To most people, the word “mitochondria” is only dimly familiar, the answer to a test question in some bygone high-school biology class. But to Shoukhrat Mitalipov, the mysterious power producers inside every human cell are a lifelong obsession.
“My colleagues, they say I’m a ‘mitochondriac,’ that I only see this one thing,” he said recently in his modest, clutter-free office at Oregon Health and Science University. He smiled. “Maybe they are right.”
With a name that most Americans can’t pronounce (it is Shoe-KHRAHT Mee-tuhl-EE-pov) and an accent that sounds like the villain’s in a James Bond film, Dr. Mitalipov, 52, has shaken the field of genetics by perfecting a version of the world’s tiniest surgery: removing the nucleus from a human egg and placing it into another. In doing so, this Soviet-born scientist has drawn the ire of bioethicists and the scrutiny of federal regulators.
The procedure is intended to help women conceive children without passing on genetic defects in their cellular mitochondria. Such mutations are rare, but they can cause severe problems, including neurological damage, heart failure and blindness. About one in 4,000 babies in the United States is born with an inherited mitochondrial disease; there is no treatment, and few live into adulthood.
A healthy rhesus monkey, born at Dr. Mitalipov’s lab after the nucleus of the mother’s egg cell was removed and placed in the egg cell of another female that is healthy.
LEAH NASH FOR THE NEW YORK TIMES
Mitochondria have their own sets of genes, inherited solely from mothers, and women who carry mitochondrial mutations are understandably eager to not pass them to their children. Dr. Mitalipov’s procedure would allow these women to bear children by placing the nucleus from the mother’s egg into a donor egg whose nucleus has been removed. The defective mitochondria, which float outside the nucleus in the egg’s cytoplasm, are left behind.
“It was a major breakthrough,” said Douglas C. Wallace, a professor of pathology and laboratory medicine at the University of Pennsylvania. “He’s an exceptionally talented person.”
But the resulting baby would carry genetic material from three parents — the mother, the host egg’s donor and the father — an outcome that ethicists have deplored.
That specter drew critics from all over the country to a hotel in suburban Maryland late last month, where Dr. Mitalipov tried to persuade a panel of experts convened by the Food and Drug Administration that the procedure, which he has pioneered in monkeys, was ready to test in people.
Stored materials at Oregon Health and Science University’s National Primate Research Center.
LEAH NASH FOR THE NEW YORK TIMES
Some told the officials that the technique could introduce new genetic mutations into the human gene pool. Others warned that it could be used later for something ethically murkier — perhaps, said Marcy Darnovsky, executive director of theCenter for Genetics and Society, “to engineer children with specific character traits.”
Back in his office, Dr. Mitalipov waved off those warnings. Mitochondrial DNA comprises just 37 genes, which direct the production of enzymes and molecules that the cell needs for energy, he noted. They have nothing to do with traits like eye and hair color, which are encoded in the nucleus.
“There are always people trying to stir things up,” said Dr. Mitalipov, an American citizen who grew up in what is now Kazakhstan. “Many of them made their careers by criticizing me.”
The United States is not the only country weighing mitochondrial replacement. In Britain, the government has issued draft regulations that would govern clinical trials in people. If accepted into law by Parliament, such trials, which are how banned, would be allowed to go forward, although regulators would have to license any clinical application.
Dr. Mitalipov’s fixation on mitochondria began in graduate school in Russia in the 1990s. After graduating from an agricultural institute — and a brief, unhappy stint as a manager on a collective farm — he began work on his doctoral thesis at theResearch Center of Medical Genetics, a prestigious state-funded institution in Moscow. He focused on embryonic stem cells, which can be grown in the laboratory and turned into any type of cell in the body.
He noticed a strange thing. When stem cells were extracted from a mouse embryo and put in a petri dish, they stopped aging but remained healthy and growing, as if frozen in time. Somewhere in the cell, it seemed, was a clock that determined its life span.
The search for the clock took him to Utah State University for postdoctoral research in the mid-1990s. He developed an interest in cloning, a process in which the cellular clock is not only stopped but reset. Why, he wondered, do cloned animals have normal life spans?
The answer to the riddle of cellular aging was not to be found in the cell’s nucleus, Dr. Mitalipov concluded, but in the surrounding cytoplasm. In the mitochondria.
“Everything was falling into place in my head,” he said.
As researchers began to suspect defective mitochondria as a cause in more diseases, Dr. Mitalipov wondered whether replacing them might be possible.
Scientists already had experimented with combining genetic material from three people to make a baby. About 15 years ago, researchers in New Jersey injected a bit of cell fluid from donor eggs into the eggs of women who were having fertility problems. Those experiments, which came shortly after the cloning of Dolly the sheep, set off such a uproar that the F.D.A. eventually told researchers that they could not perform them without special permission.
Dr. Mitalipov persevered. At Oregon Health and Science University’s National Primate Research Center, one of eight in the country, he spent years perfecting a way to create monkey eggs with donated mitochondria. He persuaded software developers to adapt a program that would allow real-time viewing of the necessary microsurgery. A special microscope was developed so that human hands, too blunt an instrument on their own, could conduct the operation with joysticks that look like upside-down flashlights.
“He’s just a really practical guy,” said Daniel M. Dorsa, senior vice president for research at the university. “He just nose-to-the-grindstone plowed through and figured out what it took.”
Success came in 2008 in a darkened, hot laboratory room. On April 24, 2009, twin male rhesus monkeys, Mito and Tracker, were born with replaced mitochondria. Later, with some adjustments Dr. Mitalipov replicated the procedure in human eggs. Because of federal rules against genetic manipulation, the eggs were not allowed to mature.
His research has brought persistent criticism. “If these procedures are carried out, it crosses a very bright line,” said Ms. Darnovsky of the genetics center.
She said that the current goal, mitochondrial replacement, may be narrow, but that Dr. Mitalipov’s genetic techniques could lead to broader applications and eventually to a situation in which scientists or governments “compete to enhance future generations,” such as producing soldiers who never need sleep.
Sheldon Krimsky, a bioethicist who attended the F.D.A. meeting on behalf of theCouncil for Responsible Genetics, argues that mitochondrial replacement is simply unnecessary. There are other options for women with mitochondrial defects to have healthy children, such as getting an egg from a donor, or having prenatal genetic diagnosis to find eggs with fewer mutations, he said.
“There’s that genetic chauvinism that says unless my DNA is in the child, it will not be truly my child,” he said.
Would-be parents, on the other hand, have been following Dr. Mitalipov’s work with the intensity of the hungry waiting for food. When he came back from the meeting in Maryland, his inbox contained an avalanche of emails from women with mitochondrial mutations and other fertility problems.
Dr. Dorsa said the university still has not decided whether to formally ask the F.D.A. for permission to move forward with clinical trials.
Dr. Mitalipov, for his part, is determined.
“We are ready now to move on to the next stage,” he said. “Not in 10 years, but in the next few years.”