BIBLIOGRAPHY and TIMELINE
What follows on this Web page is a timeline of developments in the scientific development of same-sex procreation techniques, which have been gradually developing over the last twenty years, but which will rapidly develope in the next twenty years. In the lifetimes of most people reading this Web page, there will be children born to same-sex couples, children for which the genetic rule will be "Honor Your Mother and Mother" or "Honor Your Father and Father". In light of the law, such procreation entitles marriage.
There is much science, engineering, politics, religion, ethics and some entertainment to be had with regards to same-sex procreation. If you are interested in learning as much as possible, we have prepared a BIBLIOGRAPHY of references that are both informative and a pleasure to read.
Timeline of same-sex procreation scientific developments
www.samesexprocreation.com/timeline.htm
Despite the recent nature of much of the scientific research into same-sex procreation, such research on a small scale has been conducted for many decades. Additionally, implications with regards to same-sex procreation date back centuries. And there is more to come in the future.
Not related to same sex procreation, but if you like interesting timelines, check out History of Invention in the Arts.
2000s 1990s 1950s-1980s pre-1950s Ancient
Scientific developments in same-sex procreation - 2000-2009
In April 2008, a consortium of stem cell researchers called the Hinxton Group release a consensus statement that exaggerates the difficulties of creating female sperm. In their statement, at one point, they declare:Such a statement reflects a complete ignorance of techniques such as micro-cell mediated chromosome transfer (MMCT) and mammalian artificial chromosomes (MACs) that can be used to add Y chromosomes to female germ-like stem cells on their way to becoming female sperm. Such a blatant error for these very well known techniques suggests a bit of homophobic bias on the part of the Hinxton group. The group's statement also has no mention of the successful fertilization use of female chicken sperm created by Japanese scientists in 1997, using creation techniques similar to those proposed by Brinster in 1991 for human sperm. The Hinxton report is at: Consensus statement: science, ethics and policy challenges of pluripotent stem cell-derived gametes. Two articles in the Times (UK) Online by science editor Mark Henderson fail to investigate the incorrect assumptions of the Hinxton statement. The articles also fail to interview any scientist competent in human male egg and female sperm research. The articles are: Sperm and eggs from stem cells in 15 years and How artificial sperm could help infertile couples.2b) There are biological and technical reasons that will make it even more difficult, or even impossible, to derive sperm that could be used for reproduction from XX (chromosomally female) cells).
In January 2008, scientists at Stemagen (La Jolla, CA) announced the creation of the first mature cloned human embryos from adult skin cells. Five of the embryos grew to the stage that fertility doctors consider ready for transfer to a woman's womb. Click here for images of the cloned embryos. Cells from such cloned embryos can be used for creating female sperm, and males egg.
In December 2007, biotech patent analyst Gregory Aharonian files a revised formal patent application for the process of making both female sperm, and males egg, taking advantage of the ability to file one last revision before patent laws force his patent application to be published 18 months after his original July 2006 filing.
In November 2007, biologists in Kansas report on a method to obtain adult female stem cells from menstrual blood. They report that such cells can be cultured in vitro and converted to a variety of somatic cell lines, including skin, bone, and muscle stem cells. Such stem stem cells might be converted into germ cell-like stem cells, and then used to create female sperm. Their article is titled "Endometrial regenerative cells: a novel stem cell population", J. Translational Medicine, 2007, 5:57. (Full Article) .
In November 2007, two groups (one in Japan, one at Harvard/MIT) announce the ability to convert adult skin cells into embryonic stem cells in humans. This is just five months after they announced similar results for converting mouse skin cells. The quickness in adapting their techniques to humans is a promising sign that turning such techniques into clinically offerings (which satisfy health regulations) probably will be achieved within the next ten years. Such clinical offerings will provide a source of stem cells used for making sperm and eggs from adult cells. A quote from the lead Japanese scientist reflects the ongoing bias of reproductive scientists to consider the fertility needs of homosexuals:
This Web site is a very good example of another purpose. Their papers are titled "Induction of pluripotent stem cells from adult human fibroblasts by defined factors", Takahashi et al., Cell, 20 November 2007;(epub) (Article abstract) and "Induced pluripotent stem cells lines derived from human somatic cells", Yu et al., Science, 20 November 2007:(epub) (Article abstract) ."But making sperm from a female iPS cell, and eggs from a male - I think both those procedures should be banned, because the only purpose of that is to make clones.", said Shinya Yamanaka of Kyoto University.
In July 2007, biotech patent analyst Gregory Aharonian based in San Francisco files a formal patent application for the process of making female sperm, still based on methods including using cloning to prepare a diploid germ cell for an adult woman, adding an artificial Y chromosome to the germ cells, and injecting them into the testes of an adult man to insure more natural imprinting. His patent application also includes a method for making male eggs, by extracting the X chromosomes from a man, adding them to his diploid germ cells, creating XX germ cells through non-disjunctional mitosis, and then in vitro cultivation of the XX germ cells into eggs. In December 2007, he files a slightly revised version of his patent application.
On July 7, 2007, pioneer reproductive biologist Anne Mclaren dies in a tragic car accident. Her obituary. One of her last papers reflected her commitment to ethics: A Scientist's View of the Ethics of Human Embyronic Stem Cell Research.
