In a disused town hall building in Stratford, East London, a familiar sight awaits those who enter. Health care workers dressed in scrubs emerge from partitioned sections to address a quiet but steady stream of arrivals. This time, though, it’s not Covid vaccinations we’re queuing for. We’re here because we have signed up to have our genomes sequenced. It follows a public outreach call by Genomics England, the UK government’s special health care arm set up to run mass genetic data-gathering initiatives like this one.
The process is simple. Participants attend a 10-minute appointment, during which vitals are taken—height, weight, waist circumference, blood pressure—followed by finger-prick testing and filling two vials with blood. Attendees’ samples are sent away for whole-genome sequencing to create a readout of all their DNA, the results of which are then added to a giant database to further genomic research. Eventually, this data should help with developing better treatments and even cures for disease.
As I approach my designated cubicle, a friendly nurse chats to me about her plants and the weather before she asks me, just as breezily, whether I’m aware of the reasons why I’m taking part in this, the Our Future Health initiative. Such is the familiar nature of genome sequencing to many of us today. Not so long ago, this was the stuff of science fiction. Now it’s little more than a 10-minute appointment on a high street near you.
So how can I get my genome sequenced?
For now, there are two main ways. The first is to participate in research like the Our Future Health initiative. I was invited to take part as part of a pilot scheme for the program at the beginning of 2023. But the scheme has since expanded so that anyone over 18 and living in the UK can sign up. Similar projects to digitize citizens’ DNA are being undertaken in Australia, Iceland, the Netherlands, the UK, and the US. Each project varies by country, but the idea is always to gather more public data from volunteers to improve health care. Details of these projects can invariably be found online.
The other way is to pay to have your DNA analyzed. Many will be familiar with the popular mail-order DNA test kits from the likes of 23andMe and Ancestry.com, the most accessible commercial options. Millions of us around the world have already had our genetic traits and ancestral lineage analyzed for just a couple hundred dollars and a test tube worth of spit. Since the company first went online in 2007, 23andMe claims to have analyzed more than 12 million customers’ samples.
And how does sequencing work?
There is a world of difference between the service that these ancestry companies provide and the whole-genome testing currently being rolled out in research and public health care.
The majority of genetic tests available online look only at a select number of common genetic variables called single nucleotide polymorphisms (SNPs), along with some other markers of genetic variation. The human genome is made up of 6.4 billion molecules, called nucleotides, which are arranged in pairs. An SNP is a point in the genome where a nucleotide pair can differ between individuals, often influencing a trait that they might have. For example, SNPs can determine a person’s eye color or their ability to sweat. Both 23andMe and Ancestry measure between 500,000 and 700,000 different genetic markers like these.
In comparison, whole-genome sequencing determines every single base pair of DNA, and is much more expensive as a result. If you printed out all 6.4 billion letters of your whole genome, it would fill around 4,200 average-size books. A service like 23andMe provides a snapshot—around 1 percent of your DNA, a mere pamphlet by comparison. The vast majority of genetic data is assumed.
That’s not necessarily a bad thing. As Arnab Chowdry, vice president of product R&D at 23andMe points out, whole-genome data is “largely uninterpretable and kind of impractical for individual users.” In reality, we still don’t know what much of our genetic coding does—and certainly with the technology available to us today, it would be difficult for anyone to make use of all of that data, let alone be able to store it on their home computer.
23andMe and most of its competitors use what’s called a microarray platform. “We look at specific locations in the genome where we know people vary from one another,” Chowdry explains. “Over 99 percent of our DNA is exactly the same, and so we really only need to get a reading of one genetic marker in each region. From there we can fill in the gaps of your genome.”
This approach, known as genotyping, can still provide accurate health insights—consumers can typically choose whether or not to include specific mutations, such as the cancer-causing mutations in the BRCA1 and BRCA2 genes, in their DNA report. But the analysis is limited, and most companies will caveat that SNPs are only indicators of health risks, not certainties, since a great deal of information remains hidden in the wider genome.
How much does it cost?
23andMe’s and Ancestry.com’s prices begin at $99 for their most basic services. Whole-genome sequencing, because it has to read much, much more genetic material, costs more. Nonetheless, whole-genome sequencing is starting to reach the commercial market.
US company Veritas was one of the first to offer a whole-genome service to the public, for $999, in 2016. Dante Genomics, founded in Italy around the same time, now dominates in Europe with a price point of €500 ($534). Prices are steadily falling as the market grows and technologies become more accessible.
Chowdry predicts that the lower-cost commercial tests will shift toward whole-genome analysis in the near future. “I anticipate microarrays will be around for a little while yet, but I’m excited for a future where whole-genome sequencing replaces them,” he says. “If whole-genome sequencing falls to the same price point, and it provides more information for customers, why wouldn’t we do that?”
And so, why do it?
With commercial genotyping tests, you can use the information gleaned to trace your ancestry, as well as examine indications of health risks that you might be predisposed to because of your genetics—though companies are keen to stress that the information they provide should not be interpreted as disease predictions.
