Although there are healthcare providers who see the potential in microbiome testing, many clinical laboratories are not yet ready to embrace microbiome-based testing
In an unlikely string of events, no less than Nordstrom, the national department store chain, announced in September that it would offer microbiome-based test claimed to “check gut health.” Apparently, its customers were interested in this clinical laboratory test, as the Nordstrom website currently indicates that the “Health Intelligence Test Kit by Viome” is already sold out!
What does it say about consumer interest in clinical laboratory self-testing that Nordstrom has decided to offer at-home microbiome tests to its store customers? Can it be assumed that Nordstrom conducted enough marketing surveys of its customers to determine: a) that they were interested in microbiome testing; and b) they would buy enough microbiome tests that Nordstrom would benefit financially from either the mark-up on the tests or from the derived goodwill for meeting customer expectations?
Whatever the motivation, the retail giant recently announced it had partnered with Viome Life Sciences to sell Viome’s microbiome testing kits to its customers online, and in 2022, at some Nordstrom retail locations. These tests are centered around helping consumers understand the relationship between their microbiome and nutrition.
Pathologists and clinical laboratories will want to track Nordstrom’s success or failure in selling microbiome-based assays to its consumers. Microbiomics is in its infancy and remains a very unsettled area of diagnostics. Similarly, Viome, a self-described precision health and wellness company that conducts mRNA analysis at scale, will need to demonstrate that its strategy of developing precision medicine diagnostics and therapeutics based on the human microbiome has clinical relevance.
Helping Consumers with ‘Precision Nutrition’
In a September news release, Viome founder and CEO Naveen Jain, a serial entrepreneur, said, “Both Viome and Nordstrom believe that true health and beauty start from within. There is no such thing as a universal healthy food or healthy supplement. What is right for one person can be wrong for someone else, especially when it comes to nutrition which is key to human longevity and vitality. Precision nutrition is the future!”
“Precision medicine seeks to improve the personalized treatment of diseases, and precision nutrition is specific to dietary intake. Both develop interventions to prevent or treat chronic diseases based on a person’s unique characteristics like DNA, race, gender, health history, and lifestyle habits. Both aim to provide safer and more effective ways to prevent and treat disease by providing more accurate and targeted strategies.
“Precision nutrition assumes that each person may have a different response to specific foods and nutrients, so that the best diet for one individual may look very different than the best diet for another.
“Precision nutrition also considers the microbiome, trillions of bacteria in our bodies that play a key role in various daily internal operations. What types and how much bacteria we have are unique to each individual. Our diets can determine which types of bacteria live in our digestive tracts, and according to precision nutrition the reverse is also true: the types of bacteria we house might determine how we break down certain foods and what types of foods are most beneficial for our bodies.”
Medical Laboratory Testing, not Guessing
Viome Life Sciences is a microbiome and RNA analysis company based in Bellevue, Wash. The test kit that Nordstrom is selling is called the Health Intelligence Test. It is an at-home mRNA test that can provide users with some insights regarding their health. Consumers use the kit to collect blood and fecal samples, then return those samples to Viome for testing.
In a press release announcing its collaboration with Nordstrom, Viome said, “In a world overwhelmed by information relating to diet and supplement advice, Viome believes in testing, not guessing and empowering its users with actionable insights. To date, Viome has helped over 250,000 individuals improve their health through precision nutrition powered by microbial and human gene expression insights.”
Nordstrom began offering Viome’s Health Intelligence Test kit for $199 on its website starting in September. As of this writing and noted above, the kits are sold out. Nordstrom plans to stock the kit in select stores starting in 2022.
Individuals who purchase the test submit blood and stool samples to Viome’s lab which performs an analysis of gene activity patterns in the user’s cells and microbiome. Viome provides the results to consumers within two to three weeks.
“This partnership is a giant step towards making our technology more accessible, so people can understand what’s right for their unique body,” Jain said in the news release. “We are inspired each day by the incredible changes our customers are seeing in their health including improvements in digestion, weight, stress, ability to focus, and more.”
