To do so, Kono and colleagues bred a genetically modified female mouse that lacked a functional copy of an imprinted gene called H19. They took an immature egg from that mouse and transferred the egg's nucleus, containing a modified genome, into a typical adult female mouse egg (Figure 3). The resulting embryo (with two egg nuclei and no sperm contribution) began dividing, as expected, but what happened next was not expected: 28 out of 457 embryos appeared to develop normally, and eight were born alive. One mouse, Kaguya, grew into adulthood, mated with male mice, and gave birth to a typical litter.
Figure 3. The Kayuga Experiment. Kono and colleagues first made a genetically modified female mouse that lacked a functional copy of an imprinted gene H19. They took an immature egg from that mouse and transferred the egg's nucleus, containing a modified genome, into a typical adult female mouse egg. The resulting bimaternal embryo (Kayuga) developed normally.
Recall that genomic imprinting is an epigenetic process, which controls how DNA is made into protein. For most genes, protein is made from both maternal DNA and paternal DNA. But some genes are imprinted or silenced, so that protein is made from only the maternal copy or from only the paternal copy. In parthenogenesis, where exclusively maternal DNA is present, the embryo ends up with too much of some protein and entirely without other essential proteins (Figure 2). The placenta doesn't develop correctly and the pregnancy fails. In the Kaguya experiment, one mother's egg lacked H19. That lack of H19 caused many epigenetic changes, silencing some genes and activating others. When the genetically modified egg was combined with a normal egg, the combination of proteins produced in the embryo was adequate to support development and bring about the birth of Kaguya.
In 2004, Kono and colleagues published these results in Nature. The article, "Birth of parthenogenetic mice that can develop to adulthood," emphasized Kaguya's relevance to earlier ideas about genomic imprinting. They wrote:
There is no direct evidence that
genomic imprinting is the only barrier to parthenogenetic development.
Here we show the development of a viable parthenogenetic mouse
individual from a reconstructed oocyte containing two haploid sets of
maternal genome [...] These results suggest that paternal imprinting
prevents parthenogenesis, ensuring that the paternal contribution is
obligatory for the descendant. (Kono et al., 2004, p. 860)
Kaguya was the result of a search for a molecular explanation for
the failure of mammalian parthenogenesis, not an effort to make it
possible. Nevertheless, the article's title announced to the world
that
virgin birth in mammals had happened.Kaguya's birth provoked dozens of headlines about virgin birth and unnecessary men, such as "The Mouse that Roared: Virgin Birth!" (Connor, 2004) and "The Obsolescence of Men" (Highfield, 2004). Provocative first sentences included "Here' a new scientific theory: men really are useless" (Shin, 2004); and "Men, your gender just took a hit in the animal kingdom" (Ritter, 2004). Universally, reporters asked if Kaguya's birth meant that men were no longer necessary for human reproduction.6 Scientists interviewed about the meaning of Kaguya's birth were quick to dispel the idea that parthenogenesis was a reproductive option for humans. They argued that human parthenogenesis was ethically and practically impossible, and Kaguya's birth only reinforced the necessity of a paternal contribution. Kono dismissed questions about human parthenogenesis as "senseless" and "insignificant"(Weiss, 2004, p. 13). Azim Surani supported Kono's position, telling reporters that the techniques used to make Kaguya were too inefficient for human application (Connor, 2004; Rincon, 2004). Surani also insisted that Kaguya's birth did not demonstrate male redundancy, but actually "show[ed] the opposite" (Pagán Westphal, 2004). Anne Ferguson-Smith, clinical director of the Centres for Assisted Reproduction, told reporters, "This does not mean that males are obsolete. The requirement for paternal chromosomes for normal development is still with us"(Connor, 2004, p. 3; Highfield, 2004, p. 16).
These interpretations of Kaguya's birth surprised and intrigued me: how could a mouse without a father demonstrate the necessity of the paternal contribution? Perhaps the interviewed scientists were reacting to media sensationalism. Did they make similar statements in their peer-reviewed scientific publications? Did most scientists agree with this interpretation, or did any describe Kaguya as a revolutionary demonstration of all-female mammalian reproduction that foreshadows new human reproductive technology?
