Ultima Genomics says it is emerging from “stealth mode” with millions in fresh capital and technology capable of sequencing whole human genomes for a fraction of the cost
Investors seem to be optimistic that an emerging genetics company has the proprietary solution to sequence a whole human genome for just $100. If true, this is a development that would be of interest to clinical laboratory managers and pathologists.
The company, Ultima Genomics of Newark, Calif., recently announced that it had raised $600 million from the investment community. In a press release last month, the company announced it has “emerged from stealth mode with a new high-throughput, low-cost sequencing platform that delivers the $100 genome.”
The press release goes on to state that Ultima will unleash a new era in genomics-driven discoveries by developing a “fundamentally new sequencing architecture designed to scale beyond conventional approaches, including completely different approaches to flow cell engineering, sequencing chemistry, and machine learning.”
Are we at the cusp of a revolution in genomics? Ultima Genomics’ founder and CEO, Gilad Almogy, PhD, believes so.
“Our architecture is intended for radical scaling, and the $100 genome is merely the first example of what it can deliver,” he said in the press release. “We are committed to continuously drive down the cost of genomic information until it is routinely used in every part of the healthcare system.”
From an Estimated Cost of $3 Billion to $450 in Just 30 Years!
Whole genome sequencing (WGS) has decreased dramatically in cost since research into the technology required got started in the early 1990s with the publicly-funded Human Genome Project. At that time, the cost to sequence the entire human genome was estimated at around $3 billion. Then, in 1998, John Craig Venter created Celera Genomics (now a subsidiary of Quest Diagnostics) and was the first to sequence the whole human genome (his own) and at a significantly lower cost of around $300 million.
When DNA sequencer Illumina announced in 2014 the arrival of the $1,000 genome, the news was expected to put whole genome sequencing on the road to becoming routine, Forbes reported. But that prediction didn’t pan out.
Ultima Genomics’ $100 price point, however, could be game changing. It would make the cost of decoding a human genome affordable for nearly everyone and accelerate the growth of personalized medicine in clinical laboratory diagnostics.
Applied Physics versus Biological Sciences
According to GEN, Almogy brings a tech background to Ultima—his PhD is in applied physics, not the biological sciences. He founded Ultima in 2016 after serving as founder, president, and CEO at Fulfil Solutions, a manufacturer of custom automation robotics systems. At Ultima, his goal is to “unleash the same relentless scaling in sequencing” that was used to drive down the cost of computing power and transform modern life.
TechCrunch reported that Ultima’s UG100 sequencing machine and software platform can perform a complete sequencing of a human genome in about 20 hours, with precision comparable to existing options, but does so at a far lower cost per gigabase (Gb), equal to one billion base pairs.
According to the Ultima Genomics website, its breakthroughs include:
An open substrate that creates a massive, low-cost reaction surface that delivers many billions of reads while avoiding costly flow cells and complicated fluidics.
Novel scalable chemistry that combines the speed, efficiency, and read lengths of natural nucleotides with the accuracy and scalability of endpoint detection.
A revolutionary sequencing hardware that uses spinning circular wafers that enable efficient reagent use, zero crosstalk, and ultra-high-speed scanning of large surfaces.
Affordable Genomics Will Lead to ‘Millions of Tests per Year’
Exact Sciences’ Chairman and CEO Kevin Conroy—whose Wisconsin-based molecular diagnostics company recently entered into a long-term supply agreement for Ultima Genomic’s NGS technologies—believes low-cost genomic sequencing will improve cancer screening and disease monitoring.
“Exact Sciences believes access to differentiated and affordable genomics technologies is critical to providing patients better information before diagnosis and across all stages of cancer treatment,” Conroy said in a press release. “Ultima’s mission to drive down the cost of sequencing and increase the use of genomic information supports our goal to provide accurate and affordable testing options across the cancer continuum. This is particularly important for applications like cancer screening, minimal residual disease, and recurrence monitoring, which could lead to millions of tests per year.”
GEN pointed out that Ultima’s 20-hour turnaround time is fast and its quality on par with its competitors, but that it is Ultima’s $1/Gb price (noted in the preprint) that will set it apart. That cost would be a fraction of Illumina’s NextSeq ($20/Gb) and Element Biosciences’ AVITI ($5/Gb).
