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Becoming a parent for the first time is a major moment for anyone — but for Laura Gayton, giving birth to a healthy, crying baby boy felt nothing short of a ‘miracle’.
Laura, a swimming teacher from Kettering, Northants, is one of around 10,800 people in the UK with cystic fibrosis (CF), a progressive genetic disease that claims the lives of half of those affected before the age of 40.
When she was diagnosed at just two months old, Laura’s parents were told their daughter would be lucky to make it to her 30th birthday. But today, Laura, 31, has never felt fitter, thanks to a pioneering new treatment — and after four years of trying, she and her husband Nicholas, 33, a fire station commander, now have a 13-month-old son, Louis.
‘I’ve always loved kids and wanted to find someone and have a family. But I just didn’t think it could happen, because cystic fibrosis is quite a full-on illness and hard to live with,’ says Laura.
The disease is caused by a defective protein that results from mutations in a gene called CFTR.
World first: Aurea with her father Rafal Smigrodzk. Living proof of the enormous potential of genomics is Aurea Yenmai Smigrodzki, a happy and healthy two-year-old girl from Clemmons, North Carolina
As a result, the lungs and digestive system become clogged with an abnormally thick, sticky mucus and those affected are prone to frequent and potentially life-threatening lung infections, while their lungs can become increasingly damaged.
Chronic illness can also lead to reduced fertility, which is thought to be caused by abnormally thick cervical secretions.
Cystic fibrosis is an autosomal recessive genetic disease. This means that both parents have to pass on an abnormal gene for their child to develop it. As many as one in 25 people are thought to carry the mutation, often without knowing it. (Laura’s husband Nick was tested before they started trying for a baby and is not a carrier.)
Throughout her life, Laura has suffered breathing difficulties and repeated infections, among other related health problems such as extreme fatigue. The chest infections sometimes left her hospitalised and gradually reduced her lung capacity to 58 per cent.
With each infection, Laura worried about what would happen to her and ‘if there was going to be anything to help if things got worse’.
‘My doctors were coming to the end of the line, in terms of options, and I did get scared,’ she says.
Currently there is no cure for CF. While medication can ease the symptoms by, for instance, thinning the mucus, these drugs often work for only a limited time.
And Laura’s genetic make-up meant that she wasn’t suitable for Orkambi — a new combination of two drugs that boosts the function of a protein that regulates the transport of water and salt into cells, improving their function.
Then in August 2020, Laura was thrown a lifeline when a new drug called Trikafta (known in the UK as Kaftrio) was rolled out to NHS patients in England.
Kaftrio is a breakthrough that’s emerged from a relatively new field of research, genomics, the study of our genes — the blueprint that makes us who we are and determines a lot of our health outcomes.
And as I explain in my new book, Genomics: How Genome Sequencing Will Change Our Lives, it is thanks to genomic research that many ideas, which once seemed the stuff of science fiction, are rapidly becoming a reality.
The first CF mutation was identified in 1989 (there are nearly 2,000 known CF mutations) and since then there have been a number of significant breakthroughs leading to the development of Trikafta.
Genomics emerged around 50 years ago but the field was revolutionised in the mid-to-late 1990s thanks to new technologies.
As a result, an international moonshot, the Human Genome Project, launched in 1990 to map out every one of the human body’s genes to create a blueprint for researchers to investigate human health, was completed by April 2003, two years ahead of schedule.
Today, the full DNA map is commonly used in developing new drugs and other healthcare solutions. Genetic sequencing has become so cheap and accessible that doctors can create a full genetic map of a patient — taken from a simple blood, spit or tissue sample — at the click of a button.
By mapping the human body in this way, scientists are finally discovering answers to some of our longest-held questions, including the causes of infertility, and of diseases such as breast cancer.
Laura, a swimming teacher from Kettering, Northants, is one of around 10,800 people in the UK with cystic fibrosis (CF), a progressive genetic disease that claims the lives of half of those affected before the age of 40. When she was diagnosed at just two months old, Laura’s parents were told their daughter would be lucky to make it to her 30th birthday
These new genetic technologies could mean that instead of needing such treatments, one day soon no babies with diseases like Laura’s will be born at all.
Yet genomics’ successes have also raised major ethical questions about what genomics makes possible, and whether what it makes possible is desirable or ethical. These complex issues are in some ways epitomised in the disease cystic fibrosis.
Kaftrio, a triple-drug therapy, directly targets the defective protein, making it work more effectively and thinning the mucus. It helps clear the lungs, allowing patients to breathe easier and reducing the risk of infection.
The drug can help around 90 per cent of CF patients, and in September last year Laura became one of the first phase of 60 patients to be given Kaftrio, which is taken as a pill, twice daily — and ‘almost immediately’ she started to feel better.