2.2 Methodology. Given existing scholarship on media coverage of Kaguya's birth (Ingram-Waters, 2008; Lafuente Funes, 2012), my research questions focused on what scientists have said about Kaguya in peer-reviewed publications. I examined 202 scientific publications, published between 2004 and 2014, that cite the Kaguya experiment. To identify these articles, I used Thomson Reuters Web of Science, a comprehensive database that has indexed more than one billion references and is especially designed for identifying networks of citation (King, 2015). I searched for English-language scientific articles and reviews that cited the 2004 Nature article "Birth of parthenogenetic mice that can develop to adulthood" by Kono and colleagues.7 This search yielded 226 publications. After excluding book chapters, since book chapters are not necessarily peer-reviewed, there were 202 publications in my data set to analyze. For each article, I asked how the author(s) interpreted the Kaguya experiment, with the goal of identifying consensus and variability. I focused particularly on how the authors discussed the possibility of mammalian parthenogenesis and used the words maternal, paternal, parthenogenesis, and bimaternal.
Similar methods have been used to great effect by social scientists Rebecca Jordan-Young (2010) and Sarah Richardson (2013). Jordan-Young conducted an extensive critique of brain organization research by identifying a founding paper in the field and using Web of Science and other databases to collect more than three hundred peer-reviewed scientific publications that cited that paper (2010, pp. xi-xii). Sarah Richardson has also used Web of Science to identify and qualitatively analyze highly cited scientific articles that report genetic sex differences (2013, pp. 219-224). Given the size of my data set, contextualizing each and every article or author in time, geography, and discipline is beyond the scope of this paper and a limitation of these methods. However, directly engaging with hundreds of primary scientific articles published over a ten-year time period offers insight into common and unusual scientific language to describe a mouse without a father.
2.3 Scientists' mixed interpretations of the Kaguya experiment. Between 2004 and 2014, scientists from across the globe cited the Kaguya experiment in their published work, which appeared in journals specializing in genetics, reproductive and developmental biology, human and animal fertility, stem cells, cancer, and ethics (Figure 4). This diverse group of authors interpreted the Kaguya experiment differently, but after reading all 202 articles, three main trends emerged: 1) seventy-five publications (37%) explicitly stated that viable mammalian parthenogenesis is possible and/or the paternal genome is unnecessary; 2) seventy-four publications (37%) explicitly stated that mammalian parthenogenesis is impossible and/or the paternal genome is necessary; and 3) forty-three articles (21%) described mammalian parthenogenesis as artificial: something that can occur, but not in nature (Table 1).
Figure 4. Summary of peer-reviewed scientific publications that cite the Kayuga experiment. Analysis by publication year, top ten authors, top ten journal titles, and top ten author's country/territory affiliations by Thomson Reuters Web of Science.
Table 1. Interpretations of mammalian parthenogenesis after Kayuga's birth.
There were exceptions: several articles did not mention parthenogenesis at all, but cited the Kono et al. study solely for its methods (Choi et al., 2006; Kim et al., 2008; Ma et al., 2005; Oh et al., 2005; Shao et al., 2007; Sim & Min, 2014). Other authors cited the Kaguya experiment when discussing imprinted genes in early development, but they did not mention parthenogenesis explicitly (Ahmad et al., 2005; Kobayashi et al., 2012; Li et al., 2012; McConnell et al., 2005).
2.4 Viable mammalian parthenogenesis is artificial. I was most intrigued by publications that stated viable mammalian parthenogenesis was impossible but also acknowledged Kaguya's birth—an apparent contradiction. This happened in fifteen articles (7%).8 For example, an article in the International Journal of Molecular Medicine read:
Parthenotes cannot develop to term.
