Three Parent Babies

The term three-parent babies refers to children conceived using a reproductive technique that involves genetic material from three individuals — two biological mothers and one father. The method, scientifically known as mitochondrial replacement therapy (MRT), was developed to prevent the transmission of serious inherited diseases caused by defective mitochondria. This advanced form of assisted reproductive technology represents a major milestone in genetic medicine and bioethics, combining techniques from in vitro fertilisation (IVF) and mitochondrial biology.

Background and Scientific Basis

Human cells contain two types of genetic material:

• Nuclear DNA, located in the cell nucleus, which determines the majority of an individual’s genetic traits and is inherited from both parents.
• Mitochondrial DNA (mtDNA), found in small structures called mitochondria, which produce the energy required for cellular functions and are inherited exclusively from the mother.

Defects in mitochondrial DNA can lead to severe and often fatal disorders, including mitochondrial myopathy, Leigh’s syndrome, and MELAS (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes). These diseases affect approximately one in every 5,000–10,000 births and currently have no effective cure.
Mitochondrial replacement therapy was developed to allow women with such genetic defects to have genetically related children free from mitochondrial disease. The term “three-parent” arises because the resulting child inherits:

• Nuclear DNA from the mother and father, and
• Healthy mitochondrial DNA from a female donor.

Methods of Mitochondrial Replacement

There are two main scientific techniques used in creating three-parent babies:

1. Maternal Spindle Transfer (MST)
   • In this method, the nuclear DNA is removed from the egg of the mother carrying defective mitochondria.
   • This nuclear material is then transferred into a donor egg that has had its own nucleus removed but retains healthy mitochondria.
   • The reconstructed egg, containing the mother’s nuclear DNA and the donor’s mitochondria, is then fertilised with the father’s sperm.
2. Pronuclear Transfer (PNT)
   • Both the mother’s and donor’s eggs are fertilised with the father’s sperm, creating two zygotes.
   • The nuclear DNA from the donor’s zygote is replaced with the nuclear DNA from the mother’s zygote, leaving behind the donor’s healthy mitochondria.
   • The modified embryo is then implanted in the mother’s uterus.

Both methods result in an embryo with over 99.8% of genetic material from the parents and a very small fraction (less than 0.2%) from the mitochondrial donor.

Medical Rationale and Benefits

The principal aim of mitochondrial replacement therapy is disease prevention, not genetic enhancement. For women carrying pathogenic mtDNA mutations, MRT offers the only way to:

• Prevent the inheritance of mitochondrial diseases.
• Have genetically related children without the risk of fatal illness.
• Break the maternal line of disease transmission across generations.

In addition to its medical benefits, MRT contributes to scientific understanding of genetics, reproduction, and mitochondrial function.

Ethical and Legal Considerations

The development of three-parent babies has sparked extensive ethical, legal, and social debate. Key concerns include:

• Genetic Identity: The child inherits DNA from three individuals, raising philosophical and legal questions about parenthood and identity.
• Germline Modification: MRT alters the germline — meaning the genetic changes are heritable and passed on to future generations. This distinguishes it from somatic gene therapy, which affects only the treated individual.
• Safety and Long-Term Effects: Since the technology is relatively new, long-term effects on health, fertility, and genetic stability are still being studied.
• Consent and Regulation: Ethical frameworks emphasise that donors and recipients must give fully informed consent, and that procedures occur under strict regulatory oversight.

Critics argue that MRT represents a step towards human genetic modification and “designer babies,” though proponents highlight its use solely for therapeutic purposes.

Global Regulation and Implementation

Different countries have taken varied stances on mitochondrial replacement therapy:

• United Kingdom: In 2015, the UK became the first country to legally approve MRT under the Human Fertilisation and Embryology (Mitochondrial Donation) Regulations 2015. The Human Fertilisation and Embryology Authority (HFEA) oversees licensing and ensures strict ethical compliance.
• United States: MRT is not yet approved for clinical use; the U.S. Food and Drug Administration (FDA) has prohibited its application pending further ethical and safety review.
• Other Nations: Procedures have been attempted in countries with less stringent regulations, such as Mexico and Ukraine, where the first three-parent baby was reportedly born in 2016.

Scientific Achievements and Milestones

The first successful birth using mitochondrial replacement occurred in 2016, when a boy was born to a Jordanian couple using MST performed by an American research team in Mexico. The child was free of Leigh’s syndrome, the condition carried by his mother.
Following this, several other cases have been reported globally under controlled clinical trials. The Newcastle Fertility Centre in the United Kingdom has also conducted MRT procedures under regulatory approval, focusing on preventing the transmission of mitochondrial diseases.

Technical Challenges and Risks

Although promising, MRT faces several scientific and clinical challenges:

• Mitochondrial Carryover: A small amount of defective mitochondria from the mother may remain in the reconstructed egg, potentially leading to disease recurrence.
• Compatibility Issues: The interaction between nuclear and mitochondrial DNA from different individuals may influence metabolism, gene expression, and ageing.
• Embryo Viability: Manipulation during MRT can affect embryo development and reduce implantation success rates.
• Ethical Oversight: Balancing innovation with safety and public trust requires continuous monitoring and international cooperation.

Broader Implications

Beyond treating mitochondrial disease, research into three-parent techniques may have broader applications in reproductive medicine and genetics, including:

• Understanding mitochondrial–nuclear interactions and their role in ageing and disease.
• Developing methods to improve IVF success rates by rejuvenating older eggs with healthier mitochondria.
• Expanding ethical discourse on germline modification and the future of human genetic technologies.