According to the news release, Viome conducted blind studies earlier this year that revealed significant successes based on their precision nutritional approach to wellness. Study participants, Viome claims, improved their outcomes to four diseases through nutrition:
Is Microbiome Diagnostics Testing Ready for Clinical Use?
Microbiomics is a relatively new field of diagnostics research. Much more research and testing will be needed to prove its clinical value and efficacy in healthcare diagnostics. Nevertheless, companies are offering microbiomics testing to consumers and that has some healthcare providers concerned.
In the GeekWire article, David Suskind, MD, a gastroenterologist at Seattle Children’s Hospital and Professor of Pediatrics at the University of Washington, described Viome’s study methodology as “questionable,” adding, “I think this is a very interesting and exciting space and I do think there are definite potential implications, down the road. [However] we are not there in terms of looking at microbiome and making broad recommendation for individuals, as of yet.”
Will at-home clinical laboratory testing kits that analyze an individual’s microbiome someday provide data that help people lead healthier lives and ward off diseases? That’s Jain’s prediction.
In an article published in Well+Good, Jain said, “COVID-19 has, of course, been such a dark time, but one positive that did come from it is that more people are taking control of their own health. I really believe that the future of healthcare will be delivered not at the hospital, but at home.”
If this collaboration between Nordstrom and Viome proves successful, similar partnerships between at-home diagnostics developers and established retail chains may become even more common. And that should be on the radars of pathologists and clinical laboratories.
Newly combined digital pathology, artificial intelligence (AI), and omics technologies are providing anatomic pathologists and medical laboratory scientists with powerful diagnostic tools
Add “spatial transcriptomics” to the growing list of “omics” that have the potential to deliver biomarkers which can be used for earlier and more accurate diagnoses of diseases and health conditions. As with other types of omics, spatial transcriptomics might be a new tool for surgical pathologists once further studies support its use in clinical care.
Among this spectrum of omics is spatial transcriptomics, or ST for short.
Spatial Transcriptomics is a groundbreaking and powerful molecular profiling method used to measure all gene activity within a tissue sample. The technology is already leading to discoveries that are helping researchers gain valuable information about neurological diseases and breast cancer.
Marriage of Genetic Imaging and Sequencing
Spatial transcriptomics is a term used to describe a variety of methods designed to assign cell types that have been isolated and identified by messenger RNA (mRNA), to their locations in a histological section. The technology can determine subcellular localization of mRNA molecules and can quantify gene expression within anatomic pathology samples.
In “Spatial: The Next Omics Frontier,” Genetic Engineering and Biotechnology News (GEN) wrote, “Spatial transcriptomics gives a rich, spatial context to gene expression. By marrying imaging and sequencing, spatial transcriptomics can map where particular transcripts exist on the tissue, indicating where particular genes are expressed.”
In an interview with Technology Networks, George Emanuel, PhD, co-founder of life-science genomics company Vizgen, said, “Spatial transcriptomic profiling provides the genomic information of single cells as they are intricately spatially organized within their native tissue environment.
“With techniques such as single-cell sequencing, researchers can learn about cell type composition; however, these techniques isolate individual cells in droplets and do not preserve the tissue structure that is a fundamental component of every biological organism,” he added.
“Direct spatial profiling the cellular composition of the tissue allows you to better understand why certain cell types are observed there and how variations in cell state might be a consequence of the unique microenvironment within the tissue,” he continued. “In this way, spatial transcriptomics allows us to measure the complexity of biological systems along the axes that are most relevant to their function.”
According to 10x Genomics, “spatial transcriptomics utilizes spotted arrays of specialized mRNA-capturing probes on the surface of glass slides. Each spot contains capture probes with a spatial barcode unique to that spot.
“When tissue is attached to the slide, the capture probes bind RNA from the adjacent point in the tissue. A reverse transcription reaction, while the tissue is still in place, generates a cDNA [complementary DNA] library that incorporates the spatial barcodes and preserves spatial information.
