text: 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." ||||| Leigh syndrome can be caused by mutations in one of more than 75 different genes. In humans, most genes are found in DNA in the cell's , called nuclear DNA. However, some genes are found in DNA in specialized structures in the cell called . This type of DNA is known as mitochondrial DNA (mtDNA). While most people with Leigh syndrome have a mutation in nuclear DNA, about 20 percent have a mutation in mtDNA. 
   
   Most genes associated with Leigh syndrome are involved in the process of energy production in mitochondria. Mitochondria use oxygen to convert the energy from food into a form cells can use through a process called . Five protein complexes, made up of several proteins each, are involved in this process. The complexes are named complex I, complex II, complex III, complex IV, and complex V. During oxidative phosphorylation, the protein complexes drive the production of adenosine triphosphate (ATP), the cell's main energy source, through a step-by-step transfer of negatively charged particles called electrons. Many of the gene mutations associated with Leigh syndrome affect proteins in these complexes or disrupt their assembly. These mutations reduce or eliminate the activity of one or more of these complexes, which can lead to Leigh syndrome. 
   
   Disruption of complex I, also called NADH:ubiquinone oxidoreductase, is the most common cause of Leigh syndrome, accounting for nearly one third of cases of the condition. At least 25 genes involved in the formation of complex I, found in either nuclear or mitochondrial DNA, have been associated with Leigh syndrome. 
   
   Disruption of complex IV, also called cytochrome c oxidase or COX, is also a common cause of Leigh syndrome, underlying approximately 15 percent of cases. One of the most frequently mutated genes in Leigh syndrome is SURF1. This gene, which is found in nuclear DNA, provides instructions for making a protein that helps assemble the COX protein complex (complex IV). This complex, which is involved in the last step of electron transfer in oxidative phosphorylation, provides the energy that will be used in the next step of the process to generate ATP. Mutations in the SURF1 gene typically lead to an abnormally short SURF1 protein that is broken down in cells, resulting in the absence of functional SURF1 protein. The loss of this protein reduces the formation of normal COX complexes, which impairs mitochondrial energy production. 
   
   The most common mtDNA mutation in Leigh syndrome affects the MT-ATP6 gene, which provides instructions for making a piece of complex V, also known as the . Using the energy provided by the other protein complexes, the ATP synthase complex generates ATP. MT-ATP6 gene mutations, found in approximately 10 percent of people with Leigh syndrome, block the generation of ATP. Other mtDNA mutations associated with Leigh syndrome decrease the activity of other oxidative phosphorylation protein complexes or lead to reduced formation of mitochondrial proteins, all of which impair mitochondrial energy production. 
   
   Other gene mutations associated with Leigh syndrome decrease the activity of one or more oxidative phosphorylation protein complexes or affect additional steps related to energy production. For example, Leigh syndrome can be caused by mutations in genes that form the pyruvate dehydrogenase complex or coenzyme Q10, both of which are involved in mitochondrial energy production. Mutations in genes that direct the replication of mtDNA or the production of mitochondrial proteins can also disrupt mitochondrial energy production. 
   
   Although the exact mechanism is unclear, researchers believe that impaired oxidative phosphorylation can lead to cell death because of decreased energy available in the cell. Certain tissues that require large amounts of energy, such as the brain, muscles, and heart, seem especially sensitive to decreases in cellular energy. Cell death in the brain likely causes the characteristic lesions seen in Leigh syndrome, which contribute to the signs and symptoms of the condition. Cell death in other sensitive tissues may also contribute to the features of Leigh syndrome. ||||| Blackout Concepts/Alamy 
   
   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. 
   
   Meet your mitochondria: The powerful aliens that lurk within you 
   
   
   
   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. 
   
   Gene editing: A guide to the genetic revolution on our doorstep 
   
   
   
   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 ||||| Alana Saarinen loves playing golf and the piano, listening to music and hanging out with friends. In those respects, she's like many teenagers around the world. Except she's not, because every cell in Alana's body isn't like mine and yours - Alana is one of a few people in the world who have DNA from three people. 
   
   "A lot of people say I have facial features from my mum, my eyes look like my dad… I have some traits from them and my personality is the same too," says Alana. 
   
   "I also have DNA from a third lady. But I wouldn't consider her a third parent, I just have some of her mitochondria." 
   
   Mitochondria are often called the cell's factories. They are the bits that create the energy all of our cells need to work, and keep the body functioning. But they also contain a little bit of DNA. 
   
