FDA holds hearings on new method of assisted reproduction
Executive Summary
The Food and Drug Administration recently held hearings on mitochondrial manipulation to determine whether additional research is needed before proceeding to clinical trials. Ethical concerns include:
• Sensational headlines may result in misconceptions.
• Few women with mitochondrial diseases would be candidates for mitochondrial manipulation.
• There is a possibility of setting a precedent for other types of genetic modifications.
Ethical concerns were voiced during the Food and Drug Administration’s (FDA) February 2014 hearings on oocyte modification in assisted reproduction for the prevention of transmission of mitochondrial disease.
"The goal of the hearings was to determine whether any additional research is needed before proceeding to clinical trials," says Mark V. Sauer, MD, division chief of reproductive endocrinology and infertility at Columbia University Medical Center in New York City, who attended the hearings. Sauer is a member of the American Society for Reproductive Medicine’s Ethics Committee.
As a researcher who is looking to extend mitochondrial manipulation trials into the clinical arena, Sauer sees the FDA hearings as a missed opportunity. "As is commonly the case with innovative technologies involving cell manipulation, the focus was on the abuse and dangers of the technology," he says.
Profound ethical challenges
The FDA stated that looking into ethical issues involved in mitochondrial manipulation is not part of their mandate. "But it creeps in, because this is such a big issue. This is one of the most controversial areas of human genetic technology," says Marcy Darnovsky, PhD, executive director of the Center for Genetics and Society in Berkeley, CA.
Altering genes that are passed down to future generations is prohibited by more than 40 countries, she notes. "When policymakers, scientists, and bioethicists looked at this issue and decided that it made sense to prohibit it, the main reason is to avoid high-tech eugenics," says Darnovsky. "This would be a precedent for genetic modifications of other kinds."
A different standard is used to evaluate the safety and efficacy for a patient facing a terminal diagnosis with no other options, she argues. "You do risky experiments on people when you are trying to save people’s lives. This is not the case here. This doesn’t alleviate the suffering of anybody with mitochondrial disease," Darnovsky says.
Darnovsky says that there is a need to weigh the benefit "of having a genetically related child, applicable to very few people, against the profound social and ethical challenges that this presents."
Only a small subset of women with mitochondrial diseases would be candidates for mitochondrial manipulation, she adds, raising the question of whether there would be enough people to enroll in the clinical trial. "Many scientists have asserted that such a move at this time would put women and children at risk," adds Darnovsky.
Issues were lost
The hearing’s goals of understanding where the technology is, what it promises to do, and whether or not it is ready for translational research to the bedside was "somewhat lost" during the FDA public forum, according to Sauer.
Sauer has done previous controversial research, such as using assisted reproduction to achieve post-menopausal pregnancies and defending the payment of egg donors as research subjects. "So I am sensitive to the concerns of the public. Not everyone agrees with how we practice assisted reproductive technology," he says. "But this has been a world-class effort of scientists coming together with clinicians with a common goal."
The research has been carefully reviewed by the researchers’ own institutional review boards and ethics committees, adds Sauer. "What I and my colleagues are hoping for is an understanding not just of our work, but of others, and a dialogue on how we can move it along," he says.
Although the FDA has not issued an official ruling yet, the consensus seemed to be heading in the direction of recommending that more research be done before going ahead with clinical trials.
"But how much research is going to placate their worry?" Sauer asks. "When you do innovative work, you do get to a point where you have to take some risks. That is why it’s so important that it’s done correctly."
Sensational headlines such as "three-parent IVF," "designer babies," and "cloning technology" are counterproductive to the advancement of science, adds Sauer. "All that does is just make people think that what we are really doing here is trying to clone human beings," he says. "That is not even remotely or tangentially related to what we are doing."
While some regulators, in closed-door conversations, encouraged the researchers to continue their work, Sauer says it’s questionable how long that can continue when progress is being made in other countries. Mitochondrial replacement has been under consideration in Britain for some time, and may be approved there at some point in the near future.
"Restraint is not always a bad thing," says Sauer. "But to say Based on what they do, then maybe you can do it,’ when we are in a better position to advance the science, that’s a sad day," he says.
- Marcy Darnovsky, PhD, Executive Director, Center for Genetics and Society, Berkeley, CA. Phone: (510) 625-0819 ext. 305. E-mail: [email protected].
- Mark V. Sauer, MD, Division Chief of Reproductive Endocrinology and Infertility, Columbia University Medical Center, New York City. Phone: (212) 305-9175.
