FROM THE DESK OF THE GROUP EDITOR-IN-CHIEF modification” of future generations because mitochondria are usually inherited from the mother. The committee also recommends the technique be limited to women with serious mitochondrial diseases, and that regulators should take the mother’s health and the expertise of the scientists into account before approving studies (Science News, February 3, 2016).” Two mitochondrial transfer techniques have been developed to prevent transmission of human mitochondrial DNA disease. ÂÂ
Pronuclear transfer technique: In this technique, the egg from the mother and a female donor egg are fertilized with the father’s sperm via IVF. The pronuclei are then removed from each embryo, still at the single-cell stage. The pronuclei from the embryo produced from the parents is then placed in the second embryo formed using the donor egg. Most of the mother’s mutated mitochondria are left behind in the enucleated embryo, which is discarded. The nucleus from the donor’s fertilized egg is discarded. This is the approved technique in the UK to prevent transmission of mitochondrial DNA disease.
Nuclear genome transfer and Polar body genome transfer are other techniques, but these are more at an experimental stage. Because of cultural reasons, the Dr Zhang and this team did not opt for the "pronuclear transfer" technique, as they were opposed to the destruction of embryos. Hence, they opted for the "spindle nuclear transfer" technique. Five embryos were created and embryos were not destroyed; a male embryo was used, so that the child born would not pass on any inherited mitochondrial DNA. This news generated lot of excitement and hope among researchers, especially those in the field of reproductive medicine. It has also come as a ray of hope for those parents with genetic diseases who otherwise are not able to conceive a healthy child. Regardless, safety is a concern and there are significant ethical issues associated with it that need to be answered.
Spindle transfer technique: In this technique, the nucleus (metaphase II spindle) from one of the unfertilized eggs of the mother is removed, which is then transferred into a healthy donor egg from which the nucleus is removed, leaving her healthy mitochondria in the cytoplasm. The reconstituted egg is then fertilized with the father’s sperm and the resulting embryo is implanted in the mother.
There may be inheritable genetic modifications that may be passed on to future generations. Even very small amounts of mutated mitochondrial DNA may be carried over, which may replicate later on in life. Evidence shows that mitochondria are not just "powerhouses of the cell", they also impact phenotypic traits. A mitochondrial-nuclear NDA mismatch may affect gene expression. And, this genetic manipulation is not reversible. A child born of three-person IVF would have three "genetic" parents. Bioethicists say that "interfering" with genetic code may alter the identity of the person.
Earlier studies reported in reputed journals like Science, Nature have shown encouraging results in preventing transmission of mitochondrial DNA disease using these techniques in animal models.
Many such questions and more need to be answered first before the technique would be available in reproductive clinics. But, it’s no longer "the stuff that fiction is made of".
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Indian Journal of Clinical Practice, Vol. 27, No. 5, October 2016