Proposed New Gene Manipulation Technique in IVF: Is it Safe? Needed? A Precedent to Designer Babies?

Can inheritable genetic modification ever be appropriate? For many years, it’s been widely accepted that altering the human “germ line” – that is, making any genetic changes that would be passed on to future generations – is a not-to-be-crossed bright line. This line has been codified in law in some three dozen countries, including most of Europe and Canada.

Now some UK scientists are mounting a policy effort to push over the germ line – in the name of medicine, and without intentionally changing any phenotypic traits, but discarding the bright line nonetheless. In mid-September, the UK agency that regulates assisted reproduction – the Human Fertility and Embryology Authority (HFEA) – launched a public consultation about proposed IVF techniques that would constitute germline genetic modification, and has published an extensive website to explain the issue and solicit public comment. In the words of HFEA chair Lisa Jardine, the agency will “take the public temperature on this important and emotive issue.”

The techniques, known as “mitochondrial replacement,” involve creating embryos with portions of eggs from two different women. The goal is to allow a woman to pass on to her future children all her own genetic material with the exception of a small number of genes in her defective mitochondria, which are organelles outside the nucleus of an egg that are involved with cellular metabolism. The mother’s mitochondrial DNA would be replaced by material from another woman’s egg, so any child born after such procedures would inherit a small amount of DNA from that other woman.

This is portrayed as an innovative medical approach that might help people have healthy children. But it also raises thorny questions about whether attempting the techniques would be risky enough that it would constitute unethical human experimentation, and about whether allowing the techniques could open the door to additional forms of inheritable genetic modification.

The move was widely covered in the British media, where the story ran under headlines about “3-parent babies” (The Telegraph and Huffington Post UK) “3-parent families” (The Independent) or “3-parent IVF” (Reuters). It was little noticed by the US media, though the new web-TV platform HuffPost Live carried a panel discussion in which I participated.

The HFEA consultation, which runs until December 7, is supposed to address ethical concerns, not questions about safety. But the kinds of safety considerations presented by mitochondrial replacement are in fact an ethical matter. Using risky and unproven techniques is one thing when a person’s life or well-being is at stake and there are no alternatives. But that’s not the situation here. Mitochondrial replacement is aimed not at existing people, but at future children. And there is an alternative: Parents at risk of passing on mitochondrial disease could elect to use IVF with eggs provided by an unaffected woman. Though the resulting child would not be genetically related to the mother, neither would it be put at risk by a biologically radical experiment.

Many observers say that there is not nearly enough research evidence to know whether the new techniques would be safe. And similar biologically extreme technologies provide reason for concern. One example came to public attention in 2001, when U.S. scientists using a similar but less invasive technique to initiate a small number of pregnancies were told by the FDA to stop because of chromosomal and developmental problems in resulting fetuses and one child (1, 2).

Questions have also been raised about how many people might be candidates for mitochondrial replacement techniques. The HFEA press release and website state that 1 in 200 children are born with “a form of mitochondrial disease.” But that number appears to be significantly inflated: Other sources put the rate at 1 in 4000, 6500, or 8500 (1, 2, 3). The HFEA’s incidence rate might refer to conditions that are affected by mitochondrial DNA, but these involve little-understood interactions between mitochondrial and nuclear DNA, and wouldn’t necessarily be avoided by mitochondrial replacement.

The HFEA acknowledges that mitochondrial replacement is a form of germline modification, which is banned in dozens of countries, and that “this may raise important social and ethical questions.” It includes on its website a short video with people expressing a range of views. At a London news briefing, HFEA Chair Jardine said that

once we have genetic modification we have to be damn sure that we are happy. Because this is not about us. This is not about our children. It's not even about our grandchildren. It's about many generations down the line what the consequences might be.

A key concern is whether allowing mitochondrial replacement could set a policy precedent. If it were to be approved, would advocates of inheritable genetic modification use it as a wedge for more extensive “designer-baby” manipulations?

Dr. David King of Human Genetics Alert, a UK public-interest organization, has tracked the development of genetic modification techniques and the policies related to them for years. He believes that mitochondrial replacement techniques could in fact “set a precedent for allowing the creation of genetically modified designer babies,” and that this risk is not outweighed by any pressing need, since third-party eggs for those concerned about passing on mitochondrial disease provides an alternative. That the technique “is even being considered is a reflection of medical consumerism and scientists' fetish for employing the most hi-tech methods," he said.

Previously on Biopolitical Times:

• UK's HFEA Lowers the Bar, Again
• Abolishing (and Replacing) the UK HFEA
• HFEA Triples the Going Rate for Women’s Eggs in UK