American doctors led by Dr. John Zhang have performed a new type of mitochondrial donation to make a human child using three sets of DNA. The technique holds promise for helping families that suffer from a variety of diseases known as “genetic mitochondrial diseases”. However, the event has also drawn intense criticism for skirting US legal and ethical statutes by performing the operation in Mexico.

On April 6, 2016, an unnamed Jordanian mother gave birth to a baby boy that had been grown from a three-person fertilized egg. The family had previously experienced intense reproductive hardship: they had 4 miscarriages, and lost two children at 8 months and 6 years. The reason for this difficulty was a disease called Leigh syndrome.

Leigh syndrome is a neurological disorder that causes deterioration of movement and mental function, typically followed by death due to respiratory failure. It can have genetic causes in either the nucleic or, as in this case, mitochondrial DNA. The operation performed by Zhang involved taking the nucleus from the mother’s egg and moving the nucleic DNA—which determines the vast majority of a person’s traits—into a donor egg that had had its nucleus removed. The result is a cell containing almost entirely the maternal DNA, but properly-functioning mitochondria. Standard in-vitro fertilization (IVF) techniques can then be used to fertilize and implant the zygote into the mother’s womb.

This is not an entirely new idea, but it is an entirely new procedure. Approximately 30-50 children have been born via “cytoplasmic transfer”, in which the contents of a donor cell—including mitochondria, but not nuclear DNA—are transferred into an unfertilized egg. The egg then contains both malfunctioning maternal mitochondria and functioning donor mitochondria. It can be fertilized and implanted using IVF.

The controversy, therefore, is not so much with the procedure itself but in the way that the scientists performed the procedure. In the US, the FDA has ethically-approved research in the area, but not treatment. As a result, the doctors and family went to Mexico where, as Zhang puts it, “there are no rules.” He justifies the decision saying that “to save lives is the ethical thing to do.”

The choice to skirt the existing regulation environment is what is causing the trouble. For instance, Dr. David King of the pro-choice group Human Genetics Alert points out that no lives were actually saved by this operation; a new life was created. In another line of inquiry, stem cell researcher Dusko Ilic comments: “Was this the first time ever they performed the technique or were there other attempts and they are reporting this one because it was successful?” The overriding criticism is that, by going to Mexico to perform the operation without any regulation, the team has opened themselves up to questions of the safety and ethicality.

In response to the criticism, Dr. Zhang has replied that all questions will be answered when their findings are presented at the American Society for Reproductive Medicine in mid-October.

Mitochondrial DNA

A mitochondrion is a structure that exists within every animal (and plant and fungal) cell. It uses chemical energy from breaking down sugars to create a chemical called adenosine triphosphate (ATP). ATP is then used as a source of chemical energy by other parts of the cell.

The mitochondrion can best be thought of as a cell-within-a-cell because, according to our current understanding, it is; mitochondria are distant descendants of bacterial cells that were absorbed by larger cells and used as efficient ATP creation factories. As a result of this origin, the mitochondria exhibit some bacterial behaviours: they have their own bacterial-like circular DNA and undergo a cell division-type process within the cell.

When a female reproductive cell, or egg, is fertilized by a male reproductive cell, or sperm, the sperm only provides genetic material. All of the other parts of the cell, including the mitochondria, are exclusively from the egg. As a result, men cannot pass on genetic mitochondrial diseases, whereas women can. This has also lead to the concept of a “mitochondrial Eve”; genetic studies have shown that all human mitochondria from all humans are related. Slight mutations in the mitochondrial DNA suggest that all people everywhere are maternally-related to one woman who lived between 100 000 and 200 000 years ago.

While all mitochondria are related, they are different enough to be detected. If the donor of a three-child birth was closely related to the mother via female relatives, the strange circumstances of the child’s conception could not be identified. However, that would nullify the intention of introducing new mitochondria that were free of the particular genetic disease that necessitates the procedure. As a result, the donor will typically be unrelated to the mother and the child will recognizably contain about 0.1% DNA from a third individual.

Procedures like mitochondrial donation have a huge potential to prevent suffering from genetic diseases. However, there are legitimate ethical concerns about the process. For instance, what are acceptable operations? Are cosmetic operations, or selecting for “running genes” and “genius genes”, appropriate? How will unequal wealth and access to these procedures affect us as a global society and species? Some of those questions are very distant from the procedure performed here, but some are very close. For instance, as the BBC asks, “[how might] any child from the technique… feel about having DNA from three people[?]”