Mitochondrial replacement therapies in Mexico and the USA - and the FDA

Almost a year after the first live birth of a baby following a mitochondrial replacement technique (MRT) procedure (see BioNews 871), the US Food and Drug Administration has sent a very strongly-worded letter to the scientist and team responsible for the event.

The FDA's letter not only lists many of the violations – although it clearly states that it is not an all-inclusive list – that according to them Dr John Zhang and his team at the New Hope Fertility Centre in New York City have incurred, but also points out that Dr Zhang had continued to market MRTs in the USA, through private company Darwin Life Inc. and/or the New Hope Fertility Centre, as a way to 'to prevent the transmission of mitochondrial disease and to treat infertility', even when he had agreed not to do so. At this time Darwin Life website appears to have been pulled down. It is unclear what other actions the FDA will take following its letter. Though surprising, this is just the latest episode of a story that has been fraught with ethical and legal questions.

Before I explain why this development is important for MRTs in the US, let's briefly recap on what MRTs are. MRTs are new reproductive technologies that could help women at risk of passing mitochondrial DNA diseases to have genetically related children absent such conditions. One technique uses eggs and the other uses single cell human embryos (click here for a video explaining the difference). These techniques raise a number of important ethical questions, for example: should the egg donation be anonymous, are there moral differences between the two techniques that have been proposed, how should they be introduced into the clinic, are there important differences between the nuclear genome and the mitochondrial genome? But the ethical and legal questions that have haunted the birth last year relate more to how the experiment was carried out.

In September last year New Scientist broke the news about the first live birth following an MRT. One characteristic that stood out immediately was that, according to what was implied in the publication, the experiment happened in the city of Guadalajara, Mexico. This was of interest because the lead researcher Dr Zhang is a US-based fertility doctor. At that time Dr Zhang was quoted as saying that they went to Mexico because there there are 'no rules'.

My first reaction was that this was bad news for Mexico (see BioNews 871), given that at that time a very restrictive amendment to the General Health Law, a federal level legislation, was being discussed in Congress. My second reaction was of incredulity: are there really no laws in Mexico that apply to MRTs? María de Jesús Medina-Arellano and I wrote an academic paper where we explored the legal status of MRTs in Mexico. We concluded that, according to our interpretation of the law and the information that was publicly available at that point, Dr Zhang et al broke federal health regulations. For us it was important to write the paper because there we showed that there are indeed regulations in Mexico that apply directly to MRTs at the present time.

A month or so later, Dr Zhang and colleagues published a case report in Reproductive BioMedicine Online detailing their experiment. Their paper was accompanied with a critical editorial that contained a key piece of information for the legal assessment of this procedure: 'In the case described here, the MRT embryos were generated in New York through privately funded research, but the therapeutic part of the procedure – that is, transfer of the embryo to the patient – was done at an affiliated clinic in Mexico, thereby technically circumventing the federal statute.'

This, in the end, means that our legal assessment regarding this particular case was incorrect. Nevertheless, it is interesting that during media interviews Dr Alejandro Chavez-Badiola, medical director and founder of the New Hope Fertility Centre Mexico, did not previously clarify that the MRT procedure happened in the USA – even after a Mexican reporter for the programme Despierta con Loret explicitly said in front of Dr Chavez-Badiola that the experiment was carried out in Mexico.

Now, answering the question 'what does the FDA's letter mean for the clinical use of MRTs in the USA' seems to be straightforward at this point. First, a provision in a congressional spending bill bars the FDA from evaluating 'research in which a human embryo is intentionally created or modified to include heritable genetic modification', which according to them includes MRTs. Second, the FDA considers that MRT experiments fall within their rule and they will not turn a blind eye to them, even if the egg or zygote is intended for export. At this point we will have to wait and see if Dr Zhang decides to move all his MRT operation outside of the USA, or if this was a very short-lived stint.

Dr César Palacios-González is speaking in the session 'The Wild East and the Worried West: Pioneers or Outlaws?' at the Progress Educational Trust's upcoming public conference 'Crossing Frontiers: Moving the Boundaries of Human Reproduction'.