Ground-breaking science cured a baby who doctors said had only weeks to live. But are we saving lives or designing children? Madhumita Murgia reports.

Layla Richards was a bouncy 3.5kg baby with downy dark hair and plump cheeks when she was born in a London hospital in June 2014.

But 12 weeks later, Layla, who had been settling in at home in North London, suddenly stopped drinking milk and began to fuss and cry constantly. Because she had been a sunny, happy infant until then, her parents took her to see the doctor. He suspected a stomach bug, but just to be sure he took a blood test. The results that came a few days later were a shock: Layla had an acute, deadly form of leukaemia that she couldn't survive without immediate treatment. She was just 14 weeks old.

When the diagnosis came in, an ambulance rushed the family from their home to intensive care at the Great Ormond Street Hospital, the world-famous paediatric centre in Bloomsbury. Her doctors described her cancer as "one of the most aggressive forms of the disease" they had seen. For the next few weeks, she endured several rounds of chemotherapy, followed by a full bone marrow transplant to replace her damaged blood cells. This sort of aggressive therapy can often be successful in babies, but none of Layla's treatments, even the experimental ones, worked. Medically, she was out of options. Only one choice remained - admitting her to an end-of-life care facility to make her final weeks more comfortable.

Just a few doors down from the leukaemia ward at Great Ormond Street is the office of Dr Waseem Qasim, a bearded, genial immunologist who specialises in immune system disorders in children, including cancers. For several months, Qasim had been working on a new type of leukaemia treatment in which an anonymous donor's white blood cells are engineered to recognise cancer cells, by tweaking their genes. White blood cells are the body's soldiers; they fight infectious disease and foreign invaders. The engineered cells form an arsenal of targeted cancer-killer cells that can be injected into anyone. There was one problem: The procedure had only been tested in mice.


Qasim's lab is based in the University College London GOS Institute of Child Health, connected by a single corridor to Great Ormond Street.

"We move effortlessly between the two. There are no other physical or intellectual barriers, so it leads to serendipitous events," Qasim says, as we stroll through a set of double doors from his lab into the hospital.

Qasim heard about Layla's case from her transplant surgeon. "He asked as a sort of joke, 'I might be out of my mind but could [your cells] be useful here?'" Qasim recalls.

Because the therapy had never been tested in humans, there was the obvious danger of things going badly wrong, but Layla's parents and doctors knew she would die without a miracle.

After the Medicines and Healthcare products Regulatory Agency granted an emergency license, Layla became the first person to receive a vial of gene-edited cells from a stranger to attack her cancer.

What followed after Qasim's experimental gene treatment, a new technique using custom-designed molecular scissors to cut, edit and delete DNA, was described by Layla's doctors as "miraculous" and "staggering." She went into remission within four weeks and successfully survived a second bone marrow transplant. Now, nearly two years on, she remains healthy and cancer-free.

 Layla Richards with her parents Lisa Foley and Ashleigh Richards and sister Reya, 8.
Layla Richards with her parents Lisa Foley and Ashleigh Richards and sister Reya, 8.

Layla was a pioneer, the first person saved by gene editing; and without the favourable environment created by British scientists and regulators over the past decade, Qasim's experimental treatment, which gives special properties to cells, would never have been allowed.

With recent advances in gene editing and governmental approvals, the UK is set to become the unlikely pioneer in one of the most controversial, yet astonishing spheres of human knowledge: the manipulation of our genetic code. While research labs around the world are working on genetic cures to childhood and adult diseases, most have been wary of interfering with the DNA of a human embryo, fearful of unintended consequences for future generations.

Yet the UK achieved a double first in 2016: It became the first country to legally permit replacing part of an embryo with a third person's genes, and the first to allow genetic modification in humans from the embryo stage.

Opponents of the techniques believe they herald a dystopian future of "designer babies" - a world where parents will "play God" by opting to edit their unborn child's genes to make it stronger, taller and healthier.

Molecular biologist and ethicist David King, the founder of British watchdog group Human Genetics Alert, believes that embryo manipulation opens up "for the first time in human history, the possibility of consciously designing human beings, in a myriad of different ways".

A recent report from the Nuffield Council on Bioethics in London found that gene editing - particularly in embryos - demanded further scrutiny. Ethical opposition has arisen especially where, it said, the "scope for unforeseen consequences is considered to be great or editing is regarded as irreversible".

All humans have a unique "genome" sequence, the more than 3 billion molecule pairs known as DNA that define who we are, from our physical appearance to biological characteristics and even our personality. Our hair colour, preference for certain kinds of food even our ability to make deadlines - it's all rooted in our DNA. Mutations or mistakes in this genetic code can result in disease, such as diabetes or leukaemia.

Gene editing means we can now find and correct genetic errors in a lab. Once honed, the tools could be used to fix maladies like sickle cell anaemia and cystic fibrosis and even fight cancer.

