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04/03/2017

    Physician John Zhang reveals genetic details of controversial three-parent baby




    A US fertility clinic revealed in Sep. 2016 that it had created a baby boy using a controversial mitochondrial-replacement technique that mixes DNA from three people. Scientists were quick to raise the alarm with some objected on ethical grounds and others questioned the scientific claims made by the clinic’s leader, physician John Zhang.


    Now, after months of intense debate and speculation, Zhang’s team has provided more details about the child’s conception, in a paper published on 3 April in Reproductive Biomedicine Online. But major questions remain about the long-term health of the boy, and whether the experiment will ultimately advance reproductive medicine.


    In an attempt to create embryos without the mother’s faulty mitochondria, a rare neurological disease called Leigh syndrome, the clinic’s team removed the nucleus from a healthy donor egg and replaced it with a nucleus taken from the mother’s egg cell, leaving the donor’s healthy mitochondria intact. The scientists then fertilized the modified egg with the father’s sperm before implanting it into the mother’s uterus. The resulting baby was born in April 2016.

    The paper reports new details about the procedure, such as the method used to transfer the mitochondria: freezing and heating the embryo before using an electrical pulse to fuse the mother's nucleus into the donor egg. The study also reveals that some diseased DNA from the mother was carried over inadvertently into the donor egg, which could have long-term repercussions for the child's health.


    But the big question remaining is whether the child's health will be affected by the traces of the mother's mitochondrial DNA that he carries, which could prompt some of his mitochondria to function improperly. The percentage of affected mitochondria can differ between tissues. Zhang's paper reveals that just 2% of the mitochondrial DNA of cells in the boy’s urine came from the mother, but that figure rose as high as 9% in cells from the child’s circumcised foreskin. Organs such as the heart or brain are impossible to test without invasive surgery.


    The study says that the baby’s parents have refused any further mitochondrial testing on the baby unless there is a medical need. Government regulations and other guidelines for human research generally require that people be allowed to withdraw from experiments. When this happens, it can make it hard to determine whether a treatment is safe, says Alta Charo, a bioethicist at the University of Wisconsin–Madison. In this case, she says, it is unclear whether the parents received enough information to appreciate how long-term follow-up could benefit their child as well as science.


    A three-page editorial accompanying the study notes that the researchers had the baby's parents sign a consent form acknowledging that their egg was undergoing an experimental technique. But the form only described the procedure superficially, and did not inform the couple of the potential risks of using this method to create a child.


    Because the boy could not give consent, “the duties were even higher for clinicians and participants to protect the best interest of the future child”, says Rosario Isasi, a legal scholar at the University of Miami in Florida. In his paper, Zhang says that the parents received “cautious counselling for mitochondrial replacement therapy”.


    Read more:

    Zhang, J. et al. Reprod. Biomed. Online 34, 361–368 (2017). DOI: http://dx.doi.org/10.1016/j.rbmo.2017.01.013

    Alikani, M., Fauser, B. C. J., Garcia-Valesco, J. A., Simpson, J. L. & Johnson, M. H., Reprod. Biomed. Online 34, 333–368 (2017). DOI: http://dx.doi.org/10.1016/j.rbmo.2017.02.004