Fertility doctors in New York City have successfully delivered the first baby born via a technique that mixed DNA from three parents, New Scientist reported today in an exclusive story.
The healthy five-month-old boy is living proof a new and somewhat controversial method can correct genetic mutations buried in a mother’s mitochondrial DNA. However, he isn’t the first child to claim a trio of parents.
Doctors at the New Hope Fertility Center in New York City employed this technique to prevent the child from inheriting Leigh syndrome, a fatal neurological disorder, from his mother. The mutation responsible for this condition occurs DNA strands housed inside mitochondria — subunits of a cell responsible for energy production. These powerhouses come with a genetic code that is separate from the classic DNA found in the nucleus. We inherit 37 mitochondrial genes pass from our mothers, but none from our dads. As a result, mutations in mitochondrial genes can cause severe conditions, like Leigh Syndrome, which can’t be naturally masked by mixing with a father’s genetic code.
Enter “nuclear transfer,” a technique whereby a mother’s mitochondria are swapped with those of a donor. There are two types for in vitro fertilization. The first — pronuclear transfer — involves fertilizing a mother’s egg and a donor’s egg with a father’s sperm. Doctors then swap the nuclei between the two early-stage embryos, leaving one with the donor’s healthy mitochondrial DNA and a nucleus packed with the mother and father’s DNA.
The other embryo is destroyed, which wouldn’t fly with the parents, who are Muslim. So, their doctor — John Zhang — and his team used spindle nuclear transfer. This process starts prior to fertilization, with a mother’s egg and a donor’s egg. The nuclei are transferred between the two eggs, and then the healthy one — with mom’s nuclear DNA and donor mitochondria — is fertilized by the father.
Both of these procedures are banned from human use in the U.S. So, Dr. Zhang performed the treatment in Mexico for the child’s Jordanian parents.
The circuitous route required to obtain the remedy highlights the leaky regulatory barriers surrounding for such procedures. Britain approved pronuclear transfer for human use in 2013. It remains the only country that allows mitochondrial therapy for IVF.
Earlier this year, the Institute of Medicine said it is ethical to conduct research on nuclear transfer procedures in the U.S. But a Congressional prohibition prevents U.S. agencies from funding research involving inheritable genetic modification of embryos. Yet the Congressional ban doesn’t prevent doctors from conducting the procedure overseas.
Watch a conversation about mitochondrial replacement technique with Jeffrey Kahn of Johns Hopkins University and Marcy Darnovsky of the Center for Genetics and Society.
So far, the newborn hasn’t shown signs of Leigh syndrome, which tend to manifest during infancy. Genetic tests revealed one percent of his mitochondria still harbor the mutation.
“Hopefully, this is too low to cause any problems; generally it is thought to take around 18 percent of mitochondria to be affected before problems start,” Jessica Hamzelou wrote for New Scientist.
Incomplete protection ultimately doomed the first attempts at mitochondrial correction in the 1990s. Back then, doctors sucked up mitochondria from a donor egg and injected it into mother’s egg, known as cytoplasmic transfer. The idea hinged on implanting enough donor mitochondria to outcompete the unhealthy powerhouses, and it’s estimated 30 to 50 people were born via this infertility technique.
“A lot of people say I have facial features from my mum, my eyes look like my dad… I have some traits from them and my personality is the same too,” Alana Saarinen, a child birthed by cytoplasmic transfer, told the BBC in 2014. “I also have DNA from a third lady. But I wouldn’t consider her a third parent, I just have some of her mitochondria.”
Saarinen is a healthy teenager, according to her parents. But, a subset of babies by cytoplasmic transfer developed genetic disorders. The method was ultimately banned by U.S. regulators in 2002.
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