   Alana Saarinen is one of only 30 to 50 people in the world who have some mitochondria, and therefore a bit of DNA, from a third person. She was conceived through a pioneering infertility treatment in the USA which was later banned. 
   
   But soon there could be more people like Alana, with three genetic parents, because the UK is looking to legalise a new, similar technique which would use a donor's mitochondria to try to eliminate debilitating genetic diseases. It is called mitochondrial replacement and if Parliament votes to let this happen, the UK would become the only country in the world to allow children with three people's DNA to be born. 
   
   The structure of a cell 
   
   Nucleus: Where the majority of our DNA is held - this determines how we look and our personality 
   
   Mitochondria: Often described as the cell's factories, these create the energy to make the cell function 
   
   Cytoplasm: The jelly like substance that contains the nucleus and mitochondria 
   
   Alana was born through an infertility treatment called cytoplasmic transfer. 
   
   Her mum, Sharon Saarinen, had been trying to have a baby for 10 years through numerous IVF procedures. 
   
   "I felt worthless. I felt guilty that I couldn't give my husband a child. When you want a biological child but you can't have one, you're distraught. You can't sleep, it's 24-7, constantly on your mind," she says. 
   
   Cytoplasmic transfer was pioneered in the late 1990s by a clinical embryologist Dr Jacques Cohen and his team at the St Barnabus Institute in New Jersey, US. 
   
   "We felt that there was a chance that there was some element, some structure in the cytoplasm that didn't function optimally. One of the major candidates that could have been involved here are structures called mitochondria," he says. 
   
   Cohen transferred a bit of a donor woman's cytoplasm, containing mitochondria, to Sharon Saarinen's egg. It was then fertilised with her husband's sperm. As a little bit of mitochondria was transferred, some DNA from the donor was in the embryo. 
   
   Image copyright Science Photo Library 
   
   Seventeen babies were born at Cohen's clinic, as a result of cytoplasmic transfer, who could have had DNA from three people. 
   
   But there was concern about some of the babies. 
   
   "There was one early miscarriage, considering there were twelve pregnancies that is an expected number," says Cohen. 
   
   He and his team believed that miscarriage occurred because the foetus was missing an X chromosome. 
   
   "Then there was another twin pregnancy, where one [of the twins] was considered entirely normal and the other had a missing X chromosome. 
   
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   "So that's two out of the small group of foetuses that was obtained from this procedure. This did worry us and we reported that in the literature and in our ethical and review board that oversees these procedures," he says. 
   
   At the time of birth, the other babies were all fine. A year or two later, another of the children was found to have "early signs of pervasive early developmental disorder which is a range of cognitive diseases which also includes autism." Cohen told me. 
   
   He says it's difficult to know if the abnormalities happened by chance or because of the procedure. 
   
   Other clinics copied the technique and Cohen estimates that around 30 to 50 children worldwide were born who could have DNA from three people as a result. 
   
   But in 2002 the American regulator, the FDA (Food and Drug Administration) asked clinics to stop doing cytoplasmic transfer due to safety and ethical concerns. All of them did. 
   
   "There was a reaction from scientists, ethicists, the public at large, I think most of it was supportive, some of it was critical - I think this is normal, every time an experiment is done in medicine there is a reaction - what are the risks here?" says Cohen. 
   
   At the time, some were concerned because they felt this was germ line genetic modification. What "germ line" means is that a child like Alana would pass her unusual genetic code down to her children. And their children, would pass it to their children and so on. 
   
   Because we inherit our mitochondria only from our mothers, only female children would pass their unusual genetic code on. Crossing the germ line as it is known has never been done before so very little is known about what the outcome could be. 
   
   Due to a lack of funding, Cohen says, it hasn't been possible to find out about how any of the children like Alana who were born from cytoplasmic transfer are doing. But the St Barnabus Institute is now starting a follow up study to check their progress. 
   
   Sharon Saarinen says her daughter Alana is a healthy, typical teenager 
   
   "I couldn't ask for a better child. She is an intelligent, beautiful girl inside and out, she loves math and science … she does really well in school. She helps me around the house… when she's not texting!" 
   
   "She has always been healthy. Never anything more than a basic cold, or a flu every now and then. No health problems at all." 
   
   The health of the children, like Alana, born from cytoplasmic transfer is under scrutiny now because of the UK's decision to consider legalising mitochondrial replacement, where the mitochondria of a donor woman will be used to create a child. 
   
