My brother Michael was born in April 1998. He didn’t live long enough for me to meet him.
“When he was born, he wasn’t putting on any weight,” my mother tells me. “We kept persevering with breastfeeding, and tried formulas. But nothing was working.”
At two months old, they took him to be immunised.
“I remember looking around at other babies in the waiting room. They were all the same age as him, but much bigger. He was still fitting into the little Bonds onesie he wore as a newborn.”
That day, my parents took Michael to the paediatrician, who fitted them in during his lunch break. When Michael showed no sign of joint reflexes, they were told to go straight to the hospital.
“There was dread in my stomach. It was a mother’s instinct – I knew something was wrong,” she tells me.
Eventually, the hospital genetics team diagnosed Michael with a rare form of mitochondrial disease.
“He did so many tests in those months. The needles, the lumbar punctures. He was like a pin cushion.”
The doctors referred to his disease as “mito”. My parents had never heard of it before.
“It affected his liver, and his muscles. He was tube-fed. We had to crush vitamins and put them down the tube with his milk. But he’d pull out the tube, and we’d have to rush him to the hospital in the middle of the night.”
Michael was in and out of hospital until he died in December that year.
After Michael’s death, my parents took a big risk deciding to have another child (me).
“If we wanted to have another child, there was a 25% risk that it would happen again. We took the risk with you. And through the whole pregnancy, I was a wreck.”
Nineteen years later, an IVF procedure is close to being legalised in Australia that would mean carriers of mito would not have to take such a risk in starting a family.
What is ‘mito’?
In Australia, about one child a week is born with a severe form of mitochondrial disease. Most young children diagnosed with mito die by the age of five.
It is a rare genetic disorder that affects the function of the power plants of our cells – our mitochondria – effectively starving the body’s cells of energy.
Prof John Christodoulou, the chair of genomic medicine and director of the genetics research theme at Melbourne’s Murdoch Children’s Research Institute, explains that every cell in the body needs a constant supply of energy to function normally.
“If there’s a disruption, then it will affect the function of cells, tissues and organs,” he says.
Christodoulou says symptoms of mito disorders can appear at any age. They can affect any organ, and often “many organs at once”.
They can be caused by mistakes in genes in our chromosomes (nuclear genes) or genes in our mitochondria (mitochondrial genes). When the mistake is in a nuclear gene, existing prenatal testing or IVF testing procedures can tell parents about the chance of the foetus or embryo developing mito, but cannot treat it. However, in most cases involving mitochondrial genes, these tests are unreliable.
There is no effective treatment, but doctors have developed a technique to stop the disorder before birth.
“Replace the mitochondrial genome,” says Christodoulou, through mitochondrial donation.
Law reform
Mitochondrial donation is an IVF-based procedure for carriers of mito, involving an egg donor.
The UK legalised the procedure in 2015, and in March the federal health minister, Greg Hunt, introduced similar legislation to the Australian parliament.
The bill, named after five-year-old Maeve Hood, who has mitochondrial disease, would allow prospective parents to take the sperm cell from the father, and the egg cell from the mother with a mutation in her mitochondrial DNA (mtDNA). The nucleus, which has a combination of the mother’s and father’s DNA, is then transferred into a healthy donor egg cell that has had its nucleus removed.
The procedure would stop prospective mothers from passing on the mutation in their mtDNA by replacing it with healthy mtDNA from the donor egg. Men may carry the mutation but cannot pass it on to their children, except in extremely rare circumstances when the mother also has the same genetic mutation.
Christodoulou says that, with cross-party support, there is hope among the medical community that the legislation will pass by the end of the year. If it does, the federal government will commit $10.3m to implement it.
The procedure uses the mother’s and father’s nuclear DNA to encode all of the baby’s individual characteristics. The role of the nucleus of the donor egg, Christodoulou says, is to provide “a source of healthy mitochondria”.
The value of the mitochondrial donation emerges when you understand how deeply mito “impacts generations of families”, says Sean Murray, one of the founding directors of the Australian Mito Foundation.
“My grandmother is a carrier. So is my mother, my brother and me,” he says.
For many in the mito community, mito donation offers a chance to avoid the “genetic lottery” involved in reproduction.
Murray says the disease is debilitating for many children.
“Some children may never develop properly. They may have their muscular systems or their brain development impacted. They’ll be unable to walk, or communicate. And their hearing, vision and learning skills can all be impacted.”
Like my brother Michael, Toni Catton’s daughter Alana was born very small, and struggled to grow, put on weight or build muscle.
“There was nothing that could be done for her medically,” Toni says.
Alana was on at least 10 medications a day, and fed through a tube into her stomach. She was never able to walk. She lived in a wheelchair, and underwent hours of therapy a week.
“But none of that supportive intervention could stop the progression of the disease. It was rapid, and brutal, and there was no cure.” Alana died aged seven in September last year.
‘Not designer babies’
Some religious institutions have raised concerns about involving a third person in the reproductive process through mitochondrial donation.
In submissions made during public consultation on the proposed law earlier this year, churches raised “ethical issues”.
The Australian Catholic Bishops Conference said that the donation would cause problems by “creating three-parent children”, “genetic bewilderment” and “destroying human embryos”. They said the procedure was “not a necessary, life saving technology”.
The Mito Foundation rejects such rhetoric.
“It is not editing the DNA inside the nucleus, which is what gives us our eye colour, or hair colour. It is not gene editing, or human cloning, or designer babies,” Murray says.
“It is taking that very separate genetically damaged mitochondria DNA and swapping it out with healthy mitochondria DNA.”
Beth Hodge, who has grown up with a sister whose daily life is affected by a form of mito that presents with epilepsy, says that “people may deem mito donation unethical, but they have no idea what mito is like”.
For the past 27 years, she has seen her sister’s struggle first hand.
“She can’t cut up food, drink water, write.
“If you haven’t seen it first hand, people don’t understand it,” she says. “It breaks your heart.”
Everyone in Beth’s family is a carrier of the disease. Though Beth is not symptomatic, there is a chance that any children she had would be.
“I would never forgive myself if I had a baby naturally and they were burdened by this condition the way my sister is,” she says.
Beth and her partner have been in contact with an IVF clinic since January 2020.
“It has taken them until now to say our only option, apart from using a donor egg without any of my DNA, is to wait for the mitochondrial donation to be legal.”
A spokesperson for Hunt said mitochondrial donation had “the potential to change lives and reduce the burden and devastating effects of mitochondrial disease for future generations”.
“When I see that bill, all I see is hope for you and your sister,” my mother says.
“It’ll give you the chance to be tested with confidence that, if you carry the gene, you will not be left feeling optionless and helpless.
“And it’ll give you the chance to have healthy children, and a normal life. And to, essentially, break the genetic chain.”