On the research side, the benefits are largely still to be realized, but are potentially far greater. Cancer patients and children born with rare diseases are already being offered the chance to have their full genetic data mapped, in the hopes that this will provide clues as to what causes their conditions. And in the future, there’s the promise of allowing a person’s medical treatment to be personalized according to their genetics, or to use a person’s genetic information to prevent them from getting certain diseases altogether.
England is marching ahead on this front. It is the first country actively seeking to tie in whole-genome data to its National Health Service (NHS), in the knowledge that one day before long, whole-genome sequencing will be routine, and that prevention is always going to be more effective and more affordable than cure. In the UK, Our Future Health is just one public genomics initiative being rolled out this year. Another will begin at the end of 2023 to sequence the whole genomes of 10,000 newborn babies.
The main purpose of the Our Future Health and Newborn Genomes programs is to build up a wide-reaching, diverse genetic database for research. Currently, volunteers like me won’t receive their data packaged up and sent back to us—although we can consent to being contacted again if the analysis uncovers a potential health concern.
Partly for this reason, the NHS finds itself competing with commercial companies for interest. As a tactic, organizers behind Our Future Health are in the process of developing a way to provide participants with access to individual-level data and results, explains Andrew Roddam, a leading epidemiologist and CEO of Our Future Health. “How exactly we will deliver the genetic feedback to individuals is being developed with genetic counselors,” he adds.
In other words, ethical guidelines pending, it may not be long before everybody in England has the opportunity to sequence their whole genome and learn about their health and ancestry for free through the NHS. Such a move will revolutionize health care. Genetic mutations responsible for causing diseases and other health risks will be picked up much earlier in a person’s life, dramatically improving health outcomes. But there is still “a huge gap between [the idea] and sequencing everyone from birth,” says Roddam. “The system has got to evolve a long way for that to become the norm. We have to design interventions and the right courses of action for the information gleaned. But it is starting now in that there is lots of evidence being generated to show how the technology is already working to help diagnose people earlier and make a real impact.”
Is my genetic data safe?
Another major challenge—for public health care providers but also for commercial and private entities—will be safely storing the huge amount of genetic data generated through sequencing, something consumers are rightly wary of.
“While there’s no such thing as totally risk-free, the motivation for storing this data is absolutely not to mess around. It’s to do research that will help to cure horrible diseases,” says Ewan Birney, deputy director general of the European Molecular Biology Laboratory and a nonexecutive director of Genomics England. “Giving researchers responsible access to data is an important part of that,” he argues, adding: “We give away plenty of other personal information about ourselves online every day. Banking details, for example, are arguably far more dangerous.”
Data from the Our Future Health Initiative is stored in the UK Biobank, a large-scale biomedical database established to further medical research. Other countries in Europe have similar genomic data libraries that allow researchers read-only access to de-identified genetic data. Meanwhile, commercial DNA tests tend to require customer consent to contribute their data to research (around 80 percent of 23andMe’s customers agree to do so).
Given the existing public concerns around data protection, it’s reasonable for participants in any DNA testing to have concerns about privacy. In most cases, personal genetic data will only be shared where the law demands it—for example, where there has been a crime—but it’s worth thinking about the relationship between law enforcement and genetic data compliance where you live.
As a private company, 23andMe says it is resistant to sharing any data with law enforcers, stating: “We will closely scrutinize all law enforcement requests and we will only comply with court orders, subpoenas, search warrants, or other requests that we determine are legally valid. To date we have not released any customer information to law enforcement.”
What does the future hold for genomics?
In all likelihood, there will come a time when everyone living in wealthier Western countries will have their genomes sequenced from birth. “It’s becoming a commodity, and we will be able to do basic genomic annotation, calculation of risk scores, and assessment of genes with known actionable variants for the most part,” predicts Russ Altman, professor of bioengineering at Stanford University.
It’s not implausible to imagine that one day our genomes could even be used as a biometric marker, or replace ID cards as a form of identification and security. The technology is available now, but even so, experts believe we’re a long way off from that reality. Public acceptance has a ways to catch up. “People will object to taking it that far on account of privacy issues,” Altman says.
One of the most promising and realistic uses for whole-genome data will likely be in the field of pharmacogenetics, he adds: the study of how drugs metabolize in the body and impact genetic pathways. Improving our understanding of this is our best hope yet of unlocking the dream of precision medicine, whereby each patient will receive a prescription dose tailored to suit their specific genetic makeup.
This is also where public, private, and commercial offerings could be integrated to build the broadest picture possible of human genetics. “There’s a specific gene called CYP2D6, for example, that’s incredibly important to drug metabolism, that commonly-used genome-sequencing technologies really struggle with,” says Chowdry, reflecting on where he hopes attention will fall in the near future. “Filling in those gaps is going to be a core piece of how this technology improves over the coming years.”