Kono et al have demonstrated that parthenogenetic mice with a 13-kb
deletion in the maternal imprinting gene H19, which is located on the
same chromosome as the Igf2 gene, could
develop to term. (Kwak et al., 2012, p. 258, emphasis mine)
Another article stated, "Mammalian parthenogenotes [...] are
incapable of
developing to term" (Isom et al., 2013, p. 586), and then went on to
say, "Parthenogenetic mice have been born that survived into
adulthood,
but significant genetic engineering to imprinted regions of the genome
was necessary to allow this to happen" (ibid.). The authors imply
impossibility without scientific intervention and possibility with
scientific intervention. This distinction is made explicit in the
forty-three publications (21%) that described viable mammalian
parthenogenesis as artificial, not natural, or requiring genetic
modification (Table 1, column 3).The framing of viable parthenogenesis as artificial is significant with regard to the politics of stem cell research. Twenty-one publications (10%)9 stated that because mammalian parthenotes can never spontaneously or naturally develop to term, human parthenotes are distinct from human embryos, making human parthenogenetic stem cells an ethical alternative to human embryonic stem cells. For example:
Parthenote embryos exhibit defects
in genomic imprinting and cannot develop into live offspring without
significant genetic manipulation, thereby eliminating some of the
ethical controversy surrounding ES cell therapies. (Lampton et al.,
2008, pp. 448-9)
On first reading, these publications appear to uphold the
discourse of impossibility by describing live-born mammalian
parthenotes as an exception to the rule, only occurring after extensive
and deliberate scientific intervention. By emphasizing the artificial,
unnatural, and genetically altered quality of viable parthenotes,
authors demote parthenotes from potential humans to effective tools for
pluripotent stem cell creation. All-female mammalian reproduction is
artificial, and male-female reproduction is natural and spontaneous.
This dichotomy supports a heteronormative reproductive status quo.Yet one article suggested that the genetic engineering necessary to create Kaguya could be used to restore an embryo to a more natural state:
Any alteration from the
"traditional" way of conceiving, such as assisted reproduction
treatment, may carry some related risks, as has been suggested in some
publications. At the same time, with a widening understanding of the
different aspects of epigenetic mechanisms, it may be possible to
achieve genetic reprogramming to an extent that may restore all
conditions to the "natural settings" [the authors cite Kono et al.
2004]. (Nagy, Kerkis, & Chang, 2008, p. 540)
Here, genetic engineering leads to a more natural
outcome for embryos created via assisted reproductive technologies.
These examples reveal ambiguous and subjective distinctions between
natural and artificial. Feminist science scholars, Donna Haraway in
particular, have convincingly argued that "our form of social
existence
has permanently displaced the dualisms of nature and science, natural
and artificial"(1983, p. 8). Viable mammalian parthenotes, like IVF
embryos and joint replacements, embody a merging of machine and
organism; they exemplify Haraway's "cyborg" (1990) and Sarah
Franklin's "cyborg embryo" (2006). The requirement of genetic
intervention to
make
viable parthenotes does not make their existence less real, but
demonstrates an unprecedented level of control over mammalian
reproductive possibilities, thus challenging the reproductive status
quo.2.5 Genomic imprinting is a barrier to parthenogenesis. In sixteen articles (8%), the Kaguya experiment is cited for the idea that genomic imprinting prevents or blocks viable parthenogenesis (Table 2, column 1). For example, in a review of cancer epigenetics, an author wrote, "One remarkable feature of the wild type H19 ICR is that it provides a barrier to parthenogenesis via so far unknown mechanisms," and cited Kono et al. (Göndör, 2013, p. 95). The same language was used by Kono and colleagues themselves in the original 2004 Nature publication: "There is no direct evidence that genomic imprinting is the only barrier to parthenogenetic development [...]Our study shows that imprinting is a barrier to parthenogenetic development in mice"(p. 860, 863). This use of the Kaguya experiment seems to uphold the discourse of impossibility and a reproductive status quo, because Kono and colleagues are credited for discovering why parthenogenesis doesn't happen, as opposed to the accomplishment of actually making it happen. However, like the requirement for genetic modification, this barrier language also implies newfound control over reproduction. Once the barrier is known, it can be torn down. The Kaguya experiment revealed the key obstacle to parthenogenesis by overcoming it, thus demonstrating the practical tools and methods needed to make viable mammalian parthenogenesis a reality.