“Each spot contains approximately 200 million capture probes and all of the probes in an individual spot share a barcode that is specific to that spot.”
“The highly multiplexed transcriptomic readout reveals the complexity that arises from the very large number of genes in the genome, while high spatial resolution captures the exact locations where each transcript is being expressed,” Emanuel told Technology Networks.
Spatial Transcriptomics for Breast Cancer and Neurological Diagnostics
In that paper, the authors wrote “we envision that in the coming years we will see simplification, further standardization, and reduced pricing for the ST protocol leading to extensive ST sequencing of samples of various cancer types.”
Spatial transcriptomics is also being used to research neurological conditions and neurodegenerative diseases. ST has been proven as an effective tool to hunt for marker genes for these conditions as well as help medical professionals study drug therapies for the brain.
“You can actually map out where the target is in the brain, for example, and not only the approximate location inside the organ, but also in what type of cells,” Malte Kühnemund, PhD, Director of Research and Development at 10x Genomics, told Labiotech.eu. “You actually now know what type of cells you are targeting. That’s completely new information for them and it might help them to understand side effects and so on.”
The field of spatial transcriptomics is rapidly moving and changing as it branches out into more areas of healthcare. New discoveries within ST methodologies are making it possible to combine it with other technologies, such as Artificial Intelligence (AI), which could lead to powerful new ways oncologists and anatomic pathologists diagnose disease.
“I think it’s going to be tricky for pathologists to look at that data,” Kühnemund said. “I think this will go hand in hand with the digital pathology revolution where computers are doing the analysis and they spit out an answer. That’s a lot more precise than what any doctor could possibly do.”
Spatial transcriptomics certainly is a new and innovative way to look at tissue biology. However, the technology is still in its early stages and more research is needed to validate its development and results.
Nevertheless, this is an opportunity for companies developing artificial intelligence tools for analyzing digital pathology images to investigate how their AI technologies might be used with spatial transcriptomics to give anatomic pathologists a new and useful diagnostic tool.
A Penn Medicine news release noted that “The RAPID technology … transforms the binding event between the SARS-CoV-2 viral spike protein and its receptor in the human body, the protein ACE2 (which provides the entry point for the coronavirus to hook into and infect human cells), into an electrical signal that clinicians and technicians can detect. That signal allows the test to discriminate between infected and healthy human samples. The signal can be read through a desktop instrument or a smartphone.”
Though still in its early stages, the technique potentially offers dramatically lower costs and faster results than traditional RT-PCR (reverse transcription polymerase chain reaction) molecular tests. Moreover, the RAPID technology might be useful for identifying other types of biomarkers and could be the basis for diagnostic tests that help reduce the cost-per-test in medical laboratory testing while providing comparable sensitivity and specificity to existing methodologies.
Clinical trials began on January 5, 2021, and the Penn Medicine researchers say the IVD test technology can be applied to other infectious diseases, which, if proven accurate, would be a boon to clinical laboratory testing.
Diagnostic Test Results in Four Minutes for Less than $5/Test
According to the news release, the RAPID 1.0 (Real-time Accurate Portable Impedimetric Detection prototype 1.0) biosensor test costs less than $5 and can deliver results in four minutes. The researchers reported overall accuracy of 87.1% on (139) nasal swab samples and 90% on (50) saliva samples.
The technology uses electrodes that can be mass-produced at low cost on commercially-available screen printers, the researchers said. Results can be read on electronic devices connected to a PC or smartphone.
Does Penn Medicine’s RAPID 1.0 Test Replace Traditional RT-PCR Testing?
In their published study, the Penn Medicine researchers cited the need for “fast, reliable, inexpensive, and scalable point-of-care diagnostics.”
RT-PCR tests, they said, “are limited by their requirement of a large laboratory space, high reagent costs, multistep sample preparation, and the potential for cross-contamination. Moreover, results usually take hours to days to become available.”
