Fatal genetic conditions could return in some 'three-parent' babies

Troubling new findings have been discovered that could affect the lives of (misleadingly* branded) "three-parent" offspring born thanks to breakthrough mitochondrial replacement therapy.

The technique grabbed the world's attention when in September a baby was born bearing the DNA of three parents, a feat that overcame the otherwise fatal Leigh syndrome** genetic disorder carried by the child's mother.

It was heralded as a major step up from in vitro fertilisation. In the technique, the nucleus of an egg from the syndrome-affected mother is implanted into a female donor egg with healthy mitochondria which has had its nucleus removed. The resulting egg is fertilised with the father's sperm.

It has since been approved by the UK Human Fertilisation and Embryology Authority with the first treatments possible in 2018.

Now a paper (pdf) published in the journal Nature – and written by 30 researchers headed by Oregon Health and Science University Dr Shoukhrat Mitalipov – has found mitochondrial replacement therapy in 15 per cent of cases may allow the fatal defects it amends to resurface, even introducing new defects.

The researchers made the discovery by performing the mtDNA replacement therapy. In three embryos, the fatal conditions returned. About two per cent of the faulty genetic material remains in healthy children, we're told, opening avenues for possible genetic conditions in subsequent generations.

In February, the US panel of the National Academies of Sciences, Engineering and Medicine recommended mitochondrial replacement therapy be approved only for use in male embryos ensuring the mitochondrial modifications are not passed on to future generations, a feat possible only in females.

Mitalipov's team says genetic similarities between donor and recipient eggs must be far more accurately matched for the risks of fatal defects to be lowered. Mutations in mitochondria – the energy factories and metabolism regulators of a cell – occur some 30 times more frequently than in the genes of the nucleus.

Dr John Zhang of New York's New Hope Fertility Center, which conducted the breakthrough birth in September, found at the time that less than one per cent of the child's mitochondria carried a mutation, well below the 18 per cent predicted to become problematic.

The process, known as spindle nuclear transfer, resulted in five embryos, one of which survived having inherited the healthy mitochondria.

Some 30 babies have been born to spindle nuclear transfer including 15-year-old Alana Saarinen, whose mother's nuclear DNA (the identity carrying part, which encodes for the majority of the genome) was combined with the healthy mitochondria of a woman donor before the egg was inseminated. ®

* The so-called "third parent" - aka the mitochondrial donor - could not properly be considered a "parent" in its understood meaning, as mitochondria do not and cannot confer any identity-linked traits onto the baby. Mitochondria are organelles responsible for generating cellular energy. The amount of DNA provided by the mtDNA sponsor in the procedure described above amounts to a 1 per cent overall proportion of the mix.

** Sufferers of Leigh syndrome, a severe neurological disorder, are affected by defects in their mitochondrial energy production. Mostly sufferers have a mutation in their nuclear DNA, but about 20 per cent have a mutation in mitochondrial DNA (mtDNA).