Few scientific breakthroughs have proven to be as momentous – or as controversial – as the fertility treatment that has paved the way for three-parent babies. 

This extraordinary method of creating these babies is described as one of the most important advances in fertility medicine after IVF. It was created to allow families with severe inherited diseases to have healthy children.

Using genetic material from three people – sperm from the father, an egg from the mother and a donor egg from another woman – the procedure creates embryos that are virtually free of these hereditary mistakes in genes.

Mexico reported the first ever successful birth of this technique five years ago. 

Scientists in the UK have yet to make a similar announcement, even though it was eagerly anticipated. 

But now a Mail on Sunday investigation has raised questions over whether Britain’s first three-parent babies have already been welcomed – quietly and without fanfare.

Although some may argue that the process is intrusive on nature and call it Frankenscience, which creates artificial babies for 15,000 British families, it’s clear that there’s great hope. 

They are affected by hereditary defects found in the DNA in mitochondria – the batteries that power all cells – which can be passed down from mother to baby and lead to a range of devastating and often life-shortening mitochondrial diseases.

A process known as mitochondrial gift, it involves creating three-parent babies by transferring fertilised eggs of two women to the fertilised center of another woman. The egg has the DNA from both of its parents and very few traces of damaged genes. 

This happens at the earliest stages of embryo development before cells begin to reproduce.

This could be done by rectifying these genetic problems and re-inserting only healthy embryos in the mother’s womb.

After years of extensive research, no safety issues were found with this procedure. It was finally approved by both the Government and Human Fertilization and Embryology Authority (HFEA) in March 2017. 

History in the making: Dr John Zhang in a Mexican hospital with the world's only confirmed three-parent baby after its birth in 2016

Historiography in action: After its 2016 birth, Dr John Zhang was admitted to a Mexican hospital and became the only three-parent confirmed baby in the world.

Professor Sir Doug Turnbull at Newcastle University’s Wellcome Centre for Mitochondrial Research described it as a “momentous moment” after having spent many years compiling evidence for the license.

There were many ethical questions raised by critics. However, the news was that some women were lined up for the procedure. Some speculated that it could take as little as a year to have the first three-parent baby.

Since then, however, there has been no public announcement about the treatment – nor, crucially, news on whether it has actually led to any healthy babies.

But now, documents seen by this newspaper reveal that doctors at the Newcastle Fertility Centre – the only clinic licensed to perform the procedure in the UK – have applied to the HFEA for permission to use it on 26 women.

A Freedom of Information request was made two years ago and revealed that 17 of the applications had been approved. The procedure had also been performed on less than five patients.

Newcastle Hospitals NHS Foundation Trust refused to answer questions and said that they had no public updates. 

Fertility facts

1. Louise Brown, the world’s first test-tube baby, was born at Oldham General Hospital on July 25, 1978. Her age is currently 43.

2. IVF is used by approximately two percent of the children born in Britain today.

The fact that the procedure has received so many approvals suggests doctors have confidence in it. Only October saw two cases receive the approval.

All applications have been anonymised in order to keep the identities of families involved. We know 13 of 26 applications are for women with mutations that cause Leber hereditary optical neuropathy (LHON) in their children. 

This can lead to severe, sudden vision loss and may even cause neurological or heart disease.

Other families are affected by MERRF Syndrome, a rare disorder that causes seizures, muscle spasms and dementia in the early stages of life. A mutation can also cause MELAS syndrome which is a neurodegenerative disorder that could leave patients with a disability in a wheelchair.

Others have also been approved to address a mutation that causes heart disease in young people.

The University of Lancaster’s Dr David Clancy is a mitochondrial genetics researcher. He told The Mail that the HFEA has confirmed to him that there have been “less than five” pregnancies so far in December 2019, and that no live births had occurred by December 2019.

However, a patient said she was able to understand that there have been “some successful couples”.

It is a cruel form of mitochondrial disease. Many couples who have been affected by mitochondrial disease have had multiple miscarriages as a result of passing the genetic defects to their children. Many of these children died young. 

Other people with these symptoms are also determined to have unaffected children.

A 26-year-old woman whose HFEA application was accepted said that she hopes the HFEA will allow her to have a child without the LHON gene mutation which causes blindness.

Laura and her husband Leon – not their real names – are yet to successfully conceive, and know it may be a difficult road ahead, but she says: ‘We are determined to have children who are genetically related to us and who wouldn’t have the LHON mutation – by doing it this way, we cut it out of the family line for ever.’

Laura was in tears as she described how her family lost their sight suddenly in their teens. She had it first in one eye and then in the other. It took months for Laura to get over this. 

LHON eventually proved to be the reason. Laura received the news that LHON was her cause, even though she did not have any symptoms. 

She was tested, and the results – which she received the day after her wedding – confirmed her fears.

She says, “The disease struck us hard as families.” I witnessed a family member go blind, and lost all of her confidence. It was so difficult for her to do things on her own, that it made her consider suicide.

“I was aware that it was possible I would have it, but it was still shocking to hear. It was impossible to imagine that I would be able to pass on what I had seen others go through and have it continue for generations. 

It’d be something you’d keep in your thoughts. That’s not what I want.

Laura and her immediate family were unaffected by this mutation. However, a great-grandmother was reported to have lost sight.

She adds that the approval process for mitochondrial donations took six to eight months. Laura is now on the waiting list for a donor egg – and waiting times, like most treatments, have grown longer since Covid hit.

Women who are undergoing IVF can donate eggs. They may also receive reduced fees for any extras. Or, they might choose to give their eggs as a gift to infertile couples. 

