



Fertility ethics tested by three-parent babies


Kim Tingley

Countries around the world are debating whether to allow scientists to combine the genes of three people in one baby.

In August 1996, a 39-year-old mechanical engineer from Pittsburgh named Maureen Ott became pregnant. Ott had been trying for almost seven years to conceive a child through in vitro fertilisation. Unwilling to give up, she submitted to an experimental procedure in which doctors extracted her eggs, slid a needle through their shiny coat and injected not only her husband’s sperm but also a small amount of cytoplasm from another woman’s egg.


The fresh cytoplasm that entered Ott’s eggs (researchers thought it might help promote proper fertilisation and development) contained mitochondria: bean-shaped organelles that power our cells like batteries. But mitochondria also contain their own DNA, which meant that her child could possess the genetic material of three people.

In fact, the 37 genes in mitochondrial DNA pass directly from a woman’s egg into every cell of her offspring, including his or her germ cells, the sperm or eggs that eventually produce the next generation - so if Ott had a girl and the donor mitochondria injected into Ott’s egg made it into the eggs of her daughter, they could be passed along to her children. This is known as crossing the germ line - the natural lineage of genetic inheritance - something that scientists generally agree is a risky proposition.

Ott, who is Catholic, remembers weighing up whether altering the makeup of her descendants in this way was OK. “Being a person who’s been involved in science my whole life, the way I looked at it is: God gives us doctors to help us, and they help us with things like infertility,” she said recently.


In May 1997, she gave birth to a healthy baby girl. Two months later, her doctors from Saint Barnabas Medical Centre in New Jersey published her case in the journal Lancet; soon, at least seven other US clinics were doing the injection. Because the amount of donor mitochondria added to Ott’s egg was small, it was unclear how much third-party DNA would be present in the cells of her daughter. Ott says her doctors ran tests and did not find any, but it has been found in two other children born from the procedure.

Although IVF drugs and devices are regulated, IVF procedures, like all medical procedures, are generally not. But what media outlets came to call “three-parent babies” compelled authorities to take action. In 2001, IVF clinics were informed that using a third person’s cytoplasm - and the mtDNA therein - would require an application. The “drug,” such as it was, has never been approved 

Now, two research groups in the United States and one in Britain believe they have nearly enough data to begin clinical trials for a new technique based on the transfer of mitochondria - only in this case, researchers want to pair the nuclear DNA of one egg with all the mitochondria of another.

Their aim is not to cure infertility. Rather, they hope to prevent a variety of devastating diseases caused by mutations in mtDNA. The new technique, which they call mitochondrial-replacement therapy, is far more advanced than the cytoplasm injection, and the researchers have studied the procedure’s impact on animals and human cells up to a pivotal point: they have created what appear to be viable three-parent embryos. They have yet to implant one in a woman, though.

In Britain, national law prohibits altering the germ line, but parliament is very likely to vote later this year on whether to allow mitochondrial replacement to move forward. Likewise, this February, US authorities held a meeting to examine the possibility of allowing clinical trials. If either gives the go-ahead, it will be the first time a government body expressly approves a medical procedure that combines the genetic material of three people in a heritable way.

Research has identified hundreds of mitochondrial diseases that are incurable and can affect any system in the body, resulting in deafness, blindness, muscle weakness, cognitive impairments, heart, lung and kidney failure, diabetes and death. About 1 in 4000 children and adults is diagnosed with mitochondrial disease, but because symptoms are so varied, doctors think many more cases are misdiagnosed; one recent study suggests that 1 in 200 people is born with a mutation that could make him or her sick.


And for some mutations, disorders can arise at any time in a person’s life. This means that a woman who carries an mtDNA mutation that causes her only mild hearing loss might give birth to a child who has blindness and seizures, one who remains healthy throughout life or one who has symptoms in between these extremes.

Some geneticists, when describingwhat it’s like to look at mutated mtDNA in a woman’s egg and then tell herwhat her odds of having a child with severe health problems are, use the same metaphor: russian roulette.


News coverage has tended to frame the risk-benefit analysis in an even broader way: a technique meant to prevent devastating illness could be used to try to make so-called designer babies, kids who are more intelligent, who have other qualities that the parents find desirable.


Three days before the US hearing, I called a scientist who would be making a presentation there, Dieter Egli, of the New York Stem Cell Foundation, and asked him what he thought the stakes were. He said his goal was to use cells to cure disease, because we are made of cells: tiny, complex, independent ecosystems. Eggs are single cells - the largest ones in the human body - and to him, replacing their mitochondria, then putting them back into women safely and successfully, is like beginner cell therapy. Rather than open the door to eugenics, we might in fact be opening the door to curing degenerative diseases like diabetes, Alzheimer’s and Parkinson’s, even the atrophy of ageing.

At the US hearings, the work of Dr Egli and similar research would come up against other studies that had produced unsettling results. Researchers have done mitochondrial replacement on mice and flies from different subspecies to look for worst-case outcomes and have observed reduced exercise ability and cognitive function in the rodent offspring and accelerated ageing and infertility in the flies - effects that did not show up until adulthood.


The meeting convened on a Tuesday morning in February. Egli was nervous: His voice and the dot of the laser pointer he was holding quavered as he explained his slides. The committee members, culled from a variety of specialties, mostly sounded sceptical, and their non-technical remarks had a vaguely ominous cast.


By the close of the meeting the following afternoon, Egli seemed deflated. “We had to change a perception already there - that we are strange, rogue scientists,” he said. “I don’t think we are these kinds of people. I don’t see us that way.” The criticisms of the committee members, though, gave him ideas for new experiments; his mood lifted as he started typing them up on the plane ride home.

There is no timeline for when, if at all, the authorities might rule on clinical trials.



At first, Egli did not want me to watch him perform mitochondrial replacement on human eggs. He was afraid I would distract him. The eggs were precious: both challenging for researchers to obtain and a reminder of our fragile origins, and he was anxious not to slip and damage one. Eventually he relented. “If you look at what I’m doing,” he said, “there is really nothing to be afraid of, I think.”

The eggs arrived by taxi, in an incubator shaped like a tackle box. An hour earlier, an embryologist had suctioned them from a young donor; two lab technicians poured the musky pink fluid he had retrieved into dishes, which they slid under microscopes, searching for diamond-bright specks, counting, cleaning and packing them in vials.

At the lab, Egli received the box in a darkened room. He opened it, took out a test tube, and used a pipette to transfer its contents into a dish. He peered at it through a microscope. His left hand twirled the knobs of the microscope, his right controlled a hollow extraction needle. His foot worked a pedal that lasered a hole in the coat of one of the eggs. For just a moment, he flicked on the monitor and the egg appeared, a luminous round moon. He pointed at the faintest of shadows on its face - the spindle of chromosomes beneath the surface. The laser click-clicked, Egli maneuvered the needle into the hole it left behind and applied suction. The egg tugged back, released and then, there in the needle, was the genome, ready for transplant: an oblong seed, arbiter of all life. 

The New York Times Magazine

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