UK Seeks Regulatory Advice for “Mitochondrial Replacement,” Fails to Mention Cross-Generational Implications

By Jessica Cussins, Biopolitical Times | 06.17.2015

Biopolitical Times

https://www.geneticsandsociety.org/biopolitical-times/uk-seeks-regulato…

How does one go about regulating the world’s first cross-generational biological experiment in human germline modification? The regulating body in charge isn’t exactly sure. They’re seeking input via an online survey by July 1, 2015.

The technique in question, called mitochondrial replacement or three-person IVF, would combine genetic material from three different people into a single embryo, causing permanent changes to the human germline, in the hopes of allowing a woman to have a child who resembles her in all but her mitochondrial disorder.

The UK actually has a law against genetically modifying human embryos for reproductive purposes, but a tireless push from a small group of the UK science elite over many years ultimately swayed Members of Parliament in both the House of Commons and the House of Lords to allow a limited exception to be made for only this technique, and for only the prevention of serious mitochondrial disorders.

Arguably, those campaigning for this political shift didn’t always fight fair – safety requirements such as clinical testing on non-human primates were discarded half-way through when experiments failed to work; the phrase “genetic modification” was redefined to diminish the severity of the techniques; the impact of mitochondria on a wide array of traits was repeatedly misrepresented; and evidence of serious safety and efficacy concerns was routinely downplayed, if not outright ignored.

Now, the Human Fertilisation and Embryology Authority (HFEA) faces the daunting task of having to determine a system to regulate these techniques within fertility clinics before the regulations come into force October 29, 2015.They are currently seeking views from experts.

But if you look at either the “lay summary” or the “background document” they have prepared, you would not necessarily understand why anyone cared so much about these technologies in the first place. Nowhere in either of these documents does it actually explain that these technologies result in human germline modification – something people just might care about since it is banned by every country that has ever considered it, as well as the Council of Europe’s Convention on Human Rights and Biomedicine.

Because of this omission, they have a hard time getting to the heart of the matter – how does one regulate a cross-generational biological experiment?

Instead, their online survey seeks input on more discrete questions. For example, they ask how they should license a clinic to undertake the techniques. This feels somewhat disingenuous since in their lay summary they admit that only one research team in the UK is likely to be in a position to offer this at the moment (surely, the Wellcome Trust Centre for Mitochondrial Research at Newcastle University.)

They also ask how each patient should be determined to be at “particular risk” of passing mitochondrial disease to a child – a requirement of the regulations. However, they say that the presence of “a mutation” in a woman’s mitochondrial DNA (mtDNA) is enough to satisfy this requirement. Now, maybe I’m missing something. But I’m pretty sure that a substantial number of women alive today have mtDNA mutations, and in the vast majority of cases these DNA changes do not cause disease. More precise language would reflect the fact that risk is caused much more specifically by a “known disease-causing mutation in one of the 37 mitochondrial genes.” And that typically, problems only occur once a certain mutation threshold has been passed – say, if there are mutations in more than 20% of your mtDNA.

As for follow-up studies, which “many experts have recommended,” the HFEA is deferring to the clinics. They plan to encourage clinics to ask their patients to take part in studies of the clinics’ design, but will not require the patient or resulting child to take part. However, if a clinic becomes aware that a child has been born with any disease or genetic abnormality, the clinic will be required by law to report this as an “adverse incident.” Of course, in utero genetic testing could find many of these issues before the child is born, in which case the public would be unlikely to be made aware. Moreover, the genetic changes made to that child will be passed onto future generations, but there have been no recommendations for how to monitor any long-term, cross-generational issues that may arise.

For more information on the current regulatory process by the HFEA, see here. Fill out the online survey by July 1, and if you’re in the UK, consider attending their public workshop being held June 23. But be warned: they “are not asking you to comment on the wider ethical and scientific issues involved, nor the statutory framework.”