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 It’s a boy! A five-month-old boy is the first baby to be born using a new technique that incorporates DNA from three people, New Scientist can reveal. “This is great news and a huge deal,” says Dusko Ilic at King’s College London, who wasn’t involved in the work. “It’s revolutionary.” 
 
 The controversial technique, which allows parents with rare genetic mutations to have healthy babies, has only been legally approved in the UK. But the birth of the child, whose Jordanian parents were treated by a US-based team in Mexico, should fast-forward progress around the world, say embryologists. 
 
 The boy’s mother carries genes for Leigh syndrome, a fatal disorder that affects the developing nervous system. Genes for the disease reside in DNA in the mitochondria, which provide energy for our cells and carry just 37 genes that are passed down to us from our mothers. This is separate from the majority of our DNA, which is housed in each cell’s nucleus. 
 
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 Around a quarter of her mitochondria have the disease-causing mutation. While she is healthy, Leigh syndrome was responsible for the deaths of her first two children. The couple sought out the help of John Zhang and his team at the New Hope Fertility Center in New York City. 
 
 Zhang has been working on a way to avoid mitochondrial disease using a so-called “three-parent” technique. In theory, there are a few ways of doing this. The method approved in the UK is called pronuclear transfer and involves fertilising both the mother’s egg and a donor egg with the father’s sperm. Before the fertilised eggs start dividing into early-stage embryos, each nucleus is removed. The nucleus from the donor’s fertilised egg is discarded and replaced by that from the mother’s fertilised egg. 
 
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 But this technique wasn’t appropriate for the couple – as Muslims, they were opposed to the destruction of two embryos. So Zhang took a different approach, called spindle nuclear transfer. He removed the nucleus from one of the mother’s eggs and inserted it into a donor egg that had had its own nucleus removed. The resulting egg – with nuclear DNA from the mother and mitochondrial DNA from a donor – was then fertilised with the father’s sperm. 
 
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 Zhang’s team used this approach to create five embryos, only one of which developed normally. This embryo was implanted in the mother and the child was born nine months later. “It’s exciting news,” says Bert Smeets at Maastricht University in the Netherlands. The team will describe the findings at the American Society for Reproductive Medicine’s Scientific Congress in Salt Lake City in October. 
 
 Neither method has been approved in the US, so Zhang went to Mexico instead, where he says “there are no rules”. He is adamant that he made the right choice. “To save lives is the ethical thing to do,” he says. 
 
 The team seems to have taken an ethical approach with their technique, says Sian Harding, who reviewed the ethics of the UK procedure. The team avoided destroying embryos, and used a male embryo, so that the resulting child wouldn’t pass on any inherited mitochondrial DNA. “It’s as good as or better than what we’ll do in the UK,” says Harding. 
 
 A remaining concern is safety. Last time embryologists tried to create a baby using DNA from three people was in the 1990s, when they injected mitochondrial DNA from a donor into another woman’s egg, along with sperm from her partner. Two of the fetuses developed genetic disorders, and the technique was halted by the US Food and Drug Administration. The problem may have arisen from the fetuses having mitochondria from two sources. 
 
 When Zhang and his colleagues tested the boy’s mitochondria, they found that less than 1 per cent carry the mutation. Hopefully, this is too low to cause any problems; generally it is thought to take around 18 per cent of mitochondria to be affected before problems start. “It’s very good,” says Ilic. 
 
 Smeets agrees, but cautions that the team should monitor the child to make sure the levels stay low. There’s a chance that faulty mitochondria could be better at replicating, and gradually increase in number, he says. “We need to wait for more births, and to carefully judge them,” says Smeets. 
 
 Two women, one man and a baby A Jordanian couple has been trying to start a family for almost 20 years. Ten years after they married, she became pregnant, but it ended in the first of four miscarriages. In 2005, the couple gave birth to a baby girl. It was then that they discovered the probable cause of their fertility problems: a genetic mutation in the mother’s mitochondria. Their daughter was born with Leigh syndrome, which affects the brain, muscles and nerves of developing infants. Sadly, she died aged six. The couple’s second child had the same disorder, and lived for 8 months. Using a controversial “three-parent baby” technique (see main story), the boy was born on 6 April 2016. He is showing no signs of disease. 
 
 At the clinic’s request we have removed the names of the family The story has been updated to clarify that it was fetuses that developed genetic disorders in the 1990s ||||| The world's first "three parent baby" was born five months ago to Jordanian parents. The treatment, which seeks to avoid mothers passing defective mitochondrial DNA to their offspring, was performed in Mexico. 
 
