A few months ago, after a fertility procedure at a Mexican clinic, a healthy baby boy was born in New York to a couple from Jordan. It was the first live birth of a child that has been called — to the dismay of scientists who say the term is grossly misleading — a three-parent baby.
"This is huge," said Dr. Richard J. Paulson, president-elect of the American Society for Reproductive Medicine, after the birth was reported on Tuesday.
The method used to help the couple is one that reproductive scientists have been itching to try, but it is enormously controversial because it uses genetic material from a donor in addition to that of the couple trying to conceive. The purpose is to overcome flaws in a parent's mitochondria that can cause grave illnesses in babies.
Mitochondria, the cell's energy factories, are separate from the DNA that determines a child's inherited traits. But mutations in these little organelles can be devastating, resulting in fatal diseases involving the nerves, muscles, brain, heart, liver, skeletal muscles, kidney and the endocrine and respiratory systems that often kill babies in the first few years of life.
The technique that led to the healthy birth was to move the DNA from an egg of the mother, who had mutated mitochondria, and place it in the egg of a healthy egg donor — after first removing the healthy donor's nuclear DNA from her egg cell. Then that egg, with its healthy mitochondria and the mother's DNA, could be fertilized.
More than a decade ago — before controversy forced the work to stop — researchers tried a simpler technique that did not involve swapping nuclei between eggs. Instead, they injected some healthy mitochondria into an egg in an attempt to help with repeated failures at in vitro fertilization. It was not a method that could be used to prevent the birth of children with mitochondrial diseases.
The story of the Jordanian couple's procedure began in 2011 when they came to see Dr. James Grifo, a professor of obstetrics and gynecology at New York University who pioneered the method in studies with mice. He referred them to his former student Dr. John Zhang, medical director of the New Hope Fertility Center in New York. Zhang had tried the method in 2003 in China, but the 30-year-old woman's twins were born prematurely and died, though their mitochondria were normal.
When Zhang told the Jordanian couple about the technique, they hesitated. They already had a child who was terribly ill with Leigh syndrome, a mitochondrial disease, but there was a chance they could have a normal baby on their own — a quarter of the woman's mitochondria were mutated, but mitochondria are distributed at random in eggs. If an egg with mostly good mitochondria happened to be fertilized, the baby would be fine. They decided to take their chances.
The couple returned to Jordan and had a baby. But the baby had the same mitochondrial disease, Leigh syndrome. It is a terrible disease, Zhang said. Babies progressively lose their ability to move and breathe. The baby had a tracheotomy and a feeding tube, he said, and the parents had to suction the baby's lungs every hour.
The first baby died at age 6; the second baby at 8 months.
The couple returned to Zhang, ready to try the mitochondrial transfer technique. New Hope Fertility Center has a clinic in Mexico, so he suggested doing the procedure there because it is effectively banned in the United States. More than a decade ago, the Food and Drug Administration ordered clinics to file an application to do such work. Later, Congress attached a rider to a bill making it impossible to fund such research.
By six months of pregnancy, the woman said she knew this baby was different. It kicked constantly — the others, affected even in the womb, had hardly moved. Now the boy is 5 months old, healthy and has normal mitochondria. The birth was first reported on Tuesday by New Scientist magazine.
Specialists in reproductive medicine say they hope this success will change attitudes toward mitochondrial transfers. They blame in part the term three-parent baby.
That name is misleading and "caustic," Grifo said. "It degrades patients who need this," he added.
"Mitochondria," Paulson said, "do not define who you are."
The genes for traits that make up a person's appearance and other characteristics are carried in the nuclear DNA. If a white woman got mitochondria from an Asian woman, for example, her babies would be white, with no traces of the Asian mitochondrial donor. The ban, said Paulson, "is not scientific, not rational, not evidence-based."
Reproductive scientists who have been frustrated by the ban were both gratified by Zhang's success and angry that it took so long. Britain recently allowed research on mitochondrial transfers to proceed, but nothing has changed in the United States.
But the basic research showing the DNA swapping method could work was done more than 20 years ago, in Grifo's lab, using mice.
"We did all the foundational work to make it a possibility," Grifo said. "We spent probably half a million dollars of a patient's money who donated it. It is a technique we know could work."
When all work on mitochondrial transfers came to a halt in the United States, though, he abandoned his studies. The success now, he says, is long overdue.
"This could have happened in 2002," Grifo said.