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Should ‘three-parent’ baby procedure to help women with abnormal DNA be allowed here?

SINGAPORE — Should a controversial genetic modification procedure, dubbed the “three-parent” technique, be allowed in Singapore to give a small group of women their only shot at having healthy children with their genetic stock?

Should ‘three-parent’ baby procedure to help women with abnormal DNA be allowed here?

Mitochondrial Genome Replacement Technology (MGRT) aims to prevent the transmission of mitochondrial disorders from a mother to her child. Photo: Unsplash

SINGAPORE — Should a controversial genetic modification procedure, dubbed the “three-parent” technique, be allowed in Singapore to give a small group of women their only shot at having healthy children with their genetic stock?

The Bioethics Advisory Committee is inviting the public to provide feedback on the tricky issue before it makes its recommendations to the authorities.

Mitochondrial Genome Replacement Technology (MGRT) aims to prevent the transmission of mitochondrial disorders from a mother to her child, by replacing abnormal mitochondria with normal mitochondria from a healthy donor at the egg or early embryo stage.

Most of a cell’s DNA (deoxyribonucleic acid, or hereditary material that carries genetic information) is found in the nucleus and a small amount is found in tiny cellular structures called the mitochondria, which are “power houses” that provide energy for cells.

Abnormalities in mitochondrial DNA can result in diseases affecting the brain, muscles, heart and liver – organs that need the most energy. Symptoms and severity vary widely, and faulty mitochondria have also been linked to medical problems like deafness, diabetes, epilepsy, and have in some cases proven fatal before adulthood.

Image:  Bioethics Advisory Committee

MGRT substitutes the faulty DNA in a mother’s egg with healthy DNA from a healthy donor. This seeks to prevent serious disorders caused by abnormal mitochondria from being passed to children, who inherit all their mitochondria from their mothers.

Children subject to the therapy will inherit genes from two women and a man, resulting in what the media have dubbed “three-parent babies”.

However, the committee – in its consultation paper issued on Thursday (April 19) – said the mitochondrial DNA from the donor is very small compared to nuclear DNA from the prospective parents. There is also no evidence that mitochondrial DNA confers any physically noticeable traits on the baby.

The mitochondrial genome contributes a negligible 0.000005 per cent of DNA in each cell, noted Professor Kon Oi Lian, chairperson of the committee’s MGRT review group and a senior consultant at the National Cancer Centre Singapore.

“Mitochondrial genome transfer is the transfer of an intact mitochondrial genome, so it doesn’t come under the sphere of ‘engineering’. We are just taking a whole genome, from somebody who doesn’t have the mutation… It would be like an individual who has a kidney transplanted from a donor,” she said.

In Singapore, the prevalence of heritable mitochondrial diseases as well as the number of women with such disorders who wish to have children is not known.

In the United Kingdom, about 1 in 5,000 people suffer from mitochondrial diseases caused by mutations in mitochondrial DNA.

There is currently no cure for mitochondrial disorders, although some symptoms can be treated to varying degrees with medication, diet or transplants.

The UK was the first country to legalise two MGRT techniques in 2015. In February, it gave the green light to two women at risk of passing devastating and incurable genetic diseases to their newborns for the procedure.

No other jurisdiction has explicitly permitted MGRT, although Thailand does not explicitly prohibit it. Some modification procedures are also allowed under certain conditions in Israel and Italy, such as when no alternatives are available.

MGRT research in humans is banned in countries like the United States and Australia.

But feasibility of some MGRT techniques have been demonstrated in human eggs. In September 2016, a US research team announced the live birth of the world’s first baby in Mexico, that was created through a technique that transferred the prospective mother’s nuclear DNA to a donor’s egg with nuclear DNA removed, that was then fertilised.

A Ukrainian team also reported two successful births in January and February last year, but have drawn criticism for using an MGRT technique to overcome infertility (as opposed to preventing a hereditary disease).

WEIGHING THE PROS AND CONS

The advisory committee fleshed out possible risks and benefits of MGRT in their 30-page consultation paper released to the public on Friday.