Table 2. Scientific language redefining sex, parenthood, virgin birth.
2.6 Maternal and paternal are qualities within scientific control. In the 2004 Nature publication, Kono and colleagues wrote, "These results suggest that paternal imprinting prevents parthenogenesis, ensuring that the paternal contribution is obligatory for the descendant" (Kono et al., p. 860). This perspective relies on subtle distinctions between paternal, father, and sperm. One of Kaguya's mothers lacked a functional H19 gene, a genetic manipulation, which altered a vast number of imprinting genes such that the maternal genome resembled a paternally imprinted genome. Therefore, paternal imprinting was necessary for Kaguya to be born, but a father's sperm was not. But is a female genome with a paternal imprint a paternal contribution?
Seventeen scientific publications (8%) that cite the Kaguya experiment have described certain female gametes as male-like. Often a neonatal egg genome, which lacks a maternal imprinting pattern, and a genetically modified egg genome are both described as mimicking or simulating a male or paternal genetic contribution (Table 2, column 2). This language could be interpreted as upholding a heteronormative status quo by defining the manipulated egg as masculine, reflecting the idea that in two-mother families, one woman must be more masculine or act as the father figure. But there is also an interpretation that destabilizes the concept of binary sex. These authors are describing the sex of a genome as something independent of the sex of a gamete: a female egg can have a male-like genome and a paternal imprint. In this way, imprinting pattern could be considered a new sex characteristic. Anne Fausto-Sterling (2000) has convincingly argued that sex characteristics—hormone levels, chromosomes, genitalia, fat and hair deposition, internal reproductive organs—are a product of scientific and medical norms. These characteristics often do not align or fit neatly into a male-female binary. Similarly, eggs with a paternal imprinting pattern defy the biological basis of a simple two-sex system.
Moreover, after Kaguya, scientists described modifying the epigenetics of gametes to determine their maternity and paternity (Table 2, column 2). For example, "The deletion of the IG-DMR on chromosome 12 which causes paternalization of the maternal chromosome alone could restore some imbalance imposed by two maternal genomes" (Kawahara et al., 2006, p. 2877, emphasis mine). The functional maternity or paternity of eggs and sperm is not necessarily dependent on the biological sex of the parent, but on the pattern of genomic imprinting, which scientists can manipulate. This idea furthers scientific control over sex characteristics, adding to existing technologies such as hormone replacement therapy and surgery. It also challenges the alignment between father/paternal/male/sperm or the assumption that they are interchangeable terms. The egg—a female gamete—an be paternalized so that it provides a necessary paternal contribution to the embryo.
2.7 Bimaternal reproduction is not parthenogenesis. Finally, the statement Viable mammalian parthenogenesis is impossible makes sense, even in light of Kaguya's birth, if Kaguya is not considered parthenogenetic. And indeed, twenty-nine articles (14%) used gynogenetic or bimaternal to describe Kaguya, instead of parthenogenetic. The exclusion of Kaguya from parthenogenesis implies what is and is not considered virgin birth, thus challenging the role of sperm and males in the definition of virginity and sexual intercourse.
Several scientists explained why they decided to use a term other than parthenogenesis to describe Kaguya. For example, in a review of genomic imprinting in mammals, geneticists at the Russian Academy of Sciences wrote:
Recently,
Kono et al. reported striking data on obtaining two viable adult
parthenogenetic mice [...] We think, however, that these mice should be
classified with gynogenetic organisms, because the modified genome was
introduced into the ovum from outside. (Platonov & Isaev, 2006, p.
1038)
The
development of the resulting reconstructed egg was titled
"parthenogenesis", although it differed markedly from canonical
parthenogenesis, which relies solely on the egg's own chromosomes.