In June 2007, two groups (one in Japan, one at Harvard/MIT) announce the ability to convert adult skin cells into embryonic stem cells in mice. They do so by injecting four genes (Oct3/4, Sox2, c-Myc and Klf4) into the skin cells, which with in vitro cultivation converted the skin cells into embryonic-like plutipotent stem cells. The current method has problems: the mice have to be interbred, the genes are inserted with viruses, and two of the four genes can cause cancer - all of which have to be solved before using this technique for human cells. And these problems will be solved. Stem cells so created from adult skin cells could then be used in methods to produce female sperm and male eggs without cloning. Their papers are titled "Generation of germline-competent induced pluripotent stem cells", Keisuke Okita et al., Nature, 19 July 2007;448:313-317 (Article abstract) and "In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state", Marius Wernig et al., Nature, 19 July 2007:448:318-324 (Article abstract) .
In April 2007, Karim Nayernia and biologists at the University of Newcastle upon Tyne report additional results on creating, in vitro, male sperm from bone marrow stem cells in the book Gamete Biology: Emerging Frontiers on Fertility and Contraceptive Development, Univ. Nottingham Press. This work is a continuation of Nayernia's work at the University of Gottingen reported in July 2006 (see above) that suggested that sperm cells could be produced from bone marrow stem cells. The April 2007 results are reported along with an announcement that Nayernia and colleagues are seeking permission to try using the same techniques to create sperm from female bone marrow stem cells. A few newstories at the time (e.g., The prospect of all-female conception, Belfast Telegraph) repeat the speculations of similar news reports from 2006. These news reports make no mention of the use of artificial chromosomes to compensate for Y chromosome spermatogenesis genes. Nor do the news reports mention Nayernia having concerns for imprinting problems that other scientists have noticed with regards to cloning and artificially producing sperm.
In March 2007, UCLA scientists report on experiments with male mice for transplanting bone marrow stem cells into the testis, with evidence that the marrow cells start transforming into sperm cells. The article is silent about the possibility of transplanting bone marrow cells from a female to produce female sperm. Their paper is titled "Fate of bone marrow stem cells transplanted into the testis", Am. J. Pathology, v170 n3, March 2007, 899-908. (Article abstract) . However, about the same time, Chinese scientists publish a paper questioning the ability to so transform muscle stem cells into sperm. Their paper is titled "Mesenchymal stem cells do no differentiate into quasi-sperm", Zhonghua Nan Ke Xue, April 2007;13(4):309-11. (Article abstract) .
In 2007, biologists at McGill University in Canada report on the partial fertility of male mouse eggs. They show that XY eggs from sex-reversed female mice can be fertilized, but that few of the fertilized eggs divide beyond thet 2-cell stage. Since mice are genetically closer to man than fish (whose male eggs were shown to be viable), it suggests difficulties with producing human male eggs. However, the early 2000s work of Burgoyne suggests that genetic elements that interfere with the fertility of mammalian male eggs can be blocked. Their article is titled "The presence of X- and Y-chromosomes in oocytes leads to impairment in the progression of the second meiotic division", Developmental Biology, 2007, 1-13. (Article abstract) .
In January 2007, biologist Makoto Nagano of McGill university publishes a good review article on in vitro creation of sperm and eggs from embryonic stem cells, focussing on what research is needed to make such activities more successful and biologically safe. His article pretty much ignores mentions of the same-sex implications of the articles he reviews, in particular the creation of male eggs and female sperm. His article is titled "In vitro gamete derivation from pluripotent stem cells: progress and perspective", Biology of Reproduction, 2007, 76:546-551. (Article abstract) . This reporting that pretty much ignores implications of same-sex procreation is also in a slightly earlier article titled: "Germ cells from mouse and human embyronic stem cells", Reproduction, Nov. 2006, 132(5):699-707. (Article abstract) . To be so silent with a global social battle over same-sex marriage/procreation raging outside biology - is unethical.
In January 2007, the Ontario (Canada) Court of Appeal rules that a child can have three legal parents, in the case AA v. BB and CC. A lesbian couple and male sperm donor petitioned the court to have the biological mother's lesbian partner declared to be a parent with legal parental status to the biological mother and sperm donor father.
In 2006, retired family law attorney Brette McWhorter Sember publishes a book titled "Gay & Lesbian Parenting Choices", with chapters on sperm donors and surrogates. In a chapter titled "Other Parenting Options", she mentions the use of nuclear transfer cloning to combine two sperm (first add one sperm to a denucleated egg, then add the second sperm) to achieve male human samesex reproduction. While the process is impossible due to epigenetics, she is one of the few people, biologist or not, to publicly discuss the application of the latest cell biology techniques such as cloning to the reproductive needs of gays and lesbians, indeed one of the few people since Shettles injected sperm DNA into a denucleated egg in 1979.
A little later in July 2006, biotech patent analyst Gregory Aharonian based in San Francisco files an updated (from 1996) provisional patent application for the process of making female sperm, still based on methods including using cloning to prepare a diploid germ cell for an adult woman, adding an artificial Y chromosome to the germ cells, and injecting them into the testes of an adult man to insure more natural imprinting.
