YSM Issue 87.4

REINVENTING
BY ISABELLE ROSSI DE LEON
the human embryo
Leigh syndrome is an incurable neurological disease caused
by mutations to mitochondrial DNA, the circular DNA that
governs mitochondria’s ability to power the cell. The disorder
disrupts cellular respiration and results in rapid loss of muscle
movement and mental capabilities, often leading to premature
death. Leigh syndrome is passed on from mother to child by
the diseased mitochondria present in the egg, making it nearly
impossible for affected mothers to have healthy children.
However, there may be hope for women suffering from Leigh
syndrome and other mitochondrial diseases. This hope comes
in the form of the three-parent embryo, a recent scientific
innovation currently awaiting governmental approval for
human trials. The advent of a technique called mitochondrial
replacement, which creates three-parent embryos, has brought
survivors of Leigh syndrome several steps closer to having
biological children without the mother’s diseased mitochondria.
Mitochondria possess a small amount of DNA separate from the
cell’s nuclear chromosomes, a remnant from when the organelles
were free-living cells in the primordial world. Mutations in the
mitochondrial DNA can result in severe, often fatal diseases—
Leigh syndrome is just one manifestation of that. Without a
functional way to produce cellular energy, entire organisms are
at risk. In addition, because these mitochondrial diseases are
passed from a mother to her offspring in the embryo, they are
impossible to prevent and treat without altering the embryo.
Mitochondrial replacement combines two parents’
nuclear DNA, as in a normal embryo, and the mitochondria
from a third, healthy donor egg. The embryo then grows
into a child completely free of mitochondrial disease.
Of course, there are a multitude of safety and ethical issues
preventing the immediate use of mitochondrial replacement.
It is illegal in many countries to alter inheritable human DNA,
though mitochondrial replacement would not result in any
changes to nuclear DNA. Likewise, there are a variety of safety
concerns for both mother and child, including catastrophic
birth defects. Despite these hurdles, scientists are working to
make the three-parent embryo a reality within the next two years.
The numerous functions of mitochondria make it apparent why this
new therapy is an exciting advancement for the medical community.
Mitochondria take in glucose and other nutrients and produce
adenosine triphosphate (ATP), a molecule that retains and conveys
chemical energy within cells. A constant supply of ATP is necessary for
eukaryotic cells to survive, and thus for organisms, including humans,
to function properly. Mitochondria can lose their ability to produce
ATP via cellular respiration from changes in mitochondrial DNA.
IMAGE COURTESY OF BIOTE 21 WEBSITE
Mitochondrial DNA encodes much more than the structures
necessary to create cellular energy. The circular DNA plays a
role in many other normal cell functions as well.
However, mitochondria are not solely energy producers. The
organelles play a major role in each cell’s metabolic pathways, and the
3,000 genes encoded in mitochondrial DNA regulate everything from
detoxification to hormone synthesis. Mutations to mitochondrial
DNA thus have far-reaching effects. It makes sense that Leigh
syndrome and other mitochondrial diseases display such varied,
serious symptoms; these conditions tend to negatively impact cells of
the heart, brain, liver, kidneys, and skeletal muscles, resulting in severe
symptoms ranging from developmental delay to cardiac disease.
30 Yale Scientific Magazine October 2014 www.yalescientific.org