(Kiessling, 2005, p. 145)
Kono and colleagues have most clearly excluded bimaternal reproduction from parthenogenesis. Though the group originally referred to Kaguya as parthenogenetic in their 2004 article, later publications by the team refer to Kaguya and similar mice as bi-maternal conceptuses instead of parthenotes (Kawahara et al., 2006; Kawahara et al., 2007a; Kawahara et al., 2007b; Kawahara et al., 2008; Kawahara, Wu, & Kono, 2010; Kono, 2009; Wu, Kawahara, & Kono, 2008). A 2008 Nature Protocols publication clarified that this was an intentional redefinition:
The embryos
that were derived solely from maternal genomes were designated as
bimaternal embryos to clearly distinguish them from
parthenogenetic/gynogenetic embryos. (Kawahara et al., 2008, p. 197)
Figure 5. Schematic that accompanies a description of the Kayuga experiment. Note that "bi-maternal" is considered distinct from "parthenogenetic" because one of the maternal genomes has been genetically modified to more closely resemble a "paternal" imprinting pattern (shown in blue). Source: Sasaki and Matsui, 2008, p. 135. Adapted by permission from Macmillan Publishers Ltd: NATURE REVIEW GENETICS (Sasaki & Matsui), copyright 2008
A literal interpretation of this distinction between bimaternal and parthenogenetic, and the use of sperm-free rather than parthenogenesis, would be that reproduction involving two females is not virginal —an idea that suggests sperm and penetration are not necessary components of sexual intercourse. Virgin birth now refers to eggs that begin dividing and developing without sperm and without any additional genetic contribution, male or female. This redefinition of parthenogenesis means that Kaguya does not contradict the idea that viable mammalian parthenogenesis is impossible. This redefinition also defies the idea that males are necessary for sexual intercourse. Lastly, it reveals the absurdity of trying to use a word like virgin—a social concept full of ambiguity—to define a group of genetically modified, experimental organisms.
Conclusions and Future Directions
This paper has documented biologists' use of the words parthenogenesis and bimaternal reproduction to describe various developmental processes in mammals, particularly the birth of a mouse with two mothers and no father. Regarding the power of scientific language, Judith Butler has written, "The language of biology participates in other kinds of languages and reproduces that cultural sedimentation in the objects it purports to discover and neutrally describe" (1990, p. 109). Parthenogenesis presents a clear case in which the language of biology participates in other languages. Definitions of parthenogenesis are inextricably bound to definitions of virginity, and biological descriptions of dividing eggs contribute to the cultural sedimentation of maternity, paternity, male, female, sexually experienced, and virgin.
The scientific language used to describe parthenogenesis also contributes to societal beliefs about what kinds of reproduction are natural or artificial, possible or impossible. As Donna Haraway has written, "Sex, sexuality, and reproduction are central actors in high-tech myth systems structuring our imaginations of personal and social possibility" (1990, p. 211). When scientists describe the paternal genome as necessary and mammalian parthenogenesis as impossible, the myth of Adam and Eve—an ideal nuclear family composed of one heterosexual male father and one heterosexual female mother with their biological children—is maintained and naturalized. When scientists describe eggs as sperm-like or mimicking a paternal contribution, this naturalizes the idea that two-mother families are in fact impossible because one woman must act as the man or father.
Though the Kaguya experiment can solidify a heteronormative reproductive status quo, it can simultaneously disrupt it by offering bimaternal sexual reproduction as a queer alternative. I use queer to describe something outside of and counter to heteronormativity—the cultural privileging of two distinct, complementary genders (male and female), in which there is an alignment of biological sex, gender identity, gender roles, heterosexual practice and heterosexual desire. Defining queer as oppositional can be problematic, perpetuating binaries and essentialism (Walters, 2005). Others have conceptualized queer as something difficult to define, an ever-changing "perpetual dialogue between sexual identity and its critique" (Merck, 2005, p. 187). Queer can be a helpful to think about how parthenogenesis has challenged reproductive norms, which are very much tied to gender and sexual norms.
