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.
Researchers successfully isolated both plant and human RNA and DNA in the field, demonstrating the potential for their new dipstick technology to identify deadly bacteria, pathogens, and diseases in water, food, and even humans
Australian researchers at the University of Queensland (UQ) have developed an intriguing “dipstick” technology that might make it possible to use simple equipment to sequence DNA and RNA in the field. Among the potential applications that will interest clinical laboratory professionals is the ability for this technology to identify pathogens, both in humans and the environment.
Medical laboratories and anatomic pathologists are aware that gene sequencing (AKA, Nucleic Acid Sequencing) is the coming revolution in diagnostics. But the process is still costly and anchored to immovable technology that requires controlled environments and reliable resources. This promising new technology could make it simpler, cheaper, and faster to extract human DNA and RNA in settings outside a sophisticated core medical laboratory.
The UQ researchers developed technology that could affect how and where diagnostic tests for a whole range of pathogens are performed. For example, tests for bacteria such as E. coli in water supplies, pathogens in food, and diseases in humans currently are conducted in environmental and clinical laboratories. This new technology may allow such diagnostics to be done in extremely remote environments.
Isolating DNA/RNA in the Field
Jimmy Botella, PhD, Professor of Plant Biotechnology, and Michael Mason, PhD, Senior Post-doctoral researcher, both at the University of Queensland, led a team of researchers who published their findings in the journal PLOS Biology. The team developed a process they called “dipstick technology,” which allows DNA and RNA to be isolated quickly and without the use of specialized equipment.
They began by using the technology on particular plants, but soon found it could be used in many other situations.
“We found it had much broader implications as it could be used to purify DNA or RNA from human blood, viruses, fungi, and bacterial pathogens from infected plants or animals,” Botella noted in a press release.
The researchers’ objective was to investigate whether or not several different materials could be used to extract nucleic acids. “The first step in any application aiming to amplify DNA or RNA is the extraction of nucleic acids from a complex biological sample; a task traditionally requiring specialized equipment, trained technicians, and multiple liquid handling steps,” they wrote in the published study.
Holding the dipstick technology (from left) Dr. Michael Mason, Professor Jimmy Botella, and Yiping Zhou, all researchers at the University of Queensland in Brisbane, Australia. (Caption and photo copyright: University of Queensland.)
Their aim was to find a simpler process that required far less personnel and equipment. They found that cellulose-based filter paper could be used to bind nucleic acids. The filter paper, which was the control early in their investigation, even retained the nucleic acids through a purification process that removed contaminants. “We then adapted the cellulose filter to create a dipstick that can be used to purify nucleic acids from a wide range of plant, animal, and microbe samples in less than 30 seconds without the need for specialized equipment,” the researchers reported.
The team conducted its first tests on the plant species A. thaliana, a flowering plant found in Africa and Eurasia. However, wanting their dipstick technology to be useful in the field, they expanded their experiments to include various species of wheat, rice, soybean, tomato, and other plants. Citrus plants, known to be challenging, also were successfully tested.
The researchers then tested if their new technology would be useful for applications in humans, which is more complicated. HIV and hepatitis can be diagnosed using commercial kits, but those kits are not useful in many settings because the samples often require sophisticated manipulation. The researchers’ method—using cellulose paper and a one-minute wash—succeeded in amplification of the nucleic acid.
Performing Diagnostics in Hospitals, on Farms, and Even in the Jungle!
The University of Queensland’s commercialization company, UniQuest, has filed a patent application for the new technology. They are currently seeking partners to commercialize and sell the dipstick technology worldwide.
“Our dipsticks, combined with other technologies developed by our group, mean the entire diagnostic process from sample collection to final result could be easily performed in a hospital, farm, hotel room, or even a remote area such as a tropical jungle,” Botella noted in the press release.
The team conducted much of their field research on remote plantations in Papua New Guinea. They conducted tests on trees, livestock, human diseases, and to detect pathogens in food and water. “The dipstick technology makes diagnostics accessible to everyone,” Botella told Technology Networks.
Dipstick Diagnostics Not New to Point-of-Care Testing
As Modern Healthcare Executive noted, dipstick technology for various diagnostic purposes is not new, even though this particular application is, potentially, revolutionary. There are dipstick tests for everything from pregnancy to cholera. Also referred to as point-of-care testing (POCT), research and development of this technology has steadily grown, and as the UQ study shows, will likely continue.
While there are certainly advantages to quick diagnostic tests that can be conducted in the field, there are some challenges, as well. Julie L. V. Shaw, PhD, Assistant Professor, Department of Pathology and Laboratory Medicine at The University of Ottawa, argues that “there are many challenges associated with POCT, mainly related to quality assurance,” in a paper she published in the journal Practical Laboratory Testing.
Technology will continue to develop and drive innovation and change in how diagnostics are performed and thus in how clinical laboratories operate. Various initiatives driving the industry toward personalized medicine and value-based care are sure to play a role, alongside new technology and other advancements.
With all of those changes, one thing remains critically important and that is the value of human understanding and innovation.
The Cold Spring Harbor Laboratory has a long history and an enviable reputation. It was founded in 1890 to train teachers in biology. However, by 1904, the laboratory’s mission had been expanded to include research in genetics. In 1924, the research mission was further enlarged to include quantitative biology—in particular, physiology and biophysics.
It was in 1968 that Nobel laureate James Watson, then a professor at Harvard University, accepted the directorship of the Cold Spring Harbor Laboratory while also keeping his professorship at Harvard University. Watson served at some level of leadership until 2008, when he became Chancellor Emeritus. Currently CSHL laboratory houses about 200 research-related personnel. (more…)
Last week involved a full slate of pathology meetings and medical laboratory site visits on both islands of New Zealand during Dark Daily’s visit to this Pacific nation
DATELINE: CHRISTCHURCH, NEW ZEALAND—There’s a good case to be made that the health system in this South Pacific nation is farther down the path of medical laboratory regionalization and consolidation than most other developed nations.
A note of explanation about nomenclature will be helpful to Dark Daily’s international readers. In Australia and New Zealand, “pathology laboratory” is the common term for the medical laboratories that typically test blood, urine, saliva, and similar specimens. (In the United States and Canada, “clinical laboratory” is used interchangeably with medical laboratory.) “Histopathology” (or anatomic pathology) is the common term for labs that handle tissue specimens in New Zealand and Australia. (In North America, anatomic pathology, or surgical pathology laboratory is used more frequently than histopathology.) (more…)