Eight years after the United Kingdom became the first country to regulate the reproductive technique known as mitochondrial replacement, news has emerged that children have been born using the procedure.

The Human Fertilisation and Embryology Authority (HFEA), the UK fertility regulator, confirmed that “less than five” UK children had been born using the procedure as of April 2023, in response to a freedom of information request by The Guardian newspaper. The HFEA provided no further information about the procedure or the children.

“It’s exciting news, but at the same time it doesn’t tell us anything about whether the method has actually worked,” says Dagan Wells, a reproductive geneticist at the University of Oxford, UK. “There are open questions, and we need to get answers as soon as possible.”

Mitochondrial replacement therapy (MRT) is intended to prevent the inheritance of serious health conditions caused by mutations to mitochondria, cells’ energy producing organelles, often affecting the heart, brain and muscles, and was legalized in the United Kingdom 2015.

The procedure — sometimes called three-person in vitro fertilization (IVF) — involves moving nuclear genetic material from an egg or single-cell embryo with disease-causing mitochondria to a donor egg or embryo that has had its nuclear genetic material removed.

Grey regulation

The procedure has been performed in other countries where its use is not regulated. In 2016, a US doctor announced that he had used MRT successfully to prevent mitochondrial disease in a baby, in a procedure conducted in Mexico. Children have also been born through mitochondrial transfers conducted in Greece and Ukraine to treat infertility. Last year, Australia became the second country to approve MRT. But the procedure remains restricted in many other countries, including the United States.

The mitochondrial transfers uncovered by The Guardian were done at the Newcastle Fertility Centre, the only UK clinic with a licence to conduct MRT. Under current regulations, the HFEA must approve each use on a case-by-case basis.

Researchers are anxious to learn more from the UK procedures as they start to conduct their own trials. “If there are any negative things to be considered, we need to know about those sooner rather than later,” says Wells.

Knowing how well the procedures worked and whether the babies are free of mitochondrial disease is crucial, according to Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London, who gave a statement to the UK Science Media Centre. Lovell-Badge also wants to know “whether there is any risk of them developing problems later in life or, if female, if their offspring are at risk of having the disease.”

This might happen during the procedure, when inevitably a small number of mitochondria are transferred into the donor egg or embryo. Wells wants to know the extent of this ‘carry-over’ in the UK cases and whether or not very low levels of mutation-bearing mitochondria cause health problems.

Mutant mitochondria

Scientists also want to know whether the levels of mutant mitochondria that are transferred remain stable over time. Animal and cell studies have found that in some cases the carried-over mitochondria can dramatically increase over time, replacing donor mitochondria in cells, a phenomenon known as reversal ¹ .

And this can happen in humans. This year, Wells and his colleagues observed reversal after using MRT to treat infertility in a trial of 25 couples in Greece. Of the 6 children born, 5 had mitochondrial DNA almost entirely from the donor in cells from blood, umbilical cord and other tissues sampled. However, one child’s cells had high levels of mitochondria inherited from the mother — 30–60% of the total. When the embryo was implanted, less than 1% of its mitochondria were carried over from the maternal egg ² .

The reversal seems to have had no effect on the child’s health. “If we had been doing the same procedure to avoid a mitochondrial DNA disorder, then this might be a cause for concern,” says Wells. “So that’s a big question we have: has any reversal been seen in any of these children?”

It’s not clear why the proportion of potentially disease-causing mitochondria can increase so dramatically after mitochondrial transfer and during development. One possibility, is that genetic factors enable the maternal mitochondrial lineage to replicate more efficiently than mitochondria in donor egg or embryo, says Wells. If this is the case, then it might be worth matching the donor and recipient based on similarities in their mitochondrial DNA, he adds, potentially reducing the ability of one lineage to out-replicate another.

There may be other ways to prevent reversal, says Shoukrhat Mitalipov, a reproductive biologist at the Oregon Health & Science University in Portland who was part of the infertility trial. In the 5 children that gained nearly all their mitochondria from a donor, the researchers froze the mother’s eggs and transferred them into fresh donor eggs. Both eggs were fresh during the transfer that created the child in which reversal occurred. “We’re still puzzled as to whether freezing mother’s egg is actually beneficial,” he says.

The first UK births from MRT also provide an opportunity to take stock of the country’s cautious approach to allowing the procedure.