Heteronormative and queer interpretations of the Kaguya experiment produce tension and ambivalence in parthenogenesis research that is not new or exclusive to reproductive technologies. Many feminists, including Shulamith Firestone in 1971 and Donna Haraway in 1983, have noted that technologies—whether atomic energy, fertility control, or genetics—can be used to support both a feminist cause and its antithesis. Thus, to see parthenogenetic technology and its language as entirely upholding heteronormative values would be to overlook their potential for advancing queer feminist thought.
For, when scientists describe maternity or paternity as something independent of gamete sex, they destabilize the conflation of female with maternal and of male with paternal. When scientists describe all-female reproduction as not virginal, they challenge the necessity of males for sexual intercourse. This allows for the existence of genderqueer gametes and a family composed of two sexually experienced mothers and their biological children. The myth of Adam and Eve is replaced by a myth of active eggs and the (female) developmental biologist's pipette. Moreover, when scientists use the terms sperm-free and bimaternal instead of parthenogenesis, there is an acknowledgement that at times existing language, ambiguous and seeped in cultural meaning, is inadequate to describe nature.
Was this change in language an example of a productive feminist intervention in science? After all, developmental biology has an especially successful track record of feminist intervention (Gilbert & Rader, 2001; Keller, 1997; Schiebinger, 1999). Or, as Emily Martin has argued (1991), perhaps the changing language is part of a historically consistent story, one that mirrors changing social beliefs about gender and family. The Kaguya experiment and scientific articles that cite it were published during a decade of rapid changes in LGBT politics in the United States, which included the legalization of same-sex marriage. Since 2004, five scientific articles that cited the Kaguya experiment (2%) also explicitly discussed the possibility of human same-sex biological reproduction, (Testa & Harris, 2004; Edwards, 2007; Deng et al., 2011; Sparrow, 2014; Palacios-Gonzalez, Harris & Testa, 2014). For example, Bob Edwards, awarded the Nobel Prize for his role in developing IVF, wrote:
Newborn mice were created by
fusing two oocytes, and obtaining an offspring named Kaguya. This
approach has been suggested many times before as a means of enabling
two women to have their own child, but caution is needed when fusing
two eggs instead of achieving normal fertilization. (2007, p. 14)
When a group of biologists at the University of Texas reported the
birth of a mouse with two fathers and no mother in 2010, they wrote,
"Some day two men could produce their own genetic sons and
daughters"(Deng et al., 2011, pp. 614-7). These articles are
suggestive, but
further research is needed, particularly regarding the Japanese
cultural context underpinning the original Kayuga experiment, to
determine how visibility and acceptance of marginal sexualities and
families may have influenced scientists' descriptions of bimaternal
and
bipaternal organisms.Future research could also investigate the feasibility of human bimaternal reproduction, with careful consideration of the practical and ethical challenges of translating basic science results to clinical medicine. Recent advances in reproductive technology include the creation of human sperm and egg precursor cells derived from both male and female skin cells (Cyranoski, 2014; Irie et al., 2015); so-called three parent children derived from one woman's egg mitochondria, another woman's egg nucleus, and a man's sperm (Gallagher, 2015); and uterus transplantation (Brown, 2015). Scientists, physicians, and heterosexual couples are actively developing and demanding these new reproductive technologies. What about bimaternal reproduction?
Using the Kaguya experiment techniques on human eggs has been deemed "far too complicated and risky" (Connor, 2004, p. 3) and "even more complex, inefficient and unsafe than cloning" (Highfield, 2004, p. 16). But since 2004, the Kaguya experimental protocols and results—viable mice with two mothers and no father—have been replicated and optimized, with a "success rate equivalent to the rate observed with in vitro fertilization of manipulated normal embryos" (Kawahara et al., 2007a, p. 5183).
Skeptics point to the genetic engineering practices essential to mammailian bimaternal reproduction as the main reason why it is not a practical or ethical option for humans. Recall that one of Kaguya's mothers was genetically engineered to produced eggs without a functional copy of the gene H19. Indeed, the random insertion of altered genes into the genome can lead to fatal cancers. However, the development of the Crispr-Cas9 system in 2011 has made DNA editing easier and less error-prone, and in 2015, scientists at Sun Yat-sen University in China used the system in human embryos to modify the gene responsible for a life-threatening blood disorder (Liang et al., 2015).