 The news, revealed by the New Scientist, is already hailed as revolutionary advance in the field of reproductive medicine. The procedure - based on a new In vitro fertilisation technique that incorporates DNA from three parents - was necessary because the baby's mother carries mitochondrial DNA mutations for Leigh syndrome, a fatal neurological disorder. 
 
 Because of this, she and her husband had already lost two children, so they asked a US-based team of scientists – at New Hope Fertility Center in New York City – for their help. The doctors, led by John Zhang, designed a new "three-parent" technique. 
 
 The traditional way to do this is to use a method known as pronuclear transfer, which involves fertilising both the mother's egg and a donor's egg with the father's sperm. When both eggs start dividing into early-stage embryos, scientists remove the nucleus. The nucleus from the donor's egg is discarded, and the one from the mother is inserted in its place. This is the technique that was legally approved in the UK in 2015. 
 
 However, the couple rejected this technique for religious reasons – they didn't want an embryo to be discarded. Thus, another "three parent" technique, known as spindle nuclear transfer, was used: the nucleus was first removed from the mother's egg and inserted into a donor's egg, after removing its own nucleus. Only then was the resulting egg fertilised with the father's sperm. 
 
 The complete findings will be presented at the American Society for Reproductive Medicine's Scientific Congress in Salt Lake City in October, but already it represents a huge step forward for a technique that has often attracted a lot of heated debates. 
 
 The idea of three parent babies previously sparked criticism from some groups, which claimed it could pave the way for "designer babies". At the time of its approval in the UK, England's chief medical officer Dame Sally Davies commented: "The intention in making these regulations is to ensure that mothers who carry faulty mitochondria can have healthy children free from devastating and often deadly conditions caused by serious mitochondrial disease. 
 
 "It is important to remember that mitochondrial DNA represents less than 0.054 per cent of the total DNA, and is not part of the nuclear DNA, which determines our personal characteristics and traits such as personality, hair and eye colour." ||||| A promising technique to prevent mothers from passing on devastating mitochondrial diseases was thrown a biological curve ball this week: A paper published Wednesday in Nature shows that such diseases can come back to sicken a child, even when 99 percent of the mother’s own mitochondria are eliminated. 
 
 Mitochondria are the tiny power plants that provide the energy every cell needs to function. When a large percentage of these organelles malfunction, cells cannot do their jobs—and everything from weakness to death can result. Mothers with certain conditions may have such low levels of faulty mitochondria that they have no symptoms, but their kids can inherit a higher burden of these defective mitochondria, leading to devastating illness. 
 
 In attempt to combat this problem, researchers have essentially been—as one doctor described it—taking the “yellow part” of a mother’s egg and inserting it into the “white” of a donor’s egg. Because the child ends up with DNA from its mother, father and a donor, this mitochondrial replacement therapy has been nicknamed the “three-parent baby” technique. An apparently healthy boy was born using the approach in April in Mexico. He carries about 1 percent of his mother’s mitochondria, which if allowed to pass to him in full might have caused Leigh syndrome, a severe neurological disorder that is generally fatal in early childhood. His parents had two previous children who died of the disease, one at age 6 and one at 8 months, New Scientist reported. 
 
 But the new laboratory study shows that the mother’s mitochondria can sometimes replicate faster than the donor’s and come to dominate again, potentially bringing disease with it. Still, that effect is likely to be rare, says Shoukhrat Mitalipov, the developmental biologist who led the research and has used the technique on mice and monkeys, reportedly without seeing any health problems. Mitalipov and Paula Amato, a reproductive endocrinologist also at Oregon Health & Science University in Portland, said at a news conference that they think mitochondrial replacement therapy should be tested in a clinical trial—despite concerns about the mother’s defective mitochondrial DNA making a comeback. “Because these diseases are so debilitating and often fatal and there are no cures, we think it’s still worth trying to move this research forward to prevent those diseases if we can,” Amato says. Congress currently bans such three-parent procedures for clinical use in the United States, but the United Kingdom has approved a similar technique that would allow even more of the mother’s mitochondria to be passed on to the child and a trial could likely be conducted there, Mitalipov says. 
 
 Although mitochondrial diseases are fairly rare, affecting about one in 5,000 children, Mitalipov and Amato say the three-parent technique could theoretically also be used to treat infertility and help with some stem cell treatments. Mitochondria (which have their own DNA, separate from the DNA in a cell’s nucleus) are inherited solely from the mother. Some consider the three-parent procedure controversial because of this mix of DNA, and because scientists worldwide have agreed to avoid making changes to human genetic inheritance. 
 
