By Brian Alexander, NBC News Contributor
?Right now I am talking to you from bed, wrapped up in blankets because I can?t regulate my body temperature,? says Stefani Bush, a Chelmsford, Mass., mother. Bush, 35, has a gene mutation, one in a galaxy of mutations that causes often devastating conditions known collectively as mitochondrial diseases. She has been hospitalized about 16 times this year. She can?t walk more than about 20 yards and has a host of cardiovascular and gastrointestinal symptoms.
A study published Wednesday in the journal Nature might offer a way to prevent children from inheriting such conditions in the future. Scientists in Oregon have found a way to remove the damaged genetic material and replace it with healthy DNA. The catch is it?s controversial, and children born using the technique would, technically, have three genetic parents. It?s just the kind of ethical debate that stopped such science dead in its tracks a decade ago.
Bush wasn?t aware she carried her mutation until she was pregnant with her daughter, now 7. Her son, 9, has been diagnosed with the same mutation, and her daughter is showing signs she has it, too. On a recent family dream trip to Disney World, the little girl spent an entire day having seizures. ? ? ?
Mitochondria are tiny organelles in every cell of our bodies except red blood cells. They?re the cells? power plants, converting glucose to energy. Mitochondria has DNA of its own ? human mitochondria has 13 genes ? that is passed down virtually unchanged from mothers to babies.
If mitochondria don?t do their jobs properly, a wide variety of health troubles can result, especially in parts of the body, like muscle and brain, that have high energy requirements.
An estimated 1 in 4,000 children born in the U.S. are affected by some version of mitochondrial disease, according to the United Mitochondrial Disease Foundation.
Many children born with mitochondrial mutations don?t live past age 4 or 5. Mutations can cause blindness, deafness, strokes, seizures and cardiovascular problems. Often, as in Stefani Bush?s case, people go undiagnosed for many years.
Researchers have been trying for years to find ways to repair damaged mitochondria to give the kids a chance.
Shoukhrat Mitalipov at the Oregon National Primate Research Center and Oregon Health and Science University and colleagues found a way they think might work. Most of a person?s DNA is found in the nucleus of the cell, carried on structures called chromosomes.
Mitalipov?s team took the chromosomes out of one set of human egg cells. They replaced them with chromosomes from human donor eggs. Then they used fertilization techniques to inject sperm and fertilize the eggs ? about 65 in total.
Mitalipov Lab / Oregon Health & Science University
Researchers have found a way to removed damaged DNA from a woman's egg cell and replace it with healthy DNA from another woman.
When the resulting embryos developed into balls of cells called blastocysts, they took out a few of the embryonic stem cells and tested them to show they were healthy and would have developed into normal embryos. Only about half did.
Even so, Mitalipov told a news conference, the process worked ?pretty well. Mitochondrial DNA can be replaced efficiently.?
Three years ago, the same team announced they?d used the technique to create reconstituted eggs from monkeys called macaques, fertilize those eggs, and implant them into females. Three babies were born.
?At three years follow up,? Mitalipov said, ?the study showed these are normal? juvenile monkeys.
By doing such manipulations, scientists hope to prevent mitochondrial disease by removing chromosomes from the eggs of affected women, and putting them into donor eggs. Any children that would be born would not carry the mother?s mitochondrial mutations ? but would have the mitochondrial DNA from the woman who donated her eggs.
?From my point of view, this has big implications in women who have some type of mitochondrial DNA mutation,? said Carla Koehler, a mitochondrial biologist at the University of California Los Angeles who has been studying ways to repair the mutations. She uses some of the same kinds of techniques to make what she calls ?cybrids.?
?I?d hate to rush this technique and start using it in women,? she added. ?We should always have a high bar.?
In 2010, a team from Newcastle University in Britain published results of their own, similar, chromosome transfer. On behalf of that team, Mary Herbert issued a statement applauding the work of the Oregon scientists and noting that it ?confirms our previous work published in Nature, showing that, in principle, it is possible to use IVF-based techniques to reduce the risk of transmitting mitochondrial DNA disease from a mother to her child.?
The team hasn?t yet shown that an embryo made this way could be used to make a woman pregnant.
Mitalipov said the scientists think they?ve figured out why most of the manipulated eggs didn?t develop normally. He hopes to start human tests. ?I say it is safe enough to proceed,? he said.
Dr. Jamie Grifo, director of the division of endocrinology and infertility at the New York University Fertility Center, agreed. ?It?s a great paper,? he told NBC News. ?This is a kind of orphan group of patients, but they are out there, and the only thing we can offer them now is donor eggs.?
But Grifo also predicted that the Food and Drug Administration (FDA) would be very reluctant to approve any human trials
Grifo knows, because, in 1999, he published results of a similar technique in his effort to improve success rates for infertile patients.
?I think this study confirms what we were doing a long time ago,? he said.
But Grifo was working at a time when there were great concerns over the issue of human cloning. He wasn?t trying to clone anybody, just trying to make a healthy egg.
After media reports of Grifo?s work were published, ?I got a personal phone call from the assistant surgeon general of the United States who wanted to know why I was doing it and said I should not be doing it,? he recalled. ?Then I got a letter from FDA telling me to stop.?
Grifo turned his data and research over to Chinese scientists so it wouldn?t go to waste.
In fact, there are already children born with two genetic mothers. In the mid 1990s, Jacques Cohen, at St. Barnabas Medical Center in New Jersey, began transplanting cytoplasm from donor eggs into eggs from infertile women as a way to ?rescue? those eggs.
In 2001, Cohen announced that he?d found mitochondrial DNA from both the mother and the donor in the cells of babies born using this cytoplasmic transfer technique.
It was the first time the human germline ? the genetic information that?s passed down from one generation to the next ? had been deliberately altered and resulted in the birth of children.
In response, the FDA said it would require researchers to file an Investigational New Drug (IND) application, and conduct clinical trials under that IND. In the 11 years since, FDA has not issued any such INDs, according to FDA spokesperson Rita Chappelle. Given fears over altering the human germline, and the idea that any babies would be born with DNA from three people, some question if FDA will change policy now. ?
?I?m not sure what FDA?s stand is on this treatment,? Mitalipov said. ?Last time I heard, this topic was under active discussion in the FDA?s?Division of Cellular and Gene Therapies department.?
Chappelle would say only that ?any proposed process of mitochondrial transfer would be carefully evaluated before FDA could make a determination as to whether an IND would be required to conduct clinical research.?
Bush understands the concerns, but has no doubts the science should move forward. If she?d known what she risked passing on to her children, ?I would do it,? she said. ?If I could have spared my children one ounce of what they have gone though, I would.?
Brian Alexander (www.BrianRAlexander.com) is co-author, with Larry Young Ph.D., of "The Chemistry Between Us: Love, Sex and the Science of Attraction," (www.TheChemistryBetweenUs.com), now on sale.
Related link:
Ethicist says controversial technique is worth the moral risk
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