For Chuck Mohan’s daughter Gina, it started with seizures when she was 10 years old. Her arms would jerk uncontrollably. Then the convulsing would stop, only to move to another part of her body. Sometimes the seizures struck her diaphragm and she couldn’t breathe.
“There isn’t anything more frightening to a parent than to see a child in the middle of a seizure,” Mohan said. “It’s visually scary, and there’s nothing you can do except wait for it to resolve.”
It wasn’t until four years later, when Gina was 14, that doctors finally offered a diagnosis: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes — MELAS, for short.
MELAS is one of about 200 known mitochondrial diseases, a subject that has featured prominently in the news since the British Parliament’s House of Commons on Feb. 3 approved further testing and research on mitochondrial replacement IVF. The procedure has beencommonly referred to in news stories as “three-person babies” or “three-parent babies.”
But it’s a term that makes doctors wince.
Technically, “three-person baby” isn’t wrong, said Dr. Bruce Cohen, director of neurology at Akron Children’s Hospital who specializes in mitochondrial diseases, but mitochondrial transfer is a better term. The baby will inherit DNA from three people: mother, father and about .1 percent of his or her DNA from the egg donor.
But that label “implies that we’re messing with God,” Cohen said. “We’re not talking about manipulating genes. We’re talking about a fertility technique that replaces bad mitochondria with good mitochondria.”
Here’s how the procedure works. Doctors take a fertilized egg from a mother with mitochondrial DNA mutations. They remove the nucleus from the fertilized egg. They also remove the nucleus from a donor’s egg, one that has healthy mitochondria. The nucleus from the fertilized egg is transferred to the donor egg.
Critics say that allowing human clinical trials will open the door for “designer babies”, or babies selected for traits such as hair and eye color. The Catholic and Anglican Church have already voiced their disapproval, as have groups concerned about genetic manipulation.
“This will be the first time that we would intentionally manipulate the human genome. It is something that governments around the world have agreed for the last 20 years that we shouldn’t do. And once you cross that line, then it’s very hard to stop going down the slippery slope to designer babies,” David King, director of independent watch-dog group Human Genetics Alert, said in a statement.
But let’s back up for some basic biology. Every cell contains a nucleus which houses about 22,000 genes, the DNA that you inherited from your parents. That DNA is the blueprint that makes you you. It determines your eye color, your hair color, and whether you will have your dad’s nose or your mother’s chin.
Floating outside of the nucleus are mitochondria. They’re often called the powerhouses of the cell.
“Mitochondria give us the energy to do what we need to do every day,” said Devin Oglesbee, co-director of Mayo Clinic’s Biochemical Genetics Laboratory. “They absorb oxygen and food and turn it into energy so your heart can beat and your brain can think…If we don’t have functional mitochondria then our organs stop functioning.”
Mitochondria contain 37 genes, all of which are essential for the organelle to function properly. But if there is a mutation in the mitochondrial DNA, the little powerhouses fail — and so do the organs and tissues they serve.
The medical community first recognized mitochondrial disease as a new group of disorders in 1988, Oglesbee said, and new diseases are uncovered every day. The symptoms can affect every part of the body, and range from constipation to exercise intolerance, seizures, blindness, deafness and multiple organ failure.
It’s possible for infants to show symptoms from birth, but other children show no symptoms until years later, like Gina. Because mitochondrial disease is so complex, diagnosing each illness can take several doctors and several years, Mohan said.
These mitochondrial mutations pass from mother to child through her eggs. But screening for the disease is nearly impossible, Cohen said. A woman could be a carrier for the disease, and never develop an illness. The mutation load varies from egg to egg, so there’s no way to predict how much damaged mitochondria will be in any given egg, Oglesbee added.
Unless a woman had siblings who suffered from the disease, it’s hard to know if she’s a carrier. Often families don’t know they are carriers until one of their children is sick or dies, Cohen said.
“I’m seeing them after they’ve buried their first child and they’re coming in with the second or third child for investigation, and the mother is sitting there perfectly healthy,” he said.
According to the United Mitochondrial Disease Foundation, mitochondrial disease affects one out of every 1,000 to 5,000 children, depending on the disorder. But there are no FDA-approved drugs or treatments for mitochondrial disease, Cohen said. All doctors can do is treat the symptoms.
And there was nothing doctors could do for Gina Mohan. She passed away in 1995, eight months after her diagnosis. She had just turned fifteen.
Since then, Chuck has become the director for the United Mitochondrial Disease Foundation, advocating for more research, testing and talking to parents and the medical community about mitochondrial diseases. Categorized as rare diseases, these disorders don’t receive a lot of research dollars, he said. And while the U.S. has some promising studies on new therapies and treatments, mitochondrial transfer offers a way to prevent the disorders from being passed on.
“Bottom line is there are no cures, and we can only treat the symptoms which, for the most part, are ineffective,” Mohan said. If mitochondrial transfer research moves forward, it at least offers parents an option, he added.
That’s why approval in the U.K. is an important step for researchers, said Keshav Singh, senior scientist at the University of Alabama-Birmingham Comprehensive Cancer Center and editor-in-chief of the scientific journal Mitochondrion. For women who have already lost children to mitochondrial disease, mitochondrial transfer could be their only hope for having their own biological child, he said.
And there has been a lot of research on the technique already, even in the United States, Singh said. Scientists at the Oregon Health Science University have already had successful tests in monkeys. There have even been children born through this technique in the U.S. in early trials.
But since 2001, the FDA has stalled any further testing for mitochondrial transfer in humans. When asked for comment, the FDA said that its investigation into the procedure was ongoing.
Further testing in the U.K. would help the medical community understand how safe and effective the technique is, Singh said. Plus, he added, there are still ethical questions. For example: Could the mitochondria donors claim parental rights?
Early estimates suggest that if the House of Lords approves the procedure,children could be born in the U.K. via this method by 2016.