 A number of experts have also argued that mitochondrial replacement therapy is too little understood to try in people. Klaus Reinhardt, an evolutionary biologist and zoologist at Germany’s Technische Universität Dresden, thinks the mismatch between the donor’s mitochondrial DNA and mother’s nuclear DNA could cause mitochondrial problems in about one in 50 children born using the three-parent process. Inherited together, the nuclear and mitochondrial DNA can resolve each other’s defects. But when they come from different people, this mismatch can create problems for the child, says Reinhardt, who was not involved in the new research. The human genome, he explains, has 6 billion pairs of DNA and mitochondria have about 16,000, making it very challenging to predict their interactions. “We have no idea who ‘talks’ with whom,” he says. 
 
 Dan Mishmar, a mitochondrial evolutionist and geneticist atBen-Gurion University in Israel, who was not involved in the new study, says his own research shows large differences between the mitochondrial genomes of Africans and Caucasians. When the parents’ DNA match their mitochondrial DNA, these gaps don’t matter, he says. But he worries about taking the mitochondrial DNA “out of context” when the donor and the mother have very different ethnic and racial backgrounds. Like Reinhardt, he worries that the DNA mixture itself could cause illness. “If you reduce the compatibility, you increase the susceptibility to complex disabilities, such as diabetes, Parkinson’s and … Alzheimer’s. That’s the thing we are afraid of.” But Mitalipov believes such problems can largely be avoided by matching the mitochondrial DNA of the mother with that of the donor, in much the same way that organ donors are matched to recipients by immune type. 
 
 Juan Carlos Izpisua Belmonte, a stem cell scientist at the Salk Institute in California who worked on the paper with Mitalipov, suggests an additional way to reduce the risks. He says his lab has developed a technique to cull mutant mitochondria from a mother’s egg before its nucleus is transferred to the donor’s. Reducing levels of the dangerous mitochondria should limit the number that reach the child, he adds. 
 
 For the new study, four women whose children had mitochondrial diseases underwent hormone therapy typically used for in vitro fertilization and provided eggs. Researchers took the DNA from the nucleus of these egg cells and transferred it into donor egg cells whose nuclei had been removed, a process called spindle transfer. The eggs with the mother’s nuclear DNA and the donor’s mitochondrial DNA were fertilized and allowed to divide and grow for five days. Then the embryos were turned into embryonic stem cells, ending their potential for development. These stem cells were transformed into brain, heart and other types of cells to see how their mitochondria would behave. In cells from one mother, the mitochondria reverted to the mutant type that she carried before the spindle transfer. 
 
 Although the new study raises questions about the safety of mitochondrial replacement therapy, Belmonte says it should also quell any fears that the research is moving too quickly. “We have to be convinced in the laboratory that we have done every possible experiment to make sure this is safe—as safe as we can [make it],” he says. “This is a wonderful way to avoid diseases, but we found a problem and we need to make sure we have ways to minimize or solve that problem before we go into the clinic.” ||||| SiYi Qian/Getty 
 
 The first babies to be created using a “three-parent” method to overcome their parents’ infertility are due to be born in early 2017. New Scientist has learned that two women in Ukraine are both more than 20 weeks pregnant with fetuses created using such a technique. 
 
 The babies would be the first born to women who had the procedure to treat infertility, rather than to prevent hereditary disease, but some have criticised this approach, calling for it to be banned until there is more evidence that the embryos it creates are healthy. 
 
 The technique used is the same as that approved last year by the UK parliament – the only country in the world to legalise the procedure – although there it is allowed only to prevent parents passing hereditary diseases to their children. 
 
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 No three-parent babies have been born in the UK yet, but a handful have been born elsewhere. Last month, New Scientist exclusively revealed that a Jordanian couple had had a healthy baby after using a new three-parent technique. 
 
 In Ukraine, the UK-approved method was used to overcome embryo arrest, which happens when IVF embryos suddenly stop growing at around the two-cell stage, says Valery Zukin, director of the Clinic of Reproductive Medicine in Kiev. 
 
 “One, a girl, has now reached 26 weeks, and a boy has reached 20 weeks,” Zukin told New Scientist. He says his team is due to present their preliminary results at the American Reproductive Technology Congress in New York later this week. 
 
 Too risky? 
 
