Impact of gene editing breakthrough will be muted

8th Aug, 2017

The work on the repair of a gene in human eggs, reported in the journal Nature, is an important scientific achievement. It made use of “Crispr” (clustered regularly interspaced short palindromic repeats) technology to make a single specific change in the three billion units of the human genome. The work is indeed a stunning application of Crispr, with some elegant and surprising results – and the publicity is good for my science – but it is not likely to change the way reproductive medical genetics is practised and it raises no new ethical problems.

The claims made for the work, amplified by the media, will raise expectations in families carrying genes with severe medical effects and has already excited the critics who fear that geneticists are busy undermining our society. So let us first look at what has been achieved in the science, and then tease out some of the implications.

Medical genetic disorders cause a great deal of suffering and affect about one person in 25. Genetic engineering and DNA sequencing invented in the 1970s led to a revolution in genetics. Mutant genes causing many genetic disorders have been identified. Advances in human embryology led to in-vitro fertilisation (IVF) in 1978, leading to the birth of more than five million children and untold happiness in their families. The question arose whether IVF could be useful in dealing with medical genetic cases.

Genetic defects

By the early 1990s geneticists could detect mutant genes in single cells taken from IVF embryos without harming the embryos. This led to the gradual introduction of preimplantation genetic diagnosis (PGD). Today parents who are concerned that they may conceive a child with a significant genetic disorder can produce embryos by IVF, these may be tested for the genetic defect and one or more unaffected embryos can then be implanted.

PGD requires a specific “probe” for each genetic mutation. Some mutations are common, such as F508 in cystic fibrosis, but for many families the mutations have to be analysed and specific probes prepared and tested. As many people know, IVF is itself complex – PGD adds another level of complexity, meaning that the number of successful clinical cases dealt with worldwide to date is still only a few thousand. PGD is in its infancy.

So what will be the clinical impact of the new method on PGD? In their experiments, biologist Shoukhrat Mitalipov and his fellow researchers treated 58 embryos in which about 50 per cent carried the normal and half the mutant gene. After treatment they found that 42 (or 72 per cent) carried two normal genes. The mutant gene had been repaired in an estimated 13 out of 29 embryos. Crucially, not all embryos were repaired, nor was it possible to say that Crispr did not cause other unintended, off-target damage to other genes. The embryos were not implanted.

The authors suggest that repair by Crispr will increase the efficiency of PGD. In fact it will have almost no practical effect on PGD services, for two reasons. First, not all of the defective genes are repaired, so after Crispr the embryos still have to be screened by standard PGD to avoid implanting mutant genes. Second, repairing is much more complicated than the current method, which is already complicated. Two Swedish commentators who work in the field note dryly: “Embryo genetic testing [PGD] during IVF remains the standard way to prevent the transmission of inherited diseases in human embryos.”

In contrast to its use in reproductive medical genetics, use of Crispr in repairing genes in body tissues is a really promising approach to treating genetic disorders after birth, but that is another story.

What do we really need to do in developing PGD? The technical priority is to make IVF itself more efficient. Then we need to refine the current methods of PGD and apply them routinely to a much wider range of genetic mutations. The social priority is to provide PGD on national health services to all couples faced with a high chance of conceiving a child with a major genetic disorder.

Ethics

Now what about the ethics? Since PGD, which is a medical procedure, is well accepted in international medicine there is nothing new on that front. If in the past, like the Catholic Church, you opposed IVF (and PGD), or the wishes of parents to avoid having children with genetic disorders, this work will not change opinions, and should not increase your concerns.

It is possible that the Crispr techniques of changing genes will be used for non-medical purposes in reproduction, for example to alter genetic qualities which have nothing to do with health. In the UK, such use is regulated by the Human Fertilisation and Embroylogy Authority, and might be made illegal (as for example is the non-medical use of PGD for sex selection). But it may be more difficult to make all applications illegal – for example, parents might wish to have a child with blue instead of brown eyes, and if so is foolishness something we should make illegal?

One thing is clear. It is long past time that we put into effect the recommendations of the Irish Commission on Assisted Human Reproduction of 2005 dealing with these issues, which are not new, and are well known to the Government. IVF is not regulated in Ireland nor is PGD, making it difficult for pioneers in the field such as Dr John Waterstone of Cork Fertility to provide a service that is badly needed in Ireland.

David McConnell is fellow emeritus of the Smurfit institute of genetics at Trinity College Dublin. He is a former chairman of The Irish Times Trust.

 
 

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