In July 2006, Karim Nayernia and biologists at the University of Gottingen report on creating, in vitro, male sperm from embryonic stem cells and possibly from bone marrow stem cells. They report on mice born when these generated sperm cells fertilized eggs. Being all in vitro for male stem cells, there is no need - their papers do not discuss - either using artificial Y chromosomes, or transplanting the stem cells into the testes. Their articles are titled "In vitro-differentiated embryonic stem cells give rise to male gametes that can generate offspring mice", Dev Cell, 2006 Jul, 11(1):1-13. (Article abstract) and "Derivation of male germ cells from bone marrow stem cells", Lab Invest., 2006 Jul, 86(7):654-63. (Article abstract) . While their publications do not mention the use of such techniques to make female sperm, a few July 2066 news stories and Internet discussions speculate on the possibility (e.g., Women could make sperm, irishhealth.com, and accompanying posted comments). In 2005, Nayernia and colleagues at the University of Gottingen file a patent application on a method of producing embryonic-like stem cells from germs cells from the testes of adult men.
In July 2006, Japanese biologists create roundworm female sperm. They do so with the classic nematode, C. elegans, by using RNA interference to disrupt the production of a protein from the daz-1 gene, which is known to be required for oogenesis in C. elegans. Their paper is titled "The Caenorhabditis elegans homologue of deleted in azoospermia is involved in the sperm/oocyte switch", Mol Biol Cell. 2006 Jul;17(7):3147-55. (Article abstract) .
In February 2006, Japanese scientists report on creating male eggs in fish, by extracting adult male germ cells from fish testicles, and transplanting them into an undifferentiated embryonic gonad in a female fish embryo's peritoneal cavity. The male eggs so produced were able to fertilized by sperm, achieving same-sex procreation in fish. While this procedure is unacceptable for humans, it does suggest that human same-sex procreation is a solvable problem. Their article is titled "Testicular germ cells can colonize sexually undifferentiated embryonic gonad and produce functional eggs in fish", Proc Natl Acad Sci. Feb. 2006; 103(8):2725-2729. (Article abstract) .
In 2005, Giuseppe Testa and John Harris write on the ethics of human samesex procreation in the context of any sort of artificial sperm and eggs. They argue that if such techniques satisfy medical ethics in terms of health of children so born, then the social ethics will be no different than the ethics of heterosexual assisted reproduction. Their paper is titled "Ethics and synthetic gametes", Bioethics, 2005, 19(2):146-166. (Article abstract) .
In 2005, Japanese scientists report that Brinster's 1991 process for transplanting stem cells into a post-natal testicular environment to generate sperm is a process that works for stem cells produced after fertilization as early as primitive as primordial germ cells. Such sperm was then used to fertilize eggs that resulted in normal, fertile offspring. This implies many of the epigenetic transformation of germ cells during spermatogenesis can be achieved in the post-natal environment, one major concern in the production of female sperm. Their paper is titled: "Spermatogenesis from epiblast and primordial germ cells following transplantation into postnatal mouse testis", Development, 2005, 132:117-122. (Article abstract) .
In 2005, Behrouz Aflatoonian and Harry Moore at the University of Sheffield report on their work in generating human primordial germ cells from embryonic stem cells, an extension of earlier works doing the same for mice, and how the primordial germ cells can start the process of becoming sperm or eggs. Their paper discusses the possibility that germ cells could be cultivated to become both sperm and eggs, that is, the production of male eggs or female sperm. Interestingly, press accounts at the time only report on the possibility of male eggs, and not female sperm (e.g., Stem cell building-blocks hold baby hopes for gays. In 2006 and 2007, the two research publish additional reports on their work. Their papers are: "Human primordial germ cells and embryonic germ cells, and their use in cell therapy", Curr Opin Biotech, 2005, 16:530-535, (Article abstract) ; and "Germ cells from mouse and human embryonic stem cells", Reproduction, 2006, 132(5):699-707, (Article abstract) ; and "From stem cells to spermatozoa and back", Soc Reprod Fertil Suppl, 2007, 65:19-32, (Article abstract) .
In 2004, Japanese biologist Tomohiro Kono and his colleagues achieves female same-sex procreation in mice. The scientists achieve this by combining one female egg with a second female egg which had a few genes altered/delete to make the second female egg more "masculine" (e.g., they deleted part of the second egg's H19 gene which is only maternally expressed, a gene that interacts with the IGF2 gene). Only two of 457 fertilized eggs resulted in normal daughter mice. The importance of this research is not its' clinical practicality, but its demonstration of the flexibility of the procreation process to epigenetic engineering. Their paper is titled "Birth of parthenogenetic mice that can develop to adulthood", Nature, v428, 22 April 2004, 860-864. (Article abstract) . In 2007, they improve the process, resulting in more live births of mice. Their paper is titled "High-frequency generation of viable mice from engineered bi-maternal embryos", Nature Biotechnology, v25, September 2007, 1045-1050. (Article abstract) . They also file a patent application.
In Apr 2004, George Daley and colleagues at the Harvard University report on creating partial male eggs from human embryonic stem cells in a culture environment. Both female and male embyonic stem cells were cultured to become both early germ-like cells and more mature egg-like cells. None of the male egg cells were developed far enough to be tested for their ability to be fertilized by sperm. Their paper is titled "Spontaneous differentiation of germ cells from human embryonic stem cells in vitro", Science, 1 Apr 2004, 727-39. (Article abstract) .
