JUST how far could we, and should we, go in engineering reproductive science to improve human health?

It is a question that has been thrust back into the spotlight this week by important new developments in genomics and the news that the first so-called "three parent baby" has been born in the UK.

A freedom of information request to the Human Fertilisation and Embyology Authority (HFEA) - the regulator for reproductive medicine - revealed that, as of the end of April this year, at least one infant had been delivered following the use of mitochondrial replacement therapy (MRT).

HeraldScotland: The mitochondrial replacement therapy process transfers the nucleus from a fertilised egg into a donor egg containing healthy mitochondriaThe mitochondrial replacement therapy process transfers the nucleus from a fertilised egg into a donor egg containing healthy mitochondria (Image: Newcastle NHS Foundation Trust)

The technique, pioneered by doctors in Newcastle, is designed to remove the risk of certain inherited disorders being passed from mother to child.

We do not know where or when it was born, and there may in fact be more than one MRT baby - the HFEA would only confirm that there had been "less than five" on the grounds of patient confidentiality.

READ MORE: Baby with DNA from three people born in the UK for first time

Nevertheless, it represents a landmark moment nearly 45 years after the UK welcomed the world's IVF first baby, Louise Brown, in July 1978.

The UK was the first country in the world to pass laws permitting the clinical use of MRT in 2015, although the Newcastle Fertility Clinic remains the only centre licensed nationally to perform the procedure.

It is up to the HFEA to approve its use on a case-by-case basis and, to date, it has permitted at least 30 attempts.

Worldwide, the first baby known to have been born following mitochondrial replacement therapy was delivered in 2016 by a US doctor who treated a Jordanian woman at a clinic in Mexico.

The mother carried mutations in her mitochondrial DNA for neurological disorder called Leigh syndrome, which is usually fatal to sufferers within the first three years of life.

HeraldScotland: Dr John Zhang, pictured in 2016 with the world’s first baby born using mitochondrial replacement therapyDr John Zhang, pictured in 2016 with the world’s first baby born using mitochondrial replacement therapy (Image: New Hope Fertility Center)

She had previously suffered four miscarriages and given birth to two children - one who died aged six and another who survived for just eight months.

The goal of MRT is to eliminate faulty mitochondria - the tiny 'batteries' which power cell functions.

To do so, scientists fertilise the mother's egg with the father's sperm before removing the nucleus - leaving the mother's mitochondria behind.

This is then inserted into a donor egg packed with healthy mitochondria whose unfertilised nucleus has already been discarded.

The resulting offspring inherits more than 99.8 per cent of its DNA from its biological parents, plus a small amount of genetic material - around 37 genes - from the donor.

Not all babies born to to women with harmful mitochondrial mutations will become ill, but if they do the consequences can be severe as they tend to attack organs such as the brain, heart, muscles and liver causing lethal degenerative conditions.

Around one in 6000 babies suffer some form of mitochondrial disorder.

READ MORE: Boy aged one youngest to hae testicle frozen to preserve fertility in chemo battle 

MRT is not a guaranteed cure; in some cases, very tiny numbers of faulty mitochondria which are carried from the mother's egg into the donor egg go on to multiply during gestation in a process known as 'reversal'.

It is unclear why this happens in some children born from MRT, but not others.

The outcome of the UK cases is still unknown, but anonymised details are expected to be published in a peer-reviewed scientific journal in the near future.

It comes as international researchers on Wednesday released the first draft of what is known as a "reference pangenome" - a collection of DNA sequences from 47 people which provides the most comprehensive map of the human genome to date.

They hope to increase it to 350 by mid-2024.


Until now the standard reference human genome - first published in 2003 - was based on DNA from just 20 people, but most of it came from a single American man with European and African ancestry.

Although it has been used to advance our understanding of genes involved in the onset of certain inherited diseases and to improve some cancer therapies, it misses important genetic differences between populations.

For example, studies have shown that children of European ancestry are twice as likely to be diagnosed using genetic tests than those of Africa ancestry.

It is hoped that the pangenome will help correct this given that half of its DNA samples reflect sub-Saharan Africa - the birthplace for humanity and the most genetically diverse region in the globe.

READ MORE: Genomic sequencing and the future of infection control 

But could a better understanding of the human genome also spur greater interest in engineering it?

In 2018, Chinese scientist He Jianki sent shockwaves through the scientific community when he announced that he had gene-edited the embryos of twin girls to make them resistant to HIV.

It is unclear whether he actually succeeded - his work was so controversial that it has never been published, and he was jailed for three years.

HeraldScotland: He Jianki was found guilty of conducting 'illegal medical practices' by genetically editing babiesHe Jianki was found guilty of conducting 'illegal medical practices' by genetically editing babies (Image: Getty)

However, reports at the end of 2022 suggest that 'pronatalist' Silicon Valley entrepreneurs are keen to enlist experts in CRISPR gene editing science in a sort of genetic arms race to design "superior" humans.

Such ambitions are likely to remain the stuff of science fiction - but what about purely medical interventions?

In an editorial in the New York Times in March, Eben Kirksey, an associate professor of anthropology at Oxford University and author of 'The Mutant Project: Inside the Global Race to Genetically Modify Humans', wrote that the ethical questions around the potential for gene editing in humans "need to be addressed, not brushed under the rug".

There are hopes, for example, that gene editing could be used safely in embryos to cure deafness, blindness, or congenital conditions such as cystic fibrosis and sickle-cell anaemia before birth.

If the past 40 years of reproductive medicine has transformed the landscape for fertility, the next 40 years could be set to move the dial on inherited disease.