Three-Parent Embryo Created in a Lab

Scientists at the Newcastle University in the U.K. have successfully implanted embryo nucleuses, containing DNA from a mother and a father, into donor eggs. Although the nucleuses of the donor eggs had been removed, they still contained healthy mitochondria, which replaced the damaged mitochondria of the original eggs. The Newcastle research team hopes this technique may help eradicate a whole class of hereditary diseases, including some forms of epilepsy, which are passed on from mothers to their children through maternal mutated mitochondria.

Doug Turnbull Newcastle University 
Professor
Doug Turnbull
(Credit: Newcastle
University)

Mitochondria are organelles that are found in most eukaryotic cells and serve as “cellular power plants”, as they generate most of the cell’s energy supply (in the form of ATP).Although most of a cell’s genetic information is contained in its nucleus, mitochondria have their own independent genome, known as mitochondrial DNA, or mtDNA. The mtDNA is inherited solely from the mother. Unlike the cell nucleus, mitochondria do not contain DNA repair enzymes, and therefore, mtDNA mutation rates are relatively high. mtDNA mutations can affect cells’ energy production and may cause damage to the offspring’s muscles, nerves, and brain, which are the biggest energy consumers in the human body. Mitochondria-derived disorders include liver failure, stroke-like episodes, epilepsy, deafness, muscle weakness, and diabetes. It is noteworthy that currently, all of the abovementioned disorders do not have a cure.

In a research project led by Newcastle University professors Doug Turnbull and Patrick Chinnery, scientists managed to demonstrate a method of replacing an embryo’s “faulty” mitochondria with “healthy” mitochondria. The team experimented on 10 severely abnormal embryos left over from a traditional fertility treatment. Each embryo underwent a mitochondria transplant. Several hours after each embryo’s creation, its nucleus, containing DNA from the mother and father, was removed and implanted into a donor egg. The donor egg’s nucleus had previously been removed, but its intact mtDNA remained unchanged. These embryos, containing DNA from a man and two women, began to develop normally in lab tests, but were destroyed within six days, as the team has permission to carry out lab experiments only. For this reason, the team cannot yet offer this method as a treatment.  

 Professor Patrick Chinnery (Credit: Newcastle University)
Professor
Patrick Chinnery
(Credit: Newcastle
University)

Similar experiments conducted on mice have indicated that if babies will be born through this method, the DNA influencing their appearance and other traits would not be that of the women who has provided the donor egg. In other words, the babies would be affected mostly by their parents’ genetic data. The Newcastle researchers believe they can further develop this technique to ensure that women will be able to conceive without passing mitochondria-associated hereditary diseases to their children. 

However, the team’s work has attracted ethical opposition. Josephine Quintavalle, of the pro-life group ‘Comment on Reproductive Ethics’, believes the research is risky and dangerous, “It is human beings they are experimenting with. We should not be messing around with the building blocks of life” she said. Quintavalle added that in the U.S., embryo research using DNA from one man and two women was discontinued because of the “huge abnormalities” in some cases. 

The Newcastle research project has also revealed the mechanism by which mitochondria are randomly distributed in forming eggs. The existence of very different amounts of mutant mtDNA in different eggs is thought to explain the variation in the severity of the mitochondrial diseases between siblings. Since the proportion of abnormal mitochondria passed on to the child depends on which egg is fertilized, these findings may help scientists create a method for predicting a child’s risk of developing mitochondrial diseases. “Now that we understand how different levels of abnormal mtDNA are inherited, we may soon be able to predict a child’s risk of disease and the level of severity” said Professor Chinnery. It is important to note, however, that even when the precise proportion of abnormal mtDNA carried by the mother is known, scientists have been unable to predict whether and how a child will be affected. 

TFOT recently covered the topic of human genetic variation in an article explaining fairly new scientific understanding of just how genetically different we are from each other. TFOT also covered a recent breakthrough in the treatment of Parkinson’s disease achieved by Cornell Medical Center researchers. The breakthrough was achieved by utilizing a gene-therapy technique to deliver a gene encoding the inhibitory GABA molecule to the overactive brain area (subthalamic nucleus) of a dozen of Parkinson’s patients. 

You can read more on this topic in the Newcastle University press release of the mitochondria inheritance research (available here), and in the press release of the U.K. Parliament debate in this subject (available here).

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About the author

Einat Rotman

Eynat has a B.Sc in Biology and an M.Sc in Molecular Microbiology and Biotechnology from Tel-Aviv University. She is currently attending a continuing education program in the Pharma-Job Bio-Medical College towards becoming a clinical research associate.

View all articles by Einat Rotman