In Oct 2003, Chinese scientists report the creation of a two-parents-with-a-third human fetus. A BBC article reports on how Chinese scientists created a human fetus by taking the DNA from the egg of one woman, injecting the DNA into the DNA-free egg of a second woman, and then fertilizing the egg with a man's sperm. Three such fertilized eggs were implanted in the woman. One fetus was aborted at one month, and the remaining two delivered prematurely but not surviving past four months. Such a fetus in a sense has three parents, but in a very limited way, with the full DNA of one woman, the full DNA of one man, and the mitochrondrial DNA of the women donating the egg. It is unlikely any court would award parental rights solely on the basis of donating mitochrondria.
In June 2003, Brinster's and Scholer's colleague at the University of Pennsylvania, Ina Dobrinski, files for a patent on transplanting (human) testicle tissue into mice. Human germ cells can then be injected into the transplanted tissue to be converted into sperm, using the culturing environment of the mice instead of an in-vitro system. Such techniques could be used for growing human female sperm without the need for the full use of a man's testicles, with the testicle tissues transplanted into a chimpanzee (which is more genetically compatible with humans). The testicle tissue could be donated by men undergoing sex change operations. This stuff gets real creepy, doesn't it?!!!!!
In May 2003, Hans Scholer and colleagues at the University of Pennsylvania report on creating partial male eggs from mouse embryonic stem cells in a culture environment. Both female and male embyonic stem cells were cultured to become both early germ-like cells and more mature egg-like cells with a primitive zona pellucida, cells which showed markers of meiosis. None of the male egg cells were developed far enough to be tested for their ability to be fertilized by sperm. Their paper is titled "Derivation of oocytes from mouse embryonic stem cells", Science, 23 May 2003, 1251-1256. (Article abstract) . Such techniques can make use of techniques for cultivating female germ cells into eggs in vitro, as disclosed in papers such as: "Induction of oocyte-like cells from mouse embryonic stem cells by co-culture with ovarian granulosa cells", Differentiation, 2007, epub. (Article abstract) , "Factors affecting the developmental capacity of mouse oocytes undergoing maturation in vitro", Annals of the New York Academy of Sciences, 1988, 541:197-204. (Article abstract) , and "Growth and development of mouse oocytes in vitro", Annals of the New York Academy of Sciences, 1988, 541:205-210. (Article abstract) . In 2005/2006, Scholer and colleagues published additional results with reagards to the ability of mouse embryonic stem cells to start becoming male eggs, as well as reporting on the ability of mouse embryonic stem cells to become female sperm. Their papers are titled "Generating oocytes and sperm from embryonic stem cells", Seminars in Reproductive Medicine, 2005; v23(3):222-233, (Article abstract) , and "Embryonic stem cells as a potential source of gametes", Seminars in Reproductive Medicine, 2006; v24(5):322-329, (Article abstract) .
In January 2002, newswires briefly report on techniques for female sperm and female same-sex procreation being developed by Yuri Verlinsky and colleagues at the Reproductive Genetics Institute (RGI) of Chicago. The technique somehow involved extracting haploid DNA from one woman's cell, and injecting it into the egg of another women. Results to be presented at an April 2002 conference never were presented, and the RGI's Web site as of 2007 has no information on these activities. Suspicions are that the RGI researchers' techniques failed to compensate for missing Y chromosome and imprinting effects. RGI's work is based on the work of Italian biologist Dr. Severino Antinori, who one month earlier announced similar plans to recreate male sperm for men. Artificial sperm plan to avoid human cloning The Telegraph, 12 December 2001).
In March 2001, biologist Michael West proposes sex-changed induced female sperm and male eggs derived from cloned animals, that is, when cloning an animal, add/substract X and Y chromosomes to change the sex of the original animal's germ cells so that the animal's clone is of the opposite sex. For example, start with a male horse, and clone and sex-change it to produce a female horse, whose normal eggs have the non-sex chromosomes of the male horse, the equivalent of male eggs ready for fertilization. While their patent application does not discuss the use of this technique for humans, the patent claims do claim the use of the technique for "mammals". He discloses his ideas in U.S patent application 2002/174449 titled "Method for generating cloned animals using chromosome shuffling", (Patent Text)
In the early 2000s, developmental geneticist Paul Burgoyne and his colleagues, at the UK National Institute of Medical Research, note that the presence of the Rbmy gene family in XY female mice prevents their eggs from fully developing, since female XY mice with most copies of their Rbmy genes deleted can have a sufficient number of eggs fully develop to be fertile. They do not suggest, however, that this implies it is possible for male XY mice - male mice - and male humans - to have their cells transformed into male eggs, assuming the Rbmy/RBMY can be interfered with. Their work is reported at Impaired oogenesis in XY female mice - Abstract #1 and Abstract #2. One possibility is to use RNA inteference to block activity of the Rbmy/RBMY gene (see the 1999 Michigan entry that used RNAi to make roundworm male eggs). Earlier, Canadian biologists Asma Amaleh and Teruko Taketo had observed similar problems with male eggs due to the presence of one or more genes on the Y chromosome. Their paper is titled "Live-borns from XX but not XY oocytes in the chimeric mouse ovary composed of B6.Y(TIR) and XX cells", Biology of Reproduction. 1998; 58:574-582. (Article abstract) . Both Burgoyne's 2000s+ work, and the 1998 Canadian paper ignore Burgoyne's 1993 paper showing that XXY female mice are more fertile than XY female mice, which suggests that a male XY germ cell with an added X chromosome (producing an XXY germ cell) could more quickly lead to male eggs, since adding a chromosome is probably easier than an interfering with the expression of the Rbmy/RBMY gene. Burgoyne's 1993 paper is titled "Tdy-negative XY, XXY and XYY female mice: breeding data and synaptoemal complex analysis", J Reprod Fertil. 1993 Jan;97(1):151-60. (Article abstract) .
