LA JOLLA, Calif. – Veritas Genetics last week announced the availability of myGenome, a service that provides whole-genome sequencing, interpretation, and genetic counseling for $999 — a price point that experts in the field have long predicted would drive mainstream market adoption of the technology.
"This is the magic number people have been waiting for," George Church, a pioneer in the genomics field and a cofounder of Veritas, told GenomeWeb. "It may not be the ideal number, but it's what we've been waiting for."
Since the $3 billion mapping of the human genome in 2003, the cost for individuals to have their genomes sequenced has dropped rapidly. Knome, another startup Church cofounded, offered whole-genome sequencing for a $350,000 price tag in 2007. Then, two years ago, Illumina launched its HiSeq X Ten system for conducting factory-scale WGS, which the company's CEO Jay Flatley claimed would enable the "first real $1,000 genome.”
WGS prices have subsequently dropped but haven't broken the $1,000 barrier, until now. For example, at one of Illumina's "Understand Your Genome" events, attendees can have their genomes sequenced and learn if they have variations linked to 1,200 medical conditions for $2,900. Sure Genomics recently launched a $2,500 WGS service, with a $150 annual fee after the first year. Many next-generation sequencing-based tests that analyze dozens or even hundreds of genes (but not the entire genome) can cost $3,000 or more.
"A lot of people feel like $3,000 is not the right price point, even if breast cancer is on the line," said Church. "But $1,000 is something a lot more people can wrap their heads around." Even more than the price, he believes people are increasingly recognizing the value of whole-genome sequencing.
Church has wondered over the years why more people aren't getting sequenced, since costs have dropped and research has shown that genetic information can be used to improve healthcare. At a Scripps Translational Science Institute conference held here last week, Church asked how many, in a packed audience of life sciences and technology experts, had their whole genomes sequenced. He later estimated that around 10 percent of several hundred attendees had raised their hands.
Two years ago, when Church asked the same question of 150 life sciences professionals at Google's Cambridge office, according to The Boston Globe, not a single hand went up. Church, who was the fifth person in the world to get sequenced, seemed pleased last week that this once very small club is losing its exclusivity. "I think this might be the year when it really takes off," he said.
For the myGenome service, Veritas is sequencing genomes at 30X coverage using an Illumina HiSeq X system. The Boston-based firm entered the consumer-focused testing space last year with a $199 test for detecting BRCA1 and BRCA2 mutations, undercutting many other traditional labs. Then, in January, Veritas announced the launch of a $299 myBRCA HiRisk test, which gauges 26 genes (including BRCA1/2) associated with heightened predisposition for breast, ovarian, and other associated cancers.
For myBRCA HiRisk and myGenome, the customer's doctor must order testing. With all of its tests, Veritas offers free pre- and post-test genetic counseling. With the myGenome launch, Veritas is also offering on-demand video counseling.
Veritas only reports genetic markers that it deems actionable in a health or lifestyle context based on the literature and guidelines. Health-related reports include the 56 genes that the American College of Medical Genetics and Genomics recommends labs return results for when conducting whole-genome or exome sequencing, as well as reports on hundreds of markers implicated in a range of disorders and diseases, pharmacogenomics, and reproductive health.
The results are communicated through a secure digital report, and customers can use an app to explore their results. If after discussing the results with their doctor customers want a second opinion or follow-up care, Veritas can connect them to specialists around the country at institutions, such as Boston Children's Hospital, Dana-Farber Cancer Institute, and Mayo Clinic.
The service also provides customers the chance to learn about their ancestry and lifestyle-related markers for things like athleticism, nutrition, and longevity. Individuals can share these results with nutritionists and fitness coaches to help them make changes in their workout regimens, nutrition, or skin care. "People don't want to have their genomes done just to hear, 'Thank you for the $1,000. You should exercise and eat better,'" said Veritas CEO Mirza Cifric, noting that MyGenome's lifestyle reports can provide more specific insights.