Figure 6. Schematic of aberrant imprinting patterns found in Beckwith-Wiedemann Syndrome patients. Note the loss of H19 expression on the maternal allele in example b-1. Kono and colleagues genetically engineered a mouse that lacked a functional copy of H19. Some people with Beckwith-Wiedemann Syndrome do not express H19, due to aberrant imprinting. Source: Weksberg et al. 2010, p. 10. Reprinted by permission from Macmillan Publishers Ltd: EUROPEAN JOURNAL OF HUMAN GENETICS (Weksberg et al.), copyright 2010
Altering the human genome, with or without the Crispr-Cas9 system, will likely remain tightly regulated and ethically controversial (Wade, 2015). But even in the absence of genetic engineering, imprinting differences currently exist in the human population due to genetic variation. For example, a subpopulation of people with Beckwith-Wiedemann syndrome are known to have genetic errors on the chromosomal region encompassing H19—the gene missing in one of Kaguya's mothers (Figure 6; Weksberg et al., 2010). Symptoms of Beckwith-Wiedemann syndrome include subfertility (Greer, 2008). Could individuals with imprinting disorders like Beckwith-Wiedemann Syndrome have eggs with a paternal imprint or sperm with a maternal imprint? Could unintentionally combining a paternally imprinted egg with paternally imprinted sperm help explain the low success rate (~30%) of IVF (Centers for Disease Control and Prevention, 2015; Figure 7)? If so, couples struggling with IVF failure could also benefit from advances in human bimaternal reproductive technology.
Figure 7. Potential explanation for some IVF failures. A-B: Successful reproduction requires combining one maternally imprinted genome and one paternally imprinted genome, regardless of whether the paternal genome comes from sperm (A) or egg (B), as it did in the Kaguya experiment. C: If a paternally imprinted sperm is combined with a paternally imprinted egg (due to an imprinting error), the embryo will have double the amount of some protein but lack other essential proteins. Early development will progress normally in the IVF petri dish, but development will fail after the embryo is implanted into the uterus.
In an interview about Kaguya's birth in 2004, Kate Kendell, the executive director of the American National Center for Lesbian Rights, compared bioengineered same-sex reproduction to the colonization of Mars. She told reporters, "[It's] not a realistic possibility, but something that will provoke a number of interesting conversations"(Hall, 2004, para. 12). A decade later, Jennifer Pizer, the law director for a prominent LGBT rights advocacy organization stated, "I do think it's sex or sexual orientation discrimination to treat a man with a female partner and a very low or absent sperm count differently than a lesbian with a female partner and nonexistent sperm count" (Fairyington, 2015, para. 19). Pizer's statement appeared in a New York Times article about health insurance, but I believe it also applies to new reproductive technologies. Is there an ethical imperative to develop same-sex reproductive technology, given existing efforts to assist subfertile heterosexual couples? Japanese artist Ai Hasegawa's work provokes just this question. In her (Im)possible Baby project, Hasegawa outlined several potential same-sex reproductive technologies and then created computer-generated models of a lesbian couple’s potential children, based on genetic traits of the future parents (2015a; 2015b). A documentary about the simulation and its ethical implications aired on Japanese national television. Hasegawa argues, "Even if the society concludes to ban this [same-sex reproductive] procedure in the end, these potential parents must have a chance to think and raise their voice" (2015a).
All-female human reproduction has been considered imaginary, mythical, and impossible, but the Kaguya experiment, changes in LGBT politics, and advances in reproductive technology make human bimaternal reproduction feasible. IVF became a human reproductive technology nine years after demonstrating its feasibility, and only with the support of private funding (Johnson, 2011; Johnson et al., 2010). It has been ten years since the Kaguya experiment. But even if human same-sex reproduction does not become a reality, the scientific language used to describe the Kaguya experiment is significant in itself. The language and reality of bimaternal sexual reproduction contradicts the idea that biological sex, paternity, maternity, and sexual experience are easily defined and unalterable. The Kaguya experiment does not foreshadow the elimination of men, but offers a future where sex and family are chosen expressions of joy and pleasure rather than determinants of reproductive destiny.
