Human Babies Aren't Supposed to Have 3 Parents—but Now They Can
Here's what you'll learn when you read this story:
The first babies with three biological parents were born out of a new technique to prevent mitochondrial disease.
The nucleus of an egg fertilized in vitro was transferred into a donor egg without a nucleus, but with viable mitochondria.
Eight healthy babies, including a set of twins, were born with low to undetectable levels of mitochondrial mutations.
The only creatures known to conceive offspring from more than two parents are salamanders. Females from the genus Ambystoma (which are notoriously promiscuous) mate with up to three different males, and that DNA is then incorporated into what is known as a triploid genome in their offspring. Now a version of this has become possible in humans.
It seems limb regeneration isn't the only way medical intervention can put humans on salamanders' level. Being born with three genomes is not a phenomenon that occurs naturally in Homo sapiens, but in an attempt to prevent certain genetic conditions caused by mutations in the mitochondria, scientists have found a way. Mitochondrial DNA or mtDNA is exclusively passed down from the maternal side. Dysfunction in the mitochondria can lead to metabolic diseases characterized by symptoms such as seizures, developmental delays, blindness, and loss of muscular function. Some can even be fatal.
Mitochondrial diseases occur in about 1 in every 5,000 people. They were previously only preventable by using a donor egg or foregoing the conception of biological children altogether. This is why pediatric neurologist Bobby McFarland, of Newcastle University in the UK, led an experimental study that would reduce and potentially eliminate the risk of mitochondrial disease with a new method of in vitro fertilization. McFarland and his research team wanted see if removing the nucleus of an egg and placing it in a donor egg with viable mitochondria would result in healthy offspring.
'We found that pronuclear transfer, a form of mitochondrial donation, was effective in reducing the level of pathogenic mtDNA variant to substantially below the threshold for clinical disease in the offspring of women with homoplasmic (or high heteroplasmic) levels,' he said in a study recently published in the New England Journal of Medicine.
When mitochondria are homoplasmic, all copies produced by cell division have mutations. Mutation levels vary in heteroplasmic mitochondria. Preimplantation genetic testing (PGT) can screen for these abonormalities, and women with homoplasmy or high levels of heteroplasmy can benefit from what is now known as pronuclear transfer. This involves eggs from both the mother and donor being fertilized with the father's sperm in vitro. Nuclei are then removed from both eggs after ten hours. Since the nucleus carries most genetic material and has no connection to mitochondrial disease, the mother's nucleus is implanted into the donor egg to take advantage of its mitochondria.
While there is a chance that a few of the mother's mitochondria may end up in the embryo, it is unlikely to cause a debilitating disease. Levels of defective mitochondria in offspring conceived via pronuclear transfer were low enough to escape that fate. Eight pregnancies (including a set of twins) resulted from the experiment, and while there were a few minor health problems in the newborns, these were either treatable or corrected themselves. Not only were levels of heteroplasty low for the babies, but undetectable in five of them. Developmental progress also turned out to be normal.
Though one baby had a form of infant epilepsy, and another had heart arrhythmia and hyperlipidemia, or high levels of fats and lipids in the blood, both of these conditions were treated and resolved. Whether the hyperlipidemia was even caused by mtDNA is uncertain, especially because the mother also had severe hyperlipidemia during her pregnancy. Though there was a chance that any of the mothers with pathogenic mtDNA had a higher risk of complications during pregnancy, which could possibly cause their children to have health issues, there is no proof for now.
'We are assessing, over the long term, the health and extent of heteroplasmy (if detectable) of the offspring,' McFarland and his team said. 'Indeed, the role of mitochondrial donation as a choice for women with a heritable pathogenic mtDNA variant will only be established with the availability of additional data.'
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