Moreover, since the majority of clinically meaningful variants fall outside the gene-coding regions, they wouldn't be detected without sequencing the entire genome, he added. Of course, WGS will also detect variants of unknown significance. Veritas will report VUS in a supplemental report, and the myGenome website notes that in certain cases physicians may decide to look further into specific results based on a patient's medical or personal history and perform additional testing.
What we don't want is to be prevented from getting this to people who really want it and need it.
However, Church reflected that it may be more appropriate to just wait until the science advances and Veritas updates VUS findings. Not everyone will follow this advice, he said, "but you certainly don't want it to be consuming the physician's time" discussing VUS.
Evolving regulation
Veritas launched myGenome the same week that the US Food and Drug Administration held a public workshop to hear from patients and doctors about how they prefer to learn about genetic test results. Some meeting attendees told the agency that doctors lack the time and experience to interpret genetic test reports, particularly after whole-genome or exome sequencing yields hundreds of results. Doctors find it difficult, they noted, to communicate with patients about genetic variants that confer small increases in disease risk.
During the workshop, Elizabeth Mansfield, FDA's deputy director for personalized medicine, said the agency doesn't want to restrict people from getting their genomes sequenced or interfere with the practice of medicine. However, the agency does want to track how tests are used in a medical context to determine the evidence and contextual information that should be provided so doctors and patients can interpret the results.
The agency has over the years cracked down on companies, such as 23andMe, selling health-related genetic tests directly to consumers without their physicians' involvement. With the recent clearance of 23andMe's Bloom Syndrome test, the agency required that the company ensure its customers can understand test reports.
In an interview with GenomeWeb in January, Alberto Gutierrez, director of FDA's Office of In Vitro Diagnostics and Radiological Device Evaluation, said the agency is also looking into DTC testing services that rely on test orders from a physician who "somehow has a relationship not with the patient but with the company."
At Veritas, orders for myGenome have to come from the customer's own doctor. "It's not a physician associated with the company," Cifric told GenomeWeb. "What we don't want is to be prevented from getting this to people who really want it and need it."
The agency has said it intends to regulate lab-developed tests currently overseen under CLIA, a category that comprises Vertias' myGenome and thousands of currently marketed tests. Last month, the FDA sent Sure Genomics an "untitled letter" after it launched a full DNA sequencing service, wanting to know why its SureDNA test wasn't cleared by the agency. According to Cifric, Veritas has engaged in discussions with the FDA, has been following the agency's sequencing-related public workshops, and will request a pre-submission meeting with regulators.
Veritas has also built an automated interpretation tool for determining the clinical significance of variants that Cifric believes could set the industry standard. “We're going to need to openly talk about this and how it works. We want others to follow and accept it,” he said. "We don't want someone to get their genome at Veritas and go somewhere else, and get two different results.”
The variation among testing labs in interpreting genetic test results is something the FDA is concerned about. The agency is mulling how test developers and labs can employ variant databases to support the clinical validity of genetic markers gauged by next-generation sequencing panels, and it recently launched the first community challenge to compare reproducibility and accuracy of informatics pipelines in analyzing whole-genome sequences.
Impact of testing
At the Scripps conference, several CEOs of consumer-facing genetic testing companies spoke about their desire to democratize DNA information. They championed the individual who walks into a doctor's office with genetic test results in hand. That is an educational moment, they said, a golden opportunity for the doctor to encourage the behavioral changes no one wants to make, but which go a long way toward improving health without costly interventions.
After the Human Genome Project was completed, genomic tools were slow to gain adoption outside of academic labs, 23andMe CEO Anne Wojcicki said at the meeting. "It wasn't moving forward the way I wanted it to move forward," she said. "If we're going to have this genomics revolution, it's going to be driven by the consumer."
23andMe now has more than 1.2 million customers, a large enough base to push consumer genomics to "go viral," Wojcicki believes. "There's a real demand out there," she said. "That's part of tapping into the millennial mentality. People love learning about 'me.'" The reason 23andMe reports "fun" genetic traits for hair curl and ear wax, she said, is to engage people, and educate them about genetics and its potential. "People don't have to think about genetics as just death and dying."
