Three Mothers Make a Baby: Is that Sex? Yes, Or Maybe?

Perhaps you haven’t heard, but the doubt in some men’s minds regarding the age-old question “mother-baby, father-maybe?” may one day be forever removed. Results of a scientific experiment announced in April demonstrated that no paternal role was needed for the creation of a most uncommon baby mouse.1 The triumph of Japanese researchers, this mouse (named Kaguya) was the product of two female mice.

In creating Kaguya, scientists combined one normal mouse egg and one very manipulated mouse egg to form a “parthenogenic” embryo, who was then implanted into a surrogate female mouse and subsequently born.2 Though this process is not reproducible (as of yet) in humans, researchers are nevertheless uncovering the keys for controlling early human development and producing artificial gametes.

The Birds and The Bees 101

As sperm and eggs mature, some 40 genes are selectively turned on or off based on their paternal or maternal environment. This differential pattern of gene expression based on parental source is called imprinting. It turns out that both paternal and maternal imprinted genes are required in order for a fetus and placenta to develop normally. If only one gender has contributed the imprinted genes, an embryo may begin to divide but it will die early during gestation.

Does an embryo containing genes from only one gender ever arise naturally? Late in egg maturation, an egg jettisons one set of chromosomes (called a “polar body”) in preparation to receive the male chromosomal set contained in sperm. This step is crucial, as—beyond simply being a crowd—three sets of chromosomes would prove deadly. If things go according to plan, the union of sperm and egg will result in the creation of a unique genetic individual comprised of half of her mother’s chromosomes and half of her father’s chromosomes. Sometimes, though, the egg makes a mistake and discards the wrong set(s) of chromosomes, or retains all three copies. Such an error is nearly always fatal.

By definition, if all of an organism’s genetic material is derived from a female, the process is termed parthenogenesis. Conversely, if all of an organism’s genetic material is derived from a male (which can occur if both female sets of chromosomes are mistakenly jettisoned and the male chromosomal set is doubled), the process is called androgenesis. It is worth noting that the dismal survival rate of cloned embryos is believed to be due to the fact that only maternal imprinting was present. It is still a bit of a mystery how a few cloned embryos are able to beat the odds and survive beyond birth.

The Key: Making a Suitable Egg

Now onto the experiment conducted by the researchers in Japan. These scientists had been striving to discern the influence of imprinted genes on mouse development and knew that the combination of two mature eggs would not result in a normally developing embryo. Though the technique employed was quite complicated, the researchers basically tried to manipulate conditions so that an atypical “donor” egg could initiate normal fetal development when combined with a normal egg. It’s questionable whether this manipulated second egg needed a masculine influence or whether just reducing the feminine influence was sufficient. Earlier, the scientists had found a way to reduce the maternal imprinting pattern on eggs by collecting them from newborn mice, before such imprinting occurred. Combining early or “ng” (for non-growing) eggs with normal eggs resulted in improved development (compared against that evidenced when two mature eggs were joined); however, the resulting embryos still couldn’t sustain development all the way to live birth. The researchers hypothesized that the problem lay with two genes that retained a maternal expression of Igf2 and H19 in the “ng” eggs. So, the “ng” eggs were genetically manipulated by turning off H19 and orchestrating the proper expression of Igf2. Combining these genetically modified “ng” eggs with normal eggs produced embryos that survived all the way to birth—albeit not very efficiently, as 457 “reconstructed” embryos resulted in only 2 live-born pups (one of which was sacrificed for research purposes).3

Murky Definitions

While these mice were called “parthenogenic” mice, such a labeling is not consistent with current use of this term. The classic definition of parthenogenesis, derived from the Greek term for “virgin birth,” is embryonic development that originates from a single maternal source of genetic material. In mammals, organisms created this way never complete gestation. It is important to note, however, that Kaguya was not the product of a virgin birth in the truest sense, as two females contributed their genetic material to her. While it is true that these mice didn’t physically copulate, their gametes were nevertheless combined to create genetically unique offspring. While the process was uni-sexual (involving only females), it was not asexual, but, rather, was closer to the mechanism of sexual reproduction in which new organisms are propagated via the genetic recombination of material from two different individuals. While some are saying that Kaguya resulted from an unfertilized egg (since no sperm was involved), fertilization—albeit artificial fertilization—nevertheless occurred.

The Reprogenetic Revolution

The term “reprogenetic” was coined to denote the coming together of the fields of genetics, reproductive biology, and developmental biology. While historically this knowledge was aimed at helping couples overcome infertility or alleviating genetic burdens, new techniques are on the horizon that have the power to shatter our conceptions of sexuality, fertility, and propagation.

Now is the time to draw the ethical perimeter for the reprogenetic frontier. Typically, scientific breakthroughs in animal models take more than a decade before they can be applied to the human system. The application of reproductive technologies to humans, however, continues to break the normal speed barrier, often bypassing animal testing altogether. As technology progresses ever faster, the prospect of new and more frightening nightmares seems likely. Fortunately, the early commentaries on the Japanese achievement all suggest that attempts to create a human embryo from two eggs would be a crazy way for humans to reproduce. It is tragic, though, that the main support for this assertion hinges on the health consequences for these manipulated embryos and/or a lack of availability of human eggs. While we certainly wish to protect the health of unborn children and are opposed to possible exploitation of women as egg donors, these reasons totally ignore the importance of holding sacred the sexual union between a man and woman. If Kaguya’s mode of creation were to be extrapolated to humans, the very basis of our society would be shattered—opening nearly endless possibilities for overcoming the normal reproductive barriers for mammals that requires both male and female genetic contributions.

Recently, the President’s Council on Bioethics published a report entitled Reproduction and Responsibility: The Regulation of New Biotechnologies.4 Several of the report’s recommendations are especially apropos given the Japanese experiment. Among these are prohibitions against “attempts to conceive a child by any means other than the union of egg and sperm” and prohibitions against “attempts to conceive a child by using gametes obtained from a human fetus or derived from human embryonic stem cells.”5 While the relevance of the first prohibition is self-explanatory, the second is also germane because if the product of two eggs is to be viable, one of the eggs must be “immature”—which suggests the human fetus as a potential source. Admittedly, some of the Council’s wording—e.g., “prohibit attempts to conceive a child”—may open itself to ambiguity; nevertheless, we must begin somewhere. Christians and those concerned about the dignity of human life and the sacredness of human procreation must urge Congress to address reprogenetic issues now! Currently our culture is struggling with what constitutes marriage…but soon the question will be expanded to what constitutes human procreation. We must stay ahead of the technology and be proactive in outlawing any form of human procreation that deviates from the combination of a single sperm and a single egg.

1 Kono, T. et al. “Mouse Created Without Father: Scientists Turn Egg Cell Into Surrogate Sperm.” Nature 428: 860-64.

2 Ibid.

3 Ibid.

4Reproduction and Responsibility: The Regulation of New Biotechnologies. Washington, D.C.: The President’s Council on Bioethics, March 2004.

5 Ibid., Executive Summary C: Targeted Legislative Measures.