“It gives the general public some reassurance that these kinds of cutting-edge procedures — which push scientific but also ethical boundaries — are being done with appropriate oversight,” says Wells. But the fact that just one UK clinic can perform MRT has probably created a bottleneck for treatment, he adds. “There are pluses and minuses.”

article_text: Eight years after the United Kingdom became the first country to regulate the reproductive technique known as mitochondrial replacement, news has emerged that children have been born using the procedure. The Human Fertilisation and Embryology Authority (HFEA), the UK fertility regulator, confirmed that “less than five” UK children had been born using the procedure as of April 2023, in response to a freedom of information request by The Guardian newspaper. The HFEA provided no further information about the procedure or the children. “It’s exciting news, but at the same time it doesn’t tell us anything about whether the method has actually worked,” says Dagan Wells, a reproductive geneticist at the University of Oxford, UK. “There are open questions, and we need to get answers as soon as possible.” Mitochondrial replacement therapy (MRT) is intended to prevent the inheritance of serious health conditions caused by mutations to mitochondria, cells’ energy producing organelles, often affecting the heart, brain and muscles, and was legalized in the United Kingdom 2015. The procedure — sometimes called three-person in vitro fertilization (IVF) — involves moving nuclear genetic material from an egg or single-cell embryo with disease-causing mitochondria to a donor egg or embryo that has had its nuclear genetic material removed. The procedure has been performed in other countries where its use is not regulated. In 2016, a US doctor announced that he had used MRT successfully to prevent mitochondrial disease in a baby, in a procedure conducted in Mexico. Children have also been born through mitochondrial transfers conducted in Greece and Ukraine to treat infertility. Last year, Australia became the second country to approve MRT. But the procedure remains restricted in many other countries, including the United States. The mitochondrial transfers uncovered by The Guardian were done at the Newcastle Fertility Centre, the only UK clinic with a licence to conduct MRT. Under current regulations, the HFEA must approve each use on a case-by-case basis. Researchers are anxious to learn more from the UK procedures as they start to conduct their own trials. “If there are any negative things to be considered, we need to know about those sooner rather than later,” says Wells. Knowing how well the procedures worked and whether the babies are free of mitochondrial disease is crucial, according to Robin Lovell-Badge, a developmental biologist at the Francis Crick Institute in London, who gave a statement to the UK Science Media Centre. Lovell-Badge also wants to know “whether there is any risk of them developing problems later in life or, if female, if their offspring are at risk of having the disease.” This might happen during the procedure, when inevitably a small number of mitochondria are transferred into the donor egg or embryo. Wells wants to know the extent of this ‘carry-over’ in the UK cases and whether or not very low levels of mutation-bearing mitochondria cause health problems. Scientists also want to know whether the levels of mutant mitochondria that are transferred remain stable over time. Animal and cell studies have found that in some cases the carried-over mitochondria can dramatically increase over time, replacing donor mitochondria in cells, a phenomenon known as reversal1. And this can happen in humans. This year, Wells and his colleagues observed reversal after using MRT to treat infertility in a trial of 25 couples in Greece. Of the 6 children born, 5 had mitochondrial DNA almost entirely from the donor in cells from blood, umbilical cord and other tissues sampled. However, one child’s cells had high levels of mitochondria inherited from the mother — 30–60% of the total. When the embryo was implanted, less than 1% of its mitochondria were carried over from the maternal egg2. The reversal seems to have had no effect on the child’s health. “If we had been doing the same procedure to avoid a mitochondrial DNA disorder, then this might be a cause for concern,” says Wells. “So that’s a big question we have: has any reversal been seen in any of these children?” It’s not clear why the proportion of potentially disease-causing mitochondria can increase so dramatically after mitochondrial transfer and during development. One possibility, is that genetic factors enable the maternal mitochondrial lineage to replicate more efficiently than mitochondria in donor egg or embryo, says Wells. If this is the case, then it might be worth matching the donor and recipient based on similarities in their mitochondrial DNA, he adds, potentially reducing the ability of one lineage to out-replicate another. There may be other ways to prevent reversal, says Shoukrhat Mitalipov, a reproductive biologist at the Oregon Health & Science University in Portland who was part of the infertility trial. In the 5 children that gained nearly all their mitochondria from a donor, the researchers froze the mother’s eggs and transferred them into fresh donor eggs. Both eggs were fresh during the transfer that created the child in which reversal occurred. “We’re still puzzled as to whether freezing mother’s egg is actually beneficial,” he says. The first UK births from MRT also provide an opportunity to take stock of the country’s cautious approach to allowing the procedure. “It gives the general public some reassurance that these kinds of cutting-edge procedures — which push scientific but also ethical boundaries — are being done with appropriate oversight,” says Wells. But the fact that just one UK clinic can perform MRT has probably created a bottleneck for treatment, he adds. “There are pluses and minuses.” vocabulary:

{'Mitochondrial replacement therapy (MRT)': '线粒体替换疗法（MRT）：旨在防止线粒体突变引起的严重健康状况的遗传，通常影响心脏、大脑和肌肉，并于2015年在英国合法化', 'In vitro fertilization (IVF)': '体外受精（IVF）：将精子和卵子在实验室中混合，以制造受精卵的过程', 'Reversal': '逆转：细胞中携带突变线粒体的比例会随着时间的推移急剧增加，取代供体线粒体的现象', 'Mitochondria': '线粒体：细胞能量生产器官，可以产生细胞所需的能量', 'Embryo': '胚胎：受精卵发育的早期阶段', 'Umbilical cord': '脐带：胎儿与母体连接的结构，由血管和组织组成', 'Nuclear genetic material': '核遗传物质：指染色体上的基因', 'Mutation-bearing mitochondria': '携带突变线粒体：指携带突变的线粒体', 'Donor egg or embryo': '供体卵子或胚胎：指提供给接受者的卵子或胚胎', 'Freedom of information request': '信息自由请求：指公民向政府机构请求公开信息的权利', 'Case-by-case basis': '按照案件：指每个案件都要单独审查', 'Replicate': '复制：指复制或重复某种行为', 'Umbilical': '脐带：胎儿与母体连接的结构，由血管和组织组成', 'Lineage': '血统：指一个物种的祖先和后代', 'Implant': '植入：将植物或物体植入某个地方', 'Infertility': '不孕：指一对夫妇无法自然受孕的状况', 'Oversight': '监督：指对某种行为的监督和管理', 'Bottleneck': '瓶颈：指某种行为受到限制的状况', 'Appropriate': '适当：指某种行为是合适的', 'Cutting-edge': '尖端：指最先进的技术', 'Ethical': '伦理：指道德行为', 'Phenomenon': '现象：指某种现象或现象', 'Genetic factors': '遗传因素：指影响基因表达的因素', 'Replicate more efficiently': '更有效地复制：指复制或重复某种行为的效率', 'Reassurance': '保证：指某种行为的保证'} readguide:

"""{'reading_guide': '本文讲述了英国成为第一个调控线粒体替换技术的国家八年后，已经有孩子出生使用该程序的消息。文章探讨了线粒体替换治疗（MRT）的意图，以及它在其他国家的使用情况，以及研究人员如何从英国的程序中获得更多信息。文章还探讨了英国对允许该程序的谨慎方法。'}""" long_sentences:

{'sentence 1': 'Mitochondrial replacement therapy (MRT) is intended to prevent the inheritance of serious health conditions caused by mutations to mitochondria, cells’ energy producing organelles, often affecting the heart, brain and muscles, and was legalized in the United Kingdom 2015.', 'sentence 2': 'The first UK births from MRT also provide an opportunity to take stock of the country’s cautious approach to allowing the procedure.'}

Sentence 1: 米糖体替换疗法（MRT）旨在预防由线粒体突变引起的严重健康状况的遗传，线粒体是细胞的能量产生器官，通常会影响心脏，大脑和肌肉，并于2015年在英国合法化。

句子1的句子结构：主语+谓语+定语+宾语+状语。

句子1的语义：句子1描述了米糖体替换疗法（MRT）的目的，即预防由线粒体突变引起的严重健康状况的遗传，并且该疗法已经在英国合法化。

Sentence 2: 第一次英国MRT出生也为该国允许该程序的谨慎方法提供了一个机会。

句子2的句子结构：主语+谓语+宾语+定语+状语。

句子2的语义：句子2描述了英国MRT出生提供了一个机会，即评估英国允许该程序的谨慎方法。