Since the birth of Louise Brown in July 1978 after in-vitro fertilisation was pioneered by Bob Edwards in the 1960s, Cambridge has been a hub for scientific research surrounding IVF. Since her birth, over twelve million babies have been born using IVF worldwide.

The ethics surrounding the degree of interference into IVF embryos have long been discussed, both within scientific and political communities. In the UK, as with most of the world, legislation tightly regulates the practice. The question of ‘designer’ babies, where embryos are genetically engineered to seek out specific cosmetic results, has caused push-back on many projects to eliminate diseases from embryos.

“He was condemned by scientific communities across the world for his ‘monstrous’ experiments”

Despite strict laws, there have been several attempts to genetically modify IVF embryos. He Jiankui, a Chinese biophysicist, used CRISPR/Cas9, a simple system composed of gRNA (guide RNA to target the correct genetic sequence) and Cas9 (an enzyme used to specifically cut the DNA strand), to genetically engineer the sperm of an HIV-positive father. He introduced the CCR5 gene, inhibiting entrance of HIV-1 into cells. It was reported that healthy twins were born, although they were not protected from other methods of HIV attack, resulting in no real benefit from the gene manipulation. Following the discovery of his experiments, He Jiankui was sentenced to three years in prison and was condemned by scientific communities across the world for his ‘monstrous’ experiments.

However, genetic modification also offers the prospect of eliminating certain life-threatening genetic diseases. The current procedure for preventing genetic diseases is to screen IVF embryos for serious diseases, such as cystic fibrosis, and chromosomal abnormalities. This is done through an IVF service, known as Preimplantation Genetic Testing (PGT), which can increase the price of a single cycle of IVF to around £14,000. Normally, PGT will find that some, if not all the embryos, will lack any genetic faults.

“All the babies born were free from mitochondrial diseases”

However, if a mother has mitochondrial disease, all her embryos may have defective mitochondria as they are maternally inherited. Mitochondria, often taught colloquially as the ‘powerhouse of the cell’, are organelles optimised to conduct cellular respiration, releasing energy to power different cells and organs. They also contain a small genome, consisting of around 37 genes, remnant from its time as a type of bacteria before it was engulfed into a eukaryotic cell.

Mitochondrial diseases can have life-threatening results, particularly affecting organs which require a high influx of energy, such as the brain and heart. Women with mitochondrial disease risk passing it on to their children, as well as possibly exacerbating their own symptoms during pregnancy. So enters the three-parent baby.

“The donor egg allows healthy, functional mitochondria to be supplied to the parents’ embryo in place of the mother’s defective mitochondria”

Introduced to the US in 2016, the technique was first performed in the UK in Newcastle upon Tyne Hospitals in 2023. The ‘three-parent baby’ process is a mitochondrial donation, involving two eggs, one from the mother of the baby, and the other from a donor. Both mother and donor embryo are fertilised by the father’s sperm. Once the embryos have started to develop, the genetic material of the donor embryo is replaced by that of the parents’ embryo. The donor egg allows healthy, functional mitochondria to be supplied to the parents’ embryo in place of the mother’s defective mitochondria, while only contributing 0.1% of the genetic material.

Eight babies have since been born using this method in the UK, with results of the eagerly-awaited accompanying study released earlier this year in July. All the babies born were free from mitochondrial diseases. All other medical conditions that developed in the resultant children, such as a case of epilepsy, are not thought to be linked to mitochondrial diseases.

However, the study wasn’t perfect. Offspring did show relatively high levels of defective mitochondria, with some of the patients having up to 20% of their mitochondria still coming from their mother. Dr Mary Herbert, who led the research team, said that “this is higher than we would have expected.” Whilst defective mitochondria are unlikely to reach a level high enough for mitochondrial disease to manifest in these children, the variability in numbers passed on raises concerns about the technique's efficacy.

Mitochondrial replacement technology has so far solely been used for therapeutic purposes, but this type of research has caused many scientists to worry that it may pave the way, once again, to the concept of ‘designer’ babies. How long will it be until there is a case of a scientist like He Jiankui again?