February 29, 2024

US stem cell expert questions UK plans for 3-parent embryos

A noble goal, but there are too many unanswered questions.

The British Parliament will begin debating whether to legalise a controversial technique known to opponents as “3-parent embryos” or “3-parent babies” or, to its supporters as “mitochondrial transfer”. A prominent government advisor, Professor Robin Lovell-Badge, of the National Institute for Medical Research, summed up the view of the scientific establishment in New Scientist recently: “It is our considered view that the techniques are not unsafe and are likely to be effective.”

The prospect of creating embryos with genetic material from three persons has become an international issue. A prominent American stem cell scientist, Paul Knoepfler, of the University of California Davis School of Medicine, recently published an open letter in his blog questioning the wisdom of the move. He emphasises that he is not “a radical extremist or luddite”; he does embryonic stem cell research and supports IVF for infertile couples.

Here are some paragraphs:

This experimental technology has a noble goal, but in my opinion there are too many unanswered questions and risks that remain to allow it to proceed at this time. In fact, I believe that moving forward with it would most likely be a tragic mistake for the UK…

There are numerous serious risks associated with this technology. These include most notably the possibility that developmentally disabled or deceased babies will be produced. As an objective scientist, I believe the odds of this happening are at least equal to the chance that this technology will succeed in preventing mitochondrial disorders. In fact, there are precedents that would suggest that negative outcomes are reasonably likely.

In the 1990s, fertility clinics in the US, China, and elsewhere performed human reproductive procedures similar to what is being proposed now [2-6]. While the goal in those experiments was to simply create babies for infertile couples and not specifically to deal with mitochondrial disorders, the technologies employed are largely alike. In fact, these 1990s procedures were far simpler and less invasive (they only involved transfer of some oocyte cytoplasm) than what is being proposed now with mitochondrial therapies where an entire nucleus or set of chromatin is moved from one cell to another, where an entire nucleus has also been removed.

The end result from these human reproductive experiments in the 1990s was a mixture of outcomes including not only seemingly healthy children (thank goodness), but also miscarriages, a child with severe developmental disability, and chromosomal aberrations. These are very real, concerning possible outcomes for the proposed human mitochondrial transfer technology today and in the future should it be allowed to proceed…

… the proponents claim incorrectly that “mitochondrial donation” is not human genetic modification. It is in fact genetic modification. Notably, the first team to ever make this kind of technology work unambiguously stated in their paper that it was genetic modification: ““This report is the first case of human germline genetic modification resulting in normal healthy children.”

The proponents of 3-parent technology also incorrectly claim that the concerns about it or risks associated with it are just hypothetical, although in reality the concerns based on past experiences discussed earlier are quite concrete and real.

Proponents also might be overly optimistic about the chances that the technology will frequently prevent mitochondrial disorders in humans.

A scientific reality often passed over in this discussion is that while mitochondria have been studied for decades, the field of studying the mitochondrial genome is in its infancy and is far too new to support a major human intervention that involves the mitochondrial genome. The interactions between the mitochondrial genome and the nuclear genome are also only poorly understood today. It would be rash and premature to proceed with human mitochondrial transfer now given how primitive our knowledge is in this area at this time.

Creative commons
stem cells
three-parent embryos