In 2000, scientists in Europe discover a health/fertile mother and daughter with a SRY-negative 47,XXY genotype. It is not observed at the time that cloned embryonic germ/stem cells from such women could be transformed according to Brinster's testicular transplantation method to make female sperm. It is also not observed that if women with a 47,XXY genotype can produce viable eggs, then it is likely that Klinefelter men with a 47,XXY genotype could have their cells turned into male eggs, as could normal 46,XY men who have an X chromosome added to their germ cells. Their paper is titled "An SRY-negative 47,XXY mother and daughter", Cytogenetic Cell Genetics, 2000 v91(1-4):204-7. (Article abstract) . The reproductive health of the 47,XXY mother is consistent with a 1993 paper by Paul Burgoyne and others that XXY female mice are more fertile than XY female mice. Their paper is titled "Tdy-negative XY, XXY and XYY female mice: breeding data and synaptoemal complex analysis", J Reprod Fertil. 1993 Jan;97(1):151-60. (Article abstract) .
Scientific developments in same-sex procreation - 1990-1999
In 1999, Case Western biologists Mroz, Carrel and Hunt show that non-mosaic XXY males are able to produce sperm by having their XXY germ cells, at some point, experience nondisjunctional cell-division to produce some XY germ cells that then undergo regular spermatogenesis with proper X chromosome in/re-activation. The unstated implication is that XXY cells from adult females could follow a similar pathway to then produce female sperm, for example, producing female sperm from the cells of adult human XXY females who were reported about in 2000. Their paper is titled "Germ cell development in the XXY mouse: evidence that X chromosome reactivation is independent of sexual differentiation", Developmental Biology. 1999;207:229-238. (Article abstract) . In 1999, Michigan biologists create roundworm male eggs. They do so with the classic nematode, C. elegans, by using RNA interference to disrupt the production of a protein from the fog-3 gene, which is known to be required for spermatogenesis in C. elegans. Their paper is titled "A novel member of the tob family of proteins controls sexual fate in Caenorhabditis elegans germ cells", Dev Biol. 2000 Jan;217(1):77-90. (Article abstract) .In 1998, biotech patent analyst Gregory Aharonian based in San Francisco files a provisional patent application for a complete process of making female sperm. His provisional application is titled "Method for female mammal spermatogenesis" (App. Num. 60/085816). In the years to follow, he continues to refine his methods, filing additional patent applications, until filing a formal patent application in 2007. His methods include using cloning to prepare a diploid germ cell for an adult woman, adding an artificial Y chromosome to the germ cells, and injecting them into the testes of an adult man.
In 1997, Japanese biologist Takahiro Tagami and colleagues mostly create female sperm in chickens, by transplanting female primordial germ cells into chicken testes. They are unable to create complete female sperm, the assumption being that the altered female W germ cells (female chicken cells are normally heterogametic, ZW) are unable to produce vital proteins needed to make complete sperm. They make no mention of artificial chromosomes to compensate, nor do they mention creating an analogous technique for producing female sperm in humans. Their paper is titled "Differentiation of female chicken primordial germ cells into spermatozoa in male gonads", Development, Growth and Differentiation, v39, 267-271. (Article abstract) . Ten years later they publish a follow-up article on their procedure, again with no mention of artificial chromosomes, titled "Differentiation of female primordial germ cells in the male testes of Chicken", Molecular Reproduction and Development, v74, 68-75 (2007). (Article abstract) .
In 1997, Princeton biologist Lee Silver proposes a method for partial female same-sex procreation. His method comprises fertilizing eggs from two women with X sperm from a man, and then fusing the two fertilized eggs in vitro. The resulting daughter will have 25% of her DNA from her first mother, 25% of her DNA from her second mother, and 50% of her DNA from the male sperm donor. His book is titled "Remaking Eden: Cloning and Beyond in a Brave New World". In 1998, he publishes an article on the legal confusions caused by such genetic manipulations, titled "Confused Heritage and the Absurdity of Genetic Ownership", Harvard Journal of Law and Technology, Summer 1998.
In 1996, the 104th United States Congress passes the Defense of Marriage Act that defines marriage in Federal law as "a legal union between one man and one woman as husband and wife". The law rests on one philosophical argument - the impossibility of same-sex procreation. As a comment in House Report No. 104-664 at 33 states: "Rather, [marriage laws] have been the unbroken rule and tradition in this (and other) countries primarily because they are conducive to the objectives of procreation and child-rearing." More on the politics and religion of marriage and procreation.
