Understanding the Three-Parent Baby

Pilar Calva
January 5, 2017
Reproduced with Permission

While most (99.9%) of the human genome (DNA) is found in chromosomes in the cell nucleus, a small percentage (0.1%) of our DNA is found in the mitochondria - small bean-shaped structures which float around within the cell. Among other things, mitochondria use oxygen to convert the energy from food into a form cells can use. Mutations in this mitochondrial DNA (mtDNA), which can cause metabolic and degenerative diseases, and forms of cancer, are the driving force behind three-parent babies.

Each potential-mother's oocyte (egg cell) contains hundreds of mitochondria and both mutant and normal mtDNA can be present simultaneously and in different proportions. When mtDNA mutations reach 10-30% of the population, patients can manifest diabetes or, in rare cases, autism. At 50-90% mutation, patients can manifest neurological, heart and muscle problems, dementia, stroke, blindness and deafness. Total, 100% mutation, can result in infant encephalopathy and premature death.

One Example

Leigh Syndrome (LS) is one example of near total mutation. LS a neurological disorder that usually becomes apparent in the first year of life. It is characterized by progressive loss of mental and physical ability and can result in death within the first two to three years, usually due to respiratory failure. However, a small number of individuals with LS will not develop symptoms until adulthood while others may have symptoms that worsen more slowly.

LS affects roughly 1 in 40,000 newborns. It can be caused by mutations in one of more than 75 different genes. In humans, most of those genes are found in the nuclear DNA, but about 20 percent have a mutation in mtDNA.

Mitochondrial Replacement Techniques (MRTs)

The three-parent baby is the proposed solution to mtDNA aberrations. By replacing the prospective mother's aberrant mitochondria with the healthy mitochondria of another woman, the potential disease can be avoided. However, that substitution introduces the mtDNA of a third person into the baby.

How is it done?

One technique is called Maternal Spindle Transfer (MST) wherein artificial reproductive techniques are used to obtain oocytes from the prospective mother and from a donor. The donor oocyte nuclear DNA is enucleated (i.e. removed). Then the mother's nuclear DNA is transferred to the enucleated donor's oocyte. The reconstructed oocyte now has healthy mitochondria, can be fertilized in vitro, and then transferred into the mother or a surrogate.

Another technique is the Pronuclear Transfer , (PT) wherein two zygotes are created in vitro. One of them is made with the prospective parents' sperm and oocyte, and the other one with a donated oocyte and a sperm (from the father or a donor). During the first hours, after the sperm has fertilized the oocyte, but before the sperm and egg have fused, the nuclear DNA of each parent is enclosed in different membranes: the male and female pro nuclei (each has only 23 chromosomes). The two pro nuclei are removed from both zygotes. The intending parents pro nuclei is transferred to the enucleated donor's oocyte. The reconstructed zygote is then transferred into the mother or the surrogate.

Is It Ethical?

According to the Therapeutic Principle the proposed procedure must be a safe way to control the disease. However, in the procedures above, the risk for the patient (the child/children) is quite high. Both procedures risk compatibility issues between the donor mtDNA and the parental nuclear DNA which could result in significant health issues. Furthermore PT risks the killing of an embryo if pro nuclei fusion takes place before the transfer. It is not licit to kill one person to save another.

In addition, MRTs require in vitro fertilization with all its ethical issues: the conjugal act is substituted by a technique, embryos are killed and frozen, eugenic selection of embryos (because any male offspring created would be at no risk of passing on any inheritable disease associated with mitochondria this procedure easily invites child sex selection) and surrogate mothers.

Furthermore, three-progenitor-conceived children who do reach maturity could well experience some form of psychological suffering as a result of having genetic ties to three persons. What rights would the child and donor of mtDNA have to know and meet each other or would this relationship be kept in secret?

Finally, the harms are not limited to the potential children. Both techniques require egg donations from women with healthy mitochondria. The therapeutic principle is not met here because the donor has no disease and takes mild to severe medical risks from hormonal stimulation and egg retrieval. Similar to kidney donation, the therapeutic principle must be applied to both the donor and the receiver. However, neither of the techniques apply therapy to the donor or receiver while both come with risks. Rather, they are aimed for a life which has not yet come into being. To add to the canvas of harms, these procedures invite coercion and exploitation of oocyte donors.

Although MRTs might provide an opportunity to provide genetically-related healthy children for women suffering mitochondrial disease, its use more closely mirrors eugenic selection than true healing. The job of science is to heal sick people not to replace them. MRTs do not meet that standard.