Researchers who have studied the SARS-CoV-2 coronavirus know that it uses a spike-like protein to bind to angiotensin-converting enzyme 2 (ACE2) receptors on the surfaces of human cells.
As described in Penn Medicine’s published study, the biosensor contains ACE2 and other biochemical agents anchored to an electrode. When the SARS-CoV-2 coronavirus attaches to the ACE2, the biosensor transforms the chemical reaction into an electrical signal that can be measured on a device known as a potentiostat.
The researchers tested their RAPID 1.0 technology with two commercially available potentiostat models:
The researchers initially developed the electrode as a printed circuit board, which is relatively expensive. To reduce costs, they constructed a version that uses filter paper as the main component. The researchers noted that one screen printer in a lab can produce 35,000 electrodes per day, including time needed to incorporate the chemical elements. “However, it must be noted that these steps can be fully automated into a production line for industrial purposes, drastically reducing time requirements,” they wrote.
The test can be performed at room temperature, they added, and total cost per unit is $4.67. Much of that—$4.50—is for functionalizing the ACE2 recognition agent. The cost for the bare electrode is just seven cents.
“The overall cost of RAPID may be further reduced through recombinant production of ACE2 and ACE2 variants,” the researchers said, adding that the RAPID 1.0 test can detect the SARS-CoV-2 coronavirus at low concentrations correlating to the earliest stages of the COVID-19 disease.
Testing Penn Medicine’s RAPID 1.0 Test
The researchers evaluated the technology in blinded tests with clinical samples from the Hospital of the University of Pennsylvania. The evaluation included 139 nasal swab samples, of which 109 were determined to be COVID-19 positive by RT-PCR tests and clinical assessments. Among these, the RAPID test successfully detected the SARS-CoV-2 coronavirus in 91 samples, for a sensitivity rate of 83.5%. One sample was from a patient diagnosed with the highly contagious SARS-CoV-2 Alpha variant B.1.1.7, which the test correctly identified as positive.
Among the 30 samples determined to be COVID negative, the RAPID test scored a specificity rate of 100%, meaning no false positives. Overall accuracy, including sensitivity and specificity, was 87.1%.
The researchers also analyzed 50 saliva samples: 13 COVID-positive and 37 COVID-negative. The test correctly identified all 13 positive samples but produced five false-positives among the 37 negative samples, for a specificity rate of 86.5%. The researchers speculated that this could be due to interactions between ACE2 and other biomolecules in the saliva but suggested that performance “will improve when using fresh saliva samples at the point-of-care.”
Are There Other Applications for the RAPID Test?
The Penn Medicine news release said the RAPID technology can be adapted to detect other viruses, including those that cause Influenza and sexually-transmitted diseases.
Robert Michel, Editor-in-Chief of Dark Daily and its sister publication The Dark Report, said the test points to one silver lining in the COVID-19 pandemic. “Researchers around the world intensified their work to find ways to identify the SARS-CoV-2 virus that are faster, cheaper, and more accurate than the diagnostic technologies that existed at the time of the outbreak. In this regard, the COVID-19 pandemic may have accelerated the development and refinement of useful diagnostic technologies that will disrupt long-established methods of testing.”
Marcelo Der Torossian Torres, PhD, postdoctoral researcher at Penn Medicine and lead author of the study, said in the news release, “Quick and reliable tests like RAPID allow for high-frequency testing, which can help identify asymptomatic individuals who, once they learn they are infected, will stay home and decrease spread.
“We envision this type of test being able to be used at high-populated locations such as schools, airports, stadiums, companies—or even in one’s own home,” he added.
Clinical laboratory managers may want to stay current on the development and possible commercialization of the RAPID 1.0 (Real-time Accurate Portable Impedimetric Detection prototype 1.0) biosensor test by the research team at Penn Medicine.