In 1995, University of Tennessee biologist Antonin Bukovsky and colleagues announce the discovery of adult female diploid germ cells, which were generally assumed to not exist (due to undergoing some stages of meiosis in the embryonic stage, unlike adult men who use their diploid germ cells to continually make sperm throughout their lives). However, by resetting the imprinting patterns of such adult female diploid germ cells, and compensating for missing Y chromosome spermatogenesis genes, such female cells can be converted, in vitro or in vivo, into female sperm. Their papers are titled "Immunohistochemical studies of the adult human ovary: possible contribution of immune and epithelial factors to folliculogenesis", Am. J. Reproductive Immunology, 1995, v33, 323-340. (Article abstract) , and "Ovarian germ cells", Methods in Enzymology, 2006, v419, 208-258. (Article abstract) , and U.S patent application 2007/010013 titled "Oocytes derived from ovarian culture initially containing no oocytes", (Patent Text)
In 1993, Japanese biologists Etsuro Yamaha and Fumio Yamazaki create four-parent goldfish, by electrically fusing two fertilized eggs. By using eggs from one fish and sperm from two male fish, they could have created goldfish with two fathers and one mother, partial male same-sex procreation. By using sperm from just one fish, they could have created goldfish with two mothers and one father, partial female same-sex procreation. Their paper is titled "Electrically fused-egg induction and its development in the goldfish, Carassius auratus", Int. J. Dev. Biol., v37, 291-298. (Article abstract) . Four years later, biologist Lee Silvers actually suggests this latter possibility for two human females and one male.
In 1991, Korean scientists are able to artificially grow immature human eggs/oocytes. Immature follicular oocytes are extracted at the dictyate stage of their first meiotic division, cultivate in vitro, and fertilized with sperm, leading to successful pregnancies. Not considered by the Korean scientist is that their success creates a target for generating human male eggs, that is, to create an adult male diploid germ cell, properly imprinted, that has also reached this state of the first meiotic division. Their paper is titled "Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte program", Fertility and Sterility, v55, 109-113. (Article abstract) .
In 1991, University of Pennsylvania biologist Ralph Brinster, in a patent application, suggests one method to produce human female sperm. His patent application, "Repopulation of testicular seminiferous tubules with foreign cells" (WO 93/11228 - PDF file) and (issued patent), discloses how to fix male sperm by removing sperm cells from the testicles, genetically fixing the sperm cells, chemically castrating the testicles to remove the remaining defective sperm cells, and then transplanting the corrected sperm cells back into the testicles. At one point in his application, he writes at page 7: "The use of female (XX) cells is also within the scope of the present invention.", i.e., using his methods to produce human female sperm. Neither Brinster, not anyone reading his patent application (such as Kaplan's bioethics group at UPenn), comment on this possibility. Interestingly, Brinster's technique somewhat appeared in a 1985 science fiction story, Shanidar by David Zindell (appearing in L. Ron Hubbard presents Writers of the Future), who writes at one point in his story: "I irradiated his testes and bathed them with sonics, killing off the sperm. .... So I went into his tubules and painstakingly sectioned out and mutated segments of his stem cell's DNA so that the newly produced germ cells would make for him sons after his new image."
In 1990, Dutch scientists Sjef Van de Leur and Gerard Zeilmaker report on a human egg fertilized by two sperm from one man. The fertilization occurred in their IVF clinic, and they suggest that the egg experienced an immediate cleavage before fertilization, creating a two cell egg, each cell of which was fertilized by a different sperm. Their paper is titled "Double fertilization in vitro and the origin of human chimerism", Fertility and Sterility. 1990;54(2):539-540. (Article abstract) . They do not observe that this result suggests a way to combine the sperm from two men with the egg of one woman, partial male same-sex procreation.
Scientific developments in same-sex procreation - 1950-1989
In 1985, feminist author Gena Corea writes on Landrum Shettles' 1971 attempt to achieve male cloning. She comments on how few, if any other, commentators considered using Shettle's method to clone a female by inserting the diploid DNA of an adult women into an egg emptied of DNA. But much like Shettles, Corea doesn't observe that by inserting the DNA from the eggs of two women into an DNA-free egg, it is possible to achieve female same-sex procreation. Her comments here appear on page 261 of her book titled "The Mother Machine: Reproductive Technologies from Artifical Insemination to Arificial Wombs", Harper & Row Publishers.In 1984, biologists Betty Hoskins and Helen Bequaert Holmes suggest the possiblity of female same-sex procreation by the method of fusing two unfertilized eggs. Unfortunately, due to imprinting effects, this method will not work (just as somehow combining two sperm will not work). Twenty years later, Japanese scientists, by manipulating imprinting genes, successfully combine two eggs. The women mention this method in an article titled "Technology and Prenatal Femicide" in a book titled "Test Tube Women: What Future for Womanhood?", Pandora Press.
In 1980, UCLA biologists Shakti Upadhyay and Luciano Zamboni report on the partial development in mice of male eggs. They observe that in some male mice embryos, some of the germ cells that are supposed to end up in the testes region to become sperm, instead end up in the adrenal cortexes and medullas (organs not associated with making sperm and eggs). In the male mice, the germ cells undergo the same type of meiotic divisions that germ cells in female ovaries undergo. In the males, the eggs survive for a few weeks, while displaying characteristics identical to those of young eggs in the unilaminar ovarian follicles of women. While the eggs die off, the results do suggest that under more appropriate in vivo and/or in vitro environments, that viable male eggs could be created for not only mice but humans as well, though the article does not so speculate. Their paper is titled "Ectopic germ cells: natural model for the study of germ cell sexual differentiation", Proc Natl Acad Sci. November 1982;79:6584-6588. (Article abstract) .
In 1981, English biologist Anne McLaren reports that XX germ cells in fetal testes of XX sex-reversed male mice can propagate to some extent. While she did not comment, her research implies that if somehow diploid germ cells of an adult woman could be prepared, maybe if such cells are transplanted into a testicular environment, female sperm could be produced. Indeed, in 1991 (see below), American biologist Ralph Brinster, in a patent application, suggests this. Her paper is titled "The fate of germ cells in the testis of fetal sex-reversed mice", J. Reprod. Fertil. (1981), v61, 461-467. (Article abstract) .
