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Notebook Medicine

The nuclear option

(Rachel Beatty)

Medicine

The nuclear option

Should we create children with DNA from three parents?

Taylah Hollingshed, 6, was in dance rehearsal when her mother noticed something wrong: “The left side of her body wasn’t doing what it should.” Their pediatrician referred Taylah to a neurologist who diagnosed her with Leigh syndrome, a severe, progressive disease with no effective treatments. Her mother writes that since then “we have watched our active little girl who loved to dance and ride her bike with her big brother become wheelchair bound.”

Leigh syndrome is a disease of the mitochondria, the battery-like structures in cells that produce energy. Mitochondrial diseases affect parts of the body that use the most energy, such as the muscles, brain, heart, and lungs—and can lead to seizures, heart disease, and severe weakness and fatigue. Some of these diseases, including Leigh syndrome, are caused by mutations in mitochondrial DNA. Most DNA (the cell’s genetic material) resides in a structure called the nucleus and is inherited from both parents, but mitochondria have a very small amount of a cell’s DNA. This mitochondrial DNA is inherited solely from a person’s mother and its main task is to make mitochondria.

Mitochondrial diseases have no proven treatments, but in recent years scientists have experimented with reproductive techniques to prevent these conditions from happening in the first place. One procedure, maternal spindle transfer, includes several steps: Take an egg from the ovary of a woman likely to pass on mitochondrial diseases to her children. Remove the nucleus of her egg, containing nuclear DNA, and discard the rest of the egg, with unhealthy mitochondria. Remove the nucleus from another woman’s donated egg, leaving healthy mitochondria behind. Place the intending mother’s nucleus in the egg with normal mitochondrial DNA. Lastly, fertilize the hybrid egg (containing nuclear DNA from one woman and mitochondrial DNA from a second woman) with the father’s sperm.

Since the embryo created by this technique would contain genetic material from three different individuals, some call it a three-parent baby.  But the procedure’s proponents argue this is a misnomer since all meaningful traits like hair color, height, and personality come exclusively from the intended mother’s nuclear DNA. In February, the United Kingdom’s House of Commons and House of Lords voted to allow British clinicians to pursue reproductive techniques that manipulate mitochondria. In contrast, the Food and Drug Administration has declined to permit that practice in the United States until further scientific data is available.

Opponents of reproductive techniques that manipulate mitochondria raise questions: Will the children created with DNA from three different parents suffer harm in ways we cannot anticipate? Even if they suffer no adverse outcomes, how will subsequent generations be affected? Is it ethical to alter a developing person’s genes without his or her consent? Will genetically modifying sperm, egg, and embryos open the door to eugenics and creating designer babies?

It is also far from clear that these techniques would be effective at preventing mitochondrial diseases. Most mitochondrial diseases in infants are due to mutations in nuclear DNA rather than mitochondrial DNA. Even diseases due to mutations in mitochondrial DNA sometimes occur via spontaneous mutations, rather than being inherited.

Women at risk for passing on mitochondrial disease to their children can choose safe family-building alternatives, such as adoption. Given this reality, do the benefits of mitochondrial manipulation technology justify the expense, potential harms, and serious ethical concerns it generates? The FDA commissioned the Institute of Medicine to study this question. Its report is due by December.