Clinical laboratories may see increase in flu and COVID-19 specimen processing as people return to pre-pandemic social behaviors, experts predict
While SARS-CoV-2 infections continue to ravage many parts of the world, influenza (flu) cases in North America have hit a historic low. As winter approached last year, infectious disease experts warned of a “twindemic” in which the COVID-19 outbreak would combine with seasonal influenza to overwhelm the healthcare system. But this did not happen, and many doctors and medical laboratory scientists are now investigating this unexpected, but welcomed, side-effect of the pandemic.
From the start of the current flu season in September 2020, clinical laboratories in the US reported that 1,766 specimens tested positive for flu out of 931,726—just 0.2%—according to the CDC’s Weekly US Influenza Surveillance Report. That compares with about 250,000 positive specimens out of 1.5 million tested in the 2019-2020 flu season, the CDC reported. Public health laboratories reported 243 positive specimens out of 438,098 tested.
Fear of COVID-19 Linked to Fewer Flu Deaths in Children
WebMD reported that just one child in the US has died from the flu this year, compared with 195 in 2020. Why the low numbers?
Precautions people take to avoid COVID-19 transmission, including masking, social distancing, and handwashing.
Reduced human mobility, including less international travel.
Higher-than-usual flu vaccination rates. As of February 26, the CDC reported that nearly 194 million doses of flu vaccine had been distributed in the US.
WebMD noted this could be a record, but that the CDC data doesn’t indicate how many doses were actually administered.
However, Schaffner told WebMD that efforts to keep kids home from school and away from social gatherings were likely a bigger factor. “Children are the great distributors of the influenza virus in our society,” he said. But due to fears about COVID-19 transmission, kids “weren’t even playing together, because mothers were keeping them off the playground and not having play dates.”
Repercussions for Fighting Flu Next Year
Public health experts welcomed the low flu levels, however, Politico reported that limited data about flu circulation this year could hamper efforts to develop an effective vaccine for next season’s flu strains.
Each February, Politico explained, experts convened by the World Health Organization (WHO) look at data from the current and previous flu seasons to predict which strains are likely to predominate in the Northern Hemisphere next winter. That includes data about which strains are currently circulating in the Southern Hemisphere. The WHO uses these predictions to recommend the composition of flu vaccines. In the US, the final decision is made by an FDA advisory committee.
A similar WHO meeting in September guides vaccine development in the Southern Hemisphere.
The WHO issued this year’s Northern Hemisphere recommendations on Feb. 26. The advisory includes recommendations for egg-based and cell- or recombinant-based vaccines, and for quadrivalent (four-strain) or trivalent (three-strain) vaccines.
In a document accompanying the recommendations, the WHO acknowledged concerns about this year’s limited pool of data.
“The volume of data available from recently circulating influenza viruses, and the geographic representation, have been significantly lower for this northern hemisphere vaccine recommendation meeting than is typical,” the document stated. “The reduced number of viruses available for characterization raises uncertainties regarding the full extent of the genetic and antigenic diversity of circulating influenza viruses and those likely to pose a threat in forthcoming seasons.”
The report notes that experts identified changes in circulating Influenza A(H3N2) viruses this year, and that the changes are reflected in the new vaccine recommendation.
Offit suggests that efforts to mitigate the COVID-19 outbreak could be useful to combat other infectious disease outbreaks. However, both Offit and Gostin expressed doubt about that prospect.
“I mean, could we reasonably in a winter month, wear masks just at least when we’re outside in large crowds? … Or are we comfortable having hundreds of 1000s of cases of hospitalizations for flu and 10s of 1000s [of] deaths? I suspect the answer is B. We’re comfortable with that, we’re willing to have that even though we just learned, there’s a way to prevent it,” Offit told Politico.
“Remember after the 1918 flu pandemic, most people don’t realize what happened when that was over. But what happened was the roaring ‘20s,” Gostin told Politico. “People started congregating, mingling, hugging, kissing. All the things they missed. They crowded into theaters and stadiums and went back to church. That’s what’s likely to happen this fall and that makes the influenza virus very happy.”
