Three Parents and a Baby
Joann P. Galst, Ph.D.
A new reproductive technique is currently being debated, this one intended to reduce the suffering of babies and their parents. Mitochondrial donation and replacement involves scooping out the cell nucleus of the egg of a donor and replacing it with either the egg or the zygote (fertilized egg) of the intended mother. This replaces the recipient mother’s defective mitochondria with that of the healthy donor so that the intended child will not suffer from the devastating effects of mitochondrial disease.
What are Mitochondria?
Mitochondria are small (a few thousandths of a millimeter long), bean-shaped organelles found floating in the cytoplasm of our living cells. They are the power plants of our cells, generating the energy required for our bodies to function.
To help you visualize them, imagine a fried egg. The yolk is the cell nucleus, containing 20,000 to 30,000 genes that define much of what we are (e.g., physical characteristics, personality). The mitochondria are embedded in the cytoplasm, or the egg white, that surrounds the yolk. They have a separate set of genes, 37 in all, or around .1% of our total genetic makeup. Whereas nuclear DNA is inherited from both biological parents, half from the mother and half from the father, mitochondrial DNA is inherited solely from the mother.
Unlike nuclear DNA, mitochondrial DNA does not affect features of the individual such as appearance or personality. They do reproduce vigorously, however, so that individual cells can contain hundreds or thousands of copies of its mitochondrial DNA. This mitochondrial DNA will be passed down from any female to her offspring, thus crossing the germ line, and herein lies the rub of mitochondrial replacement.
What is Mitochondria DNA Disease?
The mitochondria convert glucose to energy and reside in all cells of our bodies except red blood cells. They affect body parts requiring high energy like the brain, heart, and muscle, and gene mutations in the mitochondria can cause blindness, deafness, muscle weakness, cognitive impairment, epilepsy, and heart, lung, and kidney failure. Symptom severity can vary considerably between disease sufferers, from mild to extremely debilitating, sometimes resulting in death in childhood, but symptoms can also arise at any time in a person’s life.
It has been estimated that 1 in 4.000 children and adults are diagnosed with mitochondrial disease, but because the symptoms are so varied, it is thought that many more cases may be misdiagnosed. At present, there is no cure.
How Can It Be Prevented?
Faulty mitochondrial DNA (mtDNA) from a mother’s egg cell can be replaced with healthy mtDNA from a donor’s egg cell. At present there are two techniques available to accomplish this:
Maternal Spindle Transfer. The nuclear DNA (which contains 99.9% of total cell DNA) is removed from a donor egg, leaving only the part of the cell containing healthy mitochondria. Then the nuclear DNA from the mother’s egg is inserted into this cell. The healthy egg is fertilized with sperm from the father, and the zygote (fertilized egg cell) is implanted in the mother’s uterus, as with the typical IVF procedure.
Pronuclear Transfer. This is similar to the above procedure but involves fertilizing the mother’s egg first and then transferring her nuclear DNA to the donor egg which contains healthy mitochondrial and from which the nuclear DNA has been removed. The healthy fertilized egg is then implanted in the mother’s uterus as above.
Is it Safe?
Thus far, there have only been successful maternal spindle and pronuclear transfers on monkeys and mice, and animal studies to not necessarily translate to humans. Hypothesized risks include: epigenetic changes (nongenetic influences on gene expression) provoked by the oocyte transfer procedures, which may cause problems later in life, and the impact of chemicals and drugs used at various points throughout the procedure.
The greatest concern is for the children created by these procedures. There is minimal information available about long term health effects. Many questions remain, including: Could the child still inherit mutated mtDNA from the maternal nucleus? How will future generations be affected? Since problems could show up at any point of embryonic or fetal development, throughout the child’s life, or in future generations, the offspring created would need to be followed throughout their lives and into future generations.
It is impossible to say that any new procedure would have no risk at all. However, if we opt only for zero risk, no innovation would be possible.
Relevance to Infertility
While there is no evidence as of yet that mitochondrial replacement could treat infertility, theoretically it may. As we age, the mitochondria in our cells become less efficient at generating power, so replacing the mitochondria might rejuvenate the eggs of older infertile women. This theory obviously requires testing.
Sounds Good, So What Are the Issues?
For women carriers of mitochondrial disease, there are less risky alternatives available, i.e., adoption, donor egg, preimplantation genetic diagnosis (carried out on embryos created through IVF prior to implantation – as if less than 18% mutated mitochondrial DNA is found, there is a 95% chance that a baby would be unaffected by mitochondrial disease, although the complexity of mitochondrial disease may mean that PGD will not be able to completely eliminate the transmission of mitochondrial disease), and prenatal diagnosis (although this may result in a parent’s decision to terminate a pregnancy when the fetus demonstrates the presence of mitochondrial disease, a very emotionally difficult decision for parents who wanted this baby).
In conclusion, the question we are inevitably left with is, does the potential benefit of mitochondrial replacement compensate for possible future harm? Only further experimentation through human trials will tell. And those future trials rest both on science and politics.