 Zukin’s team used a technique called pro-nuclear transfer. In each case, they fertilised both the mother’s egg and the egg of a donor with sperm from the husband. Then, using a fine needle, they extracted the “pronucleus” from the mother’s fertilised egg – the cell body that contains the chromosomes of both the mother and father. This was then used to replace the pronucleus in the fertilised donor egg, creating an embryo that had a full set of chromosomes from the parents, but potentially healthier cellular machinery around it. 
 
 The idea is that there are factors within a cell’s cytoplasm that can help or hinder fertility – such as enzymes that help cells grow and divide. By placing the pronucleus into a cell that was created using the egg of a different woman, the hope is that whatever caused the embryo arrest can be avoided. 
 
 But Dean Betts at Western University in Canada says the reasons why embryos arrest are poorly understood. While we can hypothesise why [the process] works, “it doesn’t mean the underlying reason why the embryo arrested in the first place is gone, possibly allowing development of an abnormal embryo”, he says. 
 
 “I think it’s too risky,” says Betts. “More research is needed, and I highly recommend banning this procedure in humans as we don’t know enough to ensure its safety.” 
 
 Zukin says the procedure was first approved by an ethical committee and a review board at the Ukrainian Association of Reproductive Medicine. Early DNA tests – including some conducted by an independent laboratory in Germany – have shown that the two babies are genetically healthy, he says. Zukin is also waiting before repeating the procedure. “Some patients are awaiting similar embryo transfers, but we would like to be sure first that the babies are born healthy,” he says. 
 
 Ethical issues 
 
 Zukin isn’t the first to try using such a method to treat infertility related to embryo arrest. John Zhang at the New Hope Fertility Center in New York, who treated the Jordanian couple, attempted a similar procedure in 2003 and recently published an account of his results (Reproductive Biomedicine Online, DOI: 10.1016/j.rbmo.2016.07.008). 
 
 While his team were able to produce three healthy fetuses, carried in a single pregnancy by the same woman, they all died. One fetus was removed at 33 days, to relieve the pressure of bearing triplets, but the remaining two then died at 24 and 29 weeks respectively, due to rupturing membranes and umbilical cord prolapse. 
 
 But Zhang’s analysis of fetal tissue revealed they all had normal chromosomes, leading his team to conclude that the technique could potentially be used to overcome embryo arrest. 
 
 Extending three-parent techniques to treating infertility raises ethical questions. If they work, they will dramatically increase the number of prospective parents who could benefit from mitochondrial transfer. An estimated 50 per cent of IVF procedures fail because embryos stop growing before they can be implanted. 
 
 A key argument considered in the UK parliament last year was that, for women with serious mutations in their mitochondria, there are no other possible treatments. But there are already many options for treating infertility, meaning some may be less happy to see it used for this purpose. 
 
 “There is much debate, and indeed, much pressure from the fertility world to get this treatment accepted,” says Bert Smeets at Maastricht University in the Netherlands. “It’s obvious that the fertility market is much bigger than the group of patients with mitochondrial disease.” 
 
 The DOI to Zhang’s study has been corrected
– A 5-month-old born using a "revolutionary" genetic technique is said to be the world's first baby created using DNA from three parents since the technique was banned about two decades ago, New Scientist reports. The boy, IDed by the International Business Times as Abrahim Hassan, was born in Mexico to Jordanian parents, and embryologists are hoping his successful birth will hasten using the procedure elsewhere. Abrahim's mother, Shaban, carries the gene for Leigh syndrome—a severe neurological condition that decimates mental and physical capabilities and often results in a child's death before kindergarten. Although Hassan herself is healthy, her first two children died from the disease. That's when she and her husband looked for assistance from NYC's New Hope Fertility Center, where a team led by Dr. John Zhang started them off on an alternative way to parenthood. There are a couple of different ways to pull off the three-parent technique, but the one they chose to go with is called spindle nuclear transfer, in which the nucleus from the mother's egg is placed in a donor egg whose own nucleus has been taken out; that egg, which then contains nuclear DNA from the mom and mitochondrial DNA from the donor, is fertilized with the father's sperm. Five embryos were created in this case, and when just one "took," it was implanted into Hassan, who delivered Abrahim nine months later. This all had to be done in Mexico, where Zhang says "there are no rules" (the Times labels it "relatively flexible legislation"; the procedure isn't approved in the US). One concern scientists are keeping an eye on: faulty mitochondria that could replicate, a problem that may have occurred when the technique was last tried in the '90s. (The UK has OKed a controversial gene-editing method.)