Worlds First Three-Parent Baby Raises Questions About Long-Term Health Risks

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A baby boy, the first infant to be born employing a new technique that incorporates DNA from three people, is now five months old. It is great news the birth of a healthy newborn conceived by this new procedure is a major step forward and will lead to a new route of preventing the inheritance of mitochondrial diseases.

Mitochondria are the powerhouses of cells. They produce energy for all life processes. One in 400 people has a maternally-inherited mutation in mitochondrial DNA( mtDNA )~ ATAGEND, the blueprint for some vital mitochondrial components. MtDNA mutants can cause a range of maladies, including deafness, blindness, diabetes, and heart and liver failing. People with these ailments usually have both normal and injury mtDNA, the symptoms being generally worse the higher the dose of damaged mtDNA. Sadly, there are no cures.

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Mitochondria: the part of the cell that generates energy. Wire_man/ Shutterstock.com

In Mitochondrial replacement therapy( MRT ), embryos of the couple at risk of having an affected child are generated in a test tube. In this case, the nucleus that contains all of the genetic material apart from the mitochondria was removed from the mothers egg and placed into an egg with healthy mitochondria, from which the nucleus had been removed. The egg was then fertilised with the parents sperm and the resulting embryo was placed in the mothers womb where it developed into the baby.

This entails the newborn has three genetic mothers: the parent who supplied the sperm, the mother who supplied both womb and the egg nucleus, and an anonymous donor who rendered healthy mitochondria. Of these, the mitochondrial DNA is by far the smallest contribution. This type of three-parent baby is new, although other types have existed for many years.

MRT is being developed by groups in the UK and US to help the families of patients who have mitochondrial cancer with a high recurrence risk in future children.

Unknown long-term consequences

While experimentations on monkeys and mice suggested that such newborns would probably be healthy, this procedure hadnt been used in humans until now. Eggs are highly organised cells. Replacing the nucleus does not avoid development into a newborn, but it causes damage to the cell that probably necessitates revolutionary re-organisation. So, the effects of such manipulations are still unknown and could cause problems later in life, such as an increased chance of diabetes.

According to a New Scientist report, the mother of the child, a Jordanian woman, had been trying for a family for 20 years. Her two children both died of Leigh syndrome aged eight months, and six. The female had a high risk of having further affected children.

In many countries, the mother would have been given other choices before MRT was offered. First, she would have been offered eggs from an unrelated healthy donor. These could be fertilised with her partners sperm and put into her womb, preventing transmission of the mitochondrial cancer altogether. The female with mtDNA disease is then the biological but not the genetic mother. Being born to a woman who is not your genetic mother may be acceptable to some people, given that perhaps up to one in 10 people in the UK do not identify their genetic fathers correctly but it may have been unacceptable to this family.

She would have also been offered pre-implantation genetic diagnosis whereby several embryos can be tested at an early stage and the best one selected to be placed in the mothers womb. However, this was reportedly not ethically acceptable to this family.

The birth of a healthy baby after this technique is a big step forward. In the past related manipulations to improve oocyte mitochondrial quality have been carried out so called ooplasm donation which involves donor mitochondria that are injected into a germ cell in the ovary( an oocyte ). But the following procedure reportedly caused genetic defects and perhaps autism in one case.

While it is not yet possible to give the latest baby a decisive all clear, he carries a low level of the damaging mutant, inducing it highly unlikely that he will develop Leigh syndrome.

The known unknowns

However, there are two more details of the tale that could affect what happens next. First, the procedure could be worded medical tourism: it was done in Mexico by a team based in New York City, so it was not covered by US regulations, which do not permit the procedure. The Institute of Medicines Committee on the Ethical and Social Policy Considerations of Novel Techniques for Prevention of Maternal Transmission of Mitochondrial DNA Diseases declined to give regulatory approval for clinical employ of the procedure until research to answer critical safety and efficacy questions has been done.

Another problem is that we are not told how high the level of injury mtDNA was in the mothers egg before the procedure was carried out a detail that indicates how likely the child was to be severely affected at the outset. If the level and hence the risk was high, this is a laudable technical advance that has massively reduced the childs chance of suffering a severe illness. If the level was low and compatible with a healthy life, then a procedure with significant unknowns might have been done unnecessarily exemplifying how much we need regulation to protect the rights of the future child. Reports do not clarify these vital details.

This story is the beginning of a new treatment with massive potential for good. However, rigorous regulation and checks on the unknowns of this new and controversial technology are needed.

TheJoanna Poulton, Professor, University of Oxford

This article was originally published on The Conversation. Read the original article.

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