Some people choose to have friends or family donate their eggs, but Laura is too far from Newcastle to be able to do this.

She says that the waiting can be very difficult. “It has been mentally affecting me, but I would rather go through it, even though it may take a long time. It was the right decision.

Creating a three-parent baby, known as mitochondrial donation, essentially involves transferring the fertilised centre of one woman's egg, which contains the DNA from both parents but only tiny traces of the damaged genes, into the healthy fertilised egg of a second woman, which has had most of its own DNA removed to leave only the healthy mitochondria

The process of creating a three-parent child, also known as mitochondrial donor, involves the transfer of fertilised eggs from one woman to another woman. This egg contains both the DNA of both parents, but very little of the damage genes.

Robert Pitceathly, a University College London Neurologist, is the co-lead for London NHS Highly Specialised Service for Rare Mitochondrial Disorders. He works closely with Newcastle’s team and says that the odds of having a healthy child are very low.

‘There are other reproductive choices available – adoption or egg donation. These families have no other options than to adopt or donate their mitochondrial cells to create a healthy child. 

The work helps to reduce the possibility of these potentially deadly conditions being passed on.

Liz Curtis, chief executive of mitochondrial disease charity The Lily Foundation, says: ‘Having children when you’re affected by mitochondrial disease is a real lottery – there’s a lot of guilt and fear. 

“The fact is, you never know what can happen and how severely they may be affected.

One of the 26 women whose application to the HFEA was approved says she hopes it will give her the chance to have a child free of the blindness-causing LHON genetic mutation she knows she carries

A 26-year-old woman whose HFEA application was accepted said she hopes that it would allow her to have a child who is not blinded by the LHON genetic mutation.

These diseases are devastating for families. Many people have suffered a lot and witnessed family members suffering. 

‘Mitochondrial donation offers the most wonderful thing – the chance to have a child free of these complications. Who wouldn’t?

The tiny structures found in almost every cell of the body (including eggs) that produce energy are called mitochondria. 

The nucleus, which is the center of all cells and contains approximately 20,000 genes that make up our identities, accounts for most of them. 

However, hundreds to thousands, if not millions, of mitochondria are located in the cells’ surrounding bodies. These have 37 genes. The mitochondria can cause mutations which stop cells functioning normally.

These mutations can cause no serious side effects at low levels. They can cause severe symptoms at high concentrations.

Most affected are areas of the body that require the most amount of energy – brain tissue, the heart and muscles – which is why many mitochondrial diseases have such a devastating impact on mobility, brain function and sometimes life expectancy. 

The symptoms begin in childhood, and get worse over time.

There are not licensed treatments, so patients have to be managed.

Contrary to many genetic disorders, mitochondrial disease is only passed down from the mother’s side. 

These mothers will, with total certainty, pass on their genetic conditions – the only question is how badly their children will be affected, which scientists cannot yet accurately predict. 

Even though families can be affected by the same gene mutation, the symptoms – and their severity – will vary according to the individual.

Dr Pitceathly states: “That inevitability and the unknowable is an awful thing to live with for families.”

A donor donates healthy mitochondria to replace the faulty mitochondria of eggs.

This is initially similar to standard IVF – an egg from the mother is fertilised with sperm from the father in the laboratory. 

However, at the very beginning of the embryo’s development and before the egg has started to reproduce and divide, scientists take out the nucleus from the fertilised egg and place it in a donor egg. This egg has been also fertilised with the father’s egg sperm, but has now had its nucleus removed.

The mitochondria that was defective in the mother’s first egg is then removed.

Now the egg from the donor contains both the maternal and father’s genetic material, but it is also surrounded with new, healthy mitochondria. To grow, this is implanted in the mother’s womb.

About 0.2 per cent of the baby’s resulting DNA will have come from the donor – a tiny fragment and not enough to affect individual characteristics such as eye or hair colour.

The technique allows babies to be born with limited information, just like those born via IVF or eggs donors.

It could include information about the donor or medical details. However, this information will not include contact information.

With the assistance of Dr John Zhang (a New York-based Endocrinologist), the world’s only three-parent confirmed baby was delivered to Jordanian parents in Mexico. It is unknown who the family was and that the child will now be five years old.

The secrecy is important. Any children born using the technique will be closely followed by scientists – if the family consents – to make sure they remain healthy.

There is still the possibility that mitochondrial fragments could be transmitted, even with all our best efforts.

Professor Sir Doug Turnbull is now retired, but he spoke to The Mail in 2013 about how embryos contained only 2% of the defective mitochondria in their early trials. It is possible that such evidence wouldn’t be found later in the process. [in future generations of children]He replied,

“The odds of reproducing are extremely low. What would you choose, to have the possibility of reproducing in the future or take the risk?

The world's first and only confirmed three-parent baby was born to Jordanian parents in Mexico in 2016, with the help of Dr John Zhang, a New York-based endocrinologist. The family has never been identified and the child would now be five

In 2016, Dr John Zhang from New York, helped to deliver the first confirmed triple-parent baby in the world. It has been unknown who the family is, and it would be now five.

“We won’t be able to eliminate defects completely, but we will get below detection limits.”

Newcastle Fertility Centre has to notify the HFEA of any negative outcomes after mitochondrial donation. 

HFEA responded that it wasn’t possible to give any additional information without the risk of patient identification when asked if such reports were received.

HFEA stated that mitochondrial donation was a novel technique and doctors wanted to learn as much information as they could about the effects it has on children and future generations. It will help ensure that they receive the highest quality care and contribute to the ongoing understanding of mitochondrial disease.