The UK is set to begin sequencing the genomes of 100,000 newborn babies later this year. It will be the largest study of its kind, mapping the babies’ complete set of genetic instructions, with potentially profound implications for child medicine.
The £105 million ($126 million) Newborn Genomes Programme will screen for around 200 rare but treatable genetic conditions, with the aim of curtailing untold pain and anxiety for babies and their families, who sometimes struggle to receive a diagnosis through conventional testing. By accelerating the diagnostic process, earlier treatment of infants could prevent many severe conditions from ever developing.
The study would see roughly one in 12 newborn babies in England and Wales screened on a voluntary basis over two years. It will operate as an extension of current newborn testing, with the findings intended to inform policymakers, who could pave the way for sequencing to become more commonplace.
Nevertheless, the project has raised many longstanding ethical questions around genetics, consent, data privacy, and priorities within infant healthcare.
The health game-changers of the last 500 years
In the UK, like many other countries, newborn babies are screened for a number of treatable conditions through a small blood spot sample. Also known as the heel prick test, this method has been routine for over 50 years, and today covers nine conditions including sickle cell disease, cystic fibrosis and inherited metabolic diseases.
“The heel prick is long overdue to be obsolete,” argues Eric Topol, an American cardiologist and professor of molecular medicine at The Scripps Research Institute, who is not connected with the UK sequencing initiative. “It’s very limited and it takes weeks to get the answer. Sometimes, babies that have serious metabolic abnormalities, they’re already being harmed.”
Some conditions that are tested for have variations that may not register a positive result. The consequences can be life-altering.
One example is congenital hyperthyroidism, which impacts neurological development and growth and affects “one in 1,500 to 2,000 babies in the UK,” explains Krishna Chatterjee, professor of endocrinology at the University of Cambridge. It is the result of an absent or under-developed thyroid gland and can be treated with the hormone thyroxine, a cheap and routine medicine. But if treatment doesn’t begin “within the first six months of life, some of those deleterious neurodevelopmental consequences cannot be prevented or reversed.”
The Newborn Genomes Programme will test for one or more forms of congenital hypothyroidism that are not picked up by the heel prick test. “At a stroke, you can make a diagnosis, and that can be game changing – or life changing – for that child,” Chatterjee says.
The program is led by Genomics England, part of the UK Department of Health and Social Care. Along with its partners, it has carried out a variety of preparatory studies, including a large-scale public consultation. A feasibility study is currently underway to assess whether a heel prick, cheek swab or umbilical cord blood will be used for sampling, with the quality of the DNA sample determining the final choice.
Genomics England says that each of the 200 conditions that will be screened for has been selected because there is evidence it is caused by genetic variants; it has a debilitating effect; early or pre-symptomatic treatment has a life-improving impact; and treatment is available for all through the UK’s National Health Service (NHS).
Richard Scott, chief medical officer and deputy CEO at Genomics England, says the program aims to return screening results to families in two weeks, and estimates at least one in 200 babies will receive a diagnosis.
Contracts for sequencing are still to be confirmed, although one contender is American biotech company Illumina. Chief scientist David Bentley says the company has reduced the price of its sequencing 1,000-fold compared to its first genome 15 years ago, and can now sequence the whole human genome for $200.
Bentley argues that early diagnosis via genome sequencing is cost effective in the long term: “People get sick, they get tested using one test after another, and that cost mounts up. (Sequencing) the genome is much cheaper than a diagnostic odyssey.”
But while some barriers to genetic screening have fallen, many societal factors are still in play.
Feedback from a public consultation ahead of the UK project’s launch was generally positive, although some participants voiced concerns that religious views could affect uptake, and a few expressed skepticism and mistrust about current scientific developments in healthcare, according to a report on its findings.
Frances Flinter, emeritus professor of clinical genetics and Guy’s and St Thomas’ NHS Foundation Trust and a member of the Nuffield Council on Bioethics, described the program as a “step into the unknown” in a statement to Science Media Centre in December 2022, reacting to the launch of the program.
“We must not race to use this technology before both the science and ethics are ready,” she said at the time. “This research program could provide new and important evidence on both. We just hope the question of whether we should be doing this at all is still open.”
Genome sequencing has raised many philosophical and ethical questions. If you could have aspects of your medical future laid ahead of you, would you want that? What if you were predisposed to an incurable disease? Could that knowledge alone impact your quality of life?
“People don’t generally understand deterministic or fatalistic-type results versus probabilistic, so it does require real teaching of participants,” says Topol. In other words, just because someone has a genetic predisposition to a certain condition, it doesn’t guarantee that they will develop the disease.
Nevertheless, sequencing newborn babies has made some of those questions more acute.
