Child Born with the DNA of 3 Parents

In the science fiction TV show, “The Expanse,” based on the books by James S.A. Corey, the main character, James Holden, is a Montana native born to eight parents as part of a genetic collective. Science fiction? Sure. But maybe not that far in the future.

Recently, researchers with the Institute of Life in Athens, Greece, announced that a healthy baby boy was born who basically had the DNA from three people. The child was born to a 32-year-old woman who had failed in four cycles of in vitro fertilization (IVF).

The boy was born from a technique known as maternal spindle transfer. In this procedure, the DNA found in the nucleus of a mother’s egg was removed. From a donor egg, the nucleus was emptied of DNA and the mother’s DNA was inserted. The donor egg with the mother’s genes was fertilized with sperm from the father, developed into an embryo, and transferred for pregnancy.

So there was DNA from the original mother and DNA from the father. What about the third person’s DNA? That comes from mitochondrial DNA of the woman who donated the egg.

Mitochondria are organelles found in the cytoplasm—not the nucleus—in most eukaryotic cells. They have numerous functions but are typically called the powerhouse of the cell for their role in energy production and respiration. There are several diseases related to mitochondrial dysfunction, as well as cardiac disease, heart failure and autism. They are also increasingly being implicated in some types of infertility.

The key point is that because mitochondria are in the cytoplasm, they are not passed down by males, but are passed down in the eggs of females.

In the Greece case study, the child inherited mitochondrial DNA from the woman who supplied the donor egg, as well as nuclear DNA from the mother and the father.

The technique has been performed in the U.S. as well, but not for implantation. That is because of a 2015 congressional amendment, the 1996 Dickey-Wicker Amendment, that prevents the U.S. Food and Drug Administration (FDA) from considering human research “in which a human embryo is intentionally created or modified to include a heritable genetic modification.”

In one case in the U.S., researchers at Columbia University in New York created similar embryos with genetic material from three people, but they have been frozen in hopes that a legal path forward might be found. In this case, Dietrich Egli, assistant professor of developmental cell biology at Columbia, used mitochondrial replacement therapy to create embryos for four female patients. All the women are carriers of mitochondrial genetic disorders, which is a different scenario than the one in Greece.

Because the U.S. amendment prevents the use of federal funds for creating human embryos for research purposes, Egli and his team, which includes neurologist Michio Hirano, have turned to philanthropic funds.

A STAT article also points out that a New York-based fertility specialist, John Zhang, went to Mexico in 2015 as a workaround of the U.S. law. Zhang transferred an embryo via mitochondrial replacement therapy into a woman who was a carrier of Leigh syndrome. She delivered an apparently healthy child in April 2016.

Leigh syndrome is a severe neurological disorder that typically shows signs in the first year of life. It is characterized by progressive loss of mental and movement abilities, and usually causes death within two to three years, generally from respiratory failure.

The disease can be caused by mutations in one of more than 75 different genes, most of which are found in the nuclear DNA. However, about 20% of Leigh syndrome patients have a mutation in mitochondrial DNA (mtDNA).

For the case in Greece, the mother had gone through four rounds of IVF without becoming pregnant. Something in her egg apparently prevented a viable embryo from forming when it was fertilized. Although there are potentially many causes for that, problems with mtDNA can be part of it.

Panagiotis Psathas, president of the Institute, stated, “We are now in a position to make it possible for women with multiple IVF failures or rare mitochondrial genetic diseases to have a healthy child.”

Jonathan Tilly, chair of the department of biology at Northeastern University, told Time, “All the historical data, including preclinical animal data and clinical data with people, fall into line with the idea that something significant is going on that lends itself to infertility and poor egg and embryo quality—and the bulk of those data point to mitochondrial deficiency or mitochondrial dysfunction.”

Although the motivations behind the U.S. federal government ban on these types of procedures are complex, often with religious objections, there are good reasons to question the wisdom of germ cell edits in embryos that have nothing to do with the abortion debate. The recent case of the Chinese researcher, He Jiankui, who used CRISPR gene editing within IVF to modify the CCR5 gene in human embryos, resulting in the birth of a set of twins and another pregnancy, is a good example.

The CRISPR procedures were broadly condemned worldwide for violating moral and ethical standards. That was largely because the procedure was not medically necessary and that not enough was known about the technology, such as concerns about off-target CRISPR edits that might cause unforeseen problems, such as cancer. Also, when germline embryos are edited, if viable, the babies born would pass those same edits down to their children and so on.

Some critics and ethicists are concerned that maternal spindle transfer and similar techniques will just lead to germline editing. That’s an argument that may not necessarily hold up to scrutiny and seems reminiscent of arguments against in vitro fertilization In the wake of the China CRISPR scandal, leading scientists worldwide have called for a moratorium on heritable genome editing. Whether that includes maternal spindle transfer remains to be seen, although it seems unlikely.

Of the Greece case, however, Tilly told Time, “Success like this might lead to bypassing the need to use donor eggs at all and allow us to go back and fix the problems in the egg itself. There could be a whole host of things that are defective in the egg, from enzymes, lipids and anything that floats around in the cytoplasm. To me, that’s the exciting aspect of this—moving the science forward to understand what those factors are.”