Federal regulators are reviewing a new technology aimed at eliminating genetic disease in newborns that would combine the DNA of three people, instead of just two, to create a child — potentially redrawing ethical lines for designer babies.
The process works by replacing potentially variant DNA in the unfertilized eggs of a hopeful mother with disease-free genes from a donor.
U.S. regulators this week began weighing whether the procedure, used only in monkeys so far, is safe enough to be tested in humans. The Food and Drug Administration scheduled meetings Tuesday and Wednesday to explore the issue, with doctors and researchers scheduled to talk. The FDA will then decide whether to allow scientists at Oregon Health & Science University in Portland, who engineered the approach, to move their testing program from macaque monkeys to woman.
Because the process would change only a small, specific part of genetic code, scientists say a baby would largely retain the physical characteristics of the parents. Still, DNA from all three — mother, father and donor — would remain with the child throughout a lifetime, opening questions about long-term effects for this generation, and potentially the next. Ethicists worry that allowing pre-birth gene manipulation may one day lead to build-to-order designer babies.
"Once you make this change, if a female arises from the process and goes on to have children, that change is passed on, so it's forever," Phil Yeske, chief science officer of the United Mitochondrial Disease Foundation, said by telephone. "That's uncharted territory; we just don't know what it means. Permanent change of the human germline has never been done before, and we don't know what will happen in future generations."
Potentially, the procedure may cut off mitochondrial diseases that are passed down through females and occur in about 1 in 4,000 people. One example is Melas syndrome, which causes a person to have continuing small strokes that damage their brains, leading to vision loss, problems with movement, dementia and death, according to the National Insitutes of Health.
"What the FDA needs to think about is that this isn't a procedure to repair mitochondrial disease," said Vamsi Mootha, a professor of systems biology and medicine at Harvard Medical School who studies mitochondrial disorders. "It's designed to prevent disease. It's designed to offer a woman who's a carrier for disease more options."
In early research, four macaque monkeys were born from the procedure, according to a 2009 report by the Oregon researchers in the journal Nature. They were reported as healthy at age 3.
In October 2012, Nature published reports that the technique had also been used in human egg cells. The resulting embryos were allowed to develop to the blastocyst stage, which usually occurs about five days after fertilization.
About half of the egg cells displayed normal development, the scientists found. Though the procedure is legal in the laboratory, the embryos that result from it can’t be implanted in women without the FDA’s consent, leading to today’s session.
There are two types of DNA: nuclear, which is handed down by both parents, and mitochondria, which only comes from the mother. The technology replaces a donor's nuclear DNA, which determines things like hair color and intelligence, with the same material from the prospective mother, leaving the healthy mitochondria from the donor in place.
The new lab-made egg is then fertilized with the father’s sperm in vitro and implanted in the mother’s womb.
This isn't the first time that scientists have attempted to disrupt the actions of mitochondria DNA to help fight disease, or the first time the FDA has considered the issue.
From 1997 to 2003, about 30 children worldwide were born using a method that injected donor mitochondria DNA into eggs after they were fertilized. The first baby born with this technique was reported in 1997. In 2003, though, the FDA told fertility clinics that genetically manipulated embryos were considered a biological product, and subject to regulation, essentially halting the technique in humans.
The lives of those children should be thoroughly investigated before the new procedure is cleared for use in a human trial, said Sheldon Krimsky, a professor of Urban & Environmental Policy & Planning at Tufst University in Boston.
Scientists also are concerned that the procedure may not be safe, according to a paper publishes last year the journal Science, whose lead author was evolutionary biologist Klaus Reinhardt at the University of Tuebingen .
Reinhardt' paper noted that male mice bred from this technique sometimes had altered breathing, as well as reduced learning and exploring capabilities, according to earlier research. Female mice weren't tested.
The research in mice suggests that the replacement technique may destroy some lines of communication between mitochondria and the cell' transplanted nucleus, Reinhardt's editorial said. Though the macaque monkeys don't show the same problems, there may be long-term issues from the DNA replacement, he wrote.
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