Mitochondrial replacement therapy
MRT originated as a special form of in vitro fertilisation in which some or all of the future baby's mitochondrial DNA (mtDNA) comes from a third party.
[3] Mitochondrial replacement therapy has been used to prevent the transmission of mitochondrial diseases from mother to child; it could only be performed in clinics licensed by the UK's Human Fertilisation and Embryology Authority (HFEA), only for people individually approved by the HFEA, for whom preimplantation genetic diagnosis is unlikely to be helpful, and only with informed consent that the risks and benefits are not well understood.
[5] Prior to the development of MRT, and in places where it is not legal or feasible, the reproductive options for women who are at risk for transmitting mtDNA disease and who want to prevent transmission were using an egg from another woman, adoption, or childlessness.
This egg is fertilized with sperm and allowed to form a blastocyst, which can then be investigated with preimplantation genetic diagnosis to check for mitochondrial mutations, prior to being implanted in the recipient's uterus.
[2] This technique started to be used in the late 1990s to "boost" the eggs of older women who were having problems conceiving and led to the birth of about 30 babies.
In 2001, Cohen and others reported that ten single babies, twins, and a quadruplet at his New Jersey clinic and a further six children in Israel had been born using his technique.
Using modifications of his procedure, a baby had been born at Eastern Virginia Medical School, five children at the Lee Women's Hospital Infertility Clinic in Taichung, Taiwan.
[13] In 2002, the US Food and Drug Administration (FDA) asked a Biological Response Modifiers Advisory Committee Meeting to advise on the technique of cytoplasmic transfer to treat infertility.
This committee felt that there were risks at the time of inadvertent transfer of chromosomes and enhanced survival of abnormal embryos.
[13] The FDA informed clinics that they considered the cytoplasmic transfer technique as a new treatment, and, as such, it would require an Investigational New Drug (IND) application.
[15] In 2016, 12 (out of the 13) parents of children born using cytoplasmic transfer at the Saint Barnabas Center participated in a limited follow-up inquiry via online questionnaire.
Following further research by Newcastle and the Wellcome Trust,[22][23] scientific review,[24] public consultations, and debate, the UK government recommended that mitochondrial donation be legalized in 2013.
[32][33] In 2016, John Zhang and a mixed team of scientists from Mexico and New York used the spindle transfer technique to help a Jordanian woman to give birth to a baby boy.
[39][40] In August and October 2017 the British HFEA authorized MRT for two women who had a genetic mutation in their mitichondria that causes myoclonic epilepsy with ragged red fibers.
They were helped by the Institute of Life in Athens, Greece and had obtained approval from the Greek National Authority of Assisted Reproduction.
[45] The Australian National Health and Medical Research Council issued two reports on legalising MRT in June 2020.
[46][47] In 2022, Maeve's Law was passed by the Australian Parliament, legalising MRT under a specified mitochondrial donation licence for research and training, and in clinical settings.
[3] As of February 2016, the United States had no regulations governing mitochondrial donation, and Congress barred the FDA from evaluating any applications that involve implanting modified embryos into a woman.
[55] Mitochondrial donation also has the potential for psychological and emotional impacts on an offspring through an effect on the person's sense of identity.
[56] Opponents argue that scientists are "playing God" and that children with three genetic parents may suffer both psychological and physical damage.
It recommended that initially the technique should only be used for male embryos to ensure that DNA with potential mitochondrial disease would not be passed on.
[1] In 2018 Carl Zimmer compared the reaction to He Jiankui's human gene editing experiment to the debate over MRT.
