Mitochondrial Replacement Therapy (MRT) is an advanced form of in vitro fertilization (IVF) designed to prevent mothers from passing on certain genetic diseases. The procedure allows a woman with mutations in her mitochondrial genes to have a biological child free of these conditions. This is done by combining the nuclear DNA from the intended parents with healthy mitochondria from a donor egg. The resulting embryo has genetic material from three individuals: nuclear DNA from the parents and mitochondrial DNA from a donor.
Mitochondria and Inherited Diseases
Human cells contain structures called mitochondria, often described as the cell’s powerhouses because they generate most of the energy needed for life. These organelles have their own DNA, known as mitochondrial DNA (mtDNA), which is separate from the nuclear DNA (nDNA) in the cell’s nucleus that determines most of our genetic traits. Unlike nuclear DNA, which is inherited from both parents, mtDNA is inherited exclusively from the mother.
If a mother has a mutation in her mtDNA, she can pass it to all of her children, causing a range of severe and often progressive conditions known as mitochondrial diseases. These disorders can affect any part of the body, particularly organs with high energy demands like the brain, heart, and muscles, leading to debilitating illnesses.
The severity of these diseases can vary greatly, even within the same family. This is often due to the ratio of mutated to healthy mtDNA within cells, a state known as heteroplasmy. A higher percentage of mutated mtDNA leads to more severe symptoms. As there are currently no cures for these conditions, MRT was developed as a preventative reproductive option.
How MRT Works
MRT encompasses several techniques performed during IVF, with the two most developed methods being Maternal Spindle Transfer (MST) and Pronuclear Transfer (PNT). Both procedures aim to create an embryo with nuclear DNA from the intended parents and healthy mitochondrial DNA from a donor. This ensures the child inherits personal traits from the parents while avoiding the mother’s mitochondrial disease.
In MST, the process occurs before fertilization. Scientists transfer the mother’s bundle of chromosomes from her unfertilized egg into a donor egg that has had its own chromosomes removed. This reconstructed egg, now containing the mother’s nuclear DNA and the donor’s healthy mitochondria, is then fertilized with the father’s sperm.
PNT occurs after fertilization. The pronuclei, which contain the nuclear DNA from both parents, are transferred from the mother’s zygote into a donor zygote from which the original pronuclei have been removed. The resulting embryo has genetic material from three people: nuclear DNA from the mother and father, and mitochondrial DNA from the donor.
The donor’s mtDNA is less than 0.1% of the total genetic material. This unique combination has led to the term “three-parent babies,” though the vast majority of inherited traits come from the intended parents.
Current Uses and Health Outcomes
The clinical application of MRT is in its early stages and is only legally permitted in a few countries. The United Kingdom has pioneered licensed treatments, and as of early 2023, its regulator reported that a small number of babies had been born there using MRT. The long-term health of these children is still being monitored.
Procedures have also been performed in other nations with different regulations. For example, the first reported baby born via MRT involved treatment in Mexico, and a clinic in Greece has used the technology to address infertility, which is a controversial application.
The main benefit of MRT is allowing families with mitochondrial disease to have healthy, genetically related children. However, the techniques have risks, including potential damage to the egg or embryo during transfer. A specific concern is “reversion,” where faulty mitochondria from the mother are accidentally carried over and multiply, possibly causing disease later. For this reason, long-term follow-up of children born through MRT is a necessary part of its clinical use.
Ethical Considerations
MRT has prompted significant ethical discussions. A central issue is that the procedure modifies the human germline, as the donated mitochondrial DNA is passed down through the maternal line to future generations. This raises concerns about making permanent changes to human heredity and potentially opening the door to genetic modification for non-medical enhancement.
The welfare of children born from these techniques is another focus, with questions about their long-term health and personal identity. The term “three-parent baby” has fueled public debate over family structures and genetic parentage. The rights and role of the mitochondrial donor, including anonymity and her connection to the child, are also part of the discussion.
Proponents frame MRT as a preventative medical treatment that prevents severe diseases and supports the reproductive autonomy of parents. These differing perspectives highlight the tension between using technology to reduce suffering and the caution against altering human biology, explaining why its adoption has been slow and carefully regulated.
Global Regulation of MRT
The legal landscape for MRT varies significantly worldwide. The United Kingdom has a comprehensive regulatory framework, having passed regulations in 2015 to permit its use in specific circumstances. The Human Fertilisation and Embryology Authority (HFEA) licenses clinics on a case-by-case basis to prevent serious mitochondrial disease.
In contrast, the United States has a more restrictive approach. The Food and Drug Administration (FDA) prohibits the clinical use of MRT, and federal legislation has blocked clinical trials involving heritable genetic modifications. This has limited MRT applications in the U.S. to laboratory research.
Other countries are creating their own regulations. In 2022, Australia passed “Maeve’s Law,” which legalized mitochondrial donation and allows for a staged introduction of the technology, beginning with clinical trials. Meanwhile, MRT has been performed in countries with less stringent regulations, such as Greece and Ukraine, sometimes for applications like treating infertility. This patchwork of global laws illustrates the ongoing international debate over the technology’s use.