The promise of gene editing goes beyond curing adult disease - it could even be used to modify human embryos and delete egregious genetic defects before birth. That would prevent the transmission of debilitating illnesses from parent to child, and could signal the end of devastating inherited disabilities.

The British Government's recent endorsement of gene editing research thrust the country to the forefront of the next revolution in health and science, whether the rest of the world is ready for it or not.

Nearly four decades before Layla Richards was born, another baby girl made history in Britain. In July 1978, Louise Brown was born by caesarean section to very eager parents. There was nothing particularly unusual about the birth of this healthy, 2.6kg baby - and yet her arrival into the world helped two British scientists win a Nobel Prize.

The reason: Louise was conceived in a petri dish, the world's first baby created through the process of in vitro fertilisation (IVF). Back then, Louise was called the first "test-tube baby", an indication of how bizarre the now-standard procedure was considered at the time. In 1981, The New York Times wrote that the procedure was considered "equivalent to abortion in the eyes of some opponents".

Louise's immaculate-lab conception is part of the UK's long history of developing groundbreaking biotech. With each milestone, scientists around the world face a moral dilemma concerning the definition of human life. When does a ball of cells become a foetus? Does an artificially created life form have rights? Should physical impairments like deafness be culled from our population?

After Louise's birth, the British Government convened an ethical committee, headed by philosopher Mary Warnock, to investigate the implications of creating and modifying human life in a lab. The resulting report, published in 1987, led to a nationwide consensus on the obvious social benefits of IVF.

The report also led to the establishment of the Human Fertilisation and Embryology Authority (HFEA), the first independent legislative body in the world to regulate human embryo research and IVF treatment.

HFEA recently granted two controversial licences: In February 2015, the British Government approved a pioneering gene technology to prevent potentially fatal mitochondrial disease from passing from mother to child. By placing a donor's healthy genes in an IVF embryo, the researchers say the resulting baby could avoid severe symptoms such as deafness, muscle withering, liver or kidney failure and brain damage. But critics worry that when these babies pass on the new genetic code to their children, grandchildren and every subsequent generation, there will be as-yet-unknown consequences.

Despite vocal opposition from a smattering of members of Parliament, as well as challenges from the Church of England and the Catholic clergy, the British House of Commons voted by an overwhelming majority to allow this mitochondrial donation.

And although the process has the British Government's stamp of approval, it is not approved as safe and effective by the US or Chinese authorities. In a review of the technology earlier this year, the US Food and Drug Administration warned that the evidence does not yet support the safe use of mitochondrial transfer in humans.

IN FEBRUARY 2016, geneticist Kathy Niakan of the UK's Francis Crick Institute became the first scientist in the world to receive a licence to edit healthy human embryos for research. (The embryos cannot be implanted into a human.)

Her goal is to better understand the process of early human development, not redesign babies. Even so, some lawmakers were determined to prevent this sort of research in Britain. In a parliamentary debate about the licence, Conservative Party parliamentarian Jacob Rees-Mogg said: "In a country nervous about genetically modified crops, we are making the foolhardy move to genetically modified babies."

Niakan, along with Professor Robin Lovell-Badge a scientific adviser to HFEA and the US National Academy of Sciences on issues of gene editing, became the first cohort of scientists at the newly opened Francis Crick Institute in London - the first research hub to be granted an HFEA licence to edit seven-day-old living human embryos. Their work will focus on helping improve the success rates of IVF, the technique successfully demonstrated some 300km north, when Louise Brown was born in 1978.

Headed by Nobel Prize"winning biologist Sir Paul Nurse, Francis Crick's eponymous research institution opened in September. With an investment of aboutNZ$1.1 billion and known to insiders as Sir Paul's Cathedral, the building will house 1250 scientists in four interconnected blocks, the largest biomedical research institute in Europe

Within its corridors, British scientists will be the first people ever to glimpse the molecular mysteries that result in the conception of human life.

The woman at the vanguard of this effort is 38-year-old Niakan.

The daughter of Iranian immigrants, Niakan grew up in the small town of Silverdale, Washington in the US where her father was a practicing neurologist. She has studied developmental biology at the University of California, Harvard University and the University of Cambridge, where she moved in 2009 as a postdoctoral fellow.

Her goal is to understand the earliest stages of human life, when we are nothing but a ball of 200 cells. She knows her work could ultimately help women to conceive and genetic diseases to be defeated, but that is not what drives her. Her real motivation is cracking the scientific mystery of human reproduction.

"It has the potential to really revolutionise our understanding of human biology in a petri dish," she says. "That's fascinating to me."

Using a gene-editing tool called CRISPR-Cas 9 (pronounced "crisper") that can cut and edit DNA very precisely, she wants to isolate genes thought to be important for foetal development; only then can we figure out exactly what role each plays.

