Controversial Three-Parent Baby and How Mitochondria Plays a Role
Controversy quickly struck surrounding the subject of a three-parent baby recently born. CNN covered the topic, revealing how malfunctioning mitochondria made one woman do the extreme:
(CNN)-A healthy baby boy was born on April 6 in Mexico that has some in the medical community rejoicing and others concerned.
The divide is due to the method of conception: a three-parent technique called "spindle nuclear transfer," the details of which were published Tuesday in the journal Fertility and Sterility.The process involves adding a handful of genes from a donor woman to the mother's egg and then fertilizing the egg with the father's sperm to create an embryo, which becomes a baby.The use of this reproductive technology was intended to prevent Leigh syndrome, a severe neurological condition that affects at least one in 40,000 newborns. The mother in this historic case previously had four pregnancy losses and had given birth to two children, one of whom survived less than a year and another lived only 6 years, both due to the syndrome.For religious reasons, the mother wanted to use a technique that would not require the destruction of fertilized eggs, which an approved treatment in the United Kingdom would require. The three-parent technique was the solution.
A team of doctors, led by Dr. John Zhang, founder of the New Hope Fertility Center in New York City, went to Mexico to perform the procedure. The Food and Drug Administration has not approved the technique, while Mexico is free of such regulations.And therein lies the controversy. If you cherry pick countries because the laws are looser, you undermine scientific development under controlled circumstances and add risk to the patient.Though billed by Zhang as a "first ever," a different version of this same technique had been used by fertility clinics in the past, explained Professor Hank Greely of Stanford University, who specializes in the ethical, legal and social implications of new biomedical technologies."About a dozen such babies were born in the US in the late 1990s/early 2000s before the FDA -- pushed, I think, by cloning concerns -- decided that this procedure needed FDA approval," said Greely, adding that the clinics who did this before have since stopped performing the procedure.While in the past, the procedure was used to help women conceive and give birth to healthy babies in cases of infertility, the new version was created to tackle a specific problem: mitochondrial mutations.
What are mitochondria?To understand how this procedure works, and why it's useful in some situations, requires a mini-tutorial on mitochondria.Almost all the cells in our bodies have mitochondria. These "organelles" -- a mini-version of an organ within a cell -- perform as tiny batteries do, producing much needed energy. What is unusual about mitochondria, though, is they carry 37 genes of their own and these are passed, intact, from mother to child through the egg.A sperm also carries its own battery pack, but once it fuses with an egg to form an embryo, the masculine mitochondrion withers and dies.No matter whether we are male or female, we inherit our mitochondrial DNA (or mtDNA) from our mothers, who inherited hers from her mother.But sometimes a woman may be born with a mutation in her mitochondrial DNA. Though genetic defects may not cause negative health effects for her, they could cause a mild or severe disorder if passed on to a child, said Dr. Owen K. Davis, president of the American Society for Reproductive Medicine. Zhang's results will be presented at the society's annual conference next month."To have the full-blown disease, you have to have a high percentage of these mutated mitochondria," said Davis. In the current example, about a quarter of the mother's mitochondria were mutated while the babies she lost had over a 95% mutation load."A small amount of DNA is not necessarily going to cause a full-blown syndrome," said Davis, adding that in the process of these genes passing from mother to child, defective DNA can multiply so that the child ends up with more abnormal mitochondria than the mother.The fix? Use another woman's mitochondrial DNA in order to get the load down to a really low level.Essentially, then, Zhang and his colleagues sucked the mitochondria out of the mother's egg, inserted donor mitochondria in its place and then fertilized the egg."Transfer of the [normal] embryo resulted in an uneventful pregnancy with delivery of a healthy boy at 37 weeks of gestation," wrote Zhang and his co-authors in the published study.
Questions about the baby's futureSome experts questioned the procedure."It's unfortunate to have people decide they're just going to quite willingly engage in this kind of reproductive tourism -- to go outside of a system that is in place to create the safest, most scientifically reproducible way forward," said Lori P. Knowles, assistant professor, adjunct, at the University of Alberta School of Public Health. "That's the precedent then, that if you think you can do it, then let's just hop the border and see what happens, hope for the best."Her view is supported by R. Alta Charo, a professor of law and bioethics at the University of Wisconsin at Madison. This technique, as Charo explained, has been closely examined by both the British regulatory authorities and the American National Academy of Medicine and National Academy of Sciences."It is regrettable that it is now occurring in countries that have not had similarly serious close looks at both the technical and ethical aspects," said Charo. "It's going to be difficult to use the results of this particular effort in the context of organized data collection," she said, "And that's a shame, that's a real loss of information not only to science but to every patient in the future who is considering this."More importantly, though, she is concerned for the boy who is now 6 months old. "Follow-up is going to be important to look at the health of the child," said Charo."It's always wonderful that a baby has been born and born healthy ... as far as we know," said Knowles. She is not alone in her skepticism for the future health of this baby. Tuesday, the Science Media Centre published the comments of 12 experts, many who reported similar reactions to the news."We know that the procedure is not perfect," said Dr. David J. Clancy, lecturer, Lancaster University, who explained that in 2015, a published study showed "that tissue-specific expansion of mutated mitochondrial DNA during development can occur and so could cause disease if levels are high enough."A healthy baby might eventually develop a disease, Clancy suggests.Knowles also pointed out that four out of five eggs fertilized by Zhang and his colleagues were nonviable -- only one embryo could produce a child."It shows you the technique itself is still quite fallible," said Knowles, who noted that there's no guarantee the defective mutation might not accumulate within the baby boy and eventually lead to disease. "Which is the whole reason you're supposed to go slowly ... and not jump right into creating babies."