So, what should clinical laboratories expect in future flu and COVID-19 vaccines? That is not yet clear. One thing is certain, though. New lab test panels that test for influenza and the SARS-CoV-2 coronavirus will be arriving in the marketplace.
Clinical labs and pathology groups know how advances in targeted therapies and genomics far outpace providers’ and patients’ ability to know how best to use and pay for them.
One fascinating development on the road to precision medicine is that many new cancer drugs now in clinical trials will require a companion genetic test to identify patients with tumors that will respond to a specific therapeutic drug.
This implies more genetic testing of tumors, a prospect that challenges both the Medicare program and private health insurers because they already struggle to cope with the flood of new genetic tests and molecular diagnostic assays. However, even as this genetic testing wave swamps payers, some pharmaceutical companies have cancer drugs for rare types of cancers and these companies would like to see more genetic testing of tumors.
Pathologists and clinical laboratory managers will find this to be precisely the dilemma facing specialty pharma company Loxo Oncology (NASDAQ:LOXO), a biopharmaceutical company located in San Francisco and Stamford, Conn.
Loxo is developing larotrectinib (LOXO-101), a “selective TRK inhibitor.” According to a Loxo press release, Larotrectinib is “a potent, oral, and selective investigational new drug in clinical development for the treatment of patients with cancers that harbor abnormalities involving the tropomyosin receptor kinases (TRK receptors).” In short, the drug is designed to “directly target TRK, and nothing else, turning off the signaling pathway that allows TRK fusion cancers to grow.”
How to Find Patients for This Cancer Drug
While a powerful, new, targeted cancer drug will be a boon to cancer therapy, it is only intended for a relatively small number of patients. Loxo estimates that between 1,500 and 5,000 cases of cancer are caused by TRK mutations in the United States each year. Conversely, according to the National Cancer Institute, the total number of new cancer diagnoses in the US in 2016 was 1,685,210.
An article in MIT Technology Review on larotrectinib notes, “To find patients, Loxo will need to convince more doctors to order comprehensive tests that screen multiple genes at once, including TRK.” And that is where things get complicated.
“These advanced genetic tests, which can cost $5,000 or more, are offered by companies like Foundation Medicine, Caris Life Sciences, and Cancer Genetics. The problem is, insurers still consider the tests ‘experimental’ and don’t routinely cover them, meaning patients are often stuck picking up the bill,” notes MIT Technology Review.
Data for the graph above comes from theNational Human Genome Research Institute. The graph illustrates the steep decline in cost for whole genome sequencing over the past 17 years. As the cost of genetic testing drops, development of targeted-drug cancer therapies increases. Clinical laboratories and anatomic pathology groups can expect to be performing more such tests in the future. (Graphic copyright: National Human Genome Research Institute/Simple English Wiki.)
To further confuse the market, the National Cancer Institute states that “Insurance coverage of tumor DNA sequencing depends on your insurance provider and the type of cancer you have. Insurance providers typically cover a DNA sequencing test if there is sufficient evidence to support that the test is necessary to guide patient treatment. Tests without sufficient evidence to support their utility may be considered experimental and are likely not covered by insurance.”
That, however, leads to a different conundrum for drug makers such as Loxo: the majority of doctors are not keeping up with the rapid-fire pace of discovery in the realm of genetics and targeted therapies. Some genes like BRCA1 and BRCA2 are familiar enough to doctors that they know how and why they are important. However, most other genes are less known, and critically, less understood by doctors who must also focus on all the other myriad aspects of patient care.
Further complicating the issue, there is an enormous lack of information on how multipanel screenings will affect individuals, public health, and the cost of healthcare in general. Several studies are underway, but they are so new it could be years before any real results become available.
Five years ago, it cost about $20,000 to sequence the whole human genome. Now the average price is $1,500, though there are more and less expensive types of genetic tests. As the cost continues to decline, however, more people will undergo the testing and scientists will learn more about how to identify the best therapy to treat cancers caused by genetic mutations.