"This basic biological question - which genes are critically required? - is important because it can help us understand which blastocysts will go on to develop, implant and thrive."

Today, when a woman goes to a clinic for IVF treatment, experts score her embryo quality based on physical shape, size and other visible features, rather than genetic features. Though embryos can be screened for chromosomal abnormalities, little is known about human developmental genetics at this early stage.

"There are very few molecular tools used to identify those embryos. We know there's a 50 per cent drop-off rate, so I think there's room to determine the key signatures that embryos need to successfully implant," Niakan says. "It could increase the chances [of pregnancy], or it could help to choose those embryos that will likely go on to develop successfully into a healthy baby."

Eventually, the knowledge could help us fathom causes of reproductive defects or even infertility.

The HFEA spent three years investigating Niakan's request to use the CRISPR-Cas9 scissors, conducting a series of detailed inspections of her lab work, including whether embryos were handled respectfully and carefully in the lab, and whether donors were counselled and updated appropriately. Niakan was notified of their decision in late January.

The decision was celebrated by scientists, patient groups with genetic diseases and mothers who had struggled to conceive.

Emma Benjamin, a 34-year-old woman who miscarried four times spoke widely to the press of her support. "I found it frustrating I never had answers as to why I kept miscarrying," she said. "If this research had come earlier and could have helped me provide answers then I guess it could have saved a lot of heartache."

Despite Niakan's momentous victory, it remains illegal in the UK to implant genetically modified embryos into a womb for the purpose of giving birth. That ensures modified genes are not passed on to future generations; the lab must destroy every embryo after the seven-day mark.

Although Niakan insists this research has no bearing on actual babies (for now), many in the scientific community are considering the possibility that a modified embryo could result in a living child.

In december 2015, several hundred scientists from around the world gathered in the US for the first international summit on gene editing. At its close, the chairman, Nobel Prize"winning biologist David Baltimore of the California Institute of Technology, issued its conclusions, saying, "As scientific knowledge advances and societal views evolve, the clinical use of germline [embryo] editing should be revisited on a regular basis."

The scientists have reason to be anxious: Some of their brethren have raced ahead already. In April 2015, researchers in Guangzhou, China, announced they had conducted a CRISPR gene-modification experiment on defective human embryos, to edit the gene responsible for beta-thalassaemia, a potentially fatal blood disorder. It was a resounding failure, because the CRISPR method accidentally edited the wrong genes, which ended up irreversibly scrambling the embryo's DNA.

That research sparked a hot global debate in the academic fraternity about whether to declare a moratorium on embryo modification until ethical laws and regulations could catch up with science. In response, scientists from the United States, Britain and China at the Washington summit called for a temporary freeze on altering human embryos destined for birth, calling it "irresponsible" and potentially dangerous.

The quick decision to co-operate internationally speaks to the transnational nature of this research; It is a strand of science that could change what it means to be human.

Even gene editing's strongest proponents acknowledge there could be catastrophic mistakes. For instance, CRISPR could edit genes inaccurately, causing unintended mutations and disfigurations. There's also the very real risk of rogue editing by malicious parties - wealthy people paying for genetic enhancements, which could become a form of social discrimination and could introduce novel genetic sequences into the species - a sort of genetic cosmetic surgery.

Until these safety and ethical issues have been resolved, the scientific community has proposed holding back, and re-assessing current research on a constant basis.

Though most scientists acknowledge that editing embryos will probably be a clinical option one day, some remain staunchly opposed. King, of Human Genetics Alert, refers to gene editing as the "new techno-eugenics".

Lovell-Badge believes frank discussion and public trust in the HFEA is the key to a safe clinical transition. "It is illegal in the UK to transfer any gene-edited embryo into a woman," he says. "Given the experience with the way the HFEA regulates [this research], and if the law were to be changed, I expect the public could also be reassured that any applications would be restricted to important clinical uses."

Niakan agrees, pointing to UK regulators' ability to separate church and state in the matter of controversial scientific research such as hers.

"The UK's pioneering role in advancing reproductive medicine and health, especially IVF, has a lot has to do with the regulatory framework, where people are willing to engage in frank discussions about these complex issues," Niakan says. "In other countries the message gets muddled up with politics and religion."

IN SEPTEMBER, the world's first baby with three people's genes was born in Mexico, to Jordanian parents who had lost two children and had four miscarriages due to mitochondrial disease. The genetic illness is caused by dysfunctional mitochondria, the cellular units responsible for generating energy. In the case of this baby, the malfunction was caused by mutations, or errors, in the mitochondrial DNA.

The procedure was performed by a team of doctors from New York City, although details on how it was done are scant. The only country with any legal or regulatory framework for the technology is the UK, where - as of December 2016 - an embryo can legally be modified, and implanted into a woman's uterus.