Almogy told TechCrunch that Ultima is working with early access partners to publish more proof-of-concept studies showing the capabilities of the sequencing technique, with broader commercial deployment of the technology in 2023. Final pricing is yet to be determined, he said.
If the $100 genome accelerates the pace of medical discoveries and personalized medicine, clinical laboratory scientists and pathologists will be in ideal positions to capitalize on what the executives and investors at Ultima Genomics hope may become a revolution in whole human genome sequencing and genomics.
Genomic sequencing continues to benefit patients through precision medicine clinical laboratory treatments and pharmacogenomic therapies
EDITOR’S UPDATE—Jan. 26, 2022: Since publication of this news briefing, officials from Genomics England contacted us to explain the following:
The “five million genome sequences” was an aspirational goal mentioned by then Secretary of State for Health and Social Care Matt Hancock, MP, in an October 2, 2018, press release issued by Genomics England.
As of this date a spokesman for Genomics England confirmed to Dark Daily that, with the initial goal of 100,000 genomes now attained, the immediate goal is to sequence 500,000 genomes.
In accordance with this updated input, we have revised the original headline and information in this news briefing that follows.
What better proof of progress in whole human genome screening than the announcement that the United Kingdom’s 100,000 Genome Project has not only achieved that milestone, but will now increase the goal to 500,000 whole human genomes? This should be welcome news to clinical laboratory managers, as it means their labs will be positioned as the first-line provider of genetic data in support of clinical care.
Many clinical pathologists here in the United States are aware of the 100,000 Genome Project, established by the National Health Service (NHS) in England (UK) in 2012. Genomics England’s new goal to sequence 500,000 whole human genomes is to pioneer a “lasting legacy for patients by introducing genomic sequencing into the wider healthcare system,” according to Technology Networks.
The importance of personalized medicine and of the power of precise, accurate diagnoses cannot be understated. This announcement by Genomics England will be of interest to diagnosticians worldwide, especially doctors who diagnose and treat patients with chronic and life-threatening diseases.
Building a Vast Genomics Infrastructure
Genetic sequencing launched the era of precision medicine in healthcare. Through genomics, drug therapies and personalized treatments were developed that improved outcomes for all patients, especially those suffering with cancer and other chronic diseases. And so far, the role of genomics in healthcare has only been expanding, as Dark Daily covered in numerous ebriefings.
Genomics England, which is wholly owned by the Department of Health and Social Care in the United Kingdom, was formed in 2012 with the goal of sequencing 100,000 whole genomes of patients enrolled in the UK National Health Service. That goal was met in 2018, and now the NHS aspires to sequence 500,000 genomes.
Genomics England’s initial goals included:
To create an ethical program based on consent,
To set up a genomic medicine service within the NHS to benefit patients,
To make new discoveries and gain insights into the use of genomics, and
To begin the development of a UK genomics industry.
To gain the greatest benefit from whole genome sequencing (WGS), a substantial amount of data infrastructure must exist. “The amount of data generated by WGS is quite large and you really need a system that can process the data well to achieve that vision,” said Richard Scott, MD, PhD, Chief Medical Officer at Genomics England.
In early 2020, Weka, developer of the WekaFS, a fully parallel and distributed file system, announced that it would be working with Genomics England on managing the enormous amount of genomic data. When Genomics England reached 100,000 sequenced genomes, it had already gathered 21 petabytes of data. The organization expects to have 140 petabytes by 2023, notes a Weka case study.
Putting Genomics England’s WGS Project into Action
WGS has significantly impacted the diagnosis of rare diseases. For example, Genomics England has contributed to projects that look at tuberculosis genomes to understand why the disease is sometimes resistant to certain medications. Genomic sequencing also played an enormous role in fighting the COVID-19 pandemic.
Scott notes that COVID-19 provides an example of how sequencing can be used to deliver care. “We can see genomic influences on the risk of needing critical care in COVID-19 patients and in how their immune system is behaving. Looking at this data alongside other omics information, such as the expression of different protein levels, helps us to understand the disease process better,” he said.
What’s Next for Genomics Sequencing?
As the research continues and scientists begin to better understand the information revealed by sequencing, other areas of scientific study like proteomics and metabolomics are becoming more important.
“There is real potential for using multiple strands of data alongside each other, both for discovery—helping us to understand new things about diseases and how [they] affect the body—but also in terms of live healthcare,” Scott said.