Acknowledgements
Thank you to Sarah Franklin and Helen Curry for supervising the essay and dissertation that evolved into this paper.
Notes
2 By this time, scientists had reported viable parthenogenesis in insects, reptiles, amphibians, fish, and turkeys (Bataillon, 1912; Mirouze, 1942; Olsen & Marsden, 1954; Smith, 1935).
3 For a detailed account of Hoppe and Illmensee's cloning experiments, others' conflicting results, accusations of fraud, and the aftermath, see Wilmut, Campbell and Tudge (2000) and Kolata (1999).
4 Retrospectively, Woo Suk Hwang and colleagues at Seoul National University have been credited with the first generation of human parthenogenetic stem cells in 2004. The so-called"Hwang scandal" arose in 2006, when Hwang's report of the first cloned human embryonic stem cells (Hwang et al., 2004) appeared to be falsified. Hwang and colleagues were accused of research misconduct and their results were discredited. In 2007, a group of Harvard biologists discovered that Hwang's supposed cloned human embryonic stem cells were actually parthenogenetic (Kim et al., 2007).
5 Dolly's creators provide an insightful commentary on the (im)possibility of mammalian parthenogenesis in their 2000 book, The Second Creation. They write, "Parthenogenesis in mammals'—development of a whole new animal from an unfertilised egg—really does seem 'biologically impossible' [...] In the absence of divine intervention, virgin birth for mammals is not an option" (Wilmut, Campbell, & Tudge, p. 147). But the authors go on to propose, "Parthenogenesis might be achieved in the future if biologists learn how to convert a maternally imprinted genome into a paternally imprinted genome, or vice versa. No one is even close to this but there is no present reason to doubt that it is possible" (p. 147). Only four years later, Kono and colleagues did just that.
6 See also Casci, 2004; Cookson, 2004; Dayton 2004; Fisher, 2004; Gorman, 2004; Hall, 2004; Pagán Westphal, 2004; Rincon, 2004; Utton, 2004; von Radowitz, 2004; Weiss, 2004
7 Thomson Reuters Web of Science search query: CITED TITLE: ("Birth of parthenogenetic mice that can develop to adulthood") Refined by: DOCUMENT TYPES: (ARTICLE OR REVIEW) AND RESEARCH DOMAINS: (SCIENCE TECHNOLOGY) AND LANGUAGES: (ENGLISH) Timespan: 2004-2014.
8 Krawetz, 2005; Zadeh et al., 2005; Wang et al., 2007; Lampert, 2008; Paffoni, et al. 2008; Chen et al., 2009; Hikichi et al., 2010; Neaves & Baumann, 2011; Kwak et al., 2012; Ragina et al., 2012; Strogantsev & Ferguson-Smith, 2012; Kyurkchiev et al., 2012; Han et al., 2013; Isom et al., 2013; Ma et al., 2014
9 Guenin, 2005; Hurlbut, 2005; Kiessling, 2005; Cibelli, Cunniff & Vrana, 2006; Mertes, Pennings & Van Steirteghem, 2006; Hikichi et al., 2007; Lengerke et al., 2007; Mai et al., 2007; Wakayama et al., 2007; Watt, 2007; Lampert, 2008; Lampton et al., 2008; Sanchez-Pernaute et al., 2008; Koh et al., 2009; Li et al., 2009; Bebbere et al., 2010; Schwartz, 2011; Kwak et al., 2012; Ragina et al., 2012; Li et al., 2014; Yin et al., 2014
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Bio
Eva Gillis-Buck is a medical student at the University of California, San Francisco. She received an M.Phil. in the history and philosophy of science from the University of Cambridge and an A.B. in developmental biology and gender studies from Harvard University. Her research interests include reproductive technologies and the immunology of pregnancy.