   It would not be available for people with fertility problems but for those who carry diseases of the mitochondria and would otherwise pass down these genetic abnormalities to their children. 
   
   Exactly how it is done still needs to be determined as there are two ways of doing the procedure, depending on when the eggs are fertilised. 
   
   Eggs from a mother with unhealthy mitochondria and a donor with healthy mitochondria are collected 
   
   The nucleus, containing the majority of the genetic material, is removed from both eggs. The donor nucleus is destroyed 
   
   The mother's nucleus is inserted into the donor egg - it now has healthy mitochondria. The egg is then fertilised by the father's sperm 
   
   Both the mother's and donor's eggs are fertilised with the father's sperm to create two embryos 
   
   The pronuclei, the nuclei during the process of fertilisation, contain the majority of the genetic material. They are removed from both embryos. The donor's is destroyed 
   
   A healthy embryo is created by putting the parents' pronuclei into the donor embryo 
   
   "Mitochondrial diseases tend to involve tissues or organs which are heavily dependent on energy," says Prof Doug Turnbull from The University of Newcastle. He has treated people with mitochondrial disease for decades and is one of those who has developed these new techniques to try to cure these debilitating diseases. 
   
   "The conditions can therefore involve the heart, the brain or sometimes the skeletal muscle," he says. 
   
   "People can have very bad heart problems which can cause the heart to fail eventually, they can be very weak and require respirators or be in a wheelchair. With the brain, they can get epilepsy, strokes and eventually severe dementia." 
   
   Turnbull estimates that around 1 in 3000-5000 people in the UK have a mitochondrial disease. "We can treat the symptoms. We can improve the quality and length of peoples' lives but we can't cure them." 
   
   The mitochondria carry some DNA, around 13 "important genes" says Turnbull. 
   
   That compares to the "23,000 important genes" in the nucleus where most of our DNA is held. This is the DNA that determines our traits and personality. 
   
   "We're not trying to create some characteristic that makes this person a stronger person or [someone who] will have blonde hair. We're trying to prevent disease and I think that is the only justification for doing this," he says. 
   
   Sharon Bernardi, from Sunderland in the North of England, is someone who mitochondrial replacement could have helped. 
   
   Image copyright other 
   
   Bernardi has lost seven children to mitochondrial disease. 
   
   "I have babies in three different cemeteries," she told us in her sitting room, surrounded by photographs of all her children. 
   
   "That is not the way you plan your life when you're trying to have a family. I have lovely photos and lovely memories but obviously that's all I have got now." 
   
   I have to slip back into reality and think don't be silly, Edward's not there. He's not in his room Sharon Bernardi 
   
   The doctors didn't know why Bernardi's babies kept passing away only hours after they were born. So that's why she kept trying, hoping she would have a healthy child. 
   
   With her fourth child, Edward, at first everything seemed different. He was healthy until he was about four and a half. But it was then that he was diagnosed with Leigh's disease, a type of mitochondrial disease, and his health deteriorated throughout the years. 
   
   "From the age of 20 Edward [found] getting around more difficult. He started to get new symptoms - spasms. He'd start screaming... four, five, six hours at a time. His muscles used to tense up, his hands, his face. It was like dystonic spasms - a really bad spasm. [For] eight hours he'd be in pain, screaming. His face would twist up and his hands would get really stiff. It was hard to see." 
   
   Edward Bernardi passed away three years ago, when he was 21. 
   
   "My life was totally for Edward. Even now sometimes if I have gone to sleep, I still wake up, and think, 'It's very quiet.' I have to slip back into reality and think, 'Don't be silly, Edward's not there. He's not in his room'." 
   
   "Without a heartbeat I would have gone for this [mitochondrial replacement]. I hope this is a new option. I hope people take it seriously and it's approved. 
   
   "I don't want my son to have just died for nothing. I want him to have made a difference." 
   
   "His life was robbed at 21. We're trying to stop this. People have to understand this is a life disease. We're trying not to pass it on to children and make it better for future families." 
   
   Image copyright other 
   
   But some people believe this technique could set us on a slippery slope towards genetically modified humans. 
   
   "These regulations would authorise the crossing of a rubicon for the first time. It would authorise germ line therapy... to alter the genes of an individual. This is something defined by the EU Charter of Fundamental Rights as effectively constituting eugenics," says British MP Fiona Bruce who chairs the All Party Parliamentary Pro-Life Group. 
   