Along with expanding the target of Genomics England to 500,000 genomes sequenced, the UK has published a National Genomic Strategy named Genome UK. This plan describes how the research into genomics will be used to benefit patients. “Our vision is to create the most advanced genomic healthcare ecosystem in the world, where government, the NHS, research and technology communities work together to embed the latest advances in patient care,” according to the Genome UK website.
Clinical laboratories professionals with an understanding of diagnostics will recognize WGS’ impact on the healthcare industry. By following genomic sequencing initiatives, such as those coming from Genomics England, pathologists can keep their labs ready to take advantage of new discoveries and insights that will improve outcomes for patients.
Medical laboratories are already using gene sequencing as part of a global effort to identify new variants of the coronavirus and their genetic ancestors
Thanks to advances in genetic sequencing technology that enable medical laboratories to sequence organisms faster, more accurately, and at lower cost than ever before, clinical pathology laboratories worldwide are using that capability to analyze the SARS-CoV-2 coronavirus and identify variants as they emerge in different parts of the world.
The US Centers for Disease Control and Prevention (CDC) now plans to harness the power of gene sequencing through a new consortium called SPHERES (SARS-CoV-2 Sequencing for Public Health Emergency Response, Epidemiology, and Surveillance) to “coordinate SARS-CoV-2 sequencing across the United States,” states a CDC news release. The consortium is led by the CDC’s Advanced Molecular Detection (AMD) program and “aims to generate information about the virus that will strengthen COVID-19 mitigation strategies.”
The consortium is comprised of 11 federal agencies, 20 academic institutions, state public health laboratories in 21 states, nine non-profit research organizations, and 14 lab and IVD companies, including:
Oxford Nanopore Technologies
Verily Life Sciences
‘Fundamentally Changing How Public Health Responds’
Gene sequencing and related technologies have “fundamentally changed how public health responds in terms of surveillance and outbreak response,” said Duncan MacCannell, PhD, Chief Science Officer for the CDC’s Office of Advanced Molecular Detection (OAMD), in an April 30 New York Times (NYT) article, which stated that the CDC SPHERES program “will help trace patterns of transmission, investigate outbreaks, and map how the virus is evolving, which can affect a cure.”
The CDC says that rapid DNA sequencing of SARS-CoV-2 will help monitor significant changes in the virus, support contact tracing efforts, provide information for developers of diagnostics and therapies, and “advance public health research in the areas of transmission dynamics, host response, and evolution of the virus.”
The sequencing laboratories in the consortium have agreed to “release their information into the public domain quickly and in a standard way,” the NYT reported, adding that the project includes standards for what types of information medical laboratories should submit, including, “where and when a sample was taken,” and other critical details.
Sharing Data Between Sequencing Laboratories and Biotech Companies
The CDC announced the SPHERES initiative on April 30, although it launched in early April, the NYT reported.
According to the CDC, SPHERES’ objectives include:
To bring together a network of sequencing laboratories, bioinformatics capacity and subject matter expertise under the umbrella of a massive and coordinated public health sequencing effort.
To identify and prioritize capabilities and resource needs across the network and to align sources of federal, non-governmental, and private sector funding and support with areas of greatest impact and need.
To improve coordination of genomic sequencing between institutions and jurisdictions and to enable more resilience across the network.
To champion concepts of openness, standards-based analysis, and rapid data sharing throughout the United States and worldwide during the COVID-19 pandemic response.
To provide a common forum for US public, private, and academic institutions to share protocols, methods, bioinformatics tools, standards, and best practices.
To establish consistent data and metadata standards, including streamlined repository submission processes, sample prioritization criteria, and a framework for shared, privacy-compliant unique case identifiers.
To align with other national sequencing and bioinformatics networks, and to support global efforts to advance the use of standards and open data in public health.
Implications for Developing a Vaccine
As the virus continues to mutate and evolve, one question is whether a vaccine developed for one variant will work on others. However, several experts told The Washington Post that the SARS-CoV-2 coronavirus is relatively stable compared to viruses that cause seasonal flu (influenza).
Nor, he said, is one variant likely to cause worse clinical outcomes than others. “So far, we don’t have any evidence linking a specific virus [strain] to any disease severity score. Right now, disease severity is much more likely to be driven by other factors.”
