“When Mitochondrial DNA Changes Inheritance: Babies with Three DNAs”

The term “babies with three DNAs” refers to babies conceived using an in vitro fertilization technique called Mitochondrial Donation Treatment (MDT). This technology uses genetic material from three people to prevent the transmission of serious inherited diseases.

Mitochondria are the organelles responsible for cellular respiration, the process by which nutrients are transformed into ATP, the body’s main source of chemical energy. Of endosymbiotic origin, mitochondria contain their own genetic material—mitochondrial DNA—and mutations in this DNA result in defective mitochondria. Consequently, various systems, such as the visual system, and organs like the brain, heart, and kidneys can be affected to varying degrees of severity.

What is MDT? 

MDT is an in vitro fertilization technique that combines the nuclear DNA of the mother and father with the mitochondrial DNA of an egg donor. There are two variations:

1) The nucleus of the maternal egg is transferred to a donor egg from which the nucleus has been removed and which contains healthy mitochondria. The reconstructed egg is fertilized with the father's sperm.

2) Two eggs are fertilized with the father's sperm, resulting in two zygotes: one with nuclear DNA from the mother and father, but with mutated mitochondria; the other with nuclear DNA from the father and the donor, with healthy mitochondria. The nuclear material from the maternal zygote is extracted and inserted into the donor zygote, which has been previously emptied of its own nucleus, thus preserving the healthy mitochondria.

In both variations, the result is an embryo containing nuclear DNA from the biological parents (approximately 99.8% of the total genome) and healthy mitochondrial DNA from the donor (approximately 0.2%). Thus, the resulting baby is genetically related to its parents and free of mitochondrial disease.

Why is this newsworthy?

Although this technique was legalized a decade ago in the United Kingdom, the New England Journal of Medicine recently published evidence confirming that it is resulting in children born without these types of diseases.

Scientists state that approximately one in 5,000 children suffers from a disorder related to mutations in mitochondrial DNA. For many affected families, this is the first real hope of breaking the cycle of these inherited diseases. To date, eight healthy babies have been born thanks to this experimental technique, and 35 patients have been authorized to undergo it. Undoubtedly, "a triumph of scientific innovation"

Ethical and Scientific Considerations

Ethically, this technique raises questions about genetic identity, the limits of germline modification, and trait selection. However, it is important to emphasize that MDT technology does not seek to modify genes, but rather to prevent a mother from transmitting a life-threatening disease to her child. Therefore, access is limited to carefully selected patients residing in jurisdictions where the use of this technology is legally permitted and regulated. The United Kingdom was the first country to approve it in 2015, followed by Australia in 2022. It has also been practiced in Ukraine. On the other hand, in many other countries, including the United States and Canada, this technique is prohibited or not specifically regulated for widespread clinical use.

Scientifically, the long-term stability of mitochondrial replacement is still being evaluated, especially if "remnants" of mutated mitochondria remain. This technology aims to minimize this risk by transplanting the mother's nuclear genetic information into a healthy, donated egg. However, it is not always possible to eliminate 100% of the maternal cytoplasmic material, which contains the defective mitochondria. There is a theoretical risk, observed in laboratory studies, that the remaining affected mitochondria may, over time, proliferate preferentially and reach a critical level (heteroplasmy) that causes symptoms of the disease in the child. For this reason, children born through mitochondrial DNA modification are subject to continuous medical and scientific monitoring to track the levels of affected mitochondrial DNA and detect any potential increases that could indicate a future health problem.

Undoubtedly, MDT technology is a significant medical advance for families affected by mitochondrial diseases. However, it also represents an important precedent in human germline genetic modification and has opened a crucial debate on the ethics of manipulating heritable DNA. But this technique has shown that, under strict regulatory oversight and with a clear medical purpose, society can accept certain forms of heritable genetic modification. The challenge lies in maintaining clear boundaries.

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