In April 2016, a Jordanian mother who had lost two daughters to the same neurological disease flew to Mexico with her husband to attempt something that had never been done before. The mother, whose identity has been protected across the various public reports of the case, carried the genetic mutation for Leigh syndrome, a rare and severe condition that attacks the developing nervous system of infants and toddlers. The mutation lived in her mitochondria, the small organelles inside every cell that generate the cell’s energy. Approximately twenty-five percent of her mitochondria carried the relevant mutation. The mother herself was healthy. The mutation only mattered when it was passed down to a child, at which point it produced the disease that had already taken two of her children.
The mother had also experienced four miscarriages before the procedure. The two daughters she had carried to term had both died of Leigh syndrome, one at eight months of age and the other at six years. The Fox News coverage of the case, drawing on the research summary, documents these ages directly. The disease produces a progressive deterioration of the nervous system, leading to muscle weakness, breathing difficulties, and eventually death. It is, by every available measure, devastating for the families that encounter it.
The mother and her husband, who are Muslim, wanted another child. They wanted a child who would not have to die of the same disease that had taken the previous two. The wider medical infrastructure of the United States and most other developed countries had nothing to offer them. The procedure that might, in principle, allow the mother to have a child without passing on the mutation was not legal anywhere in the United States, and the version of the procedure that was legal in the United Kingdom involved destroying fertilized eggs in ways that the couple’s religious convictions did not permit.
The couple sought help from Dr. John Zhang, a reproductive endocrinologist at the New Hope Fertility Center in New York City. Zhang agreed to attempt a particular variant of the procedure that would not require the destruction of fertilized eggs. The agreement, given that the procedure was not legal in the United States, required the team to perform the relevant medical work in a jurisdiction where the procedure was not prohibited. The team went to Mexico.
What the procedure actually involves
It is worth being precise about what the procedure actually involves, because the wider register has tended to absorb it in vaguer terms than the underlying mechanism warrants.
The procedure is called spindle nuclear transfer, sometimes also called maternal spindle transfer. The Washington Post’s documentation of the technique describes the operation directly. The team removed the nucleus from one of the mother’s eggs. The nucleus contains the mother’s chromosomal DNA, which carries the information that determines most of who any given person actually is. The team then inserted this nucleus into a donor egg from a different woman, from which the donor’s own nucleus had been removed but whose mitochondria, the ones not carrying the Leigh syndrome mutation, were left intact.
The resulting egg contained the mother’s chromosomal DNA in the center, surrounded by the donor’s healthy mitochondria. The father’s sperm was then used to fertilize the reconstructed egg in standard IVF fashion. The retrospective documentation of the case notes that of five reconstructed embryos, only one developed normally. The fertilized egg that did develop was implanted in the mother’s uterus. The pregnancy proceeded normally. The child was born on April 6, 2016, healthy, at thirty-seven weeks of gestation.
The child carries DNA from three people. The structural majority of his genome comes from his mother and father in the standard way. A small amount of his mitochondrial DNA, which is separate from the chromosomal DNA in the cell nucleus, comes from the donor woman whose egg provided the healthy mitochondria. The donor’s contribution is small. The donor contributed approximately thirty-seven genes through her mitochondrial DNA. The mother and father contributed approximately twenty thousand genes through their chromosomal DNA. The child is, in the sense that matters for inheritance and identity, the biological son of his parents. The donor’s contribution is the small correction that allowed the mother’s actual genetic offspring to be born without the disease that had taken his sisters.
Why the child had to be male
The structural feature of the procedure that the wider register has not adequately attended to is why the team specifically selected a male embryo for implantation. The selection was not arbitrary. The selection was, on close examination, a piece of careful ethical engineering calibrated to a particular concern about the long-term implications of the procedure.
The concern involves how mitochondrial DNA is actually inherited. Mitochondrial DNA, unlike chromosomal DNA, is passed down exclusively through the maternal line. A father does not, by every available measure of how reproduction operates, pass his mitochondrial DNA to his children. The mitochondria in any given person come exclusively from the mother. The implication is that if the child born in Mexico had been a girl, that girl would have, in adulthood, passed the donor’s mitochondria on to her own children, and those children would have passed it on to theirs, and so forth down the maternal line indefinitely.
The team did not, on the available ethical evidence, want to take this step without further understanding of the long-term implications. MIT Technology Review’s coverage notes that the team specifically selected a male embryo precisely so that the donor’s mitochondrial DNA would not be inherited by any future generations. The selection produced, in some real way, the same genetic outcome for the immediate child while limiting the long-term genetic implications to a single generation.
