In vitro fertilization (IVF), which includes embryo transfer (ET), is a form of human-assisted reproduction that has been bypassing some forms of fertility since the first “test-tube baby” was reported in the medical journal The Lancet in 1973. IVF involves the manual combination of egg and sperm outside the womb, resulting in fertilization as usually occurs in unassisted reproduction. The resulting embryo is then implanted in the uterus to be carried to term by the mother.
What is Three-Person IVF?
Two years ago, Newcastle University researchers announced that they had successfully developed a technique to swap the contents of two eggs. Nuclear transfer has been studied since the 1920s, and used since the 1990s for cloning somatic cells, cells that already contain the number of chromosomes needed to produce a viable human embryo. In April 2010, the research group announced that they had succeeded in developing viable embryos using this method after fertilization with sperm, a first in medical and fertility research. The technique was termed three-person IVF because it requires not only the mother’s egg and father’s sperm, but also an additional donor egg.
How Three-Person IVF Works
The procedure begins like in vitro fertilization; the mother’s egg is fertilized with the sperm in a clinical laboratory. This procedure results in chromosomal combination in the nucleus, the formation of the zygote. The nucleus is removed from a donor egg, leaving behind the cell membrane filled with the cytoplasm and organelles. The nucleus (zygote at this stage) is removed from the fertilized egg and transferred to the anucleated donor egg. The resulting embryo is transplanted into the mother as in IVF.
The resulting fetus, and thus child, would have the mother’s and father’s DNA, but the donor’s mitochondrial DNA.
Mitochondrial DNA and Inherited Disease
DNA is well known as the blueprint within human cells, making all of the proteins and signals necessary to be an individual living organism. Most DNA is carried within the cell nucleus, and is separated into chromosomes. However, humans also carry a second set of genetic instructions, mitochondrial DNA, which is inherited only from the mother via her egg. The mitochondrial genome carries a portion of the genes involved in mitochondrial function, estimated to be roughly 10% of those needed for mitochondria and 1% of the entire human genome.
The mitochondria are organelles that reside in the cytoplasm of the cell producing energy in the form of ATP via cellular respiration. This energy is used in many aspects of cell function and phsyiology. Genetic defects in the mitochondrial DNA can lead to many forms of disease, which are incurable. Mitochondrial diseases are more common in children as inherited conditions, but adult onset diseases can sometimes occur. Because most of the genes responsible for mitochondria function are specific to certain cell types, many inherited mitochondrial diseases are tissue-specific, occurring only in the, for example, heart or liver.
Reducing the Risk of Inherited Mitochondrial Disease
Three-person IVF is seen as a proof of concept that mitochondrial diseases can one day be reduced. Transferring the fertilized nucleus from the biological mother’s egg with aberrant mitochondrial DNA into an anucleated egg with healthy mitochondria can pass on healthier mitochondria to the child.
However, there are some issues surrounding this procedure. Ethicists are concerned over the fact that the child will get genetic information from the donor via the mitochondria. Also, not all mitochondrial diseases are caused only by mitochondrial DNA and are still poorly understood to some extent, so determining which mothers may pass along disease is still uncertain. Moreover, due to current reproductive research laws, the research group could not confirm that the viable embryo would become a viable fetus; the embryos had to be destroyed after 100 cells. However, the technique has been shown to create viable offspring in macaque monkeys created by first swapping the nuclei and then fertilizing the combination egg.
At the moment, this procedure should be seen as nothing more than how the researchers presented it, as a proof of concept, not a viable cure. At some point in the future, this technique may be used to prevent some inherited diseases that can be determined prior to fertilization, if ethical objections, legal limitations, and technical necessities are overcome.
Sources:
American Pregnancy Association
Craven et al. Pronuclear transfer in human embryos to prevent transmission of mitochondrial DNA disease. Nature, online publication April 14, 2010. doi:10.1038/nature08958
United Mitochondrial Disease Foundation
Alicia Mae Prater - Alicia received her doctorate in Experimental Pathology in 2007. She has been a freelance writer and scientific editor since 2008.
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