‘Three-parent’ IVF: cure or myth?

There are weighty scientific reasons for not going ahead with the world's most radical IVF technique.
Caroline Simons | Feb 24 2015 | comment  



The British House of Lords is expected to approve regulations today to permit IVF techniques which may prevent the transmission of some mitochondrial diseases from mother to child. Every cell in children produced by these techniques will have DNA from three individuals – hence the “three-parent” description. These genetic changes will be inherited by future generations.

Notwithstanding months of public consultation and years of debate, it appears that the members of the British Parliament and the public have been misled. Here are some issues which science journalists failed to cover and scientists failed to raise.

The two techniques involve the removal of the nuclear genetic material either from a woman’s egg or from an early embryo which has faulty mitochondria floating in its cytoplasm. That nuclear material is then transferred into a donated egg or embryo which has healthy mitochondria, (and from which the nuclear genetic material has already been removed). Both of these methods involve transfer of the nucleus of a cell, and do not entail, other than accidentally, transfer of mitochondria.

Scientific journals, the UK Department of Health and the UK’s fertility watchdog, the Human Fertilisation and Embryology Authority, have used the words “transfer”, “donation” and “replacement” to describe these techniques. The HFEA explained that its use of this terminology was “to enable a lay audience to understand the essential purpose of these techniques”, but not, it must be said, their mechanism.

Prominent US bioethicist Arthur Caplan said in an article last year that “the mitochondria are separate, tiny units in the egg meaning you can pick them out and transplant them”. This feat has not been attempted or even proposed in relation to these techniques.

The day before the UK House of Commons voted to pass the regulations allowing “three-parent” IVF, the editor of the Journal of Medical Ethics, Julian Savulescu, posted a video on YouTube in which he said  “every year 150 children are born [in the UK] with this condition and you have the power to cure them.” He continued “with this disease there’s no waiting – it either has to be done at the moment of conception or there’s nothing you can do about it.” Neither statement is true.  

Let’s look a little closer at some issues which have been misrepresented.

These techniques will not cure any individual, before or after birth, of mitochondrial disease. They attempt to create individuals without the mitochondrial defects which may cause disease. A child who is sick remains sick.

These techniques will only apply to some mitochondrial disease, not all. The scientists speak of mitochondrial disease as if it were always due to a defect in inherited mitochondrial genes. But it also occurs because of defects in the nuclear genes implicated in mitochondrial function and because of  a build-up of mitochondrial damage caused by external factors, like viral infections, unintended effects of anaesthesia etc.  “Three-parent” IVF will not avoid mitochondrial disease caused by these two.

Furthermore, defects in the mitochondrial genes are very rare. The painful statistics of affected families include mostly the latter two reasons. While it can be devastating and even fatal, disease caused by defects in the mitochondrial genes is very rare indeed, particularly in children. In Sweden and Australia it is estimated that 5 in 100,000 children have mitochondrial disease, with defects in the mitochondrial genes accounting for 15 percent of that figure. In most cases of diagnosis of mitochondrial mutation in childhood, suspicion of maternal inheritance is the exception rather than the rule.

The prevailing scientific theory that we inherit mitochondria exclusively from our mothers may be wrong. Some scientists believe it important to examine the possibility of paternal inheritance (which is common and recurring in other mammals). A paper published in the New England Journal of Medicine reported evidence of three cases of paternal transmission of mitochondrial disease in humans. Recent research proposes that assisted human reproduction may increase the rate of transmission of paternal mitochondria. The “three-parent” techniques would not avoid inheritance of faulty mitochondria from fathers.

The number of diagnoses has been exaggerated. In 2014, the UK team pioneering this research advised the UK Department of Health that these techniques would “prevent around 10 children a year suffering serious mitochondrial disease.” Days before the UK House of Commons passed the regulations to permit these techniques, the New England Journal of Medicine published a letter from the same team suggesting that these new techniques could benefit about 150 births per year [in the UK].

A 2014 paper examined data collected from the only clinical and diagnostic service for rare mitochondrial diseases in the UK. This National Health Service was free and unlikely to have been available elsewhere in the UK. Over nearly 7 years, 17 prenatal diagnoses of disorders due to mitochondrial defects were made, an average of 3 per annum. So how many families will benefit: 150, 10 or only 3?

There has been little consideration of gene therapies for mitochondrial diseases. A Phase 1 clinical study of a gene therapy to treat a form of the most common disease due to mitochondrial defects, LHON (which may cause blindness), began a year ago and collection of the data for assessment of the outcome will be completed in December 2015. Scientists believe that gene therapy has vast potential to treat other mitochondrial conditions. These therapies do not create inheritable changes in the human genome.

These will be the most invasive techniques the assisted reproduction industry has seen. Serious scientific concerns have been left unanswered. The literature shows that the greater the degree of manipulation of the embryo, the greater the risk of long-term adverse effects including metabolic and psychological diseases. This year, concerned scientists have highlighted the need for long-term trials and follow-up of “three-parent” IVF in sheep or cows to assess the risk of developmental defects and defects which may manifest later in life before proceeding to make these inheritable changes in humans.

The Swedish National Council on Medical Ethics has declared that the current limited scientific basis for assessing the risks these techniques pose make it unethical to use them on humans. There are legitimate ethical concerns, but the scientific concerns alone should give their Lordships pause for thought before they vote today.

Caroline Simons BCL LLM Solicitor, lives in Dublin, Ireland and is currently engaged in postgraduate legal studies in Britain. She contributed to the recent House of Commons Science and Technology Committee hearings on mitochondrial transfer.



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