What happened to the child
The child was born healthy. CBS News’s coverage at the time of the announcement, when the child was approximately six months old, reported that he appeared developmentally normal. Subsequent testing indicated that less than two percent of the child’s mitochondria carried the Leigh syndrome mutation, which is well below the threshold at which the disease typically manifests. The retrospective documentation has noted that the figure may be closer to one percent, well below the approximately eighteen percent threshold considered clinically dangerous. The child did not, by every available indication of how his early life proceeded, develop the disease that had taken his sisters.
Zhang presented the case at the American Society for Reproductive Medicine annual conference in Salt Lake City on October 19, 2016. The presentation was the first detailed public disclosure of the case. The mother reported that the pregnancy had been considerably easier than the pregnancies that had produced her two daughters with Leigh syndrome. She had been able to feel the baby kick, which had not been a typical feature of her previous pregnancies, and the delivery had proceeded without complications.
The wider scientific community has, in the years since the announcement, been considerably more cautious about the case than the immediate public reception suggested. The MIT Technology Review’s subsequent coverage documented that the United States Food and Drug Administration sent Zhang a strongly worded letter in August 2017, ordering him to stop marketing the technique in the United States. The agency’s position was that the procedure constituted genetic modification of embryos, which is prohibited by federal legislation regardless of the medical purpose.
What this represented, in the wider context
The significance of the April 2016 birth extends, on close examination, beyond the specific case of the Jordanian family. The birth represented the first documented use of mitochondrial replacement therapy to produce a live human child. Reuters’s said at the time documented Zhang himself describing the procedure as a “revolutionary approach in human reproduction.” The case demonstrated that the technique, which had been theoretically discussed for decades, could actually be performed in humans with results that, at least in the short term, matched what the theoretical models had predicted.
The wider implications for families facing mitochondrial disease are considerable. Mitochondrial diseases affect, by various estimates, approximately one in 6,500 children worldwide. The diseases are devastating for the families that encounter them. The conventional medical infrastructure had nothing to offer these families beyond the difficult choice of either avoiding biological children entirely, adopting, using donor eggs without any of the mother’s genetic contribution, or accepting the considerable risk that any biological children would inherit the disease.
The Mexico birth demonstrated that a fourth option was, at least in principle, available. CBC’s documentation of the case quoted study co-author Dr. Taosheng Huang of Cincinnati Children’s Hospital Medical Center, who treats patients with mitochondrial disease and described families affected by the condition as “so desperate,” noting that “you want to help them, but you don’t know how to do it.” The option requires considerable technical expertise. The option raises various ethical questions about how genetic modification should be regulated. The option produces, on the available evidence of the April 2016 case, a child who is biologically the offspring of the parents who wanted that child, without the mutation that would have made the child structurally similar in his medical trajectory to the sisters who had already been lost.
What the regulatory landscape actually looks like now
The regulatory landscape surrounding mitochondrial replacement has, in the years since the April 2016 birth, remained considerably more restrictive than the procedure’s medical potential would warrant. The United Kingdom legalized the procedure in 2015, with the Newcastle Fertility Centre being the only authorized clinic, and each case requiring individual approval from the Human Fertilisation and Embryology Authority. The United States has, on the available legislative record, continued to prohibit the procedure through a Congressional rider that has been renewed annually since 2015, preventing the FDA from reviewing any clinical trial involving heritable embryo modification.
Australia legalized the procedure in 2022, through what is informally called Maeve’s Law, named after a girl who died of mitochondrial disease. Mexico, Ukraine, and Greece have continued to permit the procedure in private clinics, with limited regulatory oversight. France, Germany, and Italy have not approved it. The wider regulatory landscape remains, by every available measure of how international medical regulation actually operates, considerably more fragmented than the underlying medical science would warrant.
The acknowledgment this article wants to leave
In April 2016, a Jordanian mother who had lost two daughters to Leigh syndrome and experienced four miscarriages gave birth to a healthy baby boy in Mexico. The procedure that produced the pregnancy involved the transfer of the mother’s nuclear DNA into a donor egg whose own nucleus had been removed but whose mitochondria were healthy. The resulting egg, fertilized by the father’s sperm, contained genetic material from three people, with the donor’s contribution limited to the mitochondrial DNA that would, in the absence of the procedure, have come from the mother and carried the Leigh syndrome mutation.
The child was the first in history born through this technique. The child outlived his sisters by structural design rather than by accident. The wider medical infrastructure of the developed world had nothing to offer the family before Zhang’s team agreed to attempt the procedure. The procedure required the team to operate in Mexico because the United States, where Zhang’s home practice is located, has banned the technique.
The case represents, on the available evidence, an important moment in the development of medical techniques for addressing genetic disease. The wider cultural register has been considerably slower to absorb the significance than the underlying evidence would warrant. The slow absorbing is what the coming decades of additional research, additional cases, and additional public discussion is going to be quietly working out. The wider register would benefit, on close examination, from absorbing the case for what it actually is, rather than for the rhetorically dramatic framing the case has so far been receiving.