The potential of genomics doesn't need a hard sell at a conference called "The Future of Genomic Medicine," where the master of ceremonies is Eric Topol, the renowned cardiologist who has predicted the death of paternalistic healthcare and the rise of the technology-empowered patient. Still, there were a few non-believers.
Sometimes when I get on the West Coast, you guys think that everyone's going to want this and everyone's going to love this. And it's not necessarily true.
Given the limited time a doctor has with each patient, cardiologist John Sotos thought broadly offering genetic testing to consumers will result in harm. Spending five minutes to explain the small influence that many genetic markers have on the risk of complex diseases is five minutes the doctor doesn't have to discuss things that may be more meaningful to the patient's health. "I think all this is going to go somewhere someday," Sotos said. "I worry that the state of the preventive medicine [in genomics] now is that there is virtually no benefit to the patient, with a few exceptions like the BRCA gene."
His concerns didn't find much support at the conference. "Why do we want to tell people not to learn about themselves?" Wojcicki asked, adding that genomic information can motivate people to make behavioral changes, like eating right and exercising, that doctors have a tough time convincing patients to make and stick to.
Most behavioral impact studies have been done on early adopters of genetic testing who tend to be well educated and wealthy, so it's hard to extrapolate the findings to the broader population. Still, an early investigation in 2011 that Topol was involved in, showed that among more than 2,000 people who had received DTC genetic testing, there was no significant differences in anxiety, intake of fat, or exercise over a period of three months.
As genomic testing became more prevalent in subsequent years, studies began to reveal a more nuanced picture. For example, data from the Impact of Personal Genomics (PGen) Study between 2012 and 2013 found that 42 percent of more than 1,000 surveyed individuals who had received DTC testing reported "positive" changes in terms of diet and exercise; some took supplements; a smaller subset took over-the-counter and prescription drugs with and without consulting a doctor. Only 1 percent of all study subjects changed a prescription without discussing it with a doctor.
PGen considered the impact of tests that genotype hundreds of thousands of variants, but WGS casts a much wider net and picks up a lot more. This has some people worried that results will stress out patients and physicians, leading to unnecessary healthcare utilization and increased costs.
But when researchers considered the impact of WGS in a randomized study called MedSeq, they found that in the short term there were no statistically significant differences in average healthcare costs between a group that received a report of their family medical history, and a group that received family history information and learned about medically relevant variants through genome sequencing. MedSeq also showed, however, that although doctors sometimes made mistakes in communicating genomic information to patients, they improved their understanding over time and with support from genetics experts.
Interestingly, this study has also hinted at the reality that not everybody will be enthusiastic about getting sequenced. About a third of 500 people going through the consent process for MedSeq ultimately declined, citing a variety of reasons, including fear of insurance discrimination, psychosocial issues related to the results, and privacy concerns.
This was a surprising finding, Robert Green, a geneticist at Brigham and Women's Hospital and principal investigator of the MedSeq project, said at the Scripps meeting. "Sometimes when I get on the West Coast, you guys think that everyone's going to want this and everyone's going to love this," he said. "And it's not necessarily true."
Recognizing this, Veritas is proceeding with care. Before launching its WGS service, Veritas piloted it last year among participants in the Personal Genome Project, an effort launched by Church in 2005 that hosts genomic and health information from thousands of participants who have agreed to share their data publicly for research. Several experts involved with the PGP are executives at Veritas and bring with them more than a decade of experience sequencing and interpreting whole genomes.
Several hundred PGP participants signed up for whole-genome sequencing through Veritas' initial offering, Cifric said, and the company is sequencing their genomes in batches. Now, having launched myGenome, Veritas has capped the number of genomes it will sequence in the first year at 5,000. "The reason we're doing that is because we want to do it right," he said. "We want to learn from this, and optimize the product."
But ultimately, "our goal is George's goal," Cifric said, laughing. "To sequence everybody."