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 fewer than five UK children had been born using the procedure as of April 2023. The confirmation came 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), which was legalized in the United Kingdom in 2015, is intended to prevent the inheritance of serious health conditions caused by mutations to mitochondria, cells’ energy-producing organelles; such mutations often affect the heart, brain and muscles.

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, says 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 risk could arise 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 increase markedly 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 that came 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 the donor egg or embryo, says Wells. If so, it might be worth matching donor and recipient on the basis of similarities in their mitochondrial DNA, he adds; this would potentially reduce the ability of one lineage to out-replicate another.

There may be other ways to prevent reversal, says Shoukhrat Mitalipov, a reproductive biologist at the Oregon Health & Science University in Portland who was part of the infertility trial. In the five children who gained nearly all their mitochondria from a donor, the researchers had frozen the mother’s eggs before transferring the nuclear genetic material 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 the 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 fewer than five UK children had been born using the procedure as of April 2023. The confirmation came 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), which was legalized in the United Kingdom in 2015, is intended to prevent the inheritance of serious health conditions caused by mutations to mitochondria, cells’ energy-producing organelles; such mutations often affect the heart, brain and muscles. 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, says 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 risk could arise 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 increase markedly 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 that came 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 the donor egg or embryo, says Wells. If so, it might be worth matching donor and recipient on the basis of similarities in their mitochondrial DNA, he adds; this would potentially reduce the ability of one lineage to out-replicate another. There may be other ways to prevent reversal, says Shoukhrat Mitalipov, a reproductive biologist at the Oregon Health & Science University in Portland who was part of the infertility trial. In the five children who gained nearly all their mitochondria from a donor, the researchers had frozen the mother’s eggs before transferring the nuclear genetic material 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 the 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:

{'MRT': 'Mitochondrial replacement therapy的缩写，指的是线粒体替换疗法，是一种用于预防线粒体突变引起的严重健康问题的生殖技术','HFEA': 'Human Fertilisation and Embryology Authority的缩写，指的是英国的生殖和胚胎学监管机构','IVF': 'In vitro fertilization的缩写，指的是体外受精','reversal': '反转，指的是线粒体DNA从母体卵子或胚胎中转移到供体卵子或胚胎中，而供体卵子或胚胎中的线粒体DNA会受到母体卵子或胚胎中线粒体DNA的影响，从而导致线粒体DNA的反转','mitochondria': '线粒体，指的是细胞能量生产器官，线粒体突变经常影响心脏、大脑和肌肉','nuclear genetic material': '核基因材料，指的是从卵子或单细胞胚胎中移动的核基因材料，用于替换具有疾病引起的线粒体的卵子或胚胎','replication': '复制，指的是线粒体DNA从母体卵子或胚胎中转移到供体卵子或胚胎中，而供体卵子或胚胎中的线粒体DNA会受到母体卵子或胚胎中线粒体DNA的影响，从而导致线粒体DNA的复制','fertility': '生育力，指的是一个人或一对夫妇的生育能力','umbilical cord': '脐带，指的是胎儿与母体之间的连接，由胎儿的脐带细胞和母体的血管组成','phenomenon': '现象，指的是一种现象，可以通过观察或实验来观察和研究','bottleneck': '瓶颈，指的是一种现象，当某一系统的负荷超过它的处理能力时，就会出现瓶颈现象','oversight': '监督，指的是对某一系统的监督，以确保其正常运行','pluses': '优点，指的是某一系统的优点，即它具有的有利条件','minuses': '缺点，指的是某一系统的缺点，即它具有的不利条件'} 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）的过程，以及研究人员对英国程序的关注，以及英国对允许该程序的谨慎方法。'}""" long_sentences:

{'sentence 1': 'Mitochondrial replacement therapy (MRT), which was legalized in the United Kingdom in 2015, is intended to prevent the inheritance of serious health conditions caused by mutations to mitochondria, cells’ energy-producing organelles; such mutations often affect the heart, brain and muscles.', 'sentence 2': '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 that came 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.'}

Sentence 1：Mitochondrial replacement therapy (MRT)，2015年英国合法化，旨在防止线粒体突变引起的严重健康问题的遗传，线粒体是细胞能量生产器，这种突变经常影响心脏，大脑和肌肉。句子结构：主语+谓语+定语从句+宾语+定语从句+宾语。句子语义：讲述了线粒体替换治疗的定义，以及它的用途。

Sentence 2：而且这种情况也可能发生在人类身上。今年，Wells和他的同事们在希腊的一项25对夫妇的不孕治疗试验中观察到了反转。六个孩子中，五个的线粒体DNA几乎完全来自于供体，从血液，脐带和其他组织中提取的细胞。然而，一个孩子的细胞中有大量的线粒体来自母亲——占总数的30-60％。当胚胎植入时，其线粒体中只有不到1％来自母亲的卵子2。句子结构：主语+谓语+定语从句+宾语+定语从句+宾语+定语从句+宾语+定语从句+宾语+定语从句+宾语+定语从句+宾语。句子语义：讲述了Wells和他的同事们在希腊的一项不孕治疗试验中观察到的反转情况，以及其中一个孩子的细胞中有大量的线粒体来自母亲的情况。