‘Just four hours after my first dose, I started coughing up all the mucus in my chest and it felt so much clearer,’ she says. Laura has not had any infections since and her health is otherwise ‘good’.
Kaftrio has been described by patient groups as revolutionary.
‘Studies into lung function show that Kaftrio is having a phenomenal effect on patients who have exhausted other options,’ explains Daniel Peckham, a consultant and professor of respiratory medicine at the University of Leeds. ‘It won’t necessarily repair the lungs, but it may significantly reduce infections and inflammation.’
And the drug has had an unexpected bonus.
‘We were just starting to think about IVF before I started Kaftrio,’ says Laura. ‘I’d thought that as long as it made me better, that was the main thing.’ Then just seven weeks into treatment, Laura discovered that she was pregnant. ‘I was in shock — it felt like a miracle,’ she says. ‘And now, rather than feeling tired from illness, I’m only feeling tired from being a mum.’
‘It has been surprising to see how individuals on Kaftrio are getting pregnant more easily,’ adds Professor Peckham.
‘I’ve always loved kids and wanted to find someone and have a family. But I just didn’t think it could happen, because cystic fibrosis is quite a full-on illness and hard to live with,’ says Laura. The disease is caused by a defective protein that results from mutations in a gene called CFTR
In the first year the drug became widely available in the U.S., one healthcare trust reported that 18 women with CF — nearly all of whom were taking the drug — became pregnant, a rate of 16 per cent. By comparison, the U.S. national rate of CF pregnancies in 2014 was just 2.5 per cent.
‘Until now, women with CF have often struggled to have children,’ says Professor Peckham. ‘It’s possible that a reduction in cervical secretions is suddenly enabling them to get pregnant. It’s very exciting.’
One of the challenges in treating CF is that the disease is not caused by all the same gene mutations.
However Kaftrio has been shown to work for various mutations, especially one of the most common, which means around 90 per cent of CF patients could benefit.
‘Already, in the two years since the drug has been available, our hospital admissions have dropped sharply,’ says Professor Peckham. ‘Patients are much more stable.’ He and other experts believe children being born today with cystic fibrosis are likely to lead long and healthy lives thanks to new medicines such as Kaftrio.
‘I would expect this drug to be extending life for this generation by 20-plus years,’ says Professor Peckham. ‘For children being born with cystic fibrosis today, who knows — they could enjoy a normal life expectancy.’
Living proof of the enormous potential of genomics is Aurea Yenmai Smigrodzki, a happy and healthy two-year-old girl from Clemmons, North Carolina.
Aurea was the world’s first PGT-P baby, meaning she has been scientifically selected for her genes, and is statistically less likely to develop a genetic disease or disorder in her lifetime.
PGT-P — preimplantation genetic testing for polygenic disorders — is conducted in conjunction with IVF and allows prospective parents to actively select which of their own embryos to take, based on the strength of its genes.
The difference between PGT-P and other screening tools is that PGT-P can screen for more genetically complex diseases, ie, those that are influenced by genetic variants in more than one gene.
This may include heart disease, type 2 diabetes and obesity — all of which do not have a single genetic cause, but develop due to multiple genetic factors in combination with lifestyle and environmental factors, such as exercise, diet or pollution.
This kind of broad sweep embryo test is not allowed in the UK: couples undergoing IVF can only test embryos for a few specific genetic conditions that pose a significant risk, such as cystic fibrosis. (This is also different from newborn screening through the common heel-prick test, which is used to look for a handful of specific diseases such as sickle cell and CF.)
Aurea’s parents, Thuy Phan and Rafal Smigrodzki, used PGT-P to ensure that any child they had would be given ‘the best possible genetic health outlook’.
Rafal, a 57-year-old neurologist at Novant Health Forsyth Medical Center in North Carolina in the U.S., says the couple weren’t concerned about any particular disease or family inheritance. Rather, the promising new technology fascinated them, and the prospect of having disease-free children seemed a ‘no brainer’.
‘I first read about PGT-P for human embryos in a scientific article,’ says Rafal. ‘I’ve always had an interest in genetics, so I was intrigued by this report about an amazing technology where you can do genetic sequencing on these tiny embryos.’
Rafal refers to himself as a ‘techno-optimist’ and has even signed up to have his brain cryogenically stored when he dies, in the belief it will one day be resurrected, thoughts and spirit intact.
In his view, genetic screening of embryos is nothing unusual; it is simply the natural next step for humans to take.
‘It’s like the first time someone ever made a phone call — sure, it was a unique moment, but really it was just the beginning of something that now everybody does,’ Rafal muses. ‘In ten years’ time, this kind of polygenic testing will be completely non-controversial. People will be doing it as a matter of course.’