In 1980, biologists Sharp, Wachtel and Benirschke report on the equivalent of a male egg for horses. They report on a fertile sex-reversed XY female horse, that is, a female horse with the XY genotype normally seen in males, with the female horse being fertile so that any offspring with a male horse's sperm being the genetic equivalent of male same-sex procreation. The unstated implication is that germ/stem cells of adult male mammals, under the right cellular conditions, could become male eggs. Their paper is titled "H-Y antigen in a fertile XY female horse", J. Reprod Fertil. 1980 Jan;58(1):157-60. (Article abstract) .
In 1979, American biologist Landrum Shettles attempts the first human cloning, by removing the DNA (polar body) from a human egg, and replacing it with diploid DNA remove from one spermatogonia cell (pre-sperm cell), stopping development after three day at the morula stage. He could have suggested, but didn't, the possibility of male same-sex procreation, by observing that it could be possible to remove the haploid DNA from sperm cells from two men, haploid DNA to be injected into the empty egg cell. Such a manipulation would have been possible at the time. His paper is titled "Diploid nuclear replacement in mature human ova with cleavage", Am. J. Obstet. Gynecol., 15 January 1979, 222-225. (Article abstract) . A letter in the July 1979 issue questions if Shettles was actually successful, to which Shettles replied by defending the functioning of the morula he observed.
In 1975, English biologist C. E. Ford and colleagues report on the discovery in a mouse of a male egg. The egg actually comes from a chimaeric XX/XY female mouse, with the egg definitely being "male" since the discovery was triggered by the birth of an albino son, the mother being part albino. They observe that this occurrence may not be a random accident, but that male XY eggs could be more common. They do not comment on the implications for humans. The 1975 paper thanks Anne McLaren for her advice. Their two papers are titled "A functional 'sex-reversed' oocyte in the mouse", Proc. R. Soc. Lond. B, v190, 187-197. (Article abstract) , and "Direct evidence of the capacity of the XY germ cell in the mouse to become an oocyte", Nature, v267 (1977), 430-431. (Article abstract). Twenty five years later, English biologist Paul Burgoyne and colleagues start research to make the creation of human male egg more practical.
In 1972, American biologists Ralph Brinster and Laila Moustafa report on injecting embryonic cells into the blastocyst of another embryo, creating four-parent mice, a different approach than that used by McLaren three years earlier. By using an egg from one mouse and sperm from two male mice, they could have created mice with two fathers and one mother, partial male same-sex procreation. Or, by using sperm from just one mouse and two eggs, they could have created mice with two mothers and one father, partial female same-sex procreation. Their two papers are titled "The fate of transplanted cells in mouse blastocysts", J. Exp. Zool., v181, 181-191. (Article abstract) , and "Induced chimaerism by transplanting embryonic cells into mouse blastocysts", J. Exp. Zool., v181, 193-202. (Article abstract) . Thirty years later, biologist Lee Silvers actually suggests this latter possibility for two human females and one male.
In 1969, English biologists Anne McLaren and Patricia Bowman report on fusing embryos to create four-parent mice, which while having been achieved before, in their case, the mice-pairs differed by nine genetic factors. This suggests the future success of combining DNA from more than two adult mammals. By using an egg from one mouse and sperm from two male mice, they could have created mice with two fathers and one mother, partial male same-sex procreation. Or, by using sperm from just one mouse to fertilize two eggs, they could have created mice with two mothers and one father, partial female same-sex procreation. Their paper is titled "Mouse chimaeras derived from fusion of embryos differing by nine genetic factors", Nature, v224, 238-240. (Article abstract) . Thirty years later, biologist Lee Silvers actually suggests this latter possibility for two human females and one male.
In 1968, scientists report on the possibility of feminine-man male sperm, that is spermatocytes produced by men with non-mosaic Klinefelter syndrome. Such men have an extra X chromosome (47,XXY genotype), and have male physiques with some feminine features and some physiological problems. In time, other clinics confirm sperm production by non-mosaic 47,XXY men. In the forty years that follow, no one observes that adding a SRY-negative artifical Y chromosome to a female germ cell creates a condition similar to that of germ cells in non-mosaic Klinefelter men. If the latter can produce sperm, it suggests the same for the augmented female germ cells, i.e., female sperm. Their paper is titled "Klinefelter's syndrome and it's variants: a hormonal and chromosomal study", Recent Prog. Horm. Res., v24, 321-63, (Article abstract) . More information on Klinefelter men.
In 1960, biologist Helen Crouse invents the term chromosome imprinting to refer to the phenomena where "... the 'imprint' a chromosome bears is unrelated to the genic constitution of the chromosome and is determined only by the sex of the germ line through which the chromosome has been inherited." In the decades to come, imprinting becomes a major challenge to achieving same-sex procreation. Her paper is titled "The controlling element in sex chromosome behavior in Sciara", Genetics, 1960;45:1429-1443 (Article fulltext). She continues to study chromosome behavior throughout her career, passing away at the age of 91 in 2006 (Obituary).