   "We will have approved a technique and what that technique could be used for in the future who knows. We're opening a Pandora's box." 
   
   The regulator in the UK, the HFEA or Human Fertilisation and Embryology Authority, has held three independent reviews to scrutinise the safety of this technique. The conclusions were that mitochondrial replacement is "not unsafe". 
   
   There have been few episodes I'm aware of in the history of assisted reproduction that have had to be stopped because of hazard Professor Braude, Kings College London 
   
   That means "it would be reasonable, with some additional experiments, to take it into clinical practice if all circumstances are fulfilled" says Peter Braude, emeritus professor of obstetrics and gynaecology at Kings College London. He sat on all three HFEA scientific reviews. 
   
   "In any move from science to clinical practice there is a leap of faith - it has to be done," he says. 
   
   He adds that many of the concerns being raised now about this are the same as the ones cited in the early days of IVF. The UK has for decades been a leader in assisted reproduction science and is where the world's first test tube baby, Louise Brown, was born in 1978. 
   
   "The headlines then were 'playing God' and 'genetically modified humans'," says Braude. 
   
   "There have been few episodes I'm aware of in the history of assisted reproduction that have had to be stopped because of hazard. It's all gone pretty swimmingly as far as I'm aware." 
   
   Braude says that mitochondrial replacement has gone through much more scrutiny than previous, now well established, assisted reproduction techniques did, such as IVF. 
   
   "Whereas the original techniques were used with only [experiments from] mice, rabbits, lab animals... the big difference here is we also have issue of human embryos and this work has been tested in macaque monkeys in primates. All those were very useful, reassuring… hence why we came to the conclusion that this is not unsafe." 
   
   The experiments done on macaque monkeys were done in Oregon, US and the monkeys are now five years old and seem to be healthy. 
   
   Braude also points out that having a third person's DNA in your system is "nothing particularly new". 
   
   "Think about bone marrow transplants, let's say unfortunately you have leukaemia and you have to have your bone marrow radiated for the cancer to be killed and then it is replaced by bone marrow from someone else - say me. Effectively from that time onwards, you will have circulating in your body DNA from me. You won't be related to me, you may be grateful to me, but you will have DNA from a third person circulating in your body." 
   
   What is different, say critics, about mitochondrial replacement, is that DNA from the donor will be passed down future generations. 
   
   Image copyright Science Photo Library 
   
   Dr Ted Morrow, an evolutionary biologist from the University of Sussex, and colleagues have carried out mitochondrial replacement experiments on other animals. He raised safety concerns about mitochondrial replacement to the scientific reviews. 
   
   "For mice, there were changes in cognitive ability... to learn and do things using their brain. In fruit flies and seed beetles there were changes in male fertility, changes in ageing, a range of different traits were effected in various experiments," he says. 
   
   The HFEA's scientific reviews dismissed Morrow's findings as not relevant to humans because they were done on inbred animals. 
   
   Morrow stands by his research and says the scientific panels should not have dismissed his findings so quickly. 
   
   I'm a scientist but I'm not a pro-lifer. I think this is a genuine safety concern - that's it Ted Morrow, University of Sussex 
   
   It is Morrow's evidence that critics such as Fiona Bruce cite when saying this technique is not safe enough. 
   
   She has called a debate in the House of Commons today to discuss mitochondrial replacement. She does not believe there has been enough debate about what the UK is proposing to do. "The technique itself could allow the child to inherit untried untested medical complications," she says. 
   
   Morrow says that all the coverage of his research has been "a rather odd experience". 
   
   "In the press it's sometimes portrayed that the scientists think this, and the pro-life group this. I'm a scientist but I'm not a pro-lifer. I think this is a genuine safety concern - that's it." 
   
   Alana and Sharon Saarinen have been watching the debate in the UK with interest. 
   
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   "I wish I could meet her, the donor, to tell her I am so grateful for what she did for us. How can you thank someone for giving you a life? That's impossible," says Sharon. 
   
   Alana agrees with her mum. "I think it would be nice to thank her. But I wouldn't want to have a relationship or connection with her. The DNA I have of her is just so small." 
   
   "I know she might have another person's mitochondria, [but] look what a great person she turned out to be, and healthy. Just because she'll pass it on to her children it won't bother me in the least. I know it was the right thing to do. I have the living proof every day to see how great it turned out." 
   
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target: – 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.)