Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Professor of Mitochondrial Genetics, Joanna Poulton gives her views on the recent announcement that a baby boy, the first child to be born using a new technique that incorporates DNA from three people, is now five months old.

Professor J Poulton

Joanna Poulton, University of Oxford

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

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

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 mother’s egg and placed into an egg with healthy mitochondria, from which the nucleus had been removed. The egg was then fertilised with the father’s sperm and the resulting embryo was placed in the mother’s womb where it developed into the baby.

This means the baby has three genetic parents: the father who supplied the sperm, the mother who supplied both womb and the egg nucleus, and an anonymous donor who supplied 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 disease with a high recurrence risk in future children.

Unknown long-term effects

While experiments on monkeys and mice suggested that such babies would probably be healthy, this procedure hadn’t been used in humans until now. Eggs are highly organised cells. Replacing the nucleus does not prevent development into a baby, but it causes damage to the cell that probably requires radical 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 woman 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 partner’s sperm and put into her womb, preventing transmission of the mitochondrial disease completely. The woman with mtDNA disease is then the biological but not the genetic mother. Being born to a woman who is not your genetic parent 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 mother’s 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 this 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 mutation, making it highly unlikely that he will develop Leigh syndrome.

The known unknowns

However, there are two more details of the story that could affect what happens next. First, the procedure could be termed “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 Medicine’s 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 use 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 damaging mtDNA was in the mother’s 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 child’s 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 – illustrating 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.

The Conversation

Joanna Poulton, Professor, University of Oxford

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

Similar stories

MitOX 2023- 21st April

The Nuffield Department of Women's & Reproductive Health invites you to MitOX 2023 on Friday 21st April. Our annual conference for researchers with an interest in mitochondria from academia and pharma. This year's event will be 'hybrid', so you can join in-person or virtually!

Award Winning Podcast

‘Unheard of – The hidden voice of Endometriosis ’ the podcast series co-hosted by Danielle Perro (Postdoctoral Researcher in Epidemiology) and Magda Mareckova (DPhil student) has been recognised by the Wellcome Centre for Human Genetics, with a Public Engagement with Research Project Award.

What is the impact of heavy menstrual bleeding on female health and well-being?

Many of us have no idea whether or not our period is “normal”. It’s no wonder, since not only is everyone different, but the stigma still keeps many of us from asking questions or discussing what we go through every month with friends and family. Principal Investigator Prof Suzannah Williams and DPhil student Tomi Adeniran explore what heavy periods can mean in their article published in The Conversation.

Women's Health Strategy for England Launched

The government has published the first ever Women's Health Strategy for England to tackle the gender health gap. Menopause, Endometriosis, Contraception and Fertility treatment are highlighted as some of the top issues women have asked for action on. The Nuffield Department of Women's & Reproductive Health welcome and fully support this bold and exciting strategy to help improve the health of millions of women in England.

Prof Christian Becker wins Clinical Science Award at ESHRE 2022

Congratulations to Professor Christian Becker who was presented with a Clinical Science Award for best oral presentation at the ESHRE 38th Annual Meeting in Milan, Italy this week.

Oxford's largest ever study into Varicose veins shows need for surgery is linked to genetics

Varicose veins are a very common manifestation of chronic venous disease, affecting over 30% of the population in Western countries. In America, chronic venous disease affects over 11 million men and 22 million women aged 40–80 years old. Left untreated it can escalate to multiple health complications including leg ulcers and ultimately amputations. A new international study by Oxford researchers published on 2nd June 2022 in Nature Communications establishes for the first time, a critical genetic risk score to predict the likelihood of patients suffering with Varicose veins to require surgery, as well as pointing the way towards potential new therapies.