“One of the tenets of genomics and genomics testing is the importance of maintaining people’s autonomy to make their own decisions,” says Scott, highlighting the optional nature of the program.
“We’ve been quite cautious,” he stresses. “All of the conditions that we’re looking for are ones where we think we can make a really substantial impact on those children’s lives.”
Parents-to-be will be invited to participate in the program at their 20-week scan, and confirm their decision after the child’s birth.
“These will be parents, most of whom won’t have any history of a genetic condition, or any reason to worry about one. So it will be an additional challenge for them to appreciate what the value might be for their family,” says Amanda Pichini, clinical lead for genetic counseling at Genomics England.
Part of Pichini’s remit is to ensure equal access to the program and to produce representative data. While diversity comes in many forms, she says – including economic background and rural versus urban location – enlisting ethnically diverse participants is one objective.
“(There) has been a lack of data from other ethnic groups around the world, compared to Caucasians,” says Bentley. “As a result, the diagnostic rates for people from those backgrounds is lower. There are more variants from those backgrounds that we don’t know anything about – we can’t interpret them.”
If genomics is to serve humanity equally, genome data needs to reflect all of it. Data diversity “isn’t an issue that any one country can solve,” says Pichini.
Other countries are also pursuing sequencing programs and reference genomes – a set of genes assembled by scientists to represent a population, for the purpose of comparison. Australia is investing over $500 million AUS (around $333 million) into its genome program; the “All of Us” program is engaged in a five-year mission to sequence 1 million genomes in the US; and in the Middle East, the United Arab Emirates is seeking its own reference genome to investigate genetic diseases disproportionately affecting people in the region, where Illumina’s recently opened Dubai office will add local sequencing capacity.
Richard Scott of Genomics England says he hopes findings from the UK will be useful to other countries’ health systems, especially those not in “a strong position to develop the evidence and to support their decisions as well.”
Sequenced genomes will enter a secure databank using the same model as the National Genomic Research Library, in which they are deidentified and assigned a reference number.
Researchers from the NHS, universities and pharmaceutical companies can apply for access to the National Genomic Research Library (in some cases for a fee), with applications approved by an independent committee that includes participants who have provided samples. There are plenty of restrictions: data cannot be accessed for insurance or marketing purposes, for example.
“We think it’s really important to be transparent about that,” says Pichini. “Often, drugs and diagnostics and therapeutics can’t be developed in the NHS on (its) own. We need to have those partnerships.”
When each child turns 16, they will make their own decision on whether their genomic data should remain in the system. It hasn’t yet been decided if participants can request further investigation of their genome – beyond the scope of newborn screening – at a later date, says Scott.
After the two-year sampling window closes, a cost-benefit analysis of the program will begin, developing evidence for the UK National Screening Committee which advises the government and NHS on screening policies. It’s a process that could take some time.
Chatterjee suggests an entire lifetime might be needed to measure the economic savings that would come from early diagnosis of certain diseases, citing the costs of special needs schooling for children and support for adults living with certain rare genetic conditions: “How does that balance against the technical cost of making a diagnosis and then treatment?”
“I’m quite certain that this cost-benefit equation will balance,” Chatterjee adds.
Multiple interviewees for this article viewed genome sequencing as an extension of current testing, though stopped short of suggesting it could become standard practice for all newborn babies. Even Topol, a staunch advocate for genomics, does not believe it will become universal. “I don’t think you can mandate something like this,” he says. “We’re going to have an anti-genomic community, let’s face it.”
Members of the medical community have expressed a variety of concerns about the program’s approach and scope.
In comments released last December, Angus Clarke, clinical professor at the Institute of Cancer and Genetics at Cardiff University, queried if the program’s whole genome sequencing was driven by a wish to collect more genomic data, rather than improve newborn screening. Louise Fish, chief executive of the Genetic Alliance UK charity, questioned whether following other European nations that are expanding the number of conditions tested through existing bloodspot screening may have “just as great an ability to improve the lives of babies and their families.”
If genome sequencing becomes the norm, it remains to be seen how it will dovetail with precision medicine in the form of gene therapy, including gene editing. While the cost of sequencing a genome has plummeted, some gene therapies can cost millions of dollars per patient.
But for hundreds of babies not yet born in England and Wales, diagnosis of rare conditions that have routine treatments will be facilitated by the Newborn Genomes Programme.
“So much of medicine today is given in later life, and saves people for a few months or years,” says Bentley. “It’s so good to see more opportunity here to make a difference through screening and prevention during the early stages of life.
“It is investing maximally in the long-term future as a society, by screening all young people and increasing their chances of survival through genetics so they can realize their enormous potential.”