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Some concerns have been voiced over the way in which a clinic last year created the first three-parent baby born using a new technique.

The baby’s birth was exclusively revealed by �鶹��ý in 2016. of the New Hope Fertility Center in New York and his team used a form of mitochondrial replacement therapy to help a woman have a baby without passing on a serious genetic disease carried in the DNA of her mitochondria, the compartments that generate energy in our cells.

The method involves placing the DNA from one woman into a donated egg from another, and then fertilising it with sperm. Because the egg contains some mitochondrial DNA from the donor, babies made this way carry genetic material from three different people.

The team has now published an account of this procedure and the resulting baby’s health in a peer-reviewed journal, Reproductive BioMedicine Online. It reveals that, seven months after birth, the boy remains healthy, showing no signs of Leigh syndrome – a condition that killed two of his older siblings.

Consent forms

But some researchers are raising concerns over the procedural paperwork associated with the treatment.

An accompanying editorial written by five researchers on the Reproductive BioMedicine Online editorial board describes Zhang’s work as “an achievement and stepping stone”, but points out that the consent form signed by the woman having the baby did not list the specific risks of mitochondrial replacement. “The authors explain that the patient received extensive counselling over the course of several years, but the final consent form does not record this,” says the editorial.

And the woman who donated an egg for the therapy, enabling the mother to have a child that carries someone else’s mitochondria, signed a standard egg donor consent form. “A copy of this form received by Reproductive BioMedicine Online shows that the use of the donated eggs specifically for spindle transfer (for MRT) is not mentioned,” the editorial says.

The embryo was created in New York, but Zhang’s team implanted it in the woman’s uterus in Mexico. The editorial states that the team had approval from the Mexican clinic’s Internal Review Board to do this, but had not applied for Internal Review Board approval for the work at the New York clinic.

“The editorial is detailed in its criticism,” Darren Griffin, at the University of Kent, UK, said in a statement to the UK Science Media Centre.

Criticism of the procedure followed has also come from a paper published in the Journal of Law and the Biosciences on 23 March, before Zhang’s study was released. The paper’s authors, César Palacios-González at King’s College London and María de Jesús Medina-Arellano at the National Autonomous University of Mexico, wrote that under their interpretation of the law, and with the information available at the time of publication of their paper, federal regulations may have been breached in Mexico that govern research into assisted fertilisation.

�鶹��ý was not able to reach Zhang for comment.

Escaped DNA

The study from Zhang and his colleagues reveals that some of the mother’s mitochondrial DNA has been passed on to her baby. This is likely to occur to some degree during the procedure that removes the nucleus from her egg, ready for inserting into a donor egg. It seems that about 5 per cent of the mitochondrial DNA in the embryo came from the mother in this way.

It is anticipated that this will not be enough for the boy to develop Leigh syndrome. Some studies suggest faulty DNA needs to exceed at least 60 per cent for this to occur. In his mother’s own cells, 34 per cent of her mitochondria carry the faulty DNA, and she has never shown any symptoms of the disease.

“They only had one normal-looking embryo that could be transferred to the patient,” of the Francis Crick Institute in London told the Science Media Centre. “They were lucky this was indeed normal, giving rise to a pregnancy, and they were lucky that the proportion of abnormal mitochondrial DNA remained relatively low in most tissues.”

But Zhang’s team warns of the potential risk that the mother’s faulty DNA will “bounce back” in the boy, saying it’s crucial for him to be monitored for many years. Some researchers are concerned that the percentage of faulty DNA after mitochondrial replacement might increase over time. Symptoms of Leigh syndrome are normally spotted in the first year of life and death usually results after just a couple of years, and at present the boy is just seven months old.

Since the birth of the boy described in the team’s paper, other three-parent babies have been made and born elsewhere. A clinic in Ukraine has told �鶹��ý that the second of two three-parent-babies created using a different technique in order to overcome infertility has been born. The boy was born on 19 February, following the birth of a girl in January. The clinic says both are healthy, but few further details are available yet.

Journal references:

Reproductive BioMedicine Online, DOI: 10.1016/j.rbmo.2017.01.013 (Zhang study)

Reproductive BioMedicine Online, DOI: 10.1016/j.rbmo.2017.02.004 (editorial)

Journal of Law and the Biosciences, DOI: 10.1093/jlb/lsw065 (legal study)