Should doctors be allowed to tinker with genes to produce a healthy baby?
That's the question a Food and Drug Administration panel will consider this week when it holds hearings on whether to allow a controversial fertility technique to be tested on women with mitochondrial disease.
The field's leading U.S. researcher, Shoukhrat Mitalipov, will be on hand Tuesday to explain and defend his work.
The FDA meeting was prompted by Mitalipov's research at Oregon Health & Science University in Portland, where he and his staff have produced five healthy monkeys using the DNA-replacement technique. He is seeking FDA approval to begin testing in a handful of women who carry defective genes that can lead to devastating diseases in children, including blindness, organ failure and epilepsy.
An estimated one in 5,000 U.S. children inherit such conditions because of defective DNA in their mitochondria, small energy-producing organs found in the cell. Unlike most DNA — located in the nucleus of the cell — mitochondrial DNA is passed along only by the mother, not the father.
The experimental technique, if approved for use, would allow a woman to give birth to a baby who inherits her normal nucleus DNA but not her defective mitochondrial DNA.
To accomplish this, researchers would remove the nucleus DNA from a healthy female donor's eggs and replace it with the nucleus DNA of the prospective mother. After fertilization, the resulting child would inherit the mother's nucleus DNA — which contains most inherited traits like eye color and height — but the donor's healthy mitochondrial DNA.
The technique initially made headlines as a way to create babies with three parents, but scientists say that's an overstatement, since the child would have only trace bits of DNA from the donor. Mitalipov calls the work "gene correction" rather than "gene modification."
"We want to replace these mutated genes, which by nature have become pathogenic to humans," says Mitalipov. "We're reversing them back to normal, so I don't understand why you would be opposing that."
Fifteen years ago, the United Nations endorsed a global agreement prohibiting scientists from altering the human genome, the set of genetic instructions that every child receives from its parents. In this case, the genes that would be affected are the 37 in the mitochondria — often called the cell's batteries — rather than the 20,000 in the nucleus.
Some experts, like Jeremy Gruber, president of the Council for Responsible Genetics, a New York-based advocacy group, think it's simply unethical to tinker with human genes, regardless of where they are found.
"It has implications not only for the offspring but future generations of that offspring as well," he said.
Others believe it's important to consider the needs of women with mitochondrial disease who almost certainly cannot have healthy children without the mitochondrial transfer procedure. Mitochondrial diseases vary in their severity but can be completely debilitating, with every cell in the body lacking the energy needed to perform basic functions.
"Far from opening the floodgates to genetic engineering, mitochondrial transfer offers a limited, safe and ethical alternative to the grave suffering that women with mitochondrial disease would otherwise suffer as they try to have healthy children," Nita Farahany, a professor of law, philosophy and genome sciences and policy at Duke University, said Monday via e-mail.
With the mitochondrial replacement procedure, doctors would combine the sperm of the father and egg of the mother with the mitochondria of a donor.
A similar technique, used to help infertile women have children, led to the birth of as many as 100 children worldwide in the late 1990s and early 2000s. Those children have never been studied, so it is not clear what — if any — health effects they carry from the procedure. In 2001, the FDA ordered fertility clinics to stop the procedure or go through the normal approval process, and all the American clinics stopped.
Of the 17 pregnancies that were studied back then, two fetuses had irreversible birth defects, and one child was later diagnosed with autism. (The New Jersey fertility doctor who pioneered that technique and completed that study, Jacques Cohen, said he recently received approval to check back in on the children he helped birth, but the research has not yet begun.)
Mitalipov said his research in macaque monkeys shows that mitochondrial transfer leads to healthy offspring. He initiated discussions with the FDA that helped lead to the hearings and believes mitochondrial transfer is safe and ready for human trials.
Other scientists still have concerns and suggest the procedure should be studied longer in animals before being tried in people.
Klaus Reinhardt, an evolutionary biologist at the University of Tuebingen, in Germany, said that mixing the mitochondria from one woman with the egg nucleus from another could create "language" gaps. From generation to generation, both mitochondrial DNA and nuclear DNA change in ways that complement each other. Mixing DNA from different women with a different evolutionary history could be problematic, he said.
It's not clear "that every mother can expect a definitely healthy child out of this," he said.
In the United Kingdom, an advisory panel that held extensive public hearings and studied the technique for two years has supported the idea of human testing. Parliament, which must approve any testing, has not yet ruled on the issue.
Gruber, of the Council for Responsible Genetics, a New York-based advocacy group, said there's so little basic research that he thinks it's irresponsible for the FDA to even be holding hearings on the technique.
"The agency is acting completely outside the public interest," he said.
Even if the science were ready for testing, Americans should first discuss whether they want to allow genes to be altered, he said. "We need to start asking ourselves: should we be entering a new era of human genetic engineering?"
Karen Weintraub, USA Today