LONDON — A leading expert in human embryology has predicted that the United Kingdom’s first “three-parent” child could happen as soon as next year.

His comment to the Register follows news that a Jordanian couple gave birth this year to the world’s first “three-parent” child, via a pioneering “maternal spindle transfer” IVF procedure.

The couple sought out the services of Dr. John Zhang at the New Hope Fertility Center in New York City. They did not want to pass on Leigh syndrome, a fatal mitochondrial mutation that interferes with development of the nervous system, to any future child conceived. Using this new technique, Zhang was able to assist the 36-year-old mother to conceive and give birth to a baby boy on April 6.

The news was announced by New Scientist on Sept. 27 and greeted by many assisted fertility specialists as a huge advancement, while some bioethicists criticized it as another example of destroying human life and of fragmenting the child-parent relationship.

The Register asked Dr. Dusko Ilic, a professor in stem-cell science at King’s College London and a leading stem cell and IVF authority, if he thought three-parent procedures would be carried out in the U.K. “I tend to believe that the first such baby will be born in the U.K. sometime in the next year,” he said.

Following a 2008 amendment to the 1990 Human Fertilization and Embryology Act, the U.K. became the first country to permit regulations allowing techniques to prevent the transmission of mitochondrial disease. In February 2015, the U.K. produced regulations for the use of maternal spindle transfer and pronuclear transfer procedures.

An expert panel at the Human Embryology and Fertilization Authority is currently in deliberations and is expected to give its decision on allowing three-parent procedures to go ahead by the end of the year.

The Register also spoke with Dr. Dagan Wells, an associate professor at the Nuffield Department of Obstetrics and Gynecology at the University of Oxford and the director of reprogenetics.

Wells worked with Zhang, carrying out a test to determine if the embryo transferred to the mother was affected by mitochondrial disease.

He said there have been research teams in the U.K. working toward a cure for mitochondrial disorders, notably the Wellcome Trust Center for Mitochondrial Research at Newcastle University.

“Because of the concerns about safety and ethics, as well as the scientific challenges involved, they have been progressing towards clinical application in a very careful step-by-step manner. Before the method could be used to treat patients, the law in the U.K. had to be amended,” he said.

Zhang carried out the procedure in Mexico, where there are “no rules,” he is reported as saying. However, the Mexican legislature is considering amendments to the country’s National Health Law, which would place restrictions on assisted reproduction as well as some forms of surrogacy and ban eugenics and genetically modified embryos.

The Register contacted Zhang for comment about his research, but received no reply by the time of publication.

U.S. law prevents federal government funding research that destroys human embryos or embryos created solely for research. In February this year, however, a panel of experts from the National Academy of Medicine told the Food and Drug Administration that mitochondrial replacement procedures were ethically permissible.

 

Safety and Sex-Discrimination Concerns

The world’s first mitochondrial donation procedure, cytoplasmic transfer, was carried out by clinical embryologist Dr. Jacques Cohen at St. Barnabas Medical Center in Livingston, New Jersey, in 1996, on Maureen Ott, a 39-year-old Catholic woman. Between 30 and 50 babies were conceived this way before the procedure was banned in 2002.

In a 2014 interview with the BBC, Cohen said that many of the children he helped conceive had serious genetic and development disorders, and he had been unable to track how they had developed over the years.

Maternal spindle transfer, the procedure used by Zhang, starts with emptying the mitochondrial-affected egg of its nucleus DNA (spindle), discarding the diseased egg and transferring the healthy spindle into the healthy egg of a second woman whose spindle has been removed. The egg is then fertilized by a man’s sperm and placed inside the womb of the woman wanting a child.

Zhang created five embryos. One did not develop, three others developed abnormally, and one was implanted.

“Even though the mother protested that she didn’t want to lose any more children to Leigh syndrome, another four of her offspring were actually sacrificed intentionally, rather than lost accidentally, by choosing to create a three-parent embryo via IVF,” said Father Tad Pacholczyk, director of education at the National Catholic Bioethics Center.

There also appears a sex-discrimination danger. Mitochondrial mutation is passed on from the mother, meaning any female child born would need to be monitored for the rest of her life, and so would any children that she had, to check if and how much mutation had been passed on.

Because of this concern, female embryos could be deliberately discarded as high-risk, giving male embryos preference. Meanwhile, baby boys artificially conceived this way and allowed to be born would serve as “guinea pigs” in terms of the moral, medical and identity questions engendered by the procedure.

Wells told the Register he did not know if the transfer of a male embryo was deliberate in the case of the initial “three-parent” child: “It might be the case that the only unaffected embryo available just happened to be male.”

