Engineering Disease-Free Babies?

It takes two to make a baby, or maybe three or four if you're worried about passing on select genetic diseases.

Doctors in the United Kingdom announced Tuesday that they had successfully genetically engineered embryos from parents who would have passed on mitochondrial DNA mutations by conceiving the old-fashioned way. The researchers reported the feat in the journal Nature.

"Because of the lack of a viable treatment for these patients, and their families, preventing the transmission of mtDNA [mitochondrial DNA] disease is a priority," Douglas Turnbull, of the New Castle Institute for Brain Aging and Vitality and colleagues wrote in the article.

Mitochondria can be found in the cytoplasm of the cells, where they produce most of the cells energy. They have their own DNA distinct from the 50-50 mother-father split in the nucleus of a cell. A child directly inherits only its mother's mitochondrial DNA, and in some cases will be certain to inherit a debilitating mitochondrial mutation.

Turnbull and his colleagues took 80 donated fertilized eggs that were unsuitable for in vitro fertilization, removed the nuclei and replaced the nucleus from the unhealthy egg with mutated mitochondria into the healthy egg.

All of the genetically engineered zygotes soon developed into blastocysts and were destroyed within 6 to 8 days. But conceivably, couples could go through the same process and get a baby that looks like them but doesn't carry the mother's mutated mitochondrial DNA in the cytoplasm of their cells. A different method with similar goals was completed with monkeys in 2009.

The authors of the paper argue that while some couples who know they are at risk for passing on mitochondrial diseases can already get genetic counseling or expect only mild problems from mitochondrial mutation, other families are more unfortunate.

"In some families, mtDNA disease can affect multiple family members with catastrophic consequences," wrote Turnbull and colleagues. "For these families, pronuclear transfer may be an option that mothers who carry mtDNA mutation may consider."

Mitochondria are responsible for generating 90 percent of the body's energy, according to the United Mitochondrial Disease Foundation, and can still function even with some level of mutation.

But health problems begin when 60 percent of a person's mitochondrial DNA is mutated, according to the authors of the paper.

Only a few thousand children are born with a mitochondrial disease each year in the U.S., according to the Cleveland Clinic. But by age 10, many more children -- about one in 4,000 -- will develop a mitochondrial disease.

When mitochondria malfunction. they can starve cells, or interfere with crucial chemical reactions within the body. Muscle weakness and pain, gastro-intestinal disorders and swallowing difficulties, poor growth, cardiac disease, liver disease, diabetes, respiratory complications, seizures or visual/hearing problems can all be caused by a mitochondrial disease.

Some people with a mitochondrial disease can live into adulthood, but many die within a few years.

Now That We Can Do This, Should We?

Although ethicists have come out in droves against genetic engineering at the level of a fertilized egg, some say the serious nature of these incurable diseases and the function of mitochondrial DNA should make this case of genetic engineering an exception.

"For these diseases that are very debilitating or devastating it makes sense," said Art Caplan, director of the Center for Bioethics at the University of Pennsylvania.

Starting with James Watson, who helped discover DNA's double helix, Caplan said geneticists often speak against "germ-line" engineering -- meaning genetically manipulating sperm, eggs or zygotes to change a human being.

"As recently as 2000 we had a large number of genetic experts saying, 'Don't do that,'" said Caplan, speaking about an Asilomar Symposium on Science, Ethics and Society where 247 scientists signed a position statement against it.

But Caplan argues in the case of mitochondrial DNA, "There's no intent here to interfere with the key genes that make us who we are. We're in the battery pack of the cell.

"I also think there's a little bit of coyness about it. Someone donating mitochondria. Is that person a third parent? I don't think so," said Caplan. "I don't think this is a big issue."

Not all agree.

David Prentice, a member of the lobbying organization Family Research Council, argued that replacing mitochondrial DNA was no different than other genetic engineering efforts.

"There are significant ethical concerns with this technique," said Prentice. "It involves cloning and germline genetic engineering of humans, requires destruction of young human embryos to create the recombined embryo, and is a eugenic technique that manufactures children."

Whatever the merits or disadvantages, both Prentice and Caplan agree that the technique would be legal in the United States.

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