In 1955, Japanese biologist Toki-o Yamamoto reports on the equivalent of a male egg for one species of fish, the medaka fish. He reports on fertile sex-reversed XY female medakas, that is, a female fish with the XY genotype normally seen in males, with the female fish being fertile so that any offspring with a male fish's sperm being the genetic equivalent of male same-sex procreation. In 1975, a similar result is achieved with mice, and in 1980 with horses, mammals more reproductively similar to human, which should have suggested that germ/stem cells of adult male mammals, under the right cellular conditions, could become male eggs. His paper is titled "Progeny of artificially induced sex-reversals of male genotype (XY) in the medaka (Oryzias Latipes) with special reference to YY-male", Genetics. 1955 May;40(3):406-19. (Article abstract) .
Scientific developments in same-sex procreation - pre-1950s
In 1905, Nettie Stevens, a female scientist at Bryn Mawr College, discovers the male-making Y chromosome, which later scientists prove is the chromosome that has genes to turn a developing embryo into a male, and genes that the male's sexual organs use to produce sperm. She does her research on mealworms, noticing that while mealworm eggs always have 10 large chromosomes, mealworm sperm can have either 10 large chromosomes or 9 large chromosomes plus 1 small chromosome. Her discovery sets the stage for Thomas Hunt Morgan's discovery of sex-linked inheritance.In 1892, German scientist Theodor Boveri proposed the use of the phrase "stem cell" to refer to germline cells at stages between the fertilized egg and committed germ cells in the gonads. That same year, German scientist Valentin Hacker also used "stem cell" to refer to cells that are precursors to oocytes. This use of "stem cell" was popularized by American biologist Edmund B. Wilson in his 1896 book, The Cell in Development and Inheritance. For more on this, read On the origin of the Term "Stem Cell" by UCSF researchers Miguel Ramalho-Santos and Holger Willenbring.
In 1890, German scientist Hermann Henking discovers the X chromosome, by noticing that one chromosome acted differently from the others during the production of sperm, appearing in only half of all sperm. Because it seemed to be an extra-chromosome, he names it the "x"-chromosome. In 1901, Clarence McClung at the University of Kansas, establishes that X chromsome is responsible for sex inheritance, also noticing that it appeared in some sperm but not all sperm - making it the male determining chromosome. While he was wrong, it sets the stage for the discovery of the Y chromosome.
In the 1870s, three German scientists, Oscar Hertwig, August Weismann and Herman Fol, clearly show that a sperm plus an egg equally contribute to the creation of a new life.
In the 1660s and 1670s, three European scientists, Reinier de Graaf, Jan Swammerdam and Niels Steno, prove that women have eggs, much like other mammals (proved by de Graaf in 1672 in his De Mulierum Organis Generationi Inservientibus Tractatus Novus). A few years later, in 1678, Antoni Leeuwenhoek uses a microscope to discover sperm, the 'seed' component of semen. Unfortunately, the scientists split into two camps, 'ovists' and 'spermists', in arguing that either eggs or sperm are the main contributor to a new human. It takes 200 years for science to discover the correct explanation.
In 1639, Dutch surgeon Johann can Beverwyck writes one of the first feminist books arguing equality of women, the little known (by modern day feminists :-) Excellence of the Female Sex (Van de Wtnementheyt des Vrouwelichen Geslachts). He was inspired to so write by the spectacular educational accomplishments of a young Dutch woman of his times, Anna Maria van Schurman. At one point in his arguments about the equality of women and men, he argued that women contribute as much to their offspring as do males, citing the mention of female sperm in the New Testament Book the Letters to the Hebrews (at 11:11).
Ancient historical developments in same-sex procreation
Around 1270, Christian thinker Thomas Aquinas, in his five volume Summa Theologica, writes that women come from defective sperm - "woman is defective and misbegotten". He also writes in Summa Theologica that "... when a female is produced, this is because the agent cause [that results in complete humans, i.e., males] is thwarted, either because of the unsuitability of the receiving matter [of the mother] itself or because of some deforming inteference, as from south winds, that are too wet, as we read in [Aristotle's] Animal Conception. Aquinas' scientific nonsense helps the Catholic Church poison the study of reproduction, sexuality and women's rights for centuries.Circa the year 70 (50-90), an unknown Hellenistic Jewish Christian writes a letter, the Epistle to Hebrews, most likely to fellow believers in Rome. Section 11 of Hebrews, talks about the great faith of mythical religious figures such as Enoch and Noah. Verse 11 of Section 11, Hebrews 11:11, talks about how Sarah's faith allowed her to conceive with Abraham, even though she was so old to be sterile - "By faith even Sarah herself recieved power to conceive. Interestingly, the original Greek of Hebrews associates an act with Sarah - kataboleen spermatos - that is, Sarah had a female sperm emission, a view of biology consistent with the writings of Hippocrates (probably well known to the Greek writer of Hebrews). Still, the view is false - false biology, a scientific error in the New Testament. Worse, while some early bibles such as the King James Version repeat this Biblical error in English, other bibles, including many bibles today, deliberately falsely translate the passage, attributing the sperm to Abraham. For example, today's New International Version of the New Testament has "By faith Abraham, even though he was past age - and Sarah herself was barren - was enabled to become a father ..." - a doubly erroneous statement in the New Testament.
Circa the 4th century BCE, Greek philosopher Hippocrates writes that both men and women produce sperm, i.e., that there is female sperm, in his writing On the Generating Seed and the Nature of the Child - "In fact both partners alike contain male and female sperm". About 2000 years later, scientists prove that women only contain eggs.