At the time, Thuy, an IT support worker, and Rafal, were both in their 50s and hoped that IVF would give them a better chance of having a baby. In 2019, they found an IVF provider in Charlotte, North Carolina, and then Rafal contacted a company called Genomic Prediction, which offers the PGT-P service.
But then the provider pulled out. ‘They said it would be unethical to screen embryos like that,’ says Rafal. ‘I was baffled and quite angry. As a parent I feel I have a duty to take care of my child, and that includes giving them the best potential health I can.’
Embryonic screening is controversial, particularly in countries such as the U.S. where there is a strong pro-life lobby.
Some disability campaigners are also opposed to the technology, arguing that it risks eradicating groups of people who bring value and diversity, and contribute to society. It may mean, for instance, that eventually no one is born with a condition such as CF, which has now become highly treatable.
‘Maybe, one day, they will be able to get rid of the cystic fibrosis gene in humans completely,’ says Jess Spoor, 33, a cystic fibrosis patient from Leeds who, like Laura, has benefited from Kaftrio. ‘I am very grateful, however, to have lived with cystic fibrosis, because it has shaped the person I am today.
‘It has taught me many things — especially that every moment is precious — and I have a great appreciation for life. It has made me stronger, and very driven to help others.’
Others feel uncomfortable with the idea of ‘playing God’, says Russ Altman, a professor in bioengineering at California’s Stanford University, who lectures on ethics and gene editing. In his view: ‘There is a long precedent [in most cultures] for giving parents very wide latitude in making decisions about child rearing, and there is a strong ethical argument for extending this into the area of pre-natal genetics.
‘This would allow parents to make decisions about selecting specific fertilised eggs to be implanted based on genetic information. It is not unreasonable to allow them to do this: it is one of hundreds of decisions that parents make throughout the course of a child’s life that affect the child’s life greatly.
‘There is an issue, however, of justice. It might not be fair to give this option to some [e.g. wealthy] folks but not others. If there is not a good way to make it fair, then perhaps it should not be offered to anyone.
‘Finally, it is probably not a good idea for society or a government body to make decisions about what should be “eradicated” from the gene pool, because this leads to a very slippery slope. I would leave it to the parents.’
Personally, Rafal believes it is right to eradicate all diseases if we have the tools. ‘I see the diversity argument as especially immoral. It would be wrong to increase “diversity” by randomly removing adults’ limbs or eyes. It would be wrong to increase the diversity of smiles by randomly denying some adult people access to dental care.
‘By the same token, it would be wrong to deprive some future people of good health by denying them proper genetic care before they are born.’
He and Thuy eventually found another IVF provider happy to help, and after successfully cultivating six embryos, they were given a report comparing the estimated risk of each embryo carrying genetic conditions including coronary disease, diabetes and genetic cancers.
‘It was easy to decide which embryo was the healthiest,’ says Rafal. ‘And we were lucky, because nine months later we had Aurea.’
He says he is ‘realistic’ that genetic screening is no guarantee of perfect health, but adds: ‘A healthy body requires healthy genes, and I gave my daughter the best genes I could afford.’
He also believes the technology should be available to as many people as possible.
When Aurea is older, she will no doubt be curious about her origins. But Rafal says he doesn’t think that her being the first baby born with the help of this technology is important. ‘It’s more of a curiosity’, he says. ‘By the time she is old enough to understand, there may be hundreds of thousands of babies like her, so no big deal.’
Genomic Prediction’s embryonic screening service is still relatively new, and the majority of its clients are in North and Central America.
‘In Europe [our clients are] mostly
in Scandinavia,’ says Laurent Tellier, the company’s CEO.
As well as being able to determine whether an embryo carries a risk of hundreds of genetically identifiable diseases, the company’s team can determine other traits such as skin and colour, height — even genes that factor into likely intelligence.
But co-founder Stephen Hsu says this is something that the company won’t offer, explaining: ‘We draw the line at anything that’s not disease-related or directly impacting the health of the embryo.’
In the meantime, the NHS has unveiled plans to roll out a pilot scheme for the whole genome sequencing of newborn babies using a simple heel prick test. This could then be used for informing their healthcare throughout their lives. Researchers hope it will also enable them to identify and treat rare diseases in babies much more effectively.
In Laura Gayton’s opinion, the roll-out can’t come soon enough. ‘I think giving parents the option is the right thing to do,’ she says. ‘We had the usual tests for Louis, but I would like to know the other potential health outcomes for him, to be more prepared. Because of me having cystic fibrosis, I think it’s especially important.’
Genomics: How Genome Sequencing Will Change Our Lives by Rachael Pells (Random House, £8.99).
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