“However, the fact that it was male does have some advantages,” he said. “Men do not contribute any mitochondria to their children, so a man cannot pass on a mitochondrial disorder. The child born as a result of these procedures still has some abnormal mitochondria, too low to have any clinical symptoms; but if the child had been female, there would have been a risk that any children had in the future could have inherited too many defective mitochondria and ended up seriously affected.”

Dr. Calum MacKellar, director of research at the Scottish Council on Human Bioethics, warns that, in the U.K., these children and their children would need lifelong monitoring. “This is experimentation on a generational scale that would be difficult to reverse if anything went wrong,” he said.

 

‘Third-Parent’ Concerns

The Register asked Ilic what he thought about the possible ongoing involvement of the “third parent” and whether he was concerned that children may wish to track down the third parent, with similar things reported among donor-conceived children.

“A three-parent child cannot be compared with donor-conceived children,” he said. “Egg or sperm donor-conceived children inherit half or all their genes from another person and none from one of the parents. Those genes make a significant contribution to the biological identity of a donor-conceived child.”

“This is not the case with the three-parent baby. Mitochondria carry only about 30 genes, coding enzymes for energy production and nothing more, whereas the other 30,000 genes, which carry all information from two parents, are in the nucleus.”

One child conceived by Cohen’s procedure, Alana Saarinen, 16, said she did not consider the mitochondrial donor her “third parent” and would not want a relationship with her, but would like to thank her.

Others, however, see serious moral objections around issues of parentage and identity.

“It’s impossible to not have a lot of sympathy and compassion for persons affected by mitochondrial disorders who want to have children, whom they consider to be ‘of their own,’” said MacKellar.

“Indeed, these parents may become very distressed in realizing that the children born from these procedures may not accept, later on, that they only have two parents. Instead, they may want to know and have parental relationships with all three or four persons who brought them, biologically, into existence, in order for them to develop an idea of who they are and a healthy sense of identity.”

He expressed regret that the U.K. government has enacted binding legislation, preventing children born through such procedures from contacting their egg- and sperm-donor parents: “It reflects a very limited understanding of who parents really are and may give rise to serious long-term psychological distress in the prospective children.”

Dr. Anthony McCarthy, a British bioethicist with the Society for the Protection of Unborn Children, added, “The fragmentation of parenthood and destruction of a child’s siblings are deeply, morally problematic in ways we would certainly recognize as such at later stages of development.”

 

Church Teaching

The Catechism of the Catholic Church teaches that “from the first moment of his existence, a human being must be recognized as having the rights of a person ― among which is the inviolable right of every innocent being to life” (2270).

Pope St. John Paul II said that all research using stem cells from human embryos is “morally unacceptable.”

In his 1995 encyclical Evangelium Vitae (The Gospel of Life), John Paul said, “This moral condemnation also regards procedures that exploit living human embryos and fetuses — sometimes ‘produced’ for this purpose by in vitro fertilization [IVF] — either to be used as ‘biological material’ or as providers of organs or tissue for transplants in the treatment of certain diseases.

“The killing of innocent human creatures, even if carried out to help others, constitutes an absolutely unacceptable act.”

“An ethical Rubicon was crossed when the first in vitro fertilization-conceived baby came into the world in 1978,” said Father Pacholczyk, a former research scientist who has a doctoral degree in neuroscience from Yale University. “Recent developments have exacerbated this situation, by offering additional options and choices for generating children, recasting human embryos as modular constructs to be assembled through technologies like cloning or the creation of three-parent embryos.”

 

Permissive Britain

The U.K. has long been at the forefront of assisted reproductive procedures and research, witnessing the birth of Louise Joy Brown, the world’s first child conceived through an IVF procedure, on July 25, 1978. Brown married in 2004 and now has two sons, both conceived without IVF.

However, other specialists, like John Aitken, laureate professor at the University of Newcastle, Australia, argue that IVF is producing infertile children and leaves some male children at high risk of cancer.

Why has the U.K. been so permissive in its approach to embryo research?

MacKellar says the cause is in a lack of education and hangovers from the old British class system.

“One of the reasons is the lack of education amongst the general public, who have always tended to trust the ‘ruling classes’ on these topics, which has its origins in the aristocracy. The class system in the U.K. is far more present than in other developed countries.”

“Many in the U.K. are also proud of being ‘pragmatic,’” he added, “though this is actually only ‘lazy ethics,’ suggesting that what is possible and useful is automatically ethical.”

 

Register correspondent Daniel Blackman writes from London.