Although embryo editing remains firmly confined to laboratories, scientists at Newcastle University in the north of England are taking the next step into the future by genetically modifying IVF embryos to create healthy babies.

Sir Douglass Turnbull, who has been specialising in mitochondrial disease for 35 years, says he has known some of his patients for up to 30 years.

"There can be three generations in a family who are affected, many of whom lose three or four children due to the disease. For me, that's the biggest motivation."

Since 2001, Turnbull, along with Newcastle embryologist Mary Herbert, has been working on a new IVF technique, known as mitochondrial donation, that offers women a way to have biological children who do not have the mother's mutations.

The technique is a bit like swapping the yolk of an egg: It involves removing a healthy nucleus, or yolk, of the mother's fertilised egg which contains about 99.8 per cent of genetic material that the child will inherit. This is transferred into the egg of a donor that has had its nucleus removed. The donor, who does not have mitochondrial disease, will pass on her healthy mitochondria. This way the baby will inherit the vast majority of its biological characteristics from its parents via its nuclear DNA, but will have the healthy mitochondrial genes of the donor.

In a paper published in Nature last year, Turnbull and Herbert found that their technique could reduce the risk of passing on defective mitochondrial DNA to under 5 per cent - far better than the 60 to 90 per cent risk otherwise. "For people who just watch their child fall apart before their eyes, this is a hugely positive outcome," says Herbert.

The scientists started lobbying the HFEA to approve their technique in 2012, and came up against intense opposition. Because the mitochondrial transfer method passes on genetic change from one generation to another, British MPs and even some scientists worried that it could give rise to unexpected problems.

Catholic Church ethicists were also opposed to the introduction into an embryo of a third person's genes, arguing that this "dilutes parenthood".

The Newcastle team argues that since the donor remains anonymous and has no rights over the child, she shouldn't be considered a third parent.

Other critics are uncomfortable with the idea of deleting disability out of the population completely, believing it would impact on the rights of the handicapped.

Bioethicist Tom Shakespeare, who has dwarfism and uses a wheelchair, doesn't believe "fixing" genetic mutations is necessarily what the disabled community wants, although he doesn't oppose mitochondrial donation, in principle.

"Contrary to the prevailing assumption, most people with disabilities report a quality of life that is equivalent to that of non-disabled people. Their priority is to combat discrimination and prejudice," he writes in a paper in Nature.

Fellow bioethicist and deaf researcher Jackie Leach Scully feels particularly uncomfortable about genetic cures as a solution for all disabilities, although she concedes it would be hard to find anyone opposed to correcting mitochondrial mutations, which are "generally very nasty diseases."

The Newcastle-based scientists strongly object to this reasoning - they believe every mother with genetic disease should have a choice between hoping for the best, or using science to screen for a healthy baby.

"We are often criticised because we don't value disability. I don't think that at all. I spend my whole life looking after disabled people but people should have the right to decide whether or not they want to have disabled children," says Turnbull.

While scientists are still fighting to get approval to test their cutting-edge biomedical techniques before using them on humans, Qasim, the immunologist at UCL, is saving more lives - and saving parents from the ultimate tragedy.

Around Christmas 2015, months after Layla Richards was sent home in remission, Qasim's team obtained a second emergency licence to treat another baby girl with the identical type of leukaemia, which had been diagnosed when the girl was just 4 weeks old. When she was 16 months old, the child (whose parents did not want to make her name public) was given the same dose of gene-edited killer cells Layla received. Weeks later, she was declared cancer-free; now, at 2, she is doing well.

Qasim's emergency treatment, which has now saved two children, is part of a larger trial that opened to the public in June. It will treat up to 10 children with the same type of leukemia as the two toddlers who are in remission.

If the treatment works for the 10 new patients, the introduction of modified genes could become the primary treatment for cancers like this - supplanting even chemotherapy.

With a slight tweak, Qasim says, this gene therapy could be applied to other cancers. Gene therapies are already being tested for those conditions, so the timeline for fixing a wide range of genetic defects could be as short as five years, he says.

The therapy could even be used for diseases considered incurable, like HIV.

American pharmaceutical firm Sangamo is running a trial that uses gene editing to engineer the immunity of HIV patients to the disease.

Meanwhile, nearly two years on, Layla remains cancer-free and healthy. At a charity fundraiser for the Great Ormond Street Hospital in December 2015, Layla's mother encouraged other parents with sick children to be unafraid of "guinea pig" treatments, and to "try new things".

If Qasim's therapy is approved for general use, it could be the first of thousands of similar treatments. "Layla has a purpose - to help other people. She was nearly at death's door.

"You don't normally hear a happy story with cancer," her father said during the appeal.

"One day there will be a cure for cancer. Who knows? Maybe in 40 years' time Layla may have helped to make the first step towards that."