MGRT offers an opportunity to mitigate undesirable outcomes of the “genetic lottery” and could be the only way for some women with abnormal mitochondrial DNA to have healthy, genetically-related children.

“It could be said that the main benefit of MGRT is the fulfilment of such individuals’ deep desire to have genetically-related children,” the committee wrote.

Children born from existing alternatives like adoption and in-vitro fertilisation are typically not genetically related to the women.

Some have also argued that the choice to have one’s own child through MGRT, rather than adopting someone else’s child or using a donated egg, helps uphold one’s “reproductive autonomy”.

However, little is known about the risks that could arise from the procedure as no human trials of MGRT have been conducted, the paper stated.

Even after pre-clinical studies in animals and human embryos are conducted, the long-term safety and effects can only be determined by studying several generations of descendants of the MGRT babies.

Professor Kon acknowledged that MGRT techniques are not foolproof and it is still possible for the faulty DNA to be passed on to future generations via these procedures.

One possible safeguard is to carry out trials of MGRT with only male embryos to remove the risk of transmission of unforeseen defects to subsequent generations, the paper stated.

IDENTITY AND SLIPPERY SLOPE CONCERNS

Some have also argued that children born via MGRT may have “troubling, ambiguous or conflicted” self-identities, having inherited genes from three “parents”, the paper noted.

But with IVF and adoption no longer uncommon in Singapore, “notions of genetic parents, gestational parents and social parents should no longer be unfamiliar or unacceptable in our community”, the committee wrote. Laws in Singapore also make clear the gestational mother is treated as the legal mother while egg and sperm donors are not treated as parents.

Opponents of MGRT also warn of the “slippery slope” towards enhancement for “designer babies”.

Singapore does not have laws banning such genetic modification, other than the committee’s recommendation in 2005 that it should not be allowed for the time being.

The “slippery slope” objection can be addressed by enhancing current regulations to limit the use of MGRT to the prevention of serious mitochondrial disease, an approach similar to the UK’s.

Commenting on MGRT, Virtus Fertility Centre Singapore’s scientific director Liow Swee Lian said it supports the scientific community’s investigation into mitochondrial mutations to eradicate serious illness in children born from parents with mitochondrial problems.

“The health implications of this class of diseases are serious and we would welcome legislation that provides the research community with the ability to investigate this area further, including the transfer of donor mitochondrial DNA into oocytes (immature eggs),” he said. “We are, however, conscious that there are still serious safety concerns surrounding this technology and do not support its use outside the context of treating serious childhood illness.”

The consultation paper is available at www.bioethics-singapore.org and www.reach.gov.sg from Friday and the public may submit their feedback until June 15. The advisory committee will hold dialogue sessions with the medical and research fraternities, as well as religious groups, in the coming months.

The 13-member MGRT review group, which includes experts in paediatric genetics, medical ethics and law, is also looking at three techniques to carry out MGRT.

The committee expects to present its recommendations to the Government by the end of next year.

It last sought public feedback on the ethics of brain-related studies by issuing a public consultation paper in 2013. Previous reports stated the committee could release guidelines by the end of 2013, but it is still in the midst of consolidating its recommendations.

THREE MITOCHONDRIAL GENOME REPLACEMENT TECHNIQUES BEING REVIEWED

Abnormal mitochondria can be replaced with normal mitochondria by manipulating either the egg or embryo using three techniques.

1. Maternal spindle transfer: Involves “reconstructing” a healthy egg comprising the prospective mother’s nuclear DNA and a donor’s healthy mitochondria, and then implanting this into the prospective mother’s womb.

2. Pronuclear transfer: Involves fertilising both women’s eggs with the prospective father’s sperm first and reconstructing a healthy embryo, then implanting it into the prospective mother. Pronuclear and maternal spindle transfers have been given the green light by the UK’s fertility treatment regulators.

3. Polar body transfer: Involves the use of “polar bodies”, which are small cells produced in the formation of eggs and fertilisation that contain few mitochondria. This makes them ideal candidates for MGRT as they would reduce the chances of passing on faulty DNA during the egg “reconstruction” process.

 

 

 

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