Fast improvements in gene sequencing technology have made it faster, more accurate, and cheaper to sequence. Thus, as the COVID-19 outbreak happened, there were many clinical laboratories around the world with the equipment, the staff, and the expertise to sequence the novel coronavirus and watch it mutate from generation to generation and from region to region around the globe. This capability has never been available in outbreaks prior to the current SARS-CoV-2 outbreak.
This may provide opportunities for clinical laboratories. However, some experts are concerned that genetic sequencing may not be equally available to patients of all socioeconomic classes. Nor is it clear how health systems plan to pay for the equipment and services, since health insurance companies continue to deny coverage for “elective” gene sequencing, or when there is not a “clear medical reason for it, such as for people with a long family history of cancer,” notes STAT.
Therefore, not everyone is convinced of the value of gene sequencing to either patients or hospitals, even though advocates tout gene sequencing as a key element of precision medicine.
Is Preventative Genetic Sequencing Ready for the Masses?
Brigham’s Preventive Genomics Clinic offers comprehensive DNA sequencing, interpretation, and risk reporting to both adults and children. And MGH “plans to launch its own clinic for adults that will offer elective sequencing at a similar price range as the Brigham,” STAT reported.
The Brigham and MGH already offer similar gene sequencing services as other large health systems, such as Mayo Clinic and University of California San Francisco (UCSF), which are primarily used for research and cancer diagnoses and range in price depending on the depth of the scan, interpretation of the results, and storage options.
However, some experts question whether offering the
technology to consumers for preventative purposes will benefit anyone other
than a small percentage of patients.
“It’s clearly not been demonstrated to be cost-effective to promote this on a societal basis,” Robert Green, MD, MPH, medical geneticist at Brigham and Women’s Hospital, and professor of genetics at Harvard, told STAT. “The question that’s hard to answer is whether there are long-term benefits that justify those healthcare costs—whether the sequencing itself, the physician visit, and any downstream testing that’s stimulated will be justified by the situations where you can find and prevent disease.”
Additionally, large medical centers typically charge more
for genomic scans than consumer companies such as 23andMe and Ancestry. Hospital-based
sequencing may be out of the reach of many consumers, and this concerns some
“The idea that genomic sequencing is only going to be
accessible by wealthy, well-educated patrons who can pay out of pocket is
anathema to the goals of the publicly funded Human Genome Project,” Jonathan
Berg, MD, PhD, Genetics Professor, University of North Carolina at Chapel
Hill, told Scientific
And, according to the American Journal of Managed Care, “It’s estimated that by 2021, 100 million people will have used a direct-to-consumer (DTC) genetic test. As these tests continue to gain popularity, there is a need for educating consumers on their DTC testing results and validating these results with confirmatory testing in a medical-grade laboratory.”
This is why it’s critical that clinical laboratories and
anatomic pathology groups have a genetic testing and gene sequencing strategy,
David Bick, MD, Chief Medical Officer at the HudsonAlpha Institute for Biotechnology and Medical Director of the Smith Family Clinic for Genomic Medicine, told Scientific American, “there’s just more and more interest from patients and families not only because of 23andMe and the like, but because there’s just this understanding that if you can find out information about your health before you become sick, then really our opportunity as physicians to do something to help you is much greater.”
Is Preventative Genomics Elitist?
As large medical centers penetrate the consumer genetic
testing market some experts express concerns. In a paper he wrote for Medium,
titled, “Is Preventive Genomics Elitist?” Green asked, “Is a service like this
further widening the inequities in our healthcare system?”
Green reported that while building the Preventive Genomics Clinic at Brigham, “we … struggled with the reality that there is no health insurance coverage for preventive genomic testing, and our patients must therefore pay out of pocket. This is a troubling feature for a clinic at Brigham and Women’s Hospital, which is known for its ties to communities in Boston with diverse ethnic and socioeconomic backgrounds.”
Most of Brigham’s early genetics patients would likely be “well-off,
well-educated, and largely white,” Green wrote. “This represents the profile of
typical early adopters in genetic medicine, and in technology writ large. It
does not, however, represent the Clinic’s ultimate target audience.”
More Data for Clinical Laboratories
Nevertheless, preventive genomics programs offered by large
health systems will likely grow as primary care doctors and others see evidence
Therefore, medical laboratories that process genetic
sequencing data may soon be working with growing data sets as more people reach
out to healthcare systems for comprehensive DNA sequencing and reporting.
By offering a way for customers to have their DNA sequenced without any fear of being identified, Nebula Genomics hopes to revive interest in personal genetics
Nebula Genomics is introducing a new model for genetic sequencing that emphasizes privacy and consumer ownership of data. It does this by allowing customers to anonymously submit their DNA and pay for sequencing without including any personally identifiable information. In a twist that will interest medical laboratory professionals, Nebula is using blockchain as part of this gene testing service.
Just as all clinical laboratories and anatomic pathology groups are responsible for the privacy of their customers’ protected health information (PHI), so too must personal genomics companies like Nebula, 23andMe, and Ancestry, ensure their customers’ privacy, protect their PHI, and remove all identifiable information from customers’ genetic data before sharing it with research labs and pharmaceutical companies.
For all the recent advances in sequencing, there remain serious concerns about privacy, and there’s no information more personal than that contained in a person’s DNA.
“People started seeing services they use every day not working the way they were intended. And it’s had a strong whiplash in the genomics space,” Kevin Quinn, the Chief Product Officer at Nebula Genomics, told Wired.
Thus, Nebula’s anonymous DNA sequencing kit could be the answer. The concept is, rather than risking not completely removing all of a customer’s identifying information from the data, don’t receive it in the first place.
“It doesn’t need to be de-identified on our end because it’s already intrinsically separate,” Quinn told Wired. “And that’s never really been done before.”
Blockchain, Privacy, and Lawsuits
In 2018, Nebula began using blockchain to enable its customers to control the use of their genetic data. In addition, customers can earn money from research companies that are willing to pay for their genetic data. This exchange of information for cash has been at the heart of blockchain since the technology’s inception in the cryptocurrency industry in 2008. Since then, blockchain has found use in other industries as well, including healthcare.
Nebula’s terms of privacy states: “Nebula uses blockchain technology to improve transparency and control over genetic data. We are currently in the process of developing our blockchain infrastructure to record user consent settings and requests for access to user data. This will be designed to increase transparency and immutability of data access request and user consent for sharing data. By storing data requests and consent settings on the blockchain, Nebula hopes to enable users to audit any transactions involving their data to ensure that all of the data sharing is acceptable and no misuse of data has taken place.”
Pharmaceutical and research companies are interested in genetics information to drive the development of new drugs. In order to profit, though, these companies need information from millions of genetic tests.
However, 23andMe co-founder and CEO Anne Wojcicki said during a Wall Street Journal (WSJ) Tech Health conference that growth in the genetic company’s sales have slumped, possibly because social media has made people more aware that their private genetic data may not be secure.
“The market definitely slowed last year,” she said. “My hypothesis is that you have some of the effect from Facebook, people concerned about privacy, you had Golden State killer and so people pause.”
Can Clinical Laboratories Be Held Liable for Any of Several Potential Issues?
Of greater concern to healthcare service providers, however, may be the potential for lawsuits.
People who pay for genetic tests through companies like 23andMe may not be aware that they are allowing their genetic information to be shared with other companies. Any time sensitive information is stored, there’s the possibility of it being exposed. This can lead to unique problems for clinical laboratories, as a Science article titled, “Medical DNA Sequencing Leads to Lawsuits and Legal Questions,” describes.
“What is a doctor to do when a patient has results from a direct-to-consumer testing company like 23andMe and asks what implications they have for their health? Or when a lab notifies a doctor that a genetic variant their patient carries, thought meaningless three years ago, is now known to be harmful, but they can’t locate the patient? Can a testing lab be held liable for not regularly reviewing the scientific literature, to track science’s understanding of the gene variants it tests for?”
Anonymity and Blockchain Could Be the Solution
Complete anonymity could solve the sticky issue of privacy and how to maintain it, and Nebula’s use of blockchain provides the mechanism by which customers control the use of their genetic data.
Depending on how Nebula’s use of blockchain works, the model could become useful for clinical pathology laboratories, where the requirement for privacy is not optional. If blockchain turns out to be a secure, transparent method of transmitting genomic sequencing results, then it also may turn out to be a method for transmitting other types of lab test results, which typically contain far less data.
Blockchain continues to be a technology of interest to pathology laboratories. Nebula’s using it to maintain their customers’ anonymity while simultaneously enabling them to control the use of their genetic data is worth watching